Abstract
A new and simple to use line-shape analysis method ANATOLIA (ANAlysis of TOtal LlneshApe) optimised all and F-19-F-19 and F-19-H-1 coupling constants in pentafluorobenzene (AA'BB'C'H) within 10 s. This free and open-source NMR analysis method, which works within the Bruker Topspin-4 software and can import Bruker/JEOL/Varian data, was able to accommodate grossly inaccurate input coupling constants to provide an accurate result even for the second-order interactions (4)J(AA), and (4)J(BB),. The C-13 spectrum and the F-19-C-13-satellites share the same coupling values, but required manual intervention to achieve an acceptable fit, especially for the F-19(BB),-C-13-satellites which are deceptively simple but have significant second-order effects and display Delta delta F-19(B)-F-19(B), of (similar to)100 Hz.
A real-world analysis of a new compound, that has potential anti-cancer drug activity, tetrafluoro-4-(morpholino)pyridine molecule, is shown for the first time. The F-19 spectrum consists of a spin-system of 8 coupling nuclei (AA'BB'-H-4) which was analysed within 20 s. The C-13 satellites in the F-19 spectrum consist of 9-spins (AA'BB'C-13-H-4) and the carbon spectrum shows a series of C-13 isotopomer multiplets consisting of 5 coupling nuclei (C-13-AA'BB') was optimised in less than a minute using a laptop computer.
Ab initio structure optimisations were carried out using B3LYP/6-31G*, and chemical shifts and coupling constants were calculated with the basis-set B3LYP/6-311(++)G**. Fluorine and carbon chemical shifts were in reasonable agreement with experimental values, and (n)J(FF) and (2-4)J(CF) couplings were close to the experimental values, such that these were reasonable starting values for the ANATOLIA optimisation.