Search

* Corresponding author at: Drug Delivery and Disposition, KU Leuven, Department of Pharmaceutical and Pharmacological Sciences, Campus Gasthuisberg ON2, Herestraat 49 b921, 3000 Leuven, Belgium. [Display omitted] Drug-polymer intermolecular interactions, and H-bonds specifically, play an important role in the stabilization process of a compound in an amorphous solid dispersion (ASD). However, it is still difficult to predict whether or not interactions will form and what the strength of those interactions would be, based on the structure of drug and polymer. Therefore, in this study, structural analogues of diflunisal (DIF) were synthesized and incorporated in ASDs with poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA) as a stabilizing polymer. The respective DIF derivatives contained different types and numbers of H-bond donor groups, which allowed to assess the influence of these structural differences on the phase behavior and the actual interactions formed in the ASDs. The highest possible drug loading of these derivatives in PVPVA were evaluated through film casting. Subsequently, a lower drug loading of each compound was spray dried. These spray dried ASDs were subjected to an in-depth solid-state nuclear magnetic resonance (ssNMR) study, including 1D spectroscopy and relaxometry, as well as 2D dipolar HETCOR experiments. The drug loading study revealed the highest possible loading of 50 wt% for the native DIF in PVPVA. The methoxy DIF derivative reached the second highest drug loading of 35 wt%, while methylation of the carboxyl group of DIF led to a sharp decrease in the maximum loading, to around 10 wt% only. Unexpectedly, the maximum loading increased again when both the COOH and OH groups of diflunisal were methylated in the dimethyl DIF derivative, to around 30 wt%. The ssNMR study on the spray dried ASD samples confirmed intermolecular H-bonding with PVPVA for native DIF and methoxy DIF. Studies of the proton relaxation decay times and 2D 1H–13C dipolar HETCOR experiments indicated that the ASDs with native DIF and methoxy DIF were homogenously mixed, while the ASDs containing DIF methyl ester and dimethyl DIF were phase separated at the nm level. It was established that, for these systems, the availability of the carboxyl group was imperative in the formation of intermolecular H-bonds with PVPVA and in the generation of homogenously mixed ASDs. [ABSTRACT FROM AUTHOR]

This primer article introduces a practical guide for setting up 1H detection solid-state NMR experiments under fast MAS conditions for small molecules. Sample independent adjustment/calibration including magic angle adjustment, shimming, radio-frequency field calibration, Hartmann-Hahn matching adjustments, and 1H heteronuclear decoupling are demonstrated. Experimental setups which depend on samples are also shown for 1H NMR, 1H-1H homonuclear correlation measurements, and 1H-X heteronuclear correlation/distance measurements. Information obtained from each experiment is also highlighted.

Through‐space heteronuclear correlation (D‐HETCOR) experiments based on heteronuclear multiple‐quantum correlation (D‐HMQC) and refocused insensitive nuclei enhanced by polarization transfer (D‐RINEPT) sequences have been proven to be useful approaches for the detection of the spatial proximity between half‐integer quadrupolar nuclei in solids under magic‐angle spinning (MAS) conditions. The corresponding pulse sequences employ coherence transfers mediated by heteronuclear dipolar interactions, which are reintroduced under MAS by radiofrequency irradiation of only one of the two correlated nuclei. We investigate herein using numerical simulations of spin dynamics and solid‐state NMR experiments on magnesium aluminoborate glass how the choice of the channel to which the heteronuclear dipolar recoupling is applied affects the transfer efficiency of D‐HMQC and D‐RINEPT sequences between 11B and 27Al nuclei. Experimental results show that maximum transfer efficiency is achieved when the recoupling scheme is applied to the channel, for which the spin magnetization is parallel to the B0 axis in average. [ABSTRACT FROM AUTHOR]

The novel concept of NORD (NO relaxation delay) NMR spectroscopy is introduced. The idea is to design concatenated experiments in a way that the magnetization used in the first relaxes toward equilibrium during the second and vice versa, thus saving instrument time. Applications include complete well‐resolved 1H‐1H and 1H‐13C one‐bond and long‐range correlation maps of an 80 mM solution of a trisaccharide recorded in less than two minutes and hydrocortisone with extensive spectral overlap. [ABSTRACT FROM AUTHOR]

