Melting of aqueous NaCl solutions in porous materials: shifted phase transition distribution (SIDI) approach for determining NMR cryoporometry pore size distributions.

Nuclear magnetic resonance cryoporometry (NMRC) and differential scanning calorimetry thermoporometry (DSC-TPM) are powerful methods for measuring mesopore size distributions. The methods are based on the fact that, according to the Gibbs-Thomson equation, the melting point depression of a liquid confined to a pore is inversely proportional to the pore size. However, aqueous salt solutions, which inherently exist in a broad range of biological porous materials as well as technological applications such as electrolytes, do not melt at a single temperature. This causes artefacts in the pore size distributions extracted by traditional Gibbs-Thomson analysis of NMRC and DSC-TPM data. Bulk aqueous NaCl solutions are known to have a broad distribution of melting points between the eutectic and pure water phase transition points (252-273 K). Here, we hypothesize that, when aqueous NaCl solution (saline) is confined to a small pore, the whole melting point distribution is shifted toward lower temperatures by the value predicted by the Gibbs-Thomson equation. We show that this so-called shifted phase transition distribution (SIDI) approach removes the artefacts arising from the traditional Gibbs-Thomson analysis and gives correct pore size distributions for saline saturated mesoporous silica gel and controlled pore materials analyzed by NMR cryoporometry. Furthermore, we demonstrate that the method can be used for determining pore sizes in collagen-chondroitin sulphate hydrogels resembling the composition of the extracellular matrix of articular cartilage. It is straightforward to apply the SIDI analysis for DSC-TMP data as well.

SPICY: a method for single scan rotating frame relaxometry.

T 1ρ is an NMR relaxation mode that is sensitive to low frequency molecular motions, making it an especially valuable tool in biomolecular research. Here, we introduce a new method, SPICY, for measuring T1ρ relaxation times. In contrast to conventional T1ρ experiments, in which the sequence is repeated many times to determine the T1ρ time, the SPICY sequence allows determination of T1ρ within a single scan, shortening the experiment time remarkably. We demonstrate the method using 1H T1ρ relaxation dispersion experiments. Additionally, we combine the sequence with spatial encoding to produce 1D images in a single scan. We show that T1ρ relaxation times obtained using the single scan approach are in good agreement with those obtained using the traditional experiments.

Air gap technique is recommended in axiolateral hip radiographs.

PURPOSE: To investigate the replacement of conventional grid by air gap in axiolateral hip radiographs. The optimal air gap distance was studied with respect to radiation dose and image quality using phantom images, as well as 26 patient axiolateral hip radiographs. METHODS: The CDRAD phantom, along with polymethylmethacrylate slabs with thicknesses of 10.0, 14.6, and 20.0 cm was employed. The inverse image quality index and dose area product (DAP), as well as their combination, so called figure-of-merit (FOM) parameter, were evaluated for these images, with air gaps from 20 to 50 cm in increments of 10 cm. Images were compared to those acquired using a conventional grid utilized in hip radiography. Radiation dose was measured and kept constant at the surface of the detector by using a reference dosimeter. Verbal consent was asked from 26 patients to participate to the study. Air gap distances from 20 to 50 cm and tube current-time products from 8 to 50 mAs were employed. Exposure index, DAP, as well as patient height and weight were recorded. Two radiologists evaluated the image quality of 26 hip axiolateral projection images on a 3-point nondiagnostic - good/sufficiently good - too good scale. Source-to-image distance of 200 cm and peak tube voltage of 90 kVp were used in both studies. RESULTS AND CONCLUSION: Based on the phantom study, it is possible to reduce radiation dose by replacing conventional grid with air gap without compromising image quality. The optimal air gap distance appears to be 30 cm, based on the FOM analysis. Patient study corroborates this observation, as sufficiently good image quality was found in 24 of 26 patient radiographs, with 7 of 26 images obtained with 30 cm air gap. Thus, air gap method, with an air gap distance of 30 cm, is recommended in axiolateral hip radiography.

