1H NMR chemical shift calculations as a probe of supramolecular host-guest geometry

The self-assembled supramolecular host [Ga(4)L(6)](12-) (1; L = 1,5-bis[2,3-dihydroxybenzamido]naphthalene) can encapsulate cationic guest molecules within its hydrophobic cavity and catalyze the chemical transformations of bound guests. The cavity of host 1 is lined with aromatic naphthalene groups, which create a magnetically shielded interior environment, resulting in upfield shifted (1-3 ppm) NMR resonances for encapsulated guest molecules. Using gauge independent atomic orbital (GIAO) DFT computations, we show that (1)H NMR chemical shifts for guests encapsulated in 1 can be efficiently and accurately calculated and that valuable structural information is obtained by comparing calculated and experimental chemical shifts. The (1)H NMR chemical shift calculations are used to map the magnetic environment of the interior of 1, discriminate between different host-guest geometries, and explain the unexpected downfield chemical shift observed for a particular guest molecule interacting with host 1.     

A multidimensional approach to the analysis of chemical shift titration experiments in the frame of a multiple reaction scheme

We present a method for fitting curves acquired by chemical shift titration experiments, in the frame of a three‐step complexation mechanism. To that end, we have implemented a fitting procedure, based on a nonlinear least squares fitting method, that determines the best fitting curve using a “coarse grid search” approach and provides distributions for the different parameters of the complexation model that are compatible with the experimental precision. The resulting analysis protocol is first described and validated on a theoretical data set. We show its ability to converge to the true parameter values of the simulated reaction scheme and to evaluate complexation constants together with multidimensional uncertainties. Then, we apply this protocol to the study of the supramolecular interactions, in aqueous solution, between a lanthanide complex and three different model molecules, using NMR titration experiments. We show that within the uncertainty that can be evaluated from the parameter distributions generated during our analysis, the affinities between the lanthanide derivative and each model molecule can be discriminated, and we propose values for the corresponding thermodynamic constants. Copyright © 2013 John Wiley & Sons, Ltd.     

Halide ion effect on the chloroform chemical shift in supramolecular complexation studies with tetra-n-butylammonium salts: a 1H NMR and X-ray study

A ¹H NMR spectroscopic study of tetra-n-butylammonium halides (TBAX: X = Cl^? , Br^?  or I^? ) in CDCl₃ solutions was conducted. Complexation studies of TBAX salts with different host molecules using ¹H NMR in CDCl₃ have previously revealed that the reference residual CHCl₃ proton signal had been shifted downfield. The aim of the study was to quantify the extent of these chemical shift changes with TBAX salts. Linear concentration–chemical shift relationships in each case were obtained from the resulting titration plots obtained from the addition of the TBAX salts alone to CDCl₃. Interactions in the solid state as determined by X-ray crystallography support the solution-state investigations indicating halide ion–chloroform proton interactions.     

Methyl thiirane: Kinetic gas-phase titration of sulfur atoms in SX OY systems

The reaction SO + SO →l S + SO₂(2) was studied in the gas phase by using methyl thiirane as a titrant for sulfur atoms. By monitoring the C₃H₆ produced in the reaction \documentclass{article}\pagestyle{empty}\begin{document}$ {\rm S} + {\rm CH}_3\hbox{---} \overline {{\rm CH\hbox{---}CH}_2\hbox{---} {\rm S}} \to {\rm S}_2 + {\rm C}_3 {\rm H}_6 (7) $\end{document}, we determined that k₂ ? 3.5 × 10^?15 cm³/s at 298 K.     

NMR chemical shift method in magnetic susceptibility measurements applied to studies of the reaction of cobalt complexes with cumene hydroperoxide

The NMR chemical shift method was applied for the determination of the magnetic susceptibility of paramagnetic transition metal complexes in solution. The method was found to be very useful for the determination of magnetic susceptibility changes during a chemical reaction in which one paramagnetic compound produced another. The concentrations of two paramagnetic cobalt complexes [Co₃O(O₂CCH₃)₆(HO₂CCH₃)₃] and Co(O₂CCH₃)₂, were calculated from the chemical shift value observed during their reaction with cumene hydroperoxide. The results are consistent with those obtained from electronic spectra.     

