1H NMR analysis of O‐methyl‐inositol isomers: a joint experimental and theoretical study

Density functional theory (DFT) calculations of ¹H NMR chemical shifts for l ‐quebrachitol isomers were performed using the B3LYP functional employing the 6‐31G(d,p) and 6‐311 + G(2d,p) basis sets. The effect of the solvent on the B3LYP‐calculated NMR spectrum was accounted for using the polarizable continuum model. Comparison is made with experimental ¹H NMR spectroscopic data, which shed light on the average uncertainty present in DFT calculations of chemical shifts and showed that the best match between experimental and theoretical B3LYP ¹H NMR profiles is a good strategy to assign the molecular structure present in the sample handled in the experimental measurements. Among four plausible O‐methyl‐inositol isomers, the l ‐quebrachitol 2a structure was unambiguously assigned based only on the comparative analysis of experimental and theoretical ¹H NMR chemical shift data. The B3LYP infrared (IR) spectrum was also calculated for the four isomers and compared with the experimental data, with analysis of the theoretical IR profiles corroborating assignment of the 2a structure. Therefore, it is confirmed in this study that a combined experimental/DFT spectroscopic investigation is a powerful tool in structural/conformational analysis studies. Copyright © 2012 John Wiley & Sons, Ltd.     

99Tc NMR as a promising technique for structural investigation of biomolecules: theoretical studies on the solvent and thermal effects of phenylbenzothiazole complex

The phenylbenzothiazole compounds show antitumor properties and are highly selective. In this paper, the ⁹⁹Tc chemical shifts based on the (^99mTc)(CO)₃(NNO) complex conjugated to the antitumor agent 2‐(4′‐aminophenyl)benzothiazole are reported. Thermal and solvent effects were studied computationally by quantum‐chemical methods, using the density functional theory (DFT) (DFT level BPW91/aug‐cc‐pVTZ for the Tc and BPW91/IGLO‐II for the other atoms) to compute the NMR parameters for the complex. We have calculated the ⁹⁹Tc NMR chemical shifts of the complex in gas phase and solution using different solvation models (polarizable continuum model and explicit solvation). To evaluate the thermal effect, molecular dynamics simulations were carried, using the atom‐centered density matrix propagation method at the DFT level (BP86/LanL2dz). The results highlight that the ⁹⁹Tc NMR spectroscopy can be a promising technique for structural investigation of biomolecules, at the molecular level, in different environments. Copyright © 2014 John Wiley & Sons, Ltd.     

Multiply Borylated Arenes: X‐ray Crystal Structure Analyses and Quantum Chemical Calculations

Optimised synthesis procedures and results of X‐ray single crystal structure analyses for 4‐(dibromoboryl)toluene, 1, 3‐bis(dibromoboryl)benzene, 1, 4‐bis(dibromoboryl)benzene, and 1, 3, 5‐tris(dibromoboryl)benzene are reported. These compounds have also been studied by Hartree‐Fock (HF), density functional theory (DFT), and Mßller‐Plesset second‐order perturbation (MP2) methods in combination with the polarized double‐ζ valence (SVP) and polarized triple‐ζ valence (TZVP) basis sets of Ahlrichs and coworkers. A comparison of the quantum chemical results for optimised geometries and computed NMR chemical shifts with experiment is presented to test the quality of the various methods for this class of compounds. All DFT methods tested yield optimised geometries within the experimental error bars of 3σ for bond lengths, whereas larger deviations among the methods are observed for computed NMR chemical shifts. This calibration recommends the B3LYP/SVP combination as a reliable and computationally efficient level of theory to assess the structures and absolute and relative ¹H‐, ¹³C‐ and ¹¹B NMR shift values of borylated aromatic compounds in future investigations.     