Abstract The sensitivity of solid-state NMR experiments that utilize 1H zero-quantum heteronuclear dipolar recoupling, such as D-HMQC, is compromised by poor homonuclear decoupling. This leads to a rapid decay of recoupled magnetization and an inefficient recoupling of long-range dipolar interactions, especially for nuclides with low gyromagnetic ratios. We investigated the use, in symmetry-based 1H heteronuclear recoupling sequences, of a basic R element that was principally designed for efficient homonuclear decoupling. By shortening the time required to suppress the effects of homonuclear dipolar interactions to the duration of a single inversion pulse, spin diffusion was effectively quenched and long-lived recoupled coherence lifetimes could be obtained. We show, both theoretically and experimentally, that these modified sequences can yield considerable sensitivity improvements over the current state-of-the-art methods and applied them to the indirect detection of 89Y in a metal-organic framework. Graphical abstract Image 1 Highlights • Accelerated signal decay under 1H-X dipolar recoupling limits the sensitivity of D-HMQC experiments. • This signal decay can be slowed through better homonuclear decoupling. • The use of an R element performing homonuclear decoupling significantly enhances long-range 1H-X correlations. • The new recoupling scheme is applied to detect sensitivity-enhanced 89Y spectra of a metal-organic-framework. [ABSTRACT FROM AUTHOR]

Multiple pulse sequences are often used to manipulate spin Hamiltonians in solid-state nuclear magnetic resonance spectroscopy. In this paper, we analyze multiple pulse sequences using the well-known average Hamiltonian theory. We first expand the resulting average Hamiltonian into a reachable set of sub-Hamiltonians and then develop a general procedure using both flip-angle and phase of the applied pulses as control variables to select any of those sub-Hamiltonians. We use this method to analyze solid-echo based sequences and to design new proton-proton homonuclear decoupling sequences in static solids. It is found that this newly designed decoupling scheme, in the presence of finite pulse length, effectively suppresses the 1 H– 1 H homonuclear dipolar interactions while establishes variable scaling factors on the heteronuclear dipolar interactions and chemical shift interactions, depending on the flip-angle of the applied pulses. When the pulse flip-angle is close to 54.7°, this sequence possesses a large scaling factor with relatively low average decoupling field. When the pulse flip-angle becomes ∼120°, the scaling factor is almost zero. A static 15 N-acetyl-valine crystal sample has been used as an example to confirm and validate the performance of this new decoupling scheme. [ABSTRACT FROM AUTHOR]

We demonstrate that dynamic nuclear polarization (DNP)-enhanced 1 H-X heteronuclear correlation (HETCOR) measurements of hydrogen-rich surface species are better accomplished by using proton-free solvents. This approach notably prevents HETCOR spectra from being obfuscated by the solvent-derived signals otherwise present in DNP measurements. Additionally, in the hydrogen-rich materials studied here, which included functionalized mesoporous silica nanoparticles and metal organic frameworks, the use of proton-free solvents afforded higher sensitivity gains than the commonly used solvents containing protons. We also explored the possibility of using a solvent-free sample formulation and the feasibility of indirect detection in DNP-enhanced HETCOR experiments. [ABSTRACT FROM AUTHOR]

We demonstrated that the heteronuclear correlation experiments between two quadrupolar nuclei, 23 Na and 27 Al, with close Larmor frequencies can be achieved via D -HMQC and D -RINEPT approaches by using a diplexer connected to a conventional probe in magic-angle-spinning solid-state NMR. Low-power heteronuclear dipolar recoupling schemes can be applied on 23 Na or 27 Al to establish polarization transfers between the central transitions of 23 Na and 27 Al for a model compound, NaAlO 2 . Further, we showed a practical implementation of the two dimensional 23 Na- 27 Al dipolar-based heteronuclear correlation experiment on a heterogeneous catalyst, Na 2 CO 3 /γ-Al 2 O 3 . This allows to determine spatial proximities between different 23 Na and 27 Al sites, thus the surface Na species adjacent to octahedral-coordination Al can be clearly discriminated. [ABSTRACT FROM AUTHOR]

