Ab initio investigations on the local anesthetics procaine, lidocaine and heptacaine

Abstract

A minimal basis set ab initio SCF MO method has been used to find the stable conformations of the polar COO, NHCO and NHCOO groups in the methyl ester of 4-aminobenzoic acid (I), 2,6-dimethylacetanilide (II) and the methyl ester of 2-methoxyphenylcarbamic acid (III) which are models for the local anesthetics procaine, lidocaine and heptacaine, respectively. For both I and III the most stable conformations were found to be the planar forms in which COO and NHCOO groups lie in the plane of the aromatic ring. For II the most stable conformer is nonplanar with the angle of rotation of the NHCO group out of the benzene ring plane equal to 60°. Further, the electrostatic molecular potential contour maps were evaluated for models I–III. The calculations show that the aromatic parts of these drugs possess large negative potential regions which are essentially a superposition of substituent nitrogen and oxygen atoms, as well as resulting from the π-electrons of the aromatic ring. Therefore, the parts of the local anesthetics investigated may act as electron donor sites in drug—receptor interaction.