Pseudo‐Contact NMR Shifts over the Paramagnetic Metalloprotein CoMMP‐12 from First Principles

Long‐range pseudo‐contact NMR shifts (PCSs) provide important restraints for the structure refinement of proteins when a paramagnetic metal center is present, either naturally or introduced artificially. Here we show that ab initio quantum‐chemical methods and a modern version of the Kurland–McGarvey approach for paramagnetic NMR (pNMR) shifts in the presence of zero‐field splitting (ZFS) together provide accurate predictions of all PCSs in a metalloprotein (high‐spin cobalt‐substituted MMP‐12 as a test case). Computations of 314 ¹³C PCSs using g‐ and ZFS tensors based on multi‐reference methods provide a reliable bridge between EPR‐parameter‐ and susceptibility‐based pNMR formalisms. Due to the high sensitivity of PCSs to even small structural differences, local structures based either on X‐ray diffraction or on various DFT optimizations could be evaluated critically by comparing computed and experimental PCSs. Many DFT functionals provide insufficiently accurate structures. We also found the available 1RMZ PDB X‐ray structure to exhibit deficiencies related to binding of a hydroxamate inhibitor. This has led to a newly refined PDB structure for MMP‐12 (5LAB) that provides a more accurate coordination arrangement and PCSs.     

Quantum‐chemical analyses of aromaticity,UV spectra,and NMR chemical shifts in plumbacyclopentadienylidenes stabilized by Lewis bases

We carried out a series of zeroth‐order regular approximation (ZORA)‐density functional theory (DFT) and ZORA‐time‐dependent (TD)‐DFT calculations for molecular geometries, NMR chemical shifts, nucleus‐independent chemical shifts (NICS), and electronic transition energies of plumbacyclopentadienylidenes stabilized by several Lewis bases, (Ph)₂(^tBuMe₂Si)₂C₄PbL₁L₂ (L₁, L₂ = tetrahydrofuran, Pyridine, N‐heterocyclic carbene), and their model molecules. We mainly discussed the Lewis‐base effect on the aromaticity of these complexes. The NICS was used to examine the aromaticity. The NICS values showed that the aromaticity of these complexes increases when the donation from the Lewis bases to Pb becomes large. This trend seems to be reasonable when the 4n‐Huckel rule is applied to the fractional π‐electron number. The calculated ¹³C‐ and ²⁰⁷Pb‐NMR chemical shifts and the calculated UV transition energies reasonably reproduced the experimental trends. We found a specific relationship between the ¹³C‐NMR chemical shifts and the transition energies. As we expected, the relativistic effect was essential to reproduce a trend not only in the ²⁰⁷Pb‐NMR chemical shifts and J[Pb‐C] but also in the ¹³C‐NMR chemical shifts of carbons adjacent to the lead atom. © 2014 Wiley Periodicals, Inc.     

Substitution effects in the 15N NMR chemical shifts of heterocyclic azines evaluated at the GIAO‐DFT level

A systematic study of the accuracy factors for the computation of ¹⁵N NMR chemical shifts in comparison with available experiment in the series of 72 diverse heterocyclic azines substituted with a classical series of substituents (CH₃, F, Cl, Br, NH₂, OCH₃, SCH₃, COCH₃, CONH₂, COOH, and CN) providing marked electronic σ‐ and π‐electronic effects and strongly affecting ¹⁵N NMR chemical shifts is performed. The best computational scheme for heterocyclic azines at the DFT level was found to be KT3/pcS‐3//pc‐2 (IEF‐PCM). A vast amount of unknown ¹⁵N NMR chemical shifts was predicted using the best computational protocol for substituted heterocyclic azines, especially for trizine, tetrazine, and pentazine where experimental ¹⁵N NMR chemical shifts are almost totally unknown throughout the series. It was found that substitution effects in the classical series of substituents providing typical σ‐ and π‐electronic effects followed the expected trends, as derived from the correlations of experimental and calculated ¹⁵N NMR chemical shifts with Swain–Lupton's F and R constants.     

