1

February 26, 2010

Prediction of SAMPL2 Aqueous Solvation Free Energies and

Tautomeric Ratios Using the SM8, SM8AD, and SMD Solvation Models

Raphael F. Ribeiro, Aleksandr V. Marenich, Christopher J. Cramer,* and Donald G. Truhlar*Department of Chemistry and Supercomputing Institute,

University of Minnesota, 207 Pleasant Street SE, Minneapolis, MN 55455-0431

Abstract: We applied the solvation models SM8, SM8AD, and SMD in combination with the

Minnesota M06-2X density functional to predict vacuum-water transfer free energies (Task 1)

and tautomeric ratios in aqueous solution (Task 2) for the SAMPL2 test set. The bulk-

electrostatic contribution to the free energy of solvation is treated as follows: SM8 employs the

generalized Born model with the Coulomb field approximation, SM8AD employs the

generalized Born approximation with asymmetric descreening, and SMD solves the

nonhomogeneous Poisson equation. The non-bulk-electrostatic contribution arising from short-

range interactions between the solute and solvent molecules in the first solvation shell is treated

as a sum of terms that are products of geometry-dependent atomic surface tensions and solvent-

accessible surface areas of the individual atoms of the solute. On average, three models tested in

the present work perform similarly. In particular, we achieved mean unsigned errors of 1.4

(SM8), 2.0 (SM8AD), and 2.6 kcal/mol (SMD) for the aqueous free energies of 30 out of 31

compounds with known reference data involved in Task 1 and mean unsigned errors of 2.7

(SM8), 1.8 (SM8AD), and 2.4 kcal/mol (SMD) in the free energy differences (tautomeric ratios)

for 21 tautomeric pairs in aqueous solution involved in Task 2.

Keywords: Free energy; Generalized Born; Implicit Solvation; Poisson Equation; Solvation;

Solvation Modeling; Tautomerism

* Corresponding author e-mail: cramer@umn.edu (C.J.C) and truhlar@umn.edu (D.G.T.)

2

Introduction

The annual SAMPL challenges organized by OpenEye Scientific Software present the

unique opportunity to make an assessment of various solvation protocols with respect to the

prediction of solvation effects for very diverse solutes including many containing functionality of

interest to the pharmaceutical industry. Accurate theoretical description of solvation is critically

important in modeling because solvation effects are essential components of all liquid-state

chemistry, and it is impossible to understand liquid-phase organic, biological, or inorganic

chemistry without including them. For example, solvation effects influence solvent-dependent

changes in reaction rates and reaction mechanisms, chromatographic retention behavior,

interfacial transport effects, protein folding, ligand-receptor binding, and pharmaceutical

bioavailability. Various explicit and implicit solvation models have been employed for prediction

of pharmacokinetic and thermodynamic properties of drug-like compounds in biological fluids,

for instance, in the evaluation of protein-ligand binding free energies using the free energy of

solvation (or desolvation) of the ligand as a key component [1, 2]. In addition, accurate

computational methods used in solvation modeling may be a viable alternative to experimental

measurement, especially for highly polar solutes for which experimental determinations of

solvation free energies are difficult or inaccurate. Solvation models differ in their representation

of the solvent, their adoption of a classical or quantum description of the solute, and their

computational cost [3–10]. As a consequence, their accuracy for the prediction of free energies

of solvation and their range of applicability are also different. The SAMPL initiative is especially

useful because it allows for evaluation of current solvation methods in terms of their predictive

abilities on mostly unpublished and obscure data sets that are unlikely to have been part of the

training set of any tested protocol. The testing of different models against common test sets is a

3

particularly valuable exercise that facilitates comparison of their relative strengths and

weaknesses. The insight that one can gain with such an exercise will serve well for further

improvement of existing solvation models and liquid-phase simulation techniques.

The present SAMPL2 challenge is focused on the prediction of vacuum-water transfer

energies (Task 1) and the prediction of tautomer ratios (Task 2) for compounds in solution, many

of which have been selected to be pharmaceutically relevant. The SAMPL2 data set includes

compounds from three different categories: obscure, explanatory, and investigatory. Obscure

compounds have known but not readily available experimental data. Explanatory compounds,

which have unexpected or interesting experimental values, have been included in hopes that the

solvation models involved in the SAMPL2 challenge might explain their unusual properties.

Measured solvation free energies are not available for investigatory compounds. In the present

paper, we evaluate the performance of our most recent implicit solvation models, namely, SM8,

SM8AD, and SMD, over the SAMPL2 test set. Section 2 places the solvation models used in the

present study in the context of recent advances in the field. Section 3 summarizes further

computational details. Section 4 presents results and discussion. Section 5 summarizes our

conclusions.

Review of computational methods

Computational methods that include the solvent implicitly have been recognized as a

powerful alternative to explicit simulation techniques because they allow one to treat the solute

with quantum mechanical calculations at the same high levels as those used in the gas phase [5–

10]. Reliable calculations of solutes in solution must take account of electrostatics, cavitation,

dispersion, and solvent structure. In the most complete implicit solvation models, the solute is

4

polarized self-consistently by the reaction field, and it is the interaction of the mutually polarized

solute and solvent subsystems that is called the electrostatic contribution. The electrostatic

contribution can be evaluated by solving the Poisson equation for a nonhomogeneous dielectric

medium with the free charge being that of the continuous charge density of the solute or by using

alternative approaches, for instance, the generalized Born (GB) approximation [11–13], which

represents the solute as a system of point charges located at the nuclear positions.

We have recently introduced three successively improved self-consistent reaction-field

continuum solvation models, namely Solvation Model 8 (SM8) [14], Solvation Model 8 with

Asymmetric Descreening (SM8AD) [15], and Solvation Model D (SMD) [16]. “Continuum”

denotes that the solvent is not represented explicitly in any of these models, but rather it is

treated as a dielectric medium with variable surface tension at the solute-solvent boundary. These

models separate the observable solvation free energy into three components. One of

these, depends on solute concentration and vanishes for an ideal solution with the same

concentration as the vapor. The other two are independent of concentration and correspond to a

dilute solution. Thus the standard-state free energy of solvation is

,Δ οconcG

CDSENPconcS GGG ++= GΔΔΔ οo (1)

where ΔGENP is the bulk electrostatic contribution resulting from the interaction of a solute with

its reaction field, which is the electric field produced by the polarized charge density that the

solute induces in the solvent, and GCDS is explained below. The solute cavity for the bulk

electrostatic calculation is taken as a superposition of nuclear-centered spheres, and the solvent

dielectric constant is taken as its bulk value right up to cavity boundary. The final component in

Eq. 1 accounts for everything except concentration and that part of the electrostatic contribution

5

that is modeled with the bulk dielectric constant. It is nominally associated with cavity

formation, dispersion, and solvent-structure effects, but it also includes the deviation from the

assumed bulk behavior of the solute electrostatic interaction with the first solvent shell. Since the

third contribution is semiempirical it also makes up for any systematic errors such as the inexact

treatment of solutes. The third contribution will be called the CDS term, denoting the nominal

ingredients of cavitation, dispersion, and solvent structure. All the three models are used in the

present study in their standard, published form, with no changes for the present applications.

The bulk electrostatic contribution is treated differently in SM8, SM8AD, and SMD. The

SMD model is based on the polarized continuous quantum mechanical charge density of the

solute (the “D” in the name stands for “density”). The SMD bulk electrostatic contribution to the

free energy of solvation arises from a self-consistent reaction field treatment that involves

solution of the nonhomogeneous Poisson equation (NPE) by the Integral-Equation-Formalism

Polarizable Continuum Model (IEF-PCM) algorithm [17]. In contrast to SMD, the SM8 and

SM8AD models treat the bulk electrostatics using the GB approximation based on partial atomic

charges, whose interaction with the solvent and with each other is dielectrically screened by the

polarized solvent and descreened by other parts of the solute. The SM8 and SM8AD models treat

dielectric descreening effects in terms of the so-called Born radii of individual atoms in the

solute molecule. The SM8 model employs the Born radius based on the Coulomb field

approximation of Still et al. [13]. The SM8AD model improves on the earlier SM8 model by

using a new asymmetric descreening algorithm with a modified formula for the Born radius

suggested by Grycuk [18]. Both the SM8 and SM8AD models employ class IV charge models

[19], in particular, Charge Model 4 (CM4) [20] and Charge Model 4M (CM4M) [21]. In the

present work we use only CM4M.

6

The CDS contribution to the free energy of solvation computed by SM8, SM8AD, and

SMD is a sum of terms that are proportional (with geometry-dependent proportionality constants

called atomic surface tensions) to the solvent-accessible surface areas of the individual atoms of

the solute. The CDS terms were parameterized [14–16] to include all of the deviations of the

electrostatics from the assumed bulk model, such as the inexactness of the solvent permittivity

model, including assumed values for intrinsic Coulomb radii, uncertainties in the treatment of

solute charge outside the solute cavity in the case of SMD, and the inexactness of the solute

charge model in the case of SM8 and SM8AD.

The SM8, SM8AD, and SMD models have been recently tested using 26 combinations of

various basis sets and density functionals over a set of 2892 solvation data including 345 free

energies of solvation for neutral solutes in water, 2072 free energies of solvation for neutral

solutes in 90 nonaqueous solvents, 143 transfer free energies for neutral solutes between water

and 15 organic solvents, and 332 free energies of solvation for ions in acetonitrile, dimethyl

sulfoxide, methanol, and water [15]. The number of solvation energy calculations performed in

this testing totals 75192 for each of the three models. The mean unsigned error averaged over 26

theoretical levels for 2560 solvation data for neutral solutes is 0.6, 0.7, and 0.8 kcal/mol for

SM8AD, SM8, and SMD, respectively. The mean unsigned error averaged over 26 theoretical

levels for 332 free energies of solvation for ions is 4.0 (SM8AD), 4.4 (SM8), and 4.3 kcal/mol

(SMD). Although all the three models perform nearly equally well, one should consider that the

SM8 and SM8AD models employ partial atomic charges, and their accuracy for a particular level

of electronic structure theory may depend on whether consistent partial charges can be computed

for that level of theory, but the ability to compute such partial atomic charges is not guaranteed

for all possible theory levels and basis sets. For this reason, solvation models that solve the NPE

7

such as the density-based model SMD are deemed to be less sensitive to the choice of basis set,

although basis sets containing diffuse functions can lead to errors due to charge lying outside the

solute cavity [22]. On the other hand, the GB models such as SM8 and SM8AD can be favored

for their lower computational cost compared to the cost of NPE solvers; one SCF iteration

typically takes 1.5 – 2 times longer with SMD than with SM8 or SM8AD. Comparing the two

GB approaches, we note that the SM8AD model based on the asymmetric descreening

approximation [15, 18] is expected to be more realistic than the SM8 model, which is based on

the Coulomb field approximation of Still et al. [13], particularly for cases when the individual

partial atomic charges are asymmetrically situated in the molecule, i.e., located near the

dielectric boundary rather than at the center of the molecular surface [15, 18].

Computational details

All the solvation free energies are given for the gas-phase solute having a standard state

of an ideal gas at a gas-phase concentration of 1 mol/L and for the liquid-phase solute being

dissolved in an ideal solution at a liquid-phase concentration of 1 mol/L, and the temperature is

298 K. In this case in Eq. 1 becomes Free energies that employ this standard

state definition will be denoted by the superscript “*”. When one uses the same geometry in the

gas phase and in solution (as we do here), ΔGENP reduces to ΔGEP.

οΔ concG .0Δ ο ≡concG

Following our earlier work on the SAMPL1 challenge [23] all free energies of solvation

calculated for Task 1 (Transfer Energies) were computed using the Minnesota solvation models

outlined above with the density functional M06-2X [24], and the 6-31G(d) [25, 26] basis set. We

8

used the geometries included in the instructions for SAMPL2, except (as discussed below) for

glycerol.

In order to gather further insights into our results, we also computed the free energy of

solvation for the molecules present in the explanatory subset using solvent-solute clusters

composed of the solute and one or two water molecules in chemically intuitive positions, i.e.,

interacting via hydrogen bonding or dipole-dipole forces. Gas-phase structures of the water-

solute clusters were optimized using M06-2X [24]/MG3S [27].

For the solvent-solute clusters with a single water molecule, the free energy of solvation

of a given solute is evaluated using the corresponding thermochemical cycle that relates

to the calculated free energy of solvation of the water-solute cluster, as

follows

(M)S*ΔG

(M)S*ΔG M),O(H2S ⋅*ΔG

]ln[ΔΔΔΔΔ **ο* OHO)(HM)O(H(B.E.) (M) 22S2S*o

gS RTGG −−⋅+−= → GGG (2)

In Eq. 2, is the computed gas-phase binding free energy of the solute-water cluster

that corresponds to the ideal-gas standard state of 1 atm denoted by the superscript “o”,

refers to the free energy change between one mole of an ideal gas taken at

1 atm (24.46 mol/L) and one mole taken at the concentration of 1 mol/L, is the

experimental free energy of solvation of water, and

(B.E.)gοΔG

)46.24ln(Δ RTG ≡→*o

O)(H2S*ΔG

)34.55ln(]ln[ RTRT ≡OH2 refers to the free

energy change between one mole of H2O ideal gas taken at the concentration of H2O in liquid

water (55.34 mol/L) and one mole taken at the concentration of 1 mol/L [16, 28]. A procedure

for calculation of using the solvent-solute clusters with more than one solvent molecules

is described elsewhere [

(M)S*ΔG

28].

9

Task 2 (Tautomeric Teasers) involved the calculation of the free energy difference

between two tautomeric forms in solution. The free energy of each tautomer in solution is

calculated as a sum of the corresponding gas-phase free energy and the aqueous free energy of

solvation for a given tautomer. For all the compounds involved in Task 2, the gas-phase free

energies at 298 K were calculated at the M06-2X/MG3S level of theory using the gas-phase

molecular geometries optimized at the same level. The corresponding aqueous free energies of

solvation were computed at the M06-2X/6-31G(d) level of theory at the M06-2X/MG3S gas-

phase geometries using the SM8, SM8AD, and SMD continuum solvation models. To examine

the accuracy of the M06-2X gas-phase free energies, we compared them with those calculated

using the BMC-CCSD multicoefficient correlation method [29] for selected cases in Task 2. In

these computations noted further as BMC-CCSD//M06-2X/MG3S we used the BMC-CCSD total

electronic energies calculated at the M06-2X/MG3S gas-phase geometries with the 298 K

thermal free energy corrections calculated at the M06-2X/MG3S level.

All calculations in this work were performed using two locally modified versions of the

Gaussian03 [30] electronic structure package, namely, Minnesota Gaussian Functional Module

(MN-GFM) [31] and Minnesota Gaussian Solvation Module (MN-GSM) [32].

Results and discussion

Task 1: aqueous free energies of solvation

Task 1 involved the prediction of aqueous free energies of solvation (air-water transfer

energies) for 41 polyfunctional molecules selected by Guthrie (see introduction to SAMPL2

challenge in this issue of the journal) and divided into three groups: a) obscure compounds, b)

explanatory compounds, and c) investigatory compounds. With respect to the explanatory

10

compounds, the corresponding experimental aqueous free energies of solvation were provided in

advance, so that unusual trends in the relevant properties of these compounds could be

reproduced and explained. There were no experimental data provided for the investigatory group,

and to the best of our knowledge, there are no experimental solvation energies available for these

compounds in the literature.

TABLE 1

Table 1 compares aqueous free energies of solvation calculated by SM8, SM8AD, and

SMD for 30 out of 31 compounds originally present in the obscure and explanatory subsets to the

corresponding experimental values. Note that we excluded 1-iodouracil from consideration here

because the tested solvation models were not parameterized for iodine-containing compounds.

The biggest outlier among the obscure compounds is diflunisal. Apart from diflunisal, the

accuracy of SM8, SM8AD, and SMD depends on the nature of a tested compound. For example,

SM8AD gives an error of 5.6 kcal/mol for ketoprofen whereas SM8 and SMD show much

smaller deviations of 1.8 (SM8) and 2.1 kcal/mol (SMD), respectively, for the same compound.

In addition, SM8AD overestimates the aqueous free energy of solvation of acetylsalicylic acid by

4.1 kcal/mol whereas the error for SM8 and SMD is only –1.6 kcal/mol on average. SM8AD is

more accurate than SMD and SM8 in the case of sulfolane apparently due to a better

representation of compounds with oxidized sulfur functionalities in the SM8AD training set [15].

In the case of D-xylose and D-glucose, the SMD model is less accurate than SM8 and

SM8AD. However, caution should be exercised before consideration of the experimental data

given in the SAMPL2 database for these carbohydrates because the experimental procedures for

estimating the free energies of solvation of highly polar molecules are prone to a variety of

problems, such as the decomposition of the solute at the high temperatures needed to achieve a

11

reasonable vapor pressure, and inherent numerical errors in the extrapolation of the high-

temperature results to the corresponding room-temperature values. On the other hand, the

substantially more negative solvation free energies predicted for the two sugars by SMD may

reflect enhanced outlying charge errors in these molecules heavily functionalized with oxygen

lone pairs near the cavity boundary. Overall, for the set of obscure compounds, SM8 is slightly

more accurate (within the uncertainty of the experimental data) than SM8AD and SMD, with

50% of its predictions giving errors of 1 kcal/mol or less, and only four molecules having errors

greater than 2 kcal/mol.

Table 1 indicates that over the set of explanatory compounds all of our models did poorly

in predicting the experimental solvation free energy of glycerol, with errors ranging from 4 to 8

kcal/mol when we used the geometry of glycerol as provided by OpenEye Scientific Software

without any further structural optimization (and thus with only one conformation of glycerol

being taken into account; see footnote b in Table 1). To further investigate the problem with

glycerol, we performed a conformational search for the global minimum of glycerol using the

MMFF94 [33] force field with the GMMX algorithm present in the PCModel software [34], and

then we re-optimized the two lowest energy conformers at the mPW1PW [35]/MIDI! [36] level.

The aqueous free energies of solvation for the two conformations were calculated using the SM8,

SM8AD, and SMD solvation models. The lowest energy conformer is preferred over the next

higher one by 3.5 kcal/mol in the gas phase and 2.9 kcal/mol in solution (complete details of

solvation free energies with SM8, SM8AD, and SMD are included in the Electronic

Supplementary Material along with the Cartesian coordinates for both glycerol structures). The

resulting SM8, SM8AD, and SMD aqueous solvation free energies calculated for the lowest

conformer in solution are reported in Table 1. These values are in much better agreement with

12

experiment (the average deviation is 1.6 kcal/mol) than those calculated using the SAMPL2

original geometry for glycerol (the average deviation is 5.8 kcal/mol). Over all the explanatory

set, SM8 is more accurate than SM8AD and SMD for predicting the aqueous free energy of

solvation of 3 out of the 8 molecules in this group with the accuracy of 1 kcal/mol or less

whereas SM8AD and SMD show such an accuracy for only two molecules of the given subset.

Table 1 also shows mean signed and mean unsigned errors (MSE and MUE, respectively)

as well as root mean squared errors (RMSE) in the predicted energies with respect to experiment.

We conclude that all our models perform reasonably well on either obscure or explanatory set of

compounds in the SAMPL2 challenge, with the MUE ranging from 1.4 kcal/mol (SM8) to 2.6

kcal/mol (SMD) on average.

TABLE 2

Table 2 shows the SM8, SM8AD, and SMD results for the investigatory compounds, for

which no experimental data were given. The investigatory group may be subdivided into three

classes: (i) phosphorous oxidized compounds, (ii) sulfur oxidized compounds, and (iii) azoles.

For the 25 organophosphorus compounds tested in previous work [15], the mean unsigned errors

(relative to the corresponding experimental data) in the SM8, SM8AD, and SMD aqueous free

energies of solvation calculated at the M06-2X/6-31G(d) level of electronic structure theory were

equal to 1.5 (SM8) , 1.3 (SM8AD), and 1.7 kcal/mol (SMD) [15]. These errors are comparable

with the absolute deviations in the SM8, SM8AD, and SMD predictions on

hexamethylphosphoramide, dimethyl methylphosphonate, and methyl dimethylphosphinate,

which are between 0.3 and 3 kcal/mol (Table 2). The mean signed errors in the aqueous free

energies of solvation calculated by SM8, SM8AD, and SMD for the five sulfonylureas tested in

previous work [15] were equal to –10.8 (SM8), –5.5 (SM8AD), and –7.4 kcal/mol (SMD) [15].

13

These compounds contain the S–O functionality; therefore, they structurally resemble the

sulfones and sulfoxides presented in Table 3. Thus, for the four sulfones and sulfoxides from the

investigatory set, the SM8AD model should provide the most accurate predictions whereas the

SM8 model (along with SMD for two cases out of four) is likely to overestimate the

corresponding solvation free energies. For oxazole, thiazole, and isothiazole, the absolute

deviations in the corresponding solvation free energies predicted by any two of SM8, SM8AD,

and SMD are between 0.1 and 2 kcal/mol. These deviations are comparable with those obtained

in previous work [15] for imidazole (0.3 – 1.5 kcal/mol) using SM8, SM8AD, and SMD with

M06-2X and 6-31G(d).

Sometimes adding one or more solvent molecules to the solute molecule explicitly can

substantially improve the performance of implicit solvation models [37, 38]. We have examined

such an approach in the present work by clustering all of the molecules in the explanatory

SAMPL2 test set, except glycerol. We added one water molecule to each tested solute molecule

except 4-nitroaniline, for which we added two explicit water molecules. The resulting molecular

structures of the water-solute clusters are presented in Figure 1. Table 3 shows SM8, SM8AD,

and SMD aqueous free energies of solvation of unclustered solutes calculated by Eq. 1 with the

use of the corresponding solvation free energies of the clusters.

