Acid�/base and metal ion binding properties of pyridine-type ligandsin aqueous solution.
Effect of ortho substituents and interrelation between complexstability and ligand basicity
Larisa E. Kapinos, Helmut Sigel *
Institute of Inorganic Chemistry, University of Basel, Spitalstrasse 51, CH-4056 Basel, Switzerland
Received 28 February 2002; accepted 19 April 2002
This study is dedicated to Professor Dr. Karl E. Wieghardt on the occasion of his 60th birthday with the very best wishes of the authors for all his
future endeavours
Abstract
The stability constants of the complexes formed between Mg2�, Ca2�, Sr2�, Ba2�, Mn2�, Co2�, Ni2�, Cu2�, Zn2� and Cd2�
(�/M2�) and two sets of pyridine-type ligands (�/L) were determined by potentiometric pH titration in aqueous solution (25 8C;
I�/0.5 M, NaNO3). One set consists of the simple and at the N1 site sterically unhindered pyridine-type ligands 3-chloropyridine, 4-
bromopyridine, 4-(chloromethyl)pyridine, pyridine, b-picoline (�/3-methylpyridine) and 3,5-lutidine (�/3,5-dimethylpyridine); the
other set includes the following pyridine derivatives with an ortho substituent, 2-methyl-5-bromopyridine, 2-amino-5-bromopyr-
idine, tubercidin (�/7-deazaadenosine), a-picoline (�/2-methylpyridine) and 2-aminopyridine. The acidity constants of the
monoprotonated ligands H(L)� were also measured. Plots of log KMM(L) versus pKH
H(L) give straight lines for each mentioned set of
pyridine derivatives. The equations for the corresponding least-squares lines allow calculation of the expected stability constant for a
complex of any pyridine-type ligand (with or without an ortho substituent) provided its pKHH(L) value is known (in the pKa range 3�/
7). The differences between the plots for these two sets of ligands reflect the steric influence of the ortho substituent on metal ion
binding at the N1 site of pyridine. It is shown that the steric effects of amino and methyl groups are equal. The extent of the steric
inhibition depends on the metal ion; it is most pronounced for Ni2� and nearly not existent for the alkaline earth ions. Furthermore,
for the latter ions complex stability is independent of the basicity of the pyridine nitrogen and this indicates that in these instances
outersphere complexes dominate. In the case of the divalent transition metal ions, the slopes of the straight lines are smaller for the
complexes of the ortho -substituted ligands, except for the Cu2� complexes where the slopes are identical; this indicates that Cu2�
forms with both sets of ligands mainly innersphere complexes, whereas for the other metal ions and their complexes with ortho -
substituted pyridine-type ligands outersphere binding becomes important. The present results permit in addition the determination
of the extent of the steric inhibition of the (C6)NH2 group on metal ion binding at N1 of the adenine residue.
# 2002 Elsevier Science B.V. All rights reserved.
Keywords: Acid�/base equilibria; Metal ion complexes; ortho -Substituted pyridine-type ligands; Pyridine derivatives; Stability constants; Steric
effects
1. Introduction
Pyridine and its derivatives are known to be suitable
ligands for d-transition metal ions and are therefore
often used in the design and synthesis of multifunctional
compounds [1]; studies involving Fe(II) [2], Ni(II),
Co(II) [3], and especially Cu(II) [4,5] are prominent.
Some of these pyridine derivatives are also of biological
and pharmacological relevance. For example, certain
peptide ligands with pyridine moieties seem to have a
potential as anti-HIV metal chelators [6], 4-methyl-2-
aminopyridine-palladium(II)-chloride inhibits the re-* Corresponding author. Fax: �/41-61-267 1017
E-mail address: [email protected] (H. Sigel).
Inorganica Chimica Acta 337 (2002) 131�/142
www.elsevier.com/locate/ica
0020-1693/02/$ - see front matter # 2002 Elsevier Science B.V. All rights reserved.
PII: S 0 0 2 0 - 1 6 9 3 ( 0 2 ) 0 0 9 9 3 - 3
verse transcriptase of disrupted retroviruses [7], and
metal ion complexes of bis[di-1,1-(2-pyridyl)ethyl]amine
have been used in DNA cleavage studies [8].
In addition, the pyridine residue also occurs in several
molecules directly involved in biological processes [9],
like nicotinamide (pyridine-3-carboxamide), nicotina-
mide adenine dinucleotide (NAD) and its phosphory-
lated partner NADP, or vitamin B6, also named
pyridoxine [�/2-methyl-3-hydroxy-4,5-bis(hydroxy-
methyl)pyridine]. Furthermore, pyridine is structurally
and chemically related [10] to 1,3-diazine, which is a part
of pyrimidine and purine nucleobases. In fact, the N1
and N3 nitrogens of adenosine (Fig. 1) and cytidine,
respectively, are often addressed as pyridine-type nitro-
gen atoms [11�/14]. The importance of these nitrogens,
next to N7 of purines, as potential binding sites for
metal ions in their interactions with nucleotides or
nucleic acids, has long been recognized (for reviews see
[11,14�/17]).With the above situation in mind, it is surprising to
find [18�/20] that aside from some early data [21�/24],
including a study [25] dealing with the steric effect of
ortho substituents on the stability of Cu2��/pyridine
complexes, there are no comprehensive studies dealing
with the acid�/base properties of pyridine derivatives
and their corresponding metal ion affinities. The few
available attempts [11,13,14] to obtain a relation be-
tween nitrogen basicity and complex stability were based
on ‘mixed’ data, i.e. constants determined under differ-
ent conditions [12,21,22,25�/28].
To make the present study relevant for conclusions
regarding biological systems, we investigated not only
the acid�/base and metal ion binding properties of the
six simple pyridine derivatives seen in Fig. 2, but also of
the five ones given in Fig. 3, all of which have an ortho
substituent next to the N atom. This is important
because it is known [28] that the (C6)NH2 group in
adenosine (see Fig. 1) exerts a steric hindrance for metal
ion binding to N1. We have now quantified this steric
effect for the alkaline earth ions and the divalent 3d ions
Fig. 1. Chemical structure of adenosine (Ado), together with that of
1,4-dimethylbenzimidazole (DMBI), also named 6,9-dimethyl-1,3-
dideazapurine, a model compound for the adenine residue (see Section
4).
Fig. 2. Chemical structures of 3-chloropyridine (3ClPy), 4-bromopyr-
idine (4BrPy), 4-(chloromethyl)pyridine (4ClMPy), pyridine (Py), 3,5-
lutidine (�/3,5-dimethylpyridine, 3,5DMPy) and b-picoline (�/3-
methylpyridine, 3MPy).
Fig. 3. Chemical structures of ortho -substituted pyridine derivatives:
2-methyl-5-bromopyridine (2M5BrPy), 2-amino-5-bromopyridine
(2A5BrPy), a-picoline (�/2-methylpyridine, 2MPy), 2-aminopyridine
(2APy) and tubercidin (�/7-deazaadenosine, Tu).
