Research

, Volume: 12( 3) DOI: 10.37532/0974-7540.22.12.3.241

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Complexation Behaviour and Speciation Equilibria of Multimetal Multiligand Complexes of Bioactive Transition Metals Involving α – ε – diaminocaproate and 5-methyl-2,4-dioxopyrimidine

*Correspondence:

Surabhi Sinha Department of Chemistry United College of Engg. & Research, Allahabad-211010, India Tel: 9984569975, E-mail: rush2surabhi@yahoo.com

Abstract

Chelation tendency of α-ε-diaminocaproate (lysine=A) to form heterobinuclear complexes with some bioactive transition metal ions (viz. Co II , Ni II , Cu II , Zn II ) in the presence of 5-methyl-2,4-dioxopyrimidine (thymine = B) have been examined potentiometrically in aqueous medium. Speciation constants of complexes at 37± 1º and at constant ionic strength 0.1 M NaNO3 have estimated using SCOGS computer program and complex formation equilibria were interpreted. Species distribution curves are finally sketched by running the computer program ORIGIN 4.0. The relevant stability constant of binary, ternary( mixed ligand ), quaternary (multimetal, multiligand) (MA, MB, MAB, M1M2AB ) complexes follow Irving William order. The results are discussed to obtain the order of formation constants of the above mentioned complexes and probable solution structures of metal complexes with said ligand have been discussed.

Keywords

Quaternary; Equilibria

Introduction

The complexation of polynuclear metal chelates  and multimetal multiligand equilibria are very common in enzymatic process , so  mixed-metal, mixed-ligand complexes may help in examining  such equilibria found  in biological system [1-3]. The metal chelates continues to activate fields of medicinal [4], industrial [5], and analytical [6,7] importance. Biological units comprises of various vital and unimportant or potentially hazadarous metal ions [8,9,10]  like sodium, calcium, manganese, cobalt, copper, zinc, lead, mercury and cadmium etc. The correlation between metal and amino acids have gain considerable importance as chelation phenomenon prototype for interrelationship between metal and protein. Lysine(α-ε-diaminocaproate) is a prime producer of carnitine, chemical which helps body turn fat into energy thereby controlling the level of cholesterol. Humans require lysine for healthy functioning of body. Apart from its role in helping growth and repair of body tissue it also helps the body absorb calcium and restrain its loss by urination. It may also prevent bone deterioration accompanying osteoporosis [11, 12]. Key value of complexes of metal pyrimidine bases in biological context   is as model of  nucleic acid ion interactions [13]. Thymine (5-methyl-2,4-dioxopyrimidine ) is associated with  biosynthesis of DNA and genetic conductance [14,15].  Product of transition metal and nucleic acid are investigated for examining structure and function of nucleic acid  as artificial nuclease metallopharmaceuticals [16] for construction and advancement of restrictive enzymes. In extension to our recent work [17-25] on quaternary ( multi-metal multi-ligand) complexes, relative order of stability of quaternary metal complexes of Cu, Ni, Co, and  Zn metal ions with Lysine and Thymine as primary and secondary ligand respectively is addressed using pH meter in aqueous medium. The species distribution at different pH, speciation constant, presumed structure and feasible equilibria for the formation of species are communicated in the present paper.

Experimental

All the solutions were prepared in double distilled water. Potentiometric titrations of each ligand with standard carbonate free sodium hydroxide were carried out with an electric digital pH meter (Century-modelCP901-S) with glass electrode at 37±10º C and I = 0.1M NaNO₃. Relatively low concentrations of metals and ligands are used. A steam of nitrogen was passed through the solutions throughout the titration. All the metal salts used were of A.R. grade (sigma) and were standardised volumetrically by titration with the disodium salt of EDTA in presence of suitable indicators, as described by Schwarzen batch [26]. Binary M:A/M:B (1:1), ternary M:A:B(1:1:1) and quaternary (M1:M2:A:B) metal-ligand solution mixture have been titrated against standardized NaOH (0.01M) solution, keeping total volume 50ml in each case. Strength of metal and ligand = 0.001M and I = 0.1 M NaNO₃ . Where M1(II) and M2(II) are Co/Ni/Cu and Zn, A = Primary ligand and B = Secondary ligand. The pH meter reading with progressive addition of alkali to the titration mixtures were noted, when the reading of pH meter stabilized. The titration was discontinued at the appearance of turbidity. The pH values were plotted against the volume of NaOH and titration curves were obtained.

