Ortho-Methoxy Group as a Mild Inhibitor of the Reactions Between Carboxylic Acid and Phenols

According to the current database of natural products, over 25,000 compounds contain a vanillyl ring in their structure. The reasoning behind the high occurrence of the vanillyl ring structure seemed to be poorly understood, specifically the preference for a methoxy-substituted phenol structure as opposed to its dihydroxy analogue. To better understand this, we investigated the reaction mechanisms of two methoxyphenol structures, in syn and anti conformations, two hydroxyphenol structures, also in syn and anti conformations, and phenol as a reference structure, with acetic acid. Of the starting structures, the syn hydroxyphenol was found to be kinetically the most reactive, and formed the most stable product, while both hydroxyl-substituted phenols reacted more favorably with acetic acid than the methoxyphenols. A preference for the methoxyphenol molecule may exist as a way to hinder the formation of stable covalent bonds between natural products and cellular components. This work is licensed under a Creative Commons Attribution 4.0 International License

Computational Study of the Reactions of Interstellar Molecules: CH2 Reacting with HCNO and HNCO

Association reactions among small molecules known to exist in the interstellar medium are interesting for theories on the origins of life. A screening of thousands of reactions, using machine learning estimates of energy barriers, identified the reaction of CH2 with HCNO and HNCO as particularly interesting. We report reaction mechanisms, including energies of transition states and products, computed with density functional theory and coupled cluster theory. The lowest energy pathway on the triplet ground state surface of CH2 + HNCO has a barrier of 11 kcal/mol and produces CH2(CO)NH. Singlet CH2 is 9 kcal/mol above the ground state. It can react with HCNO or HNCO without barrier giving four products: CH2NCHO, N-methyleneformamide, the thermodynamically favoured product; NHCHCHO; NHCHOCH; and (CH2OC)NH, oxiran-2-ylazanide. If triplet to singlet crossing occurs, an upper bound of roughly 10 kcal/mol is implied for the barrier to formation of these four products

Ketene and Ammonia Forming Acetamide in the Interstellar Medium

Background: Peptide bonds are among the fundamental building blocks of life, polymerizing amino acids to form proteins that make up the structural components of living cells and regulate biochemical processes. The detection of glycine by NASA in comet Wild 2 in 2009 suggests the possibility of the formation of biomolecules in extraterrestrial environments through the interstellar medium. Detected in the dense molecular cloud Sagittarius B2, acetamide is the largest molecule containing a peptide bond and is hypothesized to be the precursor to all amino acids; as such, viability of its formation is of important biological relevance. Methods: Under a proposed mechanism of ammonia and ketene reactants, which have also been detected in dense molecular clouds in the ISM, the reaction pathway for the formation of acetamide was modelled using quantum chemical calculations in Gaussian16, using Austin-Frisch-Petersson functional with dispersion density functional theory at a 6-31G(d) basis set level of theory to optimize geometries and determine the thermodynamic properties for the reaction. Stability of the reactants, transition states, and products were examined to establish a reasonable mechanism. Conclusion: Product formation of acetamide was found to be highly exergonic and exothermic with a low energy barrier, suggesting a mechanism that is viable in the extreme density and temperature conditions found in ISM

Quantum Chemical Study of the Formation of Urea in Interstellar Medium

Background: Many observational studies have found the presence of organic molecules in interstellar medium (ISM) via spectroscopy. NH2CONH2 (urea) was first detected in ISM in 2014. Containing two NH2 groups, urea is an important biological molecule in metabolism as a carrier for waste nitrogen. The discovery of urea in ISM suggests the possibility of the formation of other biomolecules which contain peptide bonds, such as proteins. This supports the origin of life theory proposing that these biomolecules were initially formed in space and later arrived to Earth. Methods: This study investigates two possible reaction pathways for the formation of protonated urea (ureaH+) in dense molecular clouds via molecules previously observed in the ISM, formamide (HCONH2) and protonated hydroxylamine (NH2OH2+). The thermodynamics and optimized geometries were calculated for the final steps of the formation of ureaH+ using Gaussian16 at the APFD/6-31G(d,p) level of theory and a transition state was confirmed. Results: The overall mechanism, as well as the studied proton rearrangement of an intermediate to ureaH+, were found to be exothermic and exergonic processes. Conclusion: From the calculations, the conditions of ISM provide an adequate environment for the formation of ureaH+ and urea

Predicted Reversal in N-Methylazepine/N-Methyl-7-azanorcaradiene Equilibrium upon Formation of Their N-Oxides

Density functional calculations and up to five different basis sets have been applied to the exploration of the structural, enthalpy and free energy changes upon conversion of the azepine to the corresponding N-oxide. Although it is well known that azepines are typically much more stable than their 7-azanorcaradiene valence isomers, the stabilities are reversed for the corresponding N-oxides. Structural, thermochemical as well as nucleus-independent chemical shift (NICS) criteria are employed to probe the potential aromaticity, antiaromaticity and nonaromaticity of N-methylazepine, its 7-azanorcaradiene valence isomer. For the sake of comparison, analogous studies are performed on N-methylpyrrole and its N-oxide

Predicted Reversal in N-Methylazepine/N-Methyl-7-azanorcaradiene Equilibrium upon Formation of Their N-Oxides

Density functional calculations and up to five different basis sets have been applied to the exploration of the structural, enthalpy and free energy changes upon conversion of the azepine to the corresponding N-oxide. Although it is well known that azepines are typically much more stable than their 7-azanorcaradiene valence isomers, the stabilities are reversed for the corresponding N-oxides. Structural, thermochemical as well as nucleus-independent chemical shift (NICS) criteria are employed to probe the potential aromaticity, antiaromaticity and nonaromaticity of N-methylazepine, its 7-azanorcaradiene valence isomer. For the sake of comparison, analogous studies are performed on N-methylpyrrole and its N-oxide

An Improved Two-Rotor Function for Conformational Potential Energy Surfaces of 20 Amino Acid Diamides

Predicting the three-dimensional structure of a protein from its amino acid sequence requires a complete understanding of the molecular forces that influences the protein folding process. Each possible conformation has its corresponding potential energy, which characterizes its thermodynamic stability. This is needed to identify the primary intra- and intermolecular interactions, so that we can reduce the dimensionality of the problem, and create a relatively simple representation of the system. Investigating this problem using quantum chemical methods, albeit produces accurate results, this also entails large computational resources needed. In this study, an improved two-rotor potential energy function is proposed to represent the backbone interactions in amino acids, through a linear combination of a Fourier series and a mixture of Gaussian functions. This function is applied to approximate the 20 amino acid diamide Ramachandran-type PESs, and results yielded an average RMSE of 2.36 kJ路molThe accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

A Prelude to Building Mathematical Models for Polypeptide Folding: Analysis on the Conformational Potential Energy Hypersurface Cross-Sections of N-Acetyl-Glycyl-Glycine-N'-Methylamide

Finding a relationship on how a three-dimensional protein folds from its linear amino acid chain gets more complex with increasing chain length, so working on a smaller peptide conformational problem can provide initial ideas on what are the main molecular forces and how these influence the folding process. Following the study of conformations of amino acid units entering the proteins to understand the secondary structure of small peptides, this paper proposes mathematical models for the several two-rotor cross-sections of the 5D N-acetyl-glycyl-glycine-N'-methylamide potential energy hypersurface. These cross-sections are extracted along the first glycine subunit, with its coordinates fixed at the five energy minima of the glycine diamide. The resulting mathematical models yield an average RMSE of 1.36 kJ·molThe accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author