L.E. Kapinos, H. Sigel / Inorganica Chimica Acta 337 (2002) 131�/142132
of Mn2�, Co2�, Ni2�, Cu2�, and Zn2�, as well as for
Cd2�. One among several interesting results is that the
extent of the steric inhibition also depends on the
basicity of the N liganding site, i.e. the log K versuspKa straight-line relations observed for the two series of
ligands (Figs. 2 and 3) are not parallel to each other for
most of the metal ions studied. It may be added that the
steric effect on the N7 site of the adenine residue has
recently been quantified [29] by studies with benzimida-
zole derivatives [30], including 1,4-dimethylbenzimida-
zole (DMBI). The use of this model compound allows
some interesting comparisons regarding the metal ionbinding sites N1 and N7 of the adenine residue (see
Section 4).
2. Experimental
2.1. Materials
3,5-Lutidine (�/3,5-dimethylpyridine, ]/97%), b-pi-coline (�/3-methylpyridine; ]/98%), pyridine (]/
99.8%), 4-(chloromethyl)pyridine hydrochloride (]/
98%), 4-bromopyridine hydrochloride (]/97%), 3-chlor-
opyridine (]/98%), a-picoline (�/2-methylpyridine; ]/
98%), tubercidin (�/7-deazaadenosine, ]/99%), 2-ami-
no-5-bromopyridine (]/97%), and 2-methyl-5-bromo-
pyridine (]/99%) were from Fluka, Buchs
(Switzerland), and 2-aminopyridine (]/99.9%) wasfrom Sigma�/Aldrich Co., Buchs (Switzerland). All these
substances were used as obtained; however, our poten-
tiometric pH titrations proved that they were free of any
acid�/base impurities.
The aqueous stock solutions of the ligands were
freshly prepared daily by dissolving the compounds in
deionized, ultrapure (MILLI-Q185 PLUS; from Milli-
pore S.A., F-67120 Molsheim, France) CO2-free waterand their exact concentrations were measured each time
by titrations with NaOH [31]. All the other chemicals
were the same as used previously [29,31], and the titres
of the metal ion stock solutions were also determined as
described [31].
2.2. Potentiometric pH titrations
The equipment, including the desk computers, was the
same as used recently [31,32]. All equilibrium constants
were calculated by curve-fitting procedures using a
Newton�/Gauss non-linear least-squares program.
The acidity constants determined [33] are so-called
practical, mixed or Brønsted constants [34]. Their
negative logarithms, given for aqueous solution at I�/
0.5 M (NaNO3) and 25 8C may be converted into thecorresponding concentration constants by subtracting
0.03 from the listed pKa values [34]. The ionic product of
water (Kw) does not enter into the calculations because
the differences in NaOH consumption between solutions
with and without ligand (see below) are evaluated. The
stability constants presented are, as usual, concentration
constants.
2.3. Determination of the acidity constants
The acidity constants KHH(L) of H(L)�, where L�/Py,
4BrPy, 4ClMPy, 3,5DMPy, 3MPy, 2M5BrPy, 2A5BrPy,
2MPy, 2APy or Tu (see Figs. 2 and 3), were determined
by titrating 50 ml 1.8 mM HNO3 (25 8C; I�/0.5 M,
NaNO3) in the presence and absence of 1.0 mM Py or
one of its mentioned derivatives under N2 with 1 ml of0.1 M NaOH and by using the differences in NaOH
consumption between such a pair of titrations for the
calculations. In the case of 3ClPy, because of its low
basicity, the acidity constant KHH(3ClPy) of H(3ClPy)� was
determined by titrating 25 ml of 7.2 mM HNO3 (25 8C;
I�/0.5 M, NaNO3) in the presence and absence of 2 mM
3ClPy with 1.85 ml of 0.1 M NaOH.
All acidity constants for monoprotonated species(KH
H(L)) were calculated as described [31] from the pH
range corresponding to about 3�/97% neutralization for
the equilibrium H(L)�/L. In the case of 3ClPy only the
pH range corresponding to about 20�/97% neutraliza-
tion for the equilibrium H(L)�/L was accessible. The
final results for the various acidity constants are the
averages of 16�/30 independent pairs of titrations.
2.4. Determination of the stability constants
The stability constants KMM(L) of the M(L)2� com-
plexes, where L�/Py, 4BrPy, 3ClPy, 4ClMPy,
3,5DMPy, 3MPy, 2M5BrPy, 2A5BrPy, 2MPy, 2APy
or Tu were determined under the same conditions as the
acidity constants, but NaNO3 was partly or fully
replaced by M(NO3)2 (I�/0.5 M, 25 8C).For the systems containing Mg2�, Ca2�, Sr2�, Ba2�,
and Mn2�, NaNO3 was always replaced completely by
M(NO3)2 because of the low stability of the correspond-
ing complexes; that is, [M(NO3)2] was equal to 0.1667 M
and consequently, the ratio for these systems was
M2�:L�/167:1, except for 3ClPy (see below).
For the other M2� complexes of pyridine and those
of its derivatives without an ortho substituent, thefollowing concentrations of M(NO3)2 were employed
and at least two different [M(NO3)2] were used for a
given ligand: 0.1667 M (M2�:L�/167:1 for Co2�,
Ni2�, Zn2�, and Cd2�), 0.0833 M (M2�:L�/83:1 for
Co2�, Cu2�, Zn2�, and Cd2�), 0.0417 M (M2�:L�/
42:1 for Co2�, Ni2�, Zn2�, and Cd2�), 0.0208 M
(M2�:L�/21:1 for Ni2�), 0.0104 M (M2�:L�/10:1 for
Ni2�). In the Cu2� systems also lower [Cu(NO3)2] wereused; i.e. 0.0083 M (M2�:L�/8.3:1), 0.0052 M
(M2�:L�/5.2:1), 0.0042 M (M2�:L�/4.2:1), 0.0033 M
(M2�:L�/3.3:1), and 0.0026 M (M2�:L�/2.6:1). For
L.E. Kapinos, H. Sigel / Inorganica Chimica Acta 337 (2002) 131�/142 133
the determination of the stability of the M(3ClPy)2�
complexes always the highest possible M2� concentra-
tion (0.1667 M) was employed for all metal ions giving
the ratio M2�:L�/83:1.In the case of the 2-methyl- or 2-amino-substituted
pyridines large M(NO3)2 concentrations were also
required because most of their metal ion complexes are
quite weak, except those containing Cu2�. Therefore,
NaNO3 was fully replaced by M(NO3)2 in most cases, so
that [M(NO3)2]�/0.1667 M and consequently,
M2�:L�/167:1. For the Ni2� and Zn2� systems with
tubercidin and 2-methylpyridine also half of the men-tioned concentration was used; i.e. [M(NO3)2]�/0.0083
M (M2�:L�/83:1). In the case of the Cu2� systems
further variations were possible, namely [Cu(NO3)2]�/
0.1333 M (133:1), 0.0834 M (83:1), 0.0417 M (42:1),
0.0333 M (33:1), 0.0167 M (17:1), and 0.0083 M (8.3:1).
The stability constants were calculated exactly as
described in [31]. The evaluations were carried out in
the pH range where no hydrolysis of M(aq)2� occurs;this was evident from the titrations of metal ion
solutions in the absence of ligand. The results showed
no dependence on the excess of the metal ion concen-
tration employed. The final results listed in the tables are
in each instance the averages of at least six independent
pairs of titrations. The relatively large error limits given
with the stability constants for the Cu2� and Zn2�
complexes of 2-aminopyridine (see Table 3, vide infra)are due to the relatively early M(aq)2� hydrolysis in
these systems which only allowed to reach a formation
degree of about 3% for the Cu(2APy)2� and
Zn(2APy)2� species.
