NMR Chemical Shifts Research Articles

Synergy in the Microbial Cyclic Lipopeptide/Petroleum-Derived Surfactant Mixture Can Reduce the Total Surfactant Consumption

We report the synergistic effect of the addition of a microbial cyclic lipopeptide, surfactin (SF), to the most common petroleum-derived surfactant, sodium dodecyl sulfate (SDS). The addition of a small amount of SF (0.1 mol %) to an aqueous solution of SDS reduces the critical micelle concentration (CMC) of SDS from 10–3 to 10–6 M order. The addition of SF to SDS at various ratios lowered the surface tension at the CMC of SDS, indicating CMC reduction and, thus, the minimization of total SDS consumption without loss of surface activity. Surface tension measurement and nuclear magnetic resonance spectroscopy were conducted to analyze the synergy between SDS and SF in aqueous solutions as a function of composition. The interaction parameters of the mixed monolayer and mixed micelles were negative, indicating the occurrence of attractive interactions between SDS and SF, which were stronger than those among the individual surfactants. Moreover, the surface tension at the CMC, area occupied per surfactant molecule, difference in the interaction parameter, and 1H NMR chemical shift values of the SDS/SF mixtures as a function of their composition exhibited an extremum at a mole fraction of 0.7. These results suggest that SF has the peculiarities of encapsulation of the anionic surfactant of SDS within the inner cavity and can screen the electrostatic repulsion of SDS via the formation of their inclusion complex at SDS:SF = 2:1, which facilitates the formation of mixed monolayers and micelles in a more stable state.

1H NMR-Based Metabolomics to Assess the Impact of Soil Type on the Chemical Composition of Nero d’Avola Red Wines

In this study, the soil effect on the micro-component composition of Nero d'Avola wines obtained from different locations was investigated through 1H NMR-based metabolomics. Two different approaches were applied: the targeted (TA) and the non-targeted one (NTA). The former differentiated the wines by profiling (i.e., by identifying and quantifying) a number of different metabolites. The latter provided wine fingerprinting by processing the entire spectra with multivariate statistical analysis. NTA also allowed investigation of the hydrogen bond network inside wines via the analysis of 1H NMR chemical shift dispersions. Results showed that the differences among wines were due not only to the concentrations of various analytes but also to the characteristics of the H-bond network where different solutes were involved. The H-bond network affects both gustatory and olfactory perceptions by modulating the way how solutes interact with the human sensorial receptors. Moreover, the aforementioned H-bond network is also related to the soil properties from which the grapes were taken. Therefore, the present study can be considered a good attempt to investigate terroir, i.e., the relationship between wine quality and soil characteristics.

Intramolecular O···H Hydrogen Bonding of Salicylic Acid: Further Insights from O 1s XPS and 1H NMR Spectra Using DFT Calculations.

Intramolecular hydrogen bonding (HB) is a complex phenomenon that extends beyond a simple valence event, affecting the core electrons of a molecule. Salicylic acid (SA) and its conformers provide an excellent model compound for studying intramolecular HB as the proton donor (H) and acceptor (O) can be toggled by rotating the C-O and C-C bonds to form up to seven potential conformers through various HB. In this study, we computationally investigated intramolecular interactions in SA conformers with and without such HB, by examining their calculated O 1s core electron-binding energy (CEBE) and 1H NMR chemical shifts validated using recent measurements. The quantum mechanically stable SA conformers are fully defined by three rotatable bonds in the compound, which are abstracted as SA(η1η2η3) digital structures, where ηi = 0 if the ηi angles match the most stable SA conformer (000) and ηi = 1 otherwise. Our findings suggest that the stability is dominated by the appearance of the intergroup intramolecular HB of Hp···O (where O is in the carboxylic acid functional group and Hp is the phenolic proton in -OHp), and η3 serves as a switch of such HB. As a result, the (η1η20) SA conformers containing such Hp···O HB are more stable than other SA conformers (η1η21) without such the Hp···O HB. The present density functional theory calculations reveal that this Hp···O HB results in splitting of the O 1s CEBEs of two hydroxyl groups (-OH) by up to 1 eV and deshielding the Hp proton 1H NMR (δHp) up to 11.68 ppm for the (η1η20) conformers. Without such Hp···O HB, the O 1s XPS binding energies of two -OH groups will be closely located in the same band, and the 1H NMR chemical shift of the Hp atom will be as small as an 4.09 ppm SA conformer [SA-G(101)]. The present study indicates that the O 1s CEBE splitting between two -OH groups serves as an indicator of the presence of the Hp···O HB in SA conformers, which is also supported by the 1H NMR results.

