Uncatalyzed peptide bond formation between two double amino acid molecules in the gas phase

Abstract

The gas phase mechanism for peptide bond formation between two double amino acid (DAA) molecules ((NH2)2C(COOH)2) is investigated in the absence of any catalysts. Two different paths, concerted and stepwise, each leading to both cis and trans DAA‐DAA dipeptide products (four mechanisms total) are examined on the basis of theoretical calculations carried out at the CCSD(T)/aug‐cc‐pVDZ//MP2/aug‐cc‐pVDZ level. The investigation indicates that the concerted mechanism leading to the trans configuration of the peptide bond in the DAA‐DAA dipeptide product is thermodynamically favored by about 5 kcal mol−1 and requires slightly less energy than the remaining pathways considered. Moreover, the peptide bond formation process between two DAA molecules in the gas phase resembles the analogous reactions between two natural amino acids.

Gas Phase Bond Formation in Dipeptide Clusters

“…A natural environment for such abiotic synthesis to occur is within amino acid clusters. Various amino acids (although not all) are known to form stable noncovalent complexes both in solution and in the gas phase. − Theory suggests that the orientation of the OH···H mode of hydrogen bonding between neighboring amino acid molecules in clusters is suitable for bond formation, suggesting that peptides can be formed even in the gas phase . Nevertheless, for bond formation energy must be deposited into the cluster, and consequently the evaporation of molecules from the cluster will compete with peptide bond formation.…”

Water-assisted peptide bond formation between two double amino acid molecules in the gas phase

“…The presence of a water molecule during the formation of DAA-DAA dipeptide has been proven important regardless of the conformation of the final product as the energy barriers predicted for the water-assisted mechanisms are significantly reduced in comparison to the barriers found for the corresponding uncatalyzed reactions [27]. In order to explain the catalytic role of the H 2 O molecule in this process, one may follow the speculation provided in ref.…”

“…Its stability with respect to both unimolecular deamination and decarboxylation reactions has already been addressed in order to show that spontaneous detachment of either ammonia or the carbon dioxide molecule in gas and aqueous phases is not operative [24,25]. Moreover, we demonstrated that the DAA system acts similarly to various natural amino acids when the noncatalyzed peptide bond formation process between two DAA molecules or the cyclization involving two DAAs in gas phase are considered [26,27].…”

“…The analysis of both concerted mechanisms reveals that the peptide bond is formed through a transition state structure containing a six-membered ring Fig. 1 Equilibrium structure of the most stable canonical isomer of double amino acid (DAA) molecule in the gas phase involving a water molecule (unlike the highly strained fourmembered ring TS structures found earlier for the corresponding noncatalyzed concerted mechanisms [27]). It is important to notice that in these two TS structures (for which the imaginary vibration frequencies are equal to 837i cm −1 and 630i cm −1 for the trans and cis route, respectively) the water molecule acts as both a hydrogen atom acceptor and donor with respect to the amino group of one DAA and the OH group of the second DAA molecule.…”

Polypeptide formation in clusters of β-alanine amino acids by single ion impact

“…Amino acid clusters (dimer and tetramer clusters of α-alanine) have been studied by theory as precursors for polypeptide formation as the orientation of the OH ⋯ NH mode of hydrogen bonding is found to be suitable for chemical condensation 15 . In the case of two glycine molecules 16 or double amino acids 17 , different mechanisms for peptide bond formation have been mapped out with quantum mechanical electronic structure methods. Furthermore, peptide bond formation has also been suggested to be initiated by glycine protonated at the hydroxyl oxygen 18 .…”