Assisted dipeptide bond formation: glycine as a case study

Abstract

Peptide bond formation is a crucial chemical process that dominates most biological mechanisms and is claimed to be a governing factor in the origin of life. Dipeptides made from glycine are studied computationally via Density Functional Theory (DFT) using two different basis sets. This reaction was investigated from both a thermodynamic and kinetic point of view. The effect of explicit assistance via the introduction of discrete solvent molecules was investigated. Water, methanol, and cyclohexane were all employed as solvent media in addition to gas to investigate their effects on the mechanism of peptide bond formation. This computational investigation revealed that methanol is slightly better than water to leverage peptide bond formation both kinetically and thermodynamically, while cyclohexane, a non-polar and non-protic solvent, is the least effective after gas as a medium of solvation. Energetic results in the gas environment are very close to those obtained in polar and protic solvents, suggesting that peptide bonds can be formed under interstellar conditions.

Peptide condensation and hydrolysis mechanisms from a proton-transfer network perspective

“…2) start- ing materials is −44 kJ mol −1 . However, counter to what is reported in earlier computational models, 13 the employment of polarizable continuum model SMD does not universally lower energy barriers. Comparing Fig.…”

“…The longer distances increase the reorganization energy needed to enter the catalytic transition state. Previous computational work showing a catalytic effect of water molecules 2,13 have potentially a bias due to the absence of a water continuum, since a water molecule can mitigate the lack of a stabilizing environment for charge separation associated with proton transfer.…”

“…More recently, implicit and explicit solvation models were considered that allowed for evaluation of the role of the zwitterionic forms and the solvation effects on the barrier heights, the overall thermodynamics, and the catalytic effect of water solvent molecule(s). [11][12][13] In addition, Brigiano et al looked at a more complex mechanism in a periodic water bath through mapping multiple intermediates that can be formed on a silica surface using ab initio molecular dynamic approach. 14 The key observation by Gale et al was that addition of up to 5 explicit solvating water molecules in vacuo decreased the overall free energy barrier of the 1-step trans mechanism from 221 to 173 kJ mol −1 at the PW91/6-311++G** level.…”

“…More recently, implicit and explicit solvation models were considered that allowed for evaluation of the role of the zwitterionic forms and the solvation effects on the barrier heights, the overall thermodynamics, and the catalytic effect of water solvent molecule(s). 11–13 In addition, Brigiano et al looked at a more complex mechanism in a periodic water bath through mapping multiple intermediates that can be formed on a silica surface using ab initio molecular dynamic approach. 14…”

Mechanisms and Origins of Regio- and Stereoselectivities in NHC-Catalyzed [3 + 3] Annulation of α-Bromoenals and 5-Aminoisoxazoles: A DFT Study

“…All calculations in this work were performed using the Gaussian 16 (Revision A03) program . Given the proven excellent performance of DFT in organocatalytic reactions and transition-metal catalytic reactions, we use M06-2X/6-31G­(d,p) to optimize the geometry of all stationary points (e.g., transition states and intermediates) in THF using the IEF-PCM solvation model to simulate solvent effects. The nature of the optimized structure is checked by frequency analysis at the same computational level, where reactants, products, and intermediates have no imaginary frequency, while transition states show one.…”