Mixed-ligand zinc(II) complexes with diethylenetriamine (or triethylenetetramine) and α-(or β-)...

Mixed-ligand zinc(II) complexes with diethylenetriamine(or triethylenetetramine) and a-(or b-) alaninehydroxamic acids

in water solution. Potentiometric and NMR studies

Danuta Kroczewska a, Barbara Kurzak a,*, Ewa Matczak-Jon b

a Institute of Chemistry, University of Podlasie, 3-Maja 54, 08-110 Siedlce, Polandb Institute of Inorganic Chemistry, Wrocl aw University of Technology, Wybrzeze Wyspianskiego 27, 50-370 Wrocl aw, Poland

Received 15 May 2002; accepted 18 July 2002

Abstract

Stabilities of the mixed-ligand complexes of ZnII ion with diethylenetriamine [bis(2-aminoethyl)amine, dien) or triethylenete-

tramine [ethylenebis(2?-aminoethylamine, trien] as a primary ligand A and a-alaninehydroxamic acid [2-amino-N -hydroxypropa-

namid, a-Alaha] or b-alaninehydroxamic acid [3-amino-N -hydroxypropanamid, b-Alaha] as a secondary ligand L and their NMR

behaviour are reported. The NMR spectra show that in the binary systems a- and b-Alaha are capable of binding zinc(II) in either

(O,O) or (N,N) chelating mode. In contrast, in the ternary systems both behave as simple hydroxamic acids, thus, co-ordinate

zinc(II) exclusively through the oxygens of the hydroxamate groups. This is reflected in the same basicity-adjusted stability

constants, log KZn(dien)(a-Alaha)(b-Alaha)�/pKNHOHmicro .

# 2002 Elsevier Science B.V. All rights reserved.

Keywords: Zinc(II) complexes; Mixed-ligand complexes; Aminohydroxamic acids; Polyamines; NMR spectra; Potentiometry

1. Introduction

The importance of mixed-ligand complexes in bio-

chemical systems is beyond question. These types of

complexes are implicated in the storage and transport of

metal ions and of active substances through membranes.

So, it is worthwhile to assemble information on their

formation, stability and structure and on the mutual

influence of two ligands bound to the same metal ion.

Previously we reported stabilities and structures of the

mixed-ligand complexes of CuII ion with diethylenetria-

mine as a primary ligand and a-alanine-/b-alaninehy-

droxamic acid [1] or histidine�/methioninehydroxamic

[2] acid as a secondary ligand L and their absorption and

EPR spectra at various pH values.

The knowledge for ternary systems of ZnII is still

limited because studies on zinc(II) complexes are

difficult, as far as co-ordination modes are concerned,

due to the limitations of the available techniques.Some studies have focused on model complexes of

zinc(II) ions to improve the understanding of the

structure-reactivity relationship of the active site in

zinc-enzymes [3�/7]. In some of the model complexes

the chelating ligands (e.g. polyamines) have been

selected to bind to three or four co-ordination sites of

ZnII via N donor atoms, with the next sites being

occupied by other ligands [8�/11].

As part of our program on the co-ordination chem-

istry of ZnII, we have set out to elucidate the molecular

structures and reactivities of the mixed-ligand complexes

of ZnII of simple polyamines and aminohydroxamic

acids (Scheme 1).

Polyamines*/because zinc(II) in carbonic anhydrase

(CA) is similarly bound to three nitrogen atoms (of

imidazoles); aminohydroxamic acids*/because some of

these ligands inhibit proteolytic enzymes and apart from

they have different affinities to metal ions [12] (oxygen

being a harder base and nitrogen being a border line

base), from very hard AlIII and FeIII [13] across border

* Corresponding author. Tel.: �/4825-644-10-97; fax: �/4825-644-

20-45

E-mail address: [email protected] (B. Kurzak).

Polyhedron 21 (2002) 2183�/2193

www.elsevier.com/locate/poly

0277-5387/02/$ - see front matter # 2002 Elsevier Science B.V. All rights reserved.

PII: S 0 2 7 7 - 5 3 8 7 ( 0 2 ) 0 1 1 6 3 - 4

mailto:[email protected]

line acids ZnII, CuII and NiII [14�/16] to softer CdII [17].

Both donor sets (O,O) and (N,N) of a-alaninehydroxa-

mic acid form, when co-ordinated, very stable five-

membered chelate rings, b-alaninehydroxamic acid

forms less stable six-membered chelate ring when co-

ordinated via Namino, Nhydroxamate donor atoms.

The aim of the study in this paper was to obtaininformation on preferred sets of donor atoms of a- and

b-alaninehydroxamic acids in mixed-ligand complexes,

as well as to collect information about their spectro-

scopic data. The co-ordination tendencies of studied

ligands towards zinc(II) ions in aqueous solution were

studied by potentiometry and NMR spectroscopy.

2. Experimental

2.1. Materials

a- and b-Alaha were prepared by us via the methyl

ester of the respective amino acid as described in [18].

