Determination of the chlorine kinetic isotope effect, on the 4-chlorobenzoyl-CoA dehalogenase-catalyzed nucleophilic aromatic substitution

The chlorine kinetic isotope effect (KIE) on the de-halogenation of 4-chlorobenzoyl-CoA catalyzed lay 4-chlorobenzoyl-CoA dehalogenase has been measured at room temperature and optimal pH. The measured value of (37)k = 1.0090 +/- 0.0006 is larger than the KIEs recently measured for haloalkane and fluoroacetate dehalogenase. This indicates that the transition state for dissociation of chloride ion from the Meisen-heimer intermediate is sensitive to the chlorine isotopic substitution. Simple modeling suggests that this sensitivity originates in the high isotopic sensitivity of the C-Cl bond bending modes. (C) 2002 Elsevier Science (USA).