On the Mechanism of Reduction by Reduced Nicotinamide Adenine Dinucleotide Dependent Alcohol Dehydrogenase. α-Halo Ketones as Mechanistic Probes

Article abstract of DOI:10.1021/jo00243a009

α-Haloacetophenones have been used as mechanistic probes for the enzyme (HLADH) controlled reductions by NADH.The cofactor, NADH, itself reduced the α-haloacetophenones and yielded the product diagnostic of free radical reduction, acetophenone.In the presence of NADH/HLADH both the α-fluoro- and α-chloroacetophenones, although they were only slightly reactive with NADH, yielded the hydride reduction products, optically active 1-phenyl-2-haloethanol.The more reactive α-bromoacetophenone was reduced by a radical chain process, which did not involve the enzyme.Ahalo ketone of intermediate reactivity, α,α-dichloroacetophenone, was reduced by the enzyme to give the products of heterolytic reduction.The suitability of the α-haloacetophenones as diagnostic mechanistic probes for enzyme reactivity and of dihydropyridines as NADH/HLADH models is discussed.