Dendrillic Acids A and B: Nitrogenous, Rearranged Spongian Nor-Diterpenes from a Dendrilla sp. Marine Sponge.

Two nitrogenous rearranged spongian nor-diterpenoids, dendrillic acids A and B, were isolated from a marine sponge Dendrilla sp. (order: Dendroceratida; family: Darwinellidae). The structures of the metabolites were elucidated on the basis of spectroscopic analysis as well as density functional theory prediction of NMR chemical shifts and application of the DP4+ algorithm. The absolute configuration of the metabolites was established via comparison of experimental and time-dependent density functional theory predicted electronic circular dichroism data. An unusual epimerization reaction was observed leading to the interconversion of the metabolites upon storage in dimethyl sulfoxide solution, which is proposed to proceed via an anionic pathway as probed via isotopic incorporation experiments. Evaluation against a panel of micro-organisms and cell lines revealed that the compounds were devoid of any significant biological activity against all organisms tested, with the exception of mild antiprotozoal activity displayed by dendrillic acid B (2) against Giardia duodenalis.

New Bisabolane-Type Sesquiterpenoids from Curcuma longa and Their Anti-Atherosclerotic Activity.

To explore the sesquiterpenoids in Curcuma longa L. and their activity related to anti-atherosclerosis. The chemical compounds of the rhizomes of C. longa were separated and purified by multiple chromatography techniques. Their structures were established by a variety of spectroscopic experiments. The absolute configurations were determined by comparing experimental and calculated NMR chemical shifts and electronic circular dichroism (ECD) spectra. Their anti-inflammatory effects and inhibitory activity against macrophage-derived foam cell formation were evaluated by lipopolysaccharide (LPS) and oxidized low-density lipoprotein (ox-LDL)-injured RAW264.7 macrophages, respectively. This study resulted in the isolation of 10 bisabolane-type sesquiterpenoids (1-10) from C. longa, including two pairs of new epimers (curbisabolanones A-D, 1-4). Compound 4 significantly inhibited LPS-induced nitric oxide (NO), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2) production in RAW264.7 cells. Furthermore, compound 4 showed inhibitory activity against macrophage-derived foam cell formation, which was represented by markedly reducing ox-LDL-induced intracellular lipid accumulation as well as total cholesterol (TC), free cholesterol (FC), and cholesterol ester (CE) contents in RAW264.7 cells. These findings suggest that bisabolane-type sesquiterpenoids, one of the main types of components in C. longa, have the potential to alleviate the atherosclerosis process by preventing inflammation and inhibiting macrophage foaming.

Solid-State 19F NMR Chemical Shift in Square-Planar Nickel-Fluoride Complexes Linked by Halogen Bonds.

The halogen bond (XB) is a highly directional class of noncovalent interactions widely explored by experimental and computational studies. However, the NMR signature of the XB has attracted limited attention. The prediction and analysis of the solid-state NMR (SSNMR) chemical shift tensor provide useful strategies to better understand XB interactions. In this work, we employ a computational protocol for modeling and analyzing the 19F SSNMR chemical shifts previously measured in a family of square-planar trans NiII-L2-iodoaryl-fluoride (L = PEt3) complexes capable of forming self-complementary networks held by a NiF···I(C) halogen bond [Thangavadivale, V.; Chem. Sci. 2018, 9, 3767-3781]. To understand how the 19F NMR resonances of the nickel-bonded fluoride are affected by the XB, we investigate the origin of the shielding in trans-[NiF(2,3,5,6-C6F4I)(PEt3)2], trans-[NiF(2,3,4,5-C6F4I)(PEt3)2], and trans-[NiF(C6F5)(PEt3)2] in the solid state, where a XB is present in the two former systems but not in the last. We perform the 19F NMR chemical shift calculations both in periodic and molecular models. The results show that the crystal packing has little influence on the NMR signatures of the XB, and the NMR can be modeled successfully with a pair of molecules interacting via the XB. Thus, the observed difference in chemical shift between solid-state and solution NMR can be essentially attributed to the XB interaction. The very high shielding of the fluoride and its driving contributor, the most shielded component of the chemical shift tensor, are well reproduced at the 2c-ZORA level. Analysis of the factors controlling the shielding shows how the highest occupied Ni/F orbitals shield the fluoride in the directions perpendicular to the Ni-F bond and specifically perpendicular to the coordination plane. This shielding arises from the magnetic coupling of the Ni(3d)/F(2p lone pair) orbitals with the vacant σNi-F* orbital, thereby rationalizing the very highly upfield (shielded) resonance of the component (δ33) along this direction. We show that these features are characteristic of square-planar nickel-fluoride complexes. The deshielding of the fluoride in the halogen-bonded systems is attributed to an increase in the energy gap between the occupied and vacant orbitals that are mostly responsible for the paramagnetic terms, notably along the most shielded direction.