FIGURE 1

TABLE 3

In general, the use of explicit solvent molecules for calculation of the solvation free

energy (microsolvation) should improve on only using CDS terms to account for such effects as

charge transfer between the solute molecule and the first solvation shell and the partial covalent

character of strong hydrogen bonds. Table 3 indicates that on average the use of water-solute

14

clusters has little effect on the performance of SM8, degrades the performance of SM8AD, and

improves the performance of SMD. When the continuum approximation is justified, that is, when

no “special” first-shell interactions mandate the inclusion of specific first-shell solvent

molecules, the inclusion of one or more explicit solvent molecules should not degrade the

performance of a continuum model (except for the issue that when includes explicit solvent

molecules, one should average properly, in a free energy sense, over their locations, but this is

not done here), and this is the case for SM8. In the SMD model, improvement is observed after

clustering, but derives almost entirely from the two chlorocarbons, suggesting that the atomic

surface tension for Cl may be somewhat too hydrophobic in SMD (so that burying some of the

exposed Cl surface with a clustering solvent molecule leads to an improved solution free

energy). The reason for the poor effect of clustering on the predicted SM8AD solvation free

energies is not clear, but it should be kept in mind that experimental uncertainties are high here.

Task 2: tautomeric teasers

The prediction of tautomeric equilibria presents a number of challenges from a modeling

standpoint. For example many of the tautomeric forms explicitly provided as part of the

challenge can themselves exist in multiple rotameric forms, and to complicate matters further the

lowest-energy rotamer of a given tautomer may be different in the gas phase than in aqueous

solution. In addition, the proximity of multiple hydrophilic functional groups in several of the

tautomers suggests that consideration of explicit first-shell water molecules may be important in

certain instances. A careful consideration of all of these issues, together with proper statistical

averaging over equilibrium populations, should be done in order to make meaningful

comparisons to experiment. Unfortunately, such careful attention devoted to each of the many

15

tautomeric equilibria included in this challenge was not possible within the time frame of the

exercise; instead, we elected to begin from the molecular structures provided by the SAMPL2

organizers and not to consider any others. This allows for a comparison of the results from the

SM8, SM8AD, and SMD models to those from solvation models surveyed by other groups as

part of this overall effort, but suggests that it may be dangerous to go beyond such internal

comparison to consider additionally the experimental situation. Certainly we think that it will be

worthwhile to return to many of these tautomeric equilibria in the future and explore all relevant

conformational and methodological issues in detail, but the results presented below should be

recognized as having restricted value beyond method-to-method comparison.

Task 2 involves the prediction of the free energy difference between two tautomers in

aqueous media for twelve cases selected by Taylor and divided into three categories: a) obscure,

b) explanatory, and c) investigatory subsets. The obscure subset comprises cases 1 – 3, the

explanatory subset comprises cases 4 – 6, the investigatory subset comprises cases 7 – 12. The

experimental values for the explanatory compounds are given along with the SAMPL2

assignment while the obscure subset constitutes a blind test for which the answer was known but

not revealed at the time when the challenge was given. For the investigatory subset, the reference

data are either absent or evaluated only qualitatively, and the purpose of this exercise is to

predict them quantitatively using existing theoretical techniques. Figure 2 shows the molecular

structures of all compounds involved in Task 2.

FIGURE 2

TABLE 4

TABLE 5

16

Table 4 compares the difference between the free energies of the two tautomers for each

compound in the obscure and explanatory subsets as calculated in the gas phase and in aqueous

solution using the SM8, SM8AD, and SMD continuum solvation models, to the corresponding

reference data in aqueous solution. The SM8AD model achieves the lowest mean unsigned errors

in all three cases of the obscure subset with respect to the corresponding experimental data

(Table 4). The SM8, SM8AD, and SMD models predict the dominant tautomer correctly for six

tautomeric pairs in the obscure subset but fail to predict the dominant tautomer qualitatively for

the tautomer pair 4A and 4B and for 6A and 6Z. Concerning the latter pair, the failure of our

models can be related to the zwitterionic nature of 6Z which cannot be described adequately by

the methods used in the present study. According to the SAMPL2 manual for Task 2

(Tautomeric Teasers), the corresponding equilibrium constant in the case of 5B and 5C is known

to be very sensitive to solvent variation. Indeed, all the models tested in this study confirm that

the difference in the free energies of 5B and 5C in aqueous solution can differ from that in the

gas phase by factors of 5 – 9 (Table 4). All of our models predict the reference data for case 4

(cis and trans-α-diketones) and case 6 (xanthine tautomerism) in the explanatory subset

quantitatively correctly (within the given uncertainties of the corresponding experimental

energies). To the contrary, the tested models fail to qualitatively reproduce the dominant

tautomer for five out of ten tautomeric pairs in case 5 (pyrazolones and isoxazolones). We

investigated the failure of our models in regard to case 5 as well as in regard to the tautomeric

pair 6A and 6Z in view of the possible error in the M06-2X/MG3S gas-phase free energies for

the corresponding molecules. Table 5 compares the free energy differences for the problematic

tautomeric pairs calculated using the M06-2X/MG3S//M06-2X/MG3S gas-phase free energies to

those calculated using the BMC-CCSD//M06-2X/MG3S gas-phase free energies. In general, the

17

BMC-CCSD method does not improve the resulting free energy differences for the given

tautomeric pairs in solution, producing even larger errors as compared to M06-2X/MG3S. Thus

we conclude that the failure of our methods to correctly predict the reference data for the given

tautomeric pairs in aqueous solution can be attributed to the inaccuracy of our solvation models

for these particular cases. However, some of the reference data were evaluated using empirical

linear structure energy relationship techniques involving the use of empirical solvent parameters

to derive solute-specific equations for equilibrium constants. Therefore, one can speculate that

the uncertainty in the corresponding reference data can be larger than previously estimated (0.1 –

0.7 kcal/mol in Table 5). On the other hand, we notice very good agreement with the

experimental value for the tautomeric pair 16A and 16C (Table 4) obtained by direct UV

observation [39] which is the most accurate datum for case 5. It would also be interesting to

examine solvent clustering in these instances, but we did not undertake this task.

TABLE 6

Table 6 presents the free energy difference predicted for the corresponding tautomers in

the investigatory subset for which the experimental tautomeric ratios are known at least

qualitatively. Tetronic acids (20A/B.o) are believed to be enolized in solution, and this

assumption is confirmed by SM8 and SM8AD. The SMD model predicts that the diketone form

is slightly dominating. Substitution of oxygen by sulfur results in a stronger preference for the

enolized form, whereas the addition of an N-methyl or a CH2 group results in the contrary trend

with all of the tested models. Case 8 comprises cyclic lactams and similar compounds. All our

models correctly predict that the oxo-form should be dominant in aqueous solution. Case 9

comprises cyclic triketones for many of which our models predict that their tautomeric ratios in

aqueous solution are close to those in the gas phase in accord with a suggestion given in the

18

SAMPL2 manual that the cyclic triketones can be highly polar and their polarity is likely to

remain the same between tautomers and, therefore, their tautomeric ratios may not be affected by

solvation. Case 10 involves the nitrogen-nitrogen tautomerism in compounds with bridgehead

nitrogen. Our results indicate that for the tautomeric pair 29A and 29B and for 31A and 31B the

solvation effects favor the enolized (B) form whereas for the tautomeric pair 28A and 28B and

30A and 30B the solvation effects only slightly influence the tautomeric ratio as well as for

diazepines (case 11). For five membered ring 2-oxoheterocycles involved in case 12, all three

models reasonably agree with one another and predict correctly (in accord with the SAMPL2

manual) that tautomer 35C is dominant, regardless of the substituent (z = N, O, or N-CH3). With

respect to the 35A.x_35B.x tautomerism, our results indicate that solvation is not the major

factor in the process, and the ketone form is predicted to be dominant in both the gas phase and

aqueous solution, regardless of the nature of the heteroatom z.

Conclusion

The quantum mechanical continuum solvent models SM8, SM8AD, and SMD predict

experimental aqueous free energies of solvation (vacuum-water transfer free energies) for 30 out

of 31 polyfunctional compounds involved in the SAMPL2 test set with mean unsigned errors of

1.4 (SM8), 2.0 (SM8AD), and 2.6 kcal/mol (SMD). Mean unsigned errors in the free energy

differences (tautomeric ratios) for 21 tautomeric pairs in aqueous solution tested in the present

study are 2.7 (SM8), 1.8 (SM8AD), and 2.4 kcal/mol (SMD). Given the complex character of the

compounds involved in the SAMPL2 challenge as well as in view of the possibility of larger than

reported uncertainties in several reference data (especially, for the tautomer ratios), all three

models tested in the present work perform well. Nevertheless, further improvement of these

19

models will merit consideration, especially with respect to improving the representation of

zwitterionic functionality in existing training sets.

Given our comparison of SM8, SM8AD, and SMD, it is natural to inquire as to whether

one is clearly to be preferred over the others. The significant variation in mean unsigned errors

over the molecular and tautomeric test sets noted above does not provide a single endorsement,

however—SM8 clearly outperforms SM8AD and SMD for the former set while SM8AD does

best for the latter. We have already noted that we consider uncertainty in the experimental data to

remain too high to consider the observed differences to be decisive. Moreover, the test sets

themselves are not especially diverse, so that model differences may be associated more with

individual functionalities (e.g., the better performance of SM8AD for oxidized sulfur

functionality, which derives from its training on a test set that had better representation of such

functional groups compared to SM8 and SMD). In addition, however, there may be other reasons

to choose one solvation model over another that are not readily tested by the SAMPL2 data. For

example, the SM8 and SM8AD models rely on underlying charge models that are used in the

computation of generalized Born electrostatic free energies of solvation, and such models have

been defined primarily for a set of balanced, medium-sized basis sets; by contrast, SMD does not

depend on a charge model, and thus it may be used with more extended basis sets or with basis

sets for which a charge model just does not happen be available. Similarly, by construction, we

expect SM8AD to be more accurate for large solutes with complex shapes having very

asymmetric charge distributions. And, of course, individual users may have empirically observed

one model to be more effective than another for certain classes of problems, or such observations

may have been made in the literature. Thus, rather than recommend a single model as the “best”

20

for all situations, we encourage users to consider all of the above factors when making a choice

of SMx model and proceed accordingly.

Acknowledgements. This work was supported by the Office of Naval Research under Grant

N 00014-05-01-0538, the Army Research Office under Grant US ARMY RES LAB/W911NF09-

1-0377, and the National Science Foundation (Grant CHE06-10183 and Grant CHE07-04974).

Computational resources were provided by Minnesota Supercomputing Institute.

References

1 Bamborough P, Cohen FE (1996) Modeling protein-ligand complexes. Curr Opin Struct Biol

6(2):236-241

2 Pei J, Wang Q, Zhou J, Lai, L (2004) Estimating protein-ligand binding free energy: Atomic

solvation parameters for partition coefficient and solvation free energy calculation. Proteins

54(4):651-664

3 Schiffer CA, Caldwell JW, Stroud RM, Kollman PA (1992) Inclusion of solvation free

energy with molecular mechanics: alanyl dipeptide as a test case. Protein Sci 1(3):396-400

4 Kollman P (1993) Free energy calculations: applications to chemical and biochemical

phenomena. Chem Rev 93(7):2395-2417

5 Rivail J-L, Rinaldi DL, Ruiz-Lopez MF The self-consistent reaction field model for

molecular computations in solution. In Formosinho SJ, Arnaut L, Csizmadia I (eds),

Theoretical and computational models for organic chemistry, Kluwer Academic Publishers,

1991, pp 79-92

21

6 Tomasi J, Persico M (1994) Molecular interactions in solution: an overview of methods

based on continuous distributions of the solvent. Chem Rev 94(7):2027-2094

7 Hawkins GD, Zhu T, Li J, Chambers CC, Giesen DJ, Liotard DA, Cramer CJ, Truhlar DG

Universal solvation models. In Gao J, Thompson MA (eds), Combined quantum mechanical

and molecular mechanical methods, American Chemical Society, Symposium Series,

Volume 712, Washington, DC, 1998, pp 201-219

8 Cramer CJ, Truhlar DG (1999) Implicit solvation models: equilibria, structure, spectra, and

dynamics. Chem Rev 99(8):2161-2200

9 Tomasi J, Mennucci B, Cammi R (2005) Quantum mechanical continuum solvation models.

Chem Rev 105(8):2999-3094

10 Mennucci B, Cammi R (eds) Continuum solvation models in chemical physics: from theory

to applications, Wiley, New York, 2008

11 Hoijtink GJ, de Boer E, van der Meij PH, Weijland WP (1956) Reduction potentials of

various aromatic hydrocarbons and their univalent anions. Recueil des Travaux Chimiques

des Pays-Bas et de la Belgique 75: 487-503

12 Tucker SC, Truhlar DG (1989) Generalized born fragment charge model for solvation effects

as a function of reaction coordinate. Chem Phys Lett 157(1-2): 164-170

13 Still WC, Tempczyk A, Hawley RC, Hendrickson T (1990) Semianalytical treatment of

solvation for molecular mechanics and dynamics. J Am Chem Soc 112(16):6127-6129

14 Marenich AV, Olson RM, Kelly CP, Cramer CJ, Truhlar DG (2007) Self-consistent reaction

field model for aqueous and nonaqueous solutions based on accurate polarized partial

charges. J Chem Theory Comput 3(6):2011-2033

22

15 Marenich AV, Cramer CJ, Truhlar DG (2009) Universal solvation model based on the

generalized Born approximation with asymmetric descreening. J Chem Theory Comput

5(9):2447-2464

16 Marenich AV, Cramer CJ, Truhlar DG (2009) Universal solvation model based on solute

electron density and a continuum model of the solvent defined by the bulk dielectric constant

and atomic surface tensions. J Phys Chem B 113(18):6378-6396

17 Tomasi J, Mennucci B, Cancès E (1999) The IEF version of the PCM solvation method: an

overview of a new method addressed to study molecular solutes at the QM ab initio level. J

Mol Struct (Theochem) 464(1):211-226

18 Grycuk T (2003) Deficiency of the coulomb-field approximation in the generalized Born

model: an improved formula for Born radii evaluation. J Chem Phys 119(9):4817-4826

19 Storer JW, Giesen DJ, Cramer CJ, Truhlar DG (1995) Class IV charge models: a new

semiempirical approach in quantum chemistry. J Comp-Aided Mol Des 9:87-110

20 Kelly CP, Cramer CJ, Truhlar DG (2005) SM6: A density functional theory continuum

solvation model for calculating aqueous solvation free energies of neutrals, ions, and solute-

water clusters. J Chem Theory Comput 1(6):1133-1152

21 Olson RM, Marenich AV, Cramer CJ, Truhlar DG (2007) Charge Model 4 and

intramolecular charge polarization. J Chem Theory Comput 3(6):2046-2054

22 Baldridge K, Klamt A (1997) First principles implementation of solvent effects without

outlying charge error. J Chem Phys 106:6622-6633

23 Marenich AV, Cramer CJ, Truhlar DG (2009) Performance of SM6, SM8, and SMD on the

SAMPL1 test set for the prediction of small-molecule solvation free energies. J Phys Chem B

113(14):4538-4543

23

24 Zhao Y, Truhlar DG (2008) The M06 suite of density functionals for main

group thermochemistry, kinetics, noncovalent interactions, excited states, and transition

elements: two new functionals and systematic testing of four M06 functionals and twelve

other functionals. Theor Chem Acc 120:215-241

25 Francl MM, Pietro WJ, Hehre WJ, Binkley JS, Gordon MS, DeFrees DJ, Pople JA (1982)

Self-consistent molecular orbital methods. XXIII. A polarization-type basis set for second-

row elements. J Chem Phys 77:3654-3666

26 Hariharan PC, Pople JA (1973) The influence of polarization functions on molecular orbital

hydrogenation energies. Theoret Chimica Acta 28(3):213-222

27 Lynch BJ, Zhao Y, Truhlar DG (2003) Effectiveness of diffuse basis functions for

calculating relative energies by density functional theory. J Phys Chem A 107(9):1384-1388

28 Bryantsev VS, Diallo MS, Goddard WA (2008) Calculation of solvation free energies of

charged solutes using mixed cluster/continuum models. J Phys Chem B 112:9709-9719

29 Lynch BJ, Zhao Y, Truhlar DG (2005) The 6-31B(d) basis set and the BMC-QCISD and

BMC-CCSD multicoefficient correlation methods. J Phys Chem A 109(8):1643-1649

30 Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Montgomery

Jr JA, Vreven T, Kudin KN, Burant JC, Millam JM, Iyengar SS, Tomasi J, Barone V,

Mennucci B, Cossi M, Scalmani G, Rega N, Petersson GA, Nakatsuji H, Hada M, Ehara M,

Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Klene

M, Li X, Knox JE, Hratchian HP, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R,

Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Ayala PY,

Morokuma K, Voth GA, Salvador P, Dannenberg JJ, Zakrzewski VG, Dapprich S, Daniels

AD, Strain MC, Farkas O, Malick DK, Rabuck AD, Raghavachari K, Foresman JB, Ortiz JV,

24

Cui Q, Baboul AG, Clifford S, Cioslowski J, Stefanov BB, Liu G, Liashenko A, Piskorz P,

Komaromi I. Martin RL, Fox DJ, Keith T, Al-Laham MA, Peng CY, Nanayakkara A,

Challacombe M, Gill PMW, Johnson B, Chen W, Wong MW, Gonzalez C, Pople JA,

Gaussian03, revision E.01, Gaussian, Inc., Pittsburgh, PA, 2003.

31 MN-GFM: Minnesota Gaussian Functional Module, version 4.1; University of Minnesota:

Minneapolis, MN, 2008

32 MN-GSM: Minnesota Gaussian Solvation Module, version 2009; University of Minnesota:

Minneapolis, MN, 2009

33 Halgren TA (1996) Merck molecular force field. I. Basis, form, scope, parameterization, and

performance of MMFF94. J Comp Chem 17(5):490-519

34 PCModel, version 9.1 for Windows, 2006, Serena Software, Bloomington, IN 47402

35 Adamo C, Barone V (1998) Exchange functionals with improved long-range behavior and

adiabatic connection methods without adjustable parameters: The mPW and mPW1PW

models. J Chem Phys 108(2):664-676

36 Easton RE, Giesen DJ, Welch A, Cramer CJ, Truhlar DG (1996) The MIDI! basis set for

quantum mechanical calculations of molecular geometries and partial charges. Theor Chim

Acta 93(5):281-301

37 Kelly CP, Cramer CJ, Truhlar DG (2006) Adding explicit solvent molecules to continuum

solvent calculations for the calculation of aqueous acid dissociation constants. J Phys Chem

A 110(7):2493-2499

38 Ribeiro RF, Marenich AV, Cramer CJ, Truhlar DG (2009) Solvent dependence of 14N

nuclear magnetic resonance chemical shielding constants as a test of the accuracy of the

25

computed polarization of solute electronic densities by the solvent. J Chem Theory Comput

5(9):2284-2300

39 Katritzky AR, Øksne S, Boulton AJ (1962) The tautomerism of heteroaromatic compounds

with five-membered rings – III: Further isoxazol-5-ones. Tetrahedron 18(6):777-790

26

TABLE 1: Aqueous free energies of solvation (kcal/mol) for the obscure and explanatory

SAMPL-09 sets a

compound SM8 SM8AD SMD expobscure subset

uracil –16.76 –16.56 –14.15 –16.59 ± 0.285-bromouracil –16.39 –16.74 –14.09 –18.17 ± 0.555-chlorouracil –16.59 –14.09 –14.34 –17.74 ± 0.785-fluorouracil –17.38 –16.69 –13.88 –16.92 ± 0.885-trifluoromethyluracil –16.52 –16.30 –13.46 –15.46 ± 0.166-chlorouracil –14.24 –14.09 –11.32 –15.83 ± 1.22cyanuric acid –20.32 –17.90 –14.77 –18.26 ± 0.27caffeine –11.90 –12.36 –10.34 –12.64 ± 0.74methyl paraben –9.85 –11.38 –9.09 –9.51 ± 0.26ethyl paraben –9.50 –10.92 –9.17 –9.20 ± 0.30propyl paraben –9.24 –10.60 –9.01 –9.37 ± 0.22butyl paraben –8.42 –9.54 –8.36 –8.72 ± 0.27acetylsalicylic acid –11.93 –13.98 –11.12 –9.94 ± 0.18diflunisal –13.96 –16.41 –14.38 –9.40 ± 0.20flurbirprofen –9.03 –10.46 –9.26 –8.42 ± 0.16ibuprofen –6.88 –7.54 –7.42 –7.00 ± 0.64ketoprofen –12.56 –16.42 –12.91 –10.78 ± 0.18naproxen –10.90 –12.61 –11.29 –10.21 ± 0.18phthalimide –11.99 –11.75 –8.61 –9.61 ± 0.50sulfolane –13.26 –7.10 –12.29 –8.61 ± 0.31D-glucose –25.29 –29.27 –36.00 –25.47 ± 0.22D-xylose –21.71 –24.98 –28.31 –20.52 ± 0.27MUE 1.28 2.17 2.73

explanatory subset hexachlorobenzene –0.23 –1.01 1.39 –2.30 ± 1.16hexachloroethane –0.04 –0.70 1.24 –1.41 ± 0.10octafluorocyclobutane 3.60 3.82 4.42 3.01 ± 0.03trimethyl o-trifluoroacetate –1.67 –3.61 –0.67 –0.80 ± 0.20trimethyl phosphate –7.46 –10.18 –7.45 –8.70 ± 0.104-nitroaniline –10.48 –12.00 –9.30 –10.01 ± 0.11glycerol b –11.71 –12.20 –11.65 –13.40 ± 1.00pentachloronitrobenzene –1.73 –2.08 1.41 –5.22 ± 0.25MUE 1.47 1.68 2.28 RMSE c 1.78 2.61 3.54 MUE c 1.33 2.04 2.61 MSE c –0.24 –0.95 0.43

27

a Experimental aqueous free energies of solvation (or vacuum-water free energies of transfer)

were provided by OpenEye Scientific Software. Theoretical (SM8, SM8AD, and SMD) aqueous

free energies were calculated using the Cartesian geometries provided by OpenEye Scientific

Software unless noted otherwise. RMSE, MUE, and MSE refer to root mean squared error, mean

unsigned error, and mean signed error, respectively. Note that we excluded 1-iodouracil

originally present in the obscure subset from consideration here because the tested solvation

models were not parameterized for iodine-containing compounds.

b Calculated using a re-optimized geometry as discussed in the text; the aqueous free energies of

solvation calculated using OpenEye’s Cartesian geometries are –17.0 (SM8), –18.8 (SM8AD),

and –21.0 (SMD) kcal/mol.

c Calculated by summation over the 30 compounds of the obscure and explanatory subsets (see

also a comment on 1-iodouracil in footnote a)

28

TABLE 2: Aqueous free energies of solvation (kcal/mol) for the investigatory SAMPL2 set a

compound SM8 SM8AD SMDhexamethylphosphoramide –7.47 –9.91 –10.19dimethyl methylphosphonate –9.53 –11.22 –10.09methyl dimethylphosphinate –9.79 –12.34 –12.81methyl phenyl sulfoxide –11.53 –10.24 –9.21trifluoromethyl phenyl sulfoxide –7.63 –5.52 –4.76methyl phenyl sulfone –13.55 –8.54 –11.79trifluoromethyl phenyl sulfone –8.32 –2.11 –5.20oxazole –5.94 –4.58 –3.88thiazole –4.86 –4.84 –4.15isothiazole –6.22 –5.92 –3.98

a SM8, SM8AD, and SMD aqueous free energies of solvation (or vacuum-water free energies of

transfer) were calculated using the Cartesian geometries provided by OpenEye Scientific

Software.

