Effect of ortho-SR groups on O-H bond strength and H-atom donating ability of phenols: a possible role for the Tyr-Cys link in galactose oxidase active site?
Rotation about the Ar-S bond in ortho-(alkylthio)phenols strongly affects the bond dissociation enthalpy (BDE) and the reactivity of the OH group. Newly synthesized sulfur containing heterocycles 3 and 4, where the -SR group is almost coplanar with the phenolic ring, are characterized by unusually low BDE(O-H) values (79.6 and 79.2 kcal/mol, respectively) and by much higher reactivities toward peroxyl radicals than the ortho-methylthio derivative 1 (82.0 kcal/mol). The importance of the intramolecular hydrogen bond (IHB) in determining the BDE(O-H) was demonstrated by FT-IR experiments, which showed that in heterocycles 3 and 4 the IHB between the phenolic OH group and the S atom is much weaker than that present in 1. Since the IHB can be formed only if the -SR group adopts an out-of-plane geometry, this interaction is possible only in the methylthio derivative 1 and not in 3 and 4. The additive contribution to the phenolic BDE(O-H) of the -SR substituent therefore varies from -3.1 to +2.8 kcal/mol for the in-plane and out-of-plane conformations, respectively. These results may be relevant to understanding the role of the tyrosine-cysteine link in the active site of galactose oxidase, an important enzyme that catalyzes the two-electron aerobic oxidation of primary alcohols to aldehydes. The switching of the ortho -SR substituent between perpendicular and planar conformations may account for the catalytic efficiency of this enzyme.
Amorati
Riccardo
R
Dipartimento di Chimica Organica "A. Mangini", Università di Bologna, Via S. Donato 11, 40126 Bologna, Italy.
Catarzi
Francesca
F
Menichetti
Stefano
S
Pedulli
Gian Franco
GF
Viglianisi
Caterina
C
D001665:Binding Sites; D002384:Catalysis; D003545:Cysteine; D005692:Galactose Oxidase / Q000737:chemistry*; D006860:Hydrogen Bonding; D010636:Phenols / Q000737:chemistry*; D011485:Protein Binding; D014443:Tyrosine
D010636:Phenols; D014443:Tyrosine; D005692:Galactose Oxidase; D003545:Cysteine