Dien and trien were from Aldrich (Germany) used

without further purification and its purity was greater

than 99%.

The exact concentrations of the stock solutions of thehydroxamic acids and polyamines were determined by

Gran’s method [19]. Zinc(II) chloride solution was

purchased from Titrisol ampoule (Merck). Zinc(II)

nitrate (Aldrich) was used as a source of ZnII in the

NMR studies.

2.2. Methods

2.2.1. Potentiometric measurements

The potentiometric measurements were carried out at25.09/0.1 8C. A summary of the experimental details is

given in Table 1.

The data for the ZnII�/a-Alaha and ZnII�/b-Alaha

binary systems can be found in our early papers [14,20]

and some of them are included in Table 2. Data for the

ZnII�/dien binary system can be found in the literature

[21], but for a comparison we had to determine stability

constants under identical conditions to those of theternary systems, i.e. at 25.0 8C and ionic strength of 0.2

M (KCl). For the binary system 1:1, 1:2 and 1:4 metal to

ligand ratios were used. For the determination of the

stability constants of the mixed ligand complexes the

concentration ratios of metal�/dien/trien�/a-Alaha/b-

Alaha were 1:1:1, 1:1:2, 1:2:1 and 1:2:2. All the pH-

metric titrations were carried out with carbonate-free

KOH solution of known concentration (ca. 0.2 M).

Titration emf data were used to calculate the hydrogen

ion concentration, [H�]. Stability constants bpqrs �/

[MpAqLrHs ]/[M]p [A]q [L]r [H]s were calculated with the

aid of the SUPERQUAD computer program [22].

For clarity, the charges of the complexes have been

omitted in the tables. It has to be mentioned, however,

that the fully deprotonated forms of aminohydroxamic

acids are negative (L�) while the polyamines are neutral

(A).

2.2.2. NMR spectra

NMR spectra were recorded on a Bruker DRX

spectrometer operating at 300.13 MHz for 1H and

75.46 MHz for 13C at 300 K, unless otherwise noted.

The chemical shifts are given in relation to SiMe4. All

downfield shifts are denoted as positive.

The assignments for carbon atoms of dien and trien(Scheme 1) follow those presented in ref. [23]. In order

to correlate the 1H and 13C chemical shift assignments

for the studied ligands inverse detected [1H�/13C]

HMQC NMR experiments were performed using STAN-

DARD BRUKER program.

The samples for NMR studies were prepared in

deuteriated water. The measurements were performed

only for freshly prepared solutions. In the ZnII�/hydro-xamate binary systems the metal to ligand molar ratios

were 1:1 and 1:2, the ligand concentration was 2�/10�2

M. The binary ZnII�/polyamine and ternary ZnII�/

Scheme 1.

Table 1

Summary of experimental parameters for the potentiometric measure-

ments

Systems Binary:dien, trien, a-Alaha or b-Alaha with H�

or ZnII in water solution; ternary�/dien/trien and

a-Alaha/b-Alaha with ZnII in water solution

Solution

composition

[dien], [trien], [a-Alaha] and [b-Alaha] range*/

0.002�/0.004 M, [ZnII] range*/0.001�/0.004 M;

ionic strength*/0.200 M; electrolyte KCl

Experimental

method

pH-metric titration of 5 cm3 samples in the range

of pH 2�/11; pKw�13.73

Instruments Microburette ABU-80 (Radiometer), Radelkis

OP-208/1 pH-meter, micro combination pH elec-

trode (Mettler-Toledo, Type 2)

Calibration By periodic titrations of a HCl solution (5�10�2

M KCl) against standard KOH soution

T (8C) 25.090.1

ntota 50�/70

ntitb 6�/8

Method of

calculation

SUPERQUAD [22]

a Number fo titration points per titration.b Number of titration per metal�/ligand (or metal�/ligand A�/ligand

L) systems.

D. Kroczewska et al. / Polyhedron 21 (2002) 2183�/21932184

polyamine�/hydroxamate systems were prepared with a

zinc(II) concentration of 1�/10�1 M at the 1:1 or 1:1:1

metal to ligand A to ligand L molar ratios, respectively.The pH of the samples was measured using a Radio-

meter pHM83 instrument equipped with a 2401c

combined electrode and given as meter readings without

correction for pD.

3. Results and discussion

3.1. Solution equilibria

The acid dissociation constants of the studied ligands

are given in Table 2, together with the values previously

published by us for dien, trien, a- and b-Alaha. The

values of the stability constants obtained for the

complexes in the studied systems are listed in the same

Table 2.The general four-component equilibria can be written

as:

pZn�qA�rL�sHXZnpAqLrHs

where p , q , r and s are the stoichiometric coefficientscorresponding to the zinc(II) metal ion, A�/dien or

trien, L�/a-Alaha or b-Alaha, and H, respectively;

charges are omitted for simplicity.

