Click Chemistry to Fluorescent Amino Esters: Synthesis and Spectroscopic Studies

• Published in: European Journal of Organic Chemistry 2010-04, Vol.2010 (12), p.2395-2405
• Main Authors: Li, Chun, Henry, Etienne, Mani, Naresh Kumar, Tang, Jie, Brochon, Jean-Claude, Deprez, Eric, Xie, Juan
• Format: Article
• Language: English
• Subjects: Amino acids; Chemical Sciences; Chemistry; Click chemistry; Condensed benzenic and aromatic compounds; Exact sciences and technology; Fluorescence; Fluorescent probes; Heterocyclic compounds; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Organic chemistry; Preparations and properties; Solvent effects
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201000042

A new series of fluorescent amino esters have successfully been prepared by click chemistry by introducing different fluorophores (fluorescein, dansyl, 4‐nitro‐2,1,3‐benzoxadiazole, coumarin and benzothiadiazole) into the side‐chain of either serine, lysine or phenylalanine. The newly synthesized fluorescent amino esters displayed spectroscopic properties similar to their native fluorophores, with high quantum yields and fluorescence in the visible region (420–520 nm). Steady‐state as well as time‐resolved studies indicated that benzothiadiazole derivatives 22–25 are promising probes for studying protein dynamics or molecular interactions, especially in the cell, due to their emissions in the visible region, their high quantum yields and their relatively long lifetimes (14.7–18.3 ns). Moreover, the fluorescence of 7‐hydroxycoumarin‐substituted amino ester 27 was very sensitive to the solvent proticity and pH value. This compound appears to be a suitable pH‐sensitive amino acid for probing the local pH in cell compartments. Fluorescent amino esters can be readily prepared from azido‐ or alkyne‐functionalized amino acids and fluorophores by click chemistry. Benzothiadiazole‐substituted amino esters, which exhibit fluorescence in the visible region, display highquantum yields and relatively long lifetimes. The 7‐hydroxycoumarin derivative proves to be a suitable pH‐sensitive probe for local pH measurement.