Synthesis of Ag(I)-N-Heterocyclic Carbene and Cyclonickellated Complexes for Chemical and Biological Studies

Abstract

Metal complexes exhibit a wide variety of functional groups in drug designing and development due their vaious chemical properties, coordination modes, geometries and reactivities. Organonikellated and silver complexes have become attractive tool in the field of catalytic as well as medicinal chemistry. The present project was designed to synthesize new series of silver-N-Heterocyclic carbene (NHC) and cyclonickellated complexes. Various NHC based as well as phosphine/phosphinite based precursors were designed leading to the synthesis of target silver and nickel complexes, respectively. Three series (A-C) of novel mono- and bisimidazolium salts (1a-16a, 1b-12b, 1c-7c) as ligands and their mono, di, tri and polynuclear silver complexes (17a-20a, 13b-20b, 8c-12c) were synthesized. The corresponding silver(I) aducts were afforded by the in situ deprotonation of the NHC based ligands. Some of the NHC salts (7a-12a) of series A were found to be difficult to react with silver due to steric factor (bulky alkyl substituents attached to them), so their silver complexes could not be synthesized. The synthetic approaches of the ligands of series B were controlled by the methyl substituents attached to the backbone of benzimidazole imposing significant impact on the reactivity by the virtue of their aptitude to enhance sigma electron donating ability of ligands. The precursors and silver complexes were well characterized by FTIR, GC-MS, 1H, 13C (one and two dimensional), 31P and 19F NMR, elemental analysis, melting points, ESI-MS and single crystal X-ray crystallographic techniques. Adopting a different protocol of synthesis using excess of reactant, an interesting trinuclear silvercomplex (8c) was synthesized. After successful syntheses, the silver complexes were employed to study their redox potentials by cyclic voltammetry. The quasi reversibility and irreversibility of redox events in the electrochemical study of silver complexes indicated that the reduction event produces unstable decomposed species and oxidation event may be ascribed to decomposed species. Azolium salts and their Ag(I)-NHC complexes were tested in vitro against Bacillus subtillis, Macrococcus brunensis, and Bacillus cereus to study their antibacterial activity and against MDA-MB-231 and HCT116 cells to study their anticancer potential. All compounds were observed to pose potential antibacterial and anticancer activity, however, silver-NHC complexes were found relatively more potent compared to the corresponding NHC precursors (salts). Only few salts were found inactive, while their complexes were observed to be active concluding that the silver imparts greater anticancer potential to the compounds. Being air and moisture sensitive, cyclonickellated complexes could not be utilized for evaluation of their antimicrobial, anticancer or redox potential, however, the attempts were made to study their functionalization

behaviour under inert atmosphere. It was observed that the coordination of PR2 moiety into CNi bond is apparent from the initial colour change and shift of 31P NMR and 19F NMR signals but final products of insertion remained difficult to be analyzed as they usually decomposed or appeared NMR silent after workup. In order to understand the feasibility of reaction and to evaluate the properties of product of insertion, further attempts were made to get target complexes via different way by synthesizing phosphine-phosphinite ligands and reacting them with nickel precursor. Appearance of specific signals in NMR spectra of few products provided some evidences of formation of the target products but later the products decomposed and signals disappeared. Thus the products of all reactions were very difficult to identify by NMR either due to paramagnetic nature or decomposition of products and crystallization attempts remained unsuccessful so their structures remained ambiguous as no other technique could help to study them due to their air/moisture sensitivity. On the whole the present project provided useful information for drug designing and chemical transformation studies.