THEORETICAL-STUDIES OF THE 2-HYDROXYBENZOIC AND 4-HYDROXYBENZOIC ACIDS WITH COMPETING HYDROGEN-BONDS IN THE GAS-PHASE AND AQUEOUS-SOLUTION

MP2/6-31G//6-31G* ab initio quantum chemical calculations in the gas phase and Monte Carlo simulations for isothermal-isobaric (NPT) ensemb les in aqueous solution have been carried out for 2- and 4-hydroxybenz oic acid. After total geometry optimization of eight planar conformers for the 2-OH derivative and four conformers for the 4-OH derivative i n the gas phase, the structure with the 2-OH phenolic hydroxyl with an intramolecular hydrogen bond to the carbonyl oxygen was found to be t he most stable conformer. Normal frequency analyses were carried out u sing the 6-3 1 G optimized geometries, and thermal corrections were o btained at 298 K and 1 atm. Structures for the 2-OH isomer, with the c arboxylic hydrogen trans to the carbonyl oxygen or without intramolecu lar hydrogen bonds, are higher in free energy by at least 8 kcal/mol. The most stable 4-OH isomer with the cis carboxylic hydrogen is higher in free energy by 4.4 kcal/mol than the most stable 2-OH isomer. Rela tive hydration free energies, using the statistical perturbation metho d, were calculated for three conformers of 2-hydroxybenzoic acid with and without intramolecular hydrogen bonds. Hydration prefers the inter nally less stable forms by 1.5-5.5 kcal/mol. In total, however, the co nformer most stable in the gas phase remains the dominant conformer al so in the aqueous solution. Solution structure simulations emphasize t he importance of water-solute hydrogen bond formation. The 4-hydroxybe nzoic acid solute forms four to five hydrogen bonds with the surroundi ng water molecules. This value is two to four for the 2-OH isomers dep ending on the number of the intramolecular hydrogen bonds. Solute-wate r hydrogen bonds are shorter and more localized with acceptor rather t han with donor water molecules. The water molecules around the nonpola r part of the solute are located at a distance of 3-4 angstrom from th e ring atoms. Calculated hydrogen bond geometries were compared with e xperimental values referred to the crystalline phase and available in the literature. Intermolecular hydrogen bonds with water in solution e xhibit geometries similar to those in the crystalline phase. These hyd rogen bonds are slightly bent in contrast to the intramolecular hydrog en bonds in the 2-OH derivative, in both the gas and the crystalline p hases.