Synthesis,spectral, DFT calculations and antibacterial studies of Fe(III) complexes of new fluorescent Schiff bases derived from imidazo[4',5':3,4]benzo[1,2‐c]isoxazole

New fluorescent heterocyclic ligands were synthesized by the reaction of 8‐(4‐chlorophenyl)‐3‐alkyl‐3H‐imidazo[4',5':3,4]benzo [1,2‐c]isoxazol‐5‐amine with p‐hydroxybenzaldehyde and p‐chlorobenzaldehyde in good yields. The coordination ability of the ligands with Fe³⁺ ion was examined in an aqueous metanolic solution. Schiff base ligands and their metal complexes were characterized by elemental analyses, IR, UV–vis, mass, and NMR spectra. The optical properties of the compounds were investigated and the results showed that the fluorescence of all compounds is intense and their obtained emission quantum yields are around 0.15 – 0.53. Optimized geometries and assignment of the IR bands and NMR chemical shifts of the new complexes were also computed by using density functional theory (DFT) methods. The DFT‐calculated vibrational wavenumbers and NMR chemical shifts are in good agreement with the experimental values, confirming suitability of the optimized geometries for Fe(III) complexes. Also, the 3D‐distribution map for HOMO and LUMO of the compounds were obtained. The new compounds showed potent antibacterial activity and their antibacterial activity (MIC) against Gram‐positive and Gram‐negative bacterial species were also determined. Results of antibacterial test revealed that coordination of ligands to Fe(III) leads to improvement in the antibacterial activity.     

The Stereostructure of Porphyra‐334: An Experimental and Calculational NMR Investigation. Evidence for an Efficient ‘Proton Sponge’

The mycosporine‐like amino acid (MAA) porphyra‐334 ( 1 ) is subjected to extensive ¹H‐ and ¹³C‐NMR analysis as well as to density‐functional‐theory (DFT) calculations. All ¹H‐ and ¹³C‐NMR signals of 1 are assigned, as well as the resonances of prochiral proton pairs. This is achieved by 500‐MHz standard COSY, HMQC, and HMBC experiments, as well as by one‐dimensional (DPFGSE‐NOE) and two‐dimensional (NOESY) NOE experiments. Diffusion measurements (DOSY) confirm that 1 is monomeric in D₂O solution. DFT Calculations yield ¹³C‐NMR chemical shifts which are in good agreement for species 6 which is the imino N‐protonated form of 1 . An exceptionally high proton affinity of 265.7 kcal/mol is calculated for 1 , indicating that 1 may behave as a very powerful ‘proton sponge’ of comparable strength as synthetic systems studied so far. Predictions of ¹³C‐NMR chemical shifts by the ‘NMRPredict’ software are in agreement with the DFT data. The absolute configuration at the ring stereogenic center of 1 is concluded to be (S) from NOE data as well as from similarities with the absolute configuration (S) found in mycosporine‐glycine 16 . This supports the assumption that 1 is biochemically derived from 3,3‐O‐didehydroquinic acid ( 17 ). The data obtained question the results recently published by a different research group claiming that the configuration at the imino moiety of 1 is (Z), rather than (E) as established by the here presented study.     

Deuterium‐induced isotope effects on the 13C chemical shifts of α‐d‐glucose pentaacetate

1,2,3,4,6‐Penta‐O‐acetyl‐α‐d ‐glucopyranose and the corresponding [1‐²H], [2‐²H], [3‐²H], [4‐²H], [5‐²H], and [6,6‐²H₂]‐labeled compounds were prepared for measuring deuterium/hydrogen‐induced effects on ¹³C chemical shift ⁿΔ (DHIECS) values. A conformational analysis of the nondeuterated compound was achieved using density functional theory (DFT) molecular models that allowed calculation of several structural properties as well as Boltzmann‐averaged ¹³C NMR chemical shifts by using the gauge‐including atomic orbital method. It was found that the DFT‐calculated C–H bond lengths correlate with ¹Δ DHIECS. Copyright © 2013 John Wiley & Sons, Ltd.     

