Research ArticlesMolecular Modeling Study Of Chiral Drug Crystals: Lattice Energy Calculations
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INTRODUCTION
Molecular modeling uses computational methods to study various chemical and biological systems. In recent years this technique has emerged as an important tool for predicting and correlating the energies and properties of molecules of known and unknown structures in chemical, biological, and pharmaceutical research.1,2 One of the major advantages of computer modeling over experiment is that the interaction energy and its variation with structure may be investigated at the atomic and molecular
EXPERIMENTAL SECTION
The model compounds used in this work were selected based on the availability of crystal structural data, and are listed in Table 1 together with the acronyms that are employed in this report.
RESULTS AND DISCUSSION
The crystal structures of a number of homochiral and racemic crystals are available either through structural determination reported in this work or through a search of the CSD (Table 1). Ephedrine and its N‐methyl derivatives and their salts were used as structurally related model compounds, collectively termed ephedrine derivatives. Although the crystal structures of many chiral compounds are available, few have known structures for both the homochiral and racemic crystals, and even fewer for
CONCLUSION
The contributions of the individual energy components, namely van der Waals interactions, electrostatic interactions, and hydrogen bonding, to the total lattice energy were calculated for a number of organic pharmaceutical crystals, and the individual correlations with their physical properties were investigated. Among the ephedrine bases and their salts, the electrostatic interaction correlates with the relatively large increases of melting temperatures of the salts, while the van der Waals
ACKNOWLEDGEMENTS
The authors thank the following: Dr. William B. Gleason, Department of Laboratory Medicine and Pathology, University of Minnesota, for advice on crystal structure analysis of several compounds; Ms. Shuxuan Chao of 3M Pharmaceuticals for statistical analysis; the Pharmaceutical Research and Manufacturers of America Foundation for an Advanced Predoctoral Fellowship for Z. J. Li; and the Supercomputer Institute of the University of Minnesota for supporting our use of the Medicinal
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