Collect. Czech. Chem. Commun. 2011, 76, 1223-1238
Published online 2011-09-22 09:11:23

Modeling of the ribonucleotide reductases substrate reaction. Hydrogen atom abstraction by a thiyl free radical and detection of the ribosyl-based carbon radical by pulse radiolysis

Stanislaw F. Wnuka,*, Jaidev A. K. Penjarlaa, Thao Danga, Alexander M. Mebela, Thomas Nauserb and Christian Schöneichc

a Department of Chemistry and Biochemistry, Florida International University, Miami, Florida 33199, USA
b Department of Chemistry and Applied Bioscience, ETH Zurich, CH-8093, Switzerland
c Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas 66047, USA


The 1,4-anhydro-5-deoxy-6-thio-D-ribo-hexofuranitol (1) was prepared from 1,2-O-isopropylidene-α-D-glucose in 10 steps. In a key step treatment of the 1,2-O-isopropylidenehexofuranose derivative with BF3/Et3SiH effected deacetonization and reductive deoxygenation at carbon 1. Pulse radiolysis experiments with 6-thiohexofuranitol 1 and its disulfide derivative demonstrated formation of the ribosyl-based carbon-centered radical upon generation of 6-thiyl radical in basic medium. The proposed [1,5]-hydrogen shift abstraction with generation of the C3 radical mimics the initial substrate reaction of RNRs. The reversible H-atom transfer has been quantified and was correlated with the computed rate constants for the internal H atom abstraction from C1, C2, C3 and C4 by the thiyl radical. The energy barrier for the H3 and H4 abstractions were calculated to be most favorable with the corresponding barriers of 11.1 and 11.2 kcal/mol, respectively.

Keywords: Radicals; Thiosugars; Pulse radiolysis; Ribonucleotide reductase; Carbohydrates; Bioorganic chemistry.

References: 33 live references.