Relationship between the longitudinal relaxation rates of water protons and of well defined paramagnetic centers at low temperature in hydrated vermiculite

A good agreement has been observed between the proton longitudinal relaxation rate in the two and one layer hydrate of the Na-Llano vermiculite, the location of the Fe³⁺ paramagnetic centers within the octahedral and tetrahedral layers of the lattice and the electronic longitudinal relaxation rate using the dipolar electronic—proton spin interaction. The water content influences noticeably the electronic longitudinal relaxation time.     

Monitoring dendrimer conformational transition using 19F and 1H2O NMR

The conformational transition of a fluorinated amphiphilic dendrimer is monitored by the ¹H signal from water, alongside the ¹⁹F signal from the dendrimer. High-field NMR data (chemical shift δ, self-diffusion coefficient D, longitudinal relaxation rate R₁, and transverse relaxation rate R₂) for both dendrimer (¹⁹F) and water (¹H) match each other in detecting the conformational transition. Among all parameters for both nuclei, the water proton transverse-relaxation rate R₂(¹H₂O) displays the highest relative scale of change upon conformational transition of the dendrimer. Hydrogen/deuterium-exchange mass spectrometry reveals that the compact form of the dendrimer has slower proton exchange with water than the extended form. This result suggests that the sensitivity of R₂(¹H₂O) toward dendrimer conformation originates, at least partially, from the difference in proton exchange efficiency between different dendrimer conformations. Finally, we also demonstrated that this conformational transition could be conveniently monitored using a low-field benchtop NMR spectrometer via R₂(¹H₂O). The ¹H₂O signal thus offers a simple way to monitor structural changes of macromolecules using benchtop time-domain NMR.     

Proton transfer in the 1,1-dinitroethane/n-dibutylamine complex

The ¹H NMR spectra of 1,1-dinitroethane/n-dibutylamine solutions in CCl₄ have been investigated. It is shown that two types of complexes, the CH … N hydrogen bond complex and the ion pair are present in the solution simultaneously, with slow exchange through proton transfer between them. The exchange rates, activation energy and enthalpy of proton transfer are determined. It can be concluded that the act of proton transfer from carbon to nitrogen and back is kinetically determined.     

Thermodynamic Stability and Physicochemical Characterization of Ligand (4S)‐4‐Benzyl‐3,6,10‐tris(carboxymethyl)‐3,6,10‐triazadodecanedioic Acid (H5[(S)‐4‐Bz‐ttda]) and Its Complexes Formed with Lanthanides,Calcium(II), Zinc(II), and Copper(II) Ions

A derivative of H₅ttda (=3,6,10‐tris(carboxymethyl)‐3,6,10‐triazadodecanedioic acid=N‐{2‐[bis(carboxymethyl)amino]ethyl}‐N‐{3‐[bis(carboxymethyl)amino]propyl}glycine), H₅[(S)‐4‐Bz‐ttda] (=(4S)‐4‐benzyl‐3,6,10‐tris(carboxymethyl)‐3,6,10‐triazadodecanedioic acid=N‐{(2S)‐2‐[bis(carboxymethyl)amino]‐3‐phenylpropyl}‐N‐{3‐[bis(carboxymethyl)amino]propyl}glycine; 1 ) carrying a benzyl group was synthesized and characterized. The stability constants of the complexes formed with Ca²⁺, Zn²⁺, Cu²⁺, and Gd³⁺ were determined by potentiometric methods at 25.0±0.1° and 0.1M ionic strength in Me₄NNO₃. The observed water proton relaxivity value of [Gd{(S)‐4‐Bz‐ttda}]²⁻ was constant with respect to pH changes over the range pH 4.5–12.0. From the ¹⁷O‐NMR chemical shift of H₂O induced by [Dy{(S)‐4‐Bz‐ttda}]²⁻ at pH 6.80, the presence of 0.9 inner‐sphere water molecules was deduced. The water proton spin‐lattice relaxation rate for [Gd{(S)‐4‐Bz‐ttda}]²⁻ at 37.0±0.1° and 20 MHz was 4.90±0.05 mM ⁻¹ s⁻¹. The EPR transverse electronic relaxation rate and ¹⁷O‐NMR transverse‐relaxation time for the exchange lifetime of the coordinated H₂O molecule (τ_M), and ²H‐NMR longitudinal‐relaxation rate of the deuterated diamagnetic lanthanum complex for the rotational correlation time (τ_R) were thoroughly investigated, and the results were compared with those previously reported for the other lanthanide(III) complexes. The exchange lifetime (τ_M) for [Gd{(S)‐4‐Bz‐ttda}]²⁻ (2.3±1.3 ns) was significantly shorter than that of the [Gd(dtpa)(H₂O)]²⁻ complex (dtpa=diethylenetriaminepentaacetic acid). The rotational correlation time τ_R for [Gd{(S)‐4‐Bz‐ttda}]²⁻ (70±6 ps) was slightly longer than that of the [Gd(dtpa)(H₂O)]²⁻ complex. The marked increase of relaxivity of [Gd{(S)‐4‐Bz‐ttda}]²⁻ mainly resulted from its longer rotational time rather than from its fast water‐exchange rate. The noncovalent interaction between human serum albumin (HSA) and the [Gd{(S)‐4‐Bz‐ttda}]²⁻ complex containing the hydrophobic substituent was investigated by measuring the solvent proton relaxation rate of the aqueous solutions. The association constant (K_A) was less than 100 M ⁻¹, indicating a weaker interaction of [Gd{(S)‐4‐Bz‐ttda}]²⁻ with HSA.     

