Diffusion measurements to understand dynamics and structuring in solutions involving a homologous series of ionic liquids

The self-diffusion coefficients of each of the components in mixtures containing pyridine and each of the homologous series 1-alkyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imides in acetonitrile were determined using NMR diffusometry (i. e., Pulsed Gradient Spin Echo). The nature of solvation was found to change significantly with the proportion of salt in the mixtures. Increased diffusion coefficients (when corrected for viscosity) for the molecular components were observed with increasing proportion of ionic liquid and with increasing alkyl chain length on the cation. Comparison of the molecular solvents suggests increased interactions in solution of the pyridine with other components of the mixture, consistent with the proposed interactions shown previously to drive changes in reaction kinetics. Discontinuities were seen in the diffusion data for each species in solution across different ionic liquids between the hexyl and octyl derivatives, suggesting a change in the structuring in solution as the alkyl chain on the cation changes and demonstrating the importance of such when considering homologous series

Shortening NMR diffusion experimental times

NMR diffusion measurements have become the method of choice for measuring diffusing due to their wide applicability, speed of measurement, enormous range of accessible diffusion coefficients (from gas ~10-6 m2s-1 to large polymers ~10-15 m2s-1), and the ability to measure diffusion over a specified timescale, Δ, which greatly adds to the power of NMR diffusion measurements as it allows the ability to probe porous media [1,2]. The weakness of NMR diffusion measurements lies in their inherent insensitivity. Consequently, many experiments are in theory possible but in practice would simply consume too much spectrometer time and therefore become impractical. Even in cases where the total measurement time is not a limitation, making the measurement faster expands the horizons of diffusion measurements to study reaction kinetics [3,4], as well as simply increasing throughput

Ultra-high field MRI for evaluation of rectal cancer stroma ex vivo : correlation with histopathology

Purpose or Objective: Current clinical MRI techniques in rectal cancer are unable to differentiate Stage T1 from T2 (invasion of muscularis propria) tumours, and the differentiation of tumour from desmoplastic reaction or fibrous tissue remains a challenge1. Diffusion tensor imaging (DTI) MRI has potential to assess collagen structure and organisation (anisotropy). To our knowledge, there have been no MRI studies assessing DTI MRI for rectal cancer ex vivo. The purpose of this study was to examine DTI MRI derived biomarkers of rectal cancer stromal heterogeneity at high field strength ex vivo

Better, faster, more versatile NMR diffusion measurements

The range of applications and versatility of NMR diffusion measurements [1,2] increase with the speed, accuracy, and the practical lower concentration limits that can be used. For example, faster measurements expand the horizons of diffusion measurements to study reaction kinetics [3,4], as well as simply increasing throughput. Our group has been investigating various approaches for improving the performance of NMR diffusion measurements. Here we present some of our recent advances

Magnetic resonance imaging detects placental hypoxia and acidosis in mouse models of perturbed pregnancies

Endothelial dysfunction as a result of dysregulation of anti-angiogenic molecules secreted by the placenta leads to the maternal hypertensive response characteristic of the pregnancy complication of preeclampsia. Structural abnormalities in the placenta have been proposed to result in altered placental perfusion, placental oxidative stress, cellular damage and inflammation and the release of anti-angiogenic compounds into the maternal circulation. The exact link between these factors is unclear. Here we show, using Magnetic Resonance Imaging as a tool to examine placental changes in mouse models of perturbed pregnancies, that T2 contrast between distinct regions of the placenta is abolished at complete loss of blood flow. Alterations in T2 (spin-spin or transverse) relaxation times are explained as a consequence of hypoxia and acidosis within the tissue. Similar changes are observed in perturbed pregnancies, indicating that acidosis as well as hypoxia may be a feature of pregnancy complications such as preeclampsia and may play a prominent role in the signalling pathways that lead to the increased secretion of anti-angiogenic compounds

