NMR Chemical Shift Calculations Research Articles

Quantum chemical investigation of beta-CD–catechin flavonoid encapsulation in solution through NMR analysis: an adequate controlled drug-delivery system

DFT–PCM–water calculations of 1H NMR chemical shifts for 28 optimized catechin–beta-CD complex structures revealed that adsorption mode of complexion should be predominant in aqueous media, with full-inclusion 1 : 1 structure being in total disagreement with experimental 1H NMR profile (D2O).

Structure elucidation of a novel cyclic tripeptide from the marine-derived fungus Aspergillus ochraceopetaliformis DSW-2

A novel cyclic tripeptide, sclerotiotide M (1), was isolated from the culture of a marine derived fungus Aspergillus ochraceopetaliformis DSW-2, together with four known compounds (2–5). The planar structure of 1 was established by 1 D and 2 D NMR data, supported by mass spectrometry, and the relative configuration was established by calculated NMR chemical shifts coupled with a statistical method (DP4+). All the compounds (1–5) displayed weak cytotoxic activities against cancer cell lines HPAC and BXPC3, with IC50 values over 20 μM.

Spirocollequins A and B, new alkaloids featuring a spirocyclic isoindolinone core, from Colletotrichum boninense AM-12-2

A pair of new diastereomeric isoindolinone alkaloids, spirocollequins A and B, were isolated from an endophytic fungus, Colletotrichum boninense AM-12-2. Their structures are featuring a 4,5-dihydro-spiro[furan-2,1′-isoindolin]-3′-one core. Their structures were determined by 1D/2D NMR, the Mosher’s ester method, and DFT-GIAO NMR chemical shift calculations, coupled with advanced statistical procedures. Spirocollequins A and B exhibited in vitro antiplasmodial activity at the IC50 (μM) values of 9.72 ± 0.61 and 4.71 ± 0.77, respectively.

Recent advances in computational liquid-phase 77Se NMR

This review aims to highlight significant progress in the calculation of 77Se NMR chemical shifts and spin – spin coupling constants involving selenium substantiated with a vast amount of experimental data. The material is arranged in two basic sections: the first one dealing with the calculation of 77Se NMR chemical shifts and the second one dealing with the computation of spin – spin coupling constants involving 77Se nucleus, namely 77Se–1H, 77Se–13C and 77Se–77Se together with some more exotic types of couplings, 77Se – 15N, 77Se–19F, 77Se–29Si and 77Se–31P. A special attention is focused on the stereoelectronic effects involving selenium atom and their manifestation in the 77Se NMR spectra of organoselenium compounds studied with the aid of the modern calculation of 77Se NMR parametres in combination with experimental results.The bibliography includes 114 references.

Ent-Kaurane-Based Diterpenoids, Dimers, and Meroditerpenoids from Isodon xerophilus.

Eight new diterpenoids (1-8) with varied structures were isolated from the aerial parts of Isodon xerophilus. Among them, xerophilsin A (1) was found to be an unusual meroditerpenoid representing a hybrid of an ent-kauranoid and a long-chain aliphatic ester, xerophilsins B-D (2-4) are dimeric ent-kauranoids, while xerophilsins E-H (5-8) are new ent-kauranoids. The structures of 1-8 were elucidated mainly through the analyses of their spectroscopic data. The absolute configurations of 2, 6, and 8 were confirmed by single-crystal X-ray diffraction, and the configuration of C-16 in 7 was established through quantum chemical calculation of NMR chemical shifts, as well as modeling of key interproton distances. Bioactivity evaluation of all isolated compounds revealed that 2, 3, and 5 inhibited NO production in LPS-stimulated RAW264.7 cells.

Comprehensive Benchmark Study on the Calculation of 29Si NMR Chemical Shifts

A comprehensive and diverse benchmark set for the calculation of 29Si NMR chemical shifts is presented. The SiS146 set includes 100 silicon containing compounds with 146 experimentally determined reference 29Si NMR chemical shifts measured in nine different solvents in a range from -400 to +828 ppm. Silicon atoms bound to main group elements as well as transition metals with coordination numbers of 2-6 in various bonding patterns including multiple bonds and coordinative and aromatic bonding are represented. The performance of various common and specialized density functional approximations including (meta-)GGA, hybrid, and double-hybrid functionals in combination with different AO basis sets and for differently optimized geometries is evaluated. The role of scalar-relativistic effects is further investigated by inclusion of the zeroth order regular approximation (ZORA) method into the calculations. GGA density functional approximations (DFAs) are found to outperform hybrid DFAs with B97-D3 performing best with an MAD of 7.2 ppm for the subset including only light atoms (Z < 18), while TPSSh is the best tested hybrid functional with an MAD of 10.3 ppm. For 29Si cores in the vicinity of heavier atoms, the application of ZORA proved indispensable. Inclusion of spin-orbit effects into the 29Si NMR chemical shift calculation decreases the mean absolute deviations by up to 74% compared to calculations applying effective core potentials.

