Nuclear Magnetic Resonance Dispersion Profiles Research Articles

Slow water dynamics in polygalacturonate hydrogels revealed by NMR relaxometry and molecular dynamics simulation

Diffusions in gels are of prime importance, but their measurements are mainly focused on the diffusion in the pores or through the mesh of the gels. In this study, we performed a deeper dynamic analysis of the water in close interaction with the fibers structuring two heterogeneous polygalacturonate (polyGalA) hydrogels formed by Ca and Zn ions (crosslinking agents). Nuclear magnetic resonance dispersion (NMRD) profiles recorded in-situ by fast-field cycling relaxometry allow to observe the very slow dynamics of water within the gels. Two distinct interpretations of the NMRD profiles are discussed, the first in regard of rotational and translational dynamics in the fibers and the second with respect to a Levy-walk on the fibers' surface. These discussions are confronted with molecular dynamics simulations on a model Ca-polyGalA fiber.

Characterization of Pectin-Based Gels: A 1H Nuclear Magnetic Resonance Relaxometry Study.

Rare sugars are monosaccharides and their derivatives that are not commonly found in nature. d-Allulose is a rare sugar that is C-3 epimer of fructose and presents an alternative to sucrose with potential health benefits. In this study, different amounts of sucrose, d-allulose, and soy protein isolate (SPI) were used to prepare a set of pectin gels. The effect of these ingredients on the gels was studied at both a molecular level, by 1H nuclear magnetic resonance (NMR) relaxometry, and a macroscopic level, through the assessment of viscoelastic properties as well as hardness and moisture content measurements. The NMR dispersion profiles were analyzed considering relaxation mechanisms associated with rotational and translational diffusion motions of mono- and disaccharides as well as bound water molecules. Significant variations of the local diffusion coefficient for the studied formulations were evidenced by the model fitting analysis. The viscosity trends observed within each group of samples having the same amount of SPI were mostly in agreement with the diffusion coefficients obtained from the NMR relaxometry. The observed discrepancies could be explained considering hardness and moisture content results, which put into evidence the fact that decreasing the moisture (mainly free water) affects the macroscopic properties of the systems, such as hardness and viscosity, but not the local diffusion processes probed by NMR relaxometry. These findings show the importance of combining both micro- and macroscopic information to analyze the different properties of food products.

Exploring the tumour extracellular matrix by in vivo Fast Field Cycling relaxometry after the administration of a Gadolinium-based MRI contrast agent.

1 H Fast Field Cycling NMR (FFC-NMR) relaxometry is proposed as a powerful method to investigate tumour stroma in vivo upon the administration of a Gd-based contrast agent. To perform this study, an FFC-NMR equipment endowed with a wide bore magnet was used for the acquisition of Nuclear Magnetic Resonance Dispersion profiles on healthy muscle and tumour tissue in living mice. At magnetic field strengths < of ca. 1MHz, the differences in the relaxation rates of the intra and extracellular compartment become of the same order of magnitude of the exchange rate across the cellular membranes. Under this condition, the water exchange rate between the two compartments yields to a biexponential magnetization recovery that can be analysed by fitting the experimental data with the two-Site eXchange (2SX) model. Using this model, it was possible to obtain, for the two compartments, both relaxation properties and water kinetic constants for water exchange across cell membranes. The method allowed us to determine the effect of the "matrix" on the water proton relaxation times and, in turn, to get some insights of the composition of this compartment, till now, largely unknown.

