Quantum chemical calculations on the intramolecular hydrogen bond of cis-urocanic acid

Abstract

The intramolecular hydrogen bond (IMHB) of the neutral, cationic, and anionic cis-urocanic acid ( cis-UCA, (Z)-3-(I′ H-imidazol-4′(5′)-yl)propenoic acid) is studied using ab initio calculations up to the MP2/6-31+G** level of theory. The IMHB energies are estimated by first showing a near to perfect linear correlation between the hydrogen bond energies of modified cis-urocanic acid structures and the Mulliken bond orders of their hydrogen bonds — the electron densities at the critical points of the hydrogen bonds have a weaker correlation with the hydrogen bond energies than the bond orders — and then using this correlation in order to evaluate the IMHB energies of the cis-UCA structures themselves. This method gives high (>50 kJ mol −1) IMHB energies for the neutral and cationic cis-UCA structures and very high (>100 kJ mol −1) IMHB energies for the anionic cis-UCA structures in the gas phase. The effect of salvation on the IMHB in cis-UCA is studied using both MP2/6-31G* water–UCA supermolecule optimizations and HF/6-31G* SCI-PCM (self-consistent isodensity polarized continuum model) reaction field calculations. Solvation changes the IMHB energies by upto 30 kJ mol −1. The IMHB of the imidazole protonated structures is weakened, while that of the carboxylate group protonated structures is strengthened in aqueous solution. Solvation does not change the optimal conformation of cis-UCA from the IMHB-ed closed conformation to an open conformation. The supermolecule calculations and the SCI-PCM calculations give consistent changes of the IMHB strengths in aqueous solution. Inclusion of only 1–3 water molecules nearest to the IMHB seems to be enough to demonstrate most of the solvent effect on the IMHB. The semiempirical AM l method is shown to be a valuable tool in finding good initial positions for the water molecules in ab initio calculations. The adequacy of cis-UCA as a model compound for the hydrogen bonded His–Asp component of the catalytic triad in serine proteases is investigated. The IMHB in the anionic cis-UCA is a low-barrier hydrogen bond (LBHB) in the gas phase, while the IMHB in the neutral cis-UCA is not. In aqueous solution, modeled by HF/6-31G* SCI-PCM calculations, the IN4HB in both the neutral and the anionic cis-UCA seems to be an LBHB. The anionic cis-UCA is suggested as an experimental model for the initial state, and the neutral cis-UCA as that for the final state of the proton transfer process in the His–Asp system of the catalytic triad