Fluorescent Small Molecules Are BIG Enough To Sense Biomacromolecule: Synthesis of Aromatic Thioesters and Understanding Their Interactions with ctDNA

[Image: see text] The visible fluorescent chromophoric moiety present in the water-soluble photoactive yellow protein (PYP) of Ectothiorhodospira halophila is p-hydroxycinnamic acid linked to the cysteine residue (Cys-69) by a thioester bond and it controls the key photoinduced biological processes of the host organism. In the present work, we have synthesized and characterized three structurally different thiophenyl esters [viz., p-hydroxycinnamic-thiophenyl ester (1), p-N,N-dimethylaminocinnamic-thiophenyl ester (2), and S-phenyl-3-(4-chlorophenyl)-3-(phenylthio)propanethioate (3)] in addition to a novel (to the best of our knowledge) stilbene-type olefinic compound, N(1),N(1),N(2),N(2)-tetramethyl-1,2-bis(phenylthio)ethene-1,2-diamine (4), under the same reaction condition. All of these four compounds showed characteristic and distinguishable chromophoric/fluorophoric behavior in ethanol and also at pH 7.4. However, we have observed that the intrinsic chromophoric/fluorophoric activities of (1) and (2) were greatly influenced during their interactions with calf-thymus DNA, studied by a range of spectroscopic and physicochemical measurements. We have also applied density functional theory [B3LYP, 6-311G(+)(d,p)]-based method to get optimized structures of (1) and (2), which were explored further for molecular docking studies to understand their mode of interaction with DNA. The present study opens up their possible applications as fluorescence probes for biomacromolecules like DNA in future.