Ab Initio Study of Microsolvated Al3+-Aromatic Amino Acid Complexes

J. Larrucea,† E. Rezabal,*,‡ T. Marino,§ N. Russo,§ and J. M. Ugalde†

Kimika Fakultatea, Euskal Herriko Unibertsitatea and Donostia International Physics Center (DIPC), P. K.1072, 20080 Donostia, Euskadi, Spain, Institut fur Anorganische und Analytische Chemie, Johann WolfgangGoethe-UniVersitat Frankfurt Max-Von-Laue-Str. 7, D-60438 Frankfurt am Main, Germany, and Dipartimentodi Chimica and Centro di Calcolo ad Alte Prestazioni per Elaborazioni Parallele e Distribuite-Centrod’Eccellenza MIUR, UniVersita della Calabria, I-87030 ArcaVacata di Rende (CS), Italy

ReceiVed: March 2, 2010; ReVised Manuscript ReceiVed: May 17, 2010

The systematic microhydration of Al3+-aromatic amino acid complexes is studied by both B3LYP/G03 andPBE/CPMD methods, considering the different binding sites available. The binding affinity of water moleculestogether with the structural and thermochemical changes triggered by the solvation of the metal are discussed,which are found to be dominated by the charge and size of the metal cation, yielding a very subtle equilibriumbetween the steric hindrance and the charge transfer to the metal. Some structures previously seen to beunfavored in the gas phase are stabilized upon microhydration, without the need of including bulk solventeffects.

Introduction

Most biological processes take place in aqueous environ-ments, where biological reactions are triggered by specificinteractions which take place within the first solvation shellsaround the solvated biological species. Full solution studies canhardly provide much detailed insight into these features, whilemicrohydration studies do yield sensible information on ther-mochemical and structural changes arising upon the sequentialincrement of water molecules in the nearest shell of thebiological solute species.1 Within this context, metalloproteinsrepresent an example where microhydration studies are crucial,due to the subtle balance between metal-hydration by the solventmolecules and metal-ligation by the amino acid side chainligands. Thus, the careful study of the effects of microhydrationbecomes mandatory for unveiling the role of the solventmolecules in the final structure and, therefore, the reactivity ofthe metalloprotein in the solvent.

Our particular interest toward the Al3+ arises from its capacityof altering and blocking the activity of many enzymes, crucialfor many chemical reactions in living systems.2 Due to thehighly sophisticated structure and big size of the proteins, smallbiological models are normally used for understanding the basicfeatures governing their structure and chemical activity. Inparticular, gas phase studies of metal-amino acid complexesas a model for bigger systems have provided a new theoreticaland experimental insight on the contributions of the differentinteractions within a metalloprotein, including the role ofdifferent degrees of hydration of the metal binding site.

Many experimental and theoretical studies on the hydrationof metalated amino acids are available in the literature, most ofthem related to alkali metals and aliphatic and acidic aminoacids.1,3–9 Few of them considered aromatic amino acids(AAAs)1,9,10 or dicationic metals.11–13 Nevertheless, to the bestof our knowledge, the study of triply charged metals has not

been addressed yet. Instead, several studies regarding complexformation between Al3+ and various bidentate and potentiallytridentate amino acids (Gly, Ser, Thr, Gln, Asn, Glu, and Asp)and some model compounds have been carried out in aqueoussolution by means of pH-potentiometric and multinuclear (1H,13C, and 27Al) NMR techniques.

The present manuscript reports on the microhydration of thecomplexes formed by the triply charged aluminum cation Al3+

and AAAs, in particular, phenylalanine (Phe), tyrosine (Tyr),and tryptophane (Trp). The aromatic ring in the side chains ofthese amino acids provides the possibility of exploring also thecation-π interaction,14 which is now recognized as one of thestrongest noncovalent binding forces in the gas phase andclaimed to occur also on protein surfaces, exposed to aqueoussolvation.15–17 Due to the abundance of AAAs in proteins, thecation-π interactions should play a crucial role in the structureand activity of the proteins and must therefore be includedtogether with the different interactions likely to take placebetween a metal and the protein.