Total synthesis of the proposed structure of trichodermatide A.

A short total synthesis of the published structure of racemic trichodermatide A is reported. Our synthesis involves a Knoevenagel condensation/Michael addition sequence, followed by the formation of tricyclic hexahydroxanthene-dione and a diastereoselective bis-hydroxylation. The final product, the structure of which was confirmed by X-ray crystallography, has NMR spectra that are very similar, but not identical, to those of the isolated natural product. Quantum chemically computed (13)C shifts agree well with the present NMR measurements.

Curie-type paramagnetic NMR relaxation in the aqueous solution of Ni(II).

Ni(2+)(aq) has been used for many decades as a model system for paramagnetic nuclear magnetic resonance (pNMR) relaxation studies. More recently, its magnetic properties and also nuclear magnetic relaxation rates have been studied computationally. We have calculated electron paramagnetic resonance and NMR parameters using quantum-mechanical (QM) computation of molecular dynamics snapshots, obtained using a polarizable empirical force field. Statistical averages of hyperfine coupling, g- and zero-field splitting tensors, as well as the pNMR shielding terms, are compared to the available experimental and computational data. In accordance with our previous work, the isotropic hyperfine coupling as well as nuclear shielding values agree well with experimental measurements for the (17)O nuclei of water molecules in the first solvation shell of the nickel ion, whereas larger deviations are found for (1)H centers. We report, for the first time, the Curie-type contribution to the pNMR relaxation rate using QM calculations together with Redfield relaxation theory. The Curie relaxation mechanism is analogous to chemical shift anisotropy relaxation, well-known in diamagnetic NMR. Due to the predominance of other types of paramagnetic relaxation mechanisms for this system, it is possible to extract the Curie term only computationally. The Curie mechanism alone would result in around 16 and 20 s(-1) of relaxation rates (R1 and R2 respectively) for the (1)H nuclei of water molecules bonded to the Ni(2+) center, in a magnetic field of 11.7 T. The corresponding (17)O relaxation rates are around 33 and 38 s(-1). We also report the Curie contribution to the relaxation rate for molecules beyond the first solvation shell in a 1 M solution of Ni(2+) in water.

X-ray scatter in projection radiography.

Projection radiography is the most common radiological modality, and radiation safety of it concerns both radiation workers and the public. We measured and generated a series of scattered radiation maps for projection radiography and estimated effective doses of the supporting person during exposure. Measured adult patient protocols included chest posterior-anterior, chest lateral, pelvis anterior-posterior (AP), abdomen AP and bedside chest AP. Maps concretise spatial distribution and the scattered radiation dose rates in different imaging protocols. Highest and lowest rates were measured in abdomen AP and bedside chest AP protocols, respectively. The effective dose of supporting person in abdomen AP examination at distance of 0.5 m was 300 nSv and in bedside supine chest AP examination at distance of 0.7 m was 0.5 nSv. The estimated annual effective dose of emergency unit radiographer was 0.11 mSv. The obtained effective dose values are small compared to annual dose limits of radiation workers and the public.

Molecular tweezers with varying anions: a comparative study.

Selective binding of the phosphate-substituted molecular tweezer 1a to protein lysine residues was suggested to explain the inhibition of certain enzymes and the aberrant aggregation of amyloid petide Aß42 or α-synuclein, which are assumed to be responsible for Alzheimer's and Parkinson's disease, respectively. In this work we systematically investigated the binding of four water-soluble tweezers 1a-d (substituted by phosphate, methanephosphonate, sulfate, or O-methylenecarboxylate groups) to amino acids and peptides containing lysine or arginine residues by using fluorescence spectroscopy, NMR spectroscopy, and isothermal titration calorimetry (ITC). The comparison of the experimental results with theoretical data obtained by a combination of QM/MM and ab initio(1)H NMR shift calculations provides clear evidence that the tweezers 1a-c bind the amino acid or peptide guest molecules by threading the lysine or arginine side chain through the tweezers' cavity, whereas in the case of 1d the guest molecule is preferentially positioned outside the tweezer's cavity. Attractive ionic, CH-π, and hydrophobic interactions are here the major binding forces. The combination of experiment and theory provides deep insight into the host-guest binding modes, a prerequisite to understanding the exciting influence of these tweezers on the aggregation of proteins and the activity of enzymes.

