Vibrational and 29Si NMR spectroscopies of soluble silicate oligomers

Vibrational spectroscopy has been used to correlate the features of silicate solution spectra with ²⁹Si NMR spectra, as a function of SiO₂:Na₂O ratio and SiO₂ concentration. Assignments of infrared and Raman component bands have been made for different anion types and are consistent with results reported for crystalline silicates and silicate glasses. The extent of depolymerization of larger anions has been found to differ, depending on both the degree of dilution and alkalinity. The relative amounts of polymeric (Q⁴) silica and larger three dimensional (Q³_4R) anions are greater for the more siliceous solutions (3.3 and 2.95 ratio) at high concentrations. These large anions continue to be major contributors to the anion distribution even at 15 to 50 fold dilution. In the case of more alkaline solutions, especially below 2.5 ratio, the relative contribution of the large anions to the distribution drops rapidly, even with 2 or 3 fold dilution. At low concentrations, in very alkaline solutions, the anion distribution is mainly monomer, dimer and cyclic trimer. Vibrational spectroscopies show great promise for observing changes in anion distribution on a much shorter time scale than is possible with ²⁹Si NMR and can be useful for following reactions involving silicate solutions.     

Conformational analysis of ochratoxin a by NMR spectroscopy and computational molecular modeling

Two-dimensional NMR spectroscopy has been used for a complete assignment of the proton and carbon-13 spectra of the metabolite from Aspergillus ochraceus, ochratoxin A. In addition, phase-sensitive nuclear Overhauser effect spectrometry experiments and computational molecular modeling (MM2 and MMFF force field programs) have been employed to examine the conformational properties of ochratoxin A in chloroform solutions. Particular attention has been given to intramolecular hydrogen-bonding formation involving the phenolic group on dihydroisocoumarin, which may be responsible for the toxic mechanism of ochratoxin A.     

Internal rotation in enaminonitriles: Investigation by dynamic NMR spectroscopy and molecular modeling

Rotational isomerism in enaminonitriles was studied using dynamic NMR spectroscopy and molecular modeling. It was found that the barrier to rotation about C_vinyl-NH bond was higher for enaminonitriles derived from aliphatic amines than that of enaminonitriles derived from aromatic amines. It was also found that the rotational isomerism about the C_ar-C_vinyl bond also exists in enaminonitriles.     

Application of NMR spectroscopy in molecular weight determination of polymers

Determination of molecular weights of polymers by ¹H-NMR spectroscopy is discussed. A brief survey of application of NMR; both ¹H and ¹⁴C, in the analysis of monomer sequence, copolymer composition, polymer microstructure, end-group and relaxation phenomenon is also made. NMR offers an elegant and simple yet fairly accurate method for determination of molecular weights of polymers.     

29Si NMR spectroscopy of cyclosiloxanes

Journal of Structural Chemistry -     

Total assignment and structure in solution of tetrandrine by NMR spectroscopy and molecular modelling

High-resolution 1- and 2D NMR spectra of tetrandrine and molecular modelling were employed to characterise its structure in solution. Complete and unambiguous assignment of all proton and carbon resonance signals is reported. Scalar couplings were determined from dihedral angles with the Karplus equation. Inter-proton distances were evaluated from NOE correlation peaks. Comparison of simulated and X-ray conformations of tetrandrine reveals only small differences.     

Conformational analysis of phorboxazole bis-oxazole oxane fragment analogs by NMR spectroscopy and molecular modeling simulations

We present a detailed conformational study of a simplified synthetic analog of the bis-oxazole oxane fragment found in the cytostatic agents phorboxazole A and B based on results from NMR spectroscopy and molecular modeling simulations. Complete 1H and 13C resonance assignments for the bis-oxazole oxane system were carried out through the use of COSY, HSQC, HMBC, TOCSY, and HSQC-TOCSY experiments, and its conformational preferences in solution were investigated by analysis of 3J(HH) coupling constants and NOE enhancements obtained from 1D and 2D NOESY experiments. In order to solve inconsistencies from our preliminary structural studies, simulated annealing studies were performed to thoroughly sample the phase space available to the molecule. Our results reveal that the six-membered oxane ring, which constitutes the most important moiety regarding the three-dimensional (3D) structure and flexibility of the analog, exists in rapid equilibrium between its two accessible chair conformers in an approximate ratio of 70:30. The information gathered from these studies will be of critical importance in our efforts to prepare novel compounds with phorboxazole-like structure and activity.     

