Thymine carboxylation: nucleophilic addition of carbon dioxide radical anion.
OBJECTIVE
The nucleophilic addition properties of carbon dioxide radical anion (CO2*-) towards N1-substituted thymine derivatives in aqueous solution is studied for comparison with their one-electron reducing reactivity.


METHODS
N2O-Saturated aqueous solutions of 1-methylthymine, 1,3-dimethylthymine, and thymidylyl(3'-->5')-thymidine containing excess formate ions were gamma-irradiated at 1.0Gy min(-1). Several carboxylated thymines were isolated by preparative HPLC and identified by GC-MS, NMR and X-ray crystallography.


RESULTS
Along with one-electron reduction yielding N-substituted 5,6-dihydrothymines and C5--C5'-linked dihydrothymine dimers, the addition of CO2 radical anion(s) to the C5--C6 double bond of N-substituted thymines produced several mono- and di-carboxylic acids, among which N-substituted derivatives of 5,6-dihydrothymine-6-carboxylic acid [5-methyldihydroorotic acid (5-methyl-DHO)] were produced in the highest yield. Similar carboxylation by CO2 radical anions was also observed for thymine dinucleoside monophosphate. The X-ray structure of cis-5,6-dihydro-1-methylthymine-6-carboxylic acid (cis-1,5-dimethyl-DHO) was determined to show a chair conformation in the crystal.


CONCLUSIONS
The CO2 radical anion is a nucleophilic radical with rather low reduction potential, thereby possessing a dual reactivity of radical addition preferentially at C6 and one-electron reduction towards thymine-related compounds.
Ito
T
T
Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Japan.
Hatta
H
H
Nishimoto
S
S
D000838:Anions; D001665:Binding Sites; D002245:Carbon Dioxide / Q000737:chemistry / Q000378:metabolism*; D002264:Carboxylic Acids / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D018360:Crystallography, X-Ray; D004583:Electrons; D005720:Gamma Rays; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011485:Protein Binding / Q000528:radiation effects; D011743:Pyrimidines / Q000096:biosynthesis; D013941:Thymine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism*
D000838:Anions; D002264:Carboxylic Acids; D011743:Pyrimidines; D002245:Carbon Dioxide; C030630:1-methylthymine; D013941:Thymine