Nuclear spin-spin coupling in a van der Waals-bonded system: xenon dimer.

Nuclear spin-spin coupling over van der Waals bond has recently been observed via the frequency shift of solute protons in a solution containing optically hyperpolarized (129)Xe nuclei. We carry out a first-principles computational study of the prototypic van der Waals-bonded xenon dimer, where the spin-spin coupling between two magnetically non-equivalent isotopes, J((129)Xe - (131)Xe), is observable. We use relativistic theory at the four-component Dirac-Hartree-Fock and Dirac-density-functional theory levels using novel completeness-optimized Gaussian basis sets and choosing the functional based on a comparison with correlated ab initio methods at the nonrelativistic level. J-coupling curves are provided at different levels of theory as functions of the internuclear distance in the xenon dimer, demonstrating cross-coupling effects between relativity and electron correlation for this property. Calculations on small Xe clusters are used to estimate the importance of many-atom effects on J((129)Xe - (131)Xe). Possibilities of observing J((129)Xe - (131)Xe) in liquid xenon are critically examined, based on molecular dynamics simulation. A simplistic spherical model is set up for the xenon dimer confined in a cavity, such as in microporous materials. It is shown that the on the average shorter internuclear distance enforced by the confinement increases the magnitude of the coupling as compared to the bulk liquid case, rendering J((129)Xe - (131)Xe) in a cavity a feasible target for experimental investigation.

Assessing post-traumatic changes in cartilage using T1ρ dispersion parameters.

Degeneration of cartilage can be studied non-invasively with quantitative MRI. A promising parameter for detecting early osteoarthritis in articular cartilage is T1ρ, which can be tuned via the amplitude of the spin-lock pulse. By measuring T1ρ at several spin-lock amplitudes, the dispersion of T1ρ is obtained. The aim of this study is to find out if the dispersion contains diagnostically relevant information complementary to a T1ρ measurement at a single spin-lock amplitude. To this end, five differently acquired dispersion parameters are utilized; A, B, τc, T1ρ/T2, and R2 - R1ρ. An open dataset of an equine model of post-traumatic cartilage was utilized to assess the T1ρ dispersion parameters for the evaluation of cartilage degeneration. Firstly, the parameters were compared for their sensitivity in detecting degenerative changes. Secondly, the relationship of the dispersion parameters to histological and biomechanical reference parameters was studied. Parameters A, T1ρ/T2, and R2 - R1ρ were found to be sensitive to lesion-induced changes in the cartilage within sample. Strong correlations of several dispersion parameters with optical density, as well as with collagen fibril angle were found. Most of the dispersion parameters correlated strongly with individual T1ρ values. The results suggest that dispersion parameters can in some cases provide a more accurate description of the biochemical composition of cartilage as compared to conventional MRI parameters. However, in most cases the information given by the dispersion parameters is more of a refinement than complementary to conventional quantitative MRI.

Dipolar Relaxation of Water Protons in the Vicinity of a Collagen-like Peptide.

Quantitative magnetic resonance imaging is one of the few available methods for noninvasive diagnosis of degenerative changes in articular cartilage. The clinical use of the imaging data is limited by the lack of a clear association between structural changes at the molecular level and the measured magnetic relaxation times. In anisotropic, collagen-containing tissues, such as articular cartilage, the orientation dependency of nuclear magnetic relaxation can obscure the content of the images. Conversely, if the molecular origin of the phenomenon would be better understood, it would provide opportunities for diagnostics as well as treatment planning of degenerative changes in these tissues. We study the magnitude and orientation dependence of the nuclear magnetic relaxation due to dipole-dipole coupling of water protons in anisotropic, collagenous structures. The water-collagen interactions are modeled with molecular dynamics simulations of a small collagen-like peptide dissolved in water. We find that in the vicinity of the collagen-like peptide, the dipolar relaxation of water hydrogen nuclei is anisotropic, which can result in orientation-dependent relaxation times if the water remains close to the peptide. However, the orientation-dependency of the relaxation is different from the commonly observed magic-angle phenomenon in articular cartilage MRI.