We introduce novel sequences using indirect detection to correlate quadrupolar nuclei and spin-1/2 isotopes, other than 1 H and 19 F. These sequences use γ-encoded symmetry-based R N n ν schemes that reintroduce the space component | m | = 1 of the heteronuclear dipolar coupling. These schemes can be applied to the indirectly detected spin in Dipolar-mediated Heteronuclear Multiple-Quantum Correlation ( D -HMQC) sequence or to the detected isotope in a novel sequence, named Dipolar-mediated Heteronuclear Universal-Quantum Correlation ( D -HUQC). We show that the signal of these sequences using γ-encoded recoupling does not depend on the γ Euler angle relating the inter-nuclear vector between the coupled spins to the MAS rotor-fixed frame. Therefore, the transfer efficiency of these sequences is in principle higher than that of D -HMQC methods using non-γ-encoded recoupling. Furthermore, numerical simulations show that the heteronuclear correlation experiments employing γ-encoded recoupling are more robust to Chemical Shift Anisotropy (CSA) of the irradiated spin and MAS frequency fluctuations. These results are confirmed by 13 C-{ 15 N} heteronuclear correlation on glycine and 31 P- 27 Al ones on VPI-5 and Na 7 (AlP 2 O 7 ) 4 PO 4 . These experiments indicate that R 16 3 5 recoupling produces the highest signal-to-noise ratio in heteronuclear correlation 2D experiments when the detected spin-1/2 nuclei are subject to large CSA. [ABSTRACT FROM AUTHOR]

[Display omitted] • Molecular interaction of morin and amylose is detected by solid-state NMR. • Inter-molecular hydrogen bonds are confirmed by 2D 1H–13C HETCOR spectra. • Hydroxy groups are the mainly binding sites of hydrogen bonds. • Hydrogen bonds are not strong enough to interfere antioxidant capacity of morin. Interaction of polyphenols and starch significantly governed the further applications on polyphenol-starchy foods. Elucidation of inter-molecular interaction is, however, a challenge because conventional characterizations could not detect the change of micro-environment caused by weak interactions. Herein, a facile strategy for molecular detection of amylose-polyphenol interactions was reported using two-dimensional solid-state NMR spectroscopy. Amylose-morin complex was prepared and characterized using 1H NMR, FT-IR, DSC, XRD and SEM. Significantly, variation of chemical shifts, splitted peaks and peak width, monitored by 13C CP/MAS and 1H NMR spectra, identified the strong inter-molecular interaction and binding sites. Furthermore, correlated signals from 1H–13C HETCOR confirmed the binding sites of interactions. These findings confirmed the interaction was inter-molecular hydrogen bonds, which generated between hydroxy-3,5,7 of morin and hydroxy groups of amylose. Besides, DPPH radical scavenging and reducing power assay indicated inter-molecular hydrogen bonds are not strong enough to interfere antioxidant capacity of morin. [ABSTRACT FROM AUTHOR]

Starch can readily form complexes with polyphenols. However, its two components, namely amylose and amylopectin, differ significantly in their ability to complex with phenolic compounds. Given that the mechanism of their interaction is still poorly studied, this work investigated intermolecular interactions between apigenin and starch with different amylose/amylopectin ratios using 1H NMR, FT-IR, XRD, DSC and solid-state NMR. Results showed that corn starch with high amylose/amylopectin ratios had a better complexing ability and higher complexing index with apigenin than amylopectin. Besides, solid-state NMR suggested that the molecular mechanism behind the strong intermolecular interactions between corn starch and apigenin involved hydrogen bonds. Furthermore, the detailed binding sites of hydrogen bonds, that linked by hydroxyl-starch and phenyl-apigenin were also confirmed by 1H 13C heteronuclear correlation (HETCOR) spectra. This study revealed the molecular mechanism on amylose/amylopectin complexing with apigenin and provides a theoretical basis for further developing polyphenols in starchy food. [Display omitted] [ABSTRACT FROM AUTHOR]

Silicon and oxygen are the two most abundant elements in most technological and geological glasses and glass-forming liquids, and extensive studies of the structures of these materials have been made using 29 Si and 17 O high-resolution solid-state NMR. Double resonance NMR experiments hold great potential for revealing new details about the network structures of such important materials but have not yet been done for this particular pair of spins because of several technical challenges. Using a crystalline model compound, Ca 3 SiO 5 (calcium trisilicate or the ‘alite’ phase of Portland cement), which contains oxide ion sites bonded either to one Si 4 + or only to Ca 2 + , we demonstrate that the 17 O → 29 Si Cross-Polarization Heteronuclear Correlation (CP-HETCOR) experiment can clearly distinguish between these two types of oxygen sites. The latter species, so-called ‘free’ oxide ions that are bonded to no network cations such as Si 4 + , play an important role in models of glass and melt structure but have been difficult to directly detect in many systems. In two Ca/Mg silicate glasses near to the orthosilicate composition (O/Si ≥ 4), the HETCOR experiment clearly shows the presence of such ‘free’ oxide ions, whose 1D 17 O NMR signals are actually completely hidden under those for the predominant non-bridging oxygens. Their observed chemical shifts suggest coordination by predominantly Mg 2 + cations, an ordering that may be expected from the smaller size and stronger bonding interactions of this cation relative to those of Ca 2 + . The estimated abundances of ‘free’ oxide ions in these glasses are consistent with previous, indirect estimates based on analyses of 1D 29 Si NMR spectra. [ABSTRACT FROM AUTHOR]