29

TABLE 3: Aqueous free energies of solvation (kcal/mol) for selected compounds calculated with

and without adding explicit water molecules a

compound SM8 SM8/C SM8AD SM8AD/C SMD SMD/C exphexachlorobenzene –0.23 –0.78 –1.01 –1.29 1.39 0.81 –2.30hexachloroethane -0.04 –1.65 –0.70 –2.03 1.24 –0.64 –1.41octafluorocyclobutane 3.60 4.55 3.82 4.52 4.42 4.05 3.01trimethyl o-trifluoroacetate –1.67 –1.50 –3.61 –3.23 –0.67 –1.34 –0.80trimethyl phosphate –7.46 –7.15 –10.18 –11.17 –7.45 –8.66 –8.704-nitroaniline –10.48 –12.81 –12.00 –14.77 –9.30 –10.62 –10.01pentachloronitrobenzene –1.73 –0.70 –2.08 –0.86 1.41 1.90 –5.22MUE 1.47 1.61 1.68 2.45 2.28 1.65

a Experimental aqueous free energies (exp) of solvation (or vacuum-water free energies of

transfer) were provided by OpenEye Scientific Software. The SM8, SM8AD, and SMD aqueous

free energies of solvation for unclustered solutes were calculated without adding explicit water

molecules. The SM8/C, SM8AD/C, and SMD/C aqueous free energies of solvation for

unclustered solutes were calculated by Eq. 2 using the calculated free energies of solvation of the

corresponding water-solute clusters. MUE refers to mean unsigned error.

30

TABLE 4: Free energy difference (kcal/mol) for tested tautomeric pairs in the obscure and

explanatory subsets a

tautomeric pair gas SM8 SM8AD SMD exp b obscure subset

case 1 1A_1B –3.5 –1.7 –3.0 –1.9 –4.8 ± 0.32A_2B –8.3 –5.1 –6.1 –5.7 –6.1 ± 0.33A_3B –4.4 –5.7 –6.7 –6.6 –7.2 ± 0.34A_4B 3.2 2.3 0.8 2.3 –2.3 ± 0.4MUE 2.6 1.3 2.1

case 2 5A_5B –4.7 –3.4 –4.4 –2.8 –4.8 ± 0.55B_5C 8.7 1.0 1.5 1.9 0.5 ± 0.2MUE 0.9 0.7 1.7

case 3 6A_6Z 10.7 2.0 0.8 2.0 –2.4 ± 0.36A_6B –10.7 –8.4 –9.7 –9.5 –9.2 ± 0.4MUE 2.6 1.9 2.3

explanatory subset case 4

7A_7B 9.3 7.1 6.5 6.8 7.0 ± 1.58A_8B –4.2 –2.9 –2.9 –2.9 –3.0 ± 3.0MUE 0.1 0.3 0.1

case 5 10B_10C 2.5 1.1 0.0 0.9 –2.9 ± 0.410D_10C 3.1 4.5 2.6 4.1 –1.2 ± 0.211D_11C 4.9 5.8 4.0 4.5 –0.5 ± 0.212D_12C 6.9 5.3 3.1 3.7 –1.8 ± 0.713D_13C 3.2 4.8 3.3 3.5 0.1 ± 0.114D_14C 3.1 2.0 0.8 2.1 0.3 ± 0.315A_15B 4.4 3.1 3.6 3.0 0.9 ± 0.315A_15C 5.3 2.9 2.3 2.0 –1.2 ± 0.315B_15C 0.9 –0.2 –1.2 –1.0 –2.2 ± 0.316A_16C 3.1 0.4 0.4 1.8 0.5 ± 0.1MUE 3.8 2.7 3.3

case 6 17F_17B 8.1 4.3 3.6 2.3 3.4 RMSE c 3.4 2.4 3.0

MUE c 2.7 1.8 2.4

MSE c 2.7 1.7 2.3

31

Footnote to TABLE 4

a Notations used in the table for tautomeric pairs refer to the notations given in the SAMPL2

manual. For example, the notation M1_M2 refers to the free energy of the M1 → M2 reaction

defined as the difference between the free energy of tautomer M2 and the free energy of

tautomer M1. The SM8, SM8AD, and SMD free energy differences between two tautomeric

forms in aqueous solution were calculated using the SM8, SM8AD, and SMD continuum

solvation models, respectively. The free energy difference between two tautomeric forms in the

gas phase was calculated as well (“gas”). MUE refers to mean unsigned error.

b SAMPL2 reference data evaluated from the corresponding experimental tautomeric ratios in

aqueous solution and provided by OpenEye Scientific Software.

c RMSE, MUE, and MSE refer to root mean squared error, mean unsigned error, and mean

signed error, respectively, calculated over all 21 data.

32

TABLE 5: Comparison of the free energy difference (kcal/mol) for selected tautomeric pairs

calculated using the M06-2X/MG3S and BMC-CCSD//M06-2X/MG3S methods a

tautomeric pair M06-2X/MG3S BMC-CCSD//M06-2X/MG3S exp b gas SM8 SM8AD SMD gas SM8 SM8AD SMD

case 3 6A_6Z 10.7 2.0 0.8 2.0 13.5 4.7 3.6 4.7 –2.4 ± 0.36A_6B –10.7 –8.4 –9.7 –9.5 –15.9 –13.5 –14.8 –14.6 –9.2 ± 0.4MUE 2.6 1.9 2.3 5.8 5.7 6.3

case 5 10B_10C 2.5 1.1 0.0 0.9 2.4 1.0 –0.1 0.8 –2.9 ± 0.410D_10C 3.1 4.5 2.6 4.1 3.3 4.6 2.8 4.3 –1.2 ± 0.211D_11C 4.9 5.8 4.0 4.5 5.0 5.9 4.2 4.6 –0.5 ± 0.212D_12C 6.9 5.3 3.1 3.7 6.8 5.2 3.1 3.6 –1.8 ± 0.713D_13C 3.2 4.8 3.3 3.5 3.4 5.0 3.5 3.7 0.1 ± 0.114D_14C 3.1 2.0 0.8 2.1 3.8 2.7 1.5 2.8 0.3 ± 0.315A_15B 4.4 3.1 3.6 3.0 5.2 3.9 4.4 3.8 0.9 ± 0.315A_15C 5.3 2.9 2.3 2.0 6.2 3.8 3.3 3.0 –1.2 ± 0.315B_15C 0.9 –0.2 –1.2 –1.0 1.0 0.0 –1.1 –0.9 –2.2 ± 0.316A_16C 3.1 0.4 0.4 1.8 4.5 1.8 1.8 3.3 0.5 ± 0.1MUE 3.8 2.7 3.3 4.2 3.1 3.7

a See footnote a to Table 4 and the main text for more detail

b See footnote b to Table 4

33

TABLE 6: Free energy difference (kcal/mol) for tested tautomeric pairs in the investigatory

subset a

tautomeric pair gas SM8 SM8AD SMDcase 7

19A.h_19B.h 1.5 0.5 0.4 0.120A.ch2_20B.ch2 4.9 1.2 0.7 0.220A.o_20B.o 2.8 –0.2 –0.7 0.220A.s_20B.s 2.3 –1.8 –2.4 –1.820A.nch3_20B.nch3 4.7 1.8 1.5 2.921A_21B 13.9 13.0 12.7 12.7

case 8 22A_22B –10.1 –10.0 –11.5 –11.323A_23B –11.7 –10.9 –12.5 –11.824A_24B –21.8 –12.8 –14.1 –13.525A_25B –25.5 –15.1 –16.7 –14.226A_26B –19.8 –15.6 –17.1 –16.2

case 9 27A.o_27B.o –0.9 –1.0 –0.1 –0.227A.o_27C.o 0.4 –1.0 –0.3 –0.227A.o_27D.o 13.4 7.1 7.8 7.227A.s_27B.s 0.2 0.3 0.2 2.127A.s_27C.s 14.1 6.4 4.8 6.527A.s_27D.s 16.5 10.9 9.4 11.327A.nh_27B.nh –0.8 –0.4 –0.2 –0.427A.nh_27C.nh 1.5 0.6 1.0 0.627A.nh_27D.nh 1.8 1.5 1.5 0.5

case 10 28A_28B 0.1 0.4 0.6 0.529A_29B 3.7 –0.8 –0.1 0.130A_30B –4.0 –4.0 –3.0 –3.531A_31B –2.3 –6.9 –5.8 –5.9

case 11 32A_32B –9.3 –9.6 –8.9 –8.633A_33B 11.2 10.0 10.5 10.634A_34B 5.1 4.5 5.0 4.7

34

TABLE 6: Continued a

tautomeric pair gas SM8 SM8AD SMDcase 12

35C.nch3_35A.nch3 –0.3 2.4 2.8 1.535A.nch3_35B.nch3 6.4 5.9 6.4 5.435C.o_35A.o 1.8 4.8 5.0 4.235A.o_35B.o 9.0 8.9 8.8 8.135C.s_35A.s 2.8 4.7 4.9 4.435A.s_35B.s 3.2 2.6 2.3 1.8

a See footnote a to Table 4 and the main text for more detail

35

hexachlorobenzene hexachloroethane

octafluorocyclobutane trimethyl o-trifluoroacetate

trimethyl phosphate 4-nitroaniline

pentachloronitrobenzene

Figure1: Water-solute clusters for selected solutes involved in Task 1.

36

case 1

1A 1B 2A

2B 3A 3B

4A 4B

case 2

5A 5B 5C

37

case 3

6A 6B 6Z

case 4

7A 7B 8A 8B

case 5

10B 10C 10D

11C 11D 12C

38

12D 13C 13D

14C 14D 15A

15B 15C 16A

16C

39

case 6

17B 17F

case 7

19A 19B 20A-CH2

20A-NCH3 20A-O 20A-S

20B-CH2 20B-NCH3 20B-O

40

20B-S 21A 21B

case 8

22A 22B 23A

24B 25A 25B

26A 26B

41

case 9

27A-NH 27A-O 27A-S

27B-NH 27B-O 27B-S

27C-NH 27C-O 27C-S

27D-NH 27D-O 27D-S

42

case 10

28A 28B 29A

29B 30A 30B

31A 31B

case 11

32A 32B 33A

43

33B 34A 34B

case 12

35A-NCH3 35A-O 35A-S

35B-NCH3 35B-O 35B-S

35C-NCH3 35C-O 35C-S Figure 2: Molecular structures for solutes involved in Task 2.

1

Electronic supplementary information (ESI)

For

Reactivity of Copper(II)-Alkylperoxo Complexes

Tetsuro Tano,a Mehmed Z. Ertem,b Satoru Yamaguchi,c Atsushi Kunishita,a Hideki Sugimoto,a

Nobutaka Fujieda,a Takashi Ogura,*c Christopher J. Cramer*b and Shinobu Itoh*a

aDepartment of Material and Life Science, Division of Advanced Science and Biotechnology,

Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, Suita, Osaka 565-0871, Japan.

E-mail: shinobu@mls.eng.osaka-u.ac.jp bDepartment of Chemistry and Research Computing Center, University of Minnesota, 207 Pleasant

St. SE, Minneapolis, MN 55455, USA. E-mail: cramer@umn.edu cResearch Institute of Picobiology, Graduate School of Life Science, University of Hyogo, 3-2-1

Kouto, Kamigori-cho, Ako-gun, Hyogo 678-1297, Japan. E-mail: ogura@sci.u-hyogo.ac.jp

2

Fig. S1

2.0

1.5

01

[CmOOH] / mM

Abs

388

0 2

0.5

1.0

3

(a)

4

8

6

2

00 2 4 6 10

104{[CmOOH]0–[Cu]0(A–A0)/(A∞–A0)} / M

(A–A

0)/(A

∞–A

)

4

(b)

8

Fig. S1. (a) Spectrophotometric titration for the formation of cumylperoxo copper(II) complex from the reaction of 1aH (1.0 mM) and CmOOH in the presence of Et3N (10 mM) in CH3CN at –40ºC. (b) Plot of (A – A0)/(A∞ – A) against [[CmOOH]0–[Cu]0(A – A0) /(A∞ – A0)].

3

Fig. S2 and S3

1.0

0.8

0.6

0300 500 800 1000

430

Wavelength / nm

Ab

so

rban

ce

400 600 700 900

0.2

0.4

Fig. S2 Spectral change for the reaction of 1b (1.0 mM) with CmOOH (2.5 mM) in the presence of Et3N (10 mM) in CH3CN at –40ºC.

0.8

0.6

01

[CmOOH] / mM

Abs

43

0

0 2

0.2

0.4

(a)

60

40

20

00 4 6 8

104{[CmOOH]0–[Cu]0(A–A!)/(A!–A0)} / M

(A–A

0)/

(A!–A

)

(b)

2

Fig. S3 (a) Spectrophotometric titration for the formation of cumylperoxo copper(II) complex from the reaction of 1b (1.0 mM) and CmOOH in the presence of Et3N (10 mM) in CH3CN at –40ºC. (b) (A – A0)/(A∞ – A) against {[CmOOH]0–[Cu]0(A – A0) /(A∞ – A0)}.

4

Fig. S4

500 505 510 515

m /z

504.2

EXP.

500 505 510 515

SIM.

500 505 510 515

m /z

508.2

EXP.

500 505 510 515

SIM.

506.2

510.2

m /z m /z

(a) (b)

Fig. S4 Experimental (bottom) and simulated (top) peak envelopes in the positive-ion ESI-MS spectra of the product derived from the reaction of 1b (1.0 mM) with CmOOH (1.0 mM) in the presence of Et3N (1.0 mM) in CH3CN at –40ºC; (a) with Cm16O2H and (b) with Cm18O2H.

5

Fig. S5

858

589

600 900

528

Wavenumber / cm–1

500 700 800

797

S

879

607535

832

S

400

Fig. S5 Resonance Raman spectra of the product derived from the reaction of 1b (4.0 mM) with CmOOH (12 mM) in the presence of Et3N (40 mM) generated by using Cm16O2H (solid line, below) and Cm18O2H (doted line, above) obtained with λex = 441.6 nm in CH3CN –40℃; s denotes the solvent band.

6

Fig. S6

Fig. S6 (a) ESR spectrum of 1b (starting material) (2.0 x 10–3 M) in CH3CN at –196℃. ESR parameter g⊥ = 2.112. (b) ESR spectrum of the 2b generated in the reaction of 1b (2.0 x 10–3 M) and CmOOH (1.0 x 10–2 M) in the presence of Et3N (2.0 x 10–3 M) in CH3CN at –196℃. ESR parameters g⊥ = 2.118. Low resolution of the spectrum prohibits precise assignment of the g// value.

7

Fig. S7

350 360 370 380

m / z

352.2

354.2

369.2

378.2

371.2

(a)

(b)

(c)

380.2

Figure S7. ESI-MS (pos.) spectrum after the self-decomposition of 2aH in CH3CN. (a) m/z =

352.2 ([CuI(bpaH)]+), (b) m/z = 369.2 ([CuII(bpaH)(OH)]+), (c) m/z = 378.2 ([CuII(bpaH)(CN)]+).

8

Fig. S8

Fig. S8 HPLC diagram of the self-decomposition products of 2a. Peak 1: cumyl alcohol (CmOH); peak 2: acetophenone (PhCOMe); peak 3: anisole (internal standard material).

9

Fig. S9

Fig. S9 HPLC diagram of the self-decomposition products of 2b. Peak 1: cumyl alcohol (CmOH); peak 2: acetophenone (PhCOME); peak 3: anisole (internal standard material).

10

Fig. S10

350 360 370 380

m / z

351.8

353.8

368.8

377.8

(a)

(b)

(c)

Fig. S10 ESI-MS (pos.) spectrum of the final reaction mixture of 2a and CHD. (a) m/z = 351.8 ([CuI(bpa)]+), (b) m/z = 368.8 ([CuII(bpa)(OH)]+), (c) m/z = 377.8 ([CuII(bpa)(CN)]+).

11

Fig. 11

Fig. S11 HPLC diagram of the products derived from the reaction of 2a and CHD. Peak 1: cumyl alcohol (CmOH); peak 2: acetophenone (PhCOMe) ; peak 3: anisole (internal standard material); peak 4: benzene.

12

Fig. S12

Fig. S12 HPLC diagram of the products of derived from the reaction of 2b and CHD. Peak 1: cumyl alcohol (CmOH); peak 2: acetophenone (PhCOMe); peak 3: anisole (internal standard material); peak 4: benzene.

13

Fig. S13

0.5

0.3

0300 500 800

430

Wavelength / nm

Ab

so

rban

ce

400 600 700

0.1

900 1000

0.4

0.2

0.6

–2.5

4000Time / s

ln(A

-A!)

0

–2

2000 30001000

(a)

1.5

0.5

00 0.10

[CHD] / M

10

3k

ob

s /

s–1

0.05 0.15

1.0

(b)

Fig. S13 (a) Spectral change for the reaction of 2b (1.0 mM) and CHD (30 mM) in CH3CN at 30 °C under anaerobic conditions; Inset: the pseudo-first-order plot based on the absorption change at 430 nm. (b) Plots of kobs vs substrate concentration for the reaction of 2b with CHD.

14

DFT calculation results

I – Cartesian Coordinates (ang) and Energies (Eh, doublet electronic states)

1) – [CuII(bpa)(CH3CN)]2+

Energy: -1229.29162036 a.u.

C -1.90034300 -2.91672300 -0.40538600 C -1.59170000 -4.26747700 -0.36107500 C -0.40265500 -4.66204100 0.24649700 C 0.43989600 -3.69295600 0.78585100 C 0.06858400 -2.35762000 0.71358200 N -1.09166900 -1.98149700 0.12370600 H -0.12953700 -5.71357900 0.29426500 H -2.81073400 -2.55225200 -0.87499000 H -2.27131500 -4.99213000 -0.80015800 H 1.37853200 -3.96789800 1.26247100 C 0.87213900 -1.23935700 1.30959800 H 0.54770700 -1.06208700 2.34422700 H 1.94450600 -1.47578500 1.34735200 N 0.63393900 -0.00040100 0.53733000 C 0.87280900 1.23811200 1.31010500 H 1.94531500 1.47388400 1.34805200 H 0.54817300 1.06063000 2.34463500 C 0.06999200 2.35709000 0.71443600 C 0.44209100 3.69217800 0.78726000 N -1.09039500 1.98187900 0.12424800 C -0.39978800 4.66196100 0.24811400 H 1.38081200 3.96638300 1.26413500 C -1.89840300 2.91777600 -0.40466900 C -1.58895200 4.26832800 -0.35983200 H -0.12605100 5.71331900 0.29631300 H -2.80889200 2.55398500 -0.87462300 H -2.26802500 4.99355100 -0.79881100 C 1.36894100 -0.00033000 -0.79820300 H 1.00873500 0.88597000 -1.33590000 H 1.00851100 -0.88640500 -1.33612000 C 2.85992800 -0.00051800 -0.67821900 C 3.56836700 -1.20840500 -0.62993200 C 3.56862400 1.20720300 -0.62956500 C 4.95494000 -1.20899200 -0.52056300 H 3.03064500 -2.15485400 -0.71707800 C 4.95519500 1.20746700 -0.52019500 H 3.03110000 2.15379200 -0.71642200 C 5.64781700 -0.00084500 -0.45865300 H 5.49832700 -2.15071100 -0.50057500 H 5.49878100 2.14906400 -0.49992000 H 6.73242500 -0.00097200 -0.37991100 Cu -1.35882000 0.00029300 0.06167500 C -4.47374600 0.00129900 -0.47138200 N -3.31836200 0.00092300 -0.34882800 C -5.90467000 0.00155800 -0.62851100 H -6.34141000 -0.86207000 -0.11530300 H -6.33216900 0.91470300 -0.20031500

15

H -6.16863700 -0.04761200 -1.69063000

2) – [CuII(bpa)(CH3CN)2]2+

Energy: -1362.07096036 a.u.

