Structural basis of antibacterial photodynamic action of curcumin against S. aureus.

Antimicrobial photodynamic therapy (aPDT) is an alternative tool to commercial antibiotics for the inactivation of pathogenic bacteria (e.g., S. aureus). However, there is still a lack of understanding of the molecular modeling of the photosensitizers and their mechanism of action through oxidative pathways. Herein, a combined experimental and computational evaluation of curcumin as a photosensitizer against S. aureus was performed. The radical forms of keto-enol tautomers and the energies of curcumin's frontier molecular orbitals were evaluated by density functional theory (DFT) to point out the photodynamic action as well as the photobleaching process. Furthermore, the electronic transitions of curcumin keto-enol tautomers were undertaken to predict the transitions as a photosensitizer during the antibacterial photodynamic process. Moreover, molecular docking was used to evaluate the binding affinity with the S. aureus tyrosyl-tRNA synthetase as the proposed a target for curcumin. In this regard, the molecular orbital energies show that the curcumin enol form has a character of 4.5% more basic than the keto form - the enol form is a more promising electron donor than its tautomer. Curcumin is a strong electrophile, with the enol form being 4.6% more electrophilic than its keto form. In addition, the regions susceptible to nucleophilic attack and photobleaching were evaluated by the Fukui function. Regarding the docking analysis, the model suggested that four hydrogen bonds contribute to the binding energy of curcumin's interaction with the ligand binding site of S. aureus tyrosyl-tRNA synthetase. Finally, residues Tyr36, Asp40, and Asp177 contact curcumin and may contribute to orienting the curcumin in the active area. Moreover, curcumin presented a photoinactivation of 4.5 log unit corroborating the necessity of the combined action of curcumin, light, and O2 to promote the photooxidation damage of S. aureus. These computational and experimental data suggest insights regarding the mechanism of action of curcumin as a photosensitizer to inactivate S. aureus bacteria.

Synthesis, characterization, and computational study of a new heteroaryl chalcone.

This work presents the synthesis of the chalcone (E)-3-(2,6-difluorophenyl)-1-(furan-2-yl)-prop-2-en-1-one molecule through the equimolar reaction between 1-(furan-2-yl)-ethenone and 2,6-difluorobenzaldehyde. The crystallographic characterization and the extensive theoretical study regarding electronic properties were obtained. The supramolecular arrangement was described by X-ray diffraction and Hirshfeld surfaces. Optimized geometrical structure was obtained by density functional theory, and the electronic study for differences between the solid and gas phases was carried out with M062-X at 6-311++G(2d,2p) basis set. Natural bond orbital, frontier molecular orbitals (HOMO-LUMO), and molecular electrostatic potential map were determined to elucidate the information related to the charge transfer in the molecule. The theoretical and experimental vibrational spectra were plotted, which included the IR intensities, the calculated and experimental vibrational frequencies, and the assigned vibrational modes for the main groups of DTP.