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

Abstract

Potassium salts of phenolate based polydentate xanthate ligands 4,4′-bis(2-dithiocarbonatobenzylideneamino)diphenyl ether (K₂xan¹) and 4,4′-bis(2-dithiocarbonatonaphthylmethylideneamino)diphenyl ether (K₂xan²) have been synthesized and characterized, prior to use. The reaction of K₂xan¹ or K₂xan² with M(OAc)₂ in Et₃N affords access to a rare series of binuclear metallomacrocyclic xanthate complexes of the type [M₂-μ²-bis-(κ²S,S-xan¹/xan²)] (1–4) which quickly forms [2 : 2] binuclear N,O-bidentate Schiff base macrocyclic complexes of the type [M₂-μ²-bis-(κ²N,O-L¹/L²)] (L¹ = 4,4′-bis(2-hydroxybenzylideneamino)diphenyl ether, L² = 4,4′-bis(2-hydroxynaphthylmethylidene-amino)diphenyl ether) 5–8via evolution of CS₂ 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 MTT assay. Remarkably, the binuclear copper(II) xanthate complexes were found to be extremely active against both the cell lines (IC₅₀: 8.1 ± 0.8 μM (3), 8.8 ± 1.7 μM (4) against HEP 3B and 1.9 ± 0.3 μM (3) and 7.3 ± 0.6 μM (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 K₂xan¹, 1, 3, 6 and 7.