Search

The surfaces of handsheets containing polydiallyl-dimethylammonium chloride (PDADMAC) and anionic polyacrylamide (A-PAM) were analyzed using X-ray photoelectron spectroscopy (XPS). The observed N1s chemical shifts were compared with those of the strength additives. Chemical covalences on paper surfaces due to a small amount of polymer additives were clarified and determined by an XPS curve-fitting technique. Some of the problems associated with surface analysis of paper by XPS are discussed. The effects of strength additives on the fiber surface or between fibers are illustrated. This technique appears promising as a tool to analyze paper surfaces treated with small amounts of polymer additives.

The first comprehensive solid‐state nuclear magnetic resonance (NMR) characterization of geminal alane‐phosphane frustrated Lewis pairs (Al/P FLPs) is reported. Their relevant NMR parameters (isotropic chemical shifts, direct and indirect 27Al‐31P spin‐spin coupling constants, and 27Al nuclear electric quadrupole coupling tensor components) have been determined by numerical analysis of the experimental NMR line shapes and compared with values computed from the known crystal structures by using density functional theory (DFT) methods. Our work demonstrates that the 31P NMR chemical shifts for the studied Al/P FLPs are very sensitive to slight structural inequivalences. The 27Al NMR central transition signals are spread out over a broad frequency range (>200 kHz), owing to the presence of strong nuclear electric quadrupolar interactions that can be well‐reproduced by the static 27Al wideband uniform rate smooth truncation (WURST) Carr‐Purcell‐Meiboom‐Gill (WCPMG) NMR experiment. 27Al chemical shifts and quadrupole tensor components offer a facile and clear distinction between three‐ and four‐coordinate aluminum environments. For measuring internuclear Al⋅⋅⋅P distances a new resonance‐echo saturation‐pulse double‐resonance (RESPDOR) experiment was developed by using efficient saturation via frequency‐swept WURST pulses. The successful implementation of this widely applicable technique indicates that internuclear Al⋅⋅⋅P distances in these compounds can be measured within a precision of ±0.1 Å., The first comprehensive solid‐state NMR characterization of geminal alane‐phosphane frustrated lewis pairs (Al/P FLPs) is reported. For measuring internuclear Al⋅⋅⋅P distances a new resonance‐echo saturation‐pulse double‐resonance (RESPDOR) experiment was developed by using efficient saturation via frequency‐swept wideband uniform rate smooth truncation (WURST) pulses. By using this widely applicable technique, Al⋅⋅⋅P distances in these compounds can be measured within a precision of ±0.1 Å.

A parallel quadruplex derived from the Myc promoter sequence was extended by a stem‐loop duplex at either its 5′‐ or 3′‐terminus to mimic a quadruplex–duplex (Q–D) junction as a potential genomic target. High‐resolution structures of the hybrids demonstrate continuous stacking of the duplex on the quadruplex core without significant perturbations. An indoloquinoline ligand carrying an aminoalkyl side chain was shown to bind the Q–D hybrids with a very high affinity in the order K a≈107 m −1 irrespective of the duplex location at the quadruplex 3′‐ or 5′‐end. NMR chemical shift perturbations identified the tetrad face of the Q–D junction as specific binding site for the ligand. However, calorimetric analyses revealed significant differences in the thermodynamic profiles upon binding to hybrids with either a duplex extension at the quadruplex 3′‐ or 5′‐terminus. A large enthalpic gain and considerable hydrophobic effects are accompanied by the binding of one ligand to the 3′‐Q–D junction, whereas non‐hydrophobic entropic contributions favor binding with formation of a 2:1 ligand‐quadruplex complex in case of the 5′‐Q–D hybrid., An indoloquinoline‐based G4 ligand binds with very high affinity at the quadruplex–duplex junction of a parallel G‐quadruplex featuring a stem‐loop duplex extension. Thermodynamic profiles and modes of binding differ for hybrids with duplex extensions at either the 5′‐ or 3′‐face of the G‐quadruplex.

Purpose To describe a new method for encoding chemical shift using asymmetric readout waveforms that enables more SNR-efficient fat/water imaging. Methods Chemical shift was encoded using asymmetric readout waveforms, rather than conventional shifted trapezoid readouts. Two asymmetric waveforms are described: a triangle and a spline. The concept was applied to a fat/water separated RARE sequence to increase sampling efficiency. The benefits were investigated through comparisons to shifted trapezoid readouts. Using asymmetric readout waveforms, the scan time was either shortened or maintained to increase SNR. A matched in-phase waveform is also described that aims to improve the SNR transfer function of the fat and water estimates. The sequence was demonstrated for cervical spine, musculoskeletal (MSK), and optic nerve applications at 3T and compared with conventional shifted readouts. Results By removing sequence dead times, scan times were shortened by 30% with maintained SNR. The shorter echo spacing also reduced T 2 blurring. Maintaining the scan times and using asymmetric readout waveforms achieved an SNR improvement in agreement with the prolonged sampling duration. Conclusions Asymmetric readout waveforms offer an additional degree of freedom in pulse sequence designs where chemical shift encoding is desired. This can be used to significantly shorten scan times or to increase SNR with maintained scan time.

