Anthracene-thymine luminophores: Synthesis, photophysical properties, and imaging in living HeLa cells

Abstract

This paper presents a report of the synthesis and chemical transformations of anthracene-thymine and 4-thiothymine derivatives. In a reaction of 1-(anthracen-9-yl)-1-hydroxy-3-(N1-thyminyl)-propane with ethylene glycol either an elimination or substitution product is preferentially formed depending on reaction conditions. In the presence of Yb(OTf)3, the elimination product was the major one; while in the absence of Yb(OTf)3, the substitution reaction product prevailed. Thus, six fluorescent nucleic base derivatives were obtained. The three anthracene-thymine derivatives (2, 3, and 4) show strong fluorescence with emission quantum yields from 65% to about 100% in solution at ambient temperature. The emission of anthracene-thymine 1 and two anthracene-thiothymines is weaker due to the carbonyl substituents and the sulphur atom of thiothymine. Tests of antiproliferative activity on human cancer HeLa cells performed at 24 h and 5 h treatment times, respectively, revealed no detectable toxicity at the latter interval. Thus, confocal microscopy imaging studies were carried out on HeLa cells at 5 h incubation time. All six compounds under study were found in the interior of the cells, albeit the intensity of the compounds’ luminescence stemming from the interiors was different. All compounds localised in the lipid membranes of cytoplasmic compartments in general follow the same staining pattern. In addition, compounds 3 and 6 were also detected in the nucleus. Notably, no signs of photocytotoxicity or photobleaching in the timespan of imaging studies were observed. The new fluorescent nucleic base derivatives represent attractive leading structures for the development of preferably more selective luminescent probes in the future.