A study of the proton exchange in tissue water by spin relaxation in the rotating frame

The exchange rate of the water protons in mouse tissues was determined for the first time. The process was studied by proton spin relaxation in the rotating frame. The exchange correlation time was found to be ≈5 × 10^?6 sec. The actual residence time of a water proton on one water molecule in tissue was estimated to be ≈ 10^?6 sec. It is shown that because of the fast exchange the estimate (≈10%) of the amount of ordered water is too low.     

An NMR relaxation study of hydrogen exchange and its deuterium isotope effects in aqueous carboxylic acid solutions

Exchange-rate measurements of water protons and deuterons in aqueous solutions of acetic, malonic and glutaric acid by the NMR T₂ Carr-Purcell method, employing oxygen-17-enriched water, are reported. In contrast to previous results on acetic-acid solutions, intermolecular proton exchange via solvent between COOH and COO^? groups is found to contribute considerably to the exchange rate for all three acids investigated. The rate constants necessary for the calculation of the proton residence time in the COOH groups have been determined. Observed deuterium isotope effects on the rate constants for hydrogen-ion and acetic-acid-catalyzed exchange are discussed in terms of fractionation-factor theory.     

Spin-echo NMR studies of chemical exchange in cyclohexane,dioxane and water

Prevously derived equations for NMR chemical-exchange effects are used in proton spin-echo studies at 60 and 90 MHz of the chair-to-chair isomerisation of cyclohexane, dioxane and proton chemical exchange of water. The isomerisation rates are found to be 2.5 × 10⁶ and 1.8 × 10⁶ for cyclohexane and dioxane respectively and the proton exchange rate in water is found to be 1.9 × 10⁶s^?1. The rates are compared with the results of several previous studies at low fields.     

Temperature dependence of the proton exchange time in pure water by NMR

The temperature dependence of the proton spin-spin relaxation rate 1/T₃ on 180° pulse spacing (Meiboom dispersion) was measured for pure water enriched at 4% ¹⁷O to obtain the proton exchange time. At 58°C, the dispersion of the proton spin-lattice relaxation in the rotating frame (T_1ρ) was shown to be explained by a comparable proton exchange time.     

Oxidative Conversion of a Europium(II)‐Based T1 Agent into a Europium(III)‐Based paraCEST Agent that can be Detected In Vivo by Magnetic Resonance Imaging

The Eu^II complex of 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA) tetra(glycinate) has a higher reduction potential than most Eu^II chelates reported to date. The reduced Eu^II form acts as an efficient water proton T₁ relaxation reagent, while the Eu^III form acts as a water‐based chemical exchange saturation transfer (CEST) agent. The complex has extremely fast water exchange rate. Oxidation to the corresponding Eu^III complex yields a well‐defined signal from the paraCEST agent. The time course of oxidation was studied in vitro and in vivo by T₁‐weighted and CEST imaging.     

