Theoretical calculation of NMR shifts in newly developed antibacterial 4-formylbenzoic acid-based thiazoles

Abstract

We evaluated the proton chemical shieldings and the corresponding chemical shifts of ten newly developed antibacterial 4-formylbenzoic acid-based thiazoles, using computational chemistry methodology. Due to the large size of the studied molecules, we resorted to density functional theory. After a systematic method and basis set selection study carried out on methane, benzene, and thiazole, we selected the M06 DFT functional together with the aug-pcS-1 basis set to carry out the calculations on the larger systems. This combination of functional and basis set seems to be very efficient in providing shifts close to the experimental data available at a relatively low computational cost. The theoretical results for the molecules under investigation were compared to the experimental chemical shifts available, and reasonable agreement was reached in all cases, allowing the theoretical calculations a more detailed analysis of the one-dimensional experimental spectra, i.e. the assignment of individual experimental aromatic signals to specific protons of the phenyl rings, that was not possible based solely on the experimental results. Considering this, we can recommend the M06 functional and the aug-pcS-1 basis set for the evaluation of proton shifts in larger 4-formylbenzoic acid-based thiazoles.