Chiral enantiomers [Cu(phen)(L-threo)(H2O)]NO3 1 and [Cu(phen)(D-threo)(H2O)]NO3 2 (threo = threoninate) underwent aldol-type condensation with formaldehyde, with retention of chirality, to yield their respective enantiomeric ternary copper(II) complexes, viz. L- and D-[Cu(phen)(5MeOCA)(H2O)]NO3·xH2O (3 and 4; phen = 1,10-phenanthroline; 5MeOCA = 5-methyloxazolidine-4-carboxylate; x = 0-3) respectively. These chiral complexes were characterized by FTIR, elemental analysis, circular dichroism, UV-Visible spectroscopy, fluorescence spectroscopy (FL), molar conductivity measurement, ESI-MS and X-ray crystallography. Analysis of restriction enzyme inhibition by these four complexes revealed modulation of DNA binding selectivity by the type of ligand, ligand modification and chirality. Their interaction with bovine serum albumin was investigated by FL and electronic spectroscopy. With the aid of the crystal structure of BSA, spectroscopic evidence suggested their binding at the cavity containing Trp134 with numerous Tyr residues in subdomain IA. The products were more antiproliferative than cisplatin against cancer cell lines HK-1, MCF-7, HCT116, HSC-2 and C666-1 except HL-60, and were selective towards nasopharyngeal cancer HK-1 cells over normal NP69 cells of the same organ type.
Two ternary Zn(II) complexes, with 1,10-phenanthroline (phen) as the main ligand and a carboxylate-containing ligand [dipicolinate (dipico) or L-threoninate (L-Thr)] as the subsidiary ligand, were prepared and characterized by elemental analysis, Fourier transform IR, UV, and fluorescence spectroscopy, X-ray diffraction, molar conductivity, and electrospray ionization mass spectrometry. X-ray structure analysis shows that both [Zn(phen)(dipico)(H(2)O)]·H(2)O (1) and [Zn(phen)(L-Thr)(H(2)O)Cl]·2H(2)O (2) have octahedral geometry about the Zn(II) atom. Both complexes can inhibit topoisomerase I, and have better anticancer activity than cisplatin against nasopharyngeal cancer cell lines, HK1 and HONE-1, with concentrations causing 50 % inhibition of cell proliferation (IC(50)) in the low micromolar range. Complex 2 has the highest therapeutic index for HK1. Both Zn(II) complexes can induce cell death by apoptosis. Changing the subsidiary ligand in the Zn(II) complexes affects the UV-fluorescence spectral properties of the coordinated phen ligand, the binding affinity for some DNA sequences, nucleobase sequence-selective binding, the phase at which cell cycle progression was arrested for treated cancer cells, and their therapeutic index.