The overarching theme of the proposed research program is to design modular organic receptors containing recognition elements that are optimized to bind anions in solution. The modularity allows for facile substitution of inherently fluorescent organic cores, recognition elements, linkers and functionality. This research will aid in the development of the next generation of molecular probes, sensors and binding agents for anions. The proposed receptors will also help provide a fundamental understanding of the structural role anions play in self-assembly and their interactions with electron- deficient aromatic rings. Long-term applications of this research include cellular and in vitro imaging of anions.
The specific aims of the proposed research are: 1) to synthesize and to study a series of receptors for anions resulting from the proposed modular design strategy, 2) to study the modular receptors as fluorescent molecular probes for applications in chemical biology, and 3) to study the interaction of anions with electron-deficient aromatic rings and design recognition elements to exploit this emerging anion-binding motif. The modularity of the proposed design strategy allows for exploration of a variety of recognition motifs for anions, including electrostatic attractions, hydrogen bond interactions and attractions with electron-deficient arenes (anion-pi, CH---X- hydrogen bonds and weak-sigma complexes). This flexibility allows for the possibility of selectively binding anions that are challenging to target with traditional approaches. Core and linker substitution provides another approach to tuning the selectivity of the receptors by changing the shape and size of the binding pocket. The functionality of the receptors can also be adjusted to provide a route to make the molecules water-soluble or even permeable to cell membranes, as applications in cellular imaging are pursued once the solution chemistries are worked out. Studying new recognition motifs for anions, such as the emerging interaction between anions and electron-deficient arenes, requires understanding the basic science of manipulating these new theoretical binding motifs in order to design novel receptors. Applications from this research have the potential to be transferred to the design of new materials for remediation and sensing and may provide insights on the interaction between anions and biological substrates. The proposed research may also shed light on self-assembly processes in more complex biological systems. Therefore understanding anion binding on a molecular level is of paramount importance if one wishes to elucidate the roles of anions in the much more complicated biological processes.
Anions are problematic environmental contaminants and are vital to many processes in nature, with anion binding proteins and transport channels implicated in the mechanisms of many disease pathways. The research proposed in this application will lead to new organic receptors that selectively bind and sense anions. These molecules will have long-term applications in sensing, imaging and/or remediating anions, which will impact public health in both discovering and removing environmental contaminants and imaging the role anions play in biological processes.
| Tresca, Blakely W; Brueckner, Alexander C; Haley, Michael M et al. (2017) Computational and Experimental Evidence of Emergent Equilibrium Isotope Effects in Anion Receptor Complexes. J Am Chem Soc 139:3962-3965 |
| Eytel, Lisa M; Gilbert, Annie K; Görner, Paul et al. (2017) Do CH-Anion and Anion-? Interactions Alter the Mechanism of 2:1 Host-Guest Complexation in Arylethynyl Monourea Anion Receptors? Chemistry 23:4051-4054 |
| Vonnegut, Chris L; Shonkwiler, Airlia M; Zakharov, Lev N et al. (2016) Harnessing solid-state packing for selective detection of chloride in a macrocyclic anionophore. Chem Commun (Camb) 52:9506-9 |
| Tresca, Blakely W; Berryman, Orion B; Zakharov, Lev N et al. (2016) Anion-directed self-assembly of a 2,6-bis(2-anilinoethynyl)pyridine bis(amide) scaffold. Supramol Chem 28:37-44 |
| Hartle, Matthew D; Hansen, Ryan J; Tresca, Blakely W et al. (2016) A Synthetic Supramolecular Receptor for the Hydrosulfide Anion. Angew Chem Int Ed Engl 55:11480-4 |
| Berryman, Orion B; Johnson 2nd, Charles A; Vonnegut, Chris L et al. (2015) Solid-State Examination of Conformationally Diverse Sulfonamide Receptors Based on Bis(2-anilinoethynyl)pyridine, -Bipyridine, and -Thiophene. Cryst Growth Des 15:1502-1511 |
| Tresca, Blakely W; Hansen, Ryan J; Chau, Calvin V et al. (2015) Substituent Effects in CH Hydrogen Bond Interactions: Linear Free Energy Relationships and Influence of Anions. J Am Chem Soc 137:14959-67 |
| Vonnegut, Chris L; Shonkwiler, Airlia M; Khalifa, Muhammad M et al. (2015) Facile Synthesis and Properties of 2-?(5)-Phosphaquinolines and 2-?(5)-Phosphaquinolin-2-ones. Angew Chem Int Ed Engl 54:13318-22 |
| Watt, Michelle M; Engle, Jeffrey M; Fairley, Kurtis C et al. (2015) ""Off-on"" aggregation-based fluorescent sensor for the detection of chloride in water. Org Biomol Chem 13:4266-70 |
| Vonnegut, Chris L; Tresca, Blakely W; Johnson, Darren W et al. (2015) Ion and molecular recognition using aryl-ethynyl scaffolding. Chem Asian J 10:522-35 |
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