Establishing the binding topology of structural zinc ions in proteins is an essential part of their structure determination by NMR spectroscopy. Using 113Cd NMR experiments with 113Cd-substituted samples is a useful approach but has previously been limited mainly to very small protein domains. Here we used 113Cd NMR spectroscopy during structure determination of Bud31p, a 157-residue yeast protein containing an unusual Zn3Cys9 cluster, demonstrating that recent hardware developments make this approach feasible for significantly larger systems. [ABSTRACT FROM AUTHOR]

Water plays an essential role in the structure and function of proteins, lipid membranes and other biological macromolecules. Solid-state NMR heteronuclear-detected 1 H polarization transfer from water to biomolecules is a versatile approach for studying water–protein, water–membrane, and water–carbohydrate interactions in biology. We review radiofrequency pulse sequences for measuring water polarization transfer to biomolecules, the mechanisms of polarization transfer, and the application of this method to various biological systems. Three polarization transfer mechanisms, chemical exchange, spin diffusion and NOE, manifest themselves at different temperatures, magic-angle-spinning frequencies, and pulse irradiations. Chemical exchange is ubiquitous in all systems examined so far, and spin diffusion plays the key role in polarization transfer within the macromolecule. Tightly bound water molecules with long residence times are rare in proteins at ambient temperature. The water polarization-transfer technique has been used to study the hydration of microcrystalline proteins, lipid membranes, and plant cell wall polysaccharides, and to derive atomic-resolution details of the kinetics and mechanism of ion conduction in channels and pumps. Using this approach, we have measured the water polarization transfer to the transmembrane domain of the influenza M2 protein to obtain information on the structure of this tetrameric proton channel. At short mixing times, the polarization transfer rates are site-specific and depend on the pH, labile protons, sidechain conformation, as well as the radial position of the residues in this four-helix bundle. Despite the multiple dependences, the initial transfer rates reflect the periodic nature of the residue positions from the water-filled pore, thus this technique provides a way of gleaning secondary structure information, helix tilt angle, and the oligomeric structure of membrane proteins. [ABSTRACT FROM AUTHOR]

A new NMR experiment that exploits the advantages of proton double quantum (DQ) NMR through a proton DQ-carbon single quantum (SQ) correlation experiment in the solid state is proposed. Analogous to the previously proposed 2D ¹H (DQ)-13C refocused INEPT experiment (Webber et al., 2010), the correlation between ¹H and 13C is achieved through scalar coupling evolution, while the double quantum coherence among protons is generated through dipolar couplings. However, the new experiment relies on 13C transverse coherence for scalar transfer. The new experiment dubbed MAS-J-¹H (DQ)-13C-HMQC, is particularly suited for unlabeled molecules and can provide higher sensitivity than its INEPT counterpart. The experiment is applied to four different samples. [ABSTRACT FROM AUTHOR]

In this article, we describe third-spin assisted heteronuclear recoupling experiments, which play an increasingly important role in measuring long-range heteronuclear couplings, in particular N-C, in proteins. In the proton-assisted insensitive nuclei cross polarization (PAIN-CP) experiment (de Paëpe et al. in J Chem Phys 134:095101, ), heteronuclear polarization transfer is always accompanied by homonuclear transfer of the proton-assisted recoupling (PAR) type. We present a phase-alternating experiment that promotes heteronuclear (e.g. N → C) polarization transfer while simultaneously minimizing homonuclear (e.g.C → C) transfer (PAIN without PAR). This minimization of homonuclear polarization transfer is based on the principle of the resonant second-order transfer (RESORT) recoupling scheme where the passive proton spins are irradiated by a phase-alternating sequence and the modulation frequency is matched to an integer multiple of the spinning frequency. The similarities and differences between the PAIN-CP and this het-RESORT experiment are discussed here. [ABSTRACT FROM AUTHOR]

