Ab initio calculations were performed on CH3CH2OOH, CH3CHClOOH, and CH3CCl2OOH molecules using the Gaussian92 system of programs. Geometries of stable rotational conformers and transition states for internal rotation were optimized at the RHF/6-31G* and MP2/6-31G* levels of theory. Harmonic vibrational frequencies were computed at the RHF/6-31G* level of theory. Potential barriers for internal rotations were calculated at the MP2/6-31G**/HF/6-31G* level. Parameters of the Fourier expansion of the hindrance potentials have been tabulated. Standard entropies (S°298) and heat capacities (C p (T)'s, 300 ≤ T/K ≤ 1500) were calculated using the rigid-rotor−harmonic-oscillator approximation based on the information obtained from the ab initio studies. Contributions from hindered rotors were calculated by summation over the energy levels obtained by direct diagonalization of the Hamiltonian matrix of hindered internal rotations. Enthalpies of formation for these three molecules were calculated using isodesmic reactions. Enthalpies of formation were calculated to be ΔH f°298(CH3CH2OOH) = −41.5 ± 1.5 kcal mol-1, ΔH f°298(CH3CHClOOH) = −50.9 ± 3.4 kcal mol-1, and ΔH f°298(CH3CCl2OOH) = −55.3 ± 2.2 kcal mol-1. Entropies (S°298) are calculated to be 76.1, 79.2 and 86.6 cal mol-1 K-1 for CH3CH2OOH, CH3CHClOOH, and CH3CCl2OOH, respectively.

Ab initio molecular orbital calculations optimized with the 6-31G* basis set were employed to investigate the structures, resonance energies, and protonation sites of the two bridgehead bicyclic lactams l-azabicyclo[2.2.2]octan-2-one (2-quinuclidone) and 1 -azabicyclo[3.3.1] nonan-2-one. The structures and resonance energies reflect the absence of resonance stabilization in the first molecule and somewhat reduced resonance in the second molecule. While planar amides protonate on oxygen, 2-quinuclidone very strongly favors N-protonation while the Nand O-protonated forms in the 3.3.1 system are almost equal in energy. Discussion of structures and energies is given in the context of resonance theory.

A rigid-body systematic search technique was applied to stacked complexes of the novel AT-specific intercalator, amiloride, with each of the four DNA bases (A, T, C, G) and two Watson−Crick base pairs (AT and GC). Gas-phase calculations were carried out using the Cornell empirical molecular potential with a set of ab initio-optimized atomic charges. At selected points on the ligand−nucleobase potential energy surface, empirical intermolecular interaction energy values were found to be in good agreement with the ab initio MP2/6-31++G(d,p) energies corrected for basis set superposition errors. This result supports the application of the systematic search technique to larger model systems. The general features of the amiloride−base and amiloride−base pair intermolecular potential energy surfaces were found to be different in the case of adenine and thymine compared to guanine and cytosine, resulting in more orientational and translational freedom for amiloride in the former case. In addition, the interaction of amiloride with adenine and thymine nucleobases is significantly more dispersion-controlled than that with guanine and cytosine, where the electrostatic energy contributes up to a third of the total intermolecular energy. Amiloride in the base pair complexes is overlapped with guanine and adenine. Thymine and cytosine are exposed, and the interaction of the ligand with the pyrimidine nucleobases appears to be exclusively due to electrostatic forces.

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