1H AND 13C NMR SPECTRA OF STRYCHNOS ALKALOIDS: SELECTED NMR UPDATES

The PBE0/pcSseg-2//pcseg-2 calculations of 1H and 13C NMR chemical shifts were&#x0D; performed for a classical series of 12 Strychnos alkaloids (except for the earlier studied parent&#x0D; strychnine), namely akuammicine, isostrychnine, rosibiline, tsilanine, spermostrychnine, diaboline,&#x0D; cyclostrychnine, henningsamide, strychnosilidine, strychnobrasiline, holstiine, and icajine. It was&#x0D; found that calculated 1H and 13C NMR chemical shifts demonstrated markedly good correlations with&#x0D; available experimental data characterized by a mean absolute error of 0.22 ppm for the range of 8&#x0D; ppm for protons and 1.97 ppm for the range of 180 ppm for carbons. Complimentary, present results&#x0D; provide essential NMR update and fill a gap in the NMR data of this distinguished group of the vitally&#x0D; important natural products.

Dimeric and monomeric dihydrostilbenes from the roots of Stemona mairei together with their hypoglycemic activities

A carefully performed phytochemical investigation of the roots of Stemona mairei (Stemonaceae) led to the discovery of six so far undescribed dihydrostilbene dimers maistilbene A – F and four monomers maistilbene G – J. This is the first report of stilbenoids of this plant species and the first report of dimeric dihydrostilbenes from this plant family. The absolute configuration of these compounds was determined by a combination of Mo 2 (AcO) 4 -induced ECD spectra and quantum chemical calculation of NMR chemical shift, ECD and spin-spin coupling constants. Maistilbene G could increase the glucose consumption in L6 myotubes, disclosing a new hypoglycemic candidate. • Six undescribed dihydrostilbene dimers and four monomers were isolated from roots of Stemona mairei. • The absolute configuration was determined by a quantum chemical calculation of NMR, ECD and coupling constants. • Maistilbene G could increase the glucose consumption in L6 myotubes model.

The relationship between stereochemical and both, pharmacological and ADME-Tox, properties of the potent hydantoin 5-HT7R antagonist MF-8

This study concerns synthesis and evaluation of pharmacodynamic and pharmacokinetic profile for all four stereoisomers of MF-8 (5-(4-fluorophenyl)-3-(2-hydroxy-3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl)-5-methylimidazolidine-2,4-dione), the previously described, highly potent 5-HT7R ligand with antidepressant activity on mice. The combination of DFT calculations of 1H NMR chemical shifts with docking and dynamic simulations, in comparison to experimental screening results, provided prediction of the configuration for one of two present stereogenic centers. The experimental data for stereoisomers (MF-8A-MF-8D) confirmed the significant impact of stereochemistry on both, 5-HT7R affinity and antagonistic action, with Ki and Kb values in the range of 3–366 nM and 0.024–99 μM, respectively. We also indicated the stereochemistry-dependent influence of the tested compounds on P-glycoprotein efflux, absorption in Caco-2 model, metabolic pathway as well as CYP3A4 and CYP2C9 activities.

Rapid and accurate determination of atomistic RNA dynamic ensemble models using NMR and structure prediction

Biomolecules form dynamic ensembles of many inter-converting conformations which are key for understanding how they fold and function. However, determining ensembles is challenging because the information required to specify atomic structures for thousands of conformations far exceeds that of experimental measurements. We addressed this data gap and dramatically simplified and accelerated RNA ensemble determination by using structure prediction tools that leverage the growing database of RNA structures to generate a conformation library. Refinement of this library with NMR residual dipolar couplings provided an atomistic ensemble model for HIV-1 TAR, and the model accuracy was independently supported by comparisons to quantum-mechanical calculations of NMR chemical shifts, comparison to a crystal structure of a substate, and through designed ensemble redistribution via atomic mutagenesis. Applications to TAR bulge variants and more complex tertiary RNAs support the generality of this approach and the potential to make the determination of atomic-resolution RNA ensembles routine.

Ginkgobilol, a new diarylpentanoid and an osteogenic diarylpentanoid analog from Ginkgo biloba leaves

Phytochemical analysis of methanol extracts of Ginkgo biloba leaves resulted in the isolation of a novel diarylpentanoid, ginkgobilol (1) and a known diarylpentanoid analog (2). The structure of the new compound was elucidated by analyzing NMR spectroscopic data and HR-ESIMS, and the absolute configuration was determined using gauge-including atomic orbital NMR chemical shift calculations, followed by DP4+ analysis and specific rotation value. Diarylpentanoids comprise two aromatic rings linked by a five-carbon bridge; these are relatively unique examples in natural products. To the best of our knowledge, the present study is the first to report the presence of diarylpentanoids in G. biloba. Compound 2 increased alkaline phosphatase (ALP) production in C3H10T1/2, a murine mesenchymal stem cell line, in a dose-dependent manner. The promotion of osteogenic differentiation by the active compound 2 mediated by induction of transcriptional ALP and osteopontin (OPN) gene expression was confirmed using quantitative real time polymerase chain reaction, thus indicating its remarkable bone formation activity.