3. Results and discussion
3.1. Acid�/base properties of pyridine and several
derivatives
Pyridine and all of the derivatives shown in Figs. 2
and 3 accept a proton at their endocyclic nitrogen giving
the monoprotonated species H(L)�, where L�/pyridine
or derivative. As far as aminopyridines and a possible
protonation of their exocyclic nitrogens are concerned,
already Sun and Brewer [22] had concluded: ‘‘Thebasicities of the �/NH2 groups in aminopyridines were
too weak to be detected and certainly had no effect on
the hydrogen ion concentration in a moderately acidic
pH range’’. This agrees with our own observations for 2-
aminopyridine and 2-amino-5-bromopyridine, that is,
pKHH2(L)51:3: Similarly, the most basic nitrogen in
tubercidin (Tu; Fig. 3) is N1, which undergoes proto-
nation by forming H(Tu)� [35]. No further protonationoccurs in the pH range down to 2 [35]. Neutral
tubercidin may release a proton from the ribose residue
[36], but this reaction only occurs at pH�/12 and does
not play a role in the physiological pH range. Hence, in
the present context, i.e. in the pH range 2�/12, only
H(Tu)� needs to be taken into account.
To conclude, for all pyridine ligands and pH rangesconsidered in this study only monoprotonated species
are of relevance and therefore, only equilibrium (1a) was
needed to explain the experimental data of the potentio-
metric pH titrations (25 8C; I�/0.5 M, NaNO3).
H(L)�XH��L (1a)
KHH(L)� [H�][L]=[H(L)�] (1b)
The results for the acidity constants (Eq. (1b)) of the
H(L)� species are given in Table 1. The value for
H(Tu)� has been determined before in this laboratory
and the result given in [28] is in excellent agreement with
the present one. This is also true, within the error limits,
for the ‘critically selected’ constants given in [18] for
H(Py)�, H(3MPy)�, H(3,5DMPy)�, H(2A5BrPy)�,
and H(2APy)�, as well as for the value of H(2MPy)�
given in Ref. [20]. For the acidity constants of
H(3ClPy)�, H(4BrPy)�, H(4ClMPy)�, and
H(2M5BrPy)� (Table 1, entries 1, 2, 3, 7) no values
are listed in Refs. [18�/20].
The results assembled in Table 1, together with some
literature data, allow several comparisons and conclu-
sions; a few are given: (i) as expected, halogen-contain-
ing substituents (entries 1�/3) decrease due to theirelectron-withdrawing properties the basicity of pyridine
(entry 4), whereas methyl (entries 5, 6, 10) and amino
(entry 11) groups enhance it in accordance with their
inductive (and resonance) effects [37]; the effect of the
amino group being more pronounced (cf. entries 10, 11).
(ii) Comparison of the acidity constants of the mono-
protonated ortho , meta , and para isomers of methylpyr-
idine with the pKa value of H(Py)�
[DpKa=ortho�pKHH(2MPy)�pKH
H(Py)�(6:1490:02)�(5:34/
/90:02)�0:8090:03; DpKa=meta�pKHH(3MPy)�pKH
H(Py)�(5:8190:02)�(5:3490:02)�0:4790:03; DpKa=para�pKH
H(4MPy) (from [18])�//pKHH(Py)�(6:0790:05)�(5:349
0:02)�0:7390:05] reveals that at the ortho and para
positions the electron-donating properties of the methyl
substituent are of a comparable size and more pro-
nounced than at the meta one; this order, meta B/
ortho �/para , agrees with theoretical expectations [37].
(iii) In contrast to the addition of an amino group,
which leads to the more basic aminopyridines (cf. entries
4, 11), the addition of a further endocyclic nitrogen
leading to the diazines, results in a decreased proton
affinity [38]. (iv) Annelation of pyridine to give quino-
line (Qu) has a relatively small effect, DpKa�pKHH(Py)
(from [39])�//pKHH(Qu) (from [40])�/(5.269/0.01)�/(4.979/
0.05)�/0.3, at least when compared to 1-methylimida-
zole and 1-methylbenzimidazole where the acidification
due to annelation amounts to DpKa�/1.5 [30].
L.E. Kapinos, H. Sigel / Inorganica Chimica Acta 337 (2002) 131�/142134
The latter comparison, in which pKHH(Py)�5:2690:01
[39] was used, refers to 25 8C and I�/0.1 M. Since it is
of general interest to be aware of ionic strength effects,
we compare the values for H(Py)� at I�/0.1 and 0.5 M
and note that at the higher ionic strength the basicity is
increased by DpKa�/(5.349/0.02)�/(5.269/0.01)�/
0.089/0.02. This result is in excellent agreement with
comparisons that may be made for 2APy, 2MPy, and3MPy, based on the ‘critically selected’ values listed in
Ref. [18], and it agrees further with earlier values for Tu
[28]. An increase of the ionic strength from 0.1 to 1 M
enhances the basicity by DpKa#/0.15 based on the
values given for 2APy and 4APy in Ref. [18]. This latter
effect is somewhat smaller than the one observed
recently [41] for the deprotonation of a positively
charged (N)H� site in purine derivatives where thechange of I from 0.1 to 1 M resulted in a basicity
increase of DpKa�/0.299/0.09.
3.2. Stabilities of metal ion complexes formed with simple
and ortho-substituted pyridine-type ligands
All the experiments aimed to determine stability
constants of the metal ion complexes formed with the
ligands shown in Figs. 2 and 3 were carried out with the
metal ion (M2�) concentrations in excess of the
concentrations of the ligands (L). This means that underthese conditions only 1:1 complexes form and therefore
the experimental data of the potentiometric pH titra-
tions can be described completely by equilibrium (1a)
given above and equilibrium (2a)
M2��LXM(L)2� (2a)
KMM(L)� [M(L)2�]=([M2�][L]) (2b)
for complex formation. The only restriction is that the
evaluation of the experimental data is not carried into
the pH range in which hydroxo complex formationoccurs; however, this was evident from the titrations of
the metal ion solutions in the absence of ligand (see
Section 2.4). The results for the M(L)2� complexes of
Ba2�, Sr2�, Ca2�, Mg2�, Mn2�, Co2�, Ni2�, Cu2�,
Zn2�, and Cd2� are collected in Table 2.
Of the 110 stability constants listed in Table 2 only
about 25, the largest set for M2��/pyridine complexes at
varying conditions [18,19], have been measured before
[18�/20]. The early results by Sun and Brewer [22] for the
Cu2� complexes of Py, 3MPy, 3,5DMPy, 2MPy, and
2APy as well as for the Ni2� complexes of Py, 3MPy,
and 3,5DMPy are in excellent agreement with the
present ones. In general, there is also excellent agree-
ment with the ‘critically selected’ values given in [18] for
the Co2�, Ni2�, Cu2�, Zn2�, and Cd2� complexes of
3MPy, for the Ni2� and Cu2� complexes of 3,5DMPy,
and for the Cu2� complexes of 2MPy and 2APy. Aside
from the systems mentioned, there are also constants
listed in [19] for the Co2� and Cd2� complexes of
3,5DMPy, as well as for the Ni(2MPy)2�, Ni(2APy)2�,
and Zn(2APy)2� species. These earlier values [19] are at
least in part in fair agreement with the present ones; this
is also true for the M(Py)2� values given in Ref. [18].
