Inverse-Polarity Approach Towards Modular, Red-Shifted, and Soluble Polymethine Fluorophores
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.
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BibTeX
@misc{tang2026inversepolarity,
title = {{Inverse-Polarity Approach Towards Modular, Red-Shifted, and Soluble Polymethine Fluorophores}},
author = {Fung-Kit Tang and Wenjun Liu and Xinyuan Li and Lei Guo and Xuemei Chen and Kevin D. Belfield and Shang Jia},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15004512/v2},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15004512/v2},
note = {CC BY},
}
RIS
TY - UNPB
TI - Inverse-Polarity Approach Towards Modular, Red-Shifted, and Soluble Polymethine Fluorophores
AU - Fung-Kit Tang
AU - Wenjun Liu
AU - Xinyuan Li
AU - Lei Guo
AU - Xuemei Chen
AU - Kevin D. Belfield
AU - Shang Jia
PY - 2026
DA - 2026/10/21
PB - ChemRxiv
DO - 10.26434/chemrxiv.15004512/v2
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15004512/v2
AB - 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.
ER -