Crystal plane dependent dispersion of cobalt metal on metastable aluminas

Metallic Co nanoparticles, widely used and studied as supported heterogeneous catalysts for Fischer-Tropsch synthesis (FTS), display catalytic properties that can vary significantly depending on their size and crystal structure. In this work, we used 59Co Internal Field NMR (59Co IF NMR) complemented by high-resolution transmission electron microscopy (HRTEM) to demonstrate the influence of strong metal-support interaction on two noticeably different metastable alumina phases - γ-Al2O3 and χ-Al2O3. According to 59Co IF NMR and HRTEM, the metallic particles supported on χ-Al2O3 were larger and displayed a significantly higher content of Co in its hcp phase, which is known to be more active and selective to C5+ in FTS. The 1H NMR chemical shifts of hydroxyl groups anchored to the (110) and (111) spinel crystal planes were calculated by DFT. It revealed that the hydroxyl coverage of γ-Al2O3 facilitates the dispersion of Co precursor over the surface of the support, ultimately leading to the formation of smaller metal Co nanoparticles on γ-Al2O3 than on χ-Al2O3.

Stereochemical Study of the Super Large Tetrakis Alkaloid Alasmontamine A by Means of an Advanced Computational NMR.

1H and 13C NMR chemical shifts of the tetrakis monoterpene indole alkaloid alasmontamine A, with a molecular formula of C84H91N8O12, have been calculated within the DFT framework. Six minimum energy conformers of this alkaloid were identified, and three key configurations that contribute to its NMR shielding constants were established. Several ambiguities in the reported assignment of the NMR chemical shifts of alasmontamine A have been resolved.

Drug-Repurposing Screening Identifies a Gallic Acid Binding Site on SARS-CoV-2 Non-structural Protein 7.

SARS-CoV-2 is the agent responsible for acute respiratory disease COVID-19 and the global pandemic initiated in early 2020. While the record-breaking development of vaccines has assisted the control of COVID-19, there is still a pressing global demand for antiviral drugs to halt the destructive impact of this disease. Repurposing clinically approved drugs provides an opportunity to expediate SARS-CoV-2 treatments into the clinic. In an effort to facilitate drug repurposing, an FDA-approved drug library containing 2400 compounds was screened against the SARS-CoV-2 non-structural protein 7 (nsp7) using a native mass spectrometry-based assay. Nsp7 is one of the components of the SARS-CoV-2 replication/transcription complex essential for optimal viral replication, perhaps serving to off-load RNA from nsp8. From this library, gallic acid was identified as a compound that bound tightly to nsp7, with an estimated K d of 15 μM. NMR chemical shift perturbation experiments were used to map the ligand-binding surface of gallic acid on nsp7, indicating that the compound bound to a surface pocket centered on one of the protein's four α-helices (α2). The identification of the gallic acid-binding site on nsp7 may allow development of a SARS-CoV-2 therapeutic via artificial-intelligence-based virtual docking and other strategies.

DELTA50: A Highly Accurate Database of Experimental 1H and 13C NMR Chemical Shifts Applied to DFT Benchmarking

Density functional theory (DFT) benchmark studies of 1H and 13C NMR chemical shifts often yield differing conclusions, likely due to non-optimal test molecules and non-standardized data acquisition. To address this issue, we carefully selected and measured 1H and 13C NMR chemical shifts for 50 structurally diverse small organic molecules containing atoms from only the first two rows of the periodic table. Our NMR dataset, DELTA50, was used to calculate linear scaling factors and to evaluate the accuracy of 73 density functionals, 40 basis sets, 3 solvent models, and 3 gauge-referencing schemes. The best performing DFT methodologies for 1H and 13C NMR chemical shift predictions were WP04/6-311++G(2d,p) and ωB97X-D/def2-SVP, respectively, when combined with the polarizable continuum solvent model (PCM) and gauge-independent atomic orbital (GIAO) method. Geometries should be optimized at the B3LYP-D3/6-311G(d,p) level including the PCM solvent model for the best accuracy. Predictions of 20 organic compounds and natural products from a separate probe set had root-mean-square deviations (RMSD) of 0.07 to 0.19 for 1H and 0.5 to 2.9 for 13C. Maximum deviations were less than 0.5 and 6.5 ppm for 1H and 13C, respectively.