Our own earlier determinations [28] of the stability
constants of the M(Tu)2� complexes are within the
error limits identical with the present results.
In a previous study we had determined in this
laboratory [39] the stability constants for the pyridine
1:1 complexes formed with Co2�, Ni2�, Cu2�, and
Zn2� at 25 8C and at I�/0.1 M (NaNO3). Comparison
of these earlier values, log KCoCo(Py)�1:2590:02;
log KNiNi(Py)�1:8790:01; log KCu
Cu(Py)�2:4990:02; and
log KZnZn(Py)�1:0090:03 [39], with those given in entry
4 of Table 2 for I�/0.5 M, gives the stability differences
Dlog KCo�/0.099/0.04, Dlog KNi�/0.079/0.02, Dlog
KCu�/0.119/0.04, and Dlog KZn�/0.159/0.04; i.e. these
M(Py)2� complexes are somewhat more stable at higher
ionic strength. The average increase in complex stability
of these examples, i.e. Dlog KM�/0.119/0.05 (3s), is
very close to the increased basicity of Py, i.e. DpKa�/
0.089/0.02, as described in Section 3.1, also due to the
change in ionic strength from 0.1 to 0.5 M. Hence, one
may conclude that the basicity increase (i.e. of pKHH(L))
due to an increased ionic strength leads in a first
Table 1
Negative logarithms of the acidity constants (Eq. (1)) of the simple and ortho -substituted protonated pyridine derivatives (H(L)�) shown in Figs. 2
and 3, respectively, as determined by potentiometric pH titrations in aqueous solutions at 25 8C and I�0.5 M (NaNO3) a,b
Simple pyridine derivatives ortho -Substituted pyridines
No. H(L)� /pKHH(L)/ No. H(L)� /pKH
H(L)/
1 H(3ClPy)� 3.0090.02 7 H(2M5BrPy)� 3.8690.02
2 H(4BrPy)� 3.9190.02 8 H(2A5BrPy)� 4.8790.01
3 H(4ClMPy)� 4.8390.01 9 H(Tu)� 5.2790.02
4 H(Py)� 5.3490.02 10 H(2MPy)� 6.1490.02
5 H(3MPy)� 5.8190.02 11 H(2APy)� 6.8690.01
6 H(3,5DMPy)� 6.2490.02
a The errors given are three times the standard error of the mean value or the sum of the probable systematic errors, whichever is larger.b So-called practical (or mixed) acidity constants [34] are listed; see Section 2.2.
L.E. Kapinos, H. Sigel / Inorganica Chimica Acta 337 (2002) 131�/142 135
Table 2
Logarithms of the stability constants for the 1:1 complexes (Eq. (2)) formed between several divalent metal ions (M2�) and the simple (a) or ortho -substituted (b) pyridine derivatives (L) shown in
Figs. 2 and 3, respectively, as determined by potentiometric pH titrations in aqueous solutions at 25 8C and I�0.5 M (NaNO3) a
No. L /Log KMM(L) for M2��
Ba2� Sr2� Ca2� Mg2� Mn2� Co2� Ni2� Cu2� Zn2� Cd2�
(a) Simple pyridine derivatives
1 3ClPy �0.1890.12 �0.1290.09 �0.0890.08 0.0290.05 0.1990.04 0.7990.03 1.3490.03 1.6090.03 0.5790.03 0.9390.03
2 4BrPy �0.0690.08 �0.0690.06 �0.0190.06 0.0790.06 0.3090.05 1.0390.02 1.5890.02 2.0390.02 0.7690.03 1.1490.05
3 4ClMPy �0.1290.06 �0.0690.06 �0.0690.05 0.0690.07 0.3790.04 1.2390.05 1.8490.02 2.4490.03 1.0190.05 1.3890.05
4 Py �0.2090.06 �0.1290.05 �0.1290.08 0.0390.06 0.4290.02 1.3490.04 1.9490.02 2.6090.04 1.1590.02 1.5190.05
5 3MPy �0.1690.16 �0.1990.09 �0.1290.07 0.0490.03 0.4790.03 1.3890.05 2.0090.02 2.7890.05 1.2490.04 1.5990.05
6 3,5DMPy �0.1890.13 �0.1690.08 �0.1190.15 0.0490.02 0.5490.02 1.5190.02 2.1290.02 2.9890.03 1.3790.02 1.7490.02
(b) ortho -Substituted pyridine -type ligands
7 2M5BrPy �0.2490.24 �0.1990.16 �0.0590.13 �0.0790.10 �0.0390.09 �0.0190.10 0.0190.10 0.6790.10 0.0090.12 0.4990.03
8 2A5BrPy �0.3490.11 �0.2490.13 �0.2190.12 �0.0890.08 �0.0390.08 0.0990.09 0.1790.05 0.9890.07 0.0790.07 0.5990.03
9 Tu �0.1490.13 �0.1390.09 �0.0790.09 �0.0590.12 0.1390.07 0.1390.09 0.3090.07 1.1990.06 0.1990.08 0.7190.07
10 2MPy �0.1990.10 �0.1590.08 �0.1590.07 �0.0290.06 0.0690.08 0.0590.08 0.2090.09 1.6290.03 0.2290.08 0.6890.03
11 2APy �0.2990.15 �0.2290.15 �0.1990.10 �0.0790.14 0.1390.10 0.2590.06 0.4290.07 1.8090.20 0.0590.20 0.9390.05
a For the error limits see footnote ‘a’ of Table 1. The entry numbers for the ligands correspond to those used in Table 1.
L.E
.K
ap
ino
s,H
.S
igel
/In
org
an
icaC
him
icaA
cta3
37
(2
00
2)
13
1�
/14
21
36
approximation to an equally large increase in complex
stability (i.e. of log KMM(L)): This observation promises to
be helpful for comparisons of data measured at different
values of I .
3.3. Relation between complex stability and ligand
basicity. Qualitative considerations
For families of structurally closely related ligands, a
linear relationship between log KMM(L) and pKH
H(L) is
expected [42] as expressed by Eq. (3):
log KMM(L)�m pKH
H(L)�b (3)
In Fig. 4, the values from Tables 1 and 2 for log KMM(L)
versus pKHH(L) of the simple pyridines (Fig. 2) are plotted
for six metal ions as examples. It is evident that the data
for a given metal ion fit excellently on a straight line.In an analogous way one may plot the data for the
ortho -substituted pyridine-type ligands (Tables 1 and 2,
entries 7�/11). This is done for four examples in Figs. 5
and 6 and also in these instances straight lines (filled
symbols) result.
