Document Type
Article
Publication Date
8-2024
Keywords
polymethine dye; cyanine; watersolubility; aggregation; stability; fluorescenceimaging
Abstract
As a major family of red-shifted fluorophores that operate beyond visible light, polymethine dyes are pivotal in light-based biological techniques. However, methods for tuning this kind of fluorophores by structural modification remain restricted to bottom-up synthesis and modification using coupling or nucleophilic substitutions. In this study, we introduce a two-step, late-stage functionalization process for heptamethine dyes. This process enables the substitution of the central chlorine atom in the commonly used 4′-chloro heptamethine scaffold with various aryl groups using aryllithium reagents. This method borrows the building block and designs from the xanthene dye community and offers a mild and convenient way for the diversification of heptamethine fluorophores. Notably, this efficient conversion allows for the synthesis of heptamethine-X, the heptamethine scaffold with two ortho-substituents on the 4′-aryl modification, which brings enhanced stability and reduced aggregation to the fluorophore. We showcase the utility of this method by a facile synthesis of a fluorogenic, membrane-localizing fluorophore that outperforms its commercial counterparts with a significantly higher brightness and contrast. Overall, this method establishes the synthetic similarities between polymethine and xanthene fluorophores and provides a versatile and feasible toolbox for future optimizing heptamethine fluorophores for their biological applications.
Citation
Guo, L., Yang, M., Dong, B., Lewman, S., Van Horn, A., & Jia, S. (2024). Engineering Central Substitutions in Heptamethine Dyes for Improved Fluorophore Performance. JACS Au, 4 (8), 3007-3017. https://doi.org/10.1021/jacsau.4c00343
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
