Synthesis, Structure, DNA/Protein Binding, and Anticancer Activity of Some Half-Sandwich Cyclometalated Rh(III) and Ir(III) Complexes

The
Schiff base ligands benzylidene­(4-tert-butylphenyl)­amine
4-methyl ester (L1), (4-nitrobenzylidene)­(4-tert-butylphenyl)­amine (L2), and (4-cyanobenzylidene)­(4-tert-butylphenyl)­amine (L3) and the new series
of cyclometalated mononuclear piano-stool complexes [(η5-C5Me5)­RhCl­(L1)] (1), [(η5-C5Me5)­RhCl­(L2)] (2), [(η5-C5Me5)­RhCl­(L3)] (3), [(η5-C5Me5)­IrCl­(L1)] (4), [(η5-C5Me5)­IrCl­(L2)] (5), and [(η5-C5Me5)­IrCl­(L3)] (6) have been
synthesized. The ligands L1–L3 and
complexes 1–6 have been thoroughly
characterized by satisfactory elemental analyses, spectral studies
(ESI-MS, IR, 1H and 13C NMR, UV–vis),
and structures of 1–3 authenticated
by X-ray single-crystal analyses. Efficient binding of 1–6 with calf thymus DNA (CT DNA) have been established
by UV–vis and emission spectroscopic studies. Protein binding
(bovine serum albumin, BSA) has been investigated by UV–vis,
fluorescence, synchronous, and 3D fluorescence spectroscopy. Binding
of the complexes with DNA through minor groove and hydrophobic interaction
with proteins via sub domain IIA cavity has been substantiated by
molecular docking studies. The complexes exhibited significant cytotoxicity
against the human lung cancer cell line (A549), and 1 and 2 showed better activity than cisplatin. The cytotoxicity,
morphological changes, and apoptosis have been assessed by MTT assay,
Hoechst 33342/PI staining, cell cycle analysis by fluorescence-activated
cell sorting (FACS), and reactive oxygen species (ROS) generation
by DCFH-DA dye. The complexes 1–6 induce apoptosis in the order 2 > 1 > 4 > 3 > 5 > 6.