From these two figures several conclusions are
immediately evident, i.e. without any further calcula-
tions: (i) in Fig. 5 the two lines due to the Cu2�
complexes are evidently parallel to each other and this
confirms an early observation [25]; of a similar paralle-
lism are the two lines for the Mg2� complexes, though
in this latter case the steric inhibition by the ortho
substituent is much smaller. However, (ii) from the two
examples shown in Fig. 6, it follows that this parallelism
is not a rule; the slopes due to the Ni2� and Cd2�
complexes formed with the ortho -substituted ligands are
lower than those of their complexes with the simple
pyridines. That is, for high pKHH(L) values the steric
inhibition is larger than for low pKHH(L) values. (iii) If one
compares the situations in Figs. 5 and 6 within the pH
range 3�/7, it is evident that the steric inhibition due to
an ortho substituent is most pronounced for the com-
plexes of Ni2�; indeed, for the four metal ions
considered in these two figures, the steric effect de-
Fig. 4. Relationship between log KMM(L) and pKH
H(L) for the 1:1
complexes of Mg2�, Mn2�, Ni2�, Cu2�, Zn2� and Cd2� with the
following simple and sterically unhindered pyridine-type ligands (k),
3-chloropyridine (3ClPy), 4-bromopyridine (4BrPy), 4-(chloro-
methyl)pyridine (4ClMPy), pyridine (Py), b-picoline (�/3-methylpyr-
idine, 3MPy) and 3,5-lutidine (�/3,5-dimethylpyridine, 3,5DMPy)
(from left to right) based on the results summarized in Tables 1 and
2 (entries 1�/6). The least-squares straight-reference lines are drawn
according to Eq. (3); these results are listed in Table 3, part (a). All
plotted equilibrium constants refer to aqueous solutions at 25 8C and
I�/0.5 M (NaNO3).
Fig. 5. Evidence for a reduced stability of the Mg2� (^,') and Cu2�
(k,m) 1:1 complexes of ortho -substituted pyridine-type ligands
(',m) compared with those of simple pyridine derivatives (^,k)
based on the log KMM(L) versus pKH
H(L) relationship. The reduced
complex stability reflects the steric inhibition due to an ortho -amino
or -methyl group. The sterically hindered pyridine-type ligands with an
ortho substituent (',m) are 2-methyl-5-bromopyridine (2M5BrPy), 2-
amino-5-bromopyridine (2A5BrPy), tubercidin (�/7-deazaadenosine,
Tu), a-picoline (�/2-methylpyridine, 2MPy) and 2-aminopyridine
(2APy) (from left to right). For the simple sterically unhindered
pyridine-type ligands (^,k) see Fig. 4 and its legend. All data pairs
are from Tables 1 and 2. The least-squares straight-reference lines are
drawn according to Eq. (3) and the results are listed in Table 3. All
plotted equilibrium constants refer to aqueous solutions at 25 8C and
L.E. Kapinos, H. Sigel / Inorganica Chimica Acta 337 (2002) 131�/142 137
creases in the order Ni2��/Cu2��/Cd2��/Mg2�. (iv)
A further important point that follows from Figs. 5 and
6 is that 2-methylpyridine and 2-aminopyridine and
their derivatives, including tubercidin, exert within the
error limits identical steric effects on metal ion binding
at the neighboring N site. An equal inhibitory effect of anon-bonding �/NH2 and a �/CH3 group on metal ion
binding at ortho -substituted pyridine-type ligands has
been suggested before [28,43] and this also agrees with
the recent conclusion about the shape complementarity
of the adenine and the 4-methylbenzimidazole residues
[44].
3.4. Quantitative evaluation of the log KMM(L) versus
pKHH(L) relations
Of course, the results listed in Tables 1 and 2 allow a
quantitative evaluation of the effects indicated in Sec-
tion 3.3; for each metal ion system five or six data pairs
are available. These were used to calculate by the least-squares procedure the straight-line equations summar-
ized in Table 3. From the plots of the equilibrium
constants of the Mg2� systems shown in Fig. 5, it is
evident that the data for the simple pyridines as well as
for the ortho -substituted ones can be fitted well to
straight lines. However, these two lines only show a
small dependence on pKHH(L); and this is the reason for
the low values obtained for the correlation coefficient R ,
i.e. 0.030 and 0.036 for the straight-line equations (4)
and (5), respectively:
log KMgMg(L)
�(0:00090:008) pKHH(L)�(0:04190:038) (4)
log KMgMg(L)ortho
�(0:00790:011) pKHH(L)�(0:09890:061) (5)
In fact, the slope m is in both equations zero within the
error limit (1s). This result agrees with a view on thestability constants listed in Table 2 for the Mg2�, Ca2�,
Sr2�, and Ba2� complexes; there is no dependence on
pKHH(L) observed and for a given series of complexes the
stability constants are identical within the error limits.
The results given in Table 2 for these ions are not very
precise, especially for the complexes of the ortho -
substituted pyridine-type ligands; this is understandable
because the stability of these complexes is very low.Clearly, within the error limits, the stability constants
for a given metal ion are independent of the ligand
considered, provided one stays within a given ligand
Fig. 6. Evidence for a reduced stability of the Ni2� (k,m) and Cd2�
(^,') 1:1 complexes of ortho -substituted pyridine-type ligands
(',m) compared with those of simple pyridine derivatives (^,k),
based on the log KMM(L) versus pKH
H(L) relationship. The reduced
complex stability reflects the steric inhibition due to an ortho -amino
or -methyl group. The sterically hindered pyridine-type ligands with an
ortho substituent (',m) are given in the legend of Fig. 5 and those of
the simple and sterically unhindered ones in the legend of Fig. 4. All
data pairs are from Tables 1 and 2. The least-squares straight-reference
lines are drawn according to Eq. (3) and the results listed in Table 3.
All plotted equilibrium constants refer to aqueous solutions at 25 8Cand I�/0.5 M (NaNO3).
Table 3
Straight-line parameters for M2� 1:1 complexes formed with simple
(a) and ortho -substituted (b) pyridine-type ligands, valid for aqueous
solutions at 25 8C and I�0.5 M (NaNO3) a,b
No. M2� m B R c
(a) Regression lines for simple pyridine -type ligands
1 Mn2� 0.10290.005 �0.11490.026 0.995
2 Co2� 0.21590.011 0.17090.054 0.995
3 Ni2� 0.23890.011 0.64790.057 0.995
4 Cu2� 0.41890.012 0.37490.058 0.998
5 Zn2� 0.24890.006 �0.19090.031 0.999
6 Cd2� 0.24690.006 0.18590.032 0.999
(b) Regression lines for ortho -substituted pyridine -type ligands
7 Mn2� 0.05290.026 �0.23090.145 0.754
8 Co2� 0.06690.030 �0.25490.167 0.782
9 Ni2� 0.11590.037 �0.40390.205 0.873
10 Cu2� 0.39790.027 �0.88990.146 0.993
11 Zn2� 0.10390.025 �0.39890.128 0.945
12 Cd2� 0.13190.031 �0.02890.172 0.925
a The slopes (m ) and intercepts (b ) for the straight reference lines
from plots of log KMM(L) versus pKH
H(L) were calculated by the least-
squares procedure from the experimentally determined equilibrium
constants listed in Tables 1 and 2.b Straight-line equation: y�mx�b , where x represents the pKH
H(L)
value of any (N1)-protonated pyridine derivative and y the calculated
stability constant (/log KMM(L)) of the corresponding M(L)2� complex
(Eq. (3)); the errors given with m and b correspond to one standard
deviation (1s ).c Correlation coefficient. In the case of small values for the slope
(m ) the values for R are also expected to be relatively small (see e.g.
entries 7, 8).
