NMR and Computational Studies as Analytical and High-Resolution Structural Tool for Complex Hydroperoxides and Diastereomeric Endo-Hydroperoxides of Fatty Acids in Solution-Exemplified by Methyl Linolenate

This review outlines methods to investigate the structure of natural products with emphasis on intramolecular hydrogen bonding, tautomerism and ionic structures using NMR techniques. The focus is on 1H chemical shifts, isotope effects on chemical shifts and diffusion ordered spectroscopy. In addition, density functional theory calculations are performed to support NMR results. The review demonstrates how hydrogen bonding may lead to specific structures and how chemical equilibria, as well as tautomeric equilibria and ionic structures, can be detected. All these features are important for biological activity and a prerequisite for correct docking experiments and future use as drugs.

Structure Analysis of Sulfated Polysaccharides Extracted from Scinaia interrupta: A Experimental and Density Functional Theory Studies

Asian Journal of Chemistry ◽

10.14233/ajchem.2020.22609 ◽

2020 ◽

Vol 32 (7) ◽

pp. 1589-1596

Author(s):

Nivedita Acharjee ◽

Tuhin Ghosh

Keyword(s):

1H Nmr ◽

Red Algae ◽

Density Functional ◽

Chemical Shifts ◽

Present Report ◽

Monomer Unit ◽

Absolute Error ◽

Sulfated Polysaccharides ◽

Nmr Studies ◽

Nmr Chemical Shifts

In present report, a combined experimental and theoretical study has been performed to address the isolation procedure and spectroscopic structure elucidation of polysaccharides such as xylomannan isolated from marine red algal source Scinaia interrupta. The structure of the polysaccharides obtained from the red algae of Scinaia interrupta has been studied from NMR, IR and GC-MS spectroscopy. The investigation revealed that red algae contained a backbone of α-(1→4)-linked D-mannopyranosyl residues substituted at 6-position with a single stub of β-D-xylopyranosyl residues. The major polysaccharide, which had 0.6 sulfate groups per monomer unit and an apparent molecular mass of 120 KDa. The backbone structure was optimized at DFT/B3LYP/6-311G(d,p) level of theory and GIAO-NMR studies were performed at B3LYP/6-311++G(2d,p) level of theory followed by mean absolute error calculations of the computed chemical shifts for two possible conformers resulting from the flipping of xylopyranosyl residue. The NMR calculations were in agreement with the experimental findings. The experimental 1H NMR chemical shifts were then correlated with the NBO, Merz Kollman (MK), ChelpG and Mulliken charges of the predicted conformer. A reasonable correlation with the experimental 1H NMR chemical shifts and the computed NBO charges with correlation coefficient of 0.906.

DFT calculations of O–H⋯O 1H NMR chemical shifts in investigating enol-enol tautomeric equilibria: Probing the impacts of intramolecular hydrogen bonding vs stereoelectronic interactions

Tetrahedron ◽

10.1016/j.tet.2020.130979 ◽

2020 ◽

Vol 76 (9) ◽

pp. 130979 ◽

Cited By ~ 1

Author(s):

Michael G. Siskos ◽

Panayiotis C. Varras ◽

Ioannis P. Gerothanassis

Keyword(s):

Hydrogen Bonding ◽

Dft Calculations ◽

1H Nmr ◽

Chemical Shifts ◽

Intramolecular Hydrogen Bonding ◽

Nmr Chemical Shifts ◽

Tautomeric Equilibria ◽

Intramolecular Hydrogen ◽

Stereoelectronic Interactions

Switching On/Off the Intramolecular Hydrogen Bonding of 2-Methoxyphenol Conformers: An NMR Study

Australian Journal of Chemistry ◽

10.1071/ch19600 ◽

2020 ◽

Vol 73 (3) ◽

pp. 222

Author(s):

Frederick Backler ◽

Feng Wang

Keyword(s):

Hydrogen Bonding ◽

Chemical Shift ◽

1H Nmr ◽

Density Functional ◽

Point Group ◽

Decomposition Analysis ◽

Intramolecular Hydrogen Bonding ◽

Group Symmetry ◽

Energy Decomposition Analysis ◽

Intramolecular Hydrogen

Intramolecular hydrogen bonding of 2-methoxyphenol (2-MP, guaiacol) is studied using NMR spectroscopy combined with quantum mechanical density functional theory (DFT) calculations. The hydrogen bonding of OH⋯O and HO⋯H is switched on in the conformers of anti–syn (AS, 99.64% dominance) and anti–gauche (AG), respectively, with respect to the anti–anti (AA) conformer (without either such hydrogen bonding interactions). It confirms that the 13C and 1H NMR chemical shift of AS dominates the measured NMR spectra, as the AS conformer reproduces the measurements in CDCl3 solvent (RMSD of 1.86ppm for 13C NMR and of 0.27ppm for 1H NMR). The chemical shift of hydroxyl H(1) at 5.66 pm is identified as the fingerprint of the OH(1)⋯OCH3 hydrogen bonding in AS, as it exhibits a significant deshielding from H(1) of AA (4.24ppm) and H(1) of AG (4.38ppm) without such OH(1)⋯OCH3 hydrogen bonding. The AG conformer (C1 point group symmetry) possesses a less strong hydrogen bonding of HO⋯HCH2O, with the methoxyl group out of the aromatic phenol plane. The substituent effect of AG due to the resonance interaction of methoxyl being out of plane in a concentrated solution shifts the ortho- and para-aromatic carbons, C(3)/C(5), of the AG to ~125.05/125.44ppm from the corresponding carbons in AS at 108.81/121.60ppm. The hydrogen bonding exhibits inwards reduction of IR frequency regions of AS and AG from AA. Finally, energy decomposition analysis (EDA) indicates that there is a steric energy of 45.01kcal mol−1 between the AS and AG when different intramolecular hydrogen bonding is switched on.

