Model experiments relevant to the mechanism of adenosylcobalamin-dependent diol dehydrase: further investigations of isomerisations of dihydroxyalkyl radicals

Abstract

Anaerobic photolysis of 4,5-dihydroxypentyl(pyridine)cobaloxime in 0.1M acetic acid (pH 3) gives ca. 10% of pentanal, whereas 1,1,5,5-tetradeuterio-4,5-dihydroxypentyl(pyridine)cobaloxime affords 0.6% of 1,5,5,5-tetradeuteriopentanal. Under similar conditions, 5-deuterio-5,6-dihydroxyhexyl(pyridine)cobaloxime gives ca. 1% of 6-deuteriohexan-2-one and 4% of 2-deuteriohexanal, in contrast to 5,6-dihydroxyhexyl(pyridine)cobaloxime which affords 16% of hexan-2-one and 4% of hexanal. These results support a mechanism for the photocon-version of dihydroxyalkylcobaloximes into aldehydes or ketones at pH 3, in which light-induced homolysis of the Co–C σ-bond to give a dihydroxyalkyl radical is followed by a 1,5-hydrogen shift. The resulting isomeric dihydroxyalkyl radical, possessing a hydroxy-group at the radical centre, undergoes an acid-catalysed transformation to aldehyde or ketone. With the deuteriated cobaloximes the 1,5-H shift is impeded by a primary isotope effect (k_H/k_Dca. 20). Anaerobic photolysis of 4,5-dihydroxycyclo-octyl(pyridine)cobaloxime at pH 3 yields ca. 40% of cyclo-octanone. This reaction owes its efficiency to a favourable transannular 1,5-H shift which converts the 4,5-dihydroxycyclo-octyl radical into the 1,2-dihydroxycyclo-octyl radical. The relevance of the above reactions to adenosylcobalamin-dependent reactions catalysed by diol dehydrase is discussed.