Solid‐state NMR analysis on wurtzite alloyed CdSe1−xSx crystalline nanoparticles and nanobelts provides evidence that the 113Cd NMR chemical shift is not affected by the varying sizes of nanoparticles, but is sensitive to the S/Se anion molar ratios. A linear correlation is observed between 113Cd NMR chemical shifts and the sulfur component for the alloyed CdSe1−xSx (0, Finding the right composition: The 113Cd NMR chemical shifts of anion rich alloyed CdSe1−xSx materials are not affected by the nanoparticle size, but do change depending on the bound anion about the Cd(II) cation. Based on this correlation, a rapid and easy approach to determine the composition of the alloyed nanoscale materials has been developed by utilizing 113Cd NMR spectroscopy.

We report an experimental observation of 31P NMR resonances shifted by over 10 000 ppm (meaning percent range, and a new record for solutions), and similar 1H chemical shifts, in an intermediate‐spin square planar ferrous complex [ tBu(PNP)Fe‐H], where PNP is a carbazole‐based pincer ligand. Using a combination of electronic structure theory, nuclear magnetic resonance, magnetometry, and terahertz electron paramagnetic resonance, the influence of magnetic anisotropy and zero‐field splitting on the paramagnetic shift and relaxation enhancement is investigated. Detailed spin dynamics simulations indicate that, even with relatively slow electron spin relaxation (T 1 ≈10−11 s), it remains possible to observe NMR signals of directly metal‐bonded atoms because pronounced rhombicity in the electron zero‐field splitting reduces nuclear paramagnetic relaxation enhancement., High‐resolution paramagnetic NMR resonances of a ferrous complex with an intermediate spin ground state with chemical shifts beyond ten thousand ppm were detected, the observability of which are attributed to a large rhombic zero‐field splitting resulting in an effective suppression of the dipolar relaxation mechanism.

A new NMR‐based Lewis acidity scale is suggested and its application is demonstrated for a family of silyl Lewis acids. The reaction of p‐fluorobenzonitrile (FBN) with silyl cations that are internally stabilized by interaction with a remote chalcogenyl or halogen donor yields silylated nitrilium ions with the silicon atom in a trigonal bipyramidal coordination environment. The 19F NMR chemical shifts and the 1 J(CF) coupling constants of these nitrilium ions vary in a predictable manner with the donor capability of the stabilizing group. The spectroscopic parameters are suitable probes for scaling the acidity of Lewis acids. These new probes allow for the discrimination between very similar Lewis acids, which is not possible with conventional NMR tests, such as the well‐established Gutmann–Beckett method., The basis of natural sciences is to measure complex parameters, such as Lewis acidity. A new NMR‐based probe is suggested, which allows for the scaling of stabilized Lewis acids and complements the toolbox of methods for gauging Lewis acidity.

The determination of the binding affinity quantifying the interaction between proteins and nucleic acids is of crucial interest in biological and chemical research. Here, we have made use of site‐specific fluorine labeling of the cold shock protein from Bacillus subtilis, BsCspB, enabling to directly monitor the interaction with single stranded DNA molecules in cell lysate. High‐resolution 19F NMR spectroscopy has been applied to exclusively report on resonance signals arising from the protein under study. We have found that this experimental approach advances the reliable determination of the binding affinity between single stranded DNA molecules and its target protein in this complex biological environment by intertwining analyses based on NMR chemical shifts, signal heights, line shapes and simulations. We propose that the developed experimental platform offers a potent approach for the identification of binding affinities characterizing intermolecular interactions in native surroundings covering the nano‐to‐micromolar range that can be even expanded to in cell applications in future studies., Our research targets on the quantitative determination of protein‐to‐ligand binding in complex cellular environments. Fluorine protein labelling has been utilized enabling to analyze signal height, line width and chemical shift upon DNA binding in great detail employing high‐resolution NMR spectroscopy and simulations. This approach can be easily applied to studies generally interested in interaction processes taking place in cellular environments.

As the knowledge of the predominant molecular structure of antioxidant and anticancer flavonoid rutin in solution is very important for understanding the mechanism of action, a quantum chemical investigation of plausible rutin structures including solvent effects is of relevance. In this work, DFT calculations were performed to find possible minimum energy structures for the rutin molecule. 1H NMR chemical shift DFT calculations were carried out in DMSO solution using the polarizable continuum model (PCM) to simulate the solvent effect. Analysis of the experimental and theoretical 1H NMR chemical shift profiles offers a powerful fingerprint criterion to determine the predominant molecular structure in solution. Therefore, our aim is to find the best match between experimental (in DMSO‐d) and theoretical (PCM–DMSO) 1H NMR spectrum profiles. Among 34 optimized structures located on the potential energy surface, we found that structure 32, with a B‐ring deviated 30° from a planar configuration (geometry usually assumed for polyphenols), showed an almost perfect agreement with experimental the 1H NMR pattern when compared to the corresponding fully optimized planar geometry. This structure is also predicted as the global minimum based on room‐temperature Gibbs free energy calculations in solution and, therefore, should be experimentally observed. This is new and valuable structural information regarding structure–activity relationship studies, and such information is hard to obtain by experimentalists without the aid of the X‐ray diffraction technique.