Fluorine-containing compounds are rare in biological systems, so fluorine NMR spectroscopy can selectively detect and quantify fluorinated xenobiotics in crude biological extracts. The high sensitivity of fluorine NMR allows the detection of compounds containing isolated trifluoromethyl groups at nanogramme levels. However, it only provides limited structural information about trifluoromethyl-containing compounds owing to the difficulty of interpreting fluorine chemical shifts and the low sensitivity of HOESY experiments used to correlate fluorine nuclei with protons in the same compound. This paper demonstrates that long-range fluorine-proton J-couplings can be used to correlate isolated trifluoromethyl groups with nearby protons with significantly higher sensitivity than HOESY. Fluorine-observe fluorine-proton HMQC can even give correlations when the fluorine-proton J-couplings are less than the observed fluorine resonance linewidth, so it provides a useful alternative source of structural information about fluorinated xenobiotics. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Saccharinates salts of the fluoroquinolone antibiotics norfloxacin, ciprofloxacin, ofloxacin, and enrofloxacin were obtained as pure crystalline anhydrous solids with sweet taste. The products were characterized by one- (13C) and two-dimensional (1H–13C) dimensions solid state Nuclear Magnetic Resonance and infrared spectroscopy showing ionic interactions between the saccharine amide and the fluoroquinolone piperazine. Several intermolecular bindings were also identified. Thermal behavior and powder X-ray diffraction provided complementary evidences of salt formation. The series of products showed improved properties with respect to water solubility. A solubility model was developed. These salts would be a good way forward to developing more suitable formulations of these APIs. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:3788–3801, 2009 [ABSTRACT FROM AUTHOR]

The interaction between cuminaldehyde and starch mainly governed the effect of further handling on food applications of cuminaldehyde. However, little information is available about the interactions of these components. We utilized relaxation and heteronuclear correlation (HETCOR) solid-state NMR spectroscopy to investigate the interaction between cuminaldehyde and porous starch at molecular level. We found that the interactions occurred mainly through hydrogen bonds. Cuminaldehyde molecules were restricted by starch, which resulted in the limitation of their movements and the longer 1H T 1 relaxation time. Furthermore, the well resolved correlated peaks in 2D 1H-13C HETCOR spectrum confirmed the formation of hydrogen bonds. The oxygen atoms at hydroxyl-2,3 of starch were the binding sites, which combined with hydrogens of cuminaldehyde. This present work not only afford a new approach to obtain a molecular understanding of interactions, but also expanded the application of solid-state NMR to investigation of the interaction on functional components. [Display omitted] [ABSTRACT FROM AUTHOR]

Single crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), and solid-state NMR (SSNMR) techniques are used to analyze the structures of two nonsolvated polymorphs of {4-(4-chloro-3-fluorophenyl)-2-[4-(methyloxy)phenyl]-1,3-thiazol-5-yl} acetic acid. These polymorphs are enantiotropically-related with a thermodynamic transition temperature of 35 ± 3°C. The crystal structure of Form 1, which is thermodynamically more stable at lower temperatures, was determined by SCXRD. The crystal structure of Form 2 was determined using PXRD structure solution methods that were assisted using two types of SSNMR experiments, dipolar connectivity experiments and chemical shift measurements. These experiments determined certain aspects of local conformation and intermolecular packing in Form 2 in comparison to Form 1, and provided qualitative knowledge that assisted in obtaining the best possible powder structure solution from the X-ray data. NMR chemical shifts for 1H, 13C, 15N, and 19F nuclei in Forms 1 and 2 are sensitive to hydrogen-bonding behavior, molecular conformation, and aromatic π-stacking interactions. Density functional theory (DFT) geometry optimizations were used in tandem with Rietveld refinement and NMR chemical shielding calculations to improve and verify the Form 2 structure. The energy balance of the system and other properties relevant to drug development are predicted and discussed. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:4756–4782, 2008 [ABSTRACT FROM AUTHOR]

