The Versatile Binding Mode of Transition-State Analogue Inhibitors of Tyrosinase towards Dicopper(II) Model Complexes: Experimental and Theoretical Investigations.

We describe 2-mercaptopyridine-N-oxide (HSPNO) as a new and efficient competitive inhibitor of mushroom tyrosinase (KIC=3.7 $μ$). Binding studies of HSPNO and 2-hydroxypyridine-N-oxide (HOPNO) on dinuclear copper(II) complexes [Cu2(BPMP)($μ$-OH)](ClO4)2 (1; HBPMP=2,6-bis[bis(2-pyridylmethyl)aminomethyl]-4-methylphenol) and [Cu2(BPEP)($μ$-OH)](ClO4)2 (2; HBPEP=2,6-bis{\{}bis[2-(2-pyridyl)ethyl]aminomethyl{\}}-4-methylphenol), known to be functional models for the tyrosinase diphenolase activity, have been performed. A combination of structural data, spectroscopic studies, and DFT calcns. evidenced the adaptable binding mode (bridging vs. chelating) of HOPNO in relation to the geometry and chelate size of the dicopper center. For comparison, binding studies of HSPNO and kojic acid (5-hydroxy-2-(hydroxymethyl)-4-pyrone) on dinuclear complexes were performed. A theor. approach has been developed and validated on HOPNO adducts to compare the binding mode on the model complexes. It has been applied for HSPNO and kojic acid. Although results for HSPNO were in line with those obtained with HOPNO, thus reflecting their chem. similarity, we showed that the bridging mode was the most preferential binding mode for kojic acid on both complexes. [on SciFinder(R)]

Références

Titre
The Versatile Binding Mode of Transition-State Analogue Inhibitors of Tyrosinase towards Dicopper(II) Model Complexes: Experimental and Theoretical Investigations.
Type de publication
Article de revue
Année de publication
2011
Revue
Chem. - A Eur. J.
Volume
17
Pagination
13482–13494, S13482/1–S13482/19
ISSN
0947-6539
Soumis le 12 avril 2018