1H and 13C n.m.r. Conformational Analysis of Adrenergic Drugs. Part 2. N-Isopropyl-N- {3-[4(4-Methoxybenzoylamino)Phenoxy]-2-Hydroxypropyl} Ammonium Chloride,a New β1-Blocking Agent

Abstract

Dynamic and structural features of N-Isopropyl-N- {3-[4(4-Methoxybenzoylamino)Phenoxy]-2-Hydroxypropyl} Ammonium Chloride in [²H₆]DMSO were investigated by measuring ¹³C and ¹H spin-lattice relaxation rates and ¹³C- {¹H} and ¹H- {¹H} n.O.e. Correlation times for main and internal reorientational motions were interpreted in terms of internal rotation around the two planal axes. Selective and double-selective ¹H spin-lattice relaxation rates were measured, wherefrom relevant proton-proton intramolecular distances were calculated. It was shown that the β₁? blocking agent assumes a preferred conformation where extensive intramolecular H-bonding prevents segmental motion along the quaternary ammonium sidechain.     

13C NMR Study of the Natural Glycosides Vicine and Convicine

¹³C NMR parameters have been obtained for vicine and convicine in DMSO, D₂O/DMSO and D₂O. Complete assignment of the spectra has been achieved. Interpretation of spin-lattice relaxation rates and heteronu-clear NOES has yielded evidence of intramolecular structuring in the case of vicine and not in that of ronvirine and also of a complex network of solute-solvent interactions.     

An NMR study of the origin of dioxygen-induced spin-lattice relaxation enhancement and chemical shift perturbation

Due to its depth-dependent solubility, oxygen exerts paramagnetic effects which become progressively greater toward the hydrophobic interior of micelles, and lipid bilayer membranes. This paramagnetic gradient, which is manifested as contact shift perturbations (19F and 13C NMR) and spin-lattice relaxation enhancement (19F and 1H NMR), has been shown to be useful for precisely determining immersion depth, membrane protein secondary structure, and overall topology of membrane proteins. We have investigated the influence of oxygen on 19F and 13C NMR spectra and spin-lattice relaxation rates of a semiperfluorinated detergent, (8,8,8)-trifluoro (3,3,4,4,5,5,6,6,7,7)-difluoro octylmaltoside (TFOM) in a model membrane system, to determine the dominant paramagnetic spin-lattice relaxation and shift-perturbation mechanism. Based on the ratio of paramagnetic spin-lattice relaxation rates of 19F and directly bonded 13C nuclei, we conclude that the dominant relaxation mechanism must be dipolar. Furthermore, the temperature dependence of oxygen-induced chemical shift perturbations in 9F NMR spectra suggests a contact interaction is the dominant shift mechanism. The respective hyperfine coupling constants for 19F and 13C nuclei can then be estimated from the contact shifts <(deltav/v0)19F> and <(deltav/v0)13C>, allowing us to estimate the relative contribution of scalar and dipolar relaxation to 19F and 13C nuclei. We conclude that the contribution to spin-lattice relaxation from the oxygen induced paramagnetic scalar mechanism is negligible.     

Toward an Optimal Paramagnetic Relaxation Agent for 31P NMR Spectroscopy

The dynamics of the use of relaxation agents for ³¹P NMR spectroscopy were investigated. It was found that non-lability of the associated ligand is essential, in order for line broadening to be prevented. Thus, chelates were found to be most suitable. