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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. September 2003, Volume 2, Number 9, 589-598 |
Density Functional Studies of Molecular Polarizabilities. Part 11.
The Dipole Polarizability of the Most Stable Conformation of 3'-Azido-3'-deoxythymidine AZT
Javier Hernandez, Humberto Soscun, and Alan Hinchliffe
Internet Electron. J. Mol. Des. 2003, 2, 589-598
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Abstract:
We report an ab initio Hartree-Fock HF and Density
Functional Theory DFT study of the dipole polarizability α of
3'-azido-3'-deoxythymidine (AZT) compound. Geometry was
fully optimized at the HF/6-31+G(d,p) and BLYP/6-31+G(d,p)
levels of theory using X-ray data as starting
structure. These calculations have allowed us to find the most
stable conformational structure of AZT. This structure shows
a torsion angle between thymine and furanose rings larger
than 90° and a nonlinear azido group located trans
to the C2'-C3' bond of furanose ring. This conformation, verified by
vibrational analysis, involves a hydrogen interaction between
the oxygen atom in the position 2 of the thymine ring and the
hydrogen atom in the position 3' of the furanose ring (O-H bond
lengths are 2.4618 and 2.4536 Å at HF and BLYP,
respectively). The calculated geometry of the furanose, azide
and thymine fragments agree with X-ray AZT structure and
with other DFT calculations, whereas the orientation of the
thymine ring in the optimized structure shows strong
discrepancies with the orientation in the crystal. The static dipole
polarizability a was evaluated using the 6-311++G(3d,3p)
basis sets with HF, BLYP and B3LYP methods. The
polarizability results were compared with values from the
empiric atomic methods of Miller, Thole, Swart and Jensen,
giving average polarizability for AZT that range between 166
to 214 au values, whereas the corresponding values at HF/6-311++G(3d,3p),
B3LYP/6-311++G(3d,3p) and BLYP/6-311++G(3d,3p)
approaches are 157.27, 189.77 au and 182.34
au, respectively. These results indicated that the best value
for AZT α lies in the middle of the range between the smaller
and the largest empiric polarizability value, that correspond
to the Miller and Thole methods.
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