5-Cyanoimino-4-Oxomethylene-4,5-Dihydroimidazole and 5-Cyanoamino-4-Imidazolecarboxylic Acid Intermediates in Nitrosative Guanosine Deamination: Evidence from ¹⁸O-Labeling Experiments

Author

Sundeep Rayat
Papiya S. Majumdar
Peter A. Tipton
Rainer Glaser, Missouri University of Science and TechnologyFollow

Abstract

The nitrosative deaminations (37 °C, NaNO₂, NaAc buffer, pH 3.7) of guanosine 1r in (¹⁸O)-water (97.6%) and of [6-¹⁸O]-1r in normal water were studied. [6-¹⁸O]-1r was prepared from 2-amino-6-chloropurine riboside using adenosine deaminase. The reaction products xanthosine 3r and oxanosine 4r were separated by HPLC and characterized by LC/MS analysis and ¹³C NMR spectroscopy. The ¹⁸O-isotopic shifts on the ¹³C NMR signals were measured and allowed the identification of all isotopomers formed. The results show that oxanosine is formed via 5-cyanoimino-4-oxomethylene-4,5-dihydroimidazole, 5, and its 1,4-addition product 5-cyanoamino-4-imidazolecarboxylic acid, 6. This hydration of 5 to 6 leads to aromatization and greatly dominates over water addition to the cyanoimino group of 5 to form 5-guanidinyliden-4-oxomethylene-4, 5-dihydroimidazole, 7. 5-Guanidinyl-4-imidazolecarboxylic acid, 8, the product of water addition to 6, is not involved.

Recommended Citation

S. Rayat et al., "5-Cyanoimino-4-Oxomethylene-4,5-Dihydroimidazole and 5-Cyanoamino-4-Imidazolecarboxylic Acid Intermediates in Nitrosative Guanosine Deamination: Evidence from ¹⁸O-Labeling Experiments," Journal of the American Chemical Society, vol. 126, no. 32, pp. 9960 - 9969, American Chemical Society (ACS), Aug 2004.

The definitive version is available at https://doi.org/10.1021/ja049835q

Department(s)

Chemistry

Keywords and Phrases

Aromatization; Experiments; High Performance Liquid Chromatography; Hydration; Reaction Kinetics; Isotopic Shifts; Reaction Products; Carboxylic Acids; 5 Cyanoamino 4 Imidazolecarboxylic Acid; 5 Cyanoimino 4 Oxomethylene 4,5 Dihydroimidazole; Carboxylic Acid Derivative; DNA Base; Guanosine; Imidazole Derivative; Oxanosine; Oxygen 18; Unclassified Drug; Water; Carbon Nuclear Magnetic Resonance; Deamination; Nitrosation; Reaction Analysis; DNA; Imidazoles; Isotope Labeling; Nitrites; Nuclear Magnetic Resonance; Biomolecular; Oxygen Isotopes; Pyrimidines; Spectrometry; Mass; Electrospray Ionization

International Standard Serial Number (ISSN)

0002-7863; 1520-5126

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

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

Publication Date

01 Aug 2004

PubMed ID

15303870