Motivation Time-series nuclear magnetic resonance (NMR) has advanced our knowledge about metabolic dynamics. Before analyzing compounds through modeling or statistical methods, chemical features need to be tracked and quantified. However, because of peak overlap and peak shifting, the available protocols are time consuming at best or even impossible for some regions in NMR spectra. Results We introduce Ridge Tracking-based Extract (RTExtract), a computer vision-based algorithm, to quantify time-series NMR spectra. The NMR spectra of multiple time points were formulated as a 3D surface. Candidate points were first filtered using local curvature and optima, then connected into ridges by a greedy algorithm. Interactive steps were implemented to refine results. Among 173 simulated ridges, 115 can be tracked (RMSD < 0.001). For reproducing previous results, RTExtract took less than 2 h instead of ∼48 h, and two instead of seven parameters need tuning. Multiple regions with overlapping and changing chemical shifts are accurately tracked. Availability and implementation Source code is freely available within Metabolomics toolbox GitHub repository (https://github.com/artedison/Edison_Lab_Shared_Metabolomics_UGA/tree/master/metabolomics_toolbox/code/ridge_tracking) and is implemented in MATLAB and R. Supplementary information Supplementary data are available at Bioinformatics online.

Aromaticity is a central concept in chemistry, pervading areas from biochemistry to materials science. Recently, chemists also started to exploit intricate phenomena such as the interplay of local and global (anti)aromaticity or aromaticity in non‐planar systems and three dimensions. These phenomena pose new challenges in terms of our fundamental understanding and the practical visualisation of aromaticity. To overcome these challenges, a method for the visualisation of chemical shielding tensors (VIST) is developed here that allows for a 3D visualisation with quantitative information about the local variations and anisotropy of the chemical shielding. After exemplifying the method in different planar hydrocarbons, we study two non‐planar macrocycles to show the unique benefits of the VIST method for molecules with competing π‐conjugated systems and conclude with a norcorrole dimer showing clear evidence of through‐space aromaticity. We believe that the VIST method will be a highly valuable addition to the computational toolbox., A method for the visualisation of chemical shielding tensors (VIST) is developed, which provides a graphical representation of aromaticity and antiaromaticity, their local variations, and anisotropy. The method provides unique insight into fascinating phenomena such as the interplay of aromaticity and antiaromaticity in macrocycles with competing π‐conjugated systems.

The active species of the Ishikawa´s reagent [N,N-diethyl-(1,1,2,3,3,3-hexafluoropropyl)amine] is a fluorinating hexafluoropropylamine used to convert alcohols into alkyl fluorides. On the other hand, it is also an example of model compound useful to probe conformational preferences using spectroscopic information from diastereotopic fluorines. Moreover, the possibility of experiencing both the generalized anomeric and gauche effects makes the Ishikawa´s reagent an ideal choice to study the governing stereoelectronic interactions of the conformational equilibrium of organofluorine compounds. The conformational equilibrium of the Ishikawa´s reagent was analyzed using NMR 3JH,F coupling constant data in different solvents, since the orientation of the diastereotopic fluorines relative to H-2 and F-2 changes with the medium. In nonpolar cyclohexane solvent, the preferred conformation experiences a weaker steric and electrostatic repulsion. The conformational behavior changes in the more polar pyridine solution, where the double fluorine gauche effect takes place, since F-2 is preferably gauche to both diastereotopic fluorines. An analysis of the rotation around the N–C(F2) bond indicates the manifestation of anomeric interactions (nN → σ*C–F), which can be demonstrated by means of 19F chemical shifts. The results were rationalized with the aid of theoretical calculations and natural bond orbital (NBO) analysis, allowing for the evaluation of competing steric, electrostatic and hyperconjugative interactions.

While CH–π interactions with target proteins are crucial determinants for the affinity of arguably every drug molecule, no method exists to directly measure the strength of individual CH–π interactions in drug–protein complexes. Herein, we present a fast and reliable methodology called PI (π interactions) by NMR, which can differentiate the strength of protein–ligand CH–π interactions in solution. By combining selective amino‐acid side‐chain labeling with 1H‐13C NMR, we are able to identify specific protein protons of side‐chains engaged in CH–π interactions with aromatic ring systems of a ligand, based solely on 1H chemical‐shift values of the interacting protein aromatic ring protons. The information encoded in the chemical shifts induced by such interactions serves as a proxy for the strength of each individual CH–π interaction. PI by NMR changes the paradigm by which chemists can optimize the potency of drug candidates: direct determination of individual π interactions rather than averaged measures of all interactions., CH–π interactions are crucial determinants for the affinity of arguably every drug molecule. PI by NMR can differentiate the strength of protein–ligand CH–π interactions in solution. By combining selective amino‐acid side‐chain labeling with 1H‐13C NMR, CH–π interactions can be identified based solely on 1H chemical shift values. This information serves as a proxy for the strength of each individual CH–π interaction.

A series of four ferrocenyl ester compounds, 1-methoxycarbonyl- (1), 1,1’-bis(methoxycarbonyl)- (2), 1,1’,3-tris(methoxycarbonyl)- (3) and 1,1’,3,3’-tetrakis(methoxycarbonyl)ferrocene (4), has been studied with respect to their potential use as redox mediators. The impact of the number and position of ester groups present in 1–4 on the electrochemical potential E1/2 is correlated with the sum of Hammett constants. The 1/1+–4/4+ redox couples are chemically stable under the conditions of electrolysis as demonstrated by IR and UV–vis spectroelectrochemical methods. The energies of the C=O stretching vibrations of the ester moieties and the energies of the UV–vis absorptions of 1–4 and 1+–4+ correlate with the number of ester groups. Paramagnetic 1H NMR redox titration experiments give access to the chemical shifts of 1+–4+ and underline the fast electron self-exchange of the ferrocene/ferrocenium redox couples, required for rapid redox mediation in organic electrosynthesis.