Optimized Structures and Theoretical 1H-NMR Spectral Analysis of the Methylene Protons in Dibenzyl Sulfoxide

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.391-392.1368 ◽

2011 ◽

Vol 391-392 ◽

pp. 1368-1374 ◽

Cited By ~ 1

Author(s):

Zheng Ping Wu ◽

Yuan Bing Sun ◽

Ian S. Butler

Keyword(s):

1H Nmr ◽

Density Functional ◽

Chemical Shifts ◽

Dft Methods ◽

Functional Theory ◽

H Nmr ◽

Effect Of Solvent ◽

Solvent Shift ◽

Total Energies ◽

Good Agreement

Dibenzyl sulfoxide [C6H5CH2)2SO, DBzSO] has been studied using density functional theory (DFT) methods with a particular emphasis on the theoretical 1H-NMR spectra of the methylene protons. The 1H-NMR chemical shifts of the methylene protons of DBzSO can be divided into two main types. Four possible structures of DBzSO were considered and the total energies were calculated for both a vacuum and in CDCl3 solvent. The change of length of S-O and S-C bonds in solvent was more obvious than that of the C(CH2)-C(C6H5) bonds; The S-O bond was longer and S-C bond was shorter in CDCl3. The essence effect of solvent on the properties of dibenzyl sulfoxide should come from the change of the geometrical structure. The change of shift Δx, [shift (solvent) - shift (vacuum)] showed that the effect of solvent on methylene protons of dibenzyl sulfoxide was apparent. Except of the other H of the rings, the two ortho H which were near S-O bond appeared more sensitivity on the solvent. The optimized structures in CDCl3 were in good agreement with the experimental data. The NMR peaks of methylene protons should be split more apparently in actual circumstance and the complex split of CH2 1HNMR peaks should be explained in some degree.

Electronic structure, vibrational spectra and 1H NMR chemical shifts of the ion pair composites within imidazolium functionalized geminal dicationic ionic liquids from density functional theory

Journal of Molecular Structure ◽

10.1016/j.molstruc.2019.127112 ◽

2020 ◽

Vol 1201 ◽

pp. 127112

Author(s):

Prakash L. Verma ◽

Shridhar P. Gejji

Keyword(s):

Density Functional Theory ◽

Electronic Structure ◽

Ionic Liquids ◽

1H Nmr ◽

Vibrational Spectra ◽

Density Functional ◽

Chemical Shifts ◽

Ion Pair ◽

Functional Theory ◽

Dicationic Ionic Liquids

A General Protocol for the Accurate Predictions of Molecular 13C/1H NMR Chemical Shifts via Machine Learning

10.26434/chemrxiv.11302295 ◽

2019 ◽

Author(s):

Peng Gao ◽

Jun Zhang ◽

Qian Peng ◽

Vassiliki-Alexandra Glezakou

Keyword(s):

Machine Learning ◽

1H Nmr ◽

Density Functional ◽

Organic Molecules ◽

Chemical Shifts ◽

Atomic Orbital ◽

Computational Cost ◽

Experimental Studies ◽

Dft Methods ◽

Nmr Chemical Shifts

Accurate prediction of NMR chemical shifts with affordable computational cost is of great importance for rigorous structural assignments of experimental studies. However, the most popular computational schemes for NMR calculation—based on density functional theory (DFT) and gauge-including atomic orbital (GIAO) methods—still suffer from ambiguities in structural assignments. Using state-of-the-art machine learning (ML) techniques, we have developed a DFT+ML model that is capable of predicting 13C/1H NMR chemical shifts of organic molecules with high accuracy. The input for this generalizable DFT+ML model contains two critical parts: one is a vector providing insights into chemical environments, which can be evaluated without knowing the exact geometry of the molecule; the other one is the DFT-calculated isotropic shielding constant. The DFT+ML model was trained with a dataset containing 476 13C and 270 1H experimental chemical shifts. For the DFT methods used here, the root-mean-square-derivations (RMSDs) for the errors between predicted and experimental 13C/1H chemical shifts are as small as 2.10/0.18 ppm, which is much lower than the typical DFT (5.54/0.25 ppm), or DFT+linear regression (4.77/0.23 ppm) approaches. It also has smaller RMSDs and maximum absolute errors than two previously reported NMR-predicting ML models. We test the robustness of the model on two classes of organic molecules (TIC10 and hyacinthacines), where we unambiguously assigned the correct isomers to the experimental ones. This DFT+ML model is a promising way of predicting NMR chemical shifts and can be easily adapted to calculated shifts for any chemical compound.<br>

