NIR‐II Cyazulene Fluorophores with Adjustable Cycloalkenes and Spectroscopic Properties for Imaging Applications

A series of cyazulenes (CA965, CA985, and CA1025) are constructed by convenient coupling of azulenes with different aldehydes derived from cycloketones. Adjusting the number of cycloalkene carbon atoms in the methine chain enables the cyazulenes to form different H-aggregation and J-aggregation with distinct spectral properties. Particularly noteworthy is that CA985 can form significant J-aggregates in simulated biological media (PBS) and DSPE-PEG₂₀₀₀, resulting in successful high-resolution imaging of blood vessels, and fine structures of collecting lymphatics and bone in mice.

Abstract

NIR-II fluorescence imaging has shown broad application prospects in life science because of its deeper tissue penetration and higher spatiotemporal resolution. Developing NIR-II fluorophores with special spectroscopic properties and analytical functions has become a cutting-edge but challenging topic in this field. Herein, a series of azulene-based NIR-II fluorophores (called cyazulenes) with adjustable cycloalkenes and spectroscopic properties for imaging applications is reported. Cyazulenes (CA965, CA985, and CA1025) are constructed via the convenient coupling of cycloalkenes with azulene derivatives. They exhibit different H-aggregation and J-aggregation. Particularly noteworthy is that CA985 can form significant J-aggregates with strong and sharp NIR-II emission in biological media, and can be used for in vivo imaging of blood vessels and fine structures of collecting lymphatics in mice. Moreover, CA985 displays passive bone-targeted capacity, thereby enabling bone imaging. This study demonstrates the chemical impact of varying cycloalkenes on the aggregate formation and spectral properties of cyazulenes, which will advance azulene-based NIR-II fluorophores.