L.E. Kapinos, H. Sigel / Inorganica Chimica Acta 337 (2002) 131�/142138
series. Thus, the stability constants for the complexes of
Mg2�, Ca2�, Sr2�, and Ba2� are probably best
represented in the pKHH(L) range from 3 to 7 by the
averages of the individual stability constants. Hence,from the six values listed in Table 2 for each metal ion
one obtains for the stabilities of simple pyridine-type
ligands the results given in Eqs. (6)�/(9):
log KMgMg(L)�0:0490:04 (6)
log KCaCa(L)��0:0890:07 (7)
log KSrSr(L)��0:1290:08 (8)
log KBaBa(L)��0:1590:10 (9)
For ortho -amino or ortho -methyl group-substituted
pyridine-type ligands, one obtains correspondingly the
results given in Eqs. (10)�/(13):
log KMgMg(L)ortho��0:0690:06 (10)
log KCaCa(L)ortho��0:1390:13 (11)
log KSrSr(L)ortho��0:1990:14 (12)
log KBaBa(L)ortho��0:2490:15 (13)
For the six metal ions for which finally straight-line
equations were calculated for simple and ortho -substi-
tuted pyridine-type ligands (see Table 3), it is interesting
to determine the deviation from the least-squares line for
the stability constant of each individual complex. It issatisfying to see from the results summarized in Table 4,
part (a), that all deviations of the data points from their
straight line are within 9/0.05 log unit. For complexes of
the ortho -substituted pyridine-type ligands (Table 4,
part (b)) all deviations are within 9/0.10 log unit. The
larger deviations observed in the latter cases are due to
the low stability of these complexes, which gives rise to
larger experimental errors as already indicated above.
To provide a reliable error limit for any stabilityconstant calculated with the equations of Table 3 and a
given pKHH(L) value for each of the 12 metal ion systems
listed in Table 3, the standard deviation of the six or five
data points from the relevant least-squares line was
calculated (Table 4, heading SD). Users of the results
described in this section are recommended to apply the
equations of Table 3 to simple and ortho -substituted
pyridine-type ligands in the pKHH(L) range 3�/7 and to
consider as error limits for the calculated stability
constants, log KMM(L) (Eq. (3)), two or three times the
standard deviation (SD) given in Table 4 for the
corresponding metal ion system. For calculated stability
constants in the pKHH(L) range 0�/3 and 7�/10, the error
limits given for b (intercept with the y -axis) should also
be taken into account.
No stability constants were determined in this studyfor the Fe2� complexes of these pyridine-type ligands,
despite the obvious biological significance of this metal
ion, because such measurements are difficult to carry
out and are rather error-prone if traces of Fe3� are
present or formed during the experiment. In fact, in the
three stability constant compilations [18�/20], only very
few constants for Fe2� complexes are given. If values
are needed, we recommend the following estimation:according to experience [45], based on the Irving�/
Williams sequence [46], one may propose the use of
the average of the results obtained for the Mn2� and
Co2� complexes; this view is also supported by recent
results [30].
Table 4
Logarithmic differences between the experimentally determined stability constants (/log KMM(L) of Table 2) of the M2� complexes for simple (entries 1�/
6; Fig. 2) and for ortho -substituted (entries 7�/12; Fig. 3) pyridine derivatives and the least-squares lines of the log KMM(L) versus pKH
H(L) plots (Table
3). a The column farthest to the right gives the standard deviation (SD) resulting from the listed differences.
(a) Simple pyridine -type ligands
No. M2� 3ClPy 4BrPy 4ClMPy Py 3MPy 3,5DMPy SD
1 Mn2� 0.00 0.02 �0.01 �0.01 �0.01 0.02 0.006
2 Co2� �0.03 0.02 0.02 0.02 �0.04 0.00 0.011
3 Ni2� �0.02 0.00 0.04 0.02 �0.03 �0.01 0.011
4 Cu2� �0.03 0.02 0.05 �0.01 �0.02 0.00 0.012
5 Zn2� 0.02 �0.02 0.00 0.02 �0.01 0.01 0.007
6 Cd2� 0.01 �0.01 0.01 0.01 �0.02 0.02 0.006
(b) ortho-Substituted pyridine-type ligands
No. M2� 2M5BrPy 2A5BrPy Tu 2MPy 2APy SD
7 Mn2� 0.00 �0.05 0.09 �0.03 0.00 0.024
8 Co2� �0.01 0.02 0.04 �0.10 0.05 0.027
9 Ni2� �0.03 0.02 0.10 �0.10 0.03 0.033
10 Cu2� 0.03 �0.06 �0.01 0.07 �0.03 0.023
11 Zn2� 0.00 �0.03 0.05 �0.01 �0.09 0.027
12 Cd2� 0.01 �0.02 0.05 �0.10 0.06 0.029
a The entry numbers for the various M2� systems correspond to those used in Table 3.
L.E. Kapinos, H. Sigel / Inorganica Chimica Acta 337 (2002) 131�/142 139
Another interesting observation is closely connected
with the quantitative evaluations given in this section.
We have already seen in Figs. 4 and 5, and expressed this
clearly in Eqs. (6)�/(12), that the stability of thecomplexes of the alkaline earth ions does not depend
on the basicity of the pyridine nitrogen. Why? The only
evident explanation for this experimental result is that in
these instances outersphere complexes are formed. If
there is a water molecule between the liganding N site
and the metal ion, then one expects that a change in the
basicity of the ligand is only little or not at all reflected
in the stability of the complexes. Such outerspherecomplexes are also expected to be of a low stability
and this is the case indeed. Furthermore, the steric
inhibition of the ortho substituent is very small in these
instances as is seen in Fig. 5 and as follows also from
Eqs. (6)�/(12); the inhibition only amounts to about
0.05�/0.10 log unit.
The only other example where the slopes of the
straight-line plots are identical for simple and forortho -substituted pyridine-type complexes are those of
Cu2� (see Fig. 5 and Table 3, entries 4, 10). The fact
that the slopes are identical indicates that Cu2� forms
innersphere complexes with both series of ligands; this is
also in accord with the relatively steep slopes, i.e., m #/
0.4. Indeed, from entries 1�/6 in Table 3 it follows that
the slope of the straight lines decreases for the M2�
complexes in the order Cu2��/Zn2��/Ni2��/
Co2��/Mn2�, the slope for Cd2� being close to those
for Zn2� and Ni2�. This indicates that in this order also
the amount of outersphere complexation increases; i.e.
the lower the slope, the higher the formation degree of
the outersphere species. Since an ortho -amino or ortho -
methyl substituent inhibits of course especially inner-
sphere complex formation, the slopes are expected to
decrease and this is exactly observed in all instances(except for Cu2�); however, the given order of the
slopes for the metal ions is hardly affected (Table 3,
entries 7�/12), as one would also expect. Moreover, the
slopes of the reference lines due to the Mn2� complexes
are very small (m�/0.10 and 0.05; Table 3, entries 1, 7),
that is, they are closest to the zero slopes of the Mg2�
complexes (Eqs. (4) and (6)) and this agrees with the
often described chemical kinship of these two metal ions[47�/49]; clearly, outersphere complex formation is of the
highest relevance for Mn2� among all the transition
metal ions studied here.
