Interaction between the guanidinium cation and aromatic amino acids

Abstract

The interaction of the guanidinium cation with phenylalanine, tyrosine and tryptophan has been studied using a variety of computational methods. Benchmark values for the interaction have been estimated using the CCSD(T) method extrapolated to the complete basis set limit, indicating that the complexation energy amounts to -123.0, -124.4 and -134.2 kJ mol(-1) for Phe, Tyr and Trp, respectively. Most stable minima correspond to neutral folded amino acids, with the cation interacting simultaneously with the carboxyl oxygen, the amino nitrogen and the aromatic ring. However, complexes with the amino acids as zwitterions are as stable as neutral ones. The final relative stability of the different structures results from a complex balance among different contributions to the complexation energy. Extended neutral structures are favored by larger electrostatic and smaller repulsion contributions, as well as by smaller deformation costs for bringing the amino acid to its final geometry into the complex. Zwitterions show large electrostatic and induction contributions that cancel out the huge deformation cost needed to transfer the proton to the amino group. The presence of the cation···π contact in folded minima introduces larger contributions from induction and dispersion (also as a consequence of the bulky guanidinium cation) that are able to overcome other effects, making folded minima the most stable together with zwitterionic ones.

On the interaction between the imidazolium cation and aromatic amino acids. A computational study

“…As in our previous work on guanidinium complexes, 58 the different methods reproduce fairly well the order of stability of the different complexes, though several differences arise. The largest differences correspond to the relative stability of the zwitterionic/neutral complexes.…”

“…Besides, previous work has shown the good performance of the M06-2X/6-31+G* level of calculation in describing the relative stabilities of these complexes. 58 Finally, the subset of selected minima covers all structures within 10 kJ mol −1 above the global minima, so it can be considered that all structures accessible at room temperature are already taken into account.…”

“…As expected, extended minima show smaller deformation energies around 10 kJ mol −1 , whereas in the case of zwitterions, the cost of proton transfer is huge, reaching 90 kJ mol −1 . As indicated in previous work, 58 the contribution of deformation is essential in order to understand the stability in these complexes. The same behaviour is observed in Tyr and Trp complexes, with stacked minima being penalised by conformational changes.…”

“…Also, the results obtained indicate that for amino acid⋯guanidinium complexes stacked structures are favoured due to larger induction and dispersion interactions associated with the cation⋯π contact, which have to overcome the effort of folding the amino acid. 58 Following this line of work, in the present work a study is performed on the interaction between aromatic amino acids and the imidazolium cation (C 3 N 2 H 5 + ). The imidazolium cation is a five membered planar aromatic cycle which can be formed by protonation of the amino acid histidine.…”

Aromatic Amino Acids-Guanidinium Complexes through Cation-π Interactions

“…They found that the differences in stability were mainly a consequence of the different strength of the cation···π contact [21]. On the other hand, they have recently published the study of the interaction of guanidinium with Phe, Tyr and Trp in the gas phase as neutral systems finding that the most stable minima correspond to folded amino acids, with the cation interacting simultaneously with the carboxyl oxygen, the amino nitrogen and the aromatic ring, whereas zwitterionic amino acids are as stable as neutral ones [22].…”