Increasing the sensitivity of the molecular probes for the substituent effects - The SESE approach

The application of DFT computational methods to 5-substituted derivatives of 1,2,3-trifluorobenzene and 1,2,3-tris(trifluoromethyl)benzene allows to study changes in the electronic properties of these compounds under the influence of 15 substituents (-NO, -NO2, -CN, -CF3, -COCH3, -COOH, -CHO, -CONH2, -Cl, -F, -H, -CH3, -OCH3, -OH, -NH2) with well-known Hammett-type constants (sigma(p), sigma(m), R, and F). In the case of 1,2,3-tris(trifluoromethyl)benzene, the obtained dependencies of theoretically calculated SESE (substituent effect stabilization energy) values on the empirically determined Hammett substituent constants (sigma(p), sigma(m)) are, so far, the most sensitive theoretical probes for the substituent effects in the aromatic system. The presence of as many as three substituents (-F or -CF3) of such an expressive nature significantly increases the sensitivity of the SESE to changes caused by another substitution. The obtained sensitivity is 3 times higher than in the case of standard mono-substituted molecular probes. However, the price for that is a slightly lower accuracy (correlation coefficient). (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

The study applied DFT computational methods to analyze the electronic properties of 5-substituted derivatives of 1,2,3-trifluorobenzene and 1,2,3-tris(trifluoromethyl)benzene, investigating the impact of substituents on these compounds. It was found that the presence of multiple substituents increased the sensitivity of the substituent effects, but with a slightly lower accuracy in comparison to standard mono-substituted molecular probes.