An Experimental and Molecular modelling Study of Ruthenium(II) Polypyridyl Complexes with a Thiazole-Imidazo-Phenanthroline Ligand and their DNA Affinity.

Mononuclear Ru(II)Polypyridyl complexes of type [Ru(A)2MTZIP] (ClO4)2.2H2O, where MTZIP = (2-(4-methyl thiazol-5-yl)-1 H-imidazole [4,5-f] [1, 2] phenanthroline and A = phen = 1,10 Phenanthroline (1), bpy = 2, 2'- bipyridine (2), dmp = 4,4'-dimethyl-1,10 -Ortho Phenanthroline (3) & dmb = 4, 4' -dimethyl 2, 2'- bipyridine (4) were synthesized and their biological activity were examined. Biophysical techniques (absorption, emission methods, and viscosity) ascertains that intercalation is the primary mechanism by which Ru (II) polypyridyl complexes bind to DNA.The intrinsic binding constant (kobs) data show 1 > 2>3 > 4, indicating the phen complex (1.0 × 106) has a higher binding capacity than the bpy, dmp, and dmb (4.5 × 105,3.5 × 105, 2.0 × 105), demonstrating the auxiliary ligand effect on the specificity of DNA binding. The HOMO-LUMO gap (Eg) values for the complexes 1-4 are in the range of 5.6375-5.7398 eV, ligand MTZIP (7.3026 eV), indicative of a more reactivity for complexes. The 3D contour maps show that in complexes LUMO is primarily concentrated on or near the Ru (II) metal ion and auxiliary ligands; on the contrary, the HOMO has constraints to the intercalating ligand's nitrogen. The phen complex has greater chemical reactivity than the bpy, dmp and dmb complexes, so complex 1 is more vulnerable to nucleophilic attack. All four complexes were active against Gram-positive bacterial pathogens (Staphylococcus and Bacillus strains) as well as Gram-negative bacterial species (E. Coli and Klebsiella) and antifungal activity (candida, aspergillus). All the complexes showed good anticancer activity, but the phen complex with IC50 = 22.89 ± 0.814 against the MCF-7 cell line.