CONFORMATIONAL LANDSCAPE OF 3-MERCAPTOPROPIONIC ACID AND METHYL 3-MERCAPTOPROPIONATE REVEALED BY MICROWAVE SPECTROSCOPY AND THEORETICAL CALCULATIONS

The structures of 3-mercaptopropionic acid (mpa) [HS-CH$_{2}$-CH$_{2}$-C(O)-OH] and methyl 3-mercaptopropionate (mp) [HS-CH$_{2}$-CH$_{2}$-C(O)-O-CH$_{3}$] were investigated in the range of 8-18 GHz using both chirped pulse and cavity-based Fourier transform microwave spectrometers. One (mpa1) and two (mp1 and mp2) stable conformers were assigned in the rotational spectra for the acid and the ester compound, respectively. Despite our efforts, no other energy minima predicted by theory was experimentally observed in the spectra which could be a result of their high relative energies and/or small barriers to re-arrangement (relaxation to lower energy conformers). Splitting due to the presence of the methyl internal rotor in the ester species were observed in the rotational transitions of both mp1 and mp2. The latter also presents an additional splitting related to the torsional motion of the SH group around the C-C-S-H dihedral angle that allows the interconversion between two enantiomers of mp2. The observed rotational transitions for the acid and the ester were fit using the Pickett’s SPFIT and the XIAM programs, respectively. The derived rotational parameters are well-determined and consistent with the quantum mechanical calculations performed at both DFT B3LYP-D3BJ and ab initio MP2 methods with the aug-cc-pVTZ basis set. The higher stability of conformers mpa1 and mp1 is explained by the presence of an intramolecular SH$^{...}$O=C interaction, investigated on the basis of the quantum theory of atoms in molecules (QTAIM) and the non-covalent interaction (NCI) analyses

HYDROGEN BONDING IN THE MONOHYDRATED COMPLEXES OF TRIMETHYLENE OXIDE, SULFIDE AND SELENIDE: A ROTATIONAL SPECTROSCOPIC AND THEORETICAL INVESTIGATION

The monohydrated complexes of trimethylene oxide and sulfide were investigated in the gas phase using Fourier transform microwave spectroscopy (8-18 GHz) aided by quantum mechanical calculations. In the assigned trimethylene oxide-water complex, the water subunit binds exclusively to the oxygen atom of the ring via a OH…O hydrogen bond (HB). In the sulfur containing complex, in addition to the primary OH…S HB, a secondary CH…O interaction is observed. The experimental results for the sulfur analog are consistent with the predictions from both \textit{ab initio} and density functional theory (DFT) calculations with the aug-cc-pVTZ basis set whereas for the oxygen analog, both planar and puckered ring configurations are possible depending on the level of theory. Our experimental data aligns better with the results from DFT calculations which predict the trimethylene oxide ring to adopt a planar configuration in the complex. The nature and strength of the HBs are studied in detail using topological and energy decomposition analyses. Comparisons are also made computationally with the selenium analog to evaluate the characteristics of the HB along the chalcogen series. The results show that the HBs formed by these rings with water are mostly electrostatic and dispersive in nature and that the HB strength decreases from oxygen to selenium

Conformational study of L-methionine and L-cysteine derivatives through quantum chemical calculations and 3JHH coupling constant analyses

The understanding of the conformational behavior of amino acids and their derivatives is a challenging task. Here, the conformational analysis of esterified and N-acetylated derivatives of L-methionine and L-cysteine using a combination of 1H NMR and electronic structure calculations is reported. The geometries and energies of the most stable conformers in isolated phase and taking into account the implicit solvent effects, according to the integral equation formalism polarizable continuum model (IEF−PCM), were obtained at the ωB97X-D/aug-cc-pVTZ level. The conformational preferences of the compounds in solution were also determined from experimental and theoretical 3JHH coupling constants analysis in different aprotic solvents. The results showed that the conformational stability of the esterified derivatives is not very sensitive to solvent effects, whereas the conformational equilibrium of the N-acetylated derivatives changes in the presence of solvent. According to the natural bond orbital (NBO), quantum theory of atoms in molecules (QTAIM) and noncovalent interactions (NCI) methodologies, the conformational preferences for the compounds are not dictated by intramolecular hydrogen bonding, but by a joint contribution of hyperconjugative and steric effects

Conformational preferences of N-acetyl-N-methylprolineamide in different media: a H-1 NMR and theoretical investigation

