Revelation of potential bioactive water-soluble Boc-L-valine and imidazole appended metal complexes {M = Co(II), Cu(II) & Zn(II)}: synthesis, characterization, ct-DNA binding, pBR322 cleavage, SOD mimetic, and cytotoxicity studies.

Bio-compatible water-soluble conjugates of Co(II), Cu(II) and Zn(II) (1-3), [Co(Boc-L-valine) 2 (imidazole) 2 ], [Cu(Boc-L-valine) 2 (imidazole) 2 ], and [Zn(Boc-L-valine) 2 (imidazole) 2 ], were synthesized and comprehensively characterized by various spectroscopic techniques (UV-visible, FT-IR, ESI-MS, EPR, 1 H NMR, 13 C NMR) and single crystal X-ray diffraction which showed that the complexes 1-3 crystallized in an orthorhombic crystal system, in a slightly distorted octahedral geometry having the space group P 2 1 2 1 2. Density functional theory calculations were performed to correlate the energy of frontier molecular orbitals with the stability and reactivity of the complexes. In vitro DNA binding interaction studies of complexes were performed by employing various biophysical techniques and their corroborative results revealed (i) the electrostatic mode of binding in the groove region of DNA, (ii) pBR322 plasmid cleavage at a low concentration of 5-12.5 μM via an oxidative pathway in complexes 1 and 2 and the hydrolytic mechanism in the case of 3, (iii) changes in the 1 H NMR chemical shift values of the NH 2 group of GMP after interaction with complex 3, (iv) alteration in the EPR parameters of complex 2 after complexation with DNA, (v) SOD mimetic activity of complex 2 with the IC 50 value of 2.08 μM and (vi) a good and selective cytotoxicity profile against chemo-resistant MCF-7 and MDA-MB-231 cancer cell lines by complex 1. Molecular docking studies complemented the spectroscopic results and confirmed the electrostatic interaction of complexes in the groove region of DNA.