Ternary Phenolate-Based Thiosemicarbazone Complexes of Copper(II): Magnetostructural Properties, Spectroscopic Features and Marked Selective Antiproliferative Activity against Cancer Cells.

The new diprotic ligand 3,5-di- tert -butylsalicylaldehyde 4-ethyl-3-thiosemicarbazone, abbreviated H 2 (3,5- t -Bu 2 )-sal4eT, exists as the thio-keto tautomer and adopts the E -configuration with respect to the imine double bond, as evidenced by single-crystal X-ray analysis and corroborated by spectroscopic characterisation. Upon treatment with Cu(OAc) 2 ·H 2 O in the presence of either 2,9-dimethyl-1,10-phenanthroline (2,9-Me 2 -phen) or 1,10-phenanthroline (phen) as a co-ligand in MeOH, this thiosemicarbazone undergoes conformational transformation (relative donor-atom orientations: syn,anti → syn,syn ) concomitantly with tautomerisation and double deprotonation to afford the ternary copper(II) complexes [Cu{(3,5- t -Bu 2 )-sal4eT}(2,9-Me 2 -phen)] ( 1 ) and [Cu 2 {3,5- t -Bu 2 )-sal4eT} 2 (phen)] ( 2 ). Crystallographic elucidation has revealed that complex 1 is a centrosymmetric dimer of mononuclear copper(II) complex molecules brought about by intermolecular H-bonding. The coordination geometry at the copper(II) centre is best described as distorted square pyramidal in accordance with the trigonality index (τ = 0.14). The co-ligand adopts an axial-equatorial coordination mode; hence, there is a disparity between its two Cu-N coordinate bonds arising from weakening of the apical one as a consequence of the tetragonal distortion. The axial X-band ESR spectrum of complex 1 is consistent with retention of this structure in solution. Complex 2 is a centrosymmetric dimer of dinuclear copper(II) complex molecules exhibiting intermolecular H-bonding and π-π-stacking interactions. The two copper(II) centres, which are 4.8067(18) Å apart and bridged by the thio-enolate nitrogen of the quadridentate thiosemicarbazonate ligand, display two different coordination geometries, one distorted square planar (τ 4 = 0.082) and the other distorted square pyramidal (τ 5 = 0.33). Such dinuclear copper(II) thiosemicarbazone complexes, which are crystallographically characterised, are extremely rare. In vitro, complexes 1 and 2 outperform cisplatin as antiproliferative agents in terms of potency and selectivity towards HeLa and MCF-7 cancer cell lines.