Result and Discussion

The lysine dianion offers to an incoming ligand both a functional group which is a potential hydrogen bond acceptor, the coordinated oxygen and two primary amine groups which are potential hydrogen bond donor. Thus lysine is a potentially tridentate ligand. The side ε-NH2 group of lysine residue in peptides and proteins is one of the potential donor sites for metal especially copper ion complexation. However, its coordination to the metal centre generally involves the formation of usually large chelate rings [27,28]. Proton ionization for thymine in the strongly acidic region has been reported based on spectrophotometric data. Metal complexation observed in thymine is unusal due to absence of free lone pairs. Coordination in thymine is reported to takes place through ring nitrogen and carbonyl oxygen or from both the ring nitrogen making it bidentate ligand. UV and Ultrasonic absorption studies indicate that in aqueous medium thymine primarily exist in lactum form, α-hydroxyl and ϒ-hydroxyl ionizes in alkaline medium corresponding to two pk values 9.9 and ›13 For evaluation of stability constants by the SCOGS computer program [26] in a system of the two different metal ion M1 and M2 and two different ligands A and B in aqueous medium, speciation may be described according to equilibrium. The overall stability constant( ) is defined as: may be used to calculate the species distribution curves that provides the clues for the formation equilibria of the complexes . Values of constants were supplied to the computer as input data to obtain distribution curves of the complexes occurring at different pH . Ionic product of water (k_w) and activity coefficient of hydrogen ion under the experimental conditions were obtained from literature. The dissociation of proton from thymine is from N3H [29,30] . Since thymine is the nucleoside of thymine, so it may be assumed that the first dissociation from thymine is from N3H group. Thymine shows only single dissociation since hydrogen in N1 position of the pyrimidine is substituted by sugar moiety [31]. Protonation constants for the ligands have been determined by Irving- Rossotti titration technique [32] and are presented in the table provided: Deflection of titration curve E (quaternary) from curve  D (ternary) clearly indicates formation of multinuclear complex at  pH ≈ 7.8 consumes ≈ 1.5 ml alkali. In present system, protonated species AH3, AH2, AH, BH, multimetal-multiligand complex i.e. quaternary complex species, ternary, and binary complex species, exist in sufficient concentration .The hydroxo species and free metal ions are also present throughout the entire pH range. Speciation curves (FIG. 1) clearly indicate that the concentration of AH3, AH2, AH, and BH species of both ligands are found to be decreasing with increase in pH range ≈ 3.0-7.5 whereas species AH increases with increase in pH and attains maximum concentration ≈ 42% at pH ≈ 3.5, it further decreases  in pH range ≈ 3.5-7.6, which shows their involvement in the complex formation. Binary complexes show their remarkable presence according to the following equilibria.