A morphological interpretation of water chemical exchange and mobility in cellulose materials derived from proton NMR T2 relaxation

Proton T₂ relaxation times of water in cellulosic fibres have been interpreted using a 3-term average model. Motional and chemical exchange contributions to relaxation show opposing temperature behaviour, enabling the use of Arrhenius analysis to determine proton exchange rates and water rotational correlation times. Both parameters vary dramatically with extent of hydration, with chemical exchange dominating relaxation at saturated water contents. Interpretations are based on a morphological model with two types of accessible cellulose, at void surfaces and internally within the cellulose phase. In native cellulose fibres, the presence of crystalline fibrils with low internal accessibility leads to rapid proton exchange at low moisture contents. Regenerated cellulose fibres typically have lower crystallinity and higher internal accessibility, which results in slower exchange as result of migration of water between void and internal environments. Exchange behaviour in regenerated fibres is highly dependent on structural organisation, which depends on the manufacturing process.     

Application of quadrupolar 131Xe-NMR relaxation to the study of macromolecular systems

¹³¹Xe-NMR longitudinal relaxation rates have been measured by the inversion recovery method for xenon in presence of lecithin vesicles or a small protein charybdotoxin. The transverse relaxation rates in the same spectra have been obtained by spectral deconvolution. The results show that xenon in lecithin vesicles is in a rapid exchange between free and bound sites and that averaging of the electric-field gradient at the Xe nucleus is a two-step process. From these results, estimates have been obtained for the parameters entering the ¹³¹Xe quadrupolar interaction. © 1996 John Wiley & Sons, Inc.     

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

¹H 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. 1 MHz, 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.     

Interaction between amphiphiles and water molecules in concentrated bilayer aqueous colloids

Interaction between amphiphiles and water molecules in micelle or bilayer structure has been investigated using aqueous colloids of various amphiphiles through the rheological data and the spin-lattice relaxation timeT ₁ of the proton of water molecule.T ₁ of the water proton has been measured by the inversion recovery method and determined as a single exponential relaxation process.The chemical shift of the water proton is almost independent of the amphiphilic concentration; however, it shifts toward a higher magnetic field with increasing temperature in a way similar to that in pure water and in the amphiphilic aqueous systems. These facts mean that there is no significant difference in the magnetic field environment of the water protons in these systems.The water molecule is not necessarily bound in the fully developed micelle or bilayer (rod-like or lamella) structure which induces the high viscosity or high rigidity of the colloidal system. On the other hand, the water molecule is bound in the micelle colloids of amphoteric amphiphiles or amphiphiles whose molecular assembly creates a relatively strong electrostatic field. The activation entropy of the bound water is negative and this suggests that water molecules assume some ordered structure in the bound state.     

Studies in nuclear magnetic resonance—IX. Rotational barriers in substituted N,N-dimethylbenzamides

The barriers to rotation about the C? N bond in eighteen substituted N,N-dimethylbenzamides have been determined by complete line shape analysis of the NMR spectra of the N,N-dimethyl protons. The barriers have been correlated with the substituent constants σ and σ⁺. It has been shown that polar solvents increase the barrier in N,N-dimethylbenzamide. Acid catalysis of rotation about the amide C? N bond in N-(p-N,N-dimethylcarboxamidobenzyl)-pyridinium bromide has been investigated. ¹⁸O exchange studies show that catalysis is due to N-protonation rather than the formation of a tetrahedral intermediate. The rate of rotation is a function of the Hammett acidity function, H₀, and the water activity, and it is shown that proton exchange between the N- and O-protonated species involves the intermediacy of a water molecule. The differences in chemical shifts for the non-equivalent N, N-dimethyl groups of the benzamides are also a function of the substituents. Possible explanations of this phenomenon are discussed.     

