Newly synthesized benzothiazolyl-1,2,3-triazole derivatives: Intramolecular charge transfer tuning, solvatofluorochromism and antiproliferative properties

Abstract

A family of 6 new 1-aryl-4-benzothiazolyl-1,2,3-triazoles with CH3, F, CF3, NO2, OCH3 and N(CH3)2 substituents in the R4 of the phenyl ring has been prepared from the respective aldehyde treated with ortho-aminothiophenol. The compounds are characterized in solution using multinuclear NMR spectroscopy and in the solid state by X-ray diffraction. The emission spectra of the compounds with stronger electron-donating groups, OCH3 and N (CH3)2, exhibit a red-shifted band (391 and 515 nm, respectively), the latest showing the largest Stokes shift and the highest quantum yield, which increases with the decrease polarity of the solvent. The excited-state lifetimes of all compounds showed a bi-exponential decay with a short (5-12 ns), according to an admixture of intra-molecular charge transfer (ICT) and pi-pi*, and a long (45-100 ns) component. The calculated structures of their first singlet excited state by TD-DFT in acetonitrile (ACN) solution allows to estimate the change in the dipole moments, which explains the ICT character of their first singlet excited state for the NO2 and N(CH3)2 de-rivatives. Important to note that compound with the electron-donating N(CH3)2 substituent showed strong sol-vatofluorochromism (correlated well with the ICT and the dipole moments). Interestingly, some of the compounds are active in human A2780, HeLa and A549 cancer cell lines, exhibiting IC50 values in the low micromolar range, whereas showing low cytotoxicity in healthy CHO cells. Important to note that the N(CH3)2 derivative showed cytoplasmic staining as determined by confocal fluorescent microscopy.