Since the advent of the Hammett equation (1935) and our extension of it (1962) to a generalized form for quantitative structure-activity relationships (QSAR), thousands of such equations have been published. Indeed, the plethora of equations in a wide variety of journals on numerous diversified systems (DNA, enzymes, organelles, cells, membranes, whole organisms) makes it impossible to keep account of what has been done. Our own databank, contains 6000 equations evenly split between physical organic chemistry and biological reactions. Each equation encapsulates a mechanistically based quantitative structure activity relationship from which predictions can be made about other congeneric molecules interacting with the same system. This is the first level of mechanistic understanding. A second level is possible when bond making or breaking occurs in the biological reaction. These QSAR can often be related to similar organic reactions via electronic terms in the QSAR. A third level of understanding comes-when the biological QSAR can be' related to each other in groups. The ultimate step is to develop relationships between groups of QSAR. We have developed a highly efficient computer program to make such comparative studies of QSAR. We are particularly interested in the toxicity of radicals. We plan systematic studies of chemicals for which we have found evidence that their toxicity depends on radical formation; i.e., aromatic compounds containing hydroxy, amino or benzylic hydrogens. We propose to do this using cell culture systems. The objective is to develop a mechanistic predictive toxicology based on physical organic chemistry tenets of QSAR.

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Pomona College
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Hadjipavlou-Litina, D; Garg, Rajni; Hansch, Corwin (2004) Comparative quantitative structure-activity relationship studies (QSAR) on non-benzodiazepine compounds binding to benzodiazepine receptor (BzR). Chem Rev 104:3751-94
Garg, Rajni; Kurup, Alka; Mekapati, Suresh B et al. (2003) Searching for allosteric effects via QSAR. Part II. Bioorg Med Chem 11:621-8
Hansch, Corwin; Garg, Rajni; Kurup, Alka et al. (2003) Allosteric interactions and QSAR: on the role of ligand hydrophobicity. Bioorg Med Chem 11:2075-84
Verma, Rajeshwar P; Kapur, Sanjay; Barberena, Omar et al. (2003) Synthesis, cytotoxicity, and QSAR analysis of X-thiophenols in rapidly dividing cells. Chem Res Toxicol 16:276-84
Hansch, Corwin; Steinmetz, Wayne E; Leo, Albert J et al. (2003) On the role of polarizability in chemical-biological interactions. J Chem Inf Comput Sci 43:120-5
Hansch, Corwin; Jazirehi, Ali; Mekapati, Suresh Babu et al. (2003) QSAR of apoptosis induction in various cancer cells. Bioorg Med Chem 11:3015-9
Hansch, Corwin; Bonavida, Benjamin; Jazirehi, Ali R et al. (2003) Quantitative structure-activity relationships of phenolic compounds causing apoptosis. Bioorg Med Chem 11:617-20
Kurup, Alka; Mekapati, Suresh B; Garg, Rajni et al. (2003) HIV-1 protease inhibitors: a comparative QSAR analysis. Curr Med Chem 10:1679-88
Garg, Rajni; Kurup, Alka; Mekapati, Suresh Babu et al. (2003) Cyclooxygenase (COX) inhibitors: a comparative QSAR study. Chem Rev 103:703-32
Selassie, Cynthia D; Garg, Rajni; Kapur, Sanjay et al. (2002) Comparative QSAR and the radical toxicity of various functional groups. Chem Rev 102:2585-605

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