Prediction of nucleoside-carcinogen reactivity. Alkylation of adenine, cytosine, guanine, and thymine and their deoxynucleosides by alkanediazonium ions

Journal Article · · Chemical Research in Toxicology; (USA)

DOI:https://doi.org/10.1021/tx00015a006· OSTI ID:6363421

Ford, G P ^[1]; Scribner, J D ^[2]

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1. Southern Methodist Univ., Dallas, TX (USA) Pacific Northwest Research Foundation, Seattle, WA (USA)
2. Pacific Northwest Research Foundation, Seattle, WA (USA)

MNDO semiempirical molecular orbital calculations for the S{sub N}2 alkylation of nucleic acid bases and deoxynucleosides by the methane-, ethane, and propanediazonium ions are presented. An approximate correlation is demonstrated between the calculated relative activation enthalpies for attack at alternative base sites and the related experimental quantities for DNA modification by alkylnitrosoureas. The empirically observed shift from N- to O-alkylation with increasing complexity of the alkylating agent is reproduced by the calculations and rationalized by using an extension of a model worked out previously for the analogous reactions of simple nucleophiles. According to this model, the energetics of the related S{sub N}1 reactions, while not directly involved, have a profound influence on the S{sub N}2 transition-state geometries. Consideration of the form of the electrostatic potential around the base, in conjunction with these ideas, provides a detailed explanation of the behavior of electrophiles toward the guanine N{sup 2}-, 7-, and O{sup 6}-positions.

• OSTI ID: 6363421
• Journal Information: Chemical Research in Toxicology; (USA), Vol. 3:3; ISSN 0893-228X
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
CARCINOGENS
REACTIVITY
NUCLEOSIDES
ADENINES
ALKYLATION
CALCULATION METHODS
CYTOSINE
DNA
ELECTROSTATICS
GUANINE
MOLECULAR ORBITAL METHOD
PREDICTION EQUATIONS
THYMINE
AMINES
ANTIMETABOLITES
AROMATICS
AZAARENES
AZINES
CHEMICAL REACTIONS
DRUGS
EQUATIONS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
NUCLEIC ACIDS
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PURINES
PYRIMIDINES
RIBOSIDES
URACILS
560300* - Chemicals Metabolism & Toxicology