Earlier investigations on nonhydrated Al3+-AAA systemsin the gas phase provided valuable information on their intrinsicchemical and physical properties.18 As a continuation of the baresystem gas-phase study, the present research consists of thestudy of a set of sequential hydrations of the various bareAl3+-AAA complexes characterized earlier. The stepwiseaddition of water molecules to the aluminum cation was carriedout, until an octahedral environment around the metal wasachieved, to learn more on the role the increment of the numberof water molecules plays on the coordination and stability ofthe metal center.

Computational Details

Geometry optimization for each structure was performed attwo theory levels, which will be named B3LYP/G03 and PBE/CPMD throughout the text. The former were performed withGaussian03;19 the B3LYP hybrid functional coupled with thestandard all-electron 6-31+G(d,p) basis for the aluminum ionand the compact effective core potentials and shared-exponentbasis set of Stevens, Basch, Krauss, and Jasien (SBKJ/*+) for

* To whom correspondence should be addressed. E-mail: rezabal@chemie.uni-frankfurt.de.

† Euskal Herriko Unibertsitatea and Donostia International Physics Center.‡ Johann Wolfgang Goethe-Universitat Frankfurt Max-von-Laue-Str. 7.§ Universita della Calabria.

J. Phys. Chem. B 2010, 114, 9017–9022 9017

10.1021/jp101874p 2010 American Chemical SocietyPublished on Web 06/18/2010

C, N, O, and H was chosen for geometry optimizations andfrequency calculations, which confirmed the stationary pointnature of the structures studied. Single point calculations withthe 6-311++G(2df,2p) larger basis set were done to improvethe accuracy of the binding energies. This level of theory waspreviously seen to represent a good compromise between theaccuracy and computational effort required for this kind ofsystem.20,21

The Car-Parrinello molecular dynamics simulations wereperformed22 by means of the CPMD package;23 the temperatureof the system was set to 300 K by using a Nose24-Hoover25

thermostat,26 and atoms were described by using the approximatePBE density functional27 and Vanderbilt ultrasoft pseudopoten-tials28 implemented29 for CPMD,30 with a 30 Ry plane wavecutoff. Electronic fictitious mass (µ) was set at 900 amu with atime step of 0.17 fs (7 au). Hydrogens (protiums) weresubstituted by deuteriums to increase the usable time step lengthsince the experimental properties of heavy water are well-knownand the chemistry will not be altered, as was already seen inthe literature.31

The total charge of the system was neutralized by using ahomogeneous negative background charge,32,33 and simulationsof the global minimum structures were run for over 20 ps toensure the reliability of the statistics.

The bare Al3+-AAA complexes studied previously18 wereused as a starting point in the microhydration process, and thehydration reaction of the subsequent hydrated complexes wasdefined as

with n ) 1-4 being the number of water molecules attachedto the metal. These formation free energies, together with therelative stability of the different isomers found upon each watermolecule addition, will be studied in the present paper.

Results

The AAAs have several electron-rich sites to which Al3+ canbind, namely, the aromatic ring and the N and O atoms in thebackbone. For a thorough exploration of the potential surface,in the present contribution the cation-π interaction with thearomatic ring, together with the mono- or bicoordination to theAAA backbone, was considered, for both the charge-solvated(cs) and zwitterionic (zw) forms of the AAA. Consequently, ahigh number of structures was generated, and for the sake ofbrevity, only the low lying isomers, namely, those within 20kcal/mol from the global minimum, will be discussed here.