Purpose To evaluate the dependency of the 129Xe‐red blood cell (RBC) chemical shift on blood oxygenation, and to use this relation for noninvasive measurement of pulmonary blood oxygenation in vivo with hyperpolarized 129Xe NMR. Methods Hyperpolarized 129Xe was equilibrated with blood samples of varying oxygenation in vitro, and NMR was performed at 1.5 T and 3 T. Dynamic in vivo NMR during breath hold apnea was performed at 3 T on two healthy volunteers following inhalation of hyperpolarized 129Xe. Results The 129Xe chemical shift in RBCs was found to increase nonlinearly with blood oxygenation at 1.5 T and 3 T. During breath hold apnea, the 129Xe chemical shift in RBCs exhibited a periodic time modulation and showed a net decrease in chemical shift of ∼1 ppm over a 35 s breath hold, corresponding to a decrease of 7–10 % in RBC oxygenation. The 129Xe‐RBC signal amplitude showed a modulation with the same frequency as the 129Xe‐RBC chemical shift. Conclusion The feasibility of using the 129Xe‐RBC chemical shift to measure pulmonary blood oxygenation in vivo has been demonstrated. Correlation between 129Xe‐RBC signal and 129Xe‐RBC chemical shift modulations in the lung warrants further investigation, with the aim to better quantify temporal blood oxygenation changes in the cardiopulmonary vascular circuit. Magn Reson Med 77:1399–1408, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Background: Aescin, a natural mixture of saponins occurring in Aesculus hippocastanum, exhibits important flebotonic properties, being used in the treatment of chronic venous insufficiency in legs. The inclusion of aescin into cyclodextrins (CDs) is a technical solution for its incorporation into the textile of stockings, but details of the physicochemistry of these host–guest systems are lacking. This work investigates the inclusion of aescin into the cavities of two native cyclodextrins, β-CD and γ-CD.Results: The continuous variation method applied to aqueous-phase 1H nuclear magnetic resonance (1H NMR) has demonstrated that the preferred CD/aescin inclusion stoichiometries are 2:1 with β-CD and 1:1 with γ-CD. The affinity constant calculated for γ-CD·aescin was 894 M−1, while for 2β-CD·aescin it was estimated to be 715 M−1. Density functional theory (DFT) calculations on the interaction of aescin Ib with CDs show that an inclusion can indeed occur and it is further demonstrated that the wider cavity of γ-CD is more adequate to accommodate this large guest. ROESY spectroscopy is consistent with the formation of a complex in which the triterpenic moiety of aescin is included into the cavity of γ-CD. The higher stability of this geometry was confirmed by DFT. Furthermore, DFT calculations were applied to determine the chemical shifts of the protons H3 and H5 of the CDs in the optimised structures of the inclusion complexes. The calculated values are very similar to the experimental data, validating the approach made in this study by NMR.Conclusion: The combination of experimental data from aqueous-state NMR measurements and theoretical calculations has demonstrated that γ-CD is the most suitable host for aescin, although the inclusion also occurs with β-CD. The geometry of the γ-CD·aescin complex is characterised by the inclusion of the triterpene segment of aescin into the host cavity.

Ribonucleic acid oligonucleotides (RNAs) play pivotal roles in cellular function (riboswitches), chemical biology applications (SELEX‐derived aptamers), cell biology and biomedical applications (transcriptomics). Furthermore, a growing number of RNA forms (long non‐coding RNAs, circular RNAs) but also RNA modifications are identified, showing the ever increasing functional diversity of RNAs. To describe and understand this functional diversity, structural studies of RNA are increasingly important. However, they are often more challenging than protein structural studies as RNAs are substantially more dynamic and their function is often linked to their structural transitions between alternative conformations. NMR is a prime technique to characterize these structural dynamics with atomic resolution. To extend the NMR size limitation and to characterize large RNAs and their complexes above 200 nucleotides, new NMR techniques have been developed. This Minireview reports on the development of NMR methods that utilize detection on low‐γ nuclei (heteronuclei like 13C or 15N with lower gyromagnetic ratio than 1H) to obtain unique structural and dynamic information for large RNA molecules in solution. Experiments involve through‐bond correlations of nucleobases and the phosphodiester backbone of RNA for chemical shift assignment and make information on hydrogen bonding uniquely accessible. Previously unobservable NMR resonances of amino groups in RNA nucleobases are now detected in experiments involving conformational exchange‐resistant double‐quantum 1H coherences, detected by 13C NMR spectroscopy. Furthermore, 13C and 15N chemical shifts provide valuable information on conformations. All the covered aspects point to the advantages of low‐γ nuclei detection experiments in RNA., Enlightening the blind spots: Newly established carbon‐ and nitrogen‐detection NMR experiments allow characterization of RNA structure and dynamics where traditional proton‐based techniques fail (see figure).

