Kinetic results implicating a polar radical reaction pathway in the rearrangement catalyzed by alpha-methyleneglutarate mutase.
alpha-Methyleneglutarate mutase (MGM) catalyzes the rearrangement of 2-methyleneglutarate to 3-methylitaconate (2-methylene-3-methylsuccinate). A putative mechanism for the MGM-catalyzed reaction involves 3-exo cyclization of the 2-methyleneglutaric acid-4-yl radical to a cyclopropylcarbinyl radical intermediate that ring opens to the 3-hydroxycarbonyl-2-methylenebutanoic acid-4-yl radical (3-methylitaconic acid radical). Model reactions for this mechanism were studied by laser flash photolysis kinetic methods. alpha-Ester radicals were produced by 266 nm photolysis of alpha-phenylselenyl ester derivatives. Rate constants for cyclizations of the (Z)-1-ethoxycarbonyl-4-(2,2-diphenylcyclopropyl)-3-buten-1-yl radical ((Z)-8a) and (E)- and (Z)-1,3-di(ethoxycarbonyl)-4-(2,2-diphenylcyclopropyl)-3-buten-1-yl radicals ((E)- and (Z)-8b) were determined. The ester group in (Z)-8a accelerates the 3-exo cyclization in comparison to the parent radical lacking an ester group by a factor of 3, an effect ascribed to a polarized transition state. The ester groups at C3 in radicals 8b slow the 3-exo cyclization reaction by a factor of 50. The rate constant for cyclization of the 2-methyleneglutaric acid-4-yl radical is estimated to be k approximately 2000 s(-1) at ambient temperature. When coupled with the estimated partitioning of the intermediate cyclopropylcarbinyl radical, the overall rate constant for the conversion is estimated to be k approximately equal to 1 x 10(-3) s(-1), which is much too small for any radical reaction and several orders of magnitude too small for kinetic competence for the MGM-catalyzed process. The possibility that the radical reaction in nature involves an unusual mechanism in which polar effects are important is discussed.
Newcomb
Martin
M
Department of Chemistry, University of Illinois at Chicago, 845 W. Taylor St., Chicago, Illinois 60607, USA. men@uic.edu
Miranda
Neil
N
D002384:Catalysis; D003500:Cyclization; D005609:Free Radicals / Q000737:chemistry / Q000378:metabolism; D005977:Glutarates / Q000737:chemistry* / Q000378:metabolism*; D019751:Intramolecular Transferases / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D010782:Photolysis; D013816:Thermodynamics
D005609:Free Radicals; D005977:Glutarates; C002172:2-methyleneglutaric acid; D019751:Intramolecular Transferases; C047997:2-methyleneglutarate mutase