New mononuclear gold(III) complexes: Synthesis, characterization, kinetic, mechanistic, DNA/BSA/HSA binding, DFT and molecular docking studies. (15th November 2021)

• Record Type: Journal Article
• Authors: Radisavljević, Snežana; Scheurer, Andreas; Bockfeld, Dirk; Ćoćić, Dušan; Puchta, Ralph; Senft, Laura; Pešić, Marko; Damljanović, Ivan; Petrović, Biljana
• Is Part Of: Polyhedron. Volume 209(2021)
• Publication Date: 2021-11-15
• Subjects: N-N Bidentate nitrogen-donor ligand -- L1 3-((2-((5-phenyl-1H-pyrazol-3-yl)methoxy)naphthalene-3-yloxy)methyl)-5-phenyl-1H-pyrazole -- L2 (3-((2-((5-phenyl-1H-pyrazol-3-yl)methoxy)phenoxy)methyl)-5-phenyl-1H-pyrazole -- L3 (3-((2-((5-naphthalen-2-yl)-1H-pyrazol-3-yl)methoxy)phenoxy)methyl)-5-(naphthalen-3-yl)-1H-pyrazole -- ESI-MS Electrospray-ionization MS -- 5'-GMP Guanosine-5'-monophosphate -- GSH Glutathione -- L-Met L-methionine -- Hepes 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid -- CV Cyclic voltammetry -- CT-DNA Calf thymus DNA -- EB Ethidium bromide -- HOE 2-(4-hydroxyphenyl)-5-[5-(4-methylpipera-zine-1-yl)-benzimidazo-2-yl]-benzimidazole -- BSA Bovine serum albumin -- HSA Human serum albumin -- DFT Density functional theory -- DMF N, N-Dimethylformamide -- kobsd1, kobsd2 Pseudo-first order rate constants -- ΔS≠ Entropy of activation -- ΔH≠ Enthalpy of activation -- GC electrode Glassycarbon electrode -- Kb Intrinsic binding constants -- Ksv Stern-Volmer quenching constant -- SA Serum albumin -- kq Quenching rate constant -- n Number of binding sites per albumin -- η Viscosity of DNA in the presence of complex -- η0 Viscosity of DNA alone -- ωB97XD Hybrid functionals -- def2-SVP Basis set -- PDB 1BNA Canonical B-DNA -- PDB 1Z3F DNA with an intercalation gap -- B-DNA Crystal structure of DNA in Protein Data Bank -- 4F5S Crystal structure of BSA in Protein Data Bank -- DMSO Dimethyl sulfoxide -- THF Tetrahydrofuran -- δ The chemical shifts -- ZPE Zero-point vibrational energies -- MVD Molegro Virtual Docker version 2013.6.0.1.; Gold(III) -- DNA -- BSA -- HAS -- Molecular docking; Chemistry, Inorganic -- Periodicals; Chimie inorganique -- Périodiques; Organometaalverbindingen; Anorganische chemie; 546.05
• DOI: 10.1016/j.poly.2021.115446
• Languages: English
• ISSNs: 0277-5387

Abstract

Graphical abstract: The synthesis, characterization, solution and redox stability, kinetic, mechanistic, DNA/BSA/HSA binding, DFT and molecular docking studies were performed of five new mononuclear gold(III) complexes. Abstract: Five new gold(III) complexes, with general formula [Au(NN)Cl2 ] + for complexes 1 –3 and [Au(NN)2 ] 3+ for complexes 4 –5 (where NN is 3-((2-((5-phenyl-1 H -pyrazol-3-yl)methoxy)naphthalene-3-yloxy)methyl)-5-phenyl-1 H -pyrazole – L1, (3-((2-((5-phenyl-1 H -pyrazol-3-yl)methoxy) phenoxy)methyl)-5-phenyl-1 H -pyrazole – L2, (3-((2-((5-naphthalen-2-yl)-1 H -pyrazol-3-yl)methoxy)phenoxy)methyl)-5-(naphthalen-3-yl)-1 H -pyrazole – L3), were synthesized and characterized by elemental analysis, 1 H 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.