The overall formation constants are defined as:

bpqrs� [ZnpAqLrHs]=[Zn]p[A]q[L]r[H]s

The bpqrs constant expresses the stability of the

[ZnAL]� mixed-ligand species.

3.1.1. ZnII�/dien�/a-Alaha/b-Alaha systems

The equilibrium constant, KZnAL, evaluated from the

computed values of the related bpqrs values according to

equation: log KZnAL�/log bZnAL�/log bZnA, shows howtightly L (aminohydroxamic anion) is bound to the

simple [ZnA]2� complex.

The log KZn(dien)L values are 4.65 and 5.09 for L�/a-

Alaha or b-Alaha, respectively. These values should be

compared with log bZnL. For L�/b-Alaha this compar-

ison cannot be done, since the complex with 1:1 ratio is

not formed in measurable concentrations in the ZnII�/b-

Alaha system. The log bZnL value describing the reac-tion Zn2��/a-AlahaX/[Zn(a-Alaha)]� gives 5.29. The

difference of these two values (4.65�/5.29), Dlog K ,

describes the difference between the affinities of a-Alaha

to ZnII and to [Zn(dien)]2�. Since it is similar to that

expected on a statistical basis [24,25], it indicates that a-

Alaha binds to the [Zn(dien)]2� complex as easily as to

ZnII.

Sigel’s log XZn(dien)L value (the constant due to theequilibrium [Zn(dien)2]2��/[ZnL2]X/2[Zn(dien)L]�) for

L�/a- or b-Alaha are 3.92 and 3.22, respectively, and

are abnormally high (expected on a statistical basis is 0.6

Table 2

Overall stability constants (log b ) and stepwise formation contants (log K ) for H� and ZnII complexes formed with dien/trien (A) and a-Alaha/b-

Alaha (L) in binary systems at 25 8C and I�0.2 M (KCl) in water solutions (the ion charges are omitted)

Assignments A�dien A� trien Assignments L�a-Alaha L�b-Alaha

log b [HA] 9.97(1) 9.83(1) log b [HL] 9.20(0) 9.89(1)

log b [H2A] 19.05(1) 19.30(1) log b [H2L] 16.54(1) 18.38(1)

log b [H3A] 23.40(1) 26.19(1) pK1micro (NH3

�) 7.48(2) a 8.85(2) a

log b [H4A] 29.64(1) pK2micro(CONHOH) 7.90(3) a 8.47(2) a

pK1 4.35 3.45

pK2 6.89 log b [ZnHL] 12.27(1) 14.66(5)

pK3 9.08 9.47 log b [ZnL] 5.29(1)

pK4 9.97 9.83 log b [Zn2L3] 18.77(2)

log b [ZnLH�1] �2.26(2)

log b [ZnAH] 17.43(6) log b [Zn(HL)2] 28.51(3)

log b [ZnA] 8.94(2) log b [ZnHL2] 20.36(4)

log b [Zn(AH)2] 35.38(2) log b [ZnL2] 9.32(4) 11.19(4)

log b [ZnA2H] 22.26(5) 26.51(4) log b [ZnL2H�1] 1.16(4)

log b [ZnA2] 13.96(5) 17.02(5)

log K [ZnA] 8.94 log K [ZnL] 5.29

[ZnA]�AX [ZnA2] [ZnL]�LX [ZnL2]

log K [ZnA2] 5.02 log K [ZnL2] 4.03

[ZnA]�HAX [ZnA2H] pK [ZnHL] 6.98

log K [ZnA2H] 3.35 pK [ZnL] 7.55

pK [Zn(HL)2] 8.15

pK [Zn(AH)2] 8.87 pK [ZnHL2] 9.17

pK [ZnA2H] 8.30 9.49 pK [ZnL2] 10.03

log(KZnA/KZnA2) 3.92 log(KZnL/KZnL

2) 1.26

a E. Farkas, T. Kiss, B. Kurzak, J. Chem. Soc., Perkin trans. 2 (1990) 1255.

D. Kroczewska et al. / Polyhedron 21 (2002) 2183�/2193 2185

[24,25]), which means that the formation of the mixed

complexes is strongly favoured in these systems (Table3) and there are some special causes to stabilise them. It

is notable that the denticity of the amines is certainly

different in the ternary and binary systems. This is

clearly demonstrated by the derived equilibrium con-

stant, representing the binding ability of dien to their 1:1

complex and to the 1:1 complex of a-Alaha:

Zn(dien)�dienXZn(dien)2 log K�5:02

Zn(a-Alaha)�dienXZn(a-Alaha)(dien) log K�8:31

In the second case, the derived equilibrium constant is

significantly higher, indicating that dien has a higher

denticity in the ternary complex, than in the binary one.From Table 3, it can be seen that for the ZnII�/dien�/

a-Alaha system the speciation model contains six simple

species an two mixed-ligand ones: [Zn(dien)(a-Alaha)]�

and [Zn(dien)(a-Alaha)H�1]. For this system concen-

tration distribution curves are presented in Fig. 1.