Density functional calculations of 19F and 235U NMR chemical shifts in uranium (VI) chloride fluorides UF6−nCln: Influence of the relativistic approximation and role of the exchange‐correlation functional

Relativistic density functional theory (DFT) has been applied to the calculation of the ¹⁹F nuclear magnetic resonance (NMR) chemical shifts of the title compounds. It is shown that, while large‐core effective core potentials (ECP) fail completely for the calculation of ligand NMR chemical shifts in uranium compounds, small‐core ECPs are a valid relativistic method for this purpose. In an earlier study of the same systems, certain differences between theory and experiment had been observed, for instance, in the relative chemical shift of the A₄ and X sites in UF₅Cl. The reason for these deviations has been investigated further in the current paper. By comparing different relativistic methods, it is shown that the relativistic approximation is not responsible for these deviations. The role of the approximation to the exchange‐correlation (XC) functional of DFT has been probed, and generalized gradient approximations (GGA) as well as hybrid DFT methods have been investigated. None of these methods corrects the mentioned errors. It is argued that the neglect of environmental factors (solvent effects) remains as a possible error source, although the approximate XC functional appears to be the more likely cause of the problem. ²³⁵U NMR shieldings and chemical shifts have been calculated, and the trends predicted earlier have been confirmed. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2005     

On the accuracy of the GIAO‐DFT calculation of 15N NMR chemical shifts of the nitrogen‐containing heterocycles – a gateway to better agreement with experiment at lower computational cost

The main factors affecting the accuracy and computational cost of the gauge‐independent atomic orbital density functional theory (GIAO‐DFT) calculation of ¹⁵N NMR chemical shifts in the representative series of key nitrogen‐containing heterocycles – azoles and azines – have been systematically analyzed. In the calculation of ¹⁵N NMR chemical shifts, the best result has been achieved with the KT3 functional used in combination with Jensen's pcS‐3 basis set (GIAO‐DFT‐KT3/pcS‐3) resulting in the value of mean absolute error as small as 5 ppm for a range exceeding 270 ppm in a benchmark series of 23 compounds with an overall number of 41 different ¹⁵N NMR chemical shifts. Another essential finding is that basically, the application of the locally dense basis set approach is justified in the calculation of ¹⁵N NMR chemical shifts within the 3–4 ppm error that results in a dramatic decrease in computational cost. Based on the present data, we recommend GIAO‐DFT‐KT3/pcS‐3//pc‐2 as one of the most effective locally dense basis set schemes for the calculation of ¹⁵N NMR chemical shifts. Copyright © 2014 John Wiley & Sons, Ltd.     

GIAO/DFT studies on 1,2,4‐triazole‐5‐thiones and their propargyl derivatives

Density functional theory (DFT)/Becke–Lee–Yang–Parr (B3LYP) and gauge‐including atomic orbital (GIAO) calculations were performed on a number of 1,2,4‐triazole derivatives, and the optimized structural parameters were employed to ascertain the nature of their predominant tautomers. ¹³C and ¹⁵N NMR chemical shifts of 3‐substituted 1,2,4‐triazole‐5‐thiones and their propargylated derivatives were calculated via GIAO/DFT approach at the B3LYP level of theory with geometry optimization using a 6‐311++G** basis set. A good agreement between theoretical and experimental ¹³C and ¹⁵N NMR chemical shifts could be found for the systems investigated. The data generated were useful in predicting ¹⁵N chemical shifts of all the nitrogen atoms of the triazole ring, some of which could not be obtained in solution state ¹⁵N HMBC/HSQC NMR measurements. The energy profile computed for the dipropargylated derivatives was found to follow the product distribution profile of regioisomers formed during propargylation of 1,2,4‐triazole thiones. Copyright © 2013 John Wiley & Sons, Ltd.     