Proton exchange and protonation of substituted oxadiazoles in trifluoroacetic acid

The rates of NH? COOH proton exchange between 5-amino-( 1a ) and 5-N-methylamino-( 1b )3-[2-(5′-nitro-2′-furyl)vinyl]-1,2,4-oxadiazoles and trifluoroacetic acid (TFA) have been measured by NMR spectroscopy. The values of the first-order rate constant and thermodynamic parameters for 1a and 1b , respectively, are: k_app (sec^?1) = 820 and 40 (50°C), ΔF (kcal/mole) = 14·7 and 16·5, ΔH^# (kcal/mole) = 17·3 and 24·3 and ΔS^# (e.u.) = 17 and 34. The comparison of rate constants indicates that after correction for proton equivalency proton exchange in 1a is faster than in 1b by a factor of ten. The presence of an NH₂ proton resonance ( 1a ) and an N-methyl doublet (J = 5·0 Hz) between 0 and 30° ( 1b ) suggests that 1a and 1b are present as amines and not as imines in TFA.     

Water penetration in nylon 6,6: Absorption,desorption, and exchange studied by NMR microscopy

The uptake of water by nylon 6,6 [42DB Adipure (trade name of Dupont Canada Inc.)] at 100°C has been monitored by a combination of one-dimensional proton NMR spectroscopy, relaxation time (T₁ and T₂) measurements and proton microscopic NMR imaging techniques. The relaxation times of the water absorbed into the nylon matrix are very short at room temperature, (T₂ < 1 ms and T₁ ≈ 1 s) indicating that the water is located in a highly restricted environment and suggesting that strong interactions exist between the absorbed water and the polymer. The diffusion profiles measured at room temperature indicate that the diffusion of water into nylon 6,6 at 100°C is Case I Fickian diffusion. The spatial dependence of the T₂ relaxation time constant and its variation with the water content was also examined. The results reveal that both T₂ and T₂^* decrease toward the center of the sample in samples that have a concentration gradient of sorbed water. In fully saturated samples, no spatial dependence was observed. The overall values of T₂ and T₂^* are also observed to increase as a function of exposure time. An evaluation of the desorption process at room temperature and at 100°C was performed. A continuous, exponentially decreasing solvent profile was observed for the desorption process which again indicates Case I Fickian kinetics. The exchange process of external bulk and atmospheric water with deuterium oxide (D₂O) saturated nylon rods has also been studied using the microscopic imaging technique. © 1993 John Wiley & Sons, Inc.     

Lanthanide‐Based T2ex and CEST Complexes Provide Insights into the Design of pH Sensitive MRI Agents

The CEST and T₁ /T₂ relaxation properties of a series of Eu³⁺ and Dy³⁺ DOTA‐tetraamide complexes with four appended primary amine groups are measured as a function of pH. The CEST signals in the Eu³⁺ complexes show a strong CEST signal after the pH was reduced from 8 to 5. The opposite trend was observed for the Dy³⁺ complexes where the r_2ex of bulk water protons increased dramatically from ca. 1.5 mm ⁻¹ s⁻¹ to 13 mm ⁻¹ s⁻¹ between pH 5 and 9 while r₁ remained unchanged. A fit of the CEST data (Eu³⁺ complexes) to Bloch theory and the T_2ex data (Dy³⁺ complexes) to Swift–Connick theory provided the proton‐exchange rates as a function of pH. These data showed that the four amine groups contribute significantly to proton‐catalyzed exchange of the Ln³⁺‐bound water protons even though their pK _a’s are much higher than the observed CEST or T_2ex effects. This demonstrated the utility of using appended acidic/basic groups to catalyze prototropic exchange for imaging tissue pH by MRI.     