Molecular Dynamics of Water in Wood Studied by Fast Field Cycling Nuclear Magnetic Resonance Relaxometry

Water plays a very important role in wood and wood products. The molecular motion of water in wood is susceptible to thermal activation. Thermal energy makes water molecules more active and weakens the force between water and wood; therefore, the water molecules dynamic properties are greatly influenced. Molecular dynamics study is important for wood drying; this paper therefore focuses on water molecular dynamics in wood through fast field cycling nuclear magnetic resonance relaxometry techniques. The results show that the spin-lattice relaxation rate decreases with the Larmor frequency. Nuclear magnetic resonance dispersion profiles at different temperatures could separate the relaxation contribution of water in bigger pores and smaller pores. The T1 distribution from wide to narrow at 10 MHz Larmor frequency reflects the shrinkage of pore size with the higher temperature. The dependence of spin-lattice relaxation rate on correlation time for water molecular motion based on BPP (proposed by Bloembergen, Purcell, and Pound) theory shows that water correlation time increases with higher temperature, and its activation energy, calculated using the Arrhenius transformation equation, is 9.06±0.53 kJ/mol.

High Relaxivities and Strong Vascular Signal Enhancement for NaGdF4 Nanoparticles Designed for Dual MR/Optical Imaging

Near-infrared (NIR)-to-NIR upconverting NaY(Gd)F4 :Tm(3+) ,Yb(3+) paramagnetic nanoparticles (NPs) are efficiently detected by NIR imaging techniques. As they contain Gd(3+) ions, they also provide efficient "positive" contrast in magnetic resonance imaging (MRI). Water-dispersible small (≈25 nm, "S-") and ultrasmall (<5 nm diam., "US-") NaY(Gd)F4 :Tm(3+) ,Yb(3+) NPs are synthesized by thermal decomposition and capped with citrate. The surface of citrate-coated US-NPs shows sodium depletion and high Gd elemental ratios, as confirmed by a comparative X-ray photoelectron spectroscopy (XPS)/neutron absorption analysis study. US-NaGd0.745 F4 :Tm0.005 ,Yb0.25 NPs have hydrodynamic diameters close to that measured by TEM, with the lowest relaxometric ratios (r2 /r1 = 1.18) reported for NaGdF4 nanoparticle suspensions (r1 = 3.37 mM(-1) s(-1) at 1.4 T and 37 °C). Strong relaxivity peaks in the range of 20 (0.47 T) - 300 MHz (7.05 T) are revealed in nuclear magnetic resonance dispersion profiles, with high r2 /r1 ratios at increasing field strengths for S-NPs. This indicates the superiority of US-NPs over S-NPs for achieving high positive contrast at clinical MRI field strengths. I.-v. injected citrate-coated US-NPs evidence long blood retention times (>90 min) in mice. Biodistribution studies (48 h, 8 d) show elimination through the reticuloendothelial and urinary systems, similarly to other citrate-capped US-NP systems. In summary, upconverting NaY(Gd)F4 :Tm(3+) ,Yb(3+) nanoparticles have promising luminescent, relaxometric and blood-retention properties for dual MRI/optical imaging.

The magnetic, relaxometric, and optical properties of gadolinium-catalyzed single walled carbon nanotubes

We report the magnetic behavior, relaxometry, phantom magnetic resonance imaging (MRI), and near-infrared (NIR) photoluminescence spectroscopy of gadolinium (Gd) catalyzed single-walled carbon nanotubes (Gd-SWCNTs). Gd-SWCNTs are paramagnetic with an effective magnetic moment of 7.29 μB . Gd-SWCNT solutions show high r1 and r2 relaxivities at very low (0.01 MHz) to clinically relevant (61 MHz) magnetic fields (r1 ≥ 130 mM-1 s-1, r2 ≥ 160 mM-1 s-1). Analysis of nuclear magnetic resonance dispersion profiles using Solomon, Bloembergen, and Morgan equations suggests that multiple structural and dynamic parameters such as rotational correlation time [Formula: see text], rate of water exchange [Formula: see text], and the number of fast-exchanging water molecules within the inner sphere q may be responsible for the increase in r1 and r2 relaxivity. The T1 weighted MRI signal intensity (gradient echo sequence; repetition time (TR) = 66 ms, echo time (TE) = 3 ms, flop angle = 108°) of Gd-SWCNT phantom solution is 14 times greater than the Gd-based clinical MRI contrast agent Magnevist. Additionally, these nanotubes exhibit near infrared fluorescence with distinct E11 transitions of several semiconducting SWCNTs. Taken together, these results demonstrate that Gd-SWCNTs have potential as a novel, highly efficacious, multimodal MRI-NIR optical imaging contrast agent.