C -1.52792500 -2.94647400 -0.90498000 C -1.18817200 -4.29052200 -0.85294900 C -0.06691300 -4.66756600 -0.11959300 C 0.67576800 -3.68832400 0.53477400 C 0.27366900 -2.36197800 0.44662200 N -0.81735900 -2.00231200 -0.26853200 H 0.23157600 -5.71177200 -0.06376000 H -2.38917600 -2.59655700 -1.46923200 H -1.78991300 -5.02237600 -1.38419700 H 1.56218700 -3.94695500 1.11049900 C 0.97261400 -1.23575100 1.15019600 H 0.49927300 -1.06452000 2.12687700 H 2.03318700 -1.45904600 1.33316500 N 0.81515300 0.00004100 0.35866700 C 0.97284900 1.23580200 1.15021100 H 2.03346400 1.45891400 1.33315000 H 0.49949500 1.06467400 2.12690200 C 0.27407000 2.36214600 0.44666700 C 0.67652000 3.68840000 0.53465600 N -0.81720600 2.00271500 -0.26823600 C -0.06606800 4.66778600 -0.11960100 H 1.56312300 3.94684000 1.11017900 C -1.52773100 2.94702300 -0.90453200 C -1.18761900 4.29098900 -0.85263700 H 0.23270800 5.71192000 -0.06391500 H -2.38924800 2.59733400 -1.46850700 H -1.78933800 5.02296300 -1.38375000 C 1.67537000 -0.00003300 -0.89088100 H 1.37109300 0.88472100 -1.46376300 H 1.37086600 -0.88466200 -1.46383000 C 3.14915600 -0.00022000 -0.62538300 C 3.84942700 -1.20695300 -0.50456200 C 3.84970200 1.20634400 -0.50448400 C 5.21800900 -1.20800200 -0.25440400 H 3.32188600 -2.15305900 -0.64315900 C 5.21828400 1.20706800 -0.25432900 H 3.32237900 2.15257900 -0.64302300 C 5.90153200 -0.00054900 -0.12319700 H 5.75596800 -2.15006800 -0.17792900 H 5.75645900 2.14900600 -0.17779500 H 6.97269300 -0.00067700 0.06474300 Cu -1.15835700 0.00023600 -0.23095700 C -3.90340500 0.00012300 -1.83264800 N -2.90084000 0.00034100 -1.24662100 C -2.61457200 -0.00033600 2.87691700 N -1.99571200 -0.00036500 1.89108200 C -3.37866100 -0.00012000 4.10199700 H -4.11557000 -0.80988100 4.09071600 H -2.71848700 -0.14289600 4.96384300 H -3.90609900 0.95193800 4.22141500 C -5.14643600 -0.00006300 -2.56204200 H -5.70610100 -0.91911100 -2.35782900

16

H -5.76148600 0.85574900 -2.26394400 H -4.95363800 0.06242500 -3.63850700

3) – [CuII(bpa)(CH3CN)(O2Cm)]+

3a (structure i in Figure 8)

Energy: -1729.49998905 a.u.

C -1.01104800 3.28802300 -1.24670200 C -1.90923300 4.30272900 -1.55229900 C -3.21226600 4.20607300 -1.07295100 C -3.57473500 3.10311300 -0.30447300 C -2.61912500 2.13216800 -0.02698700 N -1.36138000 2.23429400 -0.49830700 H -3.94414900 4.97745700 -1.30288000 H 0.02121300 3.27866100 -1.59603100 H -1.59249600 5.14376800 -2.16296900 H -4.58783800 2.99173500 0.07836700 C -2.88753800 0.92675000 0.83412000 H -2.59616300 1.15783100 1.86760400 H -3.95880000 0.67232600 0.84318200 N -2.05228500 -0.19582000 0.38968600 C -1.79495800 -1.19727300 1.42823200 H -2.64644900 -1.88073900 1.57260900 H -1.64612900 -0.65526000 2.37162100 C -0.54062700 -1.96115500 1.09955400 C -0.35450900 -3.28322600 1.48707500 N 0.41279200 -1.28028800 0.42525400 C 0.84694900 -3.91920600 1.18742800 H -1.14919000 -3.80332200 2.01939700 C 1.56217900 -1.90292300 0.11946600 C 1.82239200 -3.21611700 0.48961900 H 1.01089600 -4.95266200 1.48556300 H 2.27869800 -1.30733500 -0.44294400 H 2.77382900 -3.66730400 0.21937300 C -2.54163800 -0.80338500 -0.89077400 H -1.76961400 -1.51743200 -1.20596900 H -2.54947400 0.00760500 -1.63099700 C -3.88525500 -1.46690900 -0.80671300 C -5.05563800 -0.74267500 -1.06079200 C -3.99311200 -2.81913400 -0.46247000 C -6.30393400 -1.34943600 -0.95735400 H -4.98198500 0.30276900 -1.36751700 C -5.23976500 -3.42890100 -0.35735000 H -3.08538700 -3.40415700 -0.30041200 C -6.39715100 -2.69257600 -0.60005400 H -7.20520100 -0.77720200 -1.16781300 H -5.30841300 -4.48352300 -0.09839300 H -7.37199000 -3.16976500 -0.52515800 Cu -0.13110700 0.65587200 -0.03812600 C 0.58630500 1.88013500 3.11528300 N -0.10665300 1.32530900 2.36004200 C 1.45433200 2.56683100 4.04575500 H 1.78696100 3.51998100 3.62155200 H 0.93039400 2.76698400 4.98593700 H 2.33731400 1.95554300 4.26011100

17

O 1.34149800 1.60085400 -0.74757800 O 2.41217100 0.73060300 -1.07971100 C 3.62805300 1.07842900 -0.32958300 C 3.30777700 1.21161100 1.14876700 H 2.84857300 0.29780300 1.54975500 H 4.21589000 1.42850200 1.72302600 H 2.60491300 2.03834300 1.28239200 C 4.16427500 2.39457400 -0.87786200 H 5.08690400 2.68461000 -0.36198700 H 4.38319700 2.31534800 -1.94742100 H 3.41844200 3.18464700 -0.73490900 C 4.53321600 -0.09410000 -0.66424600 C 5.14473600 -0.87922400 0.31737700 C 4.72836800 -0.43414200 -2.00972500 C 5.93886100 -1.96912800 -0.03505600 H 5.01018100 -0.64232100 1.37139700 C 5.50957700 -1.52904500 -2.36209700 H 4.24478600 0.15891700 -2.78422900 C 6.12042400 -2.29988400 -1.37461500 H 6.41849600 -2.55992000 0.74359300 H 5.64616900 -1.77919200 -3.41253400 H 6.74037800 -3.15108600 -1.64952800

3b

Energy: -1729.50013576 a.u.

C 0.94054800 3.53998900 0.14988500 C 1.81482300 4.61441500 0.25425200 C 3.13504400 4.44185400 -0.15017300 C 3.53807200 3.20618500 -0.65048600 C 2.60527100 2.18030000 -0.73884600 N 1.33095500 2.35641200 -0.33991700 H 3.84805100 5.25967400 -0.07189200 H -0.10549400 3.58800700 0.45114300 H 1.46537100 5.56310700 0.65211800 H 4.56372500 3.03641400 -0.97339500 C 2.90520200 0.82712200 -1.32450000 H 2.60032000 0.82508800 -2.38071600 H 3.98400400 0.60977700 -1.30650400 N 2.11784800 -0.20501900 -0.63317700 C 1.84557100 -1.38793800 -1.46011600 H 2.70706100 -2.07177000 -1.51143500 H 1.65603000 -1.03826900 -2.48519400 C 0.61993000 -2.09471900 -0.94981000 C 0.47892100 -3.47693600 -0.98767100 N -0.35948700 -1.29494800 -0.47714700 C -0.70678800 -4.05133500 -0.53811400 H 1.29248000 -4.09078600 -1.37017900 C -1.49277100 -1.85199100 -0.02456600 C -1.71111400 -3.22353300 -0.04845500 H -0.83874600 -5.13088100 -0.56370000 H -2.24019000 -1.15141300 0.34680000 H -2.65445000 -3.62238600 0.31568800 C 2.69254100 -0.55952100 0.70798600 H 1.95820100 -1.21691400 1.18913100 H 2.69691700 0.36989800 1.29089400 C 4.05298600 -1.19038700 0.66752100

18

C 5.20788600 -0.40151600 0.72746200 C 4.19492200 -2.57942200 0.56741500 C 6.47130800 -0.98222600 0.66955100 H 5.11078200 0.67934100 0.84883800 C 5.45658300 -3.16411200 0.50900700 H 3.30251200 -3.20878100 0.56461600 C 6.59661900 -2.36479200 0.55426600 H 7.35994300 -0.35693800 0.72749500 H 5.55143400 -4.24601100 0.44140300 H 7.58352500 -2.82096500 0.51531400 Cu 0.17657600 0.68342000 -0.29641700 C -1.00587300 0.65344600 2.63880700 N 0.01863200 0.44766800 2.12096000 C -2.28586600 0.92084600 3.25287300 H -2.21077100 0.88977000 4.34454600 H -2.63797800 1.91027300 2.94258700 H -3.02329500 0.18197800 2.91889600 O -1.38403800 1.77560700 -0.27091000 O -2.52120200 1.02895900 0.13420000 C -3.53270200 0.99049000 -0.94014300 C -2.90842300 0.50839700 -2.23723400 H -2.46334200 -0.48823800 -2.13590700 H -3.66099500 0.46732300 -3.03233800 H -2.12570900 1.20642700 -2.54602800 C -4.09004800 2.39678800 -1.11534200 H -4.87023400 2.41156000 -1.88458200 H -4.52486500 2.77367700 -0.18380700 H -3.28502400 3.07405300 -1.41985300 C -4.55046000 0.03291100 -0.34525600 C -4.91744000 -1.16251100 -0.96973300 C -5.11284600 0.32868000 0.90407700 C -5.82202400 -2.03467700 -0.36598700 H -4.50548200 -1.41926200 -1.94405900 C -6.00661400 -0.54480300 1.51426900 H -4.84350400 1.26049500 1.40044600 C -6.36490600 -1.73271800 0.87909900 H -6.10689100 -2.95269500 -0.87722200 H -6.43552500 -0.29260100 2.48268800 H -7.07241100 -2.41317300 1.34870900

3c

Energy: -1729.49282065 a.u.

C -0.05486100 3.27751000 -0.75459200 C -0.63394100 4.35456700 -1.41169000 C -2.02118700 4.40757300 -1.51024000 C -2.78381900 3.38938100 -0.94477000 C -2.13825000 2.34707100 -0.29044100 N -0.79240000 2.29958000 -0.21156600 H -2.50684500 5.23311600 -2.02592800 H 1.02081900 3.16107600 -0.63664800 H -0.00608800 5.13053300 -1.84062700 H -3.87066400 3.40133900 -1.00282500 C -2.86533900 1.23994000 0.42287400 H -2.99816600 1.53334700 1.47287800 H -3.86439500 1.07021800 -0.00586200 N -2.04483600 0.01863600 0.41558600

19

C -2.35517000 -0.91209300 1.51097500 H -3.24049800 -1.52734400 1.29063100 H -2.58851800 -0.30489800 2.39608800 C -1.15276600 -1.76266100 1.82204900 C -1.24426100 -3.03532600 2.37454000 N 0.04160000 -1.18390300 1.58933200 C -0.07376600 -3.70904200 2.71130300 H -2.22127200 -3.48519100 2.54203800 C 1.17139500 -1.82577900 1.91977000 C 1.15429900 -3.09330400 2.48701800 H -0.12122400 -4.70635000 3.14332100 H 2.08801700 -1.28397000 1.69338100 H 2.08841500 -3.58857900 2.73843600 C -2.02375900 -0.65855700 -0.92647800 H -1.27375100 -1.45709400 -0.85332800 H -1.63400500 0.08278600 -1.63644800 C -3.34613400 -1.19828300 -1.38547200 C -4.22057000 -0.39961900 -2.13148500 C -3.73114700 -2.50706200 -1.07253700 C -5.45720800 -0.88972900 -2.54010000 H -3.91434400 0.60937600 -2.41534100 C -4.96722400 -3.00019000 -1.47971000 H -3.04088900 -3.15286100 -0.52594100 C -5.83366500 -2.18965700 -2.20968600 H -6.12321000 -0.26156800 -3.12804200 H -5.25002000 -4.02277200 -1.23851600 H -6.79725100 -2.57656100 -2.53418600 Cu -0.07861300 0.67638800 0.74062200 C 0.17402000 1.63538500 3.52087800 N -0.87427400 1.56208600 3.01191000 C 1.50122400 1.68962200 4.08937300 H 1.76845500 2.71774100 4.35321600 H 1.56491000 1.06797300 4.98813000 H 2.20419500 1.32079100 3.33053900 O 1.74294900 1.16363200 0.95122900 O 2.32537600 0.20650000 -0.00415600 C 3.61163500 0.70222000 -0.46578800 C 3.44332000 2.04337800 -1.15921200 H 3.07848900 2.77672600 -0.43369200 H 4.39871300 2.40987400 -1.55035000 H 2.73064700 1.97489800 -1.99006700 C 4.54879000 0.84425500 0.73157500 H 4.62932700 -0.10051000 1.28188100 H 5.55479100 1.12895600 0.40373800 H 4.17451500 1.61516300 1.41432900 C 4.06812900 -0.41838500 -1.38674000 C 4.13260600 -1.72682400 -0.89035400 C 4.44113000 -0.19431300 -2.71387400 C 4.55777200 -2.77820000 -1.69360200 H 3.84198700 -1.92021800 0.14195300 C 4.87688500 -1.24481800 -3.51898500 H 4.40262900 0.80941000 -3.13193700 C 4.93503600 -2.53930500 -3.01352700 H 4.60147500 -3.78746000 -1.28771800 H 5.17170400 -1.04661700 -4.54779400 H 5.27552000 -3.35896800 -3.64319900

3d

20

Energy: -1729.50175755 a.u.

C -0.69042800 -2.45924800 -1.27012400 C -0.64683600 -3.84761700 -1.29445900 C 0.31813100 -4.49798900 -0.53044600 C 1.20414800 -3.74379800 0.23417900 C 1.09432900 -2.35756700 0.22107800 N 0.15987400 -1.73817300 -0.52688400 H 0.38685900 -5.58375200 -0.53551000 H -1.40921200 -1.87615900 -1.84407800 H -1.34921200 -4.40380500 -1.90938700 H 1.97499800 -4.22161500 0.83661900 C 1.96423800 -1.45467200 1.06010900 H 1.46755300 -1.27876900 2.02333800 H 2.93582300 -1.92610500 1.27486500 N 2.11255600 -0.15241900 0.40018800 C 2.38688100 0.97127500 1.30519000 H 3.43923500 1.00631100 1.62698800 H 1.76822800 0.82382800 2.20082300 C 1.97911600 2.26130100 0.64087700 C 2.60984400 3.47667300 0.88076300 N 0.92816800 2.17567000 -0.20111700 C 2.13983900 4.62127500 0.24277100 H 3.45923900 3.52013100 1.56018700 C 0.48091400 3.27369900 -0.82632600 C 1.05955500 4.52005500 -0.62910800 H 2.61954900 5.58174400 0.41790700 H -0.36326500 3.11335000 -1.49655800 H 0.67252400 5.38875100 -1.15435300 C 3.05861700 -0.20788500 -0.76160800 H 2.96687700 0.75533900 -1.28041400 H 2.66454600 -0.97611700 -1.44004400 C 4.48859800 -0.48854400 -0.40264800 C 4.96796300 -1.80241700 -0.35081100 C 5.36684600 0.55981300 -0.10512400 C 6.28759400 -2.06398700 0.00593000 H 4.30337600 -2.62620500 -0.61929800 C 6.68684900 0.30189500 0.25212100 H 5.01478300 1.59076800 -0.18078300 C 7.14706700 -1.01158600 0.31276100 H 6.64993500 -3.08961800 0.03221000 H 7.36151900 1.12698900 0.47108400 H 8.18062100 -1.21434800 0.58518500 Cu 0.18720700 0.31123100 -0.39813300 C -1.65932500 -0.55278600 2.01413600 N -0.66020900 0.03526300 1.87636000 C -2.88506700 -1.29999200 2.17017500 H -3.20307500 -1.69019200 1.19530500 H -2.74336100 -2.12933800 2.87095900 H -3.68938900 -0.65393000 2.54023700 O -1.31528700 0.68832400 -1.48777700 O -2.47587200 0.12340200 -0.86197500 C -3.50208300 1.15626900 -0.70029000 C -3.00583800 2.23433100 0.24923800 H -2.05220400 2.62336100 -0.11988400 H -3.71111400 3.07110800 0.30419900 H -2.84564200 1.84973400 1.26307000 C -3.83220400 1.74543700 -2.06727000 H -4.12425900 0.95692200 -2.76901300 H -4.66274500 2.45552800 -1.98575200

21

H -2.96008900 2.26543000 -2.47708700 C -4.67575500 0.35960500 -0.15868400 C -5.00973700 -0.86293100 -0.75669500 C -5.44258500 0.80449100 0.92168300 C -6.06276300 -1.63089200 -0.26985000 H -4.42429200 -1.21482100 -1.60496900 C -6.50621800 0.04201600 1.40245400 H -5.21599700 1.75744500 1.39717100 C -6.81347100 -1.18204700 0.81543800 H -6.30490700 -2.58019200 -0.74470900 H -7.09697000 0.40950200 2.23968800 H -7.64168200 -1.77823300 1.19330400

4) – [CuII(bpa)(O2Cm)]+

4a (structure ii in Figure 8)

Energy: -1596.74023326 a.u.

C -1.56188600 -2.19384600 -0.55155500 C -1.68993800 -3.57365500 -0.44945800 C -0.68892500 -4.29320600 0.19439100 C 0.40398400 -3.61402400 0.73014600 C 0.46236400 -2.23237500 0.60591700 N -0.50461400 -1.54683200 -0.03863600 H -0.75544700 -5.37552200 0.28210700 H -2.30583300 -1.56007600 -1.03664400 H -2.56265900 -4.06477900 -0.87112600 H 1.20041000 -4.14733200 1.24624500 C 1.54568700 -1.39146100 1.23524500 H 1.21505500 -1.08664600 2.23876200 H 2.47322700 -1.96826100 1.37189700 N 1.76213900 -0.16783100 0.45119800 C 2.26971300 0.97440900 1.22220000 H 3.35835100 0.92497900 1.37830400 H 1.80503400 0.93315700 2.21808200 C 1.87223700 2.26673100 0.55427800 C 2.64506800 3.41931600 0.61573800 N 0.67804300 2.25550000 -0.07603900 C 2.16751500 4.58607200 0.02386700 H 3.60691900 3.39939100 1.12507300 C 0.21536300 3.37733100 -0.64964400 C 0.93244600 4.56638100 -0.61631600 H 2.75737300 5.49932900 0.05936200 H -0.75956500 3.28740300 -1.12604600 H 0.52746200 5.45556300 -1.09134500 C 2.55641400 -0.42087200 -0.79875500 H 2.51175900 0.50817000 -1.38308100 H 2.00146000 -1.18299600 -1.36219600 C 3.97752200 -0.84513100 -0.57327500 C 4.30858800 -2.19993600 -0.45453100 C 4.99691400 0.10874200 -0.47145000 C 5.62349200 -2.59148200 -0.22045000 H 3.52949900 -2.95530100 -0.57589600 C 6.31250700 -0.27976100 -0.23731200 H 4.75734400 1.16561200 -0.60620200 C 6.62572600 -1.63079700 -0.10596000

22

H 5.86919600 -3.64836700 -0.14103100 H 7.09704800 0.47113700 -0.17126900 H 7.65492100 -1.93628000 0.06969500 Cu -0.16337600 0.43494300 -0.24296600 O -1.77251200 0.73609600 -1.16321700 O -2.51897200 1.86181800 -0.74303600 C -3.33612900 1.52093700 0.42246400 C -4.30916100 2.69077500 0.49604200 H -4.92114100 2.74258600 -0.40988700 H -4.97788200 2.57244000 1.35495100 H -3.76925100 3.63886000 0.60673000 C -2.43749200 1.49605100 1.65260200 H -3.02052900 1.41641400 2.57675600 H -1.74358200 0.64112400 1.63203300 H -1.85608900 2.42399600 1.70494300 C -4.06083200 0.21138500 0.16765700 C -4.21143400 -0.76311300 1.15581400 C -4.60246600 -0.03094900 -1.10065100 C -4.88650300 -1.95442300 0.88614000 H -3.80349300 -0.60352100 2.15292400 C -5.26628100 -1.22075200 -1.37496400 H -4.46932600 0.71454000 -1.88299200 C -5.41162000 -2.18895200 -0.38020700 H -5.00063100 -2.69835900 1.67293200 H -5.67540000 -1.39355700 -2.36876900 H -5.94067400 -3.11661700 -0.59178500

4b

Energy: -1596.73797663 a.u.

C -1.56188600 -2.19384600 -0.55155500 C -1.68993800 -3.57365500 -0.44945800 C -0.68892500 -4.29320600 0.19439100 C 0.40398400 -3.61402400 0.73014600 C 0.46236400 -2.23237500 0.60591700 N -0.50461400 -1.54683200 -0.03863600 H -0.75544700 -5.37552200 0.28210700 H -2.30583300 -1.56007600 -1.03664400 H -2.56265900 -4.06477900 -0.87112600 H 1.20041000 -4.14733200 1.24624500 C 1.54568700 -1.39146100 1.23524500 H 1.21505500 -1.08664600 2.23876200 H 2.47322700 -1.96826100 1.37189700 N 1.76213900 -0.16783100 0.45119800 C 2.26971300 0.97440900 1.22220000 H 3.35835100 0.92497900 1.37830400 H 1.80503400 0.93315700 2.21808200 C 1.87223700 2.26673100 0.55427800 C 2.64506800 3.41931600 0.61573800 N 0.67804300 2.25550000 -0.07603900 C 2.16751500 4.58607200 0.02386700 H 3.60691900 3.39939100 1.12507300 C 0.21536300 3.37733100 -0.64964400 C 0.93244600 4.56638100 -0.61631600 H 2.75737300 5.49932900 0.05936200 H -0.75956500 3.28740300 -1.12604600 H 0.52746200 5.45556300 -1.09134500

23

C 2.55641400 -0.42087200 -0.79875500 H 2.51175900 0.50817000 -1.38308100 H 2.00146000 -1.18299600 -1.36219600 C 3.97752200 -0.84513100 -0.57327500 C 4.30858800 -2.19993600 -0.45453100 C 4.99691400 0.10874200 -0.47145000 C 5.62349200 -2.59148200 -0.22045000 H 3.52949900 -2.95530100 -0.57589600 C 6.31250700 -0.27976100 -0.23731200 H 4.75734400 1.16561200 -0.60620200 C 6.62572600 -1.63079700 -0.10596000 H 5.86919600 -3.64836700 -0.14103100 H 7.09704800 0.47113700 -0.17126900 H 7.65492100 -1.93628000 0.06969500 Cu -0.16337600 0.43494300 -0.24296600 O -1.77251200 0.73609600 -1.16321700 O -2.51897200 1.86181800 -0.74303600 C -3.33612900 1.52093700 0.42246400 C -4.30916100 2.69077500 0.49604200 H -4.92114100 2.74258600 -0.40988700 H -4.97788200 2.57244000 1.35495100 H -3.76925100 3.63886000 0.60673000 C -2.43749200 1.49605100 1.65260200 H -3.02052900 1.41641400 2.57675600 H -1.74358200 0.64112400 1.63203300 H -1.85608900 2.42399600 1.70494300 C -4.06083200 0.21138500 0.16765700 C -4.21143400 -0.76311300 1.15581400 C -4.60246600 -0.03094900 -1.10065100 C -4.88650300 -1.95442300 0.88614000 H -3.80349300 -0.60352100 2.15292400 C -5.26628100 -1.22075200 -1.37496400 H -4.46932600 0.71454000 -1.88299200 C -5.41162000 -2.18895200 -0.38020700 H -5.00063100 -2.69835900 1.67293200 H -5.67540000 -1.39355700 -2.36876900 H -5.94067400 -3.11661700 -0.59178500

4c

Energy: -1596.75394445 a.u.

C -2.08450800 2.10558300 0.09453400 C -3.19448000 2.71383500 0.66428000 C -3.78596100 2.11973000 1.77524700 C -3.25942600 0.93106300 2.26867500 C -2.14896400 0.37414800 1.64398200 N -1.56817100 0.96768900 0.58484000 H -4.65638900 2.57077700 2.24675400 H -1.56713100 2.51597600 -0.76993700 H -3.58503500 3.63437100 0.23948700 H -3.70807000 0.43009400 3.12487100 C -1.50157100 -0.89570600 2.14449800 H -0.78234800 -0.63340800 2.93383500 H -2.25493300 -1.54978200 2.61457600 N -0.76156900 -1.59933200 1.08579100 C 0.43685900 -2.31324800 1.55248400 H 0.19096200 -3.30386500 1.96845700 H 0.89057400 -1.72431900 2.36178100 C 1.44028300 -2.43533100 0.43214900

24

C 2.40667000 -3.43446100 0.38701200 N 1.37752900 -1.48206600 -0.51635000 C 3.32328700 -3.44001900 -0.66019700 H 2.43467100 -4.19837700 1.16173400 C 2.26169500 -1.48129500 -1.52381300 C 3.25085400 -2.44809300 -1.63462500 H 4.08400900 -4.21558600 -0.71676000 H 2.14335700 -0.66412200 -2.23553100 H 3.94573600 -2.42330300 -2.46960300 C -1.62937300 -2.52468900 0.29075700 H -2.16565400 -3.18828100 0.98981000 H -0.94546900 -3.15104500 -0.29655900 C -2.57530400 -1.80064200 -0.62011500 C -3.88800500 -1.52629300 -0.23280800 C -4.72422700 -0.77458900 -1.05509300 H -4.25849700 -1.90463600 0.72171200 C -2.94808200 -0.57111100 -2.67730500 C -4.25240600 -0.29039800 -2.27358400 H -5.74725400 -0.56979700 -0.74548300 H -2.57709100 -0.20569500 -3.63241500 H -4.90642100 0.29588300 -2.91586400 Cu -0.03086800 -0.06165200 -0.23461100 O 0.51746900 1.05578900 -1.66862600 O 0.66564700 2.39722700 -1.21708500 C 2.06133900 2.65759600 -0.88918900 C 2.02922000 4.10816200 -0.42315900 H 3.03374300 4.43574100 -0.13597000 H 1.67071400 4.75721100 -1.22929800 H 1.36996500 4.23572700 0.44251300 C 2.47010500 1.72796200 0.24488800 C 3.62927500 0.95143500 0.21579300 C 1.64004700 1.63822100 1.37295100 C 3.95163600 0.10362900 1.27647100 H 4.29586100 1.00185100 -0.64365100 C 1.96112200 0.79836900 2.43664100 H 0.74127500 2.25414200 1.41677300 C 3.12027800 0.02195400 2.38938700 H 4.86474300 -0.48830500 1.23405700 H 1.32164900 0.77462900 3.32002600 H 3.38405300 -0.62481400 3.22520000 C 2.90343300 2.51460300 -2.14467200 H 2.49369500 3.15559400 -2.93108500 H 3.94081200 2.81805700 -1.96434900 H 2.89737200 1.48374700 -2.51200700 C -2.11879900 -1.32923700 -1.85686900 H -1.10313700 -1.56578700 -2.18355300

4d

Energy: -1596.74171808 a.u.

C -1.67891100 -2.11462000 -1.40309900 C -2.83474800 -2.85708400 -1.59736200 C -4.05392600 -2.18987300 -1.66607900 C -4.07588200 -0.80378500 -1.55214300 C -2.88091700 -0.12092700 -1.36370100 N -1.70517800 -0.77753000 -1.28317000 H -4.98023600 -2.74245100 -1.80721900 H -0.68812800 -2.56500400 -1.34002400 H -2.77465700 -3.93790600 -1.68971600

25

H -5.01197200 -0.25047500 -1.59848700 C -2.81136300 1.38644500 -1.31552500 H -2.61979700 1.75562900 -2.33280800 H -3.78108300 1.80646700 -1.00588400 N -1.71079900 1.85174600 -0.45383500 C -1.05030600 3.08544100 -0.91905700 H -1.61532800 3.98638400 -0.62964300 H -1.02447700 3.06274500 -2.01770500 C 0.36575500 3.14695100 -0.40412200 C 1.01219800 4.32771600 -0.06505000 N 1.00277000 1.96000300 -0.35127400 C 2.35007800 4.27516500 0.32232300 H 0.47649500 5.27386700 -0.10861400 C 2.29224700 1.90297400 0.01447000 C 3.00197600 3.04675400 0.35821300 H 2.87552100 5.18809300 0.59399500 H 2.73487000 0.90614800 0.00988000 H 4.04545300 2.96401900 0.65023200 C -2.14483700 2.03636300 0.96448000 H -2.81048900 2.91573000 1.00618000 H -1.23847100 2.28601700 1.53352200 C -2.83284700 0.83569000 1.53602200 C -4.22579500 0.79180400 1.63527900 C -4.86509200 -0.35034000 2.11115000 H -4.81385500 1.66375900 1.34410200 C -2.72300100 -1.42151500 2.40894600 C -4.11484400 -1.46090300 2.49015300 H -5.94993000 -0.37057500 2.19271100 H -2.13178300 -2.27928200 2.72568000 H -4.61281900 -2.35259300 2.86540400 Cu -0.14703200 0.36349700 -0.78344100 O 1.41155900 -0.60281700 -1.23412800 O 1.43820500 -2.00527600 -1.07298500 C 2.03625600 -2.33309000 0.21880700 C 2.17887500 -3.84722800 0.14475700 H 2.64486600 -4.22610300 1.06031300 H 1.19961100 -4.32901900 0.03111600 H 2.80916700 -4.13429500 -0.70296900 C 3.38952700 -1.65039800 0.33659300 C 3.87087200 -1.17607800 1.55947900 C 4.18468300 -1.49203500 -0.80436100 C 5.11440000 -0.54956500 1.64166100 H 3.27736700 -1.28938200 2.46575600 C 5.42131200 -0.86199100 -0.72514600 H 3.80887400 -1.84201200 -1.76390200 C 5.89071800 -0.38575500 0.49876400 H 5.47453500 -0.19211400 2.60484700 H 6.02237900 -0.74058300 -1.62444400 H 6.86125500 0.10309100 0.56066300 C 1.06407600 -1.92431500 1.31612500 H 0.05993900 -2.29922800 1.07863900 H 1.34976400 -2.33423900 2.29106800 H 1.02358300 -0.83038900 1.41270300 C -2.08928400 -0.27550800 1.94164500 H -0.99967500 -0.23425600 1.88990400

5) – Self – Decomposition Structures (Bpa)

5a (structure iii in Figure 8)

26

Energy: -1596.69181842 a.u.

C 0.17641400 2.97542500 -1.61467200 C -0.19753100 4.30801400 -1.50748800 C -1.14596200 4.65953900 -0.55122400 C -1.68696400 3.67197700 0.26799000 C -1.25952100 2.35934200 0.11072000 N -0.34795100 2.02721400 -0.82637100 H -1.46337800 5.69428200 -0.44352000 H 0.92239300 2.63349400 -2.33017000 H 0.24738100 5.05120800 -2.16313200 H -2.42820000 3.91416600 1.02744200 C -1.71016800 1.22610200 0.99758000 H -1.01696700 1.14260400 1.84835100 H -2.71246100 1.41044700 1.41353200 N -1.64015900 -0.03815000 0.25091400 C -1.52779800 -1.24169100 1.09132000 H -2.49401400 -1.53099100 1.53121300 H -0.84941100 -0.99808400 1.92216700 C -0.92001200 -2.36150200 0.28510200 C -1.15688700 -3.70781400 0.53333100 N -0.06299400 -1.96745900 -0.67521900 C -0.46970200 -4.65876600 -0.21770000 H -1.86078100 -4.00426900 1.30901800 C 0.60939100 -2.87575400 -1.39049400 C 0.43247000 -4.23942600 -1.19096900 H -0.63655900 -5.71904200 -0.04108200 H 1.30638000 -2.46702400 -2.12118100 H 0.99051400 -4.95419600 -1.78936100 C -2.73192600 -0.15679900 -0.77574800 H -2.49015200 -1.04410400 -1.37407900 H -2.62706700 0.71471200 -1.43431300 C -4.11883600 -0.24543100 -0.21139100 C -4.87121000 0.91209200 0.01931000 C -4.68199100 -1.48843000 0.09990800 C -6.14951400 0.83115500 0.56366600 H -4.45826000 1.88449700 -0.25731300 C -5.95993500 -1.57249200 0.64423800 H -4.11941900 -2.39996900 -0.11221000 C -6.69280100 -0.41166100 0.88127300 H -6.72818300 1.73769400 0.72811000 H -6.39024300 -2.54545600 0.87190900 H -7.69464800 -0.47659000 1.30020700 Cu 0.19549600 0.07221000 -0.74237400 O 1.85903800 0.10246000 -1.47476700 O 1.76476000 -0.20343600 0.73369300 C 2.80765400 0.58411400 1.18673700 C 2.55645200 2.06653800 0.90908700 H 1.58317800 2.37055000 1.31743000 H 3.32684500 2.69981600 1.36107800 H 2.56000600 2.22810300 -0.17369900 C 2.74807300 0.32641400 2.72489300 H 2.88890100 -0.73600100 2.94225000 H 3.55365700 0.89434600 3.20256500 H 1.78662200 0.66046100 3.13066700 C 4.15972900 0.12042300 0.66591400 C 5.32461600 0.81398200 1.01258500 C 4.26592400 -1.01605100 -0.13847700 C 6.56593400 0.39681900 0.54484100 H 5.26720400 1.69222100 1.65689000

27

C 5.50747700 -1.43248200 -0.60976100 H 3.36212800 -1.55840200 -0.40456200 C 6.66064800 -0.72900900 -0.27077200 H 7.46152100 0.95077000 0.81942600 H 5.57576300 -2.31250100 -1.24706700 H 7.63103700 -1.05803400 -0.63719500

5b

Energy: -1596.69531235 a.u.

C 0.11300200 3.28784700 -1.87075700 C -0.18058900 4.57587800 -1.44374800 C -0.79441900 4.74407900 -0.20592600 C -1.08861800 3.62349600 0.56655800 C -0.75646400 2.36478800 0.08061000 N -0.17491700 2.21091400 -1.12761500 H -1.04223800 5.73931500 0.15632700 H 0.60505400 3.08764000 -2.82080900 H 0.06715900 5.42619600 -2.07285100 H -1.56388100 3.72034000 1.54108100 C -0.93415200 1.09510900 0.87310300 H -0.00655300 0.89520700 1.43368900 H -1.74824900 1.18631200 1.60841900 N -1.13357500 -0.03362300 -0.04662100 C -0.79310800 -1.34924900 0.52033000 H -1.58557500 -1.73193600 1.18092900 H 0.11287700 -1.21717600 1.13122900 C -0.47975600 -2.31126100 -0.59675800 C -0.65437800 -3.68638600 -0.49948000 N 0.05458900 -1.74967900 -1.69757500 C -0.24295500 -4.49144200 -1.55909100 H -1.09758300 -4.11757100 0.39649200 C 0.46894400 -2.51959800 -2.70940300 C 0.33456500 -3.90224200 -2.67978900 H -0.36933000 -5.57064600 -1.50692200 H 0.93018200 -1.98849400 -3.54020900 H 0.67617000 -4.50034800 -3.52002500 C -2.48713400 -0.01868700 -0.69471900 H -2.46443200 -0.80300700 -1.46169900 H -2.56524100 0.94247800 -1.21880800 C -3.63789100 -0.21457400 0.24767500 C -4.24712400 0.88325800 0.86609900 C -4.11697800 -1.49870400 0.53090900 C -5.29953600 0.70217600 1.75853800 H -3.90728200 1.89217500 0.62267800 C -5.16930200 -1.68306600 1.42279400 H -3.67459100 -2.35933600 0.02509300 C -5.75834400 -0.58245300 2.04116500 H -5.77164500 1.56481000 2.22412200 H -5.53946100 -2.68577500 1.62603300 H -6.58584200 -0.72490100 2.73285500 Cu 0.34757700 0.28055000 -1.48887000 O 1.83809200 0.43601100 -2.52506300 O 2.12648400 -0.22972100 -0.40714800 C 3.23442300 0.49933600 0.05769800 C 2.98500000 2.00002200 0.01080100 H 2.05835400 2.27750200 0.52830600 H 3.81450000 2.55736100 0.46156200 H 2.89050500 2.29487400 -1.03941000

28

C 4.48799100 0.14775300 -0.73170300 H 5.36984900 0.65113200 -0.31916100 H 4.67474300 -0.93005400 -0.73364500 H 4.35044900 0.46732500 -1.77032900 C 3.22086200 -0.08574200 1.47837500 C 2.90415700 0.68476100 2.60578200 C 3.44382300 -1.46440800 1.64216300 C 2.87272800 0.10275100 3.86859000 H 2.73026400 1.75414800 2.50730100 C 3.39867900 -2.04507500 2.90335500 H 3.65325200 -2.07703100 0.76793000 C 3.11449500 -1.26273400 4.02160800 H 2.66840100 0.72028300 4.74119700 H 3.58865600 -3.11056300 3.01606400 H 3.08496500 -1.71360800 5.01149700

5c

Energy: -1596.69438272 a.u.

C -1.25177800 -2.10463000 -2.47963200 C -1.23977000 -3.48966600 -2.57873200 C -0.56423700 -4.22211600 -1.60585200 C 0.06404400 -3.55101900 -0.56034600 C -0.00011900 -2.16406900 -0.51690100 N -0.63569800 -1.46289600 -1.47823200 H -0.52824900 -5.30796600 -1.66005200 H -1.76418500 -1.47243400 -3.20332600 H -1.74524800 -3.97874400 -3.40676300 H 0.58954000 -4.09306300 0.22389700 C 0.56895200 -1.32605600 0.59572200 H -0.23147000 -1.11198300 1.32274000 H 1.37500700 -1.84872500 1.13210500 N 1.01800000 -0.04375800 0.02683300 C 1.14761000 1.06010300 0.99043100 H 2.04371200 0.95696900 1.62093800 H 0.26691100 1.01628300 1.64946900 C 1.13714700 2.36811300 0.23845700 C 1.75071500 3.52409800 0.70462300 N 0.44256000 2.35689000 -0.91538000 C 1.61729700 4.69866200 -0.03250000 H 2.31777200 3.50406700 1.63383200 C 0.30071100 3.48525500 -1.61719200 C 0.87689700 4.68294800 -1.21006700 H 2.08661600 5.61735800 0.31242900 H -0.30286300 3.40588900 -2.51960300 H 0.74568000 5.58079800 -1.80764700 C 2.24649000 -0.20651900 -0.82596100 H 2.40047200 0.75435000 -1.33006300 H 1.98703400 -0.93854200 -1.60066700 C 3.47362900 -0.62907700 -0.07376100 C 3.78098500 -1.98511000 0.08495400 C 4.32910600 0.32602800 0.48743700 C 4.90779600 -2.37908100 0.80035300 H 3.14128000 -2.73731600 -0.38157900 C 5.45641800 -0.06475200 1.20364500 H 4.11896000 1.38715100 0.33795800 C 5.74390400 -1.41838000 1.36478500 H 5.14152700 -3.43631900 0.90713900 H 6.11926500 0.68761900 1.62593600

29

H 6.62875400 -1.72467000 1.91855100 Cu -0.60480700 0.54098200 -1.13184500 O -2.08513300 1.04845000 -2.02633200 O -1.89906100 1.70511900 0.19926300 C -3.02414100 1.32464400 0.93512200 C -4.30324800 1.59434800 0.13970200 H -5.18925500 1.32808200 0.72710600 H -4.35695200 2.65537900 -0.12352200 H -4.30185900 1.02432600 -0.79266100 C -2.89977700 -0.13176200 1.37529900 C -2.50434400 -0.50536200 2.66554600 C -3.13628300 -1.14513000 0.43659500 C -2.34664900 -1.84843000 3.00681700 H -2.33086500 0.25234500 3.42746800 C -2.98844200 -2.48604300 0.77769100 H -3.43319500 -0.87389500 -0.57630400 C -2.58571400 -2.84427400 2.06291000 H -2.04950100 -2.11533400 4.01947700 H -3.19004300 -3.25636300 0.03353400 H -2.47644100 -3.89338100 2.33240500 C -2.97461800 2.31587600 2.12304400 H -3.79698700 2.08650900 2.81108300 H -2.02707900 2.25464500 2.66801800 H -3.09492600 3.33668400 1.75247600

5d (structure iv in Figure 8)

Energy: -1729.45013694 a.u.

C -0.17785200 2.98304400 1.29248000 C 0.22532300 4.30986000 1.22153600 C 1.21524800 4.65559400 0.30576400 C 1.76603600 3.66896100 -0.50748300 C 1.30351800 2.36356200 -0.38523900 N 0.35003800 2.03820600 0.50725800 H 1.55794000 5.68490900 0.22628300 H -0.95557800 2.64205700 1.97534500 H -0.22734200 5.05356700 1.87153900 H 2.54196700 3.90560800 -1.23341800 C 1.76312500 1.23067900 -1.26459500 H 1.07961700 1.15195900 -2.12339100 H 2.77131400 1.41177200 -1.66759400 N 1.67975400 -0.03852400 -0.52483700 C 1.58841200 -1.22365700 -1.39550500 H 2.56617600 -1.50416400 -1.81519800 H 0.93485800 -0.95850000 -2.23939100 C 0.95476100 -2.36214900 -0.64004800 C 1.23013600 -3.70277900 -0.88326900 N 0.03650300 -1.99054100 0.26885100 C 0.51871800 -4.67086400 -0.17881000 H 1.98410800 -3.98085300 -1.61762600 C -0.65272600 -2.91488100 0.94368500 C -0.44293800 -4.27418300 0.74619400 H 0.71403300 -5.72688500 -0.35212400 H -1.39306900 -2.52053200 1.64009800 H -1.02000900 -5.00369800 1.30785300 C 2.76013600 -0.17072200 0.51389700 H 2.50691000 -1.06220500 1.10022200 H 2.63805400 0.68452800 1.18926100 C 4.15310600 -0.24869500 -0.03614300

30

C 4.90596400 0.91284200 -0.24473400 C 4.72536600 -1.48577500 -0.35465200 C 6.19115500 0.84221500 -0.77421400 H 4.48596800 1.88052700 0.03769400 C 6.01022200 -1.56036800 -0.88410000 H 4.16263300 -2.40100800 -0.15944700 C 6.74257900 -0.39503900 -1.09935600 H 6.76878200 1.75248900 -0.92164800 H 6.44613700 -2.52958800 -1.11762600 H 7.74958800 -0.45219400 -1.50711600 Cu -0.16479800 0.04910600 0.46614900 O -1.88122900 0.10154300 1.10818200 O -1.70947700 -0.06522500 -1.13345800 C -2.77188100 0.71491300 -1.54979400 C -2.56602000 2.18413500 -1.17988500 H -1.60076100 2.53919900 -1.56377800 H -3.35263400 2.82229300 -1.59587100 H -2.57495600 2.27702000 -0.08913700 C -2.69211000 0.55434000 -3.09923600 H -2.80126100 -0.49627500 -3.38286600 H -3.51008400 1.12777100 -3.54891700 H -1.73720300 0.93884300 -3.47449100 C -4.11395100 0.17450000 -1.07357400 C -5.29644100 0.87274200 -1.33965400 C -4.19074400 -1.04549100 -0.39878400 C -6.52615300 0.37573100 -0.92003300 H -5.26381200 1.81720600 -1.88392500 C -5.42035900 -1.54338100 0.02241700 H -3.27211700 -1.59065400 -0.19633900 C -6.59169400 -0.83536700 -0.23480600 H -7.43582600 0.93441500 -1.13222000 H -5.46529000 -2.49269200 0.55418600 H -7.55298600 -1.22738900 0.09182200 C -0.22933000 -0.12747800 3.76278800 N 0.54995300 -0.12756800 2.89526500 C -1.22750400 -0.13863800 4.80899600 H -1.10661500 -1.01834300 5.44918000 H -1.14485300 0.75671400 5.43332900 H -2.22723900 -0.16344000 4.36035700

5e (structure v in Figure 8)

Energy: -1729.44511464 a.u.

