Surprising effect of leaving group on the nucleophilic aromatic substitution reaction catalyzed by 4-chlorobenzoyl-CoA dehalogenase

Journal Article · Wed Jul 14 00:00:00 EDT 1993 · Journal of the American Chemical Society; (United States)

DOI:https://doi.org/10.1021/ja00067a072· OSTI ID:5712582

Crooks, G P; Copley, S D ^[1]

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1. Univ. of Colorado, Boulder (United States)

We have begun our mechanistic studies of 4-chlorobenzoyl-CoA dehalogenase with a determination of the relative leaving group abilities for bromide, chloride, and fluoride in the dehalogenation reaction. Dehalogenation of 4-bromobenzoyl-CoA is twice as fast as dehalogenation of 4-chlorobenzoyl-CoA, while dehalogenation of 4-fluorobenzoyl-CoA is over 400-fold slower. These data are in striking contrast to the relative leaving group abilities observed for the glutathione-S-transferase-catalyzed dehalogenation of 4-halo-3-nitro-1-(trifluoromethyl)benzenes. Our data also differ from those observed for nonenzymic nucleophilic aromatic substitution reactions that occur by the S[sup N]Ar mechanism. The most reasonable mechanism for the enzymic dehalogenation reaction is probably the S[sub N]Ar mechanism. Nucleophilic aromatic substitution reactions that take place by this mechanism generally proceed fastest when the leaving group is fluoride, even though fluoride is the poorest leaving group among the halogens. The nucleophilic aromatic substitution reaction catalyzed by 4-chlorobenzoyl-CoA dehalogenase shows leaving group abilities in the order opposite that expected on the basis of nonenzymic S[sub N]Ar reactions and the glutahione-S-transferase reaction. Two alternative explanations may account for these data. Our data do not permit a distinction between the various possible mechanisms for the dehalogenation reaction. 17 refs., 1 tab.

• OSTI ID: 5712582
• Journal Information: Journal of the American Chemical Society; (United States), Vol. 115:14; ISSN 0002-7863
• Country of Publication: United States
• Language: English

Related Subjects

37 INORGANIC
ORGANIC
PHYSICAL AND ANALYTICAL CHEMISTRY
59 BASIC BIOLOGICAL SCIENCES
HALOGENATED AROMATIC HYDROCARBONS
DEHALOGENATION
BACTERIA
CATALYSIS
ENZYMES
REACTION KINETICS
AROMATICS
CHEMICAL REACTIONS
KINETICS
MICROORGANISMS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
PROTEINS
400201* - Chemical & Physicochemical Properties
550200 - Biochemistry