4. Conclusions
There are a few more stability constants available in
the literature [18�/20] of complexes of pyridine-typeligands, like 3-aminopyridine, 3,4-dimethylpyridine
(�/3,4-lutidine), and 4-methylpyridine (4MPy�/g-pico-
line). We select the latter ligand to demonstrate the
usefulness of the straight-line equations listed in
Table 3 because a relatively large number of complexes
of 4MPy has been studied before, even though these
results refer to different ionic strengths (25 8C; the errorlimits are estimates): log KCo
Co(4MPy)�1:5690:06 (I �0:5 M) [18], log KNi
Ni(4MPy)�2:1190:06 (I �0:1 M)
[21], log KCuCu(4MPy)�2:8890:06 (I �0:1 M) [21],
log KZnZn(4MPy)�1:4090:08 (I �0:1 M) [21], and
log KCdCd(4MPy)�1:6290:08 (I �1 M) [18]. Application
of the acidity constant, pKHH(4MPy)�6:1890:02/
/(I �0:1 M) [21] to the straight-line equations of Table
3 (entries 2�/6) provides the following calculatedstability constants for the five M(4MPy)2� comp-
lexes: log KMM(4MPy)�1:5090:03 (Co2�); 2:1290:03 /
/(Ni2�); 2:9690:04 (Cu2�); 1:3490:02 (Zn2�); and /
/1:7190:02 (Cd2�) (25 8C; I�/0.5 M). The agreement
between the experimental and calculated constants is
excellent, although some of these values were measured
nearly 40 years ago.
A similar excellent result is obtained for the Cu2�
complex of the ortho -substituted 2,5-dimethylpyridine
(2,5DMPy�/2,5-lutidine): the measured value,
log KCuCu(2;5DMPy)�1:7890:03 (25 8C; I�/0.5 M) [22], is
in excellent agreement with the calculated value based
on the acidity constant, pKHH(2;5DMPy)�6:63 (I�/0.6 M)
[22], and the straight-line equation for ortho -substituted
pyridine-type ligands (Table 3, entry 10), i.e.
log KCuCu(2;5DMPy)calc�1:7490:07 (I�/0.5 M).
That the (C6)-amino group of the adenine residue (see
Fig. 1) hinders metal ion binding at N1 and at N7 is
known [14], but an exact quantification of this inhibition
has remained elusive. The present study with its straight-
line relations for the complexes of ortho -amino or ortho -
methyl-substituted pyridine-type ligands allows now a
quantification of the effect of the (C6)NH2 group on
metal ion binding at N1 of an adenine moiety. Similarly,very recently we have studied [29] the metal ion binding
properties of DMBI, also named 6,9-dimethyl-1,3-di-
deazapurine; a model compound for the adenine residue
[44] (see Fig. 1). Assuming that the steric hindrance on
the N7 site by a (C6)NH2 or a (C6)CH3 group is equal,
which in fact has been proven (see Section 3.3), we are
now in the position to compare for the first time the
steric effect of the (C6)NH2 group on metal ion bindingat N1 and N7 for an adenine residue.
To this end we select the acidity constant pKHH(L)�
5:78; which also quantifies the deprotonation of
H(DMBI)� [29], because in this way the basicity of
the two N sites is kept equal and any differences possibly
observed in complex stability refer then to differences in
the steric hindrance. Application of the mentioned
acidity constant to the straight-line equations given inentries 1�/6 of Table 3 leads to the results listed in the
second column of Table 5; these stability constants
reflect the affinity of a pyridine nitrogen which is not
affected by any steric hindrance. Application of the
L.E. Kapinos, H. Sigel / Inorganica Chimica Acta 337 (2002) 131�/142140
corresponding procedure to entries 7�/12 of Table 3
gives the stability constants of metal ion complexes
which suffer a steric hindrance of an ortho -ami-
no(methyl) group upon their coordination to the
pyridine nitrogen; these results are listed in column 3
of Table 5. In column 4, the stability differences
log DM(Py-type)ortho , which result from the two columns
to its left, are listed; these values quantify the steric
inhibition of the (C6)NH2 group on (N1)�/metal ion
binding of an adenine residue. The final column in Table
5 gives the log DM(DMBI) values, taken from [29], which
characterize the same effect on N7�/metal ion binding
also of an adenine residue (Fig. 1). As said above, the
basicity of N1 and N7 in this ‘hypothetical’ adenine
residue has been put equal to each other (pKHH(L)�5:78):/
Comparison of the values listed in columns 4 and 5 of
Table 5 allows several interesting conclusions: (i)
inhibition by the (C6)NH2 group, if reference is made
to an adenine residue, to binding of Mg2� at N1 or N7
is small and within the error limits identical. (ii) This
contrasts with the very large and within the error limits
again identical steric inhibition (approximately �/1.8 log
units), which is experienced by Ni2�, if binding to the
same two sites is considered. (iii) Cu2� binding to N1 is
also strongly affected by the (C6)NH2 group, but it
suffers less (by about 0.4 log unit) in its binding
tendency toward N7. (iv) This observation for Cu2�
contrasts with that for all other metal ions, i.e. Mn2�,
Co2�, Zn2�, and Cd2�, the binding of which at N1 is
less affected than that at N7 by the (C6)NH2 group.
These comparisons show that now the basic informa-
tion is available which should allow a re-evaluation of
the metal ion binding properties of cytidine [43] and of
adenosine [13]. Work on these aspects is in progress in
this laboratory.
Acknowledgements
The competent technical assistance of Mrs. Rita
Baumbusch and Mrs. Astrid Sigel in the preparation
of this manuscript is gratefully acknowledged. This
study was supported by the Swiss National Science
Foundation and within the COST D20 programme by
the Swiss Federal Office for Education and Science.
References
[1] R. Ziessel, Coord. Chem. Rev. 216�/217 (2001) 195�/223.
[2] J.R. Hagadorn, L. Que, Jr., W.B. Tolman, Inorg. Chem. 39 (2000)
6086�/6090.
[3] J.M. Holland, C.A. Kilner, M. Thornton-Pett, M.A. Halcrow,
Polyhedron 20 (2001) 2829�/2840.
[4] (a) D.S. Marlin, M.M. Olmstead, P.K. Mascharak, Inorg. Chem.
40 (2001) 7003�/7008;
(b) D.S. Rawat, P.J. Benites, C.D. Incarvito, A.L. Rheingold,
J.M. Zaleski, Inorg. Chem. 40 (2001) 1846�/1857.
[5] (a) R. Lipinski, L. Chruscinski, P. Mlynarz, B. Boduszek, H.
Kozlowski, Inorg. Chim. Acta 322 (2001) 157�/161;
(b) L. Chruscinski, P. Mlynarz, K. Malinowska, J. Ochocki, B.
Boduszek, H. Kozlowski, Inorg. Chim. Acta 303 (2000) 47�/53.
[6] H. Kurosaki, R.K. Sharma, S. Aoki, T. Inoue, Y. Okamoto, Y.
Sugiura, M. Doi, T. Ishida, M. Otsuka, M. Goto, J. Chem. Soc.,
Dalton Trans. (2001) 441�/447.
[7] G. Sydow, V. Wunderlich, L. Baumbach, E. Tonew, M. Tonew,
H.P. Schroer, Zentralbl. Bakteriol. Mikrobiol. Hyg. 262 (1986)
169�/178.
[8] C. Hemmert, M. Pitie, M. Renz, H. Gornitzka, S. Soulet, B.
Meunier, J. Biol. Inorg. Chem. 6 (2001) 14�/22.
[9] L. Stryer, Biochemie (translated by B. Pfeiffer, J. Guglielmi from
Biochemistry, Freeman, New York, 1988), Spektrum Akad.
Verlag, Heidelberg, 1991.
[10] R. Amunugama, M.T. Rodgers, J. Phys. Chem., A 105 (2001)
9883�/9892.
[11] R.B. Martin, Acc. Chem. Res. 18 (1985) 32�/38.
