Meador William E, Lewis Timothy A, Shaik Abdul K, Wijesinghe Kalpani Hirunika, Yang Boqian, Dass Amala, Hammer Nathan I, Delcamp Jared H
Department of Chemistry and Biochemistry, University of Mississippi, 322 Coulter Hall, University, Mississippi 38677, United States.
HORIBA Scientific, 20 Knightsbridge Rd, Piscataway, New Jersey 08854, United States.
J Org Chem. 2024 Mar 1;89(5):2825-2839. doi: 10.1021/acs.joc.3c01917. Epub 2024 Feb 9.
Fluorescence-based biological imaging in the shortwave infrared (SWIR, 1000-1700 nm) is an attractive replacement for modern imaging techniques currently employed in both medical and research settings. Xanthene-based fluorophores containing heterocycle donors have recently emerged as a way to access deep SWIR emitting fluorophores. A concern for xanthene-based SWIR fluorophores though is chemical stability toward ambient nucleophiles due to the high electrophilicity of the cationic fluorophore core. Herein, a series of SWIR emitting silicon-rosindolizine (SiRos) fluorophores with emission maxima >1300 nm (up to 1550 nm) are synthesized. The SiRos fluorophore photophysical properties and chemical stability toward nucleophiles are examined through systematic derivatization of the silicon-core alkyl groups, indolizine donor substitution, and the use of -tolyl or -xylyl groups appended to the fluorophore core. The dyes are studied via absorption spectroscopy, steady-state emission spectroscopy, solution-based cyclic voltammetry, time-dependent density functional theory (TD-DFT) computational analysis, X-ray diffraction crystallography, and relative chemical stability over time. Optimal chemical stability is observed via the incorporation of the 2-ethylhexyl silicon substituent and the -xylyl group to protect the core of the fluorophore.
基于荧光的短波红外（SWIR，1000 - 1700纳米）生物成像，是目前医学和研究环境中使用的现代成像技术颇具吸引力的替代方案。含有杂环供体的呫吨基荧光团，最近已成为获得深SWIR发射荧光团的一种方法。不过，由于阳离子荧光团核心的高亲电性，基于呫吨的SWIR荧光团对环境亲核试剂的化学稳定性是一个问题。在此，合成了一系列发射最大值>1300纳米（高达1550纳米）的SWIR发射硅-中氮茚（SiRos）荧光团。通过对硅核心烷基进行系统衍生、中氮茚供体取代以及在荧光团核心附加对甲苯基或二甲苯基，研究了SiRos荧光团的光物理性质和对亲核试剂的化学稳定性。通过吸收光谱、稳态发射光谱、基于溶液的循环伏安法、含时密度泛函理论（TD-DFT）计算分析、X射线衍射晶体学以及随时间的相对化学稳定性对这些染料进行了研究。通过引入2-乙基己基硅取代基和二甲苯基来保护荧光团核心，观察到了最佳的化学稳定性。
