Determination of stability constant and biological activity of mixed ligand complexes of ni(ii), cu(ii) and zn(ii) metal ions with some bi- and tri- dentate biologically active ligands

Abstract

Mixed ligand complexes play an important role in biological processes, as exemplified by many instances in which enzymes are known to be activated by metal ions. Such complexes have been implicated in the storage and transport of active substances through membranes. Many mixed ligand complexes are finding applications in the microelectronic industry, chemical vapour deposition of metals and as drugs. Mixed ligand complexes have been used in the analysis of semiconductor. Many biochemical are potential chelating ligands and several drugs have coordinating sites. This allows possible formation of complexes with the transition metal ions involved with life processes. Study of mixed ligand complexes is also important from fundamental chemistry point of view. The effect of the structural features of the ligands on the stability of the ternary complexes and corresponding binary complexes is of great fundamental significance. Hence it is interesting to study the various factors which affect the stability of the ternary complex. The present work is divided into three parts. Firstly determination of stability constant, secondly analysis of the complex by Cyclic Voltammetry (CV) and thirdly study of their biological activities. The stability of mixed ligand complexes have been determined in terms of ΔlogK = log M ML MA KMAL  logK value, i.e. the difference in the tendencies of L to bind with the free metal ion and the metal ion already bound to another ligand. From statistical consideration ΔlogK is expected to be negative. Different type of mixed ligand ii complexes of [MAL] type have been studies, where M refers to Ni(II), Cu(II), Zn(II) and A refers to Aspartic acid (Asp), Diethylenetriamine (DETA), Dipropylenetriamine (DPTA), 2,6-pyridinedicarboxylic acid (DPA), Iminodiacetic acid (IMDA) etc. tri-dented and L refers to 1,10-phenanthroline (1,10-phen), Oxalic acid (ox), Tyrosin (tyr), Tryptophans (trp), Phenylalanine (phe), α-Alanine (α-ala), Glycine (gly), Ethyldiamine (en) etc. bi-dentate biologically important ligands. The stability constant of mixed ligand complexes were determined by carrying out pH-metric titration in aqueous medium. The protonation constant, binary constant and ternary constant have been determined pH-metrically using SCOGS computer program. The proton-ligand formation constant and formation constant of binary complexes were first refined. These values were used as fixed parameters for the refinement of the formation constant of the mixed ligand complexes. It is also reported that for the mixed ligand complexes of Cu(II), ΔlogK values is more negative than corresponding Ni(II) mixed ligand complexes. This is due to the absence of Jahn-Teller distortion in Ni(II) complexes. It is also observed that the ΔlogK value is more negative with increasing the charge on the ligand L. This is because of the electrostatic repulsion between the ligands. It is observed that ΔlogK value is positive when Phenylalanine and Tyrosine is coordinated with central metal ion. This is due to the intramolecular interligand interaction between non-coordinated side group. Another reason of extra stabilization of tyrosine is due to intramolecular interligand hydrogen bonding and stacking interation of phenylalanine and tyrosine with metal ion. Additional stabilization in the complexes can occur due to the noncovalent hydrophobic interaction between non-coordinated side group phenyl and hydroxyphenyl of phenylalanine and tyrosine respectively with Aspartic acid (Asp), Diethylenetriamine (DETA), iii Dipropylenetriamine (DPTA), 2,6-pyridinedicarboxylic acid (DPA), Iminodiacetic acid (IMDA). The greater stability of Zn(II) complex as compared to those of complexes of Cu(II) and Ni(II) is due to the fact that the complex of Zn(II) prefer tetrahedral geometry in which ligand-ligand repulsion is minimum. Moreover larger size of Zn(II) metal is favorable for the accommodation of ligand more easily than Cu(II) and Ni(II). Hence, in the present investigation, the orders of the stability of the ternary complexes are as follows- [Zn(A)(L)] > [Ni(A)(L)] > [Cu(A)(L)] Secondly, the potential is required to show anodic and cathodic peak is called anodic potential (Epa) and cathodic potential (Eca). Greater the value of cathodic and anodic potential, greater will be the stability of the complexes. The potential difference between Epa and Eca also helps us to ascertain the relative stability of complexes. An increase in potential difference between Epa and Eca indicates the higher stability of the complex compound, i.e. the process is irreversible. In the light of the above discussion it is said that the order of stability of the ternary complexes is as follows: [Zn(A)(L)]> [Ni(A)(L)]> [Cu(A)(L)] An interesting fact that the study of the cyclic voltammograms of the complexes of [MA], [MA2], [MA4], [ML], [ML2] and [ML4] types predicts that [MA2], [MA4]; [ML2] and [ML4] complexes shows the similar Epa and Eca value in cyclic voltammograms. This indicates that the formation of complex compound is completed at [MA2] and [ML2] state, i.e. metal to A ratio 1:2 and metal to L ratio 1:2. iv Thirdly, the antibacterial activity of the complexes of Ni(II), Cu(II) and Zn(II) have been studied against ten pathogenic bacteria. It has beenobserved that some drug increases the activity whenadministered asmetal complexes or their metal chalets. Antibacterial activities of different bi- and tri- dentate ligands and it’s ternary complexeshave not beenstudied so far. So it is noteworthy to examine whether the ligand andcomplexes show any such activity or not. For the purpose, investigation on theantibacterial activities of Ni(II), Cu(II) andZn(II) complexes of the differentbiand tri-dentate ligands have been carried out against some important selectedbacteria which cause different fatal disease. Name of the selected bacteria which were subjected to study are listed below: Escherichia coli, Salmonellatyphe, Bacillus cereus, Shigella dysenteriae,Shigella boydii, Staphylococcusaureus, Klebsilla, Pseudomonas aeruginosa, Shigella shiga, Bacillusmegaterium. All the result are compared with the standard compound "kanamycin". The results show that the ligand andits complexes show different antibacterial activities to a measurable extent. Some of the complexes are found to exhibit higher antibacterial activities, someof exhibit lower antibacterial activities. In case of antifungal activities,different complexes also shown different activities. However, for a clearunderstanding of the functions responsible for antibacterial activities ofdifferent types of ligands and its complexes, more studies are needed to beperformed with a series of analogous ligands and their complexes against aseries of