Virtual Design of Chiral Alignment Materials for Determination of Absolute Configuration of Complex Molecules

Properties of organic molecules are defined by the chemical composition, stereochemistry and configuration. The latest are of the particular importance as molecules often exist in enantiomeric forms characterized by distinct properties, e.g. by anesthetic/ analgesic effects on pregnant women (R-Thalidomide) to teratogenic malformations of born children (S-Thalidomide). Therefore, determination of absolute configuration of chiral organic compounds has became a crucial task of chemistry and it is extremely challenging up to now. Next to time-consuming X-ray crystallography, spectroscopic methods may be used for configuration determination. However, only NMR spectroscopy is amenable to more complex molecules, as only this technique allows the extraction of atomically resolved structural information. Unfortunately, flexibility of molecules and similarity of binding affinity to conventional alignment media limit routine applications of this method. Accelerated development of new chiral alignment materials is needed. In the proposed project, we will develop new information-driven algorithms and tools towards virtual design of chiral alignment media allowing fast configurational analysis of complex bioactive molecules using atomistic and quantum mechanical calculations coupled with experimental feedback loops.