Considering the binding mode to the amino acid backbone,three coordination patterns were observed to coexist within theselected energy gap in each step of the microhydration: bindingto N and O atoms of the cs AAA (named cs-nw in the presentcontribution, n being the number of water molecules added)and coordination to one or two of the carboxylic oxygens ofthe zw form (named zw1-nw and zw2-nw, respectively, n beingthe number of water molecules added). Trp offers two aromaticrings in the side chain to which the metal can bind, and therefore,the isomers will be named considering whether the six-membered ring or the five-membered ring is the one interactingwith the metal. The gradual filling up of the first solvation shellof the metal results, in some cases, in a spontaneous water orproton migration of the second shell. This structure will bedenoted by a t (transfer) added to the name.

As expected,18 the structures found for Tyr and Phe are verysimilar and therefore will be discussed together, while the Trpcomplexes will be analyzed separately. Table 1 and Table 2present relative stabilities for all the hydrated complexesexamined, while the corresponding optimized geometries aredisplayed in Figure 1, Figure 2, and Figure 4. In general, goodagreement is found between PBE/CPMD and B3LYP/G03

[Al-AAA(H2O)n-1]+3 + H2O f [Al-AAA(H2O)n]

+3

(1)

TABLE 1: Relative Enthalpies and Electronic EnergiesArising, Respectively, from the B3LYP/G03 and PBE/CPMD(in Parentheses) Calculations of the Different[Al-Phe-(H2O)n]+3 and [Al-Tyr-(H2O)n]+3 (in Italics)Complexes Studied (in kcal/mol)a

n ) 1 n ) 2 n ) 3 n ) 4

zw1 11.2 (5.5) 0.0 (0.0) 0.0 (5.0) 0.0 (2.6)8.6 (3.1) 4.7 (0.0) 1.3 (0.0) 3.2 (0.0)

zw1t 0.0 (6.1)zw2 9.7 (2.35) 2.7 (4.4) 0.5 (0.0) 1.4 (0.0)

7.6 (4.8) 0.0 (5.5) 0.0 (5.0) 7.6 (1.0)cs 0.0 (0.0) 2.9 (7.4) 13.5 (13.5) 12.8 (20.8)

0.0 (0.0) 4.9 (7.2) 12.5 (14.8) 18.9 (14.0)cst 8.0 (10.1) 15.6 (17.7)

2.5 11.5 (14.8)cst(2) 10.2

at denotes a proton transfer from one of the water molecules

attached to the metal.

TABLE 2: Relative Enthalpies and Electronic EnergiesArising, Respectively, from the B3LYP/G03 and PBE/CPMD(in Parentheses) Calculations of the Different[Al-Trp-(H2O)n]+3 Complexes Studied (in kcal/mol)a

n ) 1 n ) 2 n ) 3 n ) 4

zw1-6 18.5 (13.4) 0.0 (0.4) 0.0 (0.0) 0.0zw2-6 8.9 (0.0) 1.7 (0.0) 9.5 (3.4) (0.0)zw2-5 17.1 15.3cs6 0.0 (1.3) 6.7 18.2cs6t 19.5cs5 8.2 12.1 (13.8) 20.0cs5t (9.7) (14.0)

at denotes a proton transfer from one of the water molecules

attached to the metal.

Figure 1. Optimized [Al-Phe-(H2O)n]+3 systems (B3LYP/G03 theorylevel).

9018 J. Phys. Chem. B, Vol. 114, No. 27, 2010 Larrucea et al.

calculations, considering the inherent differences of the methods.The occasional discrepancies will be discussed throughout thetext, together with the changes the addition of water moleculestriggers on some fundamental structural and thermodynamicproperties of the complexes.

Geometries and Coordination. The coordination of the metalarises from an equilibrium between the charge neutralizationof the metal, which tends to saturate the coordination shell ofthe metal, and the steric hindrance of the structure, which, inturn, has the opposite tendency. The magnitude of these effectsarises from the inherent characteristics of the metal, which hasa high charge that provides strong bonds, and a small ionicradius, which minimizes the space for the ligands and givesrise to a strong steric hindrance. Consequently, even when theavailable ligands permit it, Al3+ hexacoordination is not alwaysthe most stable coordination pattern, on the contrary to whathappens in solution. Even the preferred coordination geometrycannot be definitely assigned, and the global minima at thedifferent hydration levels were found to be tetra- or pentaco-ordinated, generally at the cost of losing the π coordination orexpelling one of the water molecules from the first coordinationshell.

