Specific Objectives: Based on preliminary studies on the ditopic trans-phenylvinyl-bipy framework, the group will seek to (1) incorporate highly sensitive and selective zinc-coordination motifs into the trans-phenylvinyl-bipy framework to afford zinc-selective ditopic fluorescent probes with both sensitivity and effective concentration range suitable for physiological imaging; (2) establish general principles for achieving highly efficient intramolecular photoinduced electron transfer (PET) of trans-arylvinylbipy-based ditopic ligands in the absence of zinc, which is critical in creating large fluorescence contrast between free and zinc-bound forms of the probe molecules; (3) further develop triazolyl-containing tetradetate ligands with high sensitivity and selectivity to zinc that are amenable to ditopic ligand design; (4) develop zinc probes with both high sensitivity and large effective concentration ranges with long excitation and emission wavelengths deep in the visible region to prevent autofluorescence and photodamage of live biological samples.
Intellectual Merit: (1) The heteroditopic fluoroionophoric system provides a solution to a highly challenging scientific problem, which is the development of fluorescent probes for zinc ion that are effective over its entire 6 orders of magnitude physiological concentration range. The success of the proposed project will provide fluorescent probes for zinc ion capable of quantitative profiling of zinc flux in biochemical processes over large concentration ranges. Such information is indispensable to the elucidation of the physiological roles of zinc, and, in turn, will help in the diagnosis and cure of diseases including Alzheimer's where disruption of zinc homeostasis is evident. (2) The designed molecules provide an excellent platform for studying the impact of metal ion coordination on the excited states of organic molecules, which is important on a fundamental level. In summary, the success of this application will not only fill the gap in the development of live cell imaging technologies targeting the physiologically important zinc whose concentrations may vary over enormous ranges during cellular events, but also advance understanding of zinc coordination chemistry and coordination-driven photophysical processes.
Broader Impact: (1) The long-term objective of the PI's research program is the development of sensing technologies targeting substances of large physiological concentration ranges in signal transduction and metabolic pathways based upon fundamental understanding of coordination-driven photophysical processes. The principle of extending the analytical concentration range proposed herein for zinc ion can be applied to neutral and anionic species. (2) The coordination chemistry and photophysical processes studied in this application are expected to impact the development of technologies in other areas such as molecular logics and molecular electronics. (3) The diverse range of students participating in this project will receive interdisciplinary training encompassing synthetic, coordination, and analytical chemistry.
