The Chicago Chromatography Discussion Group Presents
Molecular Modeling as a Screening Tool to Separate Enantiomers of Chiral Compounds Using Polysaccharide-based Chiral Stationary Phases for Orphan Drugs
Date: Tuesday, April 4, 2017
Speaker: Dr. David House*, Dr. Binwu Zhao*, Dr. Priyanka Sharma, Dr. Anil Oroskar (Orochem Technologies, Inc.), Xiaoyu Wang, Prof. Sohail Murad (Illinois Institute of Technology)
*presenters
Abstract:
The pharmacological activity of chiral substances in living systems differs since the human body is a highly chiral environment. Enantioselective differences exist in the pharmacokinetics and pharmacodynamics of the various pharmaceutical drugs sold as racemic mixtures. Purification of these racemic mixtures to create enantiopure drugs has become an intense priority for large pharmaceutical companies due to the findings that some enantiomeric forms of certain drugs are harmful to the human body. The design of chromatographic purification systems for the production of single enantiomer drugs is challenging and expensive for pharmaceutical companies. This is owed to the current ‘guess-and-check’ method where method development chemists must screen a large number of combinations of chiral stationary phases, mobile phases, pH, and temperatures to achieve acceptable separation and purification of racemic mixtures. To aid in the currently slow speed of chiral technology advancement, Orochem Technologies along with a molecular simulation team at the Illinois Institute of Technology (IIT) propose development of a predictive molecular model which can guide experimentation and aid its own research scientists as well as those at other drug companies to create solutions to the demanding separation problems. Our first phase of work includes modeling of Orochem’s CSP-1A chiral stationary phase, which we have validated in molecular dynamics simulations. The configurational behavior of the CSP-1A in various solvents in our simulation agrees with experimental observations. We have also developed protocols for generating parameters for both CSPs and chiral molecules utilizing Gaussian and RESP charge fitting. In our study, we have modeled the adsorption of flavanone enantiomers to CSP-1A in various solvent environments and shown agreement with experiments performed on chiral HPLC experiments. We are working to optimize the force field parameters currently to further enhance the effect of various solvents with changing polarity. The successful development of our predictive model will have a substantial impact on the drug development industry. Our proposed molecular model will accelerate drug discovery in pharmaceutical companies and allow for unique drug formulations to be available in the market to consumers that are relying on them for treatment and to extend their lives.
Dr. Binwu Zhao Binwu Zhao attended Zhejiang University in China majored in chemical engineering. He worked on aqueous two-phase polymerization and aerobic oxidative polymerization during in his undergraduate study. He came in 2010 to the US for his senior year through a program between Zhejiang University and North Carolina State University. He then joined Professor Carol K. Hall’s group in December 2010. He has been working on large-scale molecular modeling and multi-scale modeling of ordered/disordered proteins with both conventional molecular dynamics and enhanced sampling methods. He has also been working on the thermodynamic equation of state using statistical associating fluid theory (SAFT). Upon joining Orochem Technologies Inc. at the beginning of September, he has been working on developing a predicative model for chiral molecule separation on various chiral stational phases under different solvent conditions.
Dr. David House
David W. House received his Ph.D. in organic chemistry from the University of Illinois at Urbana-Champaign under the direction of Dr. William H. Pirkle. Dr. Housejoined Orochem Technologies in 2008 and is currently a Research Fellow. His responsibilities include the design, synthesis, and applications of chiral and traditional (non-chiral) liquid chromatographic stationary phases for UHPLC, HPLC, SFC (supercritical fluid chromatography), and SMB (simulated moving bed) chromatography. He also develops methods, applications, and processes for these various types of liquid chromatographic separations.
Dr. House has been instrumental in establishing, developing, and commercializing the chiral stationary phase and chiral separation business forOrochem. The chiral area focuses on polysaccharide-based chiral stationary phases. His expertise also includes novel HPLC stationary phases, column packing procedures,silica gel bonding techniques, and sub-two micron stationary phases for chiral and non-chiral applications.
Dr. House has extensive experience in polymer chemistry and organic synthesis. His numerous publications in polymer chemistry, with an emphasis in polyurethane and polyurea chemistry, address topics on synthesis, morphology, kinetics, and materials testing.
He is the inventor or co-inventor on 51 U.S. patents, 9 foreign patents, and has several patents pending. Twelve of these patents deal specifically with chiral separations. He is the author of over 35 professional publications, 18 presentations at professional society meetings, and several poster presentations.
LC School Reviews
“I now have a better understanding of how HPLC works and why column choice is so important.”
“It is a fantastic course for learning the theory of LC and method development”
“The instructor, Merlin Bicking, is very helpful. It was great to see how wiling he is to answer questions and all the variety of methods he worked on.”
“I am just beginning my position from out of school. I found the course very insightful in terms of preparation for my future career”
“It is very useful for me because having hands on experience, which helped me to understand more of HPLC.”
“Great class. Would easily take again and recommend Dr. Merlin anytime. Would love to take his other courses. If he had a book would quickly buy for reference.”
