Hydration of aluminum oxide anion clusters was studied in the gas phase using an ion trap secondary ion mass spectrometer. Hydration of both AlO2 - and Al2O4H- occurred by the consecutive addition of two H2O molecules. For hydration of AlO2 -, the rate constants for addition of the first and second water molecules are 4 × 10-11 and 4 × 10-10 cm3 molecule-1 s-1, respectively. The first and second hydration rate constants for Al2O4H- are 2 × 10-9 and 8 × 10-10 cm3 molecule-1 s-1, respectively. A comparison of the experimental rate constants to the theoretical rate constants reveals that addition of the first H2O to AlO2 - is only 2% efficient, whereas addition of the first H2O to Al2O4H- is 100% efficient. Ab initio calculations were performed to assist in the interpretation of the kinetic results. Reaction mechanisms and energetics for the hydration of the AlO2 - system were calculated using the HF/6-311+G(d(Al),p), B3LYP/6-31+G(d), B3LYP/6-311+G(2d,p), B3LYP/6-311+G(3d2f,2p), and MP2/6-311+G(2d,p) levels of theory. Calculations on the hydration of the Al2O4H- system were performed using the B3LYP/6-311+G(2d,p) level of theory. Ab initio results revealed that the addition of the first and second waters, for both the AlO2 - and Al2O4H- systems, results in the formation of four-membered transition states, with simultaneous Al−O bond formation and proton transfer. However, a significant later transition state is observed, with respect to the Al−O and H−O bond lengths, for the addition of the second water molecule in the Al2O4H- system. A comparison of the reaction mechanisms and energetics was not sufficient to account for the 2 orders of magnitude difference in rate constants; however, the reactivity differences do correlate with the dipole moment of the aluminum oxide anions, which may serve to preorient the incoming water molecule, thus enhancing the reaction rate.

MP2 and B3LYP calculations were performed on complexes of nitric acid with water using the 6-311++G-(2d,p) basis set to determine optimized geometries and binding energies for HNO 3 ‚‚‚nH 2 O systems (n ) 1-4). The structures for the global minima for n ) 1-4 have homodromic rings formed by successive hydrogen bonds. The potential energy surface for the HNO 3 ‚‚‚nH 2 O clusters is quite shallow. The first stable ion-pair configuration is obtained for a HNO 3 ‚‚‚4H 2 O complex. The ion pair, H 3 O + sNO 3 -, is separated by the three H 2 O molecules forming an Eigen-ion (H 9 O 4 + ) type structure. The transition states and activation barriers for n ) 1-4 were also determined. The zero-point corrected transition-state barrier for the ion pair is only 0.5 kcal/mol. Larger HNO 3 ‚‚‚nH 2 O clusters (n up to 32) were also determined to be dominated by the ion-pair motif.

Acetylcholinesterase (AChE) inhibition is an important research topic because of its wide range of associated health implications. A receptor-specific scoring function was developed herein for predicting binding affinities for human AChE (huAChE) inhibitors. This method entails a statistically trained weighted sum of electrostatic and van der Waals (VDW) interactions between ligands and the receptor residues. Within the 53 ligand training set, a strong correlation was found (R 2 ) 0.89) between computed and experimental inhibition constants. Leave-oneout cross-validation indicated high predictive power (Q 2 ) 0.72), and analysis of a separate 16-compound test set also produced very good correlation with experiment (R 2 ) 0.69). Scoring function analysis has permitted identification and characterization of important ligand-receptor interactions, producing a list of those residues making the most important electrostatic and VDW contributions within the main active site, gorge area, acyl binding pocket, and periferal site. These analyses are consistent with X-ray crystallographic and site-directed mutagenesis studies.