The Organic and Macromolecular Chemistry Program in the Chemistry Division at the National Science Foundation supports Professor Jack Saltiel of Florida State University, who will study photochemical processes in the vitamin D field. He will investigate their medium dependence in order to resolve experimental discrepancies and to achieve the mechanistic understanding needed for theoretical advances. Photochemical and spectroscopic observations will be employed to characterize the photochemistry and photophysics of individual ground state conformers obtained by rotation about essential single bonds. The goal is to resolve composite responses into the individual responses of each molecular entity that contributes to the measured quantity. The research also involves synthesis of molecules designed to test theories on the photophysical and photochemical responses of organic molecules to light absorption. The research aims to provide the experimental foundation to gain a theoretical understanding of the behavior of electronically excited states.
Broader impacts of the research are to understand the central role of the processes that trigger natural responses to light, as in vitamin D formation in the skin, in vision, and in photosynthesis. The theory of electronically excited states is a scientific frontier whose progress relies on valid experimental conclusions such as those provided by this research. Other broader impacts expected to result from the funded research are to continue the long and uninterrupted string of undergraduates who have prospered by participation in research with Professor Saltiel. For example, of the recent students, two have earned PhDs in biochemistry and biophysics from Rice and Stanford Universities; one student was an NSF Graduate Fellow at UC Berkeley and is now at Harvard Law School; two students are currently Biophysics graduate students at Caltech and Yale. With respect to gender, one female NSF graduate fellow in Biophysics now at Yale, was a freshman music major when she joined Professor Saltiel's research group. Finally, a female Hispanic student who spent a summer in Professor Saltiel's lab later became an NSF Graduate Fellow in Biochemistry at UNC Chapel Hill and is currently a postdoctoral fellow at Northwestern University.
Intellectual merit: Light absorption elevates molecules to higher energy states. Molecules in their normal – ground – and in their excited states differ in structure and reactivity. Easy structural changes in the ground state are difficult in the excited state and vice versa. Examples are the transformation – photochemistry – in rhodopsin that leads to light detection and vision and the light induced transformation in the skin that converts provitamin D to vitamin D. Our research has led to a better understanding of the events that lead to photochemical transformations in such molecules. Apart from advancing knowledge, such understanding provides the experimental scaffold for evaluation of theory. This is essential because, although theoretical predictions about the behavior of ground state molecules are very reliable, excited state theory is not similarly advanced. Flexible molecules exist in different interconverting structures in their ground state. Such structures – conformers – can be excited selectively because each absorbs and emits light energy of different wavelengths with different efficiency – each has different absorption and emission spectra. Freely interconverting ground state conformers do not interconvert in the excited state where each has its own photophysical and photochemical properties. Conformer specific photochemistry was first applied to explain qualitatively the photochemical responses of the previtamin D, the molecule that gives vitamin D both in the skin and industrially. We advanced that understanding from the qualitative to the quantitative, and in that process corrected wrong conclusions about the structural motions that convert the excited state of provitamin D to previtamin D and the excited state of previtamin D to its photoproducts. Required was determination and structure assignment to previtamin D and photoproduct conformer spectra – a difficult task because the spectra of the conformers overlap strongly. Their resolution required development of computer programs that allow application of statistical analysis to families of spectra. The analytical methods that we pioneered are generally applicable to the treatment of complex, multicomponent spectral mixtures that are encountered across all scientific disciplines. Using model molecular systems we studied the effect of the medium – changing the solvent or its viscosity by cooling it to a glass – on excited state reactions. The rigidity of glassy media restricts the volume available for molecular transformation, mimicking restrictions imposed on molecules in protein environments. We found that certain molecules related to rhodopsin respond to space limitations by undergoing a volume conserving transformation that resembles the motion of a bicycle pedal shaft. That motion was proposed in 1976 by A. Warshell – a 2013 Chemistry Nobel prize winner – to account for the photoreaction of rhodopsin. Our discovery of the bicycle pedal photoreaction in glassy media at low temperature and in the crystalline state at room temperature suggests that Warshell was correct in applying the concept to rhodopsin. We achieved a better understanding of the photophysical responses of diphenylacetylene – a rigid molecule used as a conduit of electrons and energy in materials science. Its lowest excited state was thought to be a "dark state" because no one had observed it to emit light. We showed that conclusion to be wrong by finding its weak emission spectrum. Implications to cancer phototherapy are exciting because our colleague, Igor Alabugin, has shown that structural analogues of diphenylacetylene selectively target cancer cells, destroying them upon light activation. We initiated extension of this research to those diphenylacetylene relatives. Broader impacts: The major impact of the research resides in the educational opportunities it provided. It was carried out by a visiting professor, 4 postdoctoral fellows, 2 graduate and 18 undergraduate students. Each was an apprentice in the art of collecting and interpreting reliable observations. With past experience as a guide, many of them will go on to outstanding careers in academia and industry, in medicine, in teaching and in other related professions. Two of the senior coworkers have college faculty positions in India, one in Poland, one in the US and the fifth is a US industrial research chemist. Both graduate students started research in my lab as undergraduates – the only two of 111 to do so. Stuart Hutchinson is now a High School Chemistry teacher and Christopher Redwood will earn his Ph.D. in the spring 2015 term and will be entering medical school in fall 2015. Redwood has demonstrated exquisite mathematical and computer skills that have advanced our research and are unmatched by any former coworkers. Several undergraduates are in or are planning to go to medical school and at least 5 – all female – are in or planning to go to graduate school. I expect much from Kelly Pawlak, a standout in my Organic Chemistry class who, after starting photochemical research, switched majors from Biology to Chemistry and then Physics. Kelly now holds a prestigious NSF fellowship as a first year Physics graduate student at UC, Santa Barbara.
