CHARACTERIZATION OF THE SHORT STRONG HYDROGEN-BOND IN BENZOYLACETONE BY AB-INITIO CALCULATIONS AND ACCURATE DIFFRACTION EXPERIMENTS - IMPLICATIONS FOR THE ELECTRONIC NATURE OF LOW-BARRIER HYDROGEN-BONDS IN ENZYMATIC-REACTIONS

The intramolecular hydrogen bond in benzoylacetone has been studied wi th high-level ab initio Hartree-Fock and density functional theory met hods. The results are compared to the experimental structure as obtain ed from low-temperature neutron and X-ray diffraction experiments. The calculations reveal that electron correlation effects are essential f or modeling the experimental low-temperature neutron diffraction struc ture of benzoylacetone. At the B3LYP/6-311G(d,p) level of theory the i ntramolecular oxygen-oxygen distance is found to be 2.51 Angstrom and the hydrogen bond energy can be estimated to be 16 kcal/mol. The trans ition state for intramolecular hydrogen transfer was located with the barrier estimated to be about 2 kcal/mol, consistent with a low-barrie r hydrogen bond. Upon addition of the zero-point vibration energies to the total potential energy, the internal barrier vanished, overall su ggesting that the intramolecular hydrogen bond in benzoylacetone is a very strong hydrogen bond. Analysis of the electron density with the ' 'atoms in molecules'' theory revealed that both oxygen-hydrogen bonds have some covalent character. Theoretical atomic charges and the dipol e moment were computed by fitting point charges to the electrostatic p otential of the molecule. Excellent quantitative agreement is found fo r most properties of the charge density whether determined computation ally or by X-ray diffraction. Both methods reveal that the oxygen and hydrogen atoms have substantial atomic charges, and consequently the r esonance assisted hydrogen bond in benzoylacetone is best described as a 3-center, 4-electron sigma-bond with considerable electrostatic as well as covalent bonding contributions. The present study implies that if low-barrier hydrogen bonds (LBHB) are formed in enzymatic reaction s, they possess covalency between the hydrogen atom and both heteroato ms in question. Furthermore, it is expected that large atomic charges will be found in the LBHB, which give rise to an additional electrosta tic stabilization of the system.