Acid–Base Properties of Xanthohumol: A Computational and Experimental Investigation

UV–vis spectrophotometry has been applied to determine acid dissociation constants of the prenylated chalcone xanthohumol. The p<i>K</i>_a values were compared with those derived from pH-metric titrations. The order of the deprotonation site in the xanthohumol molecule was estimated by quantum mechanical calculations as 2′-OH, 4′-OH, and 4-OH. Furthermore, the electronic and spectroscopic properties of xanthohumol have been investigated on the basis of the time-dependent density functional theory (TDDFT). The TDDFT method, combined with a hybrid exchange–correlation functional using the B3LYP and CAM-B3LYP levels of theory in conjunction with the SMD solvation model, was used to optimize all geometries and predict the excitation energies of the neutral form and ionized species of the chalcone depending on pH value. The computed results were in good agreement with the experimental data. Consideration of the acid–base profile in conjunction with other molecular properties has a great importance and has the potential to be used to further improve the bioavailability of xanthohumol

Interplay of Inter- and Intramolecular Interactions in Crystal Structures of 1,3,4-Thiadiazole Resorcinol Derivatives

Five new 1,3,4-thiadiazole derivatives have been synthesized, and their crystal structures have been determined by single crystal X-ray diffraction. The influence of substituents on molecular geometry and the three-dimensional arrangement of molecules has been studied by means of single crystal X-ray diffraction, fluorescence, UV–vis spectroscopy, and computational methods. The 1,3,4-thiadiazole derivatives occur in two possible conformations in their crystal lattices: with the ortho-hydroxyl group of the resorcyl ring pointing toward the S or the N atoms from the 1,3,4-thiadiazole ring. In the latter conformation, an intramolecular hydrogen bond is created which is energetically favorable for the isolated molecule as confirmed by theoretical calculations. However, for the molecules in the crystal structures in the former conformation, some intermolecular interactions between the neighboring molecules are strong enough to overrule the intramolecular OH···N hydrogen bond. In the case of one of the 1,3,4-thiadiazole derivatives, a significant disorder was observed, and both conformations were present in one crystal lattice in the ratio 80% to 20% for the two conformers, respectively. On the basis of resonance light scattering results, we explain why crystals of 1,3,4-thiadiazole derivatives can be grown from DMSO and are difficult to be grown from methanol solution