Cycloparaphenylenes and their Biological Applications
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Date
2022
Authors
Garrison, Anna
Journal Title
Journal ISSN
Volume Title
Publisher
University of Oregon
Abstract
Looking inside the human body is a critical tool researchers and physicians need to explore the human species, navigate and discover new diseases, and look for new cures or therapies. It is impossible to visualize and explore its intricate detail without an effective way to mark structures of interest with fluorescent probes. Fluorophores are chemical markers that attach to specific structures and cause them to emit visible light. They function by absorbing a light from some source and re-emit that light at a certain wavelength. It is important there are a wide variety of fluorophores as they each emit a unique wavelength that can be used for a variety of biochemical purposes. The most widely used commercially available fluorophore is the Green Fluorescent Protein (also known as GFP) which has very successfully utilized genetic encoding to embed green fluorescence in targeted molecules. One of the most important limitations with this approach is its inability to fluoresce genetically modified biomolecules. [n]cycloparaphenylenes or “CPPs” are a class of molecules with unique structure that causes a useful size-dependent fluorescence property. This property allows researchers to design various structures with varying colors. The stepwise synthetic nature with which CPPs are created allows them to be easily manipulated to insert useful chemical structures which alter the electrical and photophysical properties. These unique reactive and optical properties have made CPPs an attractive material studied for the purpose of biological imaging. Previous research has been conducted to investigate the effectiveness of CPPs as biological fluorophores. A CPP that is non-cytotoxic, water-soluble, and capable of permeating cell membranes has been reported. This is the first account that demonstrated CPPs could be suitable for cellular environments. Macrocyclic angle-strained alkyne CPPs (CPPs with a carbon-carbon triple bond incorporated into their cyclic structure) are a unique class of CPPs that can be used for tagging biological molecules through copper-free click chemistry. Copper-free click chemistry such as the strain-promoted alkyne-azide reaction (also known as the SPAAC reaction) is a unique way to attach two molecules together (ligation reaction) in a living system that avoids the cytotoxicity of copper, a common dangerous chemical. This is a simple and safe reaction that can leave biological systems unharmed. Introducing an alkyne (a carbon-carbon triple bond) into the ring of the CPP boosts the reactivity of the molecule and the ability to click to biomolecules through the SPAAC reaction. Here we explore the stability of alkyne CPPs in biological environments, demonstrating stability at physiological temperature. We also successfully click an alkyne CPP to a biomolecule. Additionally, we outline future experiments such as clicking the CPP to other biomolecules, labelling the cell surface of a cell through a metabolic labelling pathway (utilizing cell digestion to install the means of ligation), and investigating different sizes of CPPs for ligation purposes.
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Keywords
Fluorophore, Bioorthogonal, Fluorescence, Organic, Chemistry