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

Abstract

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 NICS pav 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.

The σ+π dual aromaticity of typical bi‐tetrazole ring molecule TKX‐50

“…Thus, we use the integral of the NICS curve to compare the shielding effect thereof via the methods proposed by Amnon Stanger and Wojciech M. Dudek et al. [61,135] The anisotropy of the induced current density (AICD) calculations were carried out with the AICD program. [104] Bond length and Mayer bond order calculation, NICS ZZ curve plot, NICS ZZ plane map plot, molecular orbitals plotting and orbital contributions analysis, LOL map plotting, ICSS ZZ all adopted the wave function analysis code Multiwfn.…”

“…Thus, we use the integral of the NICS curve to compare the shielding effect thereof via the methods proposed by Amnon Stanger and Wojciech M. Dudek et al. [61,135] . The anisotropy of the induced current density (AICD) calculations were carried out with the AICD program [104] …”

Aromaticity in isoelectronic analogues of benzene, carborazine and borazine: Perspective from electronic structure and magnetic property

“…The integrated values of NICSzz curve that vertically crosses a certain ring, denoted as ∫NICSzz, is a recently proposed reliable method for quantitatively measuring the aromaticity of cyclic systems. 62,63 A key advantage of ∫NICSzz compared to conventional NICSzz analysis is that it is free from the choice of the point to be studied, thus enabling more rigorous conclusions to be drawn; in the meantime, scanning…”

HOMA Index Establishes Similarity to a Reference Molecule

“…Such comparison is even more important because the chemical shift is observable. In contrast, most of the NICS indices are not, and only recently was it proven that the integral NICS index introduced by Stanger, INICS, , was physically justified through its relation to the ring current via Ampère–Maxwell’s law as demonstrated by Berger et al , …”