Structural and Topological Studies of Methionine Radical Cations in Dipeptides: Electron Sharing in Two-Center Three-Electron Bonds

Abstract

One electron oxidation of methionine in peptides is highly dependent on the local structure. The sulfur-centered radical cation can complex with oxygen, nitrogen, or other sulfur atoms from a neighboring residue or from the peptidic bond, forming an intramolecular S therefore X two-center three-electron bond (X = S, N, O). This stabilization was investigated computationally in the radical cations of three peptides, methionine glycine (Met Gly) and its reverse sequence Gly Met, and Met Met. Geometry optimizations were done at the BH&HLYP/6-31G(d) level of theory and the effect of solvation was taken into account using a continuum model (CPCM). Up to seven stable conformations were considered for each peptide, with formation of 5-10 member cycles involving nitrogen from the peptidic bond or from the amine, oxygen from the peptidic bond or from the carboxylate group, or sulfur from the other residue for Met Met. The absorption wavelengths corresponding to the sigma --> sigma* transition calculated for each complex at the TD-BH&HLYP/6-311+G(d,p)//BH&HLYP/6-31G(d) level of theory vary from the near-UV for the S therefore O bonds to the green visible for the S therefore S bonds. For X = N, they increase with the SN distance as expected for a 2c-3e bond, whereas for X = O they slightly decrease. Characterization of these 2c-3e bonds as a function of the sequence, using the ELF and the AIM topological analyses, shows the different natures of the S therefore X bonds, which is purely 2c-3e for X = S, mainly 2c-3e with a part of electrostatic interaction for X = N and mainly electrostatic for X = O.

Communication: Covalent nature of X⋯H2O (X = F, Cl, and Br) interactions

“…138, 141102 (2013) Table I are characteristic features of a 2c-3e bond. 43 The evidence strongly indicates that the X· · ·H 2 O interaction in such complexes has a covalent origin, which is fundamentally different from the conventional van der Waals forces dominated by electrostatic and dispersion interactions. Interestingly, a similar 2c-3e interpretation has been proposed to explain the "strongly" bound Cl· · ·NH 3 complex, which has been repeatedly found at various levels of theory.…”

Methionine one-electron oxidation: Coherent contributions from radiolysis, IRMPD spectroscopy, DFT calculations and electrochemistry

“…Cycles involving 6, 7 or 9 atoms were obtained. Upon solvation, the SO distances in SOpep radicals increased (by 0.07-0.12 Å) [24]. Among the 17 structures that we have explored, the energies of the entities generally tended to increase with the SX bond length.…”

“…In water, the zwitterions SNam are not stable. In all peptides, methylated or zwitterionic, among the SN5 radical cations the energy increased with the SN bond lengths [24]. The SN distance was shorter in the SN5am radicals (around 2.45 Å) than in SN5pep1 (2.57 Å).…”

“…In the SS radicals, the SS distance increased from R SS = 2.79 Å for the simplest [24,25]. In the Met-Met cation, the value is also relatively large (2.96 Å).…”

“…The structure of the methionine free radical was thoroughly explored by DFT methods and by topological approaches [23,24]. We adopted the following nomenclature: for the SN radicals, S can be linked either to N of the amine function (SNam) or to N of the peptidic bond (SNpep).…”