High Tech with a Human Touch
ALAN B. BROWN
Associate Professor of Chemistry
A.B., Middlebury College, 1979
Ph.D., University of Wisconsin-Madison, 1986
NIH Fellow, Columbia University, 1986-1988
Phone: (321) 674-7433
Office: 322 Olin Physical Sciences Building
Structural organic chemistry: the interplay of macroscopic properties and molecular structure.
The development of molecular sensors is the focus of great interest world-wide. Our program in this area is a collaboration with Clayton Baum's group, and shows how fundamental science can broaden into applied work. Carbazoles fluoresce; the fluorescence is quenched by several hydrogen-bond acceptors including pyridine. To test whether the carbazole-pyridine hydrogen bond is directly involved in quenching, or acts simply as a "hook", we prepared 1 and are in the process of preparing 2.
Each contains one carbazole grouping and one pyridine, in proximity; 1 can form an intramolecular hydrogen bond, but 2 cannot. The fluorescence of 1 is quenched as expected, but not quantitatively, even though free pyridine quenches free carbazole quantitatively. However, excess ammonia (or a hydrazine) restores the fluorescence of 1, by disrupting the hydrogen bond. Two conclusions follow: (1) the hydrogen bond is directly involved in quenching; (2) calibration of fluorescence intensity versus analyte concentration lets 1 act as a sensor. Sensor 1 can detection hydrazine concentrations down to 100 ppb, versus a regulatory limit of 10 ppb; the limitation is the background fluorescence.
A clue to the non-quantitative quenching is furnished by the X-ray crystal structure of 1, in which the pyridine part structure is twisted 53º from the carbazole plane. Apparently the sulfur bridges hold the carbazole and pyridine too far apart for internal hydrogen bonding, and twisting is needed to form the hydrogen bond. Second-generation sensors under construction incorporate oxygen bridges (3), providing a higher proportion of hydrogen-bonded conformations; substitution on the pyridine ring (e.g., 4), to keep the flexibility afforded by sulfur bridges but provide stronger hydrogen bonds; and quenching by acridine (5), whose energy levels differ from those of pyridine. The same principles can extend to sensors for other hydrogen-bonding analytes.
Other research in progress includes theoretical studies of annulation effects, particularly on valence isomerism of aromatics, in collaboration with Paul Kiprof (University of Minnesota - Duluth); experimental work on organophosphorus photochemistry, in collaboration with György Keglevich (Technical University of Budapest, Hungary); NMR studies of nitrogen heterocycles, in collaboration with Ashraf Aly (El-Minia University, Egypt); and whole-animal NMR studies of live fish, in collaboration with Jon Shenker (Florida Tech Department of Biological Sciences).