Towards the versatile DFT and MP2 computational schemes for 31P NMR chemical shifts taking into account relativistic corrections

The main factors affecting the accuracy and computational cost of the calculation of ³¹P NMR chemical shifts in the representative series of organophosphorous compounds are examined at the density functional theory (DFT) and second‐order Møller–Plesset perturbation theory (MP2) levels. At the DFT level, the best functionals for the calculation of ³¹P NMR chemical shifts are those of Keal and Tozer, KT2 and KT3. Both at the DFT and MP2 levels, the most reliable basis sets are those of Jensen, pcS‐2 or larger, and those of Pople, 6‐311G(d,p) or larger. The reliable basis sets of Dunning's family are those of at least penta‐zeta quality that precludes their practical consideration. An encouraging finding is that basically, the locally dense basis set approach resulting in a dramatic decrease in computational cost is justified in the calculation of ³¹P NMR chemical shifts within the 1–2‐ppm error. Relativistic corrections to ³¹P NMR absolute shielding constants are of major importance reaching about 20–30 ppm (ca 7%) improving (not worsening!) the agreement of calculation with experiment. Further better agreement with the experiment by 1–2 ppm can be obtained by taking into account solvent effects within the integral equation formalism polarizable continuum model solvation scheme. We recommend the GIAO‐DFT‐KT2/pcS‐3//pcS‐2 scheme with relativistic corrections and solvent effects taken into account as the most versatile computational scheme for the calculation of ³¹P NMR chemical shifts characterized by a mean absolute error of ca 9 ppm in the range of 550 ppm. Copyright © 2014 John Wiley & Sons, Ltd.     

13C GIAO DFT calculation as a tool for configuration prediction of N–O group in saturated heterocyclic N‐oxides

Tropane, tropinone, pseudopelletierine and cocaine were oxidized in situ in a nuclear magnetic resonance (NMR) tube providing mixtures of exo/endo N‐oxides. Observed ¹³C chemical shifts were correlated with values calculated by gauge‐including atomic orbitals density functional theory (DFT) OPBE/6‐31G* method using DFT B3LYP/6‐31G* optimized geometries. The same method of ¹³C chemical shift calculation was applied on series of methyl‐substituted 1‐methylpiperidines and their epimeric N‐oxides described in literature. The results show that using this undemanding calculation method enables assignment of configuration of N–O group in N‐epimeric saturated heterocyclic N‐oxides. The approach enables assigning of the configuration with high degree of certainty even if NMR data of only one isomer are available. An improved method of in situ oxidation of starting amines in an NMR tube is also described. Copyright © 2012 John Wiley & Sons, Ltd.     

Crystallographic and Dynamic Aspects of Solid‐State NMR Calibration Compounds: Towards ab Initio NMR Crystallography

The excellent results of dispersion‐corrected density functional theory (DFT‐D) calculations for static systems have been well established over the past decade. The introduction of dynamics into DFT‐D calculations is a target, especially for the field of molecular NMR crystallography. Four ¹³C ss‐NMR calibration compounds are investigated by single‐crystal X‐ray diffraction, molecular dynamics and DFT‐D calculations. The crystal structure of 3‐methylglutaric acid is reported. The rotator phases of adamantane and hexamethylbenzene at room temperature are successfully reproduced in the molecular dynamics simulations. The calculated ¹³C chemical shifts of these compounds are in excellent agreement with experiment, with a root‐mean‐square deviation of 2.0 ppm. It is confirmed that a combination of classical molecular dynamics and DFT‐D chemical shift calculation improves the accuracy of calculated chemical shifts.     

Computational NMR Spectra of o-Benzyne and Stable Guests and Their Hemicarceplexes

The incarceration of o-benzyne and 27 other guest molecules within hemicarcerand 1 , as reported experimentally by Warmuth, and Cram and co-workers, has been studied by density functional theory (DFT). The ¹H NMR chemical shifts, rotational mobility, and conformational preference of the guests within the supramolecular cage were determined, which showed intriguing correlations of the chemical shifts with structural parameters of the host–guest system. Furthermore, based on the computed chemical shifts reassignments of some NMR signals are proposed. This affects, in particular, the putative characterization of the volatile benzyne molecule inside a hemicarcerand, for which our CCSD(T) and KT2 results indicate that the experimentally observed signals are most likely not resulting from an isolated o-benzyne within the supramolecular host. Instead, it is shown that the guest reacted with an aromatic ring of the host, and this adduct is responsible for the experimentally observed signals.     

