Synthesis and binding studies of two new coumarin-squaramide-based receptors for NSAIDs

Abstract

Two new squaramide-based receptors containing coumarin units have been synthesized and characterized in both solution and solid states. L1 (3-(benzylamino)-4-((2-oxo-4-(trifluoromethyl)-2H-chromen-7-yl)amino)cyclobut-3-ene-1,2-dione) is a linear molecule, while L2 (4,4′-((1,3-phenylenebis(methylene))bis(azanediyl))bis(3-((2-oxo-4-(trifluoromethyl)-2H-chromen-7-yl)amino)cyclobut-3-ene-1,2-dione)) is an open chain ligand which results in the ditopic form of the simpler parent ligand L1. The new molecules have been designed to act as receptors for non-steroidal anti-inflammatory drugs (NSAIDs) possessing both squaramide units as double hydrogen bond (HB) donor sites that are able to interact with the carboxylate functions of the guests, and 4-trifluoromethylcoumarin moieties as aromatic photoactive domains to facilitate π-stacking or hydrophobic interactions with the drug's aromatic rings. The ability of the new receptors to interact with benzoate (BzO⁻), ibuprofen (IBU⁻), naproxen (NPX⁻) and ketoprofen (KET⁻) sodium salts was studied via UV-Vis and fluorescence spectroscopy, ¹H-NMR measurements and DFT calculations. Finally, mass spectrometry studies demonstrated that L1 showed the tendency to form adducts with a 2 : 1 ligand-to-anion stoichiometry ([L1₂-Anion]⁻), while only adducts with a 1 : 1 stoichiometry ([L2-Anion]⁻) were visible for L2.