Nonlocal density functional calculations and a semiempirical modified Born method for computing free energies of hydration were used to calculate the electrode potentials for a series of nitroimidazoles to a mean accuracy of about 80 mV. The density functional calculations used the nonlocal Becke '88 functional for exchange and either the nonlocal Lee-Yang-Parr or the local Vosko-Wilk-Nusair functionals for correlation and were performed at the HF/3-21G geometry. The most suitable geometry for these calculations was determined from a survey of various semiempirical, Hartree-Fock (HF) and density functional methods, with a variety of basis sets. The HF/3-21G method was found to yield a very favorable compromise between speed and accuracy in the determination of the geometry of 2-nitroimidazole, but the small basis set density functional calculations performed very badly. Density functional atom-optimized basis sets were found to give better overall results than traditional Pople-type basis sets. The free energy of hydration calculations employed the AM1 SM2 method. Both the gas-phase energies and the free energies of hydration made a significant contribution to the computed electrode potential. Indeed, an inverse relationship was found between the gas-phase electron affinity and the difference in free energy of hydration between the neutral nitroimidazole and its radical anion. The protocol established here may be useful for investigating novel bioreductive agents.
|Number of pages||11|
|Journal||International Journal of Quantum Chemistry|
|Publication status||Published - 1 Jan 1996|
ASJC Scopus subject areas
- Atomic and Molecular Physics, and Optics
- Condensed Matter Physics
- Physical and Theoretical Chemistry