Relaxometric properties of gadolinium-grafted mesoporous SBA-15 silica materials with varying pore size

Gadolinium loaded mesoporous silicas are interesting for MRI contrast agent application due to high r1 relaxivities. Here, gadolinium grafted mesoporous SBA-15 materials with varying pore diameters are investigated by field dependence profiling, temperature studies and high field r1 (11.7T, 500MHz) measurements. SBA-15 hybrid materials with varying pore diameters are prepared via pseudo surface organometallic chemistry (pseudo-SOMC) of Gd[N(SiHMe2)2]3(THF)2 and their Nuclear Magnetic Resonance Dispersion (NMRD) profiles (range 4–80MHz, pore diameters 5.4, 6.5 and 7.7nm) are presented. The profiles have the shape of a slowly tumbling system, with a maximum at relatively high field strength (30–50MHz) and are characterized by increasing r1 with increasing pore size and decreasing temperature. The same trends are observed at 500MHz, where r1 increases from 6.5 to 14.1mM−1s−1 when the pore diameter increases from 5.4 to 9.1nm. Modeling of the NMRD profiles proposes that the Gd-modified SBA-15s have as much as five inner-sphere water molecules (q=5), a relatively slow global (τg=100μs) and fast local rotation (τR=0.08ns) and an efficient water accessibility to the metal center (τm=1.15ns). A model originally developed for zeolites is used to describe the water dynamics in the SBA-15 silicas, and implies that the observed trend with pore size is due to a combination of an increasing number of free water molecules per Gd3+ (x) and a decreasing residence lifetime of water inside the pores (τp).

Scaling laws at the nanosize: the effect of particle size and shape on the magnetism and relaxivity of iron oxide nanoparticle contrast agents

The magnetic properties of iron oxide nanoparticles govern their relaxivities and efficacy as contrast agents for MRI. These properties are in turn determined by their composition, size and morphology. Herein we present a systematic study of the effect of particle size and shape of magnetite nanocrystals synthesized by thermal decompositions of iron salts on both their magnetism and their longitudinal and transverse relaxivities, r1 and r2, respectively. Faceted nanoparticles demonstrate superior magnetism and relaxivities than spherical nanoparticles of similar size. For faceted nanoparticles, but not for spherical ones, r1 and r2 further increase with increasing particle size up to a size of 18 nm. This observation is in accordance with increasing saturation magnetization for nanoparticles increasing in size up to 12 nm, above which a plateau is observed. The NMRD (Nuclear Magnetic Resonance Dispersion) profiles of MIONs (Magnetic Iron Oxide Nanoparticles) display an increase in longitudinal relaxivity with decreasing magnetic field strength with a plateau below 1 MHz. The transverse relaxivity shows no dependence on the magnetic field strength between 20 MHz and 500 MHz. These observations translate to phantom MR images: in T1-weighted SWIFT (SWeep imaging with Fourier Transform) images MIONs have a positive contrast with little dependence on particle size, whereas in T2-weighted gradient-echo images MIONs create a negative contrast which increases in magnitude with increasing particle size. Altogether, these results will enable the development of particulate MRI contrast agents with enhanced efficacy for biomedical and clinical applications.

Synthesis of pseudopolyrotaxanes-coated Superparamagnetic Iron Oxide Nanoparticles as new MRI contrast agent

Superparamagnetic Iron Oxide Nanoparticles (SPIONs) were synthesized and coated with pseudopolyrotaxanes (PPRs) and proposed as a novel hybrid nanostructure for medical imaging and drug delivery. PPRs were prepared by addition of α-cyclodextrin rings to functionalized polyethylene glycol (PEG) chain with hydrophobic triazine end-groups. Non-covalent interactions between SPIONs and PPRs led to the assembly of SPIONs@PRs hybrid nanomaterials. Measurements of the 1H Nuclear Magnetic Resonance (NMR) relaxation times T1 and T2 allowed us to determine the NMR dispersion profiles. Comparison between our SPIONs@PRs hybrid nano-compound and the commercial SPION compound, Endorem®, showed a higher transverse relaxivity for SPIONs@PRs. In vitro MRI experiments showed that our SPIONs@PRs produces better negative contrast compared to Endorem® and can be considered as a novel MRI contrast agent.

