化学
产量(工程)
罗丹明
组合化学
膦酸盐
衍生化
化学合成
溶解度
杂原子
基质(水族馆)
纳米技术
有机化学
材料科学
体外
荧光
烷基
生物化学
物理
高效液相色谱法
海洋学
量子力学
冶金
地质学
作者
Joshua L. Turnbull,Ryan P. Golden,Brittany Benlian,Katharine M. Henn,Soren M. Lipman,Evan W. Miller
出处
期刊:Chemical Science
[The Royal Society of Chemistry]
日期:2023-01-01
卷期号:14 (41): 11365-11373
被引量:1
摘要
Since their discovery in 1887, rhodamines have become indispensable fluorophores for biological imaging. Recent studies have extensively explored heteroatom substitution at the 10' position and a variety of substitution patterns on the 3',6' nitrogens. Although 3-carboxy- and 3-sulfono-rhodamines were first reported in the 19th century, the 3-phosphono analogues have never been reported. Here, we report a mild, scalable synthetic route to 3-phosphonorhodamines. We explore the substrate scope and investigate mechanistic details of an exogenous acid-free condensation. Tetramethyl-3-phosphonorhodamine (phosTMR) derivatives can be accessed on the 1.5 mmol scale in up to 98% yield (2 steps). phosTMR shows a 12- to 500-fold increase in water solubility relative to 3-carboxy and 3-sulfonorhodamine derivatives and has excellent chemical stability. Additionally, phosphonates allow for chemical derivatization; esterification of phosTMR facilitates intracellular delivery with localization profiles that differ from 3-carboxyrhodamines. The free phosphonate can be incorporated into a molecular wire scaffold to create a phosphonated rhodamine voltage reporter, phosphonoRhoVR. PhosRhoVR 1 can be synthesized in just 6 steps, with an overall yield of 37% to provide >400 mg of material, compared to a 6-step, ∼2% yield for the previously reported RhoVR 1. PhosRhoVR 1 possesses excellent voltage sensitivity (37% ΔF/F) and a 2-fold increase in cellular brightness compared to RhoVR 1.
科研通智能强力驱动
Strongly Powered by AbleSci AI