Conformations, energies, and intramolecular hydrogen bonds in dicarboxylic acids: Implications for the design of synthetic dicarboxylic acid receptors

Abstract The various conformers of the dicarboxylic acids HO 2 C(CH2) n CO 2 H, n = 1–4, were obtained using density functional methods (DFT), both in the gas phase and in the aqueous phase using a polarized continuum model (PCM). Several new conformers were identified, particularly for the two larger molecules glutaric ( n = 3) and adipic acid ( n =4). The PCM results show that the stability of most conformers were affected, many becoming unstable in the aqueous phase; and the energy ordering of conformers is also different. The results suggest that conformational preferences could be important in determining the design and stability of appropriate synthetic receptors for glutaric and adipic acid. Geometry changes between gas and aqueous phases were most marked in those conformers containing an intramolecular hydrogen bond. Additional calculations have probed the strength of intramolecular hydrogen bonds in these dicarboxylic acids. In the cases of glutaric and adipic acid, the strength of the intramolecular hydrogen bond were estimated to be around 28–29 kJ/mol, without any vibrational energy correction. The intramolecular hydrogen bond energies in malonic and succinic acid were also estimated from the calculated H‐bond distances using an empirical relationship. Intramolecular H‐bond redshifts of 170–250 cm −1 have been estimated from the results of the harmonic frequency analyses. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 1233–1241, 2005