Combined Experimental and Computational Studies of Pyrazinamide and Nicotinamide in the Context of Crystal Engineering and Thermodynamics

Abstract

Pyrazinamide and nicotinamide constitute small, rigid molecules, which are of importance in several areas of science, including crystal engineering, chemical synthesis, biochemistry, and pharmacy. This contribution is dedicated to the comprehensive study of experimental charge density distributions and computational analysis of the β form of pyrazinamide and α form of nicotinamide. Static electron density distribution is obtained through application of Hansen and Coppens multipolar formalism, and further analyzed via Bader’s quantum theory of atoms in molecules (QTAIM). Geometrical and electron density features of both crystals, such as atomic charges, bond critical points, electrostatic potential and experimentally derived intermolecular interactions are described and compared. The presence of the additional nitrogen atom in the aromatic ring of pyrazinamide, when compared to nicotinamide, has, as expected, a major influence on the surrounding atoms, including the amide moiety (0.2 e difference on the ca...