Relaxation anisotropy of quantitative MRI parameters in biological tissues.

Quantitative MR relaxation parameters vary in the sensitivity to the orientation of the tissue in the magnetic field. In this study, the orientation dependence of multiple relaxation parameters was assessed in various tissues. Ex vivo samples of each tissue type were prepared either from bovine knee (tendon, cartilage) or mouse (brain, spinal cord, heart, kidney), and imaged at 9.4 T MRI with T1, T2, continuous wave (CW-) T1ρ, adiabatic T1ρ and T2ρ, and Relaxation along fictitious field (RAFF2-4) sequences at five different orientations with respect to the main magnetic field. Relaxation anisotropy of the measured parameters was quantified and compared. The highly ordered collagenous tissues, i.e. cartilage and tendon, presented the highest relaxation anisotropy for T2, CW-T1ρ with spin-lock power < 1 kHz, Ad-T2ρ and RAFF2-4. Maximally anisotropy was 75% in cartilage and 30% in tendon. T1 and adiabatic T1ρ did not exhibit observable anisotropy. In the other measured tissue types, anisotropy was overall less than 10% for all the parameters. The results confirm that highly ordered collagenous tissues have properties that induce very clearly observable relaxation anisotropy, whereas in other tissues the effect is not as prominent. Quantitative comparison of anisotropy of different relaxation parameters highlights the importance of sequence choice and design in MR imaging.

Nuclear spin relaxation due to chemical shift anisotropy of gas-phase 129Xe.

Nuclear spin relaxation provides detailed dynamical information on molecular systems and materials. Here, first-principles modeling of the chemical shift anisotropy (CSA) relaxation time for the prototypic monoatomic (129)Xe gas is carried out, both complementing and predicting the results of NMR measurements. Our approach is based on molecular dynamics simulations combined with pre-parametrized ab initio binary nuclear shielding tensors, an "NMR force field". By using the Redfield relaxation formalism, the simulated CSA time correlation functions lead to spectral density functions that, for the first time, quantitatively determine the experimental spin-lattice relaxation times T(1). The quality requirements on both the Xe-Xe interaction potential and binary shielding tensor are investigated in the context of CSA T(1). Persistent dimers Xe(2) are found to be responsible for the CSA relaxation mechanism in the low-density limit of the gas, completely in line with the earlier experimental findings.

Orientation anisotropy of quantitative MRI parameters in degenerated human articular cartilage.

Quantitative magnetic resonance (MR) relaxation parameters demonstrate varying sensitivity to the orientation of the ordered tissues in the magnetic field. In this study, the orientation dependence of multiple relaxation parameters was assessed in cadaveric human cartilage with varying degree of natural degeneration, and compared with biomechanical testing, histological scoring, and quantitative histology. Twelve patellar cartilage samples were imaged at 9.4 T MRI with multiple relaxation parameters, including T1 , T2 , CW - T1ρ , and adiabatic T1ρ , at three different orientations with respect to the main magnetic field. Anisotropy of the relaxation parameters was quantified, and the results were compared with the reference measurements and between samples of different histological Osteoarthritis Research Society International (OARSI) grades. T2 and CW - T1ρ at 400 Hz spin-lock demonstrated the clearest anisotropy patterns. Radial zone anisotropy for T2 was significantly higher for samples with OARSI grade 2 than for grade 4. The proteoglycan content (measured as optical density) correlated with the radial zone MRI orientation anisotropy for T2 (r = 0.818) and CW - T1ρ with 400 Hz spin-lock (r = 0.650). Orientation anisotropy of MRI parameters altered with progressing cartilage degeneration. This is associated with differences in the integrity of the collagen fiber network, but it also seems to be related to the proteoglycan content of the cartilage. Samples with advanced OA had great variation in all biomechanical and histological properties and exhibited more variation in MRI orientation anisotropy than the less degenerated samples. Understanding the background of relaxation anisotropy on a molecular level would help to develop new MRI contrasts and improve the application of previously established quantitative relaxation contrasts.