MRI detection of hepatic n-acetylcysteine uptake in mice

This proof-of-concept study looked at the feasibility of using a thiol–water proton exchange (i.e., CEST) MRI contrast to detect in vivo hepatic N-acetylcysteine (NAC) uptake. The feasibility of detecting NAC-induced glutathione (GSH) biosynthesis using CEST MRI was also investigated. The detectability of the GSH amide and NAC thiol CEST effect at B0 = 7 T was determined in phantom experiments and simulations. C57BL/6 mice were injected intravenously (IV) with 50 g L−1 NAC in PBS (pH 7) during MRI acquisition. The dynamic magnetisation transfer ratio (MTR) and partial Z-spectral data were generated from the acquisition of measurements of the upfield NAC thiol and downfield GSH amide CEST effects in the liver. The 1H-NMR spectroscopy on aqueous mouse liver extracts, post-NAC-injection, was performed to verify hepatic NAC uptake. The dynamic MTR and partial Z-spectral data revealed a significant attenuation of the mouse liver MR signal when a saturation pulse was applied at −2.7 ppm (i.e., NAC thiol proton resonance) after the IV injection of the NAC solution. The 1H-NMR data revealed the presence of hepatic NAC, which coincided strongly with the increased upfield MTR in the dynamic CEST data, providing strong evidence that hepatic NAC uptake was detected. However, this MTR enhancement was attributed to a combination of NAC thiol CEST and some other upfield MT-generating mechanism(s) to be identified in future studies. The detection of hepatic GSH via its amide CEST MRI contrast was inconclusive based on the current results

NMR diffusometry

Over the last several decades NMR diffusion measurements have evolved into an ever more powerful suite of tools for non-invasively studying translational dynamics. Most modern spectrometers are now capable of performing standard NMR diffusion measurements. The information content available ranges from estimates of translational diffusion in free solution from which solution structure and molecular size can be studied, to information on characteristic distances when the motion occurs within restricted systems. When coupled with electric field pulses it is possible to measure electrophoretic mobility. Thus, it is now possible to separate the resonances from a sample containing a mixture of species on the basis of size or charge. Experimental and theoretical advances in NMR diffusometry have increased the accuracy, information content and range of applicable systems including clinical applications. This chapter touches upon all of these issues

NMR diffusion measurements

This review focuses on the study of self-diffusion (intra-diffusion) by NMR, although NMR in the form of magnetic resonance imaging (MRI) can provide information on mutual-diffusion as described below. Hereinafter, however, the term ‘diffusion’ will signify self-diffusion. NMR provides two ways for studying diffusion and these are as follows: (i) measurement of spin relaxation; and (ii) the imposition of magnetic field gradients. Although this review is almost completely concerned with the field gradient approach, for completeness a brief description of the relaxation method for the study of self-diffusion and the use of MRI to study mutual diffusion will be given. The literature pertaining to NMR diffusion measurements is vast and growing exponentially with time. Consequently, the references provided in this chapter are a mixture of seminal accounts together with more recent works, which are both accessible and span the literature. Extensive coverage of the field is given in ref. 2 to 10

1H NMR diffusion studies of water self-diffusion in supercooled aqueous sodium chloride solutions

The physical properties of aqueous sodium chloride solutions have been studied theoretically, but so far no experimental diffusion data have been obtained under supercooled conditions. Here the results of 1H NMR translational diffusion measurements of water in sodium chloride solutions in the temperature range 230 to 300 K and sodium chloride concentrations up to 4.2 mol/kg are presented. It was found that the diffusion data were well-described by the Vogel–Tamman–Fulcher relationship with concentration-dependent parameters D0, B, and T0. The results indicate that under supercooled conditions the influence of sodium chloride on water diffusion is much smaller than predicted by molecular dynamics simulations

Direct hydrodynamic radius measurement on dissolved organic matter in natural waters using diffusion NMR

Dissolved organic matter from natural waters is a complex mixture of various chemical components, which play vital roles in many environmental processes such as the global carbon cycle and the fate of many key anthropogenic pollutants. Despite its environmental significance, dissolved organic matter in natural form has never been studied using nuclear magnetic resonance based hydrodynamic radius measurements due to its extremely low concentration (e.g., a few mg/L) in natural waters. In this study, NMR-based hydrodynamic radius measurements were performed directly on unconcentrated pond, river, and sea waters. The key chemical components of the dissolved organic matters from different sources were identified as carbohydrates, carboxyl-rich alicyclic molecules, and aliphatic molecules. By using the Stokes-Einstein-Sutherland equation, the average hydrodynamic radii of the three key components were calculated