Phe and Tyr present very similar isomers (see Figure 1 forPhe complexes, and Tyr complexes are available in the Sup-porting Information; for the sake of brevity and considering thenegligible geometrical differences to the PBE/CPMD optimizedstructures in most of the complexes, only the B3LYP/G03optimized structures are shown in the pictures), the occasionaldifferences arising from the presence of the -OH group in thearomatic ring of Tyr, which enables hydrogen bonding sites withthe water molecules bound to the metal. The three bindingmodes, namely, cs, zw1, and zw2, are found for n ) 1-4, andboth amino acids accept up to four water molecules in the firstsolvation shell.

Regarding the coordination to Trp, the cs, zw1, and zw2binding modes were found for the different degrees of solvation.The smaller π-electron density at the five-membered ring, arisingfrom the presence of the nitrogen atom, renders the benzenering of the aromatic face more prone to interact with the metal,as confirmed by the data of Figure 2.18,21 Besides, in the specific

case studied here, the interaction of the Al with the five-membered ring results in a sterically hindered structure, whichdestabilizes further the isomer. Consequently, those complexeswhere the metal interacts with the five-membered ring lie higherin energy, and in fact, no zw1-5 binding mode was foundbetween the low lying isomers with none of the theoreticalapproximations tried in the present study. Trp complexes alsoaccept up to four water molecules in the coordination shell ofthe metal but only for the zw structure.

In the absence of water molecules, due to the enhancedelectrostatic potential arising from the intrinsic properties of thecation, the metal binds very tightly to the ligands.12,13 As watermolecules are added, the bond distances between the metal andthe O and N atoms of the backbone and water molecules areelongated due to the electron density delocalization from watermolecules to the metal, which weaken the binding to the aminoacid. The enlargement is most noticeable when the first watermolecule is included, while the effect decreases gradually forthe further additions, as was already reported in the literaturefor mono- and bivalent ions.8,13 The complete hydration of thecomplex results in a bond enlargement of roughly 0.1 Å. Onthe contrary, the loss of π interaction during the hydrationprocess results in less steric strain but also less charge transfer,and therefore, the bond distance is shortened upon this event(see Supporting Information).

Zwitterionic vs Charge-Solvated Conformations. The prefer-ence for zw isomers in aqueous solution as opposed to the csglobal minima in the gas phase is known in the literature.10

Furthermore, several works have reported the stabilization ofzw structures as compared to cs ones upon the gradual additionof water molecules to a bare amino acid and to metal-AAcomplexes found to present a cs global minimum in the gasphase.6,8,11,12 The number of water molecules required for theconversion can vary between two and six, depending on themetal and the amino acid studied.

In the present study, the one-by-one addition of watermolecules to the metal bound to the amino acid also has beenfound to trigger the preference for the zw system. In the gasphase, the cs isomer was preferred, in line with what is expectedfor small size metals complexing amino acids,3 and the addition

Figure 2. Optimized [Al-Trp-(H2O)n]+3 systems (B3LYP/G03 theory level).

