Carcinogenic alkylation of nucleic acid bases. Solid state and solution studies of O 2 -isopropyl-2′-deoxythymidine

• Published in: Canadian journal of chemistry 1988-07, Vol.66 (7), p.1628-1634
• Main Authors: Birnbaum, George I., Sadana, Krishan L., Razi, M. Tahir, Lee, Terry, Sebastian, Rudy, Buchko, Garry W., Hruska, Frank E.
• Format: Article
• Language: English
• ISSN: 0008-4042; 1480-3291
• DOI: 10.1139/v88-264

O 2 -Isopropyl-2′-deoxythymidine (i 2 dT) crystallizes in the tetragonal space group P4 3 2 1 2, and the cell dimensions are a = b = 8.7667(2), c = 37.1943(12) Å. X-ray intensity data were measured with a diffractometer, and the structure was solved by direct methods. Least-squares refinement, which included all hydrogen atoms, converged at R = 0.036 for 1780 observed reflections. In analogy with other O-alkylated bases, the exocyclic O2—C8 bond is syn-periplanar to the C2—N3 bond in the pyrimidine ring. Angular distortions in the base can be correlated with those observed in O 4 -alkylated pyrimidines and O 6 -alkylated guanines. The conformation of the glycosyl bond is anti with χ CN  = 27.1°. The furanose ring adopts a C2′ endo pucker and the conformation about C4′—C5′ is gauche + . 1 H nmr data show that these conformations are also preferred in solution.