Synthesis and Biological Activity of Mixed Ligand Metal Complexes of 6-Mercaptopurine - Nicotinamide

Abstract

Biological activity of a ligand improves when it is coordinated with a metal ion. Mixed ligand metal complexes of 6-mercaptopurine and  nicotinamide were synthesized using one-pot synthetic methods. Spectroscopic methods were used to characterize the mixed ligand  metal complexes. The spectroscopic analysis of the complexes supports the formation of the compounds in which the exocyclic sulphur  (S-6) atom on the pyrimidine ring of the 6-mercaptopurine and its N(7) atom of the imidazole ring allow the ligand to act as bidentate  while the nicotinamide coordinates as a monodentate ligand only through the nitrogen atom of its pyridinic ring. Thermogravimetric  analysis of the compounds is in agreement with the proposed structures. Evaluation of the thermodynamic activated parameters of the  complexes shows high positive values for the ΔG and negative values for the entropy of activation, which is an indication that the  decomposition of the complexes is non-spontaneous and the compounds have a more ordered structure compared to the ligands. The  DFT studies revealed low LUMO–HOMO energy gap (ΔE) values of 3.255 eV and 1.029 eV for the compounds (1) [Zn(mp)(nic)EtOH] and (2)  [Ni(mp)(nic)(Ac)].4H₂O respectively, in ethanol medium. Compound (1) is a better antioxidant agent compared to compound (2) but  compound (2) shows improved antimicrobial activity compare to compound (1). Experimental results show improved antioxidant activity  for the [Zn(mp)(nic)EtOH] complex, which correlates with the findings from the docking experiment and the complex docked alongside  allopurinol at binding pocket I with a binding affinity value of –6.4 kcal mol⁻¹ , showing its antioxidant potential.