Solution structure determination of oligoureas using methylene spin state selective NMR at 13C natural abundance

Ability of N,N'-linked oligoureas containing proteinogenic side chains to adopt a stable helix conformation in solution has been described recently. NMR as well as circular dichroism (CD) spectroscopies were employed to gain insight into their specific fold. It is herein proposed to extend the structural information available on these peptidomimetics by an advantageous use of a methylene spin state selective NMR experiment. Homodecoupling provided by the pulse scheme made it possible to readily measure conformation-dependent (3)J(HH) constants that are difficult if not impossible to obtain with standard NMR experiments. Adding those couplings to the NMR restraints improved the quality of the structure calculations significantly, as judged by a ca 30% decrease of the root mean square deviation (RMSD) obtained over an ensemble of 20 structures. Moreover, accurate determination of individual (1)J(CH) couplings within each methylene group revealed uniform values throughout the oligourea sequence, with (1)J(CH) systematically slightly larger for the pro-S hydrogen than for the pro-R. As shown in this study, the methylene spin state selective NMR experiment displays a good intrinsic sensitivity and could therefore provide valuable structural information at (13)C natural abundance for peptidomimetic molecules and foldamers bearing diastereotopic methylene protons.     

Slow diffusion by singlet state NMR spectroscopy

Small diffusion coefficients can be measured by using populations of singlet states that have a relaxation time constant, T(s), which can be much longer than the longitudinal relaxation time, T1. Spatial information can be encoded with pulsed field gradients in the manner of stimulated echo sequences. Singlet states can be excited via double-quantum coherences to enhance the efficiency of phase encoding and decoding.     

Quantitative determination of the average molecular weights of dextrans by diffusion ordered NMR spectroscopy

Diffusion ordered NMR (DOSY) was applied to the determination of the average molecular weights of polymers based on the dependence of the measured self-diffusion coefficient D on the corresponding weights of a number of polymers of the same type. As a rule, a calibration function is plotted by varying DOSY experimental parameters for each particular test sample; however, this approach is inapplicable to the development of a standard procedure for the quantitative assessment of the molecular weights of dextrans. In this article, an optimization method is considered to ensure high resolution in terms of the values of D for dextrans without varying experimental conditions; this method makes it possible to evaluate the average molecular weights of dextrans with a high accuracy over a wide range of their values.     

Solution structure of bis(acetoxy)iodoarenes as observed by O NMR spectroscopy

A group of para-substituted bis(acetoxy)iodoarenes has been studied by ¹⁷O and ¹³C NMR. Only one signal for all the oxygens of the acetoxy groups has been observed. Both ¹⁷O and ¹³C chemical shifts of this group show a strong invariance with para substitution. The absence of covalent I-O bonds and an ion pair structure is proposed for the title compounds.     

Characterization of dextrin hydrogels by FTIR spectroscopy and solid state NMR spectroscopy

Fourier transform infrared (FTIR) and ¹³C solid state nuclear magnetic resonance (NMR) spectroscopy were used to study dextrin structural changes occurring upon hydrogel formation by vinyl acrylate (VA) grafting and subsequent free radical polymerization. The degrees of VA substitution (DS) and polymerization (DP) were quantified up to 40%VA by FTIR intensity measurements and partial least squares (PLS)/FTIR, the latter being a faster and less error-prone method. Above 40%VA, both parameters are underestimated by FTIR. A spin counting NMR experiment showed high carbon observabilities for hydrogels and improved PLS/NMR models were achieved for DS and DP determination. Alternative NMR integration methods are hindered by the broad VA peaks and need for area correction, due to their CP dynamics. NMR changes in C1 profile showed that a single helical conformation predominates at lower %VA, being replaced by disordered conformations as %VA increases. Furthermore, a correlation FTIR/NMR study indicated that ring conformations are significantly affected in hydrogels, compared to unpolymerized dextrin.     