Structure determination and cytotoxic evaluation of metabolites from the entomogenous fungus Fusarium equiseti.

Investigation of the entomogenous fungus Fusarium equiseti LGWB-9 from Harmonia axyridis led to the isolation of fusarisetin B (2) and its analog, fusaketide A (1), along with two known compounds (3 and 4). Among them, fusaketide A (1) represent the first example of natural polyketide carbon skeleton with a [6/6/5/5] tetracyclic ring system. The planar structure and relative configuration of 1 was established on the basis of NMR spectroscopic data and 13C NMR chemical shift calculation. The absolute configuration of 1 was assigned by quantum chemical TDDFT calculation of its ECD spectrum and single-crystal X-ray diffraction analysis using Cu Kα radiation. Compounds 1 and 2 showed cytotoxicities against MCF-7, MGC-803, HeLa and Huh-7 cell lines with the IC50 values ranging from 2.4 to 69.7 μg ml-1. Cell invasion, migration, DAPI staining, and flow cytometry experiments were carried out to examine the effect of 2 against MGC-803 cells. Western blot results showed that 2 could induce MGC-803 apoptosis through up-regulation of Bax and down-regulation of Bcl-2.

Asperfloketals A and B, the First Two Ergostanes with Rearranged A and D Rings: From the Sponge-Associated Aspergillus flocculosus 16D-1.

Asperfloketals A (1) and B (2), two 1(10 → 6)-abeo-14,15-secosteroids featuring a novel trioxahexaheterocyclic ring system, were isolated from the sponge-associated fungus Aspergillus flocculosus 16D-1. Their structures were elucidated by extensive spectroscopic analysis and NMR chemical shifts calculations, supported by DP4+ probability analysis, and their absolute configurations were determined by ECD calculations and the modified Mosher's method. Asperfloketals A and B showed strong anti-inflammatory activity in the CuSO4-induced transgenic fluorescent zebrafish but displayed no cytotoxicity against HeLa, HepG2, and SW480 cell lines.

Remarks on the modelling of molecular binding forces in the Glue-DNT interaction

The interactions between cyanoacrylate type of glue and model compounds for TNT are investigated using mainly spectroscopic techniques. Electrostatic fields emanating from dispersion and dipole interactions are thought to dominate the energy of interaction without any evidence for hydrogen bonding between the glue and any of the substrates. Vibronic spectral data strongly suggests polarization of the vibrational manifolds of the substrates. Careful analysis of nuclear magnetic resonance spectral data reveals a good correlation between the nuclear magnetic resonance (nmr) chemical shifts and the measured infrared shifts in the glue matrix. This profound observation may have implications for theoretical calculations of nmr chemical shifts.

One new piperazinedione isolated from a mangrove-derived fungus Aspergillus niger JX-5

One new piperazinedione derivative, nigerpiperazine A (1), along with six known compounds (2–7) were isolated from the fungus Aspergillus niger JX-5 from mangrove Ceriops tagal. Nigerpiperazine A (1) was elucidated by spectroscopic analyses and 13C NMR chemical shift calculations, compounds 4 and 5 were determined by X-ray and the CD spectra. The absolute configuration of 4 was identified by X-ray for the first time. Compounds 1 and 4 showed inhibitory activities against Helicoverpa armigera Hubner with the IC50 values of 200 and 100 µg/mL, respectively.

The 1H and 13C chemical shifts of 5–5 lignin model dimers: An evaluation of DFT functionals

The calculations of 1H and 13C NMR chemical shifts were performed on three 5–5 lignin dimers, prominent substructures in softwood lignins, to compare with experimental data. Initially, 10 DFT functionals (B3LYP, B3PW91, BPV86, CAM-B3LYP, HCTH, HSEH1PBE, mPW1PW91, PBEPBE, TPSSTPSS, and ωB97XD) combined with the gage-including atomic orbital (GIAO) method and basic set 6–31G(d,p) were tested on 3,3′-(6,6′-dihydroxy-5,5′-dimethoxy-[1,1′-biphenyl]-3,3′-diyl)dipropionic acid (1), efficiently synthesized from ferulic acid. HSEH1PBE, mPW1PW91, and ωB97XD were found to be the three best performing functionals with strong correlations (r2 ≥ 0.9988) and low errors (CMAEs ≤ 0.0611 ppm for 1H and CMAEs ≤ 1.19 ppm for 13C). These functionals were also well-performed for the 1H and 13C shift calculations of dimers 3,3′-dimethoxy-5,5′-dimethyl-[1,1′-biphenyl]-2,2′-diol (2) and 5,5′-diallyl-3,3′-dimethoxy-[1,1′-biphenyl]-2,2′-diol (3). Overall, the ωB97XD functional consistently provided the calculated 1H and 13C chemical shifts with a high level of accuracy.