The ZnII�/dien 1:1 and 1:2 complexes are formed at

high concentrations at zinc(II)�/dien�/a-Alaha ratio of

1:2:2. Under these conditions the mixed-ligand com-plexes are of approximately 30% of the total zinc

content, but at 1:1:2 ratio the mixed-ligand complex

reaches of approximately 90% (Fig. 1(c)). Additionally,

Fig. 1(c) shows that the presence of dien suppresses the

formation of polymeric [Zn2(a-Alaha)3]� species in the

ternary system.

The calculated concentrations of these eight zinc(II)

complex species, as a function of pH (shown in Fig. 1(c))indicate that under these conditions the [Zn(dien)(H�/

dien)]3�, [Zn(a-Alaha)2], [Zn(dien)2]2� species are the

minor ones, so can be regarded as negligible. The first

mixed-ligand species, [Zn(dien)(a-Alaha)]�, is seen

above pH 7 whereas above pH 9.5 [Zn(dien)(a-

Alaha)H�1] appears.

In the ZnII�/dien�/b-Alaha system, the titration data

fit satisfactorily to the assumption of the presence of the

four simple species: [Zn(dien)]�, [Zn(H�/b-Alaha)2]�,

[Zn(dien)2]2�, [Zn(dien)(H�/dien)]3�, and two mixed-

ligand ones: [Zn(dien)(H�/b-Alaha)]2� and [Zn(dien)(b-

Alaha)]�. The stability constants obtained for the

complexes in the binary and ternary systems are given

in Tables 2 and 3, together with the values for the simple

complexes taken from the previous studies [14].

Concentration distribution curves are presented in

Fig. 2.

The calculated concentrations of these six zinc(II)

complex species, as a function of pH, for ZnII�/dien�/b-

Alaha 1:1:2 ratio system (shown in Fig. 2(c)) indicate

that under these conditions the first mixed-ligand

species, [Zn(dien)(H�/b-Alaha)]2�, appears above pH 6

and reaches a maximum concentration of approximately

65% at pH 8. The next mixed-ligand species [Zn(dien)(b-

Alaha)]�, is a major one (ca. 100% at pH 11). The

[Zn(dien)2]2� and [Zn(dien)(H�/dien)]3� species were

found in the ternary system with a very low (B/4%)

concentrations. However, when these species were not

included in the model the goodness of fit tests was much

worse.

The deprotonation process of [Zn(dien)(H�/b-

Alaha)]2� leading to the formation of [Zn(dien)(b-

Alaha)]� above pH 7 corresponds to the liberation of

the proton from the �/NH3� group of b-Alaha, which is

hardly likely, since the pKZn(dien)(H�b-Alaha) value equal

to 8.73 (Table 3 number 8) is characteristic for the pKb-

Table 3

Overall stability constants (log b ), deprotonation constants (pK ) and characteristic parameters for ZnII complexes formed with diethylenetriamine�/

triethylenetetramine (A) and a-Alaha/b-Alaha (L) in ternary systems at 25 8C and I�0.2 M (KCl) in wayter solutions (the ion charges are omitted)

No Assignment A�dien A� trien

a-Alaha b-Alaha a-Alaha b-Alaha

1 log b [ZnALH2] 32.12(8)

2 log b [ZnALH] 22.77(3) 24.88(7) 27.04(3)

3 log b [ZnAL] 13.60(2) 14.04(4) 17.32(9) 17.75(4)

4 log b [ZnALH�1] 2.89(3) 6.69(6)

5 log b [ZnALH]�/pKmicroNH�

3

/ 13.92 17.40 18.19

6 log b [ZnAL]�/pKmicroNHOH/ 5.70 5.57 9.42 9.28

7 pK [ZnALH2] 5.08

8 pK [ZnALH] 8.73 7.56 9.19

9 pK [ZnAL] 10.71 10.63

10 [ZnAL]�LX [ZnAL]

log K [ZnAL] 4.65 5.09

11 [ZnA]�AX [ZnA2]

log K [ZnA2] 5.02 5.02

12 D log K �0.63

13 log X 3.92 3.22 8.31 7.30

14 x2 5.04 8.13 11.07 10.30

15 s 2.86 2.92 5.08 6.41


Alahamicro (NH3

�) microconstant (8.85) (see Table 2).

Taking into account these protonation constants, hy-

droxamate type (O,O) co-ordination of H�/b-Alaha can

be supposed for the [Zn(dien)(H�/b-Alaha)]2� species.

Comparing both ZnII�/dien�/L ternary systems, it can

be seen that a-Alaha is the same effective chelating

ligand as b-Alaha. This is reflected in almost

identical basicity-adjusted stability constants,

log KZn(dien)(a-Alaha)/(b-Alaha)�/pKb-Alahamicro . These values

are �/3.25 and �/3.38 for [Zn(dien)(a-Alaha)]� and

[Zn(dien)(b-Alaha)]�, respectively (Table 4). Taking

into account these basicity-adjusted stability constants,

hydroxamate type (O,O) co-ordination of a-Alaha and

b-Alaha can be supposed for these species.

