467 Acta Chim. Slov. 2017, 64, 467–478 Nidhin et al.: AB Initio Prediction of Stable Confomeric Polymorphs ... Scientific paper AB Initio Prediction of Stable Confomeric Polymorphs of Benzocaine Molecule- a Local Anaesthatic Molecule Pallipurath Veleelath Nidhin, 1 Arputharaj David Stephen 2,* and Charles Selvaraj Arun Paul 3 1 Department of Physics, Sri Shakthi Institute of Engineering and Technology, Coimbatore, India 641062 2 * Assistant Professor of Physics, Department of Physics, Sri Shakthi Institute of Engineering and Technology, Coimbatore, India 641062, Telephone: +91995227392 3 Department of Science and Humanities, Sri Krishna Institute of Engineering and Technology, Coimbatore, India-641008 * Corresponding author: E-mail: davidstephen_dav@yahoo.co.in Received: 21-02-2017 Abstract An ab initio methodology to predict the crystal structures of thermodynamically stable polymorphs of benzocaine wit- hin the least energy region of energy landscape by analyzing the local minima from the initial gas phase optimization initiated through the flexible torsion using MP2/6-31G(d,p) method. The global search for the hypothetical dense pac- king for the structures within the energy penalty region of the local minima have revealed the possible stable conformers under a repulsion alone potential field. The generated hypothetical dense packings from the global search were selected for lattice minimization using the repulsion – dispersion potential field to authenticate the stability. The stability and the characteristics of the generated structures were analyzed from the comparative hydrogen bond analysis and second de- rivative properties with the known experimental polymorphs. The morphological studies of the global minima of benzo- caine molecule from the valid lattice energy landscape was studied in detail to find the morphological important lattice. Keywords: Polymorphism, Ab initio crystal structure prediction, PES scan, Lattice minimization, 2D Finger print plot, Morphology. 1. Introduction Polymorphism is the ability of a flexible molecule to crystallize in different crystal lattice. As the physiochemical properties of the molecule depends on the crystalline para- meters of a molecule, the prediction of different polymorp- hic structures of a molecule in a crystal phase gains its im- portance. 1 Effect of polymorphs may alter the pharmaceuti- cal nature of flexible drug molecules which indeed exposed the search of polymorphs as commercially and academi- cally vital methodology. As the experimental methods to predict, the polymorphs have been considered to be tough to analyse, theoretical ab initio prediction methodology pa- ved the way in easy procedure with more accuracy. Recent reports have been justified the accuracy of Ab initio metho- dology in predicting the polymorphs of molecular solids. 2 The prior aim of the current research was to analyze the possible conformeric polymorphs of a local anesthetic molecule of Benzocaine. The reported analysis of the fle- xible benzocaine with a ester group attached to the aroma- tic ring, and the amino group attached in the para position to the ester group revealed the presence of three poly- morphic forms. The reports suggested that the structures were found to be stabilized through the hydrogen bond in- teraction between the carbonyl and amino group. The polymorphism exhibited by benzocaine showed the three forms, mainly Form I, Form II and Form III in crystal structure database. The needle like morphological crystals of Form I showed the deviation of the terminal ethyl and carbonyl functional groups from the plane of the phenyl ring, which have justified as the conformational changes in the alkyl ring , thereby increasing the possibility of exi- stence of conformational polymorphism. The Form II crystals are found to be in orthorhombic morphology im- plementing the P2 1 /c space group. The low temperature phase transition of form II molecule resulted the forma- DOI: 10.17344/acsi.2017.3312