Researcher(s)
- Maria Carattini, Biomedical Engineering, Delaware State University
Faculty Mentor(s)
- Joseph Fox, Chemistry and Biochemistry, University of Delaware
Abstract
By utilizing controllable catalytic stimuli, bioorthogonal reactivity can be rapidly induced using air as an oxidant.1 Bioorthogonal chemistry refers to a class of chemical reactions that occur efficiently and selectively within biological systems, without causing undesired reactions with the natural functional groups present in those systems. In bioorthogonal chemistry, fast kinetics enhances selectivity, allows for working with low biologically relevant concentrations and minimizes off-target effects of cytotoxicity, making it a critical factor for successful bioorthogonal applications. One of the most remarkable bioorthogonal reactions known to date is the tetrazine ligation, exhibiting incredibly high rate constants up to 106 M-1 s-1. This ligation can be precisely controlled in both space and time through catalytic activation of bioorthogonal chemistry using light. Specifically, in the presence of trans-cyclooctene dienophiles, an inactive dihydrotetrazine can be oxidized to an active tetrazine.1 Silicon-rhodamine (SiR) dyes, originally designated as biological fluorophores, have been repurposed for photocatalysis to facilitate this process. The utilization of red light for the oxidation of dihydrotetrazine to tetrazine offers the advantage of biocompatibility and tissue penetration abilities.2 The rate of an enzymatic reaction is described as a function of substrate concentration by the Michaelis-Menten kinetics. When oxidation rates exhibit Michaelis-Menten kinetics, it is assumed that an enzyme or a catalyst with enzyme-like properties is responsible for catalyzing the oxidation reaction. Although numerous dyes, including Fluorescein, have been confirmed as photosensitizers, the detailed mechanism of photocatalysis remains poorly understood. Thus, the objective of this research is to investigate the mechanism of dihydrotetrazine oxidation by conducting a series of kinetics experiments using fluorescein, and SiR dyes.
REFERENCES
[1] J. Am. Chem. Soc. 2016, 138, 18, 5978–5983
[2] J. Am. Chem. Soc. 2021, 143, 28, 10793–10803