Owing to the larger space requirement and neutral

charge of dien (the fully deprotonated hydroxamate

group has a charge of �/1), the chelating ability of this

ligand to the [Zn(dien)]2� species is lower than that of

the hydroxamate anion. So, the mixed-ligand species are

more stable than the simple, [Zn(dien)2]2�.

Fig. 1. Species distribution patterns of ZnII complexes in the binary

and ternary systems: (a) ZnII�/dien at 1:2 molar ratio; cZnII�/4�/10�3

M; (b) ZnII�/a-Alaha at 1:2 molar ratio; cZnII�/4�/10�3 M (solid

lines) and ZnII�/a-Alaha at 1:1 molar ratio; cZnII�/2�/10�2 M (dashed

lines; simulated for conditions used in NMR studies); (c) ZnII�/dien�/a-

Alaha at 1:1:2 molar ratio; cZnII�/4�/10�3 M.

Fig. 2. Species distribution patterns of ZnII complexes in the binary

and ternary systems: (a) ZnII�/dien at 1:2 molar ratio; cZnII�/4�/10�3

M; (b) ZnII�/b-Alaha at 1:2 molar ratio; cZnII�/4�/10�3 M (solid

lines) and ZnII�/b-Alaha at 1:1 molar ratio; cZnII�/2�/10�2 M (dashed

lines; simulated for conditions used in NMR studies); (c) ZnII�/dien�/b-

Alaha at 1:1:2 molar ratio; cZnII�/4�/10�3 M.


3.1.2. ZnII�/trien�/a-Alaha/b-Alaha systems

For the determination of the stability constants of the

mixed complexes formed in the ZnII�/trien�/a-Alaha/b-

Alaha systems (presented in Table 3), potentiometric

measurements were carried out with at least twofold

excess of the total amount of moles of aminohydroxa-

mic ligands relative to the number of moles of trien and

the metal ion. Within the whole studied pH range (i.e.

from ca. 5 to 11) no precipitate was observed. The mixed

complexes start to be formed from pH of about 5 and

above pH 6.5 only mixed-ligand species exist in both

systems (Fig. 3(b and c)).

The [Zn(H�/a-Alaha)]2� and [Zn(a-Alaha)]� species

are minor ones, so may be regarded as negligible (Fig.

3(b)).

The deprotonation process of [Zn(trien)(H�/a-

Alaha)]2� leading to the formation of [Zn(trien)(a-

Alaha)]� above pH 6.5 corresponds to the liberation

of the proton from the �/NH3� group of a-Alaha, the

pKZn(trien)(H�a-Alaha) value equal to 7.56 (Table 3 number

8) is characteristic for the pKb-Alahamicro (NH3

�) microcon-

stant (7.48) (see Table 2). Thus, hydroxamate type (O,O)

co-ordination of H�/a-Alaha ligand can be supposed for

the [Zn(trien)(H�/a-Alaha)]2� species.The final deprotonation of [Zn(trien)(a-Alaha)]�

leading to the [Zn(trien)(a-Alaha)H�1] species at

pH:/9 corresponds to the ionisation of a metal-bound

water molecule.

In the ZnII�/trien�/b-Alaha system all pH-metric

titration curves were consistent with the formation of

[Zn(trien)(H�/b-Alaha)]2� and [Zn(trien)(b-Alaha)]� as

main complexes (ca. 98%). Optimisation using the

SUPERQUAD software necessitated the introduction of

[Zn(H�/trien)]3�, [Zn(H�/b-Alaha)]2� and [Zn(H�/tri-

en)(H�/b-Alaha)]3� as the additional complex species in

the complexation set. The stability constants obtained

for the complexes in the binary and ternary systems are

given in Tables 2 and 3. Concentration distribution

curves are presented in Fig. 3(c).

The deprotonation process of [Zn(trien)(H�/b-

Alaha)]2� leading to the formation of [Zn(trien)(b-

Alaha)]� above pH 8 may correspond to the liberation

of the proton from the �/NH3� group of b-Alaha, as it

was in the system with a-Alaha, but it is not univocal

(see deprotonation constants of trien in Table 2).

However, the basicity-adjusted stability constants,

log bZn(trien)(H�a-Alaha)/(H�b-Alaha)�/pKmicroNH

3� , are almost

identical with log bZn(trien)(a-Alaha)/(b-Alaha) (Table 3).

Therefore, we suggest that the amino group of either

a-Alaha or b-Alaha is out of the co-ordination sphere in

the ternary systems.

Sigel‘s log XZn(trien)L value (the constant due to the

equilibrium [Zn(trien)2]2��/[ZnL2]X/2[Zn(trien)L]�)

for L�/a-Alaha or b-Alaha are 8.31 and 7.30, respec-

tively, and are abnormally high. This means that the

formation of mixed complexes is even more strongly

favoured in these systems (Table 3) than in those

discussed in Section 3.1.1. So, the statistical effects are

more important in the systems with trien than with dien.

