5-Cyanoimino-4-Oxomethylene-4,5-Dihydroimidazole and Nitrosative Guanine Deamination. A Theoretical Study of Geometries, Electronic Structures, and N-Protonation
The 5-cyanoimino-4-oxomethylene-4,5-dihydroimidazole 1 (R = H), its N1-derivatives 2 (R = Me) and 3 (R = MOM) and their cyano-N (4, 6, 8) and imino-N protonated (5, 7, 9) derivatives were studied with RHF, B3LYP, and MP2 theory. Solvation effects were estimated with the isodensity polarized continuum model (IPCM) at the MP2 level using the dielectric constant of water. Carbodiimide 10, cyanamide 12, N-cyanomethyleneimine 13, and its protonated derivatives 14 and 15 were considered for comparison as well. Adequate theoretical treatment requires the inclusion of dispersion because of the presence of intramolecular van der Waals, charge-dipole, and dipole-dipole (including H-bonding) interactions. All conformers were considered for the MOM-substituted systems, and direct consequences on the preferred site of protonation were found. The vicinal push (oxomethylene)-pull (cyanoimino) pattern of the 5-cyanoimino-4-oxomethylene-4,5-dihydroimidazoles results in the electronic structure of aromatic imidazoles with 4-acylium and 5-cyanoamido groups. The gas-phase proton affinities of 1-3 are over 30 kcal/mol higher than that for N-cyanomethyleneimine 13, and this result provides compelling evidence in support of the zwitterionic character of 1-3. Protonation enhances the push-pull interaction; the OC charge is increased from about one-half in 1-3 to about two-thirds in the protonated systems. In the gas phase, cyano-N protonation is generally preferred but imino-N protonation can compete if the R-group contains a suitable heteroatom (hydrogen-bond acceptor, Lewis base). In polar solution, however, imino-N protonation is generally preferred. Solvation has a marked consequence on the propensity for protonation. Whereas protonation is fast and exergonic in the gas phase, it is endergonic in the polar condensed phase. It is an immediate consequence of this result that the direct observation of the cations 8 and 9 should be possible in the gas phase only.
S. Rayat and R. Glaser, "5-Cyanoimino-4-Oxomethylene-4,5-Dihydroimidazole and Nitrosative Guanine Deamination. A Theoretical Study of Geometries, Electronic Structures, and N-Protonation," Journal of Organic Chemistry, vol. 68, no. 26, pp. 9882-9892, American Chemical Society (ACS), Dec 2003.
The definitive version is available at https://doi.org/10.1021/jo0351522
Keywords and Phrases
Deamination; Amination; Derivatives; Electronic Structure; Hydrogen Bonds; Permittivity; Positive Ions; Protons; Van Der Waals Forces; Aromatic Compounds; 5 Cyanoimino 4 Oxomethylene 4,5 Dihydroimidazole; Cyanamide; Guanine; Imidazole Derivative; N Cyanomethyleneimine; Oxomethylene; Unclassified Drug; Water; Chemical Interaction; Density; Dielectric Constant; Dipole; Electronics; Gas; Geometry; Hydrogen Bond; Nitrosation; Polarization; Polymerization; Proton Transport; Solvation; Imidazoles; Imines; Isomerism; Models; Chemical; Models; Molecular; Molecular Conformation; Molecular Structure; Nucleosides; Protons; Thermodynamics
International Standard Serial Number (ISSN)
Article - Journal
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