31

C 1.49248100 3.53083300 0.27680900 C 2.46521600 4.44286400 -0.10675700 C 3.48236600 4.01419700 -0.95441900 C 3.48850000 2.69421900 -1.39569600 C 2.47332000 1.83913300 -0.98398500 N 1.49737200 2.26204400 -0.15372500 H 4.26698200 4.69982500 -1.26621100 H 0.67781800 3.80166900 0.94806300 H 2.42641500 5.46403400 0.26141200 H 4.27029400 2.32548100 -2.05702400 C 2.34497200 0.41799200 -1.46190000 H 1.70939500 0.40220300 -2.35939700 H 3.32153500 0.00306700 -1.75561900 N 1.68535800 -0.39931500 -0.43508700 C 0.98029000 -1.57643000 -0.95823200 H 1.66328900 -2.42294000 -1.12858800 H 0.56398700 -1.30648400 -1.93974100 C -0.14447700 -1.95789100 -0.03327000 C -0.64203700 -3.25269600 0.05236400 N -0.68787700 -0.94777100 0.67765700 C -1.73138500 -3.50463500 0.88111600 H -0.17989400 -4.04799500 -0.52959100 C -1.72528700 -1.19341400 1.49158300 C -2.27952800 -2.45933100 1.61650500 H -2.14253600 -4.50895100 0.95685300 H -2.11037800 -0.33850800 2.04075600 H -3.12890900 -2.61314100 2.27594400 C 2.59556700 -0.73225700 0.71953000 H 1.95787300 -1.18757700 1.48731100 H 2.92975000 0.22852800 1.13082200 C 3.75378500 -1.61525800 0.36356800 C 4.97101000 -1.06282100 -0.05231300 C 3.63804900 -3.00851000 0.43777100 C 6.04054400 -1.88143100 -0.40276200 H 5.08789600 0.02272800 -0.07122300 C 4.70567300 -3.82984700 0.08784500 H 2.70865100 -3.45045300 0.80274100 C 5.90635200 -3.26652600 -0.33844600 H 6.98474100 -1.43867300 -0.71299900 H 4.60597900 -4.91080100 0.16131000 H 6.74390800 -3.90748400 -0.60522700 Cu 0.21621400 0.83767700 0.45336100 C -0.35468800 2.01828300 2.74784200 N 0.47617000 1.18102000 2.56680300 C -1.36358100 2.95993700 2.66223400 H -1.07454500 3.98784300 2.88686100 H -1.53638000 2.63843300 1.07973600 H -2.30872200 2.67429200 3.12768300 O -1.43691600 2.16909700 0.08164100 O -2.56715600 1.23015800 0.15251600 C -3.10912900 1.03472900 -1.18627200 C -1.98931000 0.71493300 -2.16602200 H -1.40580400 -0.15222400 -1.82995100 H -2.39535000 0.48952800 -3.15828100 H -1.31992600 1.57550100 -2.26494500 C -3.85589000 2.28785700 -1.62134300 H -4.30899400 2.14571400 -2.60892200 H -4.65358400 2.53742900 -0.91487400 H -3.16570700 3.13682900 -1.67595300 C -4.03815700 -0.13940900 -0.91483600

32

C -3.92454800 -1.36040000 -1.58449600 C -5.01595000 -0.00996500 0.08102000 C -4.77454800 -2.42107900 -1.27766600 H -3.17834400 -1.49196600 -2.36612400 C -5.85627400 -1.07180500 0.39693900 H -5.10830500 0.93186200 0.61978400 C -5.73929800 -2.28233300 -0.28421500 H -4.68333200 -3.35889800 -1.82332800 H -6.61132400 -0.95108800 1.17152000 H -6.40549600 -3.10994400 -0.04804300

6) – Cyclohexadiene (CHD) Oxidation (Bpa)

6a (structure vi in Figure 8)

Energy: -1830.10369032 a.u.

C -1.03632500 -2.35038000 0.16175800 C -1.01386100 -3.71705900 0.40122200 C 0.15060400 -4.28150500 0.91333700 C 1.24551500 -3.45886900 1.16030600 C 1.14982600 -2.09644500 0.89484200 N 0.01883100 -1.55631400 0.39674100 H 0.20940800 -5.34960700 1.11174700 H -1.92017300 -1.84957800 -0.23671100 H -1.89214200 -4.32067800 0.18556600 H 2.17543200 -3.86522800 1.55525000 C 2.28127100 -1.14116300 1.19797500 H 2.13426800 -0.75072100 2.21613600 H 3.24530300 -1.67775000 1.20080600 N 2.25926200 -0.00705800 0.28557000 C 2.80038400 1.24202700 0.80277100 H 3.89596900 1.31763600 0.69580100 H 2.59114400 1.27063900 1.88250800 C 2.12645800 2.42744300 0.14977500 C 2.79799000 3.62250300 -0.08365700 N 0.81938000 2.28377600 -0.15713200 C 2.10601300 4.69802600 -0.63263400 H 3.85461700 3.70318600 0.16713600 C 0.15255800 3.32135800 -0.68891100 C 0.75744500 4.54583000 -0.93930900 H 2.61528700 5.64032400 -0.82260500 H -0.89934300 3.13760100 -0.90361800 H 0.17970700 5.35868200 -1.37095800 C 2.73730200 -0.33641200 -1.08314900 H 2.50121900 0.53289700 -1.71301700 H 2.11184500 -1.16670300 -1.43995600 C 4.19485800 -0.68657200 -1.17496300 C 4.62022200 -2.01092300 -1.01962300 C 5.15756200 0.30637100 -1.38991300 C 5.97339600 -2.33376300 -1.06181700 H 3.87629900 -2.79986300 -0.89003400 C 6.51178800 -0.01261400 -1.43237300 H 4.83604100 1.33714900 -1.55332300 C 6.92150400 -1.33319000 -1.26312200 H 6.28863200 -3.36929300 -0.95004800 H 7.24846500 0.76820800 -1.61073200 H 7.97923200 -1.58476100 -1.30285800 Cu 0.02585300 0.44174300 0.11321200

33

O -1.85687000 0.67356700 -0.71305400 O -2.65654500 1.67663400 -0.02979200 C -3.32829600 1.05687400 1.10338700 C -4.33190300 0.03227700 0.60605600 H -3.83786300 -0.79836800 0.08514300 H -4.92382700 -0.37881700 1.43148000 H -5.01795200 0.51018600 -0.10054900 C -4.04055400 2.24786300 1.73645000 H -4.59527900 1.92209500 2.62252900 H -3.32750200 3.01918200 2.04619600 H -4.74808000 2.69125900 1.02760900 C -2.27713000 0.49100800 2.04853200 C -2.37821700 -0.77320300 2.63147500 C -1.15580200 1.27754000 2.35737900 C -1.38718400 -1.24750900 3.49169600 H -3.23522600 -1.40772800 2.41146600 C -0.16466300 0.80744400 3.21872400 H -1.08107200 2.27940800 1.93409700 C -0.27711500 -0.46199500 3.78706700 H -1.48823100 -2.23724400 3.93448100 H 0.68112100 1.44902300 3.46780100 H 0.48714000 -0.82765600 4.47146500 C -4.34623900 0.50019600 -2.96849900 C -5.49694200 -0.15707400 -2.69303200 C -4.18751100 -2.26174500 -2.38443600 C -3.05971800 -1.57884100 -2.68890400 H -4.38253100 1.54995200 -3.25867500 H -6.45263600 0.36049500 -2.76604900 H -4.15071300 -3.34073500 -2.23363300 H -2.11346900 -2.11553500 -2.77800200 C -5.52428500 -1.59900000 -2.30500800 H -5.94578500 -1.70820800 -1.28497600 H -6.25451000 -2.14745800 -2.92756000 C -3.05343200 -0.14211100 -2.87749200 H -2.25968100 0.26527100 -3.51232500 H -2.46297600 0.34943000 -1.66366800

6b

Energy: -1830.09259931 a.u.

C 0.23792100 2.77218300 -1.29844000 C 0.72030600 4.04813200 -1.55530100 C 2.07916100 4.20861300 -1.80560100 C 2.90094300 3.08486100 -1.79354400 C 2.34709200 1.83575700 -1.53785400 N 1.02711800 1.68503200 -1.28802500 H 2.49605300 5.19388200 -2.00205200 H -0.81398900 2.59027800 -1.07706200 H 0.03750900 4.89444700 -1.55142800 H 3.96964300 3.16899600 -1.98433200 C 3.16414300 0.56794300 -1.58864900 H 3.02492500 0.10960300 -2.57819900 H 4.23915400 0.79484900 -1.49975500 N 2.70046200 -0.39222700 -0.58963300 C 2.85723400 -1.79615000 -0.96294100 H 3.86023000 -2.19244800 -0.73425900 H 2.73807900 -1.86155000 -2.05404500 C 1.79294900 -2.64878400 -0.31753200 C 2.05134500 -3.94855300 0.09986800

34

N 0.55761800 -2.10402000 -0.21974500 C 1.01553600 -4.71963200 0.61944600 H 3.05999800 -4.34891500 0.01039200 C -0.44033400 -2.84991500 0.28993800 C -0.25315900 -4.15922200 0.71337900 H 1.20019300 -5.73923700 0.95059500 H -1.40683900 -2.35166300 0.35827900 H -1.09319600 -4.71965500 1.11454500 C 3.18067300 -0.08821200 0.78813500 H 2.62354400 -0.75389700 1.46258100 H 2.85430800 0.93843200 1.00804400 C 4.66048300 -0.23447000 0.99669900 C 5.52378800 0.84573900 0.78041800 C 5.20633600 -1.46122400 1.39207600 C 6.89910200 0.69997700 0.93682200 H 5.10685800 1.81910400 0.51327900 C 6.58099700 -1.61072600 1.54969200 H 4.53947700 -2.29947100 1.60443100 C 7.42958200 -0.53086900 1.31647900 H 7.55752600 1.55109800 0.77518200 H 6.99054700 -2.56749500 1.86739700 H 8.50383800 -0.64450100 1.44552400 Cu 0.46830700 -0.12008500 -0.54591100 O -1.24430200 0.61808000 0.26666700 O -2.33429900 -0.33542100 0.33355400 C -3.17590900 -0.21662800 -0.86465200 C -2.33460400 -0.49140200 -2.10039100 H -1.81983300 -1.45834300 -2.03310400 H -2.95249100 -0.49477600 -3.00529100 H -1.58128700 0.29678500 -2.22457900 C -3.79296500 1.17294500 -0.93183700 H -4.41156100 1.27059300 -1.83101300 H -4.42226900 1.36399300 -0.05758100 H -3.01133600 1.94320000 -0.96583900 C -4.22098300 -1.28005800 -0.57282100 C -4.46560900 -2.35360900 -1.43259500 C -4.96064300 -1.18697800 0.61395700 C -5.44018400 -3.30069300 -1.12398400 H -3.90619900 -2.45329000 -2.36087100 C -5.92453100 -2.13741300 0.92745100 H -4.76520200 -0.36218900 1.29942100 C -6.17046400 -3.19664000 0.05564700 H -5.62775800 -4.12294700 -1.81194700 H -6.48919100 -2.05064700 1.85388200 H -6.93080400 -3.93742700 0.29515500 C -3.12816400 1.93763800 2.57969400 C -4.26649900 2.60463300 2.27420100 C -2.90216100 4.34371900 1.11008700 C -1.78361400 3.66268200 1.44640200 H -3.17746600 1.03730600 3.19203800 H -5.22618500 2.24588800 2.64569400 H -2.82723700 5.30747100 0.60707400 H -0.80502600 4.08494000 1.21316300 C -4.26926200 3.85326900 1.45565000 H -4.86433600 3.70205200 0.53280800 H -4.83344800 4.64800400 1.97712400 C -1.83294700 2.36839000 2.09817400 H -0.96990000 2.09924800 2.71711500 H -1.52816500 1.42616900 1.09067200

35

6c

Energy: -1830.09266567 a.u.

C 0.18392300 2.55821900 1.41913600 C -0.13369700 3.87516000 1.72469400 C -1.45357100 4.19289200 2.02474900 C -2.40776500 3.17967900 2.00929000 C -2.02041100 1.88094800 1.70094300 N -0.73683200 1.57699900 1.40409200 H -1.74015600 5.21524600 2.26180800 H 1.19759900 2.24936200 1.16599200 H 0.64633600 4.63177400 1.71834900 H -3.45243900 3.38761600 2.23548400 C -3.00127500 0.73221300 1.72438600 H -2.92780600 0.22684200 2.69831900 H -4.03469200 1.10994300 1.64576700 N -2.66962400 -0.24445400 0.69478500 C -3.06794400 -1.61875200 0.97045700 H -4.11466600 -1.82986400 0.69373400 H -2.99596900 -1.77580400 2.05649400 C -2.13731400 -2.58855700 0.28004400 C -2.57391100 -3.81937800 -0.19771100 N -0.84369400 -2.21407300 0.18350900 C -1.65708800 -4.69304900 -0.77525400 H -3.62619400 -4.08583700 -0.11187100 C 0.03604800 -3.05340500 -0.38635900 C -0.32493700 -4.30299600 -0.87058800 H -1.98104100 -5.66076200 -1.15198500 H 1.06339100 -2.69102000 -0.44126200 H 0.42757100 -4.94780600 -1.31807700 C -3.01189400 0.20618600 -0.68116000 H -2.54152200 -0.51055800 -1.36999000 H -2.50225900 1.16943000 -0.82836800 C -4.48257800 0.32972600 -0.95717200 C -5.15863200 1.52796300 -0.69980300 C -5.21095400 -0.76018700 -1.44740800 C -6.53060000 1.63009300 -0.91032500 H -4.59448900 2.39693800 -0.35455900 C -6.58302700 -0.66165800 -1.65933000 H -4.68788500 -1.68787600 -1.68921800 C -7.24536800 0.53283900 -1.38543700 H -7.04175200 2.57071500 -0.71512600 H -7.13498500 -1.51406800 -2.05032500 H -8.31681900 0.61316200 -1.55614500 Cu -0.39973100 -0.32232800 0.79391600 O 1.62919800 -0.62601900 0.72442000 O 2.36002900 0.57080900 0.34669700 C 2.44681100 0.67772900 -1.11481100 C 1.04888900 0.69040600 -1.71510400 H 0.41571200 1.46057800 -1.25471100 H 1.08743800 0.88089000 -2.79362300 H 0.57091100 -0.28877800 -1.57821400 C 3.25264400 -0.48476000 -1.67530700 H 3.28562500 -0.43402700 -2.76958100 H 4.27917400 -0.47103900 -1.29830200 H 2.79664500 -1.44195300 -1.38797800 C 3.18606700 1.99911100 -1.24302100 C 2.65154000 3.10104700 -1.91545800

36

C 4.44233900 2.12730900 -0.63540200 C 3.36452200 4.29534900 -1.99875100 H 1.67662200 3.03397400 -2.39474900 C 5.14907400 3.32162800 -0.70907700 H 4.85900400 1.28079400 -0.08952800 C 4.61321900 4.40953600 -1.39589600 H 2.93985700 5.13892800 -2.53978500 H 6.12324500 3.40410200 -0.23085900 H 5.16913500 5.34273100 -1.46144800 C 4.67821900 -1.51937600 1.49534600 C 5.58150900 -1.85717100 0.54431300 C 4.17386000 -3.83351500 -0.04944100 C 3.30219500 -3.47839700 0.92277100 H 4.87216800 -0.66609900 2.14519100 H 6.50108300 -1.28248700 0.43554100 H 4.03116200 -4.76245700 -0.60103600 H 2.45797200 -4.13068500 1.15226400 C 5.38816200 -3.02430100 -0.36700900 H 5.35490200 -2.68367200 -1.42154300 H 6.28480300 -3.67075000 -0.35206200 C 3.44004100 -2.24578100 1.67098700 H 2.99775100 -2.22542500 2.67241200 H 2.45540200 -1.35265200 1.12604900

6d

Energy: -1830.09259928 a.u.

C 0.23789700 2.77229400 -1.29829200 C 0.72025000 4.04826400 -1.55510900 C 2.07910000 4.20878600 -1.80541500 C 2.90090600 3.08505200 -1.79340800 C 2.34708700 1.83592600 -1.53775700 N 1.02711900 1.68516000 -1.28791900 H 2.49596800 5.19407200 -2.00183100 H -0.81400600 2.59036100 -1.07691500 H 0.03743100 4.89456200 -1.55119700 H 3.96960300 3.16921900 -1.98419900 C 3.16417700 0.56813800 -1.58861300 H 3.02501700 0.10985600 -2.57819800 H 4.23917700 0.79507300 -1.49966200 N 2.70050100 -0.39210800 -0.58966500 C 2.85725700 -1.79600600 -0.96308300 H 3.86029000 -2.19230200 -0.73456000 H 2.73794900 -1.86133400 -2.05417400 C 1.79306600 -2.64868100 -0.31758200 C 2.05152700 -3.94844700 0.09978500 N 0.55773500 -2.10394200 -0.21967800 C 1.01577900 -4.71954800 0.61945300 H 3.06017800 -4.34879200 0.01020900 C -0.44015700 -2.84985600 0.29009100 C -0.25291800 -4.15916300 0.71350700 H 1.20048400 -5.73915200 0.95057700 H -1.40666500 -2.35162200 0.35851500 H -1.09290700 -4.71961800 1.11474400 C 3.18076100 -0.08819800 0.78811300 H 2.62363000 -0.75390700 1.46253400 H 2.85443300 0.93844300 1.00809200 C 4.66057100 -0.23450700 0.99663600 C 5.52389300 0.84571200 0.78046900

37

C 5.20640600 -1.46131200 1.39187800 C 6.89920400 0.69991100 0.93685400 H 5.10697800 1.81911200 0.51343700 C 6.58106400 -1.61085400 1.54947500 H 4.53953200 -2.29957000 1.60414700 C 7.42966600 -0.53098400 1.31637800 H 7.55764200 1.55104000 0.77530700 H 6.99060000 -2.56766200 1.86707700 H 8.50392000 -0.64464600 1.44541100 Cu 0.46837700 -0.11998300 -0.54578600 O -1.24438200 0.61798000 0.26658100 O -2.33435400 -0.33556900 0.33342800 C -3.17592600 -0.21677500 -0.86480000 C -2.33461100 -0.49167300 -2.10050300 H -1.81976700 -1.45856500 -2.03307200 H -2.95250300 -0.49523500 -3.00540000 H -1.58135000 0.29654800 -2.22481100 C -3.79288100 1.17283800 -0.93209000 H -4.41151700 1.27043100 -1.83124400 H -4.42211900 1.36403100 -0.05781900 H -3.01120000 1.94303000 -0.96622500 C -4.22108500 -1.28010600 -0.57291500 C -4.46562300 -2.35383000 -1.43249700 C -4.96088200 -1.18677300 0.61375800 C -5.44026600 -3.30082300 -1.12381600 H -3.90609900 -2.45371500 -2.36068200 C -5.92483900 -2.13711300 0.92732200 H -4.76548600 -0.36186200 1.29908900 C -6.17069600 -3.19650600 0.05569900 H -5.62777600 -4.12321200 -1.81163500 H -6.48961000 -2.05014600 1.85366700 H -6.93108900 -3.93722300 0.29525900 C -3.12844800 1.93737600 2.57956200 C -4.26671700 2.60444600 2.27398600 C -2.90215300 4.34359300 1.11022700 C -1.78367700 3.66248100 1.44663100 H -3.17786600 1.03699200 3.19182200 H -5.22646500 2.24571100 2.64532800 H -2.82712400 5.30739700 0.60732900 H -0.80504000 4.08472500 1.21356700 C -4.26932100 3.85316100 1.45555500 H -4.86427900 3.70206100 0.53261900 H -4.83354400 4.64786600 1.97703400 C -1.83315200 2.36811700 2.09824700 H -0.97020000 2.09886500 2.71727300 H -1.52827500 1.42596700 1.09064700

6e

Energy: -1830.10634117 a.u.

38

C -1.46420400 -1.13221900 2.33856000 C -2.33748800 -1.88316400 3.11088900 C -2.59769700 -3.19791400 2.73331200 C -1.98334000 -3.70393400 1.59478000 C -1.11945300 -2.89104600 0.86539100 N -0.85831300 -1.62643400 1.24389200 H -3.27813100 -3.81811200 3.31290600 H -1.21485600 -0.09881200 2.58096600 H -2.80454200 -1.44201300 3.98727400 H -2.17454200 -4.72258500 1.26010800 C -0.39035700 -3.42747600 -0.35012600 H 0.51914400 -3.93834900 -0.00187400 H -1.00812600 -4.20576100 -0.83242100 N 0.01082000 -2.39023000 -1.29684900 C 1.33155400 -2.55997900 -1.89465900 H 1.32456400 -3.23637400 -2.76782700 H 1.98551800 -3.02239300 -1.14037500 C 1.92908800 -1.22650000 -2.28161000 C 2.81172300 -1.09907400 -3.34927800 N 1.59715700 -0.17052200 -1.51232200 C 3.36492400 0.14584700 -3.63194400 H 3.05567400 -1.97078900 -3.95404300 C 2.12965500 1.02902800 -1.78995000 C 3.01397600 1.23452600 -2.83951300 H 4.05358200 0.26504500 -4.46561100 H 1.82219400 1.83404100 -1.12186400 H 3.41520200 2.22672500 -3.02913500 C -1.02572200 -2.09391900 -2.31590900 H -1.30730400 -3.02345300 -2.84284300 H -0.55746900 -1.42738800 -3.05297000 C -2.21938000 -1.43267900 -1.69114200 C -3.34774300 -2.16702800 -1.32567300 C -4.37284500 -1.57167800 -0.59187600 H -3.41755000 -3.22004600 -1.60485400 C -3.15281000 0.51075700 -0.58091500 C -4.26623500 -0.23848500 -0.20198900 H -5.24886300 -2.15435200 -0.31306700 H -3.04959800 1.54967100 -0.26973500 H -5.05539300 0.21995700 0.39149500 Cu 0.31848200 -0.53299500 0.02129100 O 0.14478900 1.44195400 0.65136400 O 0.34118300 1.58740400 2.08375200 C 1.75539200 1.81175900 2.36042100 C -2.27363100 3.59097100 -2.13009700 C -3.08958700 4.20582300 0.14816000 C -1.81660600 4.13849100 0.60452900 C -1.01274100 3.53410600 -1.64203000 H -2.45851600 3.40620400 -3.18773400 H -3.89537800 4.49070100 0.82355600 H -1.60725000 4.36606900 1.65045700 H -0.18868800 3.31002600 -2.32252000 C -0.71085300 3.74733800 -0.24210300 H -0.29570400 2.45585900 0.28381200 H 0.26118600 4.19963000 -0.01590800 C -3.44481700 3.96264800 -1.28225300 H -3.94249900 4.85745500 -1.70301100 H -4.23511000 3.19115300 -1.36143100 C 1.77324400 1.81853900 3.88536100 H 2.79507700 1.97411400 4.24626400 H 1.14187200 2.62539100 4.27296700

39

H 1.41026300 0.86840400 4.29152400 C 2.56227600 0.64711700 1.80337000 C 3.70062800 0.81679600 1.01316600 C 2.13959300 -0.66034300 2.08308400 C 4.39004100 -0.28404400 0.50329700 H 4.06135600 1.81784400 0.78183100 C 2.82250300 -1.76288200 1.57337200 H 1.26838700 -0.81030400 2.72015900 C 3.95142400 -1.57644600 0.77522200 H 5.27562100 -0.12641700 -0.11045000 H 2.48030700 -2.76857300 1.81957600 H 4.49695800 -2.43426500 0.38449100 C 2.17419700 3.16585900 1.81521100 H 1.49139200 3.93828400 2.18539200 H 3.18715000 3.42851400 2.13977600 H 2.15489300 3.18246100 0.71939200 C -2.14832400 -0.07978600 -1.33992500 H -1.29051500 0.51866700 -1.65848000

6f

Energy: -1962.85346300 a.u.

