Synthesis and characterization of 1,4-chalcogenesters bearing 5-membered heterocycles

Abstract: Treatment of 1,4-(SeSiMe₃)₂-C₆H₄ (1) with two equiv of ClC(O)R (2) (a, R = 2-^cC₄H₃O; b, R = 2-^cC₄H₃S; c, R = 3-^cC₄H₃S) produced the corresponding phenylene carboselenolates 1,4-(SeC(O)R)₂-C₆H₄ (3a–c), while the reaction of 1,4-(SLi)₂-C₆H₄ (4) with ClC(O)R (2) in a 1:2 molar ratio gave phenylene carbothiolates 1,4-(SC(O)R)₂-C₆H₄ (5a–c). Compounds 3a–c and 5a–c were characterized by elemental analysis, NMR (¹H, ¹³C{¹H}, ⁷⁷Se{¹H}) and IR spectroscopy. The molecular structures of 3a–c and 5a–c in the solid state were determined by single-crystal X-ray structure analysis. The carbochalcogenato groups and the heteroatoms of the 5-membered rings are in an anti-arrangement with respect to each other. Cyclic voltammetry measurements show irreversible reduction processes for the 5-membered heterocyclic redox moiety in which reduction of these compounds lead to decomposition of the original compounds to unidentified species and show redox potentials between 1480 and 1580 mV for 3a-c and 1470−1490 mV for 5a-c, relative to the FcH/FcH⁺ redox couple. Also, thioester-functionalized systems 5a-c show significantly higher reduction potentials as compared to selenoesters 3a-c, reflecting the minor electron-donating effect of the sulfur atoms. The molecular electronic structures of the title compounds were additionally investigated by DFT calculations, revealing different degrees of HOMO-LUMO energy gaps within the series of 3a–c and 5a–c, due to a lowering in LUMO energy, depending on the nature of the heterocyclic ring. The calculations showed that the HOMO and LUMO are mainly located on the selenoester/thioester functionalized heterocyclic. The phase transition temperatures and enthalpies of the title compounds were detected by differential scanning calorimetry (DSC) analysis and the phases are confirmed by polarizing optical microscopy (POM). The mesomorphic investigation shows that compound 5a only exhibits enantiotropic smectic B (SmB) mesophase. In contrast, the other compounds do not show mesomorphic behavior, but simply changes from the solid crystalline state to the isotropic liquid. Biological activity of the compounds was evaluated using cytotoxicity assay on different cancer cell lines. Only compound 3c showed selective cytotoxic effect against MDA-231 and PC-3 cancer cell lines. Graphic abstract: The synthesis and characterization of phenylene carboselenolates 1,4-(SeC(O)R)₂-C₆H₄ (3a–c) and phenylene carbothiolates 1,4-(SC(O)R)₂-C₆H₄ (5a–c) were discussed. The solid state structures of the six compounds are reported. Electrochemical investigations show irreversible redox events. DFT calculations reveal different HOMO-LUMO gaps depending on the aryl substituent pattern. In addition, the liquid crystalline properties and the bioactivity test were carried out too.[Figure not available: see fulltext.].