Solution conformation by NMR and molecular modeling of three sulfide-free somatostatin octapeptide analogs compared to angiopeptin

Summary The conformation in dimethylsulfoxide of the somatostatin derivative angiopeptin and of three disulfide-free analogs was estimated by two-dimensional nuclear magnetic resonance spectroscopy at room temperature. The resulting 3D molecular graphics were compared and shown to reflect the observed differences in the inhibition of restenosis after rat aorta balloon injury by these octapeptide inhibitors. Angiopeptin and its active analog 2 displayed a relatively rigid conformation of the cyclic hexapeptide backbone due to the presence of two well-defined hydrogen bonds, further stabilized by a third hydrogen bond outside the ring. No such constraints were detected for the two biologically inactive analogs, which, compared to 2, had a two-atom longer or shorter hexapeptide ring. The well-defined structure of compound 2 may serve as an improved pharmacophore for this new class of drugs.     

Protein structure determination by high-resolution solid-state NMR spectroscopy: application to microcrystalline ubiquitin

High-resolution solid-state NMR spectroscopy has become a promising method for the determination of three-dimensional protein structures for systems which are difficult to crystallize or exhibit low solubility. Here we describe the structure determination of microcrystalline ubiquitin using 2D (13)C-(13)C correlation spectroscopy under magic angle spinning conditions. High-resolution (13)C spectra have been acquired from hydrated microcrystals of site-directed (13)C-enriched ubiquitin. Inter-residue carbon-carbon distance constraints defining the global protein structure have been evaluated from 'dipolar-assisted rotational resonance' experiments recorded at various mixing times. Additional constraints on the backbone torsion angles have been derived from chemical shift analysis. Using both distance and dihedral angle constraints, the structure of microcrystalline ubiquitin has been refined to a root-mean-square deviation of about 1 A. The structure determination strategies for solid samples described herein are likely to be generally applicable to many proteins that cannot be studied by X-ray crystallography or solution NMR spectroscopy.     

Protein structure determination from 13C spin-diffusion solid-state NMR spectroscopy

Proton-driven 13C spin diffusion (PDSD) is a simple and robust two-dimensional NMR experiment. It leads to spectra with a high signal-to-noise ratio in which cross-peaks contain information about internuclear distances. We show that the total information content is sufficient to determine the atomic-resolution structure of a small protein from a single, uniformly 13C-, 15N-labeled microcrystalline sample. For the example of ubiquitin, the structure was determined by a manual procedure followed by an automatic optimization of the manual structure as well as by a fully automated structure determination approach. The relationship between internuclear distances and cross-peak intensities in the spectra is investigated.     

Pyrazoles as molecular probes to study the properties of co-crystals by solid state NMR spectroscopy

Equimolar mixtures of 3,5-dimethylpyrazole (1) with four NH-imidazoles (2–5) have been studied by¹³C and ¹⁵N CPMAS NMR and by DSC. In three cases, the solid mixture behaves as the sum of the individual components [imidazole (2), 2-methylimidazole (3) and 2,4(5)-dimethylimidazole (5)]. In one case [4,5-dimethylimidazole (4)], the mixture corresponds to a new species in which the dynamic behavior of1 no longer exists.     

Solution conformation of tripeptides by NMR spectroscopy and force-field calculations

The solution conformation of three linear tripeptides Boc-Ala-Val-Val-OMe1, Boc-Ala-Pro-Val-OMe2, and Boc-Ala-(D)Pro-Val-OMe3 was studied by NMR spectroscopy and accompanying force-field calculations. In one case,2, as preferred conformation the-turnall trans conformer was found.