Observed and calculated 1H and 13C chemical shifts induced by the in situ oxidation of model sulfides to sulfoxides and sulfones

A series of model sulfides was oxidized in the NMR sample tube to sulfoxides and sulfones by the stepwise addition of meta‐chloroperbenzoic acid in deuterochloroform. Various methods of quantum chemical calculations have been tested to reproduce the observed ¹H and ¹³C chemical shifts of the starting sulfides and their oxidation products. It has been shown that the determination of the energy‐minimized conformation is a very important condition for obtaining realistic data in the subsequent calculation of the NMR chemical shifts. The correlation between calculated and observed chemical shifts is very good for carbon atoms (even for the ‘cheap’ DFT B3LYP/6‐31G* method) and somewhat less satisfactory for hydrogen atoms. The calculated chemical shifts induced by oxidation (the Δδ values) agree even better with the experimental values and can also be used to determine the oxidation state of the sulfur atom (? S? , ? SO? , ? SO₂? ). Copyright © 2010 John Wiley & Sons, Ltd.     

Theoretical Study of 13C Chemical Shifts Structures of Some ortho-Substituted 3-Anilino-2-nitrobenzo[b]thiophenes and 2-Anilino-3-nitrobenzo[b]thiophenes and Comparison with Experimental

¹³C NMR chemical shifts have been calculated for structures of some substituted 3‐anilino‐2‐nitrobenzo‐[b]thiophenes ( 2 o) and 2‐anilino‐3‐nitrobenzo[b]thiophenes ( 3 o) derivatives containing OH, NH₂, OMe, Me, Et, H, F, Cl and Br. The molecular structures were fully optimized using B3LYP/6‐31G(d,p). The calculation of the ¹³C shielding tensors employed the GAUSSIAN 03 implementation of the gauge‐including atomic orbital (GIAO) and continuous set of gauge transformations (CSGT) by using 6‐311++G(d,p) basis set at density functional levels of theories (DFT). The isotropic and the anisotropy parameters of chemical shielding for all compounds are calculated. The predicted ¹³C chemical shifts are derived from equation δ=δ₀+δ where δ is the chemical shift, δ is the absolute shielding, and δ₀ is the absolute shielding of the standard TMS. Excellent linear relationships have been observed between experimental and calculated ¹³C NMR chemical shifts for all derivatives     

NMR Spectroscopic Characterization of Isocyano‐ and 1, 1′‐Diisocyanoferrocene. The Molecular Structure of Isocyanoferrocene

Isocyanoferrocene ( 1 ) and 1, 1′‐diisocyanoferrocene ( 2 ) were prepared and studied by ¹H, ¹³C, ¹⁴N and ⁵⁷Fe NMR spectroscopy in order to gain a more complete data set. The NMR data of 1 (chemical shifts and coupling constants) were calculated by DFT methods [B3LYP/6‐311+G(d, p)] and compare favourably with experimental data. The molecular structure of 1 was determined by X‐ray structural analysis, and an almost undistorted ferrocene‐like geometry was found.     

15N NMR of 1,4‐dihydropyridine derivatives

In this article, we describe the characteristic ¹⁵N and ¹H_N NMR chemical shifts and ¹J(¹⁵N–¹H) coupling constants of various symmetrically and unsymmetrically substituted 1,4‐dihydropyridine derivatives. The NMR chemical shifts and coupling constants are discussed in terms of their relationship to structural features such as character and position of the substituent in heterocycle, N‐alkyl substitution, nitrogen lone pair delocalization within the conjugated system, and steric effects. Copyright © 2013 John Wiley & Sons, Ltd.