[12] Y. Kinjo, R. Tribolet, N.A. Corfu, H. Sigel, Inorg. Chem. 28
(1989) 1480�/1489.
Table 5
Comparison of the steric inhibition due to the (C6)NH2 group in an adenine residue on metal ion binding at N1 (�ortho -substituted pyridine-type
binding) and N7; the latter is based on results [29] obtained for DMBI (Fig. 1) a
M2�/Log KM
M(Py-type)b
/Log KMM(Py-type)ortho/
b Log DM(Py-type)ortho Log DM(DMBI)c
Mg2� 0.0490.04 �0.0690.06 �0.1090.07 �0.0690.13
Mn2� 0.4890.02 0.0790.07 �0.4190.07 �0.8690.08
Co2� 1.4190.03 0.1390.08 �1.2890.09 �1.5090.07
Ni2� 2.0290.03 0.2690.10 �1.7690.10 �1.8690.07
Cu2� 2.7990.04 1.4190.07 �1.3890.08 �0.9490.06
Zn2� 1.2490.02 0.2090.08 �1.0490.08 �1.2390.09
Cd2� 1.6190.02 0.7390.09 �0.8890.09 �1.3690.07
All values refer to aqueous solutions at 25 8C and I� 0.5 M (NaNO3).a The error limits are three times the standard errors and for the derived data (columns 4 and 5) they were calculated according to the error
propagation after Gauss.b Calculated with pKH
H(L)�5:78 (see text) and the straight-line equations listed in Table 3; the error limits are from Table 4 (�3�SD). The values
for the Mg2� complexes are those given in Eqs. (6) and (10).c These values are from Ref. [29].
L.E. Kapinos, H. Sigel / Inorganica Chimica Acta 337 (2002) 131�/142 141
[13] H. Sigel, N.A. Corfu, L.-n. Ji, R.B. Martin, Comments Inorg.
Chem. 13 (1992) 35�/59.
[14] R.B. Martin, Met. Ions Biol. Syst. 32 (1996) 61�/89.
[15] H. Sigel, Eur. J. Biochem. 165 (1987) 65�/72.
[16] H. Sigel, Chem. Soc. Rev. 22 (1993) 255�/267.
[17] H. Sigel, B. Song, Met. Ions Biol. Syst. 32 (1996) 135�/203.
[18] Data collected and selected by R.M. Smith, A.E. Martell, NIST
Critically Selected Stability Constants of Metal Complexes,
Reference Database 46, Version 6.0, US Department of Com-
merce, National Institute of Standards and Technology, Gaithers-
burg, MD, USA, 2001.
[19] Compiled by L.D. Pettit, H.K.J. Powell, IUPAC Stability
Constants Database, Release 3, Version 4.02, Academic Software,
Timble, Otley, West Yorkshire, UK, 1999.
[20] Joint Venture by K. Murray, P.M. May, Joint Expert Speciation
System (JESS), Version 6.0, Division of Water Technology, CSIR,
Pretoria, South Africa, and School of Mathematical and Physical
Sciences, Murdoch University, Murdoch, Western Australia,
1999.
[21] K. Kahmann, H. Sigel, H. Erlenmeyer, Helv. Chim. Acta 47
(1964) 1754�/1763.
[22] M.S. Sun, D.G. Brewer, Can. J. Chem. 45 (1967) 2729�/2739.
[23] Ya.I. Tur’yan, N.I. Pershakova, O.E. Ruvinskii, Zh. Obs. Him. 42
(1972) 1198�/1202 (translation: J. Gen. Chem. USSR 42 (1972)
1194�/1197).
[24] (a) Z. Warnke, B. Lenarcik, Roczniki Chemii, Ann. Soc. Chim.
Polon. 45 (1971) 1385�/1390;
(b) B. Lenarcik, M. Rzepka, Polish J. Chem. 52 (1978) 447�/455.
[25] H. Sigel, H. Wynberg, T.J. van Bergen, K. Kahmann, Helv.
Chim. Acta 55 (1972) 610�/613.
[26] J. Arpalahti, H. Lonnberg, Inorg. Chim. Acta 78 (1983) 63�/68.
[27] S.-H. Kim, R.B. Martin, Inorg. Chim. Acta 91 (1984) 19�/24.
[28] L.-n. Ji, N.A. Corfu, H. Sigel, J. Chem. Soc., Dalton Trans. (1991)
1367�/1375.
[29] L.E. Kapinos, A. Holy, J. Gunter, H. Sigel, Inorg. Chem. 40
(2001) 2500�/2508.
[30] L.E. Kapinos, B. Song, H. Sigel, Chem. Eur. J. 5 (1999) 1794�/
1802.
[31] L.E. Kapinos, B. Song, H. Sigel, Inorg. Chim. Acta 280 (1998)
50�/56.
[32] C.A. Blindauer, T.I. Sjastad, A. Holy, E. Sletten, H. Sigel, J.
Chem. Soc., Dalton Trans. (1999) 3661�/3671.
[33] A. Fernandez-Botello, R.B. Gomez-Coca, A. Holy, V. Moreno,
H. Sigel, Inorg. Chim. Acta 331 (2002) 109�/116
[34] H. Sigel, A.D. Zuberbuhler, O. Yamauchi, Anal. Chim. Acta 255
(1991) 63�/72.
[35] R. Tribolet, H. Sigel, Eur. J. Biochem. 163 (1987) 353�/363.
[36] (a) J.J. Christensen, J.H. Rytting, R.M. Izatt, Biochemistry 9
(1970) 4907�/4913;
(b) J.J. Christensen, J.H. Rytting, R.M. Izatt, J. Chem. Soc., B
(1970) 1643�/1646.
[37] M.T. Rodgers, J. Phys. Chem., Sect. A 105 (2001) 2374�/2383.
[38] M. Meot-Ner (Mautner), J. Am. Chem. Soc. 101 (1979) 2396�/
2403.
[39] D. Banerjea, T.A. Kaden, H. Sigel, Inorg. Chem. 20 (1981) 2586�/
2590.
[40] G. Anderegg, Helv. Chim. Acta 57 (1974) 1340�/1346.
[41] G. Kampf, L.E. Kapinos, R. Griesser, B. Lippert, H. Sigel, J.
Chem. Soc., Perkin Trans. 2 (2002) 1320�/1327.
[42] R.B. Martin, H. Sigel, Comments Inorg. Chem. 6 (1988) 285�/314.
[43] Y. Kinjo, L.-n. Ji, N.A. Corfu, H. Sigel, Inorg. Chem. 31 (1992)
5588�/5596.
[44] J.C. Morales, E.T. Kool, Nat. Struct. Biol. 5 (1998) 950�/954.
[45] H. Sigel, D.B. McCormick, Acc. Chem. Res. 3 (1970) 201�/208.
[46] (a) H. Irving, R.J.P. Williams, Nature 162 (1948) 746�/747;
(b) H. Irving, R.J.P. Williams, J. Chem. Soc. (1953) 3192�/3210.
[47] R.B. Martin, Met. Ions Biol. Syst. 26 (1990) 1�/13.
[48] A.L. Feig, Met. Ions Biol. Syst. 37 (2000) 157�/182.
[49] G.H. Reed, R.R. Poyner, Met. Ions Biol. Syst. 37 (2000) 183�/207.
L.E. Kapinos, H. Sigel / Inorganica Chimica Acta 337 (2002) 131�/142142
Top Related