Simulation And Computational Chemistry On Molecular Fragments Of Repaglinide Form-i

Molecular simulation is to establish a molecular model at the atomic level, to simulate the structure of the molecule, and to further simulate the physical and chemical properties of the molecular system. Researchers at home and abroad have begun to use computer to simulate drug molecules and to transform, to get the drug properties and structure information, to provide guidance for the traditional organic synthesis of drug molecules. And the current research on repaglinide still in the experimental stage, and without the application of molecular simulation technology to carry on the simulation research and infrared attribution. This paper will take repaglinide crystal I as model compounds, the application of Materials Studio simulation study on repaglinide. Specific content as follows:1, the DMOL3 program, we made a theoretical study of repaglinide crystal form I structure and related properties(vibration frequency, reaction activity and stability), the molecular geometry optimization configuration and the atomic charge distribution and frontier molecular orbital energy level. The geometric and electronic structure, there is very important reference value; calculation results show, repaglinide crystal type I molecules tend to gain electrons, and electrophilic reaction most prone to N atoms in the six membered ring and benzene ring connected. These results have a certain guiding role for the design and synthesis of similar drugs.2, the fingerprint attribution is a difficulty, in this paper, based on the vibration frequency calculation, for the first time on repaglinide crystal type I molecules do infrared attribution, help review drug production preparation process quality control factors, control the quality of the drug.3, single molecular simulation and between individual frequencies of the calculated results and the experimental values exist certain differences, because between the molecules in the existence of intermolecular forces, in the traditional simulation method does not take into account the intermolecular force. In order to improve the traditional simulation method, explores the multi molecular fragment simulation method, considering the intermolecular forces, can improve the direct optimization of single molecules in the presence of defects, effectively improves the precision and accuracy of the infrared calculation values, infrared attribution of repaglinide crystal type I molecules. The method can also expand to other molecules of similar studies.