The larger space requirement for trien, compared with

dien, is the reason that the chelating ability of trien to

the [Zn(trien)]2� species is lower than of dien to

[Zn(dien)]2� and the hydroxamate anion (which is

smaller from both polyamines) is preferred as a second-

ary ligand in these systems.

In the ZnII�/trien�/L ternary systems a-Alaha is as

effective chelating ligand as is b-Alaha. This is reflected

in almost identical basicity-adjusted stability constants,

log bZn(trien)(a-Alaha)/(b-Alaha)�/pKNHOHmicro (the same situa-

tion was observed in the systems with dien). These

values are 9.42 and 9.28 for [Zn(trien)(a-Alaha)]� and

[Zn(trien)(b-Alaha)]�, respectively (Table 3). Taking

into account these basicity-adjusted stability constants,

hydroxamate type (O,O) co-ordination of a- and b-

Alaha ligand can be supposed for these species.

Table 4

Overall stability constants (log b ), stepwise formation constants (log K ) and basicity-adjusted stability constants for ZnII mixed-ligand complexes

formed with amines (A) and a-alaninehydorxamic acid�/b-alaninehydroxamic acid (L) at 25 8C and I�0.2 M (KCl) in water solutions (the ion

charges are omitted)

A�en A�en A� trien

a-Alaha a b-Alaha b a-Alaha b-Alaha a-Alaha b-Alaha

log bZnALH 20.11(0) 22.77(3) 24.88(7) 27.04(3)

log bZnAL 11.15(2) 11.65(0) 13.60(2) 14.04(4) 17.32(9) 17.75(4)

ZnA�LXZnAL

log KZnAL 5.55 6.05 4.65 5.09

log KZnAL�pKNHOHmicro �2.35 �2.42 �3.25 �3.38

a Ref. [33].b Ref. [34].


3.2. NMR studies

In order to obtain supporting evidence for the

interpretation of the potentiometric data and to get

some structural information of the species in solution,

we undertook the 1H and 13C NMR studies. The spectra

were measured as a function of pH and compared with

those obtained for free ligand alone and for the

respective ZnII�/hydroxamate and ZnII�/polyamine bin-

ary systems. Finally, we compared the NMR titration

data with the species distribution curves recalculated for

the conditions used in NMR experiments.

3.2.1. ZnII�/a-Alaha and ZnII�/b-Alaha binary systems

There are significant differences between the spectra

of the ZnII�/a-Alaha solutions depending on the metal to

ligand stoichiometric ratio. Specifically, the zinc(II)

equimolar mixture exhibits rather complex pattern of

the resonances in the pH range �/7�/12. As an illustra-

tion, the number of doublets for the CH3 group in the

proton spectra is presented in Fig. 4(a).

As seen, most of the peaks are almost intact versuspH, whereas their intensities change when pH is varied.

The spectra are temperature sensitive. The signals move

gradually downfield with increasing temperature and

some coalescence above 330 K. Finally, at 350 K two

broad features are observed (Fig. 4(b)). Interesting is,

that under the same conditions the spectra of the 1:2

molar ratio system are significantly simplified. The

intensities of the most resonances roughly decreasewith resultant one set of signals predominating in an

evident manner in the studied range of pH (Fig. 4(c)).

Accordingly, the zinc(II) system with sarcosine hydro-

xamic acid (not discussed here) exhibits similar beha-

viour, whereas comparative study with harder

magnesium(II) ion revealed only one set of resonances

in the whole range of pH. All these facts demonstrate

that aminohydroxamic acids are capable of bindingzinc(II) not only through the (O,O) hydroxamate

function but also through the N -amino donor, which,

in turn, can enhance the (N,N) chelate binding mode

Fig. 3. Species distribution patterns of ZnII complexes of trien: (a) at

1:2 molar ratio and trien�/a-Alaha (b) and trien�/b-Alaha (c) at 1:1:2

molar ratio; cZnII�/4�/10�3 M.

Fig. 4. 1H MNR spectra (CH3 region) for the ZnII�/a-Alaha binary

systems at different molar ratios and pH values: (a), (b) 1:1 solutions,

(c) 1:2 solutions; ca-Alaha�/2�/10�2 M.


involving Namino and Nhydroxamate donor set. The

evidences for facilitating such co-ordination in the

case, when the amino group is in adjacent (a or b)

position in relation to the nitrogen of the hydroxamate

group are provided from both X-ray and solution

studies for CuII, NiII and MoVI [15,26�/30].

