Experimentation with different thermodynamic cycles used for pKa calculations on carboxylic acids using Complete Basis Set and Gaussian-n Models combined with CPCM Continuum Solvation Methods

Complete basis set and Gaussian-n methods were combined with Barone and Cossi's implementation of the polarizable conductor model (CPCM) continuum solvation methods to calculate pKa values for six carboxylic acids. Four different thermodynamic cycles were considered in this work. An experimental value of −264.61 kcal/mol for the free energy of solvation of H+, ΔGs(H+), was combined with a value for Ggas(H+) of −6.28 kcal/mol, to calculate pKa values with cycle 1. The complete basis set gas-phase methods used to calculate gas-phase free energies are very accurate, with mean unsigned errors of 0.3 kcal/mol and standard deviations of 0.4 kcal/mol. The CPCM solvation calculations used to calculate condensed-phase free energies are slightly less accurate than the gas-phase models, and the best method has a mean unsigned error and standard deviation of 0.4 and 0.5 kcal/mol, respectively. Thermodynamic cycles that include an explicit water in the cycle are not accurate when the free energy of solvation of a water molecule is used, but appear to become accurate when the experimental free energy of vaporization of water is used. This apparent improvement is an artifact of the standard state used in the calculation. Geometry relaxation in solution does not improve the results when using these later cycles. The use of cycle 1 and the complete basis set models combined with the CPCM solvation methods yielded pKa values accurate to less than half a pKa unit. © 2001 John Wiley & Sons, Inc. Int J Quantum Chem, 2001

Accurate pKa Calculations for Carboxylic Acids Using Complete Basis Set and Gaussian-n Models Combined with CPCM Continuum Solvation Methods”

Complete Basis Set and Gaussian-n methods were combined with CPCM continuum solvation methods to calculate pKa values for six carboxylic acids. An experimental value of −264.61 kcal/mol for the free energy of solvation of H+, ΔGs(H+), was combined with a value for Ggas(H+) of −6.28 kcal/mol to calculate pKa values with Cycle 1. The Complete Basis Set gas-phase methods used to calculate gas-phase free energies are very accurate, with mean unsigned errors of 0.3 kcal/mol and standard deviations of 0.4 kcal/mol. The CPCM solvation calculations used to calculate condensed-phase free energies are slightly less accurate than the gas-phase models, and the best method has a mean unsigned error and standard deviation of 0.4 and 0.5 kcal/mol, respectively. The use of Cycle 1 and the Complete Basis Set models combined with the CPCM solvation methods yielded pKa values accurate to less than half a pKa unit.

Accurate relative pKa calculations for carboxylic acids using complete basis set and Gaussian-n models combined with continuum solvation methods

The complete basis set methods CBS-4, CBS-QB3, and CBS-APNO, and the Gaussian methods G2 and G3 were used to calculate the gas phase energy differences between six different carboxylic acids and their respective anions. Two different continuum methods, SM5.42R and CPCM, were used to calculate the free energy differences of solvation for the acids and their anions. Relative pKa values were calculated for each acid using one of the acids as a reference point. The CBS-QB3 and CBS-APNO gas phase calculations, combined with the CPCM/HF/6-31+G(d)//HF/6-31G(d) or CPCM/HF/6-31+G(d)//HF/6-31+G(d) continuum solvation calculations on the lowest energy gas phase conformer, and with the conformationally averaged values, give results accurate to ½ pKa unit. © 2001 American Institute of Physics.

The Use Of Amido- And Imido-Functionalized Alpha Hydroxy Acids In The Creation Of Biodegradable Polyesters: An Exploration Of Va

The purpose of this thesis was to synthesize biodegradable polyesters from a wide array of functionalized ¿-hydroxy acids. The initial strategy was to use amido-functionalized ¿-hydroxy acids and 2-bromopropanoyl bromide to form amido-functionalized cyclic diesters. Then, the resulting cyclic diesters would be used in ring opening polymerization to create biodegradable polyesters. However, the spontaneous rapid degradation of the secondary amido-functionalized cyclic diester structure, as seen with 2-benzamido-hydroxyacetic acid, limited ring formation to tertiary amido-functionalized ¿-hydroxy acids. Also, the hydrophilic nature of most ¿-hydroxy acids allowed water into the crystal structure of the ¿-hydroxy acid. Then, when the ¿-hydroxy acid was used in ring forming reactions, the associated water deactivated reactive reagents and limited cyclic diester synthesis. These issues led to the synthesis of hydrophobic and tertiary amido- and imido-functionalized ¿-hydroxy acids, 2-phthalimido-2-hydroxyacetic acid and 2-(1-oxoisoindolin-2-yl) hydroxyacetic acid. The new ¿-hydroxy acids were used in two new polymerization techniques, melt polycondensation and solution polymerization, instead of ring open polymerization. Melt polycondensation and solution polymerization had shown previous success in forming oligomers of amido-functionalized ¿-hydroxy acids. Melt polycondensation was conducted by heating the monomer past its melting temperature under reduced pressure. The uncatalyzed melt polycondensation of 2-(1-oxoisoindolin-2-yl) hydroxyacetic acid created polyesters (¿ 960 g/mol). The scandium(III) trifluoromethanesulfonate enhanced melt polycondensation polymerization created slightly larger oligomers (¿ 1340 g/mol). However, 2-phthalimido-2-hydroxyacetic acid was not compatible with melt polycondensation because thermal degradation occurred. Thus, solution polymerization was conducted via Steglich esterification. Only oligomeric functionalized polyesters were formed (¿ 1060 g/mol). Future work should focus on optimization of the catalyst and the reaction conditions to obtain higher molecular weight polyesters. Also, 2-(1-oxoisoindolin-2-yl) hydroxyacetic acid should be utilized in the cyclic diester synthesis technique.