The NMR spectra of the porphyrins: 23—Metalloporphyrins as diamagnetic shift reagents,chemical applications

Some applications illustrating the use of zinc (II) meso-tetraphenylporphyrin (ZnTPP) as a diamagnetic shift reagent are described. The complexation shifts (ΔP) in a series of substituted pyridines are shown to be determined by both the basicity of the coordinating nitrogen atom and steric effects of ortho-substituents. The selectivity of ZnTPP (N»O) in the simplification of the spectra of multifunctional ligands is demonstrated. Addition of the reagent neither affects the rotamer populations of the Inderal side-chain nor produces any distortion of the 2-benzylmorpholine ring. In addition, the substrate-reagent solution may be shaken with D₂O to identify exchangeable protons. The application of ZnTPP in structural problems involving substituted imidazo[2,1-b]thiazoles and 2-benzyl-1,3-dioxopyrrolo[3,4-c]pyridines allows unambiguous identification of the possible structural isomers. To overcome the solvent limitations of ZnTPP, the more soluble Co(III)TPPBr can be used successfully as a shift reagent in DMSO-d₆, CD₃OD and acetone-d₆ solutions.     

From simple amphiphilic to surfactant behavior: analysis of (1)H NMR chemical shift variations

Analysis of the (1)H NMR chemical shift variations for the methyl protons of sodium decanoate and decanoic acid in D(2)O solutions using reduced variables is consonant with a narrow distribution of sizes about the mean aggregation number for decanoate ion micelles, in contrast with decanoic acid polydisperse aggregates which increase their size with concentration, until phase separation is reached. At defined temperatures between 10 and 50 degrees C, the chemical shift coefficients for the methyl group protons exhibit a negative temperature slope (shielding) for decanoate ion micelles and a positive temperature slope (deshielding) for decanoic acid aggregates. These results suggest that an increase of temperature improves the mobility of the decanoate ion chains in the micelles, thus inducing the methyl groups of the decanoate ion micelles to spend more time near the micelle-water interfaces. In turn, the size of polydisperse decanoic acid aggregates increases with temperature.     

Probing chemical transformations in organic solids via NMR techniques: The solid-state photodimerization reaction of 7-methoxy-4-methylcoumarin

It has been reported that crystalline 7-methoxy-4-methylcoumarin undergoes a [2 + 2] photodimerization reaction to give two different products; the major product is thesyn head-head dimer, whereas the minor product is thesyn head-tail dimer. In this paper, high-resolution solid-state¹³C NMR and solution-state¹H and¹³C NMR techniques have been applied to investigate various structural issues relating to this solid-state photodimerization reaction. In particular, spectra have been recorded at various stages during the progress of the photodimerization reaction with the aim of charting the structural changes in the system as a function of reaction progress, with particular interest in assessing the potential of this technique for investigating the structural reasons for the production of the minor product. Conformational and dynamic properties of the product obtained in this solid-state photodimerization reaction have also been assessed.     

Simultaneous enhancement of chemical shift dispersion and diffusion resolution in mixture analysis by diffusion-ordered NMR spectroscopy

Mixture analysis by high resolution diffusion-ordered NMR spectroscopy (HR-DOSY) requires differences in both chemical shift and diffusion coefficient; resolution can be greatly enhanced by exploiting the chemical specificity of lanthanide shift reagent binding to increase chemical shift and diffusion dispersion simultaneously.     

Configurational analysis of the natural product passifloricin A by quantum mechanical C NMR GIAO chemical shift calculations

Quantum chemical calculations at mPW1PW91 level, with full geometry optimization, using the 6-31g(d) basis set, and GIAO (gauge including atomic orbitals) ¹³C NMR chemical shifts using the 6-31g(d,p) basis set, are here utilized as a support to define the configurational features of the natural product passifloricin A, whose previously proposed relative configuration has been recently shown, by synthetic studies, to be incorrect. This study suggests that the relative stereostructure for passifloricin A corresponds to the δ-lactone of the (5R,7R,9S,11R)-tetrahydroxyhexacos-2-enoic acid.     

13C NMR chemical shifts of carbonyl groups in substituted benzaldehydes and acetophenones: substituent chemical shift increments

13C NMR Substituent chemical shift (SCS) increments have been determined for the carbonyl carbon of a variety of substituted benzaldehydes and acetophenones. The 13C NMR chemical shift of the carbonyl carbon can be predicted for many di- and trisubstituted benzaldehydes and acetophenones through simple additivity of the SCS increments. The magnitude and sign of the SCS increments have been explored using Hartree-Fock 6-31G* calculations to determine the natural atomic charges of the carbonyl carbon. When a substituent capable of intermolecular hydrogen bonding is present, deviations from additivity on the order of 2 ppm are observed in dilution experiments; deviations of up to 6 ppm can result from intramolecular hydrogen bonding.     

Automated chemical structure analysis of organic compounds: An attempt to structure determination by the use of NMR

Summary An attempt to the automated structure elucidation of organic compound was made chiefly by use of NMR as follows: Partial structures which are suitable to construct a molecular structure are selected beforehand. Spectral information afforded by the computer tied into NMR spectrometer designates the number and kind of the partial structures. Then structure building up program constructs the molecular structure(s) based on these designated partial structures and molecular formula.In 24 known compounds examined by this method, one correct structure was given for 9 compounds, and multiple number of answers including an appropriate structure were given for 15 compounds.