This paper reports the 1H, 13C and 15N NMR experimental study of five benzimidazoles in solution and in the solid state (13C and 15N CPMAS NMR) as well as the theoretically calculated (GIAO/DFT) chemical shifts. We have assigned unambiguously the "tautomeric positions" (C3a/C7a, C4/C7 and C5/C6) of NH-benzimidazoles that, in some solvents and in the solid state, appear different (blocked tautomerism). In the case of 1H-benzimidazole itself we have measured the prototropic rate in HMPA-d18.

Rh(CO)2Cl(NHC) complexes of dipyrido-annelated N-heterocyclic carbenes were prepared. From the C–H coupling constant of the respective imidazolium salts and the N–C–N angle of the N-heterocyclic carbene (NHC), a weaker σ-donor character than that of typical unsaturated NHCs is expected. However, the IR stretching frequencies of their Rh(CO)2Cl complexes suggest an electron-donor character even stronger than that of saturated NHCs. We ascribe this to the extremely weak π-acceptor character of the dipyrido-annelated NHCs caused by the conjugated 14 πe− system that thus allows for an enhanced Rh–CO backbonding. This extremely low π-acceptor ability is also corroborated by the 77Se NMR chemical shift of −55.8 ppm for the respective selenourea, the lowest value ever measured for imidazole derived selenoureas. DFT-calculations of the free carbene confirm the low σ-donor character by the fact that the σ-orbital of the carbene is the HOMO−1 that lies 0.58 eV below the HOMO which is located at the π-system. Natural population analysis reveals the lowest occupation of the pπ-orbital for the saturated carbene carbon atom and the highest for the pyrido-annelated carbene. Going from the free carbene to the Rh(CO)2Cl(NHC) complexes, the increase in occupancy of the complete π-system of the carbene ligand upon coordination is lowest for the pyrido-annelated carbene and highest for the saturated carbene.

Differential epitope mapping saturation transfer difference (DEEP‐STD) NMR spectroscopy is a recently developed powerful approach for elucidating the structure and pharmacophore of weak protein–ligand interactions, as it reports key information on the orientation of the ligand and the architecture of the binding pocket.1 The method relies on selective saturation of protein residues in the binding site and the generation of a differential epitope map by observing the ligand, which depicts the nature of the protein residues making contact with the ligand in the bound state. Selective saturation requires knowledge of the chemical‐shift assignment of the protein residues, which can be obtained either experimentally by NMR spectroscopy or predicted from 3D structures. Herein, we propose a simple experimental procedure to expand the DEEP‐STD NMR methodology to protein–ligand cases in which the spectral assignment of the protein is not available. This is achieved by experimentally identifying the chemical shifts of the residues present in binding hot‐spots on the surface of the receptor protein by using 2D NMR experiments combined with a paramagnetic probe.

We provide a detailed evaluation of nuclear magnetic resonance (NMR) parameters of the cis- and trans-isomers of azobenzene (AB). For determining the NMR parameters, such as proton–proton and proton–nitrogen J-couplings and chemical shifts, we compared NMR spectra of three different isotopomers of AB: the doubly 15N labeled azobenzene, 15N,15N′-AB, and two partially deuterated AB isotopomers with a single 15N atom. For the total lineshape analysis of NMR spectra, we used the recently developed ANATOLIA software package. The determined NMR parameters allowed us to optimize experiments for investigating singlet long-lived spin states (LLSs) of 15N spin pairs and to measure LLS lifetimes in cis-AB and trans-AB. Magnetization-to-singlet-to-magnetization conversion has been performed using the SLIC and APSOC techniques, providing a degree of conversion up to 17 and 24% of the initial magnetization, respectively. Our approach is useful for optimizing the performance of experiments with singlet LLSs; such LLSs can be exploited for preserving spin hyperpolarization, for probing slow molecular dynamics, slow chemical processes and also slow transport processes. Electronic supplementary material The online version of this article (10.1007/s00723-017-0968-8) contains supplementary material, which is available to authorized users.

Through X-ray absorption and emission spectroscopies, the chemical, electronic and structural properties of organic species in solution can be observed. Near-edge X-ray absorption fine structure (NEXAFS) and resonant inelastic X-ray scattering (RIXS) measurements at the nitrogen K-edge of para- aminobenzoic acid reveal both pH- and solvent-dependent variations in the ionisation potential (IP), 1s→π* resonances and HOMO–LUMO gap. These changes unequivocally identify the chemical species (neutral, cationic or anionic) present in solution. It is shown how this incisive chemical state sensitivity is further enhanced by the possibility of quantitative bond length determination, based on the analysis of chemical shifts in IPs and σ* shape resonances in the NEXAFS spectra. This provides experimental access to detecting even minor variations in the molecular structure of solutes in solution, thereby providing an avenue to examining computational predictions of solute properties and solute–solvent interactions.

A combined computational and (13)C NMR study was used to investigate the formation of mixed aggregates of 1-methoxyallenyllithium and lithium chloride in tetrahydrofuran (THF) solution. The observed and calculated chemical shifts, as well as the calculated free energies of mixed aggregate formation (MP2/6-31+G(d)), are consistent with the formation of a mixed dimer as the major species in solution. Free energies of mixed dimer, trimer, and tetramer formation were calculated by using the B3LYP and MP2 methods and the 6-31+G(d) basis set. The two methods generated different predictions of which mixed aggregates will be formed, with B3LYP/6-31+G(d) favoring mixed trimers and tetramers in THF solution, and MP2/6-31+G(d) favoring mixed dimers. Formation of the sterically unhindered mixed dimers is also consistent with the enhanced reactivity of these compounds in the presence of lithium chloride. The spectra are also consistent with some residual 1-methoxyallenyllithium tetramer, as well as small amounts of higher mixed aggregates. Although neither computational method is perfect, for this particular system, the calculated free energies derived using the MP2 method are in better agreement with experimental data than those derived using the B3LYP method.

