On Aromaticity of the Aromatic α-Amino Acids and Tuning of the NICS Indices to Find the Aromaticity Order.

The NICS aromaticity indices of the rings in flexible phenylalanine (Phe), tryptophan (Trp), tyrosine (Tyr), and histidine (His) chiral molecules were analyzed. These molecules have several dozens of conformers, and their rings are slightly non-planar. Therefore, the population-averaged NICSpav index was defined, and the NICS scans had to be performed with respect to planes found by the least-squares routine. A rule differentiating an obverse and a reverse ring face in aromatic amino acids was formulated. The NICS scan minima corresponding to the obverse and reverse face were unequal, which prompted us to use the term ring face aromaticity/ring face tropicity. It appeared that for Phe, Trp, Tyr, and His, the reverse face has always had higher ring face aromaticity/ring face tropicity than the obverse one. Despite the NICS modifications, uncertainty about the amino acid aromaticity order remained. This motivated us to use the integral INICS index newly proposed by Stanger as well. Then, the following sequence was obtained: Trp(phenyl) > Phe > Trp(pyrrole) > His > Tyr. The juxtaposition of the INICS indices of amino acids with that of some model rings revealed a fair transferability of the values. Finally, analysis of the substituent effect on INICS demonstrated that the aromaticity of Tyr is the lowest due to the strength of the OH group π-electron-donating effect able to perturb enough the ring charge distribution and its magnetic aromaticity. The NICS calculations were executed using the ARONICS program written within the project.

Substituent Effect in the Cation Radicals of Monosubstituted Benzenes.

In 30 monosubstituted benzene cation radicals, studied at the ωB97XD/aug-cc-pVTZ level, the phenyl rings usually adopt a compressed form, but a differently compressed form-equivalent to an elongated one-may coexist. The computational and literature ionization potentials are well correlated. The geometrical and magnetic aromaticity, estimated using HOMA and NICS indices, show the systems to be structurally aromatic but magnetically antiaromatic or only weakly aromatic. The partial charge is split between the substituent and ring and varies the most at C(ipso). In the ring, the spin is 70%, concentrated equally at the C(ipso) and C(p) atoms. The sEDA(D) and pEDA(D) descriptors of the substituent effect in cation radicals, respectively, were determined. In cation radicals, the substituent effect on the σ-electron system is like that in the ground state. The effect on the π-electron systems is long-range, and its propagation in the radical quinone-like ring is unlike that in the neutral molecules. The pEDA(D) descriptor correlates well with the partial spin at C(ipso) and C(p) and weakly with the HOMA(D) index. The correlation of the spin at the ring π-electron system and the pEDA(D) descriptor shows that the electron charge supplied to the ring π-electron system and the spin flow oppositely.