Abstract: Two-dimensional (2D) F1-1H-coupled HSQC experiments provide 3:1:1:3 and 1:0:1 multiplets for AX3 and AX2 spin systems, respectively. These multiplets occur because, in addition to the process, the coherence transfers such as occurring in t 1 period provide detectable magnetization during the t 2 period. Here, we present a 2D F1-1H-coupled 1H–15N heteronuclear correlation experiment that provides a 1:3:3:1 quartet for AX3 spin system and a 1:2:1 triplet for AX2. The experiment is a derivative of 2D HISQC experiment [J. Iwahara, Y.S. Jung, G.M. Clore, Heteronuclear NMR spectroscopy for lysine NH3 groups in proteins: unique effect of water exchange on 15N transverse relaxation. J. Am. Chem. Soc. 129 (2007) 2971–2980] and contains a scheme that kills anti-phase single-quantum terms generated in the t 1 period. The purge scheme is essential to observe in-phase single-quantum multiplets. Applications to the NH2 and groups in proteins are demonstrated. [Copyright &y& Elsevier]

Abstract: The biselective spin echo technique allows the signals of coupled proton pairs to be extracted from crowded liquid state proton NMR spectra. Its use as a preparation sequence in heteronuclear chemical shift correlation experiments requires the removal of the heteronuclear coupling interaction during the biselective echo time. The discrimination between coupled and uncoupled protons signals is achieved by double quantum filtration, which delivers antiphase magnetization states. The latter are not directly compatible with the design of an HSQC-like pulse sequence. The conversion of antiphase to in-phase magnetization states by a second biselective echo sequence solves this problem. The optimization of spin echo delays is also discussed. Lastly, the article presents modified HSQC and HMBC pulses sequences in which information is obtained solely for the biselectively selected proton pairs. A peracetylated trisaccharide was used as a test molecule. [Copyright &y& Elsevier]

Abstract: The 1H–13C solid-state NMR heteronuclear correlation (HETCOR) experiment is demonstrated to provide shift assignments in certain powders that have two or more structurally independent molecules in the unit cell (i.e. multiple molecules per asymmetric unit). Although this class of solids is often difficult to characterize using other methods, HETCOR provides both the conventional assignment of shifts to molecular positions and associates many resonances with specific molecules in the asymmetric unit. Such assignments facilitate conformational characterization of the individual molecules of the asymmetric unit and the first such characterization solely from solid-state NMR data is described. HETCOR offers advantages in sensitivity over prior methods that assign resonances in the asymmetric unit by 13C–13C correlations and therefore allows shorter average analysis times in natural abundance materials. The 1H–13C analysis is demonstrated first on materials with known shift assignments from INADEQUATE data (santonin and Ca(OAc)2 phase I) to verify the technique and subsequently is extended to a pair of unknown solids: (+)-catechin and Ca(OAc)2 phase II. Sufficient sensitivity and resolution is achieved in the spectra to provide assignments to one of the specific molecules of the asymmetric unit at over 54% of the sites. [Copyright &y& Elsevier]

Abstract: In this paper we carried out a comparison between all the possible selective versions of the basic heteronuclear correlation experiment, the FUCOUP sequence. We concluded that the best experiment is that one in which the selective pulse is given in the carbon dimension, which we called SHESSLOC (Selective HEteronuclear Simultaneous Short and LOng-range Correlations). The sensitivity of the sequence was improved with the introduction of pulsed field gradients. [Copyright &y& Elsevier]

Syntheses are reported for sulfur-and nitrogen-containing derivatives of 4-arylspiro-2-benzopyranones modified at the exocyclic oxygen atom. The structure of these products was demonstrated by correlational NMR spectroscopy. [ABSTRACT FROM AUTHOR]

Cyclohexyldihydroxanthyletin derivatives with S and N in place of the exocyclic O atom were synthesized. The structures of the products were proved by NMR correlation spectroscopy. [ABSTRACT FROM AUTHOR]

Abstract: α-Hydroxy ketones (α-ketols) are present in many compounds with biological activity. Several methods are available for the preparation of α-ketols but only a few of them describe the synthesis of steroid α-ketols from olefins. In this work, a new system consisting of KMnO4/Fe(ClO4)3·nH2O was used in order to achieve the direct conversion of Δ5-steroids to their corresponding α-ketols, in high yields. Consideration of the probable reaction mechanism is provided. 2D homo- and heteronuclear correlation NMR spectroscopic techniques were used to assign 1H and 13C resonances of some synthesized compounds. This method has potential for the preparation of α-hydroxy ketones of biological interest. [Copyright &y& Elsevier]