1H NMR Studies of Hydroxy Protons of ASN- and Ser-Linked Disaccharides in Aqueous Solution

ABSTRACT

The hydroxy protons of β-D-GlcpNAc-(1→4)-β-D-GlcpNAc, β-D-GlcpNAc-(1→4)-β-D-GlcpNAc-N-Asn, β-D-Galp-(1→3)-α-D-GalpNAc-O-Me and of β-D-Galp-(1→3)-α-D-GalpNAc-O-Ser in aqueous solution have been investigated using ¹H NMR spectroscopy. The chemical shifts, coupling constants, temperature coefficients, exchange rates and NOEs have been measured. The O(3)H proton of β-D-GlcpNAc-(1→4)-β-D-GlcpNAc and β-D-GlcpNAc-(1→4)-β-D-GlcpNAc-N-Asn, and the O(2')H proton of β-D-Galp-(1→3)-α-D-GalpNAc and β-D-Galp-(1→3)-α-D-GalpNAc-O-Ser have values which differ significantly from the other hydroxy protons. Both these hydroxy protons are shielded when compared to those of the corresponding monosaccharide methyl glycosides. This shielding is attributed to the proximity of these protons to the O(5') oxygen and to the 2-acetamido group, respectively. In β-D-GlcpNAc-(1→4)-β-D-GlcpNAc and β-D-GlcpNAc-(1→4)-β-D-GlcpNAc-N-Asn, the O(3)H proton has restricted conformational freedom with a preferred orientation towards the O(5') oxygen, and is protected from exchange with the bulk water through a weak hydrogen bond interaction with O(5'). In β-D-Galp-(1→3)-α-D-GalpNAc-O-Me and β-D-Galp-(1→3)-α-D-GalpNAc-O-Ser, the O(2')H is protected from exchange with the bulk water by the 2-acetamido group. The conformations of the disaccharides are not affected by the amino acid, and no interaction in terms of hydrogen bonding between the sugars and the amino acid residue could be observed.     

Interaction between Na+ and polymer in aqueous solution of sodium salts of poly(2-hydroxyethyl methacrylate-co-methacrylic acid) studied by 23Na-NMR

The interaction between Na⁺ and polymer was studied by ²³Na-NMR for the aqueous solution of P(HEMA-co-MAANa), sodium salt of poly(2-hydroxyethyl methacrylate-co-methacrylic acid), as a function of the polymer concentration, charge density of the polymer chain, and temperature. The NMR line width of ²³Na-NMR in 1% (w/v) aqueous solution of the P(HEMA-co-MAANa) narrowed with increasing temperature due to the rapid exchange of Na⁺ between free and polymer-bound states with a rate of exchange exceeding the quadrupolar relaxation rate in the latter state. At high concentrations of the polymer above 1.0% (w/v) at 298 K, the ²³Na-NMR relaxation fits for a single Lorentzian due to the rapid exchange between two Na⁺ states. However, it follows a biexponential decay of magnetization in dilute solutions of polymer. The biexponential decay character of relaxation increased with the increase of the fraction of the MAANa monomer unit on the polymer chain. This feature of ²³Na-NMR relaxation was used to deduce the correlation time (τ_c), the degree of binding (p_B), and the quadrupole coupling constants (X) of the polymer-bound counterion. The χ and τ_c values show that the mobilities of the polymer chain are correlated with the motion of Na⁺ in aqueous solution of the polymer and there is a small degree of the specific binding between COO^? and Na⁺. No evidence in support of the intramolecular conformational change by the charge density variation in P(HEMA-co-MAANa) was obtained. © 1993 John Wiley & Sons, Inc.     

23Na NMR in urethane cross-linked polyether solid polymer electrolytes

Sodium triflate/polyether urethane polymer electrolytes ranging in concentration from 0.05 molal to 1.75 molal have been investigated via ²³Na static solid-state NMR. Room temperature spectra and spin lattice relaxation times were consistent with a single narrow resonance indicating the presence of only mobile ionic species. The concentration and temperature dependence of relaxation times, chemical shifts, and linewidth have been investigated. The results suggest either a single species or rapid exchange between a number of species (even at temperatures below the glass transition temperature, T_g). The linewidth decreases with increasing concentration of ions and remains temperature independent below T_g. Below T_g a maximum quadrupolar interaction constant of 2 MHz is calculated. The addition of plasticizer to the polymer electrolyte causes significant chemical shift changes that depend on the solvent donicity of the plasticizer. The linewidth and T₁ relaxation times also depend on the T_g of the plasticized systems. Previous ²³Na NMR literature results are reviewed and qualitative models developed to account for the variation in results. © 1994 John Wiley & Sons, Inc.