Inverse-Polarity Approach Towards Modular, Red-Shifted, and Soluble Polymethine Fluorophores
Year: 2026
Type: preprint
Abstract: Polymethine dyes are widely used for NIR and SWIR imaging, yet their synthesis still relies on a single coupling paradigm that limits structural diversity and functionalization. Herein, we report a versatile, modular synthesis of heptamethine dyes based on an inverse-polarity approach. Readily available building blocks are converted into a ketone intermediate, which allows independent selection of heterocycles and the central ring system, as well as installation of 4′-substituents via organolithium addition. This intermediate can also be extended by aldehyde homologation to access undecamethine and longer red-shifted scaffolds. The method enables access to polymethine dyes that were previously inaccessible or difficult to synthesize, including dyes with varied central rings, alkyl substitution, and a tri-alkyne scaffold for multivalent bioconjugation. Notably, introducing a localized positive charge on the central ring greatly reduces aggregation and enhances aqueous solubility, allowing direct administration in saline for in vivo imaging without formulation. More than a route to tailored fluorophores, this inverse-polarity platform provides a general alternative to conventional polymethine synthesis and a design framework for engineering soluble, red-shifted, and targetable imaging probes.
Source: ChemRxiv
Language: English
Subfield: Materials Chemistry
Field: Materials Science
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7223173907