No abstract

The crystal structure prediction of the possible stable packings of pharmaceutical drug 4amino-2-hydroxybenzoic acid was initiated through ab initio methods. The lattice energy values of the hypothetical conformers of the molecule generated for the global search were minimized, employing the associated distributed multipolar electron density. The crystal packing with minimum global energy corresponds to the experimental crystal. The conformer generated from the valid minimization was subjected to Quantum Theory of Atoms In Molecules (QTAIM) analysis in order to improve insight on the chemical properties of the crystal on which the pharmaceutical activity depends. The electron density and the Laplacian of the electron density were analyzed in detail for the non-covalent interactions in the crystal. While the dimer formed by the COOH/COOH homo-synthon has the strongest energy and is mostly electrostatic, other dimers formed in the crystal are mostly stabilized by dispersive forces. The complementarity of the inner and exterior electrostatic potential on the Hirshfeld was analyzed in the different crystal packings generated.

The crystal structure of procarbazine molecule was predicted using first principles of quantum mechanics. The gas phase optimization was carried out by density functional theory and the resulted geometric coordinates were utilized for the search of hypothetical packings which reveals the possible stable conformers under a repulsion alone potential field with minimum cell volume. The thermodynamically favor structure was resulted from the lattice energy minimization of these hypothetical structures from the using the repulsion-dispersion potential field. The stability of global minimum structure was confirmed from the hydrogen bond interactions and second derivative properties.

The conformational stability of sulfonamide derivatives was examined in the active site of Dihydropteroate synthase enzyme. The best docked conformer was identified via molecular docking approach. Possible stable packing of best docked conformer was predicted and evaluated from the intermolecular interactions. Further, the interactions of stable conformer with the active site residue was characterized by charge density analysis based on Bader’s Quantum Theory of Atoms in Molecule.