title: Peptide synthesis in aqueous environments: the role of extreme conditions on amino acid activation.
abstract: The free energy surfaces and reaction mechanisms underlying the activation of amino acids by COS in bulk water at ambient conditions as well as extreme temperature-pressure thermodynamic conditions were studied using accelerated ab initio molecular dynamics. The results for the reaction sequence leading from glycine to its activated form, a so-called Leuchs anhydride or alpha-amino acid N-carboxyanhydride (NCA), suggest that extreme conditions not far from the critical point of water may favor the formation of this activated species. This is traced back to appropriately affecting relative stabilities of neutral versus charged or zwitterionic molecular species which shifts equilibria, affects relative barriers, and thus modifies reaction rates. Furthermore, it is shown that the N-carboxyanhydride of glycine is not formed from N-thiocarboxyl glycine by its direct cyclization, but instead an indirect mechanism, the so-called isocyanate route, is clearly preferred at both conditions. The work quantitatively underpins the impact of extreme solvent conditions on the investigated organic reactions in aqueous media which implies that the presented results are of relevance to fields such as prebiotic chemistry and green chemistry.
authors.affiliation: Lehrstuhl für Theoretische Chemie, Ruhr-Universität Bochum, 44780 Bochum, Germany.
authors.forename: Nisanth N
authors.initials: NN
authors.lastname: Nair
authors.forename: Eduard
authors.initials: E
authors.lastname: Schreiner
authors.forename: Dominik
authors.initials: D
authors.lastname: Marx
mesh_terms: D000812:Anhydrides / Q000737:chemistry; D003198:Computer Simulation; D003500:Cyclization; D005998:Glycine / Q000737:chemistry*; D017953:Isocyanates / Q000737:chemistry; D008956:Models, Chemical; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D011522:Protons; D011789:Quantum Theory; D012997:Solvents / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013499:Surface Properties; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
chemical_list: D000812:Anhydrides; D017953:Isocyanates; D010455:Peptides; D011522:Protons; D012997:Solvents; D013438:Sulfhydryl Compounds; D014867:Water; D005998:Glycine