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The Versatile Binding Mode of Transition‐State Analogue Inhibitors of Tyrosinase towards Dicopper(II) Model Complexes: Experimental and Theoretical Investigations
Author(s) -
Orio Maylis,
Bochot Constance,
Dubois Carole,
Gellon Gisèle,
Hardré Renaud,
Jamet Hélène,
Luneau Dominique,
Philouze Christian,
Réglier Marius,
Serratrice Guy,
Belle Catherine
Publication year - 2011
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201100665
Subject(s) - kojic acid , tyrosinase , chemistry , stereochemistry , chelation , adduct , enzyme , organic chemistry
Abstract We describe 2‐mercaptopyridine‐ N ‐oxide (HSPNO) as a new and efficient competitive inhibitor of mushroom tyrosinase ( K IC =3.7 μ M ). Binding studies of HSPNO and 2‐hydroxypyridine‐ N ‐oxide (HOPNO) on dinuclear copper(II) complexes [Cu 2 (BPMP)(μ‐OH)](ClO 4 ) 2 ( 1 ; HBPMP=2,6‐bis[bis(2‐pyridylmethyl)aminomethyl]‐4‐methylphenol) and [Cu 2 (BPEP)(μ‐OH)](ClO 4 ) 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 calculations evidenced the adaptable binding mode (bridging versus 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 theoretical 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 chemical similarity, we showed that the bridging mode was the most preferential binding mode for kojic acid on both complexes.