19F NMR chemical shifts are sensitive to remote functional group variations

Covalently identical ortho-F nuclei display dual 19F NMR signals in di-ortho-F substituted N-phenyl γ-lactams. We found that the deshielding 19F signal (δdown) was significantly affected by C9-substituent, especially when C9- substituents are steric bulky. Notably, the deshielded 19F chemical shift is sensitive to chirality variations at C9-alkyls, while the shielded 19F NMR signal δup manifests negligible changes among various C9-alkyl derivatives. Calculated molecular electrostatic surface potentials (ESPs) were used to interpret the experimental observations. 19F NMR signal assignments in an exemplary rotameric molecule are presented based on our understanding on structure-19F shielding relationship. Our work described here provides basics to deciphering 19F shielding in biologically important molecules and drugs, and to use of 19F chemical shifts in monitoring molecular dynamics and conformations.

Species-specific secondary metabolism by actinomycetes of the genus Phytohabitans and discovery of new pyranonaphthoquinones and isatin derivatives.

To further exploit secondary metabolic potential of a minor actinomycete genus Phytohabitans within the family Micromonosporaceae, metabolite profiling by HPLC-UV analysis, combined with 16S rDNA sequence-based phylotyping were attempted on seven Phytohabitans strains available at the public culture collection. The strains were grouped into three clades and each exhibited unique and distinct metabolite profiles, which were highly conserved among strains within the same clade. These results were consistent with previous observations on two other actinomycetes genera, reconfirming species-specificity of secondary metabolite production, which were conventionally thought to be strain-specific. A strain RD003215, belonging to the P. suffuscus clade, produced multiple metabolites, some of which were presumed to be naphthoquinones. Liquid fermentation followed by chromatographic separation of the broth extract led to the discovery of three new pyranonaphthoquinones, designated habipyranoquinones A-C (1-3), and one new isatin derivative, (R)-N-methyl-3-hydroxy-5,6-dimethoxyoxindole (4), along with three known synthetic compounds, 6,8-dihydroxydehydro-α-lapachone (5), N-methyl-5,6-dimethoxyisatin (6), and 5,6-dimethoxyisatin (7). Structures of 1-4 were unequivocally elucidated by NMR, MS, and CD spectral analysis, with assistance of density functional theory-based NMR chemical shift prediction and ECD spectral calculation. Compound 2 displayed antibacterial activity against Kocuria rhizophila and Staphylococcus aureus with MIC 50 µg/mL and cytotoxicity against P388 murine leukemia cells with an IC50 value of 34 µM. Compounds 1 and 4 also showed cytotoxicity against P388 cells with IC50 values of 29 and 14 µM, respectively.

Discovering the Solid-State Secrets of Lorlatinib by NMR Crystallography: To Hydrogen Bond or not to Hydrogen Bond

Lorlatinib is an active pharmaceutical ingredient (API) used in the treatment of lung cancer. Here, an NMR crystallography analysis is presented whereby the single-crystal X-ray diffraction structure (CSD: 2205098) determination is complemented by multinuclear (1H, 13C, 14/15N, 19F) magic-angle spinning (MAS) solid-state NMR and gauge-including projector augmented wave (GIPAW) calculation of NMR chemical shifts. Lorlatinib crystallises in the P21 space group, with two distinct molecules in the asymmetric unit cell, Z′ = 2. Three of the four NH2 hydrogen atoms form intermolecular hydrogen bonds, N30-H…N15 between the two distinct molecules and N30-H…O2 between two equivalent molecules. This is reflected in one of the NH21H chemical shifts being significantly lower, 4.0 ppm compared to 7.0 ppm. Two-dimensional 1H–13C, 14N-1H and 1H (double-quantum, DQ)-1H (single-quantum, SQ) MAS NMR spectra are presented. The 1H resonances are assigned and specific HH proximities corresponding to the observed DQ peaks are identified. The resolution enhancement at a 1H Larmor frequency of 1 GHz as compared to 500 or 600 MHz is demonstrated.

Templated Enzymatic Synthesis of δ-Cyclodextrin.

