Understanding Physiochemical Properties and Applications of Rationally Designed Merocyanine Dyes

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Van Riesen, Abigail

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University of Guelph

Abstract

Cyanine dyes have been used in industrial applications since their discovery over 200 years ago. Today, they are still viewed as highly valuable small molecules with applications in biotechnology and nanotechnology. One class of cyanine dyes is called merocyanines (MCs). MCs exhibit impressive sensitivity to their environment via negative solvatochromism as well as impressive fluorescent characteristics. Alone they can be employed to sense nucleophiles in solution by losing their bright colours upon addition of the nucleophile. Beyond sensing small molecules independently, they are capable of sensing different DNA topologies including duplex, quadruplexes (GQs), and three-way junctions (3WJs), and sensing these topologies can provide insight into essential biological processes. Their affinity to different DNA topologies can give rise to other applications involving them being utilized in aptamer platforms. DNA aptamers are a functional form of nucleic acids that can adopt shapes that can enable them to engage in target-specific binding. They are derived using an iterative process known as in vitro selection, where many DNA sequences are exposed to the target ligand, and those that do not bind the target are removed while the binders are isolated. This process has produced many different aptamers for a variety of targets (metals, small molecules, and proteins) capable of binding at low concentrations (nM to μM range). Aptamers have recently seen a rapid uptake in a broad array of biotechnological applications, due to their simple, economical, and efficient design. In this body of work, a novel family of MC dyes is synthesized, and their applications and properties are explored. In Chapter 2, temperature-sensitive thiolate sensing MCs will be investigated, and thermodynamic contributions characterized. These studies result in the development of Chapter 3 where a substituted phenolic merocyanine dye with a benzothiazolium acceptor is shown to be capable of selectively binding DNA 3WJs. The MC also exhibits impressive turn-on fluorescent signalling ability and has been utilized for sensitive small molecule detection in complex matrices. In Chapter 4, the MC family is expanded where the development and structure-activity relationship analysis results in improved sensing and binding characteristic for a variety of small molecule targets demonstrating merocyanine dye versatility.

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Keywords

DNA, absorbance, adducts, aptamers, binding site determination, biosensor, biotechnology, cholic acid, cocaine, colorimetric detection, cyanine, dyes and pigments, DNA structure sensing, duplex DNA, fluorescence, fluorescent probe, hemicyanine, host-guest detection, isothermal titration calorimetry, merocyanine, MN4, negative solvatochroism, NMR, paraquinone methide, quadruplex, quinine, solvatochomics, temperature sensing, thiolates, three-way junctions

Citation

Van Riesen, A. J., Johnson, R. E., Al-Abdul-Wahid, M. S., Liota, C., Christyanton, A., & Manderville, R. A. (2020). Temperature Sensing of Thiolate Addition by Phenolate Merocyanine Dyes: Importance of the Quinone Methide Resonance Structure. The Journal of Organic Chemistry, 86(2), 1583-1590. doi.org/10.1021/acs.joc.0c02428.
Van Riesen, A. J., Le, J., Slavkovic, S., Churcher, Z. R., Shoara, A. A., Johnson, P. E., & Manderville, R. A. (2021). Visible Fluorescent Light-up Probe for DNA Three-Way Junctions Provides Host�??Guest Biosensing Applications. ACS Applied Bio Materials, 4(9), 6732-6741. doi.org/10.1021/acsabm.1c00431.