Accurate NMR determination of C-H or N-H distances for unlabeled molecules.

Cross-Polarization with Variable Contact-time (CP-VC) is very efficient at ultra-fast MAS (νR ≥ 60 kHz) to measure accurately the dipolar interactions corresponding to C-H or N-H short distances, which are very useful for resonance assignment and for analysis of dynamics. Here, we demonstrate the CP-VC experiment with (1)H detection. In the case of C-H distances, we compare the CP-VC signals with direct ((13)C) and indirect ((1)H) detection and find that the latter allows a S/N gain of ca. 2.5, which means a gain of ca. 6 in experimental time. The main powerful characteristics of CP-VC methods are related to the ultra-fast spinning speed and to the fact that most of the time only the value of the dipolar peak separation has to be used to obtain the information. As a result, CP-VC methods are: (i) easy to set up and to use, and robust with respect to (ii) rf-inhomogeneity thus allowing the use of full rotor samples, (iii) rf mismatch, and (iv) offsets and chemical shift anisotropies. It must be noted that the CP-VC 2D method with indirect (1)H detection requires the proton resolution and is thus mainly applicable to small or perdeuterated molecules. We also show that an analysis of the dynamics can even be performed, with a reasonable experimental time, on unlabeled samples with (13)C or even (15)N natural abundance.

Theoretical study of CP-VC: a simple, robust and accurate MAS NMR method for analysis of dipolar C-H interactions under rotation speeds faster than ca. 60 kHz.

We show that Cross-Polarization with Variable Contact-time (CP-VC) allows an accurate determination of C-H dipolar interactions, which permits an easy detailed analysis of bond lengths and local dynamics, e.g. in biomolecules. The method presents a large dipolar scaling factor of 1/√2, leading to a better determination of dipolar interactions, especially for long C-H distances, and it allows the observation of very small local details such as those related either to CH(2) three spin systems, or even to hydrogen bonds. CP-VC is very simple to set up and very robust with respect to most experimental parameters, such as: rf-offsets, chemical-shift anisotropies, imperfect Hartmann-Hahn setting, and rf-inhomogeneity. The only required condition is the use of a sufficiently fast MAS spinning speed of at least ca. 60 kHz.

Solid state NMR study and density functional theory (DFT) calculations of structure and dynamics of poly(p-xylylenes).

High resolution solid state (13)C nuclear magnetic resonance (SS NMR) measurements were carried out on poly(p-xylylene) (PPX). The samples comprised vapor-deposited specimens as well as pure alpha and beta polymorphs of this polymer. The measurements were performed using cross-polarization and magic angle spinning (CP/MAS) techniques. Density functional theory gauge-including-atomic-orbital (DFT GIAO) calculations of NMR shielding parameters (13)C sigma(ii) were performed for the optimized geometry and structure of a xylylene trimer, acquired from the X-ray data, including intermolecular interactions. Two-dimensional phase adjusted spinning sideband (2D PASS) correlation was employed for the assignment of the values of the principal elements (13)C delta(ii) of the chemical shift tensor (CST). A comparative analysis of shielding (sigma(ii)) versus chemical shift (delta(ii)) parameters showed substantial differences between the molecular dynamics of alpha and beta polymorphs. This observation was further supported by the measurements of (13)C T(1) relaxation times and the analysis of cross-polarization kinetics. Frequency switched Lee-Goldburg heteronuclear correlation (FSLG HETCOR) for the (1)H-(13)C system was used in order to analyze molecular packing in both polymorphs. As a result of all of the above measurements, new insight into the mechanism of thermal phase transition from the alpha to the beta polymorph of poly(p-xylylene) is presented.

Elucidation of structural restraints for phosphate residues with different hydrogen bonding and ionization states.

Solid state NMR spectroscopy and gauge including atomic orbital (GIAO) theoretical calculations were employed to establish structural restraints (ionization, hydrogen bonding, spatial arrangement) for O-phosphorylated l-threonine derivatives in different ionization states and hydrogen bonding strengths. These structural restraints are invaluable in molecular modeling and docking procedures for biological species containing phosphoryl groups. Both the experimental and the GIAO approach show that 31P delta ii chemical shift tensor parameters are very sensitive to the ionization state. The negative values found for the skew kappa are typical for -2 phosphates. The distinct span Omega values reflect the change of strength of hydrogen bonding. For species in the -1 ionization state, engaged in very strong hydrogen bonds, Omega is smaller than for a phosphate group involved in weak hydrogen bonding. For phosphates in the -2 ionization state, Omega is significantly smaller compared to -1 species, although the kappa for -1 samples never reaches negative values. For -1 phosphate residues, in the case when 1H one pulse and/or combined rotation and multiple pulse spectroscopy (CRAMPS) sequences fail and assignment of proton chemical shift is ambiguous, a combination of 1H-(13)C and 1H-(31)P 2D heteronuclear correlation (HETCOR) correlations is found to be an excellent tool for the elucidation of 1H isotropic chemical shifts. In addition, a 2D strategy using 1H-(1)H double quantum filter (DQF) correlations [a back-to-back (BABA) sequence in this work] is useful for analyzing the topology of hydrogen bonding. In the case of a multicenter phosphorus domain, 2D 31P-(31)P proton driven spin diffusion experiments give information about the spatial arrangement of the phosphate residues.