While α-, β-, and γ-cyclodextrin (CD) are ubiquitous hosts employed by supramolecular chemists, δ-CD (formed from nine α-1,4-linked glucopyranose units) has received very little attention. α-, β-, and γ-CD are the major products of the enzymatic breakdown of starch by cyclodextrin glucanotransferase (CGTase), but δ-CD forms only transiently in this reaction, as a minor component of a complex mixture of linear and cyclic glucans. In this work, we show how δ-CD can be synthesized in unprecedented yields by employing a bolaamphiphile template in an enzyme-mediated dynamic combinatorial library of cyclodextrins. NMR spectroscopy studies revealed that δ-CD can thread up to three bolaamphiphiles forming [2]-, [3]-, or [4]-pseudorotaxanes, depending on the size of the hydrophilic headgroup and the length of the alkyl chain axle. Threading of the first bolaamphiphile occurs in fast exchange on the NMR chemical shift time scale, while subsequent threading occurs in slow exchange. To extract quantitative information for 1:2 and 1:3 binding events occurring in mixed exchange regimes, we derived equations for nonlinear curve fitting that take into consideration both the chemical shift changes for species in fast exchange and the integrals for species in slow exchange to determine Ka1, Ka2, and Ka3. Template T1 could be used to direct the enzymatic synthesis of δ-CD due to the cooperative formation of a 1:2 complex─the [3]-pseudorotaxane δ-CD·T12. Importantly, T1 is recyclable. It can be readily recovered from the enzymatic reaction by precipitation and reused in subsequent syntheses enabling preparative-scale synthesis of δ-CD.

Crystal structure, spectroscopic analysis, electronic properties and molecular docking study of costunolide for inhibitor capacity against Onchocerca volvulus main protease

Costunolide, a naturally occurring sesquiterpene lactone, was investigated experimentally and theoretically to determine the structural, electronic, spectroscopic, and chemical reactivity properties. As deduced from a single crystal X-ray diffraction (XRD) analysis, the absolute configurations of the two chiral centres were assigned as (6R,7S). Vibrational frequencies (IR, UV and NMR), electronic properties (HOMO and LUMO), and the molecular structure of costunolide were investigated by DFT calculations using Gaussian 09 molecular package at the B3LYP/6-311++G(d,p) level of theory. NMR chemical shifts were calculated from the magnetic shielding tensors obtained through the gauge-independent atomic orbital (GIAO) method, while the UV-vis spectrum was simulated by time dependent-DFT (TD-DFT) calculations. All calculations showed correlations to experimental data. The 6-311+G(2d,p) basis set was additionally used for better correlation in NMR studies. The first order hyperpolarizability value indicated that costunolide has nonlinear optical (NLO) properties. Costunolide stability arising from hyperconjugative interactions and charge delocalisation was analysed using natural bond orbital (NBO). Thermodynamic parameters also correlated in the temperature range 100–700 K. The molecular docking results showed that costunolide binds strongly to the Onchocerca volvulus main protease with a relative binding affinity of –5.94 kcal mol–1 and an inhibition constant of 44.61 µM.

S-Indacene Revisited: Modular Synthesis and Modulation of Structures and Molecular Orbitals of Hexaaryl Derivatives

Though s-indacene is an intriguing antiaromatic hydrocarbon of 12 π-electrons, it has been underrepresented due to the lack of efficient and versatile methods to prepare stable derivatives. Herein we report a concise and modular synthetic method for hexaaryl-s-indacene derivatives bearing electron-donating/-accepting groups at specific positions to furnish C2h-, D2h-, and C2v-symmetric substitution patterns. We also report the effects of substituents on their molecular structures, frontier molecular orbital (MO) levels, and magnetically induced ring current tropicities. Both theoretical calculations and X-ray structure analyses indicate that the derivatives of the C2h-substitution pattern adopt different C2h structures with significant bond length alternation depending on the electronic property of the substituents. Due to the nonuniform distribution of the frontier MOs, their energy levels are selectively modulated by the electron-donating substituents. This leads to the inversion of the HOMO and HOMO-1 sequences with respect to those of the intrinsic s-indacene as theoretically predicted and experimentally proven by the absorption spectra at visible and near-infrared regions. The NICS values and the 1H NMR chemical shifts of the s-indacene derivatives indicate their weak antiaromaticity. The different tropicities are explained by the modulation of the HOMO and HOMO-1 levels. In addition, for the hexaxylyl derivative, weak fluorescence from the S2 excited state was detected due to the large energy gap between the S1 and S2 states. Notably, an organic field-effect transistor (OFET) fabricated using the hexaxylyl derivative exhibited moderate hole carrier mobility, a result which opens the door for optoelectronic applications of s-indacene derivatives.

