Nitrosative Guanine Deamination: Ab Initio Study of Deglycation of N-Protonated 5-Cyanoimino-4-oxomethylene-4,5-dihydroimidazoles


5-Cyanoimino-4-oxomethylene-4,5-dihydroimidazoles (1) (R at N1) have been discussed as possible intermediates in nitrosative guanine deamination, which are formed by dediazoniation and deprotonation of guaninediazonium ion. The parent system 1 (R=H) and its N1 derivatives 2 (R=Me) and 3 (R=MOM) are considered here. Protonation of 1-3, respectively, may occur either at the cyano-N to form cations 4 (R=H), 6 (R=Me), and 8 (R=MOM) or at the imino-N to form cations 5 (R=H), 7 (R=Me), and 9 (R=MOM), respectively. This protonation is the first step in the acid-catalyzed water addition to form 5-cyanoimino-imidazole-4-carboxylic acid, which then leads to oxanosine. There also exists the option of a substitution reaction by water at the R group of 6-9, and this dealkylation forms N-[4-(oxomethylene)-imidazol-5-yl]-carbodiimide (10) and N-[4-(oxomethylene)-imidazol-5-yl]cyanamide (11). In the case of DNA, the R group is a deoxyribose sugar, and attack by water leads to deglycation. To explore this reaction option, the SN1 and SN2 reactions of 6-9 with water were studied at the MP2/6-31G*//RHF/6-31G* and CCSD/6-31G*//RHF/6-31G* levels, with the inclusion of implicit solvation at the IPCM(MP2/6-31G*)//RHF/6-31G* level, and the electron density distributions of tautomers 1, 10, and 11 were analyzed. The low barriers determined for the MOM transfer show that the deglycation could occur at room temperature but that the process cannot compete with water addition.



Keywords and Phrases

5 cyanoimino 4 oxomethylene 4,5 dihydroimidazole; 5 cyanoiminoimidazole 4 carboxylic acid; carboxylic acid derivative; guanine; imidazole derivative; n [4 (oxomethylene)imidazol 5 yl]carbodiimide; n [4 (oxomethylene)imidazol 5 yl]cyanamide; unclassified drug; ab initio calculation; cross linking; dealkylation; deamination; nitrosation; proton transport; reaction analysis; synthesis; thermodynamics; Dealkylation; Deamination; Guanine; Hydrolysis; Imidazoles; Imines; Kinetics; Models; Chemical; Models; Molecular; Molecular Conformation; Molecular Structure; Nitrosation; Thermodynamics

International Standard Serial Number (ISSN)

0893-228X; 1520-5010

Document Type

Article - Journal

Document Version


File Type





© 2004 American Chemical Society (ACS), All rights reserved.