Unfortunately, the character of the spectra precludes

the detailed assignments. We can only speculate that the

observed phenomena are due to a slow on the NMR

time scale equilibria for complexation reactions. A

noteworthy feature of the 1:1 molar ratio system is

that all ligand is consumed to form [Zn2(a-Alaha)3]�

and [Zn(a-Alaha)H�1] as the two major species at

pH�/7. In the former complex, the only way of co-

ordination is that one molecule serves as a bridge

between the two zinc(II) ions, involving both pairs of

available donor sets, (O,O) and (N,N), whereas the two

others bind to the dinuclear core in the chelate modes

((O,O) or (N,N)). Such co-ordination enables the

formation of four different co-ordination isomers of

this complex that could give rise to the separate set of

signals in the NMR spectra. In the latter complex, the

most likely co-ordination mode is via the N -amino and

N -hydroxamic functions. Therefore, a kinetic inertness

of both complexes may be either due to a strained

structure of [Zn2(a-Alaha)3]� imposed by the planar

disposed hydroxamate (O,O) and N-donors or due to

inert, long-lived in respect of the NMR time scale,

zinc(II)�/nitrogen bonds. Consequently, the behaviour

of the 1:2 molar ratio system may be associated with the

metal-free ligand, proved from the potentiometric data

to remain in solution over the whole range of pH. In

particular, [Zn2(a-Alaha)3]� and free ligand are the

major species contributing the spectrum at pH 8.53,

whereas [Zn(a-Alaha)H�1] and free ligand, appearing in

nearly the same concentrations, contribute the spectrum

at pH 10.90 (Fig. 4(b)). Both these complexes are shown

to be capable of a slow on the NMR time-scale complex-

formation kinetics. Therefore, may be considered as

exchanging slow with the ligand present in the system.

The comparative studies with b-Alaha having re-

versed, with respect to a-Alaha, acidity sequence for

the �/NH3� and �/CONHOH groups (Table 2) reveal

differences between both ZnII�/b-Alaha and ZnII�/a-

Alaha systems. One most important is the lack of the

dinuclear complex, besides 1:2 molar ratio complexes

are formed. In addition, due to increased basicity of the

�/NH3� group the protonated complexes dominate over

a wider range of pH (up to �/8.5) (Fig. 2(b)). As long as

the amino group remains protonated, the ligand is

capable of co-ordinating via the oxygens of the hydro-

xamate group. Accordingly, the only effects of co-

ordination are little changes in chemical shifts of the

major CH2 signals, with respect to the metal-free ligand

(Fig. 5).

However, the spectra show that the relatively inert

(N,N) bonded species may also be formed under

Fig. 5. 1H NMR spectra for the ZnII�/b-Alaha 1:1 solutions at

different pH values, cb-Alaha�/2�/10�2 M.

Fig. 6. 13C and 1H chemical shifts for C carbons (a) and CH2 protons

(b) of dien as a function of pH:free dien (k); ZnII�/dien 1:1 (D, . . .);

ZnII�/dien�/a-Alaha 1:1:1 (m) and ZnII�/dien�/b-Alaha 1:1:1 (')

ternary solutions. The assignments for C and CH2 are consistent with

those in Scheme 1.


conditions where the amino nitrogen is capable of

competing with the hydroxamate oxygens for co-ordi-

nation. This is accompanied with a significant broad-

ening of the resonance signals and their upfield shiftswith respect to free b-Alaha. Thus, we suggest that

formation of [Zn(b-Alaha)2] and further [Zn(b-

Alaha)2H�1]� is somehow accompanied with a change

in the co-ordination modes from (O,O) towards the

(N,N).

3.3. Ternary systems

The set of pH profiles of the 13C chemical shifts for

metal-free dien, dien in 1:1 molar ratio solutions withzinc(II) and of equimolar mixtures of zinc(II) and dien

with a- or b-Alaha in the 1:1:1 molar ratio is presented

in Fig. 6(a).

It is generally accepted for aliphatic polyamines that

the change in chemical shift for a particular C atom on

forming a zinc(II) chelate is typically about half that

seen on fully protonating free ligand (A) [30�/32]. The

chemical shifts for both Ca and Cb in the ZnII�/dien

system are nearly constant at pH�/6 and fulfill theabove requirement. Thus, clearly show that dien appar-

ently acts as a tridentate ligand involving all available

nitrogen donors. The same is confirmed if consider the

methylene protons of dien in the 1H NMR spectra (Fig.

6(b)). Taking into account that under conditions studied

the chemical shifts for the corresponding C and CH2 of

dien in the ZnII�/dien�/a-Alaha/b-Alaha ternary systems

are almost unchanged with respect to those of ZnII�/dienat pH�/6 (Fig. 6(a and b)) it is clear that, the

arrangement adopted by amine in the [Zn(dien)]2�

complex is retained on formation of the mixed-ligand

species with either a- or b-Alaha. A similar conclusion

holds in the case of the ternary systems with trien. (Fig.

7(a and b)).

The general invariance of the chemical shifts on pH in

the appropriate 1H and 13C NMR spectra above pH 7shows that a tetradentate co-ordination of trien is a

common feature of either [Zn(trien)(a-Alaha)]� and

[Zn(trien)(a-Alaha)H�1] or [Zn(trien)(H�/b-Alaha)]2�

and [Zn(trien)(b-Alaha)]�, respectively.