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Zusammenfassung Ein Versuch zur automatischen Strukturaufklärung organischer Verbindungen durch kernmagnetische Resonanz wurde in folgender Weise unternommen: Zunächst wurden Teilstrukturen ausgewählt, die sich zum Aufbau einer Molekülstruktur eignen. Ein an das Kernresonanzspektrometer angeschlossener Computer liefert die Information über Art und Anzahl der Teilstrukturen. Auf der Grundlage dieser Teilstrukturen und der Molekülformel liefert ein Struktur-Aufbauprogramm die Molekülstruktur. Für 24 nach diesem Verfahren geprüfte, bekannte Verbindungen wurde in 9 Fällen ein eindeutig korrektes Ergebnis erhalten; in 15 Fällen lieferte der Computer mehrere Antworten, darunter auch die jeweils richtige.

     

13C NMR chemical shift and electronic structure of polyoxymethylene in the solid state

High-resolution ¹³C NMR spectra of polyoxymethylene (POM) in the solid state have been measured in order to obtain a relationship between the conformation and ¹³C NMR chemical shift tensor (δ₁₁, δ₂₂ and δ₃₃) and its isotropic average. It was found that the ¹³C isotropic chemical shift of POM in the crystalline region appears upfield with respect to that in the noncrystalline region and that the width Δδ ( = δ₁₁ - δ₃₃) in the crystalline region is much larger than that in the noncrystalline region. These experimental findings can be reasonably explained by a theoretical calculation for an infinite POM chain based on a tight-binding molecular orbital calculation within the CNDO/2 framework.     

Origins of the proton NMR chemical shift non-equivalence in the diastereotopic methylene protons of camphanamides

The observed chemical shift non-equivalence of the diastereotopic methylene protons in primary camphanamides is rationalized in terms of chirality independent, differential shielding of H_S by the amide carbonyl, as deduced by nmr solution, X-ray structural studies and molecular mechanics calculations.     

Biomolecular NMR using a microcoil NMR probe--new technique for the chemical shift assignment of aromatic side chains in proteins

A specially designed microcoil probe for use in biomolecular NMR spectroscopy is presented. The microcoil probe shows a mass-based sensitivity increase of a minimal factor of 7.5, allowing for the first time routine biomolecular NMR spectroscopy with microgram amounts of proteins. In addition, the exceptional radio frequency capabilities of this probe allowed us to record an aliphatic-aromatic HCCH-TOCSY spectrum for the first time. Using this spectrum, the side chains of aliphatic and aromatic amino acids can be completely assigned using only a single experiment. Using the conserved hypothetical protein TM0979 from Thermotoga maritima, we demonstrate the capabilities of this microcoil NMR probe to completely pursue the sequence specific backbone assignment with less than 500 microg of (13)C,(15)N labeled protein.     

Utility of kinetic analysis in the determination of reaction mechanism

Thermal analysis has a long and prominent role in the characterization of materials, including polymeric materials. Kinetic studies in one form or another have often been employed in an attempt to assess stability, predict lifetime, establish degradation pathway, or project suitable processing conditions. The results of such studies have often formed the basis for the proposal of the ‘mechanism’ of reaction. This despite the fact that the reaction being observed is often unknown or is not a single process but rather several parallel or consecutive events. This latter is particularly true for ‘variable temperature kinetics’. The utility/value of such exercises is marginal at best and contributes nothing to an understanding of the mechanism of any of the reactions involved.     

Maximum value of the chemical shift in the 1H NMR spectrum of a hydrogen-bonded complex

The values of chemical shifts in the ¹H NMR spectra of complexes with the strongest quasisymmetrical hydrogen bond A^δ?...H...B^δ+ with a minimal A...B distance were analyzed theoretically. According to the calculations, the maximum of the chemical shift is somewhat displaced from the shift of this structure toward that of limiting structure (free acid or protonated base) in which the proton is less shielded, but the value of this displacement is insignificant and does not correlate directly with the difference between the chemical shifts of the limiting structures.     

