Ab initio prediction of the polymorphic structures of pyrazinamide: A validation study

Abstract

A validation study to predict the possible stable polymorphs of Pyrazinamide within a low energy conformational region of the flexible torsion angle was made through a potential energy surface (PES) scan by gas phase optimisation using the MP2/6-31G(d,p) method. Hypothetical crystal structures with favourable packing density for each of the stable conformers generated from the PES scan were generated using a global search with a repulsion only potential field. The densest crystal structures with stable energy were analyzed with more accurate lattice energy minimisation via distributed multipole analysis using a repulsion-dispersion potential. The stability of the predicted crystal structures with similar close packing to the known experimental polymorphs of Pyrazinamide molecule was analyzed by inspecting their intermolecular short contacts. Studies to analyze the second derivative mechanical properties from the hessian matrix were carried out to emphasise the thermodynamic stability of predicted polymorphs of Pyrazinamide.

Keywords

• Ab initio crystal structure prediction
• polymorphs
• PES scan
• Lattice energy minimisation
• Hirshfeld surface