Sensitivity of ab Initio vs Empirical Methods in Computing Structural Effects on NMR Chemical Shifts for the Example of Peptides.

The structural sensitivity of NMR chemical shifts as computed by quantum chemical methods is compared to a variety of empirical approaches for the example of a prototypical peptide, the 38-residue kaliotoxin KTX comprising 573 atoms. Despite the simplicity of empirical chemical shift prediction programs, the agreement with experimental results is rather good, underlining their usefulness. However, we show in our present work that they are highly insensitive to structural changes, which renders their use for validating predicted structures questionable. In contrast, quantum chemical methods show the expected high sensitivity to structural and electronic changes. This appears to be independent of the quantum chemical approach or the inclusion of solvent effects. For the latter, explicit solvent simulations with increasing number of snapshots were performed for two conformers of an eight amino acid sequence. In conclusion, the empirical approaches neither provide the expected magnitude nor the patterns of NMR chemical shifts determined by the clearly more costly ab initio methods upon structural changes. This restricts the use of empirical prediction programs in studies where peptide and protein structures are utilized for the NMR chemical shift evaluation such as in NMR refinement processes, structural model verifications, or calculations of NMR nuclear spin relaxation rates.

Benchmarking Hydrogen and Carbon NMR Chemical Shifts at HF, DFT, and MP2 Levels.

An extensive study of error distributions for calculating hydrogen and carbon NMR chemical shifts at Hartree-Fock (HF), density functional theory (DFT), and Møller-Plesset second-order perturbation theory (MP2) levels is presented. Our investigation employs accurate CCSD(T)/cc-pVQZ calculations for providing reference data for 48 hydrogen and 40 carbon nuclei within an extended set of chemical compounds covering a broad range of the NMR scale with high relevance to chemical applications, especially in organic chemistry. Besides the approximations of HF, a variety of DFT functionals, and conventional MP2, we also present results with respect to a spin component-scaled MP2 (GIAO-SCS-MP2) approach. For each method, the accuracy is analyzed in detail for various basis sets, allowing identification of efficient combinations of method and basis set approximations.

Pairwise additivity in the nuclear magnetic resonance interactions of atomic xenon.

Nuclear magnetic resonance (NMR) of atomic (129/131)Xe is used as a versatile probe of the structure and dynamics of various host materials, due to the sensitivity of the Xe NMR parameters to intermolecular interactions. The principles governing this sensitivity can be investigated using the prototypic system of interacting Xe atoms. In the pairwise additive approximation (PAA), the binary NMR chemical shift, nuclear quadrupole coupling (NQC), and spin-rotation (SR) curves for the xenon dimer are utilized for fast and efficient evaluation of the corresponding NMR tensors in small xenon clusters Xe(n) (n = 2-12). If accurate, the preparametrized PAA enables the analysis of the NMR properties of xenon clusters, condensed xenon phases, and xenon gas without having to resort to electronic structure calculations of instantaneous configurations for n > 2. The binary parameters for Xe(2) at different internuclear distances were obtained at the nonrelativistic Hartree-Fock level of theory. Quantum-chemical (QC) calculations at the corresponding level were used to obtain the NMR parameters of the Xe(n) (n = 2-12) clusters at the equilibrium geometries. Comparison of PAA and QC data indicates that the direct use of the binary property curves of Xe(2) can be expected to be well-suited for the analysis of Xe NMR in the gaseous phase dominated by binary collisions. For use in condensed phases where many-body effects should be considered, effective binary property functions were fitted using the principal components of QC tensors from Xe(n) clusters. Particularly, the chemical shift in Xe(n) is strikingly well-described by the effective PAA. The coordination number Z of the Xe site is found to be the most important factor determining the chemical shift, with the largest shifts being found for high-symmetry sites with the largest Z. This is rationalized in terms of the density of virtual electronic states available for response to magnetic perturbations.

