klopman_300pxCharles F. Mabery Professor Emeritus of Research in Chemistry

Professor of Oncology and Environmental Health Sciences
Director of the Laboratory for Decision Support Methodologies
Adjunct Professor of Environmental and Occupational Health, University of Pittsburgh

 

216.368.3618      gklopman@multicase.com      Millis 223

Interests: Biochemistry, Organic Chemistry, Bio-Organic Chemistry, Environmental Health Sciences, Medicinal Chemistry, Oncology, Theoretical Chemistry

L. es Sc., University of Brussels (Belgium), 1956
Dr. es Sc., University of Brussels, 1960
Postdoctoral Fellow, University of Texas, 1965-66

Structure-Activity Studies of Biologically Active Molecules

Professor Klopman has worked on problems related to the evaluation of chemical reactivity for most of his career. His interests range from experimental determination of reactivity indices and substituent constants to the development of reactivity theories . His description of the concept of charge and orbital controlled reactions is now widely used to explain the ambident selectivity of nucleophiles and links the linear free energy type correlations to more fundamental chemical concepts. His interest in quantum mechanics and in computers has led him to design and program the first semi-empirical method for the calculation of the properties of saturated molecules that later became known as MINDO. Professor Klopman’s interests have gradually moved toward problems of artificial intelligence and its general use to correlate biological data.

As part of this effort, his group has developed a set of computer packages to represent and manipulate chemical data. His group’s activity now focuses primarily on the determination of quantitative structure activity relationships in both carcinogenic and chemotherapeutic agents. This consists of developing computer simulations of the actions of drugs, such as N -nitroso derivatives (see figure) on cancer and normal cells. Correlations are then sought between the chemical structure of the drugs and their activity in order to produce better antitumor agents.

In a related project, quantitative relationships are sought between the nature and intensity of odors and their chemical structure. This project is sponsored by the perfume industry.

In both projects, experimental investigations are conducted in conjunction with their computational counterparts in an effort to gain a better picture of the chemical-receptor interaction mechanism.

Selected Publications
  • “Computer Automated Predictions of Aerobic Biodegradation Transforms in the Environment.” Klopman, G., Zhang, Z., & Balthasar, D. M . Environmental Toxicology and Chemistry, 14, (1995).
  • “Structural Basis for the Induction of Preneoplastic Glutathione S-Transferase Positive Foci by Hepatocarcinogens.” Sakai, T., Klopman, G., & Rosenkranz, H. S. Teratogenesis, Carcinogenesis and Mutagenesis, 14, 219-237 (1994).
  • “META I. A Program for the Evaluation of Metabolic Transformation of Chemicals.” Klopman, G., Dimayuga, M., & Talafous, J. J. Chem. Inf. Comput. Sci., 34, 1320-1325 (1994).
  • “Structural Determinants of Developmental Toxicity.” Takihi, N., Rosenkranz, H. S., Klopman, G., & Mattison, D. R. Risk Analysis, 14, 649-657 (1994).
  • “Application of the Multiple Computer Automated Structure Evaluation Methodology to a Quantitative Structure-Activity Relationship Study of Acidity.” Klopman, G., & Fercu, D. J. Comp. Chem., 15(9) , 1041-1050 (1994).
  • “In vitro Anti- Mycobacterium avium Activities of Quinolones: Predicited Active Structures and Mechanistic Considerations.” Klopman, G., Li, J.-Y., Wang, S., Pearson, A. J., Chang, K., Jacobs, M. R., Bajaksouzian, S., & Ellner, J. J. Antimicrobial Agents and Chemotherapy, 38, 1794-1802 (1994).