Microsolvated Al3+-Aromatic Amino Acid Complexes J. Phys. Chem. B, Vol. 114, No. 27, 2010 9019

of the first water molecule does not noticeably alter the stabilityof the species as compared to the bare Al3+-AAA system, ashas been seen to happen for other systems.5,6,8 The cs isomer isstill preferred upon the addition of the first water molecule,1

the relative stability of the zw structures being at least 7.6 kcal/mol higher in the B3LYP/G03 calculations, but much closer inthe PBE/CPMD calculations (2.3, 3.1, and -1.3 kcal/mol forPhe, Tyr, and Trp complexes, respectively). As the number ofwater molecules added is increased, this preference is invertedand for n ) 2, and the zw structures are preferred over the csones. Nevertheless, the cs complexes are found close in energy(2.9, 4.9, 6.7, 7.4, and 7.2 kal/mol for B3LYP/G03 and PBE/CPMD calculations, respectively). Observe that, in general, PBE/CPMD calculations tend to destabilize the cs conformation withrespect to the zw conformation, as compared to the B3LYP/G03 ones. The difference becomes much larger upon theaddition of the third water molecule, now pointing out a clearpreference for zw fashion. This pattern is, as expected, enforcedas the fourth water molecule is included.

The similar relative energies of cs and zw complexes foundfor the n ) 2, 3 systems suggest that this species could coexistin the gas phase. The interconversion between zw and csstructures of Na+-Val was experimentally seen to be possiblefor n ) 2;1 regretably, no such kinds of experimental data areavailable for multiply charged ions or for AAAs. The stabilityof each global minimum, in this case, was checked at roomtemperature by means of PBE/CPMD simulations, all of thembeing found to keep their initial preference for the correspondingcs or zw isomer, during 20 ps. Therefore, the simulations suggestthat the interconversion energy between zw and cs complexesis too high for such a conversion to take place and that thepresence of the complexes will depend on the experimental setupfor the generation of such complexes.8 However, experimentaldata would be highly desirable for more detailed insight intothis issue.

Consequently, the unambiguous estimation of the waternumber required for the stabilization of the zw form is notpossible, as already happened with other systems.6,8 Neverthe-less, the existence of cs isomers for n ) 4 can be ruled out,based on the high instability of such complexes.

Solvation Energies. The hydration reaction as described ineq 1 is a exothermic process, predicting the gradual inclusionof water molecules to be a spontaneous process for [Al-AAA]+3

complexes (see Figure 3). The hydration reaction implies largeentropic effects disfavoring the inclusion of one water molecule

in the shell, estimated to be ∼10 kcal/mol in each addition. Totake this effect into account, free energies will be discussed inthis section. Both enthalpies and free energies are available inthe Supporting Information.

As a consequence of the intrinsic size and charge propertiesof the metal, the stability gained upon the addition of a watermolecules is much larger for [Al-AA]+3 complexes than foralkali metal-AA complexes that have been studied in theliterature, for which the highest energy gains, those correspond-ing to the addition of the first and second water molecules, fallin the range of 10-15 kcal/mol, for both Na+ and K+, fordifferent amino acids.1,8,9 The systems chosen here present anaffinity of around 70 kcal/mol for the first water molecule. Thestepwise addition of a water molecule causes a gradual decreaseof the solvation free energies of the complexes, from -70 kcal/mol for the addition of the first water molecules to -40 kcal/mol for the third and fourth additions. Similar trends have beenobserved both theoretically and experimentally for other systemsand have been ascribed to the saturation of the coordinationshell of the cation, on one hand, and to the neutralization ofthe charge of the Al3+ by each water added.1 Observe that theless exothermic formation enthalpy occurs when hexa- andpentacoordination are achieved.

In previous works,18 the nature of the side chain was seen toinfluence the affinity of the metal toward the ligands; the moreelectron donating the ligand, the stronger the binding of themetal. This, in turn, means a looser binding to the added watermolecule, as reported in the literature.5 However, no remarkableinfluence is seen in this case, probably due to the severaldifferent factors coming into play in the present complexes,which make the electronic effect of the AAAs difficult todistinguish.

Proton Transfer. During the inclusion of water moleculesto the systems, spontaneous water migrations to the secondhydration shell were observed for the three amino acids (seeFigure 4), in particular in Tyr complexes, at both B3LYP/G03and PBE/CPMD levels of theory (see t complexes in Table 1

Figure 3. Hydration free energies of the different [Al-Phe-H2On]+3

(empty symbols), [Al-Tyr-H2On]+3 (filled symbols), and [Al-Trp-H2On]+3 (stripped symbols) complexes studied, in kcal/mol.

