Dinuclear platinum(II) complexes with 1,5-nphe bridging ligand: Spectroscopic and molecular docking study of the interactions with N-acetylated L-methionylglycine and human serum albumin

• Published in: Journal of molecular structure 2023-09, Vol.1288, p.135810, Article 135810
• Main Authors: Konovalov, Bata, Đorđević, Ivana S., Franich, Andjela A., Šmit, Biljana, Živković, Marija D., Djuran, Miloš I., Janjić, Goran V., Rajković, Snežana
• Format: Article
• Language: English
• Subjects: 1,5-Naphtiridine bridging ligand; Ac–L–Met–Gly; Dinuclear platinum(II) complexes; Docking study; HSA
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2023.135810

•Dinuclear platinum(II) complexes as potential catalytic reagents for peptide hydrolysis.•Two reaction pathways of hydrolysis were revealed by NMR spectroscopy.•Dinuclear platinum(II) complexes are hydrolytically inactive in reaction with human serum albumin (HSA).•A docking study revealed a unique (electrostatic) binding mode of the complexes to HSA. The hydrolysis of N-acetylated L-methionylglycine dipeptide (Ac-L-Met-Gly) in the presence of dinuclear platinum(II)-aqua complexes with general formula [{Pt(L)(H2O)}2(μ-1,5-nphe)]4+ (1,5-nphe is 1,5-naphthyridine; L is bidentately coordinated ethylenediamine (1w), (±)-1,2-propylenediamine (2w) and 1,3-propylenediamine (3w)) is described in detail. The hydrolytic activity of these complexes was monitored by 1H NMR spectroscopy, which confirmed the regioselective cleavage of the Met-Gly-amide bond in this peptide. Quantum-chemical calculations revealed the primary reaction path with coordination of dipeptide via the terminal amide nitrogen of methionine followed by its coordination for the sulphur atom, in which the decomposition of the resulted platinum(II)-dipeptide complex and the coordination of its glycine residue precedes the hydrolytic cleavage of the Met-Gly amide bond. In the secondary reaction path, in which Ac-L-Met-Gly is coordinated via the methionine sulphur atom, the decomposition of the starting [{Pt(L)(H2O)}2(μ-1,5-nphe)]4+ complex is followed by the regioselective hydrolysis of the investigated dipeptide. The binding affinity of the chloride derivatives of the corresponding dinuclear platinum(II)-aqua complexes, [{Pt(L)Cl}2(μ-1,5-nphe)]2+ (1–3) towards the human serum albumin (HSA), a transport protein, was investigated using electronic absorption and fluorescence emission measurements, and results indicated the static interactions between these complexes and HSA. A docking study revealed a unique binding site on HSA, based on the electrostatic and the hydrogen bonding, which does not have a methionine residue nearby, therefore does not exist danger of HSA hydrolysis by these complexes. Capability of platinum(II) complexes for the regioselective hydrolysis of the amide bond of Ac–L–Met–Gly-dipeptide was not observed in their reaction with human serum albumin (HSA), due to the strong affinity of these complexes for interactions with negatively charged amino acid residues. [Display omitted]