Solid-state NMR spectroscopy is being developed at a fast pace for the structural investigation of immobilized and non-crystalline biomolecules. These include proteins and peptides associated with phospholipid bilayers. In contrast to solution NMR spectroscopy, where complete or almost complete averaging leads to isotropic values, the anisotropic character of nuclear interactions is apparent in solid-state NMR spectra. In static samples the orientation dependence of chemical shift, dipolar or quadrupolar interactions, therefore, provides angular constraints when the polypeptides have been reconstituted into oriented membranes. Furthermore, solid-state NMR spectroscopy of aligned samples offers distinct advantages in allowing access to dynamic processes such as topological equilibria or rotational diffusion in membrane environments. Alternatively, magic angle sample spinning (MAS) results in highly resolved NMR spectra, provided that the sample is sufficiently homogenous. MAS spinning solid-state NMR spectra allow to measure distances and dihedral angles with high accuracy. The technique has recently been developed to selectively establish through-space and through-bond correlations between nuclei, similar to the approaches well-established in solution-NMR spectroscopy. [Copyright &y& Elsevier]

A suite of multiple-purpose sensitivity-enhanced 2D correlation NMR experiments based on heteronuclear J-cross polarization (HCP) techniques are introduced for isotropic liquid samples. Several pulse sequences using an adaptable heteronuclear TOCSY mixing building block are proposed for different types of effective coherence-order-selective (COS) heteronuclear coherence-transfer mechanisms. They are based on the anisotropic behaviour of the involved HCP process that is easily described and analysed in terms of cartesian product-operator formalism. A number of different versions are given for in-phase to in-phase (II-COS: S- \to I-), in-phase to anti-phase (IA-COS: S- \to 2I-Sz), in-phase to spin-state-selective (IS3-COS: S- \to 2I-Sα /β), anti-phase to in-phase (AI-COS: 2IzS- \to I-), anti-phase to anti-phase (AA-COS: 2IzS- \to 2I-Sz), anti-phase to spin-state-selective (AS3-COS: 2IzS- \to 2I-Sα /β) and spin-state-selective to spin-state-selective (S3S3-COS: 2Iα /βS- \to 2I-Sα /β ) coherence transfers. The combination of the echo/anti-echo approach, heteronuclear gradient echoes and the preservation of equivalent pathways (PEP) methodology affords a general approach to obtain sensitivity-enhanced pure-absorption 2D spectra that can be used as interesting alternatives to conventional pulse-interrupted free-precession INEPT-based pulse schemes, such as HSQC-type and TROSY-type experiments. [ABSTRACT FROM AUTHOR]

A new two-dimensional heteronuclear multiple-quantum magic-angle spinning (MQ MAS) experiment is presented which combines high resolution for the half-integer quadrupolar nucleus with information about the dipolar coupling between the quadrupolar nucleus and a spin I=1/2 nucleus. Homonuclear MQ coherence is initially created for the half-integer quadrupolar nucleus by a single pulse as in a standard MQ MAS experiment. REDOR recoupling of the heteronuclear dipolar coupling then allows the creation of a heteronuclear multiple-quantum coherence comprising multiple- and single-quantum coherence of the quadrupolar and spin I=1/2 nucleus, respectively, which evolves during t1. Provided that the t1 increment is not rotor synchronized, rotor-encoded spinning-sideband patterns are observed in the indirect dimension. Simulated spectra for an isolated IS spin pair show that these patterns depend on the recoupling time, the magnitude of the dipolar coupling, the quadrupolar parameters, as well as the relative orientation of the quadrupolar and dipolar principal axes systems. Spectra are presented for Na2HPO4, with the heteronuclear 23Na–1HMQ MAS experiments beginning with the excitation of 23Na (spin I=3/2) three-quantum coherence. Coherence counting experiments demonstrate that four- and two-quantum coherences evolve during t1. The heteronuclear spinning-sideband patterns observed for the three-spin H–Na–H system associated with the Na(2) site are analyzed. For an IS2 system, simulated spectra show that, considering the free parameters, the spinning-sideband patterns are particularly sensitive to only, first, the angle between the two IS internuclear vectors and, second, the two heteronuclear dipolar couplings. It is demonstrated that the proton localization around the Na(2) site according to the literature crystal structure of Na2HPO4 is erroneous. Instead, the experimental data is consistent with two alternative different structural arrangements, whereby either there is a deviation of 10° from linearity for the case of two identical Na–H distances, or there is a linear arrangement, but the two Na–H distances are different. Furthermore, the question of the origin of spinning-sidebands in the (homonuclear) MQ MAS experiment is revisited. It is shown that the asymmetric experimental MQ sideband pattern observed for the low-CQ Na(2) site in Na2HPO4 can only be explained by considering the 23Na chemical shift anisotropy. [Copyright &y& Elsevier]