Figure 4. Optimized [Al-AAA-(H2O)n]+3 structures showing spon-taneous proton and water transfers.

9020 J. Phys. Chem. B, Vol. 114, No. 27, 2010 Larrucea et al.

and Table 2). Although several of them were characterized, onlythose stabilizing the corresponding fully solvated complex willbe discussed here. This feature arose with the inclusion of thethird water molecule in Phe and Trp complexes but only for n) 4 complexes was seen to be more favorable than keeping itbound to the metal. On the contrary, this stabilization wasnoticed already in n ) 2 complexes for Tyr, probably as a resultof the -OH substituent in the Tyr ring, which provides thepossibility of forming favorable H-bonds with the watermolecules.

Among those isomers presenting a water molecule in thesecond coordination shell, in some cases Al3+ provokes thehydroxylation of one of the water molecules attached in itscoordination shell, the released proton interacting with the watermolecule in the second hydration shell. Similar proton and watershifts have already been discussed in the literature in otherorganic Al3+ systems,34–36 ascribing this feature to the polarizingeffect of the aluminum ion on the water molecules present inthe inner sphere.

As previously stated, these phenomena can be explained asa result of the equilibrium between the steric hindrance on themetal’s coordination shell and the favorable charge transfer fromthe water molecules to the metal. On one hand, the incomingof a water molecule into the inner shell of the metal donatescharge to the Al3+, stabilizing the complex, at the cost ofincreasing its steric hindrance. As more water molecules areadded, the steric hindrance becomes too large and the chargeon the metal lower, and therefore, expelling a water moleculeto the second hydration shell can help the overall stabilizationof the complex more than keeping it directly bound to the Al3+.On the other hand, when the charge in the metal is still largeenough to polarize the water molecules attached to it, and thereis a proton acceptor available, the ejection of a proton out ofthe inner shell of the metal is likely to happen, resulting in anegatively charged hydroxyl bound to the metal, which stabilizesthe structure, neutralizing the charge of the metal. In some ofthe complexes studied here, the steric hindrance is too high toaccept another water molecule in the inner shell, and even thecharge in the metal is still too high. The proton shift is themechanism the metal uses for neutralizing its charge, at the sametime that the steric hindrance is lowered.

This mechanism results in a rather small stabilization of about2 kcal/mol, which reflects how subtle the equilibrium betweenthe factors alluded to earlier is in this case. However, it clearlypoints out that in the competition between the metal hydrationand ligation the latter is most favorable.

Cation-π Interaction. In the present work, isomers withand without cation-π interactions were considered. Thosewithout interaction with the ring gave rise to open linearstructures, while the inclusion of cation-π interactions forcedthe structure to bend toward the ring, forming closed structures.

The study of the bare Al3+-AAA18 systems clearly showedthe additional stability gained via the cation-π interaction,which favored closed structures. This stabilization is also presentin the microhydrated structures, but as a result of the stepwiseaddition of the water molecules, the cation-π interaction isgradually weakened, as reflected by the larger distances betweenthe metal and the ring and the smaller charge transfer shown inthe NBO analysis (see Supporting Information), where second-order interactions are mantained in the B3LYP/G03 calculations,stabilizing the overall structure.