2-Haloketones are building blocks that combine physical, chemical and biological features of materials and bioactive compounds, while organic fluorine plays a fundamental role in the design of performance organic molecules. Since these features are dependent on the three-dimensional chemical structure of a molecule, simple structural modifications can affect its conformational stability and, consequently, the corresponding physicochemical/biological property of interest. In this work, structural changes in 2-fluorocyclohexanone were theoretically studied with the aim at finding intramolecular interactions that induce the conformational equilibrium towards the axial or equatorial conformer. The interactions evaluated were hydrogen bonding, hyperconjugation, electrostatic and steric effects. While the gauche effect, originated from hyperconjugative interactions, does not appear to cause some preferences for the axial conformation of organofluorine heterocycles, more classical effects indeed rule the conformational equilibrium of the compounds. Spectroscopic parameters (NMR chemical shifts and coupling constants), which can be useful to determine the stereochemistry and the interactions operating in the series of 2-fluorocyclohexanone derivatives, were also calculated.

Owing to its imidazole side chain, histidine partici- pates in various processes such as enzyme catalysis, pH reg- ulation, metal binding, and phosphorylation. The determina- tion of exchange rates of labile protons for such a system is important for understanding its functions. However, these rates are too fast to be measured directly in an aqueous so- lution by using NMR spectroscopy. We have obtained the ex- change rates of the NH3 + amino protons and the labile NH e2 and NH d1 protons of the imidazole ring by indirect detection through nitrogen-15 as a function of temperature (272 K < T < 293 K) and pH (1.3 < pH < 4.9) of uniformly nitrogen-15- and carbon-13-labeled l-histidine·HCl·H2O. Exchange rates up to 8.5 � 10 4 s � 1 could be determined (i.e., lifetimes as short as 12 ms). The three chemical shifts dHi of the invisible exchanging protons Hi and the three one-bond scalar cou- pling constants 1 J(N,Hi could also be determined accurately.

Interface properties of cobalt(II) phthalocyanine (CoPc) and cobalt(II) hexadecafluoro-phthalocyanine (CoPcF16) to gold are investigated by photo-excited electron spectroscopies (X-ray photoemission spectroscopy (XPS), ultraviolet photoemission spectroscopy (UPS) and X-ray excited Auger electron spectroscopy (XAES)). It is shown that a bidirectional charge transfer determines the interface energetics for CoPc and CoPcF16 on Au. Combined XPS and XAES measurements allow for the separation of chemical shifts based on different local charges at the considered atom caused by polarization effects. This facilitates a detailed discussion of energetic shifts of core level spectra. The data allow the discussion of site-specific charge-transfer processes.

The performance of a fully automatically generated tailor-made force field in the field of NMR crystallography is evaluated and compared with existing benchmarks. The advantages and limitations of NMR crystallography with motional averaging are revealed in this study., Motional averaging has been proven to be significant in predicting the chemical shifts in ab initio solid-state NMR calculations, and the applicability of motional averaging with molecular dynamics has been shown to depend on the accuracy of the molecular mechanical force field. The performance of a fully automatically generated tailor-made force field (TMFF) for the dynamic aspects of NMR crystallography is evaluated and compared with existing benchmarks, including static dispersion-corrected density functional theory calculations and the COMPASS force field. The crystal structure of free base cocaine is used as an example. The results reveal that, even though the TMFF outperforms the COMPASS force field for representing the energies and conformations of predicted structures, it does not give significant improvement in the accuracy of NMR calculations. Further studies should direct more attention to anisotropic chemical shifts and development of the method of solid-state NMR calculations.

The conformational properties of 1,3-diindolylureas and thioureas were studied by a combination of heteronuclear NMR spectroscopy and quantum mechanics calculations. NOE experiments showed that the anti–anti conformer along the C7–N7α bonds was predominant in DMSO-d6 solution in the absence of anions. Anion-induced changes in the 1H and 15N chemical shifts confirm the weak binding of chloride anions with negligible conformational changes. Strong deshielding of ureido protons and moderate deshielding of indole NH was observed upon the addition of acetate, benzoate, bicarbonate and dihydrogen phosphate, which indicated that the predominant hydrogen bond interactions occurred at the urea donor groups. Binding of oxo-anions caused conformational changes along the C7–N7α bonds and the syn–syn conformer was preferred for anion–receptor complexes. The conformational changes upon anion binding are in good agreement with energetic preferences established by ab initio calculations.

Density functional theoretical calculations have been utilized to investigate the interaction of the amino acid arginine with the (100) surface of anatase and the reproduction of experimentally measured 49Ti NMR chemical shifts of anatase. Significant binding of arginine through electrostatic interaction and hydrogen bonds of the arginine guanidinium protons to the TiO2 surface oxygen atoms is observed, allowing attachment of proteins to titania surfaces in the construction of bio-sensitized solar cells. GIAO-B3LYP/6-31G(d) NMR calculation of a three-layer model based on the experimental structure of this TiO2 modification gives an excellent reproduction of the experimental value (-927 ppm) within +/- 7 ppm, however, the change in relative chemical shifts, EFGs and CSA suggest that the effect of the electrostatic arginine binding might be too small for experimental detection. Electronic supplementary material The online version of this article (doi:10.1007/s00894-010-0853-y) contains supplementary material, which is available to authorized users.

