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Investigation of nucleoside analogs with anti‐HIV activity
Author(s) -
Arissawa Márcia,
Taft Carlton Anthony,
Felcman Judith
Publication year - 2003
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.10580
Subject(s) - chemistry , computational chemistry , mulliken population analysis , ab initio , phosphoramidate , basis set , atomic charge , fukui function , nucleoside , hydrogen bond , nucleoside reverse transcriptase inhibitor , reverse transcriptase , stereochemistry , electrophile , density functional theory , molecule , organic chemistry , rna , biochemistry , gene , catalysis
Abstract Although a relatively large number of drugs that inhibit human immunodeficiency syndrome (HIV)‐1 reverse transcriptase have been developed—such as AZT, d4T, ddI, 3TC, and ddC, which are chain terminating nucleoside analogs—resistance is still a major problem. Atomic charges, regioselective patterns of chemical reactivity, and other indices of biochemical activity may help us acquire a better understanding of how the drugs work and the mechanism of drug resistance. In this work, we investigated the above‐mentioned nucleoside analogs using the ab initio Hartree–Fock method with 3‐21G, 3‐21G*, 6‐31G, 6‐31G*, 6‐31G**, and 6‐31+G** basis sets as well as B3LYP/6‐31G**, including thus diffusion, polarization, and correlation effects to obtain fully optimized geometric parameters. Vibrational frequencies were calculated and we also investigated the effects of solvents, Mulliken, and natural bond orbital charge distribution, as well as hydrogen bond effects. We tried to correlate very low and very high anti‐HIV activity with charges, vibrational stretching frequencies, interatomic distances, and the effect of solvents. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem 93: 422–432, 2003