Phenolate based metallomacrocyclic xanthate complexes of CoII/CuII and their exclusive deployment in [2:2] binuclear N,O-Schiff base macrocycle formation and in vitro anticancer studies

Potassium salts of phenolate based polydentate xanthate ligands 4,4"-bis(2-dithiocarbonatobenzylidene-amino)diphenyl ether (K(2)xan(1)) and 4,4'-bis(2-dithiocarbonatonaphthylmethylideneamino)diphenyl ether (K(2)xan(2)) have been synthesized and characterized, prior to use. The reaction of K(2)xan(1) or K(2)xan(2) with M(OAc)(2) in Et3N affords access to a rare series of binuclear metallomacrocyclic xanthate complexes of the type [M-2-mu(2)-bis-(kappa S-2,S2.5,5-xan(1)/xan(2))] (1-4) which quickly forms [2: 2] binuclear N,O-bidentate Schiff base macrocyclic complexes of the type [M-2-mu(2)-bis -(kappa N-2,O-L-1/L-2)] (L-1 =4,4'bis(2-hydroxybenzytideneamino) diphenyl ether, L-2 = 4,4'-bis(2-hydroxynaphthylmethylidene-amino)diphenyl ether) 5-8 via evolution of CS, in solution. The compounds were characterized by microanalysis, relevant spectroscopy (FT-IR, UV visible), mass spectrometry (ESI-MS), and powder and single crystal XRD techniques. In vitro anticancer activity of all the compounds was evaluated against HEP 3B (hepatoma) and IMR 32 (neuroblastoma) by the M I I assay. Remarkably, the binuclear copper(s) xanthate complexes were found to be extremely active against both the cell lines (IC30: 8.1 +/- 0.8 mu M (3), 8.8 +/- 1.7 mu M (4) against HEP 3B and 1.9 0.3 mu M (3) and 7.3 +/- 0.6 mu M (4) against IMR 32) and this projects them as good candidates for potent antitumor agents and the IC50 values confirm their better potency than the reference drug cisplatin. The flow-cytometric density plot illustrates the induction of apoptosis in HEP 3B and IMR 32 cells after treatment with K(2)xan(1), 1, 3, 6 and 7.