Methylation of zebularine: a quantum mechanical study incorporating interactive 3D pdf graphs

Methylation of a cytidine deaminase inhibitor, 1-(beta-D-ribofuranosyl)-2-pyrimidone (i.e., zebularine (zeb)), which produces 1-(beta-D-ribofuranosyl)-5-methyl-2-pyrimidinone (d5), has been investigated using density functional theory models. The optimized structures of zeb and d5 and the valence orbitals primarily responsible for the methylation in d5 are presented using state-of-the-art interactive (on a computer or online) three-dimensional (3D) graphics in a portable document format (pdf) file, 3D-PDF (http://www.web3d.org/x3d/vrml/ ). The facility to embed 3D molecular structures into pdf documents has been developed jointly at Swinburne University of Technology and the National Computational Infrastructure, the Australian National University. The methyl fragment in the base moiety shows little effect on the sugar puckering but apparently affects anisotropic properties, such as condensed Fukui functions. Binding energy spectra, both valence space and core space, are noticeably affected; in particular, in the outer-valence space (e.g., IP < 20 eV). The methyl fragment delocalizes and diffuses into almost all valence space, but orbitals 8 (57a, IP = 12.57 eV), 18 (47a, IP = 14.70 eV), and 37 (28a, IP = 22.15 eV) are identified as fingerprint for the methyl fragment. In the inner shell, however, the impact of the methyl can be localized and identified by chemical shift. A small, global, red shift is found for the O-K, N-K and sugar C-K spectra, whereas the base C-K spectrum exhibits apparent methyl-related changes.