High-resolution heteronuclear NMR correlation experiments and strategies are proposed for the assignment of fully13 C/15N-labelled polypeptides in the solid state. By the combination of intra-residue and inter-residue13 C-15N correlation experiments with13 C-13C spin-diffusion studies, it becomes feasible to partially assign backbone and side-chain resonances in solid proteins. The performance of sequences using 15N instead of13 C detection is evaluated regarding sensitivity and resolution for a labelled dipeptide (L-Val-L-Phe). The techniques are used for a partial assignment of the 15N and 13C resonances in human ubiquitin. [ABSTRACT FROM AUTHOR]

• Concatenated experiments with single relaxation delay deliver full H/C correlations. • Double application of BANGO pulse allows to tap same pool of magnetization twice. • Higher sensitivity from reducing offset and 1 J CH dependence with adiabatic X-pulse. It is shown how the same pool of magnetization can be tapped twice in two different concatenations of three experiments into a single pulse sequence with only one relaxation delay. This is accomplished by using the BANGO pulse sequence element twice for independent rotations of 1H magnetization attached or not attached to 13C and it includes a refinement of BANGO with an adiabatic 13C inversion pulse resulting in improved tolerance to a spread in 1 J CH coupling constants that translates directly into improved sensitivity of the modular experiment relying on 1H magnetization attached to 13C. The two new pulse sequences are SEA XLOC–HMBC–H2OBC/2BOB and SEA XLOC(ZQ)–SEA XLOC(2Q)–H2OBC/2BOB which both represent a rapid route to complete heteronuclear one-bond and long-range J CH correlation maps for small molecules, as is demonstrated on ibuprofen and prednisolone. [ABSTRACT FROM AUTHOR]

We have applied one-dimensional (1D) ¹H MAS NMR, 27Al → ¹H CP MAS NMR, as well as 2D 27Al triple-quantum (3Q) MAS NMR, 27Al → ¹H heteronuclear correlation (HETCOR) and high-resolution 3QMAS/HETCOR NMR techniques to KAlSi3O8 (Or), NaAlSi3O8 (Ab) and NaAlSiO4 (Ne) glasses containing 0∼2 wt% H2O to shed light on the dissolution mechanisms of water in aluminosilicate melts (glasses). An Al Q3-OH group, characterized by 1H chemical shifts of 1.3-1.9 ppm, was identified for all hydrous glasses. Its abundance increases with bulk Al/Si ratio. The 27Al chemical shifts (δiAl) of this species are 64-68 ppm, larger than those of Al Q4 by 3-6 ppm. Despite this difference, it is only through 27Al → ¹H HETCOR and 3QMAS/HETCOR, but not 27Al MAS or 3QMAS NMR that the peaks are resolved. This study has demonstrated that depolymerization and formation of AlOH/SiOH is a general water dissolution mechanism for polymerized aluminosilicate melts (glasses), and HETCOR NMR experiments involving 1H are the key to its revelation. [ABSTRACT FROM AUTHOR]

Oriented solid-state NMR (O-ssNMR) spectroscopy is a major technique for the high-resolution analysis of the structure and topology of transmembrane proteins in native-like environments. Unlike magic angle spinning (MAS) techniques, O-ssNMR spectroscopy requires membrane protein preparations that are uniformly oriented (mechanically or magnetically) so that anisotropic NMR parameters, such as dipolar and chemical shift interactions, can be measured to determine structure and orientation of membrane proteins in lipid bilayers. Traditional sample preparations involving mechanically aligned lipids often result in short relaxation times which broaden the (15)N resonances and encumber the manipulation of nuclear spin coherences. The introduction of lipid bicelles as membrane mimicking systems has changed this scenario, and the more favorable relaxation properties of membrane protein (15)N and (13)C resonances make it possible to develop new, more elaborate pulse sequences for higher spectral resolution and sensitivity. Here, we describe our recent progress in the optimization of O-ssNMR pulse sequences. We explain the theory behind these experiments, demonstrate their application to small and medium size proteins, and describe the technical details for setting up these new experiments on the new generation of NMR spectrometers., (Copyright © 2013 Elsevier B.V. All rights reserved.)