C 0.05282200 2.52030200 1.57255400 C -0.33197900 3.73770100 2.12069200 C -1.65318400 3.90306900 2.52187800 C -2.54178300 2.84455100 2.35748900 C -2.08616000 1.65157600 1.80768600 N -0.80215100 1.49549200 1.41692800 H -1.99128700 4.84466700 2.94941900 H 1.07095000 2.33208200 1.23173100 H 0.39585700 4.53855900 2.22058800 H -3.58662200 2.93596900 2.65084100 C -2.98852500 0.45302800 1.63488900 H -2.83942300 -0.23044500 2.48410100 H -4.04722900 0.76428600 1.65296900 N -2.62169000 -0.27444700 0.42712400 C -2.98597500 -1.68327200 0.39349300 H -4.03439300 -1.85495500 0.09462200 H -2.87732400 -2.07485700 1.41565200 C -2.04794700 -2.44232600 -0.51599300 C -2.45429700 -3.56176900 -1.23536200 N -0.77618100 -1.99481000 -0.56738900 C -1.52429600 -4.24941100 -2.00973000 H -3.49218800 -3.88753800 -1.18294300 C 0.11492100 -2.65441000 -1.32066800 C -0.21175600 -3.78904700 -2.05156600 H -1.82291400 -5.12847400 -2.57694500 H 1.12721000 -2.24686100 -1.31277100 H 0.54887100 -4.29019000 -2.64528500 C -2.95238100 0.44999500 -0.82698800 H -2.45900400 -0.09647600 -1.64305400 H -2.46111700 1.43062500 -0.76028400 C -4.42279000 0.60311600 -1.09192400 C -5.12549500 1.70490800 -0.59106100 C -5.12479500 -0.36835000 -1.81416800 C -6.49693700 1.82694500 -0.79415500 H -4.58151600 2.48644500 -0.05620200 C -6.49640800 -0.24983900 -2.01961400 H -4.58112000 -1.21422200 -2.24038300

40

C -7.18509500 0.84638600 -1.50528100 H -7.02859200 2.69419300 -0.40734300 H -7.02752800 -1.00776500 -2.59215100 H -8.25612600 0.94354500 -1.67033800 Cu -0.37755800 -0.37425100 0.67158000 O 1.64934900 -0.44844700 0.41035300 O 2.33020600 0.81627200 0.18814900 C 2.40843200 1.10095900 -1.24796600 C 1.00699500 1.14795000 -1.83680200 H 0.36102900 1.84356600 -1.28591400 H 1.03368800 1.45954600 -2.88720000 H 0.55034300 0.15132700 -1.80068800 C 3.24444500 0.03644400 -1.94491000 H 3.27497000 0.22172600 -3.02471500 H 4.27115100 0.02639500 -1.56710000 H 2.81294000 -0.95963300 -1.77698800 C 3.11565100 2.44603400 -1.22437200 C 2.55682600 3.60012600 -1.77872500 C 4.36930600 2.53843900 -0.60493100 C 3.24223600 4.81246500 -1.73448200 H 1.58343600 3.56090000 -2.26376300 C 5.04866600 3.74951300 -0.55066100 H 4.80679000 1.64891300 -0.15204400 C 4.48808000 4.89127800 -1.12038300 H 2.79785100 5.69849100 -2.18417300 H 6.02120700 3.80300500 -0.06483200 H 5.02255900 5.83865800 -1.08641800 C 4.73268600 -1.54394100 0.97417400 C 5.53312300 -1.84933400 -0.07344000 C 3.91126400 -3.62268600 -0.75649700 C 3.14814200 -3.30708900 0.31470100 H 5.04995800 -0.78776900 1.69243300 H 6.49115700 -1.34458600 -0.19458300 H 3.64114500 -4.46630900 -1.39180800 H 2.25403200 -3.89763800 0.52976100 C 5.16547500 -2.88035400 -1.09100900 H 5.07470200 -2.40935600 -2.09103800 H 5.99988700 -3.59134700 -1.23299700 C 3.44475800 -2.17321600 1.16566800 H 3.07164300 -2.21099900 2.19480500 H 2.48189900 -1.18261200 0.73851200 C 0.14465800 -2.29598600 3.28930500 N -0.42017800 -1.62583400 2.52127700 C 0.84936400 -3.12657600 4.24030100 H 0.14688300 -3.58635400 4.94302900 H 1.39460000 -3.92263800 3.72160800 H 1.56748400 -2.52709000 4.80959800

7) – [CuII(tpa)(O2Cm)]+

7a

Energy: -1612.79766701 a.u.

41

C -1.66522600 3.00459100 -0.54824000 C -2.47745400 4.11950200 -0.38993900 C -3.70547400 3.96366000 0.24583100 C -4.08658200 2.69747000 0.68026400 C -3.22725700 1.62483300 0.46851000 N -2.02699800 1.78626900 -0.12039200 H -4.36215200 4.81705900 0.39943100 H -0.69280400 3.04846500 -1.03836400 H -2.14791700 5.08882500 -0.75387500 H -5.04492700 2.53795400 1.17105800 C -3.61097200 0.20489600 0.79496600 H -4.35882900 0.17110100 1.60489100 H -4.09166700 -0.23398100 -0.09216000 N -2.43862200 -0.62255300 1.09943300 C -1.92470100 -0.40951900 2.45722500 H -2.55477800 -0.89644200 3.22092600 H -1.97025900 0.67305400 2.65097900 C -0.49750800 -0.88068100 2.55701300 C 0.01918400 -1.44811300 3.71599500 N 0.25334600 -0.70462500 1.44985000 C 1.35564700 -1.83840200 3.74040000 H -0.62010800 -1.58047600 4.58694900 C 1.53497300 -1.10254900 1.47139000 C 2.12617700 -1.66544600 2.59631900 H 1.78233600 -2.28094900 4.63791500 H 2.08853900 -0.94520500 0.54662700 H 3.17094100 -1.96354600 2.56151700 C -2.64917300 -2.04101100 0.77526700 H -3.62028000 -2.40586800 1.14868800 H -1.87434000 -2.61334500 1.30560400 C -2.50514500 -2.28875300 -0.70594400 C -3.20111400 -3.29083500 -1.37308800 C -2.94613800 -3.49734600 -2.72657300 H -3.92729100 -3.90207900 -0.83991700 C -1.36810700 -1.70337200 -2.63824100 C -2.01102400 -2.69397200 -3.37158900 H -3.47636000 -4.27567900 -3.27104600 H -0.63247700 -1.02790300 -3.07488400 H -1.78622300 -2.82517600 -4.42669500 Cu -0.81537200 0.10921100 -0.19031000 N -1.61104100 -1.50713300 -1.33671500 O 0.36154400 0.83729400 -1.48929200 O 1.66511800 0.34099700 -1.24995000 C 2.58134200 1.43058300 -0.86763900 C 2.70731300 2.38092800 -2.05133200 H 3.05990200 1.85218700 -2.94274100 H 1.73200500 2.82581800 -2.27888900 H 3.41793900 3.18426200 -1.82712900 C 2.04913300 2.16303800 0.35255200 H 1.97877000 1.50914000 1.22922600 H 2.69506700 3.00986300 0.60934500 H 1.05095200 2.55669600 0.13741700 C 3.87108600 0.67110900 -0.61341300 C 4.60769600 0.81320700 0.56616600 C 4.33687200 -0.21941600 -1.58993000 C 5.78304800 0.09017900 0.76199700 H 4.27385200 1.50043600 1.34181000 C 5.50304100 -0.94948700 -1.39053000 H 3.76663200 -0.34680100 -2.50854300 C 6.23217000 -0.79537900 -0.21290100

42

H 6.35067600 0.22473100 1.68120800 H 5.84745900 -1.63830700 -2.15969300 H 7.15021700 -1.35927400 -0.05918800

7b

Energy: -1612.79060311 a.u.

C 0.90822900 -2.25278000 -0.05084500 C 0.98981300 -3.62397500 -0.26393200 C 0.08891900 -4.22131700 -1.13816800 C -0.85764100 -3.42348200 -1.77489300 C -0.86994500 -2.05711800 -1.52214200 N 0.00364100 -1.47852600 -0.67219800 H 0.11632300 -5.29361900 -1.31952900 H 1.57735800 -1.72811200 0.62929000 H 1.74462100 -4.20631700 0.25769200 H -1.58260500 -3.85346300 -2.46380500 C -1.81952300 -1.12416100 -2.22756700 H -1.28433800 -0.65650000 -3.06575600 H -2.66170800 -1.68455600 -2.66559000 N -2.28752900 -0.04396800 -1.34522600 C -2.53213800 1.23032600 -2.04027700 H -3.51305800 1.25080500 -2.54264800 H -1.77093900 1.32742400 -2.82688100 C -2.39046900 2.38893500 -1.08697200 C -3.13569500 3.55687800 -1.19691200 N -1.44660000 2.24169300 -0.13736600 C -2.88837500 4.60085700 -0.30927700 H -3.89650100 3.64602300 -1.97014200 C -1.20999400 3.24420100 0.72031600 C -1.90784500 4.44396400 0.66546300 H -3.45943400 5.52416100 -0.37630000 H -0.43103000 3.04334200 1.45637300 H -1.68761700 5.23404700 1.37813400 C -3.45804700 -0.44221200 -0.53343200 H -4.21351000 -0.94291200 -1.16139400 H -3.91468200 0.48547800 -0.15930500 C -3.07917000 -1.29373100 0.64895200 C -3.78237600 -2.43490500 1.01735300 C -3.38312900 -3.12563100 2.15983600 H -4.62804500 -2.77619800 0.42252500 C -1.64059500 -1.51248700 2.44223800 C -2.29517000 -2.65700200 2.88841000 H -3.91398300 -4.02234400 2.47235700 H -0.76653200 -1.10664400 2.95234500 H -1.95173100 -3.17012200 3.78291300 Cu -0.64791200 0.36586700 0.07303400 N -2.02736200 -0.84209500 1.35242000 O 0.62936000 0.87518400 1.38819000 O 1.91231200 0.36333600 1.09162900 C 2.77376300 1.39591800 0.49559800 C 2.10017600 1.98295100 -0.74005900 H 1.77843600 1.19165500 -1.43054300 H 1.22357300 2.57670100 -0.45844200 H 2.79803200 2.63374800 -1.27853300 C 3.01325600 2.47171100 1.53913500 H 3.47738100 2.05612600 2.43916800 H 3.65353300 3.27043400 1.14786200 H 2.05302600 2.91136200 1.82623900

43

C 4.00862400 0.59800500 0.11569800 C 5.27580000 0.88789200 0.62500100 C 3.87964000 -0.47044700 -0.78099500 C 6.38457200 0.13379500 0.24556400 H 5.40994300 1.71251700 1.32180600 C 4.98150800 -1.23060600 -1.15404500 H 2.89749000 -0.70671600 -1.19125800 C 6.24157700 -0.92858500 -0.64079600 H 7.36485100 0.37924300 0.64949800 H 4.85934100 -2.05771100 -1.85172300 H 7.10825100 -1.51788600 -0.93382800

7c

Energy: -1612.79286012 a.u.

C -2.08887200 -2.45578300 -0.93292000 C -3.26149400 -3.16270400 -1.16369600 C -4.39511400 -2.45959000 -1.56001000 C -4.31160000 -1.08025000 -1.72504300 C -3.09666000 -0.44473300 -1.49178000 N -2.00671500 -1.12710800 -1.09645900 H -5.33592600 -2.97713200 -1.73439800 H -1.17269100 -2.93219400 -0.58360200 H -3.28427700 -4.23990400 -1.02254800 H -5.17904300 -0.49916500 -2.03351800 C -2.90664300 1.03144700 -1.73892400 H -2.59349800 1.16361500 -2.78387900 H -3.86544700 1.56425800 -1.63824100 N -1.87374200 1.63072200 -0.87467400 C -0.97088000 2.55316100 -1.57680700 H -1.42960600 3.54230800 -1.74296600 H -0.77416400 2.12427700 -2.56941400 C 0.33713800 2.69250600 -0.84325400 C 1.07400400 3.86998600 -0.87782100 N 0.77994400 1.59164000 -0.19754300 C 2.31615300 3.91344500 -0.25010500 H 0.67816800 4.73940300 -1.39955800 C 1.97074800 1.64372100 0.42247300 C 2.77281100 2.77823300 0.40866800 H 2.91185100 4.82339600 -0.27268300 H 2.27370900 0.72782700 0.92575100 H 3.73507600 2.75783500 0.91394200 C -2.45280500 2.25307700 0.33343400 H -3.26629500 2.94764500 0.06510000 H -1.65571700 2.84945900 0.80038400 C -2.92118700 1.21081700 1.31121000 C -4.15847000 1.25445300 1.94311200 C -4.48252900 0.24281000 2.84530300 H -4.85522400 2.06451100 1.73397600 C -2.34915200 -0.74360400 2.40070900 C -3.56404000 -0.77491300 3.07969700 H -5.44408400 0.24860800 3.35417500 H -1.59073900 -1.51664300 2.52707600 H -3.78239800 -1.58261800 3.77347700 Cu -0.56281500 0.01661600 -0.12895500 N -2.03350800 0.22825100 1.54004200 O 0.30590500 -1.55164700 0.51332700 O 1.67116200 -1.31267400 0.74136400 C 2.51124900 -1.87331800 -0.33819400

44

C 2.49093900 -3.38960500 -0.20490100 H 2.85725000 -3.70385000 0.77762100 H 1.46608300 -3.75954300 -0.32642500 H 3.12270200 -3.85490100 -0.96995800 C 1.97945200 -1.44594100 -1.69478000 H 1.94678200 -0.35320700 -1.79251200 H 2.61175500 -1.84201600 -2.49683600 H 0.96889100 -1.84006700 -1.84123900 C 3.86594700 -1.28068700 0.00603900 C 4.63411300 -0.56964100 -0.91992100 C 4.34769500 -1.41070700 1.31574000 C 5.85459800 -0.00785400 -0.54996000 H 4.28792900 -0.45232700 -1.94510000 C 5.55819900 -0.83759200 1.68980400 H 3.75408100 -1.95209600 2.05077300 C 6.31789700 -0.13494500 0.75604800 H 6.44475000 0.53108500 -1.28911300 H 5.91356000 -0.94582500 2.71291300 H 7.27077600 0.30467300 1.04466700

8) – Self – Decomposition Structures (Tpa) (structure vii in Figure 8)

Energy: --1612.74308465 a.u.

C -2.13245200 -2.22350000 1.12975900 C -2.92626700 -3.29377800 0.73732500 C -3.09372100 -3.53120900 -0.62425100 C -2.45544500 -2.70420700 -1.54453400 C -1.66855300 -1.65872200 -1.07267900 N -1.52403300 -1.42880600 0.24287600 H -3.71584000 -4.35461900 -0.96834400 H -1.95229400 -1.97252000 2.17531200 H -3.40444700 -3.92229600 1.48369700 H -2.56167000 -2.86920300 -2.61522600 C -0.84725200 -0.77440100 -1.97707800 H 0.15362700 -1.22267100 -2.06408000 H -1.27242800 -0.74107800 -2.99325600 N -0.66849400 0.58131100 -1.42251100 C 0.62262400 1.19542900 -1.79105600 H 0.60863600 1.58653000 -2.82124000 H 1.38586800 0.40472300 -1.75090200 C 1.01392200 2.26364800 -0.80177500 C 1.92268100 3.27125000 -1.10824800 N 0.50603000 2.12651400 0.43347900 C 2.33008500 4.13476600 -0.09570400 H 2.31305300 3.36702100 -2.11993500 C 0.90742500 2.94339800 1.41255900 C 1.82137700 3.96568600 1.18914800 H 3.04265000 4.92905400 -0.30757700 H 0.48659000 2.73367900 2.39438100 H 2.12581200 4.61327600 2.00690300 C -1.79780800 1.48129000 -1.75217800 H -2.03957400 1.41347800 -2.82527900 H -1.45142300 2.50537800 -1.55824600 C -3.00835800 1.21518900 -0.89976700 C -4.27790700 1.02777800 -1.43557100 C -5.34713000 0.81729200 -0.56709900 H -4.42759400 1.04786100 -2.51402700 C -3.80244000 0.99007300 1.24900800 C -5.10770400 0.80035700 0.80218100

45

H -6.35150800 0.66695000 -0.95708500 H -3.56048100 0.97280100 2.31211700 H -5.91317700 0.64162600 1.51469000 Cu -0.56587000 0.35568500 0.69522100 N -2.77209600 1.19516400 0.42374200 O -0.06228400 0.00463300 2.41406200 O 1.53059100 -0.36515200 0.85253500 C 2.29886500 -1.42096600 1.35113200 C 2.87470200 -1.09034900 2.72232500 H 3.42967500 -0.14694400 2.70516700 H 2.04887500 -0.98175100 3.43391200 H 3.54670200 -1.88203600 3.07340200 C 1.50209300 -2.71681800 1.39863300 H 1.03235500 -2.93683000 0.43212100 H 2.12712100 -3.56908500 1.69070800 H 0.70764400 -2.59524200 2.14302400 C 3.34579300 -1.36938700 0.22651700 C 3.52438700 -2.41316500 -0.68964600 C 4.07769600 -0.18073000 0.05332500 C 4.45885500 -2.29453600 -1.71367700 H 2.96457500 -3.33933300 -0.57955600 C 4.99588200 -0.05871600 -0.98155000 H 3.90807300 0.65080000 0.73579600 C 5.19242700 -1.11807000 -1.86682000 H 4.61974700 -3.12843300 -2.39438200 H 5.56352500 0.86283300 -1.09727700 H 5.91716900 -1.02959900 -2.67379300

9) – Cyclohexadiene (CHD) Oxidation (Tpa)

9a (structure viii in Figure 8)

Energy: -1846.15236083 a.u.

C 1.72951600 -1.33066500 2.49124600 C 2.70090400 -2.15976300 3.03667700 C 4.03844800 -1.80664800 2.89194900 C 4.35006600 -0.63071200 2.21621000 C 3.32329500 0.15800300 1.70926300 N 2.02563900 -0.19184200 1.84010700 H 4.82835100 -2.43805800 3.29285300 H 0.66740000 -1.57313600 2.54019700 H 2.40826100 -3.06952000 3.55434400 H 5.38508300 -0.32018300 2.08132900 C 3.61061100 1.48745400 1.04833700 H 3.50061900 2.27227200 1.80983500 H 4.66394500 1.52148800 0.72013900 N 2.69064900 1.79819800 -0.04737400 C 2.24004300 3.18813800 -0.11862400 H 2.92789900 3.83093200 -0.69487400 H 2.23150000 3.58312200 0.90688700 C 0.83878500 3.29890200 -0.67369300 C 0.43500200 4.39287600 -1.43155900 N -0.02154700 2.31440800 -0.33712200 C -0.89338000 4.49163700 -1.83625500 H 1.15858000 5.16272100 -1.69467300 C -1.30294300 2.41330700 -0.73011000 C -1.78176100 3.48449800 -1.47157200 H -1.22670300 5.34111700 -2.42825800

46

H -1.94909900 1.58933300 -0.42239100 H -2.82977700 3.51728800 -1.75993200 C 3.14077700 1.28256700 -1.34550500 H 4.18387800 1.57827300 -1.55606600 H 2.51095500 1.75412100 -2.11443700 C 2.97836800 -0.21225600 -1.44763200 C 3.97703600 -1.04821900 -1.93505800 C 3.72757400 -2.41652300 -2.01649700 H 4.93566100 -0.63338900 -2.24268500 C 1.54159300 -1.99416800 -1.14120100 C 2.48681100 -2.89991900 -1.61396500 H 4.49459300 -3.09454200 -2.38485400 H 0.55046500 -2.31438800 -0.81027300 H 2.25252100 -3.96127800 -1.65519100 Cu 0.78787300 0.60205900 0.40647000 N 1.78020100 -0.68133400 -1.05586600 O -0.94208700 -0.49879300 0.40936600 O -1.36627600 -1.24292200 1.57838800 C -2.29363700 -0.42413700 2.35903500 C -1.59759600 0.85377500 2.79750800 H -0.67257200 0.60588100 3.33141400 H -1.33638400 1.49189200 1.94552200 H -2.23322600 1.43314200 3.47712700 C -0.73331100 -1.40482800 -3.59863100 C -1.64998400 -3.42896700 -2.46090900 C -2.38638000 -2.62417500 -1.66039500 C -1.47632600 -0.62921400 -2.77722300 H -0.12723500 -0.94781700 -4.38073700 H -1.74403300 -4.51129700 -2.37937700 H -3.06557500 -3.06595700 -0.93073900 H -1.46020300 0.45463700 -2.90758900 C -2.28612900 -1.17947900 -1.70691600 H -1.58709600 -0.86793200 -0.52472500 H -3.18452000 -0.61568200 -1.42826400 C -0.74197500 -2.89541800 -3.51970800 H -1.01651000 -3.32413200 -4.50223500 H 0.28939000 -3.27462100 -3.37379000 C -3.55119200 -0.20194400 1.53399200 C -4.25370700 -1.31560800 1.05724300 C -4.02450200 1.06995900 1.20204500 C -5.38656600 -1.16613200 0.26606200 H -3.89122500 -2.31541400 1.29556000 C -5.15859100 1.22555700 0.40444500 H -3.51170800 1.95743500 1.57070300 C -5.84170200 0.10917300 -0.06778000 H -5.91520100 -2.04676700 -0.09515800 H -5.51363900 2.22602700 0.16169400 H -6.72831500 0.22972200 -0.68700600 C -2.56107900 -1.31550700 3.56662500 H -3.28740900 -0.83433000 4.22973900 H -2.96534000 -2.28826400 3.27050300 H -1.63774000 -1.48410300 4.13311200

9b

Energy: -1846.14680416 a.u.