Calvatianone, a Sterol Possessing a 6/5/6/5-Fused Ring System with a Contracted Tetrahydrofuran B-Ring, from the Fruiting Bodies of Calvatia nipponica.

Calvatia nipponica is an extremely rare mushroom with a limited number of studies on its chemical components and biological activities published. Here we report the isolation of a novel sterol, calvatianone (1), possessing a 6/5/6/5-fused ring system with a contracted tetrahydrofuran B-ring, and four known steroids (2-5) from the fruiting bodies of C. nipponica. The structure of calvatianone including its absolute configuration was determined by NMR spectroscopic analyses, HR-ESIMS, gauge-including atomic orbital NMR chemical shift calculations, and ECD calculations. Ergosterol peroxide (3) and cyathisterol (4) suppressed the cell viability increase induced by 17β-estradiol in MCF-7 breast cancer cell lines, suggesting a possible approach for these compounds to serve as ERα antagonists.

Penctrimertone, a bioactive citrinin dimer from the endophytic fungus Penicillium sp. T2-11

Penctrimertone (1), a novel citrinin dimer bearing a 6/6/6/6 tetracyclic ring scaffold, along with two known compounds xerucitrinic acid A (2) and citrinin (3) were isolated from the endophytic fungus Penicillium sp. T2-11. Their structures were unequivocally established by a comprehensive interpretation of the spectroscopic data, with the stereochemistry for 1 was defined by a combination of TDDFT-ECD calculations and the DP4+ probability analysis based on NMR chemical shift calculations. Bioassays revealed that compound 1 exhibited noticeable antimicrobial activities and moderate cytotoxicity. A plausible biosynthetic pathway of 1 was also proposed.

Insight and performance of LC‐DFT vs DFT in the NMR shielding and chemical shift calculations: Case of CHClCHCF3

AbstractFifteen density functional theory (DFT) methods and fifteen long‐range corrected density functional theory (LC‐DFT) methods were used in the present work to assess nuclear magnetic resonance parameters such as nuclear shielding constant (NSC), nuclear chemical shift (NCS), and nuclear anisotropic shielding constant (NAS). These different methods were associated with the full basis set 6‐311++G(3df,3pd). The gauge‐independent atomic orbital was used for the calculation of nuclear shielding tensors of the nuclei contained in the stereoisomers cis‐ and trans‐CHClCHCF3. Thus, the effects of LC are clearly observed for heavy nuclei (13C, 19F, 35Cl). The results of NSC, NCS, and NAS from DFT are better described than LC‐DFT with regard to the KT3 method. Moreover, the results from the LC‐DFT are better described than the standard DFT with regard to CCSD(T). Based on the latter method used as the benchmark, the NSCs of nuclei are well fitted by the competitive functionals LC‐TPSSTPSS and LC‐PKZBPKZB. In the particular case of the trans‐isomer, mPWPKZB was found to be the best method. For the NCSs, the more accurate methods include the latter two LC functionals and the non‐LC functionals TPSSTPSS and mPWPKZB. The accuracy of NAS depends strongly on the nuclei. Thus, CAM‐B3LYP describes it well for 19F and LC‐PKZBPKZB for 35Cl. The rest of nuclei are well fitted by all the methods except 13C1 and 13C2, which are better reproduced by the LC‐DFT except the LC‐PKZBPKZB, LC‐TPSSTPSS, and CAM‐B3LYP functionals.

Computational Protocols for the 19F NMR Chemical Shifts. Part 1: Methodological Aspects

The DFT calculation of 19F NMR chemical shifts was performed for two benchmark compounds, perfluoroquinoline and perfluoroisoquinoline, each involving seven non-equivalent fluorine atoms, with using a variety of functionals and basis sets. Performed calculations provided a markedly good correlation of calculated fluorine chemical shifts with experiment. Best result was achieved for the BHandHLYP functional in combination with the quadruple zeta Jensen’s segmented basis set pcSseg-3 characterized by a mean absolute error of 2.5 ppm in the range of about 120 ppm, corresponding to a 2% error in the percentage terms. Proposed computational protocol BHandHLYP/pcSseg-3 showed a remarkably good performance on a benchmark series of eight fluorinated condensed heteroaromatic compounds.