Synthesis of 2-acetylpyridine-N-substituted thiosemicarbazonates of copper(ii) with high antimicrobial activity against methicillin resistant S. aureus, K. pneumoniae 1 and C. albicans

Abstract

The basic interest in the present study pertains to developing metal based antimicrobial agents, as several microorganisms have built resistance to the conventional drugs. In this respect, reactions of 2-acetylpyridine-N¹-substituted thiosemicarbazones, {(C₅H₄N⁴)–(CH₃)C²N³–N²(H)–C¹(S)-N¹HR} (abbrev. HL^3R: R = H, Me, Et, and Ph), with copper(I) halides in equimolar ratios have been carried out and consequently mononuclear copper(II) complexes, [Cu^IIX(N⁴,N³,S-L^3R)] (R = H, Me, Et, and Ph; X = Cl, 1–4; Br, 5–8; I, 9–12), have been isolated. The formation of these complexes with Cu^II–halogen bonds, especially with iodide anions, occurred via a proton coupled electron transfer mechanism (PCET), which involved the simultaneous release of electrons from Cu^I to combine with protons derived from the N²H moiety, and the metal itself converting to Cu^II. The analytical data, spectroscopy (IR, ESR, UV-visible, and ESI-mass) and X-ray crystallography confirmed their molecular structures. These pseudo square planar copper(II) complexes have been tested for their antimicrobial activity against methicillin resistant Staphylococcus aureus (MRSA) bacteria, Staphylococcus aureus (MTCC740), Klebisella pneumoniae 1 (MTCC-109), Salmonella typhimurium 2 (MTCC1251) and Candida albicans (MTCC 227). In particular, the antimicrobial activity against MRSA, Klebisella pneumoniae 1 (MTCC-109) and Candida albicans (MTCC 227) is comparable to or better than that of the reference compounds gentamicin and amphotericin B. Significantly, several complexes have shown in vitro high cell viability (88–92%) determined using MTT assay {MTT = 3-[(4,5-dimethylthiazol-2-yl)-2,5-diphenyl]tetrazolium bromide}.