Interestingly, co-ordination exerts relatively small

effect on the chemical shifts of bound a- and b-Alaha

(Fig. 8).

Moreover, in contrast to the binary ZnII�/a-Alaha andZnII�/b-Alaha systems both 1H and 13C NMR spectra

comprise a single set of sharp signals indicating that

exchange of hydroxamate between complex species is

fast throughout. Under conditions where the mixed-

ligand complexes emerge as the major species the

resonance attributed to CaH of a-Alaha in the 1H

spectra shifts downfield (Dd�/0.15 ppm) with respect

to the fully deprotonated free ligand form (L�) (Fig.8(a)). A comparative study with b-Alaha reveal little

differences in the 1H NMR behaviour between both

acids (Fig. 8(b)). All these facts demonstrate that there is

no binding to the amino group in the mixed-ligand

species, thus confirm, that in principal complexes

([ZnAL]� with a-Alaha and [ZnA(LH)]2� with b-

Alaha) hydroxamic acids coordinate zinc(II) exclusively

through the (O,O) hydroxamate donor set. The sameevidence is provided from the 13C NMR experiments

where upfield shifts due to zinc(II) complexation are

detected for either CaH of a-Alaha or CaH2 of b-Alaha

(Fig. 8(c and d)).

The above results are fully consistent with the

previous studies on zinc(II) mixed-ligand complexes of

aliphatic polyamines with a range of small potentially

bidentate O- and N-binding ligands (L) [30�/32]. Thenoteworthy feature of all these complexes is a little

transmission of inductive effects from ligand L to the

polyamine moiety through the zinc(II) ion resulting in

apparent similarities of the chemical shifts for respective

Fig. 7. 13C and 1H chemical shifts for C carbons (a) and CH2 protons

(b) of trien as a function of pH: free trien (k); ZnII�/trien�/a-Alaha

1:1:1 (m) and ZnII�/trien�/b-Alaha 1:1:1 (') ternary solutions. The

assignments for C and CH2 are consistent with those in Scheme 1.


carbons of polyamines between the simple ZnII�/poly-

amine and mixed-ligand complexes (Figs. 9�/11).

4. Conclusion

A comparison of the stability constants of the mixed-

ligand complexes obtained from the studied ternarysystems: ZnII�/en�/a-Alaha/b-Alaha [33,34], ZnII�/dien�/

a-Alaha/b-Alaha and ZnII�/trien�/a-Alaha/b-Alaha re-

veals that the stability constants of mixed-ligand species

Fig. 8. 1H and 13C chemical shifts for CaH (a) Ca (b) of a-Alaha and CH2(a), CH2(b) (c), Ca, Cb (d) of b-Alaha as a function of pH:free ligand (k)

and ZnII�/dien-hydroximate 1:1:1 (m), ZnII�/trien-hydroxamate 1:1:1 (%) termary solutions. The assignments for C, CH and CH2 are consistent with

those in Scheme 1. For comparison the 1H NMR titration curves for the major peaks of the ZnII�/b-Alaha 1:1 solutions, cL�/2�/10�2 M (dashed

lines).

Fig. 9. Plot of log b[ZnA(b-Alaha)] as a function of log b[ZnA(a-Alaha)].

Fig. 10. Plot of log bZnAL as a function of a number of nitrogen

donors in polyamine.

Fig. 11. Plot of log X as a function of number of nitrogen donors in

polyamine.


with a-Alaha are lower than those with b-Alaha. This

can probably be explained by the higher basicity of the

hydroxamic oxygen of b-Alaha. There is a strong

evidence from our pH-metric and NMR results thattwo oxygen donors of the aminohydroxamic anion are

involved in the zinc(II) co-ordination sphere. Besides,

we found a linear correlation between stability constants

of the mixed-ligand complexes. Plot of log b[ZnA(b-Alaha)]

as a function of log b[ZnA(a-Alaha)] (A�/en, dien or trien)

is presented in Fig. 9. Taking into account that ‘A’

represents polyamine that forms a very stable complex

and aminohydroxamic anions are compounds of thesame type this plot, to a first approximation, can be

interpreted as reflecting the same type of co-ordination

in these complexes.

Plotting log b of the mixed-ligand species as a

function of the number of nitrogen donors in polyamine

(Fig. 10) we found that the correlation between these

two parameters is a function of the number of the co-

ordinated nitrogens in the mixed-ligand species. As thelog K values of [ZnA2] and [ZnAL] are very close, one

can conclude that sterical hindrance is the major factor,

which determinates a formation of the mixed-ligand

complexes. Accordingly, the smaller a- or b-Alaha are

bound preferentially over second dien or trien to form

the mixed-ligand [ZnAL] species. Plot of log X as a

function of a number of nitrogen donors in polyamines

(Fig. 11) shows that the formation of mixed complexes ismore favoured if polyamine has more nitrogen donors.

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