The concentration of binary complexes CuA and CuB are maximum at pH ≈4.5.The species [Co(II )^- BH] attains maximum value ≈ 25% at higher pH ≈ 9.1, while [Co(II ) ^- A] complex species does not exist throughout entire pH range. The concentration of all binary species are decreasing with further increase in pH , probably due to the formation of ternary and quaternary complexes. Mixed ligand complexes with Cu2+ (aq.) and Co2+ (aq.) are found to be the remarkable species in the pH range ≈ 6.5-10.0, as follows: It is clearly evident from the distribution curves that the [Cu(II )^- A^- BH] is the major ternary species attaining ≈40% at higher pH ≈ 10.0 whereas [Co(II )^- A^- BH] does not exist in the present system. The speciation curves indicate the formation of heterobinuclear complex according to the following equilibria: Formation curves shows that there is concomitant decline in the concentration of Cu2+ and Co2+ aqueous ions with the incline in the concentration of quaternary complex species . The concentration of multinuclear complex is increasing gradually with the gradual increase in pH and attains a maximum value ≈ 76% in the pH range ≈ 7.5-8.5. The metal hydroxo species Co(II)(OH)+, Co(II)(OH)2 exist in the pH range ≈ 8.0-10.0 involving the following equilibrium: Ni (II)-Zn (II)- Lysine-Thymine (1:1:1:1) system: Potentiometric curves clearly indicate that the complexation starts at pH ≈ 8.0. According to Speciation curve (FIG. 2) following species are assumed to prevail in the present system: AH3, AH2, AH, BH, Ni(OH), Ni(OH)2, Zn(OH), Zn(OH)2, [Ni(II)-A], [Ni(II)- B], [Zn(II)-A], Zn(II)B], [Ni(II)-A-B ], [Zn(II)-A-B] and [Ni(II)-Zn(II)-A-B]. The protonated ligand species of both the ligands and free metal ions Ni2+ (aq.) and Zn2+ (aq.) have been found to a declining pattern of their concentration with rise in pH. The concentration of AH3, AH2, AH and BH species of both the ligands are found to be decreasing with increase in the pH range ≈ 3.0- 7.0, which shows their involvement in the complex formation. The binary complexes show their remarkable presence according to the following equilibria:

Binary complexes NiA and NiB shows their existence in the present system. Their formation start right from the beginning of the titration and after a gradual incline, their concentration becomes maximum at higher pH ≈10.0 and 9.0 respectively. At still higher pH, these follow a declining pattern of their concentrations. Mixed ligand complexes with Ni2+ (aq.) and Zn2+ (aq.) are found to be remarkable species in the pH range ≈ 8.3-10.5 as follows: For quaternary system, the species distribution curve indicates the formation of heterobinuclear complex according to the following equilibria: It is clear from the speciation curves , that there is gradual rise in the concentration of multimetal-multiligand complex with the progressive addition of alkali. Maximum concentration of the complex is ≈ 93% at pH ≈ 8.0. There is concomitant decline in the concentration of Ni2+ and Zn2+ aqueous ions with the incline in the concentration of quaternary complex species. The multinuclear complex species are predominant species in the present system. The metal hdroxo species are formed in the system which indicates the dissociation of multinuclear species. Refined values of binary,ternary and quaternary constants are listed in TABLE , which are in good agreement with those in literature. The overall stability constants of mixed metal-mixed ligand [Lysine-Thymine-M1-M2] systems have been found to follow the following order.

Table: Stability constants and other related constants of Binary, Ternary, and Quaternary complex of α-ε-diaminocaproate (lysine = A) and 5-methyl. 2,4dioxopyrimidine (thymine=B) with different metal ions in aqueous solution at 37±1ºC, I = 0.1M NaNO3 .

Cu²⁺ in aqueous solution is coordinated by six water molecules. However, tetragonal coordination is possible as two water molecules lie at longer distance. Hydrated nickel ion usually show regular octahedral configuration unless tetragonal distortion is forced by some strong field ligand which ultimately leads to square planar configuration. Isomeric complex species of hexacoordinated nickel is expected to have in greater number in comparison to copper, with predominant geometry of four equatorial bonds. Depending upon the nature of ligand bounded configuration of zinc can easily move from tetrahedral to octahedral geometry. Metal –A complex which has higher value of log β will be the first to attach ligand A, which further attaches to ligand B to satisfy its coordination number. Uncoordinated sites of ligands will then be occupied by another metal ion. (FIG. 3 and 4).

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