AB-INITIO STUDY OF ENERGETICS OF X-H-CENTER-DOT-CENTER-DOT-CENTER-DOT-PI (X = N, O, AND C) INTERACTIONS INVOLVING A HETEROAROMATIC RING

The possibility of the pi-face of a heterocyclic ring acting as a hydr ogen-bond acceptor has considerable significance in the structure and binding of cofactors and nucleic acids to proteins. This interaction h as been modeled using ab initio calculations on various complexes of p yridine with water, ammonia, methane, and benzene. Both Hartree-Fock ( HF) and MP2/6-31G(d,p) calculations, including counterpoise correction s, have been carried out on a number of representative geometries. In addition to the expected hydrogen-bonded structure involving the nitro gen lone pair, a number of other orientations in which X-H is placed a bove the pi-face are also found to be energetically favorable. The max imum stabilization is found directly above the pyridine nitrogen for w ater and ammonia, whereas for methane it is shifted to a point halfway toward the ring center. The corresponding complexation energies are 2 .9 (X = O), 1.8 (N), and 0.8 (C) kcal mol(-1), which are 0.45, 0.56, a nd 0.71, respectively, of the values obtained when the interaction is in the conventional hydrogen-bonded geometry. Bifurcated structures, w ith the XH2 group above the pyridine ring but displaced from the cente r toward the nitrogen, are also found to be fairly stabilized. A herri ngbone structure with two of the benzene C-H bonds facing the pyridine ring is computed to have a stabilization energy of 2.7 kcal mol(-1), which is greater by 0.4 kcal mol(-1) than that for the linear C-H...N hydrogen-bonded geometry involving the nitrogen lone pair. The interac tion energies with the pi-face are of comparable magnitude for benzene and pyridine. The computed relative energetics for various geometries should be useful in developing potential functions for modeling the b inding of cofactors and nucleic acids with proteins.