High-resolution solid-state NMR spectroscopy as a tool for investigation of enantioselective inclusion complexation.

In this paper, we showed the application of solid state-NMR (SS NMR) spectroscopy in structural studies of chiral compounds employing sample of (E)-1-diphenylphosphinoylpent-3-en-2-ol 1 as a model compound. Racemate of 1 was fully characterized by NMR techniques (both in liquid and solid phase) and X-ray crystallography. Theoretical calculations employing the GIAO approach were used to explain the influence of hydrogen bonding on 31P NMR shielding parameter in racemate. Enantioselective inclusion complexation (EIC) method with TADDOL as host molecule was applied to separate of enantiomers. The formation of host-guest complex and decomplexation procedure was monitored by means of the SS NMR. The liquid-state NMR, due to similarity of 13C and 31P spectral parameters was not able to distinguish racemate from enantiomer. In the solid phase, owing to distinction of hydrogen bonding and molecular packing in the crystal lattice, racemate and enantiomers were easy recognized by NMR spectroscopy.

Distance measurements in disodium ATP hydrates by means of 31P double quantum two-dimensional solid-state NMR spectroscopy.

POST-C7 measurements provide constraints allowing distinguishing crystal lattice organization and establishing intra and/or intermolecular distances between phosphorus atoms of triphosphate chains for different hydrates of disodium ATP salts. Double-quantum efficiency in function of excitation time obtained from series of two-dimensional spectra for POST-C7 experiments was used to set up of buildup curves and semi-quantitative measure of 31P-31P length.

Two-dimensional and variable temperature 31P solid-state NMR studies of single crystals containing symmetrical/unsymmetrical bis[6-O,6-O'-(1,2:3,4-diisopropylidene-alpha-D- galactopyranosyl)thiophosphoryl] dichalcogenides.

The organisation and phase transition of single crystals containing three isostructural bis[6-O,6-O'-(1,2:3,4-diisopropylidene-alpha- D-galactopyranosyl)thiophosphoryl] dichalcogenide derivatives: disulfide 1, diselenide 2 and mixed seleno-sulfide 3, was deduced upon 1D, 2D and variable temperature 31P NMR experiments.

X-ray and 13C solid-state NMR studies of N-benzoyl-phenylalanine.

A crystalline sample of N-benzoyl-DL-phenylalanine 1 and a polycrystalline sample of N-benzoyl-L-phenylalanine 2 were studied using 13C high-resolution solid-state NMR spectroscopy. The X-ray structure of the DL form was established. Sample 1 crystallizes in a monoclinic form with a P21/c space group, a=11.338(1) A, b=9.185(1) A, c=14.096(2) A, beta=107.53(3) degrees, V=1400(3) A3, Z=4 and R=0.053. The principal elements of the 13C chemical shift tensors deltaii for 1 and 2, selectively 13C (99%) labeled at the carboxyl groups were calculated. On the basis of 13C (delta)ii analysis the hydrogen bonding pattern for sample 2 was deduced. Enriched samples were used to establish the intermolecular distance between chemically equivalent nuclei for 1 and spatial proximity in heterogeneous domain for 2, employing the ODESSA pulse sequence. The consistence of the complementary approach covering X-ray data, analysis of the 13C (delta)ii parameters and ODESSA results is revealed.

13C high-resolution solid state NMR studies of the structure and dynamics of 1,6:3,4-dianhydro-2-O-tosyl-beta-D-galactopyranose.

13C CP/MAS, dipolar dephasing MAS and theoretical GIAO calculations were employed to assign 13C resonances to the molecular structure of 1,6:3,4-dianhydro-2-O-tosyl-beta-D-galactopyranose 1. From spinning sideband intensities, employing the graphical method of Herzfeld and Berger the 13C delta(ii) parameters for aromatic residue were calculated. The experimental data were compared with computed results obtained by means of the B3PW91 hybrid method and 6-311G (df, p) basis set. The X-ray geometry of 1 with the correlated position of hydrogen atoms was taken as input data for theoretical calculations. As concluded from Cambridge Crystallographic Database (CSD) search, there are two reports describing the X-ray studies of 1 that show the slightly different geometry of the compound under investigation. This work shows that such discrepancies in geometry can generate differences between computed 13C delta(ii) parameters up to 6 ppm. 13C T1 and 1H T1rho relaxation times reveal that 1 is very rigid in crystal lattice. This structure is characterized by extremely long 1H T1rho, found to be in range ca. 200 ms.

Nucleophilic N1-->N3 rearrangement of 5'-O-trityl-O2,3'-cycloanhydrothymidine.