47

C -0.79657300 2.48219400 -0.15649800 C -0.88029500 3.81628500 0.22101600 C 0.17286100 4.66774700 -0.09450700 C 1.26446500 4.15089400 -0.78583100 C 1.27163900 2.80779600 -1.14569600 N 0.25184100 1.97956900 -0.83305100 H 0.15086200 5.71548100 0.19752400 H -1.57453000 1.76182400 0.09482000 H -1.75351000 4.16949900 0.76360700 H 2.11241700 4.78241200 -1.04676700 C 2.40122400 2.21960300 -1.95911400 H 2.09157100 2.20858300 -3.01356900 H 3.28646400 2.87678300 -1.90243100 N 2.71871400 0.84246200 -1.57682200 C 3.05516700 -0.05337600 -2.68290900 H 4.11976500 0.00062200 -2.96957800 H 2.47799200 0.27518800 -3.55855000 C 2.67242400 -1.47996900 -2.37106400 C 3.42917800 -2.55773200 -2.81705500 N 1.52485000 -1.65444100 -1.68089700 C 2.98972200 -3.85347700 -2.56207400 H 4.35387500 -2.37728500 -3.36266700 C 1.10645100 -2.90726700 -1.43694100 C 1.80167300 -4.03150000 -1.86033700 H 3.56841300 -4.70908800 -2.90270400 H 0.17455900 -2.98067700 -0.87482800 H 1.41798300 -5.02390000 -1.63857000 C 3.67731000 0.75293900 -0.46754500 H 4.57642000 1.36358400 -0.66332800 H 4.00438700 -0.29548700 -0.40962900 C 3.04591200 1.13606500 0.84552200 C 3.62248500 2.04932700 1.72095800 C 2.95765600 2.35583000 2.90642600 H 4.57195000 2.52081200 1.47199200 C 1.24348200 0.82020100 2.25224700 C 1.74416600 1.73263400 3.17697300 H 3.37889200 3.07754100 3.60316700 H 0.29133100 0.30706800 2.41166600 H 1.18435600 1.95237500 4.08353400 Cu 0.77157900 -0.01475500 -0.72521300 N 1.87543800 0.52719600 1.11110900 O -0.76338500 -0.98212100 0.22910600 O -2.08704000 -0.38046000 0.17470500 C -2.89496200 -1.04316100 -0.85531100 C -2.19541800 -0.93856800 -2.20558800 H -1.93251500 0.09888000 -2.44224200 H -1.27297500 -1.53162200 -2.21024700 H -2.84687400 -1.31362700 -3.00298900 C -3.09614800 -2.49919500 -0.47372600 H -3.52020300 -2.59669800 0.53184400 H -3.76071700 -3.00469700 -1.18313100 H -2.13286400 -3.02078500 -0.49134200 C -4.16663700 -0.20997100 -0.81244900 C -5.39326600 -0.74073000 -0.40487200 C -4.11717100 1.14123000 -1.17945400 C -6.53836100 0.05189200 -0.37495100 H -5.46983100 -1.78656500 -0.11607600 C -5.25611800 1.93680800 -1.14218800 H -3.17299000 1.57644100 -1.50508800 C -6.47396500 1.39256800 -0.74010100

48

H -7.48543600 -0.38433400 -0.06341000 H -5.19526600 2.98335900 -1.43569300 H -7.36929000 2.01059600 -0.71577100 C 1.22462500 -2.33127900 3.67364600 C -0.89048700 -1.21086500 4.38817600 C -1.51629100 -1.74212800 3.31193700 C 0.57129200 -2.84359900 2.60614700 H 2.27112900 -2.58154100 3.84450600 H -1.45273500 -0.60993100 5.10223600 H -2.57901900 -1.55243300 3.15960500 H 1.10403100 -3.50745400 1.92330100 C -0.81367600 -2.52824300 2.31815200 H -0.77876900 -1.66035000 1.19830100 H -1.39607800 -3.30269300 1.80611200 C 0.55043300 -1.46739000 4.68747900 H 0.65148500 -1.91817100 5.69324700 H 1.10066200 -0.51205100 4.79864800

9c

Energy: -1846.15636108 a.u.

C -1.26146300 -0.69252400 2.63393600 C -2.25303400 -1.22612600 3.44701100 C -2.66561000 -2.53565600 3.22211900 C -2.05760700 -3.26449900 2.20424300 C -1.06293500 -2.66572000 1.43833200 N -0.67653700 -1.39038800 1.64548900 H -3.45011100 -2.98420800 3.82775700 H -0.90877600 0.33357900 2.74740100 H -2.69602300 -0.62004000 4.23306000 H -2.35099800 -4.29322700 1.99979900 C -0.31143600 -3.43694700 0.37588900 H 0.61860700 -3.81309900 0.82541300 H -0.89120000 -4.32727500 0.07606200 N 0.05475100 -2.61211700 -0.77632000 C 1.38868900 -2.85578900 -1.32393400 H 1.41747200 -3.71655900 -2.01513600 H 2.04825800 -3.10367600 -0.47944100 C 1.94161000 -1.62557300 -2.00284900 C 2.81537800 -1.71466100 -3.08139300 N 1.58482900 -0.43741600 -1.47635200 C 3.34029900 -0.54857500 -3.63037700 H 3.07757800 -2.69130900 -3.48494100 C 2.08885900 0.68360500 -2.01198900 C 2.96768700 0.67645700 -3.08657800 H 4.02312500 -0.59702300 -4.47582400 H 1.76510800 1.60832800 -1.53356300 H 3.34843500 1.61292900 -3.48615900 C -0.98584500 -2.57294600 -1.81263700 H -1.28841400 -3.59071100 -2.11679700 H -0.54398200 -2.08746000 -2.69473500 C -2.18012400 -1.77313300 -1.36108300 C -3.48178000 -2.25705700 -1.43323300 C -4.52282700 -1.45936300 -0.96273300 H -3.67464900 -3.24802300 -1.84140700 C -2.89533100 0.20794500 -0.41940100 C -4.22475600 -0.20573200 -0.43999700 H -5.54946200 -1.81815500 -0.99512800 H -2.60651700 1.18170500 -0.01519100

49

H -5.00392900 0.44270500 -0.04501900 Cu 0.16152300 -0.46379900 -0.01368700 N -1.89297200 -0.55413100 -0.86823800 O 0.16345800 1.54808500 0.41331900 O 0.45464600 1.91930500 1.78929000 C 1.86861200 2.25111000 1.91423700 C -2.59708700 3.01062300 -2.39757900 C -3.32010000 3.82008900 -0.14767100 C -2.01984100 3.99569800 0.18726700 C -1.30822600 3.19435600 -2.02862700 H -2.83256400 2.66147500 -3.40234600 H -4.10514700 4.08904100 0.55842200 H -1.76675300 4.39712300 1.16937500 H -0.51403300 2.99115600 -2.74882000 C -0.93654000 3.63640400 -0.70172000 H -0.35684800 2.47332400 -0.05796700 H -0.01528500 4.22247000 -0.61786000 C -3.74274300 3.33111100 -1.49505100 H -4.40291000 4.07857900 -1.97589100 H -4.41022100 2.45193500 -1.40017300 C 1.98652500 2.52645500 3.40985800 H 3.02054700 2.78488400 3.66040500 H 1.33949800 3.36126100 3.70099500 H 1.70571300 1.64582000 3.99765300 C 2.70666200 1.04589300 1.51226800 C 3.80420100 1.13456300 0.65399800 C 2.36951600 -0.21094600 2.02915100 C 4.53590100 -0.00186200 0.30821400 H 4.09880100 2.09766900 0.23949100 C 3.09407300 -1.34782200 1.68584400 H 1.52261600 -0.29366300 2.70901600 C 4.18058000 -1.24737700 0.81666100 H 5.38786200 0.09074200 -0.36365300 H 2.81709700 -2.31243200 2.11274600 H 4.75805000 -2.13226800 0.55206400 C 2.16807100 3.50700100 1.11419000 H 1.46753600 4.29957500 1.39948100 H 3.18307000 3.86966300 1.31027000 H 2.07268900 3.33056900 0.03645700

9d

Energy: -1846.14697952 a.u.

50

C -1.47205000 1.86059000 1.59716600 C -2.37876700 2.81632300 2.03581100 C -3.67255600 2.41041300 2.34773400 C -3.99902400 1.06262100 2.22587900 C -3.03108500 0.16361400 1.79070000 N -1.78391700 0.56136600 1.46647200 H -4.41774200 3.13000300 2.67987200 H -0.45338700 2.12778600 1.31064900 H -2.07190300 3.85634100 2.12129900 H -4.99969200 0.70541100 2.46499900 C -3.30285300 -1.32236200 1.72253200 H -2.93594500 -1.77508000 2.65430900 H -4.39044300 -1.50684300 1.69889600 N -2.61723000 -1.97674700 0.60564000 C -1.99445200 -3.26128100 0.91754900 H -2.70995800 -4.10212200 0.89506500 H -1.61674300 -3.19720900 1.94821100 C -0.82866800 -3.54852100 0.00309200 C -0.51984800 -4.84548900 -0.39029800 N -0.06566000 -2.49237500 -0.35630400 C 0.61913300 -5.07359700 -1.15670700 H -1.16735600 -5.66742600 -0.08950000 C 1.03573800 -2.71811400 -1.09535500 C 1.41446700 -3.98894600 -1.50864200 H 0.87832800 -6.08164000 -1.47286300 H 1.62530700 -1.83414700 -1.33169800 H 2.31755600 -4.11567800 -2.09965200 C -3.42794700 -2.02510900 -0.61519800 H -4.41181300 -2.49229700 -0.43083200 H -2.89406100 -2.66464000 -1.33354000 C -3.59308300 -0.65215500 -1.20811200 C -4.83137900 -0.13947600 -1.57907600 C -4.89906400 1.14644200 -2.10948300 H -5.72999900 -0.74042600 -1.44881500 C -2.52693000 1.28199700 -1.86206100 C -3.72324900 1.87469600 -2.25230300 H -5.85625500 1.57308700 -2.40139800 H -1.57767400 1.81048800 -1.95302200 H -3.72680300 2.88288300 -2.65900800 Cu -0.84264400 -0.64240200 0.03132300 N -2.45199000 0.04928600 -1.34899000 O 0.64046600 0.73608600 -0.35899100 O 1.97177700 0.16381500 -0.40158500 C 2.61026900 0.23494300 0.91981900 C 2.78121500 1.68729300 1.34151600 H 3.43379600 2.22808700 0.65047200 H 1.80870800 2.19786800 1.36402900 H 3.21938700 1.74125800 2.34458900 C 1.77216200 -0.51419400 1.94212000 H 1.58349800 -1.54854700 1.63178000 H 2.27471500 -0.53096700 2.91604400 H 0.80663000 -0.01263100 2.07667500 C 3.94465800 -0.42339100 0.60996500 C 4.38764000 -1.57072100 1.27227400 C 4.75489100 0.12778300 -0.39172500 C 5.61820600 -2.14260700 0.95591300 H 3.78031500 -2.02247600 2.05410600 C 5.97735000 -0.44846400 -0.71589000 H 4.41173200 1.01331200 -0.92664000 C 6.41518200 -1.58535200 -0.03893900

51

H 5.95369400 -3.02845400 1.49211700 H 6.59314600 -0.00734100 -1.49754900 H 7.37592300 -2.03305400 -0.28571700 C 3.02579100 4.09060000 -1.14100700 C 2.27872700 3.21070500 -1.84750500 C 0.24153200 3.97709000 -0.69612400 C 0.96198300 4.84721700 0.04626000 H 4.08891600 4.19961300 -1.35415100 H 2.74472000 2.61142400 -2.62961600 H -0.84726800 3.96541200 -0.60510900 H 0.46016600 5.53367800 0.72798400 C 0.86655300 3.02333800 -1.59271400 H 0.27174600 2.69313300 -2.45271700 H 0.76874900 1.77178400 -0.90526100 C 2.44831100 4.95150800 -0.06566600 H 2.92129000 4.70943800 0.90746200 H 2.74189500 6.00534600 -0.22210800

9e

Energy: -1846.15326491 a.u.

C 1.64164500 1.30850500 1.58710900 C 2.34429500 2.33392200 2.20558200 C 1.64334400 3.46312500 2.61725500 C 0.26796200 3.51097100 2.40787900 C -0.36533900 2.43942400 1.78650200 N 0.31834500 1.35484100 1.36969700 H 2.15748500 4.29547000 3.09297700 H 2.14726300 0.41201900 1.22341600 H 3.41861300 2.24452000 2.34933400 H -0.31587600 4.37546600 2.72083900 C -1.86671100 2.39940000 1.60835800 H -2.29085400 1.83050300 2.44794100 H -2.28257700 3.41922600 1.68478800 N -2.27451000 1.73518400 0.37056600 C -3.44339400 0.86514900 0.48049400 H -4.39660300 1.42018100 0.42560000 H -3.40579400 0.38920600 1.47102400 C -3.41840300 -0.22578800 -0.56213200 C -4.59425000 -0.75615200 -1.08245100 N -2.20647100 -0.69382300 -0.92482600 C -4.52446100 -1.80275800 -1.99624100 H -5.55375100 -0.34693200 -0.77049800 C -2.14261500 -1.70239200 -1.80975800 C -3.27366600 -2.28398700 -2.36745500 H -5.43284300 -2.22909700 -2.41647100 H -1.13731300 -2.04751100 -2.04738900 H -3.16863400 -3.09625800 -3.08211200 C -2.36358900 2.65372200 -0.77026900 H -3.01355500 3.51731000 -0.54181200 H -2.83570700 2.10036900 -1.59473800 C -0.99978400 3.11463200 -1.20879200 C -0.68243500 4.45808200 -1.37988100 C 0.60907200 4.80244900 -1.77171700 H -1.43701200 5.22285000 -1.20190700 C 1.12898300 2.47128300 -1.79961600 C 1.53684300 3.78882500 -1.98349700 H 0.88555500 5.84621600 -1.90458200 H 1.81749500 1.64018600 -1.95532200

52

H 2.55708500 4.00850600 -2.28891900 Cu -0.58416800 0.28001400 -0.17541700 N -0.10557300 2.13040200 -1.41729200 O 1.07472100 -0.88929300 -0.60188100 O 0.87026700 -2.28078900 -0.94864700 C 0.85408500 -3.12566300 0.25347000 C 2.12156500 -2.92259700 1.06760400 H 2.99385800 -3.23455600 0.48507600 H 2.26752000 -1.87284200 1.34275700 H 2.08125500 -3.51427300 1.98905800 C 4.96867300 -2.32760700 -0.96000700 C 4.01381400 -1.80840700 -1.76697900 C 4.16452100 0.35158500 -0.59912800 C 5.10011000 -0.14323000 0.24290200 H 5.34652400 -3.33384400 -1.13828200 H 3.62050500 -2.40330100 -2.59089800 H 3.89520000 1.40919300 -0.53943500 H 5.58491100 0.50888000 0.96933500 C 3.47542900 -0.48097800 -1.56435100 H 3.09022100 0.01697300 -2.46177300 H 2.15565900 -0.70280900 -1.00010100 C 5.55362100 -1.56574200 0.18392300 H 5.32261700 -2.08041200 1.13890300 H 6.65727400 -1.60898700 0.14747800 C 0.86099500 -4.50898200 -0.38299400 H 0.73507800 -5.28302200 0.38159500 H 0.06081100 -4.62124400 -1.12229900 H 1.81346000 -4.67587400 -0.89604500 C -0.41357200 -2.82787500 1.04478100 C -0.42980400 -1.80602400 2.00170200 C -1.60944500 -3.51449800 0.80299700 C -1.59693500 -1.47798800 2.68948000 H 0.48539500 -1.26274500 2.22725300 C -2.77876100 -3.19188400 1.48634300 H -1.63696000 -4.32201700 0.07381100 C -2.77801900 -2.17059800 2.43397600 H -1.57143000 -0.69170200 3.44475400 H -3.69152200 -3.75101400 1.28615500 H -3.68756300 -1.93216600 2.98427200

9f

Energy: -1846.14536742 a.u.

C -0.43539900 -1.99008000 1.18532700 C -0.53320900 -3.31404400 1.59286500 C 0.55955900 -3.90015600 2.22234800 C 1.70439600 -3.13325600 2.42144100 C 1.72513100 -1.81252900 1.98758500 N 0.66613500 -1.24415700 1.37186200 H 0.52640100 -4.93736600 2.54876600 H -1.26324900 -1.49550600 0.67758800 H -1.45160200 -3.86646400 1.40817400 H 2.58247300 -3.55370600 2.90925800 C 2.91385400 -0.91479800 2.23021100 H 2.68298200 -0.26720900 3.08773200 H 3.79202000 -1.51812300 2.51980300 N 3.19566700 -0.04774600 1.08711400 C 3.66395100 1.29625500 1.42283200 H 4.74735000 1.33654000 1.63112000

53

H 3.15328700 1.59684300 2.34890800 C 3.30548500 2.28024300 0.33684200 C 4.16051100 3.31389100 -0.02772700 N 2.08826900 2.12837600 -0.22904600 C 3.75147900 4.22991600 -0.99266200 H 5.13689100 3.39756100 0.44665900 C 1.69795600 3.01392400 -1.16200100 C 2.49468000 4.07718800 -1.56799200 H 4.40617900 5.04545500 -1.29175400 H 0.70110200 2.84669100 -1.56866600 H 2.13184000 4.76623500 -2.32620800 C 4.01208600 -0.69497700 0.05561300 H 4.87614600 -1.22229900 0.49720800 H 4.42008100 0.10302700 -0.58211700 C 3.21403600 -1.62883500 -0.81922700 C 3.68582100 -2.88403600 -1.18980500 C 2.92043600 -3.66831700 -2.04921400 H 4.64198200 -3.24025700 -0.80959400 C 1.31236200 -1.90389800 -2.09248300 C 1.70961200 -3.16786300 -2.51548300 H 3.26633700 -4.65519500 -2.34913000 H 0.37134300 -1.46307400 -2.42411900 H 1.08115200 -3.74147500 -3.19254600 Cu 1.14014600 0.35038100 0.10940200 N 2.03709500 -1.14781000 -1.26069900 O -0.79676600 0.55364200 -0.57499300 O -1.25426900 1.89030400 -0.88357500 C -1.89031200 2.52300700 0.28191600 C -4.74335000 -0.78623200 -1.58183100 C -3.63205200 -0.21358800 -2.09801400 C -2.34597500 -2.26682500 -1.66343500 C -3.43559500 -2.86028000 -1.12602300 H -5.68505400 -0.23980500 -1.57857800 H -3.68488400 0.79474200 -2.50889000 H -1.42099500 -2.84119600 -1.75652000 H -3.38702800 -3.90033900 -0.80256200 C -2.34858400 -0.88319600 -2.10030400 H -1.68571800 -0.63625300 -2.94012700 H -1.54448600 -0.13200000 -1.20077800 C -4.75086400 -2.16602700 -1.01638000 H -5.08232700 -2.13328800 0.03976400 H -5.53754100 -2.77406400 -1.50126000 C -2.22593000 3.88643500 -0.30577000 H -2.75337100 4.50085800 0.43134100 H -1.30589300 4.40938700 -0.58828400 H -2.85244900 3.79723800 -1.19920400 C -0.87198200 2.67908000 1.40472700 H -1.33950800 3.14259200 2.28113100 H -0.45883400 1.71210800 1.71793100 H -0.03883400 3.31334000 1.08085900 C -3.10941900 1.73769400 0.73863700 C -4.41243800 2.15076900 0.44395700 C -2.94685100 0.57250600 1.49962000 C -5.51428500 1.42837400 0.89517900 H -4.58295200 3.05730800 -0.13293300 C -4.04329300 -0.16445500 1.93332500 H -1.94569800 0.24926100 1.77479700 C -5.33530000 0.26413900 1.63613300 H -6.51861400 1.78193100 0.66794600 H -3.88658100 -1.06819600 2.52281400

54

H -6.19716200 -0.29873200 1.99149200

II – Calculated UV-Vis Spectra

TD-DFT spectra (see Computational Methods section for details) generated by applying Gaussian broadening to

computed peak positions and scaling arbitrary absorption intensities to predicted oscillator strengths.

a) [CuII(bpa)(CH3CN)(O2Cm)]+

b) [CuII(bpa)(O2Cm)]+

55

c) [CuII(tpa)(O2Cm)]+

III - Selected M06-L vibrational frequencies (cm–1) with mode assignment and 18O2 isotope shift

56

a) Computed for structure i

896.5 (Δν =32.7) — mixed O–O stretching mode

812.4 (Δν = 15.4) — mixed O–O stretching mode

619.4 (Δν = 7.4) — C–C–O deformation mode

499 (Δν = 16) — Cu–O stretching mode

b) Computed for structure ii

903.4 (Δν =41.6) — mixed O–O stretching mode

833.4 (Δν = 17.2) — mixed O–O stretching mode

604.8 (Δν = 7.9) — C–C–O deformation mode

515.7 (Δν = 15.7) — Cu–O stretching mode