Quantum chemical modeling was used to investigate the electron-donating properties of the amino group in a series of meta- and para-X-substituted anilines (X = NMe2, NH2, OH, OMe, CH3, H, F, Cl, CF3, CN, CHO, COMe, CONH2, COOH, NO2, and NO). Different methods (HF, B3LYP, and M06-2X) and basis sets (6-31+G(d,p), 6-311++G(d,p), and aug-cc-pVDZ) were applied and compared with the MP2 approach. The B3LYP/6-311++G(d,p) method was chosen as the most appropriate one. The substituent properties were described by σ, cSAR(X) and SESE descriptors; the amino group was characterized by structural (dCN, dNH and ΣNH2) and electronic [δ(N) and cSAR(NH2)] parameters; whereas the transmitting moiety was characterized by aromaticity indices HOMA and NICS, as well as by QTAIM characteristics at the ring critical point. All the used parameters were found to be mutually interrelated with much better correlations for the para-derivatives than the meta-derivatives. It was numerically confirmed that sensitivity of the amino group to the substituent effect was greater by over three times when the substituent was located in the para-position. In the case of the meta-derivatives, variability of characteristics for both the reaction center and the substituent was small. The reverse substituent effect was clearly shown by comparison of the cSAR(X) characteristics for monosubstituted benzenes, and meta- and para-substituted anilines.

The application of ab initio and DFT computational methods at six different levels of theory (MP2/cc-pVDZ, MP2/aug-cc-pVTZ, B3LYP/cc-pVDZ, B3LYP/aug-cc-pVTZ, M06/cc-pVDZ, and M06/aug-cc-pVTZ) to meta- and para-substituted fluoro- and trifluoromethylbenzene derivatives and to 1-fluoro- and 1-trifluoromethyl-2-substituted trans-ethenes allowed the study of changes in the electronic and geometric properties of F- and CF3-substituted systems under the impact of other substituents (BeH, BF2, BH2, Br, CFO, CHO, Cl, CN, F, Li, NH2, NMe2, NO, NO2, OH, H, CF3, and CH3). Various parameters of these systems have been investigated, including homodesmotic reactions in terms of the substituent effect stabilization energy (SESE), the π and σ electron donor-acceptor indexes (pEDA and sEDA, respectively), the charge on the substituent active region (cSAR, known earlier as qSAR), and bond lengths, which have been regressed against Hammett constants, resulting mostly in an accurate correspondence except in the case of p-fluorobenzene derivatives. Moreover, changes in the characteristics of the ability of the substituent to attract or donate electrons under the impact of the kind of moiety to which the substituent is attached have been considered as the indirect substituent effect and investigated by means of the cSAR model. Regressions of cSAR(X) versus cSAR(Y) for any systems X and Y allow final results to be obtained on the same scale of magnitude.

An application of a charge of the substituent active region concept to 1-Y,4-X-disubstituted derivatives of bicyclo[2.2.2]octane (BCO) [where Y = NO 2 , COOH, OH, and NH 2 and X = NMe 2 , NH 2 , OH, OMe, Me, H, F, Cl, CF 3 , CN, CHO, COMe, CONH 2 , COOH, NO 2 , and NO] provides a quantitative information on the inductive component of the substituent effect (SE). It is shown that the effect is highly additive but dependent on the kind of substituents. An application of the SE stabilization energy characteristics to 1,4-disubstituted derivatives of BCO and benzene allows the definition of inductive and resonance contributions to the overall SE. Good agreements with empirical approaches are found. All calculations have been carried out by means of the B3LYP/6-311++G(d,p) method.

Substituents effects in cyclic diene derivatives are studied using quantum chemical modeling and compared to the corresponding effects in aromatic (benzene) and fully saturated (bicyclo[2.2.2]octane) compounds. In particular, electronic properties of the fixed group Y in a series of 3-and 4-X-substituted cyclohexa-1,3-diene-Y derivatives (where Y = NO 2 , COOH, COO − OH, O − , NH 2 , and X = NMe 2 , NH 2 , OH, OMe, Me, H, F, Cl, CF 3 , CN, CHO, COMe, CONH 2 , COOH, NO 2 , NO) are examined using the B3LYP/6-311++G(d,p) method. For this purpose, quantum chemistry models of the substituent effect: cSAR (charge of the substituent active region) and SESE (substituent effect stabilization energy) as well as traditional Hammett's substituent constants (σ) and their inductive (F) and resonance (R) components are used. π-electron delocalization of the transmitting moiety (butadiene fragment of the CHD) is described by the HOMA index. This comparative study reveals interplay between inductive and resonance contributions to the substituent effect.

Inductive substituent constants were obtained for systems lacking the resonance effect. The application of the charge of the substituent active region concept to study the substituent effect in 1-X-substituted bicyclooctane derivatives (B3LYP/6-311++G** calculations, X = NMe 2 , NH 2 , OH, OMe, CH 3 , H, F, Cl, CF 3 , CN, CHO, COMe, CONH 2 , COOH, NO 2 , NO) has revealed inductive interactions, which are through bonds.