Toward direct determination of conformations of protein building units from multidimensional NMR experiments VI: chemical shift analysis of his to gain 3D structure and protonation state information

NMR--chemical shift structure correlations were investigated by using GIAO-RB3LYP/6-311++G(2d,2p) formalism. Geometries and chemical shifts (CSI values) of 103 different conformers of N'-formyl-L-histidinamide were determined including both neutral and charged protonation forms. Correlations between amino acid torsional angle values and chemical shifts were investigated for the first time for an aromatic and polar amino acid residue whose side chain may carry different charges. Linear correlation coefficients of a significant level were determined between chemical shifts and dihedral angles for CSI[(1)H(alpha)]/phi, CSI[(13)C(alpha)]/phi, and CSI[(13)C(alpha)]/psi. Protonation of the imidazole ring induces the upfield shift of CSI[(13)C(alpha)] for positively charged histidines and an opposite effect for the negative residue. We investigated the correspondence of theoretical and experimental (13)C(alpha), (13)C(beta), and (1)H(alpha) chemical shifts and the nine basic conformational building units characteristic for proteins. These three chemical shift values allow the identification of conformational building units at 80% accuracy. These results enable the prediction of additional regular secondary structural elements (e.g., polyProlineII, inverse gamma-turns) and loops beyond the assignment of chemical shifts to alpha-helices and beta-pleated sheets. Moreover, the location of the His residue can be further specified in a beta-sheet. It is possible to determine whether the appropriate residue is located at the middle or in a first/last beta-strand within a beta-sheet based on calculated CSI values. Thus, the attractive idea of establishing local residue specific backbone folding parameters in peptides and proteins by employing chemical shift information (e.g., (1)H(alpha) and (13)C(alpha)) obtained from selected heteronuclear correlation NMR experiments (e.g., 2D-HSQC) is reinforced.     

Ab initio and NMR studies on the effect of hydration on the chemical shift of hydroxy protons in carbohydrates using disaccharides and water/methanol/ethers as model systems

Density functional theory (DFT) and Hartree-Fock (HF) quantum mechanical calculations have been performed on the disaccharides, [small beta]-l-Fucp-(1[rightward arrow]4)-[small alpha]-d-Galp-OMe, [small beta]-l-Fucp-(1[rightward arrow]4)-[small alpha]-d-Glcp-OMe, and [small beta]-l-Fucp-(1[rightward arrow]3)-[small alpha]-d-Glcp-OMe. The [capital Delta][small delta]-values (difference between the chemical shift in the disaccharide and the corresponding monosaccharide methyl glycoside) for the exchangeable hydroxy protons have been calculated and compared to experimental values previously measured by NMR spectroscopy for samples in aqueous solutions. The calculations performed on molecules in vacuum showed that hydroxy protons hydrogen bonded to the neighboring ring oxygens have large positive [capital Delta][small delta]-values, indicating that they are deshielded relative to those in the corresponding methyl glycoside. The NMR experiments showed instead that these hydroxy protons close to the neighboring ring oxygens were shielded. This discrepancy between calculated and experimental data was attributed to solvent effects, and this hypothesis has been confirmed in this work by monitoring the chemical shift of the hydroxy proton of methanol in water, ethers and water/ether solutions. Shielding of the hydroxy proton of methanol is observed for increased ether concentrations, whereas deshielding is observed for increased concentration of water. The shielding observed for hydroxy protons in disaccharides is a consequence of reduced hydration due to intermolecular hydrogen bonding or steric effects. In strongly hydrated systems such as carbohydrates, the hydration state of a hydroxy proton is the key factor determining the value of the chemical shift of its NMR signal, and the [capital Delta][small delta] will be a direct measure of the change in hydration state.     

Stability constants: comparative study of fitting methods. Determination of second-order complexation constants by (23)Na and (7)Li NMR chemical shift titration

NMR chemical shift titration has been widely used as a method for the determination of stability constants. Systems involving metal-ligand complexation have been investigated using a number of methodologies. There are significant differences in the values reported for stability constants obtained by different experimental methods, such as calorimetry and ion selective electrode (ISE) titrations; nor has NMR chemical shift titration always yielded consistent results. Different researchers have obtained different results for the same system with results differing by as much as an order of magnitude. The chemical shift data are generally plotted against the concentration ratio of the metal and ligand for a set of solutions. A nonlinear least squares fitting method using an analytical solution of the cubic equation for the equilibrium concentration of the free ligand is used in this study and compared with methods used in the literature. Second-order association constants for the LiClO(4):12-crown-4 system in acetonitrile and the NaClO(4):12-crown-4 system in methanol are reported. Formation of both 1:1 and 1:2 metal-ligand complexes are considered. The LiClO(4):12-crown-4 acetonitrile system had been investigated previously by NMR titration but only 1:1 complexation was considered in that study. This study provides convincing evidence that both 1:1 and 1:2 complexes are important, at least, in the lithium system. A Monte Carlo investigation of the propagation of errors from the chemical shifts to the stability constants shows that the choice of data analysis methods may, in part, contribute to discrepancies and that the nonlinear nature of the model can dramatically affect the error limits on the stability constants.