Thiazolidine derivatives from fluorescent dithienyl-BODIPY-carboxaldehydes and cysteine

Abstract

Fluorescent dithienyl-borondipyrromethene (BODIPY) dyes formylated in the β'-position (2b, 2c) have been treated with L-cysteine to provide thiazolidine derivatives. N-Protection of the thiazolidine unit by ethoxycarbonylation facilitated isolation of the two major diasteroisomers 6 and 7. These stereoisomers have been fully characterized by (1)H NMR spectroscopy, allowing assignment of their stereochemistry as 2R,4R,aS and 2S,4R,aR, respectively. The optical properties of the thiazolidine dyes differ markedly in both absorption (λ(abs) = 612 nm for 6 and 615 nm for 7) and emission (λ(em) = 669 nm, Φ(F) = 62% for 6 and λ(em) = 672 nm, Φ(F) = 19% for 7) from those of the BODIPY-carboxaldehydes 2b (λ(abs) = 643 nm and λ(em) = 719 nm, Φ(F) = 26%) and 2c (λ(abs) = 636 nm and λ(em) = 710 nm, Φ(F) = 36%). In a mixed solvent [phosphate buffer saline (PBS), pH = 7.4/ethanol 1:9], the fluorescence response of the dyes in the presence of L-cysteine is slow, but a ratiometric detection process in the therapeutic window (650 to 800 nm) is evident.