New mononuclear gold(III) complexes: Synthesis, characterization, kinetic, mechanistic, DNA/BSA/HSA binding, DFT and molecular docking studies

Abstract

Five new gold(III) complexes, with general formula [Au(N[sbnd]N)Cl2]+ for complexes 1–3 and [Au(N[sbnd]N)2]3+ for complexes 4–5 (where N[sbnd]N is 3-((2-((5-phenyl-1H-pyrazol-3-yl)methoxy)naphthalene-3-yloxy)methyl)-5-phenyl-1H-pyrazole – L1, (3-((2-((5-phenyl-1H-pyrazol-3-yl)methoxy) phenoxy)methyl)-5-phenyl-1H-pyrazole – L2, (3-((2-((5-naphthalen-2-yl)-1H-pyrazol-3-yl)methoxy)phenoxy)methyl)-5-(naphthalen-3-yl)-1H-pyrazole – L3), were synthesized and characterized by elemental analysis, 1H NMR, IR, UV–Vis, ESI-MS and conductometry. Also, ligand L2 was characterized by X-ray analysis. Stability of complexes in water and in Hepes buffer was confirmed by UV–Vis. Kinetics and mechanism of the substitution reactions of 1–3 with guanosine-5′-monophosphate (5′-GMP), glutathione (GSH) and. L-Methionine (L-Met) were studied by stopped-flow technique. Obtained results have shown that complex 1 is the most reactive, while the reactivity of the nucleophiles decreases in order: GSH > 5′-GMP > L-Met. Calculated values of the entropy of activation support an associative mechanism. Redox stability of complexes 1–3 was investigated in the presence of the same biomolecules by cyclic voltametry. Obtained voltammograms showed reduction of gold(III) up to gold(0). DNA binding studies in the presence of ethidium bromide (EB) and 2-(4-hydroxyphenyl)-5-[5-(4-methylpipera-zine-1yl)-benzimidazo-2-yl]-benzimidazole (HOE) were performed by UV–Vis, fluorescence spectroscopy and viscosity measurements, in order to assess the binding mode. The results showed that gold(III) complexes interact with calf-thymus (CT-DNA) via covalently binding mode rather than via intercalation. Also, all complexes shown high values of binding constants for the interactions with bovine serum albumin (BSA) and human serum albumin (HSA). Furthermore, the binding studies with CT-DNA and BSA/HSA were supported by molecular docking. The strong connection between structure and reactivity of gold(III) complexes toward biologically important molecules was confirmed.