Elucidating Structures of Complex Organic Compounds Using a Machine Learning Model Based on the 13C NMR Chemical Shifts

We present a protocol that combines the support vector machine (SVM) model with accurate 13C chemical shift calculations at the xOPBE/6-311+G(2d,p) level of theory, denoted as SVM-M (i.e., SVM for magnetic property). We show here that this SVM-M protocol is a versatile tool for identifying the structural and stereochemical assignment of complex organic compounds with high confidence. Of particular significance is that, by utilizing the dual role of the decision values in SVM, the present SVM-M protocol provides an accurate yet efficient solution to simultaneously handle the classification issue (i.e., “is a given structure correct or incorrect?”) and the comparison-based problem (i.e., “which structure is more likely to be correct or wrong among several candidate structures?”). A significantly high success rate has been reached (i.e., ∼100% on a set of 760 sample molecules with 15928 13C chemical shifts), which makes the SVM-M protocol a powerful tool for routine applications in structural and stereochemical assignments, as well as in detecting mis-assignments, for complex organic compounds, including natural products.

NMR and DFT studies of monounsaturated and ω-3 polyunsaturated free fatty acids in the liquid state reveal a novel atomistic structural model of DHA

Structures of low-energy conformers of caproleic acid (CA; 10:1 cis-9), oleic acid (OA; 18:1 cis-9), α-linolenic acid (ALA; 18:3 cis-9,12,15 ω-3), eicosapentaenoic acid (EPA; 20:5 cis-5,8,11,14,17 ω-3), and docosahexaenoic acid (DHA; 22:6 cis-4,7,10,13,16,19 ω-3) in the liquid state, based on detailed 1D NOE and density functional theory calculations of 1H NMR chemical shifts are presented. Transient 1D NOE experiments with variable mixing time showed significant through-space proximity of the CH2–COOH protons and the terminal CH3– groups. Variable temperature 1H NMR experiments revealed strong intermolecular centro-symmetric cyclic hydrogen bond interactions of the carboxylic groups of the monounsaturated oleic and caproleic acids (δ(COOH) ∼ 12.0–12.4 ppm), ALA and EPA (δ(COOH) ∼ 11.0 ppm). On the contrary, the carboxylic proton of DHA is strongly shielded with δ(COOH) ∼ 8.5 ppm. DFT calculations were interpreted in terms of aggregates of dimerized fatty acids with parallel and antiparallel interdigitated structures. The antiparallel arrangement was found to be in excellent agreement with experimental 1D NOE NMR data. For the dimeric DHA, a flip-flop process between a classical intermolecular centro-symmetric hydrogen bond through carboxylic groups and a novel intramolecular hydrogen bond between the carboxylic group and the terminal ω-3 double bond is demonstrated.

Computational studies of [1]benzothieno[2,3-c]naphtho[1,2-f]quinoline.

Early NMR studies of several heterohelicenes containing an annular nitrogen atom and a thiophene ring in their structure suggested the possibility of the lengthening of the carbon-carbon bonds in the interior of the helical turn of the molecule based on the progressive moreshieldednature of 13 C resonances toward the center of the helical turn. Computational chemistry capabilities when those NMR studies were performed were primitive in comparison to what is now possible. We now report the optimized geometry and a comparison of the calculated versus observed 1 H and 13 C NMR chemical shift assignments for [1]benzothieno[2,3-c]naphtho[1,2-f]quinoline that confirms these suspicions.

Computational 19 F NMR of trifluoromethyl derivatives of alkenes, pyrimidines, and indenes.

The 19 F NMR chemical shifts of 13 trifluoromethyl derivatives of alkenes, pyrimidines, and indenes were calculated at the DFT level using the BhandHLYP, BHandH, PBE, PBE0, O3LYP, B3LYP, KT2, and KT3 functionals in combination with the pcS-2 basis set. Best result was documented for the BHandHLYP functional: The mean absolute error (MAE) of 0.66 ppm for the scaled values was achieved for the range of about 20 ppm. Solvent, vibrational, and relativistic corrections were found to be rather small, especially when taken in combination, generally demonstrating a slight decrease in the difference between calculated and experimental fluorine chemical shifts. As a measure of the practical importance of these compounds, one should recall that the growing number of life science products that contain trifluoromethyl groups provides a continuing driving force for the development of an effective methodology that enables both regio- and stereoselective introduction of trifluoromethyl groups into both aliphatic and aromatic systems.