A General Protocol for the Accurate Predictions of Molecular 13C/1H NMR Chemical Shifts via Machine Learning

10.26434/chemrxiv.11302295.v1 ◽

2019 ◽

Author(s):

Peng Gao ◽

Jun Zhang ◽

Qian Peng ◽

Vassiliki-Alexandra Glezakou

Keyword(s):

Machine Learning ◽

1H Nmr ◽

Density Functional ◽

Organic Molecules ◽

Chemical Shifts ◽

Atomic Orbital ◽

Computational Cost ◽

Experimental Studies ◽

Dft Methods ◽

Nmr Chemical Shifts

Accurate prediction of NMR chemical shifts with affordable computational cost is of great importance for rigorous structural assignments of experimental studies. However, the most popular computational schemes for NMR calculation—based on density functional theory (DFT) and gauge-including atomic orbital (GIAO) methods—still suffer from ambiguities in structural assignments. Using state-of-the-art machine learning (ML) techniques, we have developed a DFT+ML model that is capable of predicting 13C/1H NMR chemical shifts of organic molecules with high accuracy. The input for this generalizable DFT+ML model contains two critical parts: one is a vector providing insights into chemical environments, which can be evaluated without knowing the exact geometry of the molecule; the other one is the DFT-calculated isotropic shielding constant. The DFT+ML model was trained with a dataset containing 476 13C and 270 1H experimental chemical shifts. For the DFT methods used here, the root-mean-square-derivations (RMSDs) for the errors between predicted and experimental 13C/1H chemical shifts are as small as 2.10/0.18 ppm, which is much lower than the typical DFT (5.54/0.25 ppm), or DFT+linear regression (4.77/0.23 ppm) approaches. It also has smaller RMSDs and maximum absolute errors than two previously reported NMR-predicting ML models. We test the robustness of the model on two classes of organic molecules (TIC10 and hyacinthacines), where we unambiguously assigned the correct isomers to the experimental ones. This DFT+ML model is a promising way of predicting NMR chemical shifts and can be easily adapted to calculated shifts for any chemical compound.<br>

NMR and DFT Studies of 2-Oxo-1,2,3,4-tetrahydropyridines: Solvent and Temperature Effects

Australian Journal of Chemistry ◽

10.1071/ch18018 ◽

2018 ◽

Vol 71 (5) ◽

pp. 380 ◽

Cited By ~ 2

Author(s):

Hamid R. Memarian ◽

Mahdieh Kalantari ◽

Hassan Sabzyan

Keyword(s):

1H Nmr ◽

Electrostatic Interactions ◽

Density Functional ◽

Nmr Spectra ◽

Parent Compound ◽

Heterocyclic Ring ◽

1H Nmr Spectra ◽

Oxidation Products ◽

Free Energies ◽

Aryl Ring

Various 5-carboethoxy-2-oxo-1,2,3,4-tetrahydropyridines and their corresponding oxidation products containing methoxy or nitro groups on different positions of the C4-aryl ring were synthesized and the effect of steric and electrostatic interactions of these aryl substituents on the characteristic peaks in 1H NMR spectra were investigated. In addition, the intermolecular interaction of the parent compound and its oxidized form with solvent was experimentally investigated. For this, 1H NMR spectra of these compounds at different concentrations and temperatures in [D6]DMSO and CDCl3 were investigated. For comparison of the dimerization ability of these heterocyclic compounds with different conformations, the binding electronic energies, the total enthalpies and free energies of dimerization in the gas and solution phases, and the QTAIM (quantum theory of atoms-in-molecules) analysis were determined. These interactions were also studied using density functional theory at the B3LYP/6–311++G(d,p) level. The theoretical results are in good agreement with the experimental results and indicate that the electronic effect of the methoxy and nitro groups on the C4-aryl ring influences the electron density of the heterocyclic ring via the σ bond and, consequently, the chemical shift of the heterocyclic ring protons.

Correlation between 1H NMR chemical shifts of hydroxyl protons in n-hexanol/cyclohexane and molecular association properties investigated using density functional theory

Chemical Physics Letters ◽

10.1016/j.cplett.2015.12.025 ◽

2016 ◽

Vol 644 ◽

pp. 276-279 ◽

Cited By ~ 7

Author(s):

Mario E. Flores ◽

Toshimichi Shibue ◽

Natsuhiko Sugimura ◽

Hiroyuki Nishide ◽

Ignacio Moreno-Villoslada

Keyword(s):

Density Functional Theory ◽

1H Nmr ◽

Density Functional ◽

Chemical Shifts ◽

Molecular Association ◽

Functional Theory ◽

Nmr Chemical Shifts ◽

Hydroxyl Protons