A computational investigation of boron-nitrogen containing complexes and their putative physiological activity

Some boronated molecules have shown surprising physiological action, however, the mode of action of these compounds is not understood. Our hypothesis is that the boron moiety is attracted to Lewis base sites on an enzyme and the resulting interaction causes an inhibition of the physiological pathway. To study this problem, quantum mechanical calculations of boron-nitrogen bond dissociation energies for twelve molecules have been calculated and compared with certain physiological activities. Results of linear correlation analysis between bond dissociation energy and physiological action have shown evidence that our hypothesis has merit. Possible locations of enzyme inhibition by boronated compounds are presented. In addition, structural and energetic features of boronated molecules, including intramolecular electrostatic interactions and Lewis acidity, are discussed.; Ab initio calculations were carried out on a series of amine boranes to investigate the nature of competitive Lewis acid/base chemistry for these systems. Barrier height, bond dissociation energy and reaction energies were determined for all borane transfer reactions with additional free energy calculations performed in some systems. In general, barrier heights of transfer were lower than the energy required to dissociate the B-N adduct bonds. The lowest energy transfer pathway appears to be a S_N2 type reaction.; Molecular mechanics parameterization for tetravalent boron containing molecules has been performed utilizing the geometries, vibrational frequencies and torsional energy profiles from ab initio optimizations and known experimental values. Using a class of 12 training molecules, the MM3 force field has been expanded for studies of boronated compounds. The new parameters have been found to reproduce molecular geometries and vibrational spectra for the training set.; The university-student traditional model is being challenged by the emergence of web-based distance education. Presently, lower level courses are made very general so as to appeal to a focused local student base with diverse interests. With the web, courses can be designed to appeal to a dispersed student base with a focused interest. Our project is the design of a specific one such course in chemical toxicology we are developing for members of hazardous materials squads of fire departments.