Hybrid pharmacophore approach for bio-relevant di-imines based homobimetallic complexes incorporating functionalized dicarboxylates as co-ligands: Synthesis, spectral and structural activity dependent biological insights (in-vitro DNA and HSA binding, antioxidant and cytotoxicity).

Synthesis of bio-efficient homobimetallic complexes, [Cu2(L1)2(dipic)](NO3)2.3H2O (1), [Zn2(L1)2(dipic)](NO3)2.4H2O (2), [Cu2(L2)2(oxa)](NO3)2.4H2O (3) and [Zn2(L2)2(oxa)] (NO3)2.5H2O (4) was carried out using Schiff bases [(N1E,N2E)-N1,N2-bis(5-chlorothiophen-2-ylmethylene)-4-chlorobenzene-1,2-diamine; L1] and [(N1E,N2E)-N1,N2-bis(5-chlorofuran-2-ylmethylene)-4-chlorobenzene-1,2-diamine; L2] as main ligands and dicarboxylate moieties of 2,6-pyridine dicarboxylic acid (H2-dipic) and oxalic acid (H2-oxa) as co-ligands, respectively in order to apprehend their structure activity relationships on the basis of pharmacophore hybrid approach. The stoichiometry, geometry, thermal stability, morphology and crystallite size of the compounds were inferred by analytical, spectral (FT-IR, 1H NMR and 13C NMR and Mass), thermal (TGA/DTA), SEM and XRD studies. In-vitro DNA and HSA binding profiles of complexes were analysed by different biophysical measurements. The absorption study divulged that the observed alterations in the physico-chemical properties of complexes upon binding with DNA connoted their intercalative binding mode while fluorescence quenching mechanism was quantified by using Stern Volmer constant (KSV); 1.73×104 (1), 1.47×104 (2), 5.65×103 (3) and 3.60×103M-1 (4) which discerned that hybrid pharmacophore active metal complexes (1 and 2) exhibited efficient quenching effect with Ct-DNA in comparison to complexes (3 and 4) due to greater planarity and extent of conjugation (π-π interactions). The intercalative binding mode of complexes is further supported by competitive displacement assay by using fluorogenic dyes (EtBr and Hoechst 33258). The results of HSA fluorescence study divulged static quenching of the complexes (1-4) with KSV values of 7.24×104 (1), 6.03×104 (2), 5.06×104 (3) and 2.85×104 (4) while Kb values; 1.16×105 (1), 2.01×104 (2), 5.84×103 (3) and 8.60×102 (4) suggested them potent avid binder of HSA. Additionally, comparative estimation of scavenging properties using DPPH, superoxide(O2.-), hydroxyl (OH-) and ABTS method and in-vitro cytotoxicity against different cell lines (MCF-7, HeLa and Hep G2) brought out distinct biopotency of complexes due to diverse structural features and chelation effect.