The presence of the cation-π interactions during the micro-hydrated process is seen to depend on the binding mode of themetal. For cs and zw1 structures, the open structures are found

more than 20 kcal/mol higher than the global minimum,mantaining the interaction for the fully solvated structures andovercoming the opposing distortion energy. Instead, open zw2structures are predicted to lie within 20 kcal/mol, for n ) 2 inPhe. From n ) 3 on, the gap between open and closedcomplexes becomes smaller for Phe and Tyr, and zw2 openstructures are considered more stable, even if within a fewkilocalories/mole. The gap between the open and closedstructures is larger in dynamics calculations, which, in fact,predict the Trp to show the same behavior, while B3LYP/G03calculations, even if located in the open zw2 complex within20 kcal/mol for n ) 3, favor the closed formation (seeSupporting Information). The bond to two oxygen atoms in thezw2 complexes supposes a larger charge transfer than the otherbinding mode. Therefore, when the hydration degree is highenough, the additional stabilization gained via the cation-πinteraction does not compensate the steric hindrance payed inclosed structures.

These discrepancies point out that the cation-π interactionis more labile as the water molecules are added and that it doesnot provide a strong stabilization of the overall complex whenthe metal is bound to strong electron-donating atoms. Neverthe-less, the data supports the existence of such interactions inhydrated environments for the low lying isomers, in line withthe results of the PBE/CPMD calculations on Na+-Phe com-plexes in solution,10,37 who predicted the cation-π interactionto be present even in the aqueous solution, for the zw1 bindingmode.

Conclusions

The microhydrated environment promotes the stabilizationof some conformers which are less populated in the absence ofwater molecules, in particular, the zw2 binding mode in Trpcomplexes and, in general, the zw structures of all the aminoacids. Moreover, the latter is predicted to coexist with the csstructures already when two water molecules are bound to themetal and is the most stable conformer when the fourth watermolecule is added. This feature is widely known to happen inbulk solvent, but in fact, this study points out that it is ratherrelated to the change in the metal’s properties, as the zw formis seen to be preferred already in the gas phase upon theattachment of bigger cations.

Al3+ retains the coordination pattern seen in the bareAl+-AAA systems, in line with its hard metal nature, preferringthe harder O binding sites to the softer N ones. The metal acceptsup to four water molecules in its shell, the attachment of thefirst and the second being especially exothermic and, therefore,highly stabilizing the complex. At this point the metal is rathersaturated, and the addition of new water molecules, even ifexothermic, does not suppose such a big energy gain anymore.

This hydration results in an alteration of structural andthermochemical properties, which have been seen to be domi-nated by the charge neutralization of the metal and the overallsteric hindrance of the complex: the coordination mode, thedegree of hydration of the metal, and solvation energies are theresult of a subtle equilibrium between these forces, enhancedby the high charge and small size of the metal. Instead, themain features are not remarkably influenced by the differentside chains considered, whose effect is attenuated as comparedto the nonhydrated complexes.

As reflected by the migration of waters to the second solvationshell, the metal-ligation is preferred to metal-hydration. In fact,when the metal is fully solvated, it prefers to adopt a penta- ortetracoordinated binding fashion (lower coordination number

Microsolvated Al3+-Aromatic Amino Acid Complexes J. Phys. Chem. B, Vol. 114, No. 27, 2010 9021

than that found in aqueous environment) to minimize the sterichindrance by losing water interactions and maintaining theinteraction with the ligands. The attachment of water molecules,furthermore, leads to a weaker cation-π interaction; neverthe-less, in most of the cases, it is strong enough to overcome thesteric hindrance arising from such a closed structure, maintainingsuch a conformation even in the most solvent exposed situations.

Acknowledgment. This research was funded by EuskalHerriko Unibertsitatea (the University of the Basque Country),Gipuzkoako Foru Aldundia (the Provincial Government ofGipuzkoa), and Eusko Jaurlaritza (the Basque Government). TheSGI/IZO-SGIker UPV/EHU (supported by the National Programfor the Promotion of the Human Resources within the NationalPlan of Scientific Research, Development and Innovation, FondoSocial Europeo and MCyT) is gratefully acknowledged forassistance and generous allocation of computational resources,together with the Universit’a degli Studi della Calabria andMIUR (PRIN 2008).

Supporting Information Available: Additional Tables1-12 and Figures 1 and 2. This material is available free ofcharge via the Internet at http://pubs.acs.org.

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