Binwu Zhao and David House
The Chicago Chromatography Discussion Group Presents
Molecular Modeling as a Screening Tool to Separate Enantiomers of Chiral Compounds Using Polysaccharide-based Chiral Stationary Phases for Orphan Drugs
Date: Tuesday, April 4, 2017
Speaker: Dr. David House*, Dr. Binwu Zhao*, Dr. Priyanka Sharma, Dr. Anil Oroskar (Orochem Technologies, Inc.), Xiaoyu Wang, Prof. Sohail Murad (Illinois Institute of Technology)
*presenters
Abstract:
The pharmacological activity of chiral substances in living systems differs since the human body is a highly chiral environment. Enantioselective differences exist in the pharmacokinetics and pharmacodynamics of the various pharmaceutical drugs sold as racemic mixtures. Purification of these racemic mixtures to create enantiopure drugs has become an intense priority for large pharmaceutical companies due to the findings that some enantiomeric forms of certain drugs are harmful to the human body. The design of chromatographic purification systems for the production of single enantiomer drugs is challenging and expensive for pharmaceutical companies. This is owed to the current ‘guess-and-check’ method where method development chemists must screen a large number of combinations of chiral stationary phases, mobile phases, pH, and temperatures to achieve acceptable separation and purification of racemic mixtures. To aid in the currently slow speed of chiral technology advancement, Orochem Technologies along with a molecular simulation team at the Illinois Institute of Technology (IIT) propose development of a predictive molecular model which can guide experimentation and aid its own research scientists as well as those at other drug companies to create solutions to the demanding separation problems. Our first phase of work includes modeling of Orochem’s CSP-1A chiral stationary phase, which we have validated in molecular dynamics simulations. The configurational behavior of the CSP-1A in various solvents in our simulation agrees with experimental observations. We have also developed protocols for generating parameters for both CSPs and chiral molecules utilizing Gaussian and RESP charge fitting. In our study, we have modeled the adsorption of flavanone enantiomers to CSP-1A in various solvent environments and shown agreement with experiments performed on chiral HPLC experiments. We are working to optimize the force field parameters currently to further enhance the effect of various solvents with changing polarity. The successful development of our predictive model will have a substantial impact on the drug development industry. Our proposed molecular model will accelerate drug discovery in pharmaceutical companies and allow for unique drug formulations to be available in the market to consumers that are relying on them for treatment and to extend their lives.
Dr. Binwu Zhao
Binwu Zhao attended Zhejiang University in China majored in chemical engineering. He worked on aqueous two-phase polymerization and aerobic oxidative polymerization during in his undergraduate study. He came in 2010 to the US for his senior year through a program between Zhejiang University and North Carolina State University. He then joined Professor Carol K. Hall’s group in December 2010. He has been working on large-scale molecular modeling and multi-scale modeling of ordered/disordered proteins with both conventional molecular dynamics and enhanced sampling methods. He has also been working on the thermodynamic equation of state using statistical associating fluid theory (SAFT). Upon joining Orochem Technologies Inc. at the beginning of September, he has been working on developing a predicative model for chiral molecule separation on various chiral stational phases under different solvent conditions.
Dr. David House
David W. House received his Ph.D. in organic chemistry from the University of Illinois at Urbana-Champaign under the direction of Dr. William H. Pirkle. Dr. Housejoined Orochem Technologies in 2008 and is currently a Research Fellow. His responsibilities include the design, synthesis, and applications of chiral and traditional (non-chiral) liquid chromatographic stationary phases for UHPLC, HPLC, SFC (supercritical fluid chromatography), and SMB (simulated moving bed) chromatography. He also develops methods, applications, and processes for these various types of liquid chromatographic separations.
Dr. House has been instrumental in establishing, developing, and commercializing the chiral stationary phase and chiral separation business forOrochem. The chiral area focuses on polysaccharide-based chiral stationary phases. His expertise also includes novel HPLC stationary phases, column packing procedures,silica gel bonding techniques, and sub-two micron stationary phases for chiral and non-chiral applications.
Dr. House has extensive experience in polymer chemistry and organic synthesis. His numerous publications in polymer chemistry, with an emphasis in polyurethane and polyurea chemistry, address topics on synthesis, morphology, kinetics, and materials testing.
He is the inventor or co-inventor on 51 U.S. patents, 9 foreign patents, and has several patents pending. Twelve of these patents deal specifically with chiral separations. He is the author of over 35 professional publications, 18 presentations at professional society meetings, and several poster presentations.
LC School Reviews
“I now have a better understanding of how HPLC works and why column choice is so important.”
“It is a fantastic course for learning the theory of LC and method development”
“The instructor, Merlin Bicking, is very helpful. It was great to see how wiling he is to answer questions and all the variety of methods he worked on.”
“I am just beginning my position from out of school. I found the course very insightful in terms of preparation for my future career”
“It is very useful for me because having hands on experience, which helped me to understand more of HPLC.”
“Great class. Would easily take again and recommend Dr. Merlin anytime. Would love to take his other courses. If he had a book would quickly buy for reference.”