Motivation: Complementing its traditional role in structural studies of proteins, nuclear magnetic resonance (NMR) spectroscopy is playing an increasingly important role in functional studies. NMR dynamics experiments characterize motions involved in target recognition, ligand binding, etc., while NMR chemical shift perturbation experiments identify and localize protein–protein and protein–ligand interactions. The key bottleneck in these studies is to determine the backbone resonance assignment, which allows spectral peaks to be mapped to specific atoms. This article develops a novel approach to address that bottleneck, exploiting an available X-ray structure or homology model to assign the entire backbone from a set of relatively fast and cheap NMR experiments. Results: We formulate contact replacement for resonance assignment as the problem of computing correspondences between a contact graph representing the structure and an NMR graph representing the data; the NMR graph is a significantly corrupted, ambiguous version of the contact graph. We first show that by combining connectivity and amino acid type information, and exploiting the random structure of the noise, one can provably determine unique correspondences in polynomial time with high probability, even in the presence of significant noise (a constant number of noisy edges per vertex). We then detail an efficient randomized algorithm and show that, over a variety of experimental and synthetic datasets, it is robust to typical levels of structural variation (1–2 AA), noise (250–600%) and missings (10–40%). Our algorithm achieves very good overall assignment accuracy, above 80% in α-helices, 70% in β-sheets and 60% in loop regions. Availability: Our contact replacement algorithm is implemented in platform-independent Python code. The software can be freely obtained for academic use by request from the authors. Contact: gopal@cs.purdue.edu; cbk@cs.dartmouth.edu

In this paper the stereostructural investigation of two new oxygenated polyketides, plakilactones G and H, isolated from the marine sponge Plakinastrella mamillaris collected at Fiji Islands, is reported. The stereostructural studies began on plakilactone H by applying an integrated approach of the NOE-based protocol and quantum mechanical calculations of 13C chemical shifts. In particular, plakilactone H was used as a template to extend the application of NMR-derived interproton distances to a highly flexible molecular system with simultaneous assignment of four non-contiguous stereocenters. Chemical derivatization and quantum mechanical calculations of 13C on plakilactone G along with a plausible biogenetic interconversion between plakilactone G and plakilactone H allowed us to determine the absolute configuration in this two new oxygenated polyketides.

A short segment of the disordered p53 transactivation domain (p53TAD) forms an amphipathic helix when bound to the E3 ubiquitin ligase, MDM2. In the unbound p53TAD, this short segment has transient helical secondary structure. Using a method that combines broad sampling of conformational space with re-weighting, it is shown that it is possible to generate multiple, independent structural ensembles that have highly similar secondary structure distributions for both p53TAD and a P27A mutant. Fractional amounts of transient helical secondary structure were found at the MDM2 binding site that are very similar to estimates based directly on experimental observations. Structures were identified in these ensembles containing segments that are highly similar to short p53 peptides bound to MDM2, even though the ensembles were re-weighted using unbound experimental data. Ensembles were generated using chemical shift data (alpha carbon only, or in combination with other chemical shifts) and cross-validated by predicting residual dipolar couplings. We think this ensemble generator could be used to predict the bound state structure of protein interaction sites in IDPs if there are detectable amounts of matching transient secondary structure in the unbound state.

X-ray absorption and scattering spectroscopies involving the 3dtransition-metalK- andL-edges have a long history in studying inorganic and bioinorganic molecules. However, there have been very few studies using theM-edges, which are below 100 eV. Synchrotron-based X-ray sources can have higher energy resolution atM-edges.M-edge X-ray absorption spectroscopy (XAS) and resonant inelastic X-ray scattering (RIXS) could therefore provide complementary information toK- andL-edge spectroscopies. In this study,M2,3-edge XAS on several Co, Ni and Cu complexes are measured and their spectral information, such as chemical shifts and covalency effects, are analyzed and discussed. In addition,M2,3-edge RIXS on NiO, NiF2and two other covalent complexes have been performed and differentd–dtransition patterns have been observed. Although still preliminary, this work on 3dmetal complexes demonstrates the potential to useM-edge XAS and RIXS on more complicated 3dmetal complexes in the future. The potential for using high-sensitivity and high-resolution superconducting tunnel junction X-ray detectors below 100 eV is also illustrated and discussed.

Platinum(IV) am(m)ine complexes are of interest as potential anticancer pro-drugs, but there are few reports of their acid-base properties. We have studied the acid-base properties of three photoactivatable anticancer platinum(IV)-diazidodiam(m)ine complexes (cis,trans,cis-[Pt(IV)(N(3))(2)(OH)(2)(NH(3))(2)], trans,trans,trans-[Pt(IV)(N(3))(2)(OH)(2)(NH(3))(2)], and cis,trans-[Pt(IV)(N(3))(2)(OH)(2)(en)]) using multinuclear NMR methods and potentiometry. In particular, the combination of both direct and indirect techniques for the detection of (15)N signals has allowed changes of the chemical shifts to be followed over the pH range 1-11; complementary (14)N NMR studies have been also carried out. A distinct pK(a) value of approximately 3.4 was determined for all the investigated complexes, involving protonation/deprotonation reactions of one of the axial hydroxido groups, whereas a second pH-dependent change for the three complexes at approximately pH 7.5 appears not to be associated with a loss of an am(m)ine or hydroxido proton from the complex. Our findings are discussed in comparison with the limited data available in the literature on related complexes.

