Chemistry & Biochemistry Colloquium | Biomimicry with Synthetic Receptors: Molecular Recognition, Catalysis and Sensing, March 20

The Chemistry & Biochemistry colloquium series presents Dr. Richard Hooley  discussing " Biomimicry with Synthetic Receptors: Molecular Recognition, Catalysis and Sensing "on March 20 from 4:10 to 5:05 p.m. in Walter 135.

Hooley is Professor of Chemistry at the University of California, Riverside.

The host is Eric Masson.

Abstract: The confined interior spaces of self-assembled host molecules can be exploited for a variety of catalytic processes, as well as incorporating optical markers for biosensing. Complex, multistep processes require the binding and activation of multiple different species along a reaction pathway, which is not trivial for rigid, inflexible synthetic hosts. We have synthesized a variety of self-assembled host complexes ^[1,3] that present reactive functional groups to their substrates, and are capable of selective molecular recognition, size-selectivity and catalysis. ^[1-3] Selective molecular recognition of substrates controls the reactivity, and the cages are capable of binding and activating multiple different species along multistep reaction pathways. In addition, modulation of sidechain acidity and basicity is key in enzyme mechanism, controlled by hydrogen bonds (and other forces) in the superstructure, and these effects can be seen in functionalized cage hosts also: ^[3] the properties of complex enzymatic catalysis are displayed by simple self-assembled cages, synthesized from the ground up.

Other types of synthetic hosts, called self-folding deep cavitands, when applied in an arrayed, fluorescent indicator displacement assay system can detect a variety of biomolecules, from steroids and drugs of abuse to post-translationally modified (PTM) peptides and non-canonically folded nucleotides such as G-Quadruplexes ^[4,5] in multiple types of biological media. Multiple recognition mechanisms can be exploited, either direct cavity-based binding of species such as trimethyllysine (KMe ₃ ), or indirect charge-based recognition of differentially functionalized peptides or DNA G4s. The synergistic application of multiple variables in a single arrayed sensor system allows dual-mode deep cavitands to approach levels of recognition selectivity usually only seen with antibodies.

Figure 1. Moderated basicity of Endohedral Amine Groups in an Octa-Cationic Self-Assembled Cage. ^[3]

References

[1]  Holloway, L.R.; Bogie, P.M.; Lyon, Y.; Ngai, C.; Miller, T.F.; Julian, R.R.; Hooley, R.J. J. Am. Chem. Soc. 2018 , 140, 8078.

[2]  Ngai, C.; Sanchez-Marsetti, C. M.; Harman, W.H.; Hooley, R.J. Angew. Chem. Int. Ed. 2020 , 59 , 23505.

[3]  Ngai, C.; Wu, H.-T.; da Camara, B.; Williams, C. G.; Mueller, L. J.; Julian, R. R.; Hooley, R. J. Angew. Chem. Int. Ed. 2022 , 61 , e202117011

[4] Chen, J.; Gill, A.D.; Hickey, B.L.; Gao, Z.; Cui, X.; Hooley, R.J.* ; Zhong, W.* J. Am. Chem. Soc. 2021 , 143 , 12791.

[5] Chen, J.; Hickey, B.L.; Wang, L.; Lee, J.; Gill, A.D.; Favero, A.; Pinalli, R.; Dalcanale, E.; Hooley, R.J.* ; Zhong, W.* Nat. Chem. 2021 , 13 , 488.