SYNTHESIS, ANALYSIS, TOXICITY SCREENING AND COMPUTATIONAL CHEMISTRY OF ARYLPHOSP

这个子项目是众多研究子项目之一

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Synthesis and characterization, toxicity screening, chromatography, and computational analysis of arylphosphonium cations conjugated with lipids or polypeptides will be done by undergraduate chemistry and biology students in which they will use experimental bench, instrumental, and computational chemistry methods learned in organic chemistry and microbiology and apply and refine them in application to a research project. The compound type is generally cytotoxic. It accumulates in mitochondria of malignant cells, binds to acetylcholineserase, shifts the melting curve of native DNA, kills a variety of gram-postive bacteria, and malignant cells in culture. QSAR, molecular mechanics, and molecular dynamics calculations will be done, repectively; to find correlations with and predictors of activity (QSAR), to determine DNA/Binder docking geometries and energies (mm), and to observe thermal degradation of dsDNA with and without a binder present (md). Reversed-phase HPLC and TLC using ion-pair techniques will be used to determine chromatographic constants that are physical correlates of bioavailability. Microscale synthesis, purification and analysis of compounds at the 50-100 mg scale will help students develop accuracy and precision in experimental technique. They will routinely prepare samples and acquire and analyze IR, NMR, UV and (in some cases) fluoresence spectra. LC-MS will be used in lieu of elemental analysis as verification of structure for new compounds. One or more will do Kirby-Bauer antibacterial screening. The students will earn money to support their education while gaining experience in laboratory research under the direction of faculty mentors. This will provide support and training for individuals who intend to pursue graduate work in chemistry, biology, medicine, or pharmacology, as well as help prepare them for entry-level (BA and BS) positions in chemistry, biology or health-related positions in industry. The high-profile presence of these students doing this work in our departments will help attract others to consider careers in research.