Relativistic effects in the intermolecular interaction-induced nuclear magnetic resonance parameters of xenon dimer.

Relativistic effects on the (129)Xe nuclear magnetic resonance shielding and (131)Xe nuclear quadrupole coupling (NQC) tensors are examined in the weakly bound Xe(2) system at different levels of theory including the relativistic four-component Dirac-Hartree-Fock (DHF) method. The intermolecular interaction-induced binary chemical shift delta, the anisotropy of the shielding tensor Deltasigma, and the NQC constant along the internuclear axis chi( parallel) are calculated as a function of the internuclear distance. DHF shielding calculations are carried out using gauge-including atomic orbitals. For comparison, the full leading-order one-electron Breit-Pauli perturbation theory (BPPT) is applied using a common gauge origin. Electron correlation effects are studied at the nonrelativistic (NR) coupled-cluster singles and doubles with perturbational triples [CCSD(T)] level of theory. The fully relativistic second-order Moller-Plesset many-body perturbation (DMP2) theory is used to examine the cross coupling between correlation and relativity on NQC. The same is investigated for delta and Deltasigma by BPPT with a density functional theory model. A semiquantitative agreement between the BPPT and DHF binary property curves is obtained for delta and Deltasigma in Xe(2). For these properties, the currently most complete theoretical description is obtained by a piecewise approximation where the uncorrelated relativistic DHF results obtained close to the basis-set limit are corrected, on the one hand, for NR correlation effects and, on the other hand, for the BPPT-based cross coupling of relativity and correlation. For chi( parallel), the fully relativistic DMP2 results obtain a correction for NR correlation effects beyond MP2. The computed temperature dependence of the second virial coefficient of the (129)Xe nuclear shielding is compared to experiment in Xe gas. Our best results, obtained with the piecewise approximation for the binary chemical shift combined with the previously published state of the art theoretical potential energy curve for Xe(2), are in excellent agreement with the experiment for the first time.

Calculation of binary magnetic properties and potential energy curve in xenon dimer: second virial coefficient of (129)Xe nuclear shielding.

Quantum chemical calculations of the nuclear shielding tensor, the nuclear quadrupole coupling tensor, and the spin-rotation tensor are reported for the Xe dimer using ab initio quantum chemical methods. The binary chemical shift delta, the anisotropy of the shielding tensor Delta sigma, the nuclear quadrupole coupling tensor component along the internuclear axis chi( parallel ), and the spin-rotation constant C( perpendicular ) are presented as a function of internuclear distance. The basis set superposition error is approximately corrected for by using the counterpoise correction (CP) method. Electron correlation effects are systematically studied via the Hartree-Fock, complete active space self-consistent field, second-order Møller-Plesset many-body perturbation, and coupled-cluster singles and doubles (CCSD) theories, the last one without and with noniterative triples, at the nonrelativistic all-electron level. We also report a high-quality theoretical interatomic potential for the Xe dimer, gained using the relativistic effective potential/core polarization potential scheme. These calculations used valence basis set of cc-pVQZ quality supplemented with a set of midbond functions. The second virial coefficient of Xe nuclear shielding, which is probably the experimentally best-characterized intermolecular interaction effect in nuclear magnetic resonance spectroscopy, is computed as a function of temperature, and compared to experiment and earlier theoretical results. The best results for the second virial coefficient, obtained using the CCSD(CP) binary chemical shift curve and either our best theoretical potential or the empirical potentials from the literature, are in good agreement with experiment. Zero-point vibrational corrections of delta, Delta sigma, chi (parallel), and C (perpendicular) in the nu=0, J=0 rovibrational ground state of the xenon dimer are also reported.