Motivation: Nuclear magnetic resonance (NMR) spectroscopy has been used to study mixtures of metabolites in biological samples. This technology produces a spectrum for each sample depicting the chemical shifts at which an unknown number of latent metabolites resonate. The interpretation of this data with common multivariate exploratory methods such as principal components analysis (PCA) is limited due to high-dimensionality, non-negativity of the underlying spectra and dependencies at adjacent chemical shifts. Results: We develop a novel modification of PCA that is appropriate for analysis of NMR data, entitled Sparse Non-Negative Generalized PCA. This method yields interpretable principal components and loading vectors that select important features and directly account for both the non-negativity of the underlying spectra and dependencies at adjacent chemical shifts. Through the reanalysis of experimental NMR data on five purified neural cell types, we demonstrate the utility of our methods for dimension reduction, pattern recognition, sample exploration and feature selection. Our methods lead to the identification of novel metabolites that reflect the differences between these cell types. Availability: www.stat.rice.edu/~gallen/software.html Contact: gallen@rice.edu Supplementary Information: Supplementary data are available at Bioinformatics online.

The high sensitivity of silole- and silafluorene-containing polymers for detecting organic nitro, nitrate, and nitramine explosives cannot be solely attributed to favorable analyte–polymer hydrophobic interactions and amplified fluorescence quenching due to delocalization along the polymer chain. The Lewis acidity of silicon in conjugated poly(silafluorene-vinylene)s is shown to be important. This was established by examining the 29Si NMR chemical shifts (Δ) for the model trimer fragment of the polymer CH3–silafluorene–(trans-C2H2)–silafluorene–(trans-C2H2)–silafluorene–CH3. The peripheral and central silicon resonances are up-field from a TMS reference at −9.50 and −18.9 ppm, respectively. Both resonances shift down-field in the presence of donor analytes and the observed shifts (0 to 1 ppm) correlate with the basicity of a variety of added Lewis bases, including TNT. The most basic analyte studied was acetonitrile and an association constant (Ka) of 0.12 M−1 was calculated its binding to the peripheral silicon centers using the Scatchard method. Spin-lattice relaxation times (T1) of 5.86(3) and 4.83(4) s were measured for the methyl protons of acetonitrile in benzene-d6 at 20 °C in the absence and presence of the silafluorene trimer, respectively. The significant change in T1 values further supports a binding event between acetonitrile and the silafluorene trimer. These studies as well as significant changes and shifts observed in the characteristic UV–Vis absorption of the silafluorene group support an important role for the Lewis acid character of Si in polymer sensors that incorporate strained silacycles. The nitro groups of high explosives may act as weak Lewis-base donors to silacycles. This provides a donor–acceptor interaction that may be crucial for orienting the explosive analyte in the polymer film to provide an efficient pathway for inner-sphere electron transfer during the electron-transfer quenching process. Figure Electronic supplementary material The online version of this article (doi:10.1007/s00216-009-2846-1) contains supplementary material, which is available to authorized users.

The structure of a representative pyrazolo[3,4]pyran derivative was determined by 1D and 2D NMR techniques. Complete 1H and 13C chemical shifts for this compound are reported. Careful analysis of the HMBC (Heteronuclear Multi-Bond Correlation) spectrum helped to elucidate the configuration of the derivative around C7 and C8. The results showed that the characteristic double-strong and double-weak cross peak pattern in the HMBC spectrum for C7 and C8 might be useful for establishing the structures of other pyrazolo[3,4]pyran derivatives.

A simple method is described for the preparation of the beta-hydroxyethyl esters of nucleoside 5'-phosphates by treatment of the appropriate 2',3'-isopropylidene nucleoside with 2-chloro-2-oxo-1,3-dioxaphospholane. Unambigous structural assignments were based on 13C nmr spectroscopy. Chemical shifts and 13C-31P spin-spin coupling constants are discussed.

The "activation factor" for phosphofructokinase was shown by chemical analysis, by synthesis, and by 13C NMR spectroscopy to be beta-D-fructose-2,6-P2. This compound was prepared from D-fructose-1,2-cyclic 6-P2 by alkaline hydrolysis. D-Fructose-1,2-cyclic 6-P2 is ineffective in activating phosphofructokinase while synthetic D-fructose-2,6-P2 has the same specific activity toward phosphofructokinase as the "activation factor" isolated from rat liver, and it exhibits the same characteristics on paper and ion exchange chromatography. Acid treatment of both the synthetic and the natural product destroys the biological activity and yields 1 mol each of fructose-6-P and Pi; alkaline phosphatase treatment of the compound followed with acid hydrolysis yields fructose. The natural abundance 13C NMR spectra of the synthetically prepared and purified D-fructose-1,2-cyclic 6-P2 and D-fructose-2,6-P2 have been obtained and all resonances have been assigned. The spectra also show that both samples contain predominantly one anomer and the 13C chemical shifts and 31P-13C coupling constants are consistent only with the beta-anomer.