5'-O-Trityl-O2,3'-cycloanhydrothymidine (1) heated at 150 degrees C in the presence of O,O-diethyl phosphate or O,O-diethyl phosphorothioate anions undergoes rearrangement into N3-isomer (2); its structure was established by both advanced NMR methods and X-ray crystallographic studies. The most probable mechanism of 1-->2 rearrangement relies upon reversibility of glycosidic bond cleavage process.

X-ray and high resolution selenium-77 solid state NMR spectroscopy as complementary probes to structural studies of organophosphorus diselenides.

77Se high resolution solid state NMR spectroscopy was employed to study structural properties of bis(diisopropoxyphosphorothioyl) diselenide 1 and bis(dineopentoxyphosphorothioyl) diselenide 2. The principal elements Tii of 77Se effective dipolar/chemical shift tensor were calculated from spinning sideband intensities employing the WIN-MAS program. The values of anisotropy and asymmetry parameters reflect the distortion of the selenium environment. It was found that the T33 component mostly contributes to changes in the isotropic chemical shifts. 77Se CP/MAS experiments were used to decide the assignment of space group by counting the number of crystallographically unique selenium centers in the unit cell. Crystals of diselenide 1 are triclinic, space group P1 with a = 8.485(3) A, b = 8.508(1) A, c = 8.511(2) A, alpha = 98.835(15) degrees, beta = 111.653(24) degrees, gamma = 93.524(21) degrees, V = 559.5(3) A3, Dc = 1.544(2) g/cm3 and Z = 1. Refinement using 2222 reflections for 157 variables gives R = 0.037. Crystals of diselenide 2 are triclinic, space group P1 with a = 9.1418(8) A, b = 9.1465(8) A, c = 9.9200(9) A, alpha = 74.751(8) degrees, beta = 74.629(7) degrees, gamma = 82.216(7) degrees, V = 769.7(1) A3, Dc = 1.365(2) g/cm3 and Z = 1. Refinement using 3316 reflections for 297 variables gives R = 0.0272.

Comment to 13C-NMR studies of alpha and gamma polymorphs of glycine.

Glycine provided to research laboratories by chemical companies can contain different polymorphs and/or mixture of polymorphs. The alpha- and gamma-glycine differ slightly in 13C shielding parameters and very much in dynamic properties. The isotropic values of chemical shifts for carboxyl groups of alpha- and gamma-glycine are found to be delta(iso) = 176.50 ppm and delta(iso) = 174.60 ppm, respectively. By using cross-polarization contact time equal to 20 ms, the intensity of carboxyl signal arising from gamma-glycine is reduced almost to zero, while that of alpha-glycine is only slightly depleted compared to the intensity of signal recorded at contact time of 1 ms. In contrast, for alpha-form, the 13C T1 relaxation time of carboxyl carbon is five times shorter compared to gamma-form.

Anisotropy of chemical shift and J coupling for P-31 and Se-77 in trimethyl and triphenyl phosphine selenides.

The 31P and 77Se magic angle spinning (MAS) nuclear magnetic resonance (NMR) experiments for selenium-77 enriched (70%) trimethylphosphine selenide 1 and triphenylphosphine selenide 2 were carried out in order to determine the nuclear magnetic shielding tensors of both nuclei and to establish values of the phosphorus-selenium indirect spin-spin coupling anisotropy delta J. The m = +1/2 and m = -1/2 subspectra were analysed by the dipolar-splitting-ratio method of Eichele and Wasylischen. For the C(S) molecule 1, delta J was obtained to be +640 +/- 260 Hz from the 31P spectrum and +550 +/- 140 Hz from the 77Se spectrum. Density functional theory (DFT) calculations give a delta J value of about +705 Hz. The value of delta J could not be determined unambiguously by analysis of the 31P spectra for the C1 molecules 2; nevertheless, an estimation of delta J was possible. The principal axis 3 of the phosphorus shielding tensor was determined to be nearly parallel to the PSe bond in 1 and 2. For the selenium shielding of 1, the same orientation was found, whereas in 2, the principal axis 2 of the selenium shielding was found to be oriented nearly along the PSe bond. The experimentally determined phosphorus nuclear magnetic shielding tensors agree well with those calculated by the IGLO method. For those two principal values of the selenium-shielding tensors corresponding to directions nearly perpendicular to the SeP bond, the agreement between calculated and experimental values is satisfactory. For the third one, corresponding to the principal axis close to the SeP bond, the calculated deshielding contributions are distinctly too small for both compounds investigated. Trends observed for the calculated molecular orbital (MO) contributions to the shielding as well as possible reasons for the underestimation of the deshielding contributions along the SeP bond are discussed.

31P and 15N solid-state nuclear magnetic resonance spectroscopic study of some monophospha-lambda 5-azenes.

31P Cross-polarization magic-angle spinning nuclear magnetic resonance (CP-MAS NMR) spectra of eight monophospha-lambda 5-azenes were measured at room temperature. Three of these compounds, with 2-OH substituents, are in principle capable of taking part in the equilibrium process. However, only the open form, tautomer A, is found in the present study. 15N CP-MAS NMR spectra support the results. The most shielded component of the 31P chemical shift tensor lies in the direction of the P = N bond.