A simple to use nuclear magnetic resonance analysis method has been tested on complex
1H,
19F, and
13C multiplets. This open-source line-shape analysis method analysis of total lineshape (ANATOLIA)
1 provides some significant advantages over traditional assign-iterate methods of NMR spectral analysis by avoiding false minima and progressing optimisation to the global minimum. The target molecules are 1-perfluorotol-4-yl-2-perfluorotol-4-yl-oxymethyl-1H-benzimidazole (molecule-I) and 1-tetrafluoropyrid-4-yl-2-tetrafluoropyrid-4-yl-thio-1H-benzimidazole (molecule-II) which were produced as part of a family of fluorinated drug scaffolds prepared for anticancer and antiparasitic screening. Spectra display significant second-order effects with
1H Δδ = 3.68 and 4.67 Hz for the aromatic hydrogen “triplets”, with
19F
4J
AA',
4J
BB',
4J
XX', and
4J
YY' coupling constants range from +4.8 to −14.0 Hz and for
13C-isotopomers
19F Δδ of up to 111.56 Hz. A spin-system of six coupling nuclei (H
aH
bH
cH
d F
YF
Y') was analysed in 12 s, a spin-system of nine coupling fluorine nuclei (AA'BB'CCC-YY') was analysed within 2 min, and 10 coupling nuclei (XX'YY'ZZZ-BB'-H
d) was optimised in 6 min using a laptop computer. ANATOLIA was also robust enough to be able to yield accurate spectral values from inaccurate input values. In both compounds, a fluorine–fluorine coupling constant was identified between the two fluoro-aromatic rings (F
BB' and F
YY') of +4.05 and +4.67 Hz and attributed to a through-space interaction. Ab initio structure optimisations and coupling constant calculations provided useful input data for spectral analysis. A modern
19F nuclear magnetic resonance spectrum of perfluorotoluene (octafluorotoluene) and analysis from 1975 was used as a test data set to assess ANATOLIA.
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