A comprehensive description on the conformational behaviour of small peptide models is of primary importance to elucidate polypeptide and protein structures and folding pathways. In this paper, an extensive conformational investigation of N-acetyl-N-methylprolineamide (Ac-Pro-NHMe) in both isolated phase and in solution is reported. The joint use of H-1 NMR spectroscopy and DFT calculations allowed to determine the most stable conformers of Ac-Pro-NHMe and to evaluate its conformational preferences in different media. Theoretical calculations at the M06-2X/aug-cc-pVTZ level of theory led to the identification of two and six stable conformers in isolated phase and solution, respectively. These geometries reveal the presence of two isomers, where the -NC(O)Me bond can assume a trans ( = 180 degrees) or cis ( = 0 degrees) orientation in relation to the -(CO)NHMe group of backbone. The theoretical results show that the trans,trans-IId in a down-puckered -turn-like structure and = 180 degrees, is the most populated conformer in isolated phase. In polar solvents, like acetonitrile and DMSO, there is a mixture of both polyproline II and -helix-like conformers, while in water, the trans,trans-IIu, in an up-puckered polyproline II-like geometry, is the less energetic. Therefore, our results show that conformer populations change upon solvent variation, indicating that the conformational equilibrium of Ac-Pro-NHMe is sensitive to solvent effects. The experimental population values, obtained through the integration of the peaks in the H-1 NMR spectrum, confirm the change of conformer populations in different solvents. The results reveal that the theoretical level employed in this study is in good agreement with experimental data. QTAIM and NCI analyses combined with orbital-based NBO calculations reveal that the conformers trans,trans-IId and trans,trans-IIu are stabilized by an intramolecular hydrogen bond (IHB) C?OHN in isolated phase. However, these geometries are completely destabilized in solution by the weakening of this interaction. Although IHB is essential to the stability of the two conformers in isolated phase, it represents only a secondary factor to the conformational preferences of the compound. The highest stability of trans,trans-IId in isolated phase can be attributed to hyperconjugative interactions. In solution, an interplay of hyperconjugative, steric and electrostatic effects rules the conformational preferences of Ac-Pro-NHMe43417571763CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP300821/2013-12016/24109-0; 2012/18567-4; 2016/12005-5

Revealing the conformational preferences of proteinogenic glutamic acid derivatives in solution by 1H NMR spectroscopy and theoretical calculations

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOThe conformational preferences of proteinogenic glutamic acid esterified (GluOMe) and N-acetylated (AcGluOMe) derivatives have been determined in solution for the first time. Theoretical calculations at the ωB97X-D/aug-cc-pVTZ made possible the assignment1221845554561FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO2015/08541-62016/24109-02016/12005-5sem informaçã

The Role Of Nonbonding Interactions And The Presence Of Fluoride On The Conformational Isomerism Of 1,2-ethanediol

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)This work reports the analysis of the effects ruling the conformational preference of 1,2-ethanediol (1,2-ED) using theoretical calculations, since there is no general consensus about the role of intramolecular hydrogen bond on the conformational isomerism of 1,2-ED. While the predominance of the gauche conformers along with the O-C-C-O fragment relative to the trans ones was found to be mainly due to hyperconjugation, the orientation of the hydroxyl groups is better described by a balance between low steric hindrance and high stabilization from hyperconjugation than by intramolecular hydrogen bond. Nevertheless, the presence of a fluoride anion induces a conformational change in 1,2-ED that maximizes hydrogen bonds between the fluoride and the hydroxyl groups. This effect was observed experimentally by the shift of H-1(O) and F-19 NMR signals upon complexation, then suggesting that compounds containing the 1,2-ED moiety can be possible anion transporters. (C) 2016 Elsevier B.V. All rights reserved.4731723FAPEMIG [CEX - RED-00010-14]CNPqFAPESPConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Conformational preferences of diallylamine: A rotational spectroscopic and theoretical study

The conformational space of diallylamine (DAA) was investigated using rotational spectroscopy from 7 to 19 GHz aided by quantum chemical calculations. Extensive conformational searches using density functional theory B3LYP-D3(BJ) and the ab initio MP2 method with the aug-cc-pVTZ basis set identified a total of 42 minima for DAA within similar to 22 kJ mol(-1). This reveals a strikingly rich conformational landscape for this secondary amine with two equivalent substituents. Experimentally, transitions belonging to four low energy conformers (I, II, III, and IV) were unequivocally assigned in the rotational spectrum, and their patterns were confirmed by the presence of the hyperfine structure owing to the N-14 quadrupolar nucleus. The relative intensities of the observed transitions suggest a conformational energy ordering of I < II < III < IV. Natural bond orbital and non-covalent interaction calculations reveal that the geometric preferences for the observed conformers are governed by an interplay of subtle attractive interactions (including hyperconjugation involving the lone pair at nitrogen) and repulsive effects

Revealing the Conformational Preferences of Proteinogenic Glutamic Acid Derivatives in Solution by ¹H NMR Spectroscopy and Theoretical Calculations

The conformational preferences of proteinogenic glutamic acid esterified (GluOMe) and <i>N</i>-acetylated (AcGluOMe) derivatives have been determined in solution for the first time. Theoretical calculations at the ωB97X-D/aug-cc-pVTZ made possible the assignment of six and eight stable conformers for GluOMe and AcGluOMe, respectively. The conformational equilibrium of the studied compounds was evaluated in different organic solvents using a combination of the integral equation formalism polarizable continuum model (IEF-PCM) and ¹H NMR spectroscopy data. The results showed that the conformational equilibrium of both derivatives change in the presence of solvent. According to the quantum theory of atoms in molecules (QTAIM), non-covalent interactions (NCI), and natural bond orbitals (NBO) analyses, the conformational preferences observed for GluOMe and AcGluOMe are not dictated by the presence of a specific interaction but are due to a combination of hyperconjugative and steric effects