Aromatic Amino Acids-Guanidinium Complexes through Cation-π Interactions

Abstract

Continuing with our interest in the guanidinium group and the different interactions than can establish, we have carried out a theoretical study of the complexes formed by this cation and the aromatic amino acids (phenylalanine, histidine, tryptophan and tyrosine) using DFT methods and PCM-water solvation. Both hydrogen bonds and cation-π interactions have been found upon complexation. These interactions have been characterized by means of the analysis of the molecular electron density using the Atoms-in-Molecules approach as well as the orbital interactions using the Natural Bond Orbital methodology. Finally, the effect that the cation-π and hydrogen bond interactions exert on the aromaticity of the corresponding amino acids has been evaluated by calculating the theoretical NICS values, finding that the aromatic character was not heavily modified upon complexation.

Guanidinium export is the primal function of SMR family transporters

“…Despite the obvious difference in size between Gdm + and the bulky substrates transported by EmrE, the substrates share a chemical essence that alludes to the familial relationship: cationic aromaticity. Gdm + is a chemically unusual "Y-aromatic"-a planar molecule with electrons delocalized in pi orbitals over both faces (20,21). It is easy to imagine how a Gdm + exporter might share common traits with a promiscuous exporter of larger substrates with shared chemical attributes (Scheme 1).…”

Activation/Inactivation Role of Ionic Liquids on Formate Dehydrogenase from Pseudomonas sp. 101 and Its Mutated Thermostable Form

“…The Bmim cation does not induce changes in the protein structure by formation of stable interactions. However, it can undergo π–π stacking interactions with solvent‐exposed imidazole groups of His and Trp residues (Figure A,C) and sometimes cation–π interactions with solvent‐exposed Arg residue of the enzyme, so also influencing protein structure and exposing Trp to the solvent …”

A computational insight into the interaction of methylated lysines with aromatic amino acid cages

“…We formulated aromatic cages consisting of 1, 2, and 3 model aromatic amino acids, and we analyzed the binding of model Lys cations to these model cages. The M06‐2X functional was shown to describe noncovalent interactions superior than other DFT functionals, and it was used in the studies involving cation‐π interactions . The structure of model Lys and aromatic amino acids was simplified so as to have only cation‐π interactions solely in our calculations.…”

“…The M06-2X functional was shown to describe noncovalent interactions superior than other DFT functionals, [25] and it was used in the studies involving cation-π interactions. [26] The structure of model Lys and aromatic amino acids was simplified so as to have only cation-π interactions solely in our calculations. In the literature, even though there exist some computational studies regarding the interaction of cations with aromatic groups, [20] a systematic study pertaining to the interaction of Lys with different methylation degrees with different aromatic amino acids as well as aromatic cages made up of different combinations of aromatic amino acids was not reported.…”