Role of the Iron Axial Ligands of Heme Carrier HasA in Heme Uptake and Release

The hemophore protein HasA from Serratia marcescens cycles between two states as follows: the heme-bound holoprotein, which functions as a carrier of the metal cofactor toward the membrane receptor HasR, and the heme-free apoprotein fishing for new porphyrin to be taken up after the heme has been delivered to HasR. Holo- and apo-forms differ for the conformation of the two loops L1 and L2, which provide the axial ligands of the iron through His(32) and Tyr(75), respectively. In the apo-form, loop L1 protrudes toward the solvent far away from loop L2; in the holoprotein, closing of the loops on the heme occurs upon establishment of the two axial coordination bonds. We have established that the two variants obtained via single point mutations of either axial ligand (namely H32A and Y75A) are both in the closed conformation. The presence of the heme and one out of two axial ligands is sufficient to establish a link between L1 and L2, thanks to the presence of coordinating solvent molecules. The latter are stabilized in the iron coordination environment by H-bond interactions with surrounding protein residues. The presence of such a water molecule in both variants is revealed here through a set of different spectroscopic techniques. Previous studies had shown that heme release and uptake processes occur via intermediate states characterized by a Tyr(75)-iron-bound form with open conformation of loop L1. Here, we demonstrate that these states do not naturally occur in the free protein but can only be driven by the interaction with the partner proteins.

Physicochemical Characterization, and Relaxometry Studies of Micro-Graphite Oxide, Graphene Nanoplatelets, and Nanoribbons

The chemistry of high-performance magnetic resonance imaging contrast agents remains an active area of research. In this work, we demonstrate that the potassium permanganate-based oxidative chemical procedures used to synthesize graphite oxide or graphene nanoparticles leads to the confinement (intercalation) of trace amounts of Mn2+ ions between the graphene sheets, and that these manganese intercalated graphitic and graphene structures show disparate structural, chemical and magnetic properties, and high relaxivity (up to 2 order) and distinctly different nuclear magnetic resonance dispersion profiles compared to paramagnetic chelate compounds. The results taken together with other published reports on confinement of paramagnetic metal ions within single-walled carbon nanotubes (a rolled up graphene sheet) show that confinement (encapsulation or intercalation) of paramagnetic metal ions within graphene sheets, and not the size, shape or architecture of the graphitic carbon particles is the key determinant for increasing relaxivity, and thus, identifies nano confinement of paramagnetic ions as novel general strategy to develop paramagnetic metal-ion graphitic-carbon complexes as high relaxivity MRI contrast agents.

Magnetic and relaxometric properties of Mn ferrites

We present the magnetic properties and the 1H nuclear magnetic resonance dispersion profiles of Mn-ferrites-based compounds, as possible novel contrast agents (CAs) for magnetic resonance imaging (MRI). The samples consist of nanoparticles (NPs) with the magnetic core made of Mn1+xFe2−xO4, obtained by the rapid decomposition of metalcarbonyl into a hot solvent containing an oxidizer and a coordinating surfactant; by this procedure, monodisperse capped NPs with different sizes have been obtained. We have performed structural and morphological investigation by x-ray powder diffraction and transmission electron microscopy techniques and SQUID magnetometry experiments to investigate the magnetic behaviour of the samples. As required for MRI applications using negative CAs, the samples are superparamagnetic at room temperature, having blocking temperatures in the range 14–80 K. The longitudinal r1 and transverse r2 nuclear relaxivities appear to vary strongly with the magnetic core size, their values being comparable to commercial compounds in the high-frequency range ν > 100 MHz. The experimental results suggest that our samples are suitable for high-frequency MRI imagers in general and in particular for the 3 T clinical imager, as indeed suggested by a recent report (Tromsdorf et al 2007 Nanoletters 7 2422).

NMRD of polyaniline-based conducting polymers

Nuclear magnetic resonance dispersion (NMRD) is a technique for measuring NMR relaxation times, which is commonly used to study dynamics in condensed matter. In this paper, we present NMRD profiles, for polyanilines doped with trifluoromethanesulfonic acid (TFSA), recorded as a function of temperature and dopant concentration. This work demonstrates that NMRD can be used to characterise the critical processes that determine the conductivity of the materials. The NMRD profile of the bulk polymer is sensitively dependent on the concentration of the dopant, while the response of the dopant is insensitive to concentration. Complete analysis of the NMRD profiles of these ICPs will give important information, including the rates of spin diffusion and of charge transport between dopant-rich domains.

Metabolic pathways of carcinogenic chromium.

The products of hexavalent chromium [Cr(VI)] reduction by glutathione (GSH) alone or in the presence of equimolar quantities of aspartate (Asp) and/or glutamate (Glu) and a chromium-containing material extracted from bovine liver were studied by ultraviolet-visible spectrum (UV-vis) studies, electrospray mass spectrometry (ES-MS), electron paramagnetic resonance (EPR), and nuclear magnetic resonance (NMR). Reduction of chromate by GSH was followed by UV-vis and NMR, revealing the formation of a paramagnetic complex in which GSH acts as a ligand. ES-MS and EPR measurements provided unequivocal evidence of a dimeric Cr(V)(2)GSH(2) species in which the two metal ions are bridged by the Gamma-Glu carboxylate. The analysis of the (1)H and (13)C shifts experienced by GSH protons and the values of paramagnetic contributions to proton spin-lattice relaxation rates provided a set of constraints for structural determination. The same experiments were repeated in the presence of an equimolar concentration of Asp, revealing the formation of a dimeric Cr(V) paramagnetic complex in which the two metals are now bridged by Asp. Nuclear magnetic resonance dispersion profiles show that water is not displaced by Asp and that the correlation time of this complex is slowed by the increased complexity. When Glu is also included in the solution in equimolar concentration to GSH and Asp, data are consistent with the formation of many mono- and dinuclear species, with the three ligands competing with each other. Finally, the spectroscopic investigation of the chromium-containing material extracted from bovine liver revealed the presence of a complicate mixture of Cr(IV) or Cr(V) complexes, among which some Cr(V)-GSH species are present alone or with other ligands in the metal coordination sphere.

Molecular dynamics simulations of MRI-relevant GdIII chelates: direct access to outer-sphere relaxivity.

The structure and dynamics of the surrounding water were studied through molecular dynamics (MD) simulations for several GdIII polyaminocarboxylate and polyaminophosphonate complexes in aqueous solution. The radial distribution functions (rdf) show that a few water molecules are bonded to the ligand through hydrogen bonds to hydrophilic groups such as carboxylates and phosphonates. Residence times are of the order of 20-25 ps for the polyaminocarboxylate and 56ps for the polyaminophosphonate chelates. No preferred orientation or bonding of water molecules is observed in the hydrophobic region of the anisotropic macrocyclic complexes. Our rdf allow calculation of the outer-sphere contribution to the nuclear magnetic resonance dispersion (NMRD) profiles using Freed's finite differences method, including electronic relaxation. The results show that the commonly used analytical force-free model is only an empirical relationship. When experimental outer-sphere NMRD profiles are available ([Gd(teta)]- and [Gd(dotp)]5-(teta=N,N',N",N"'-tetracarboxymethyl-1,4,8,11- tetraazacyclotetradecane; dotp = N,N',N",N"'-tetraphosphonatomethyl-1,4,7,10-tetraazacyclododecane) the calculated curves are in good agreement. In the case of [Gd(teta)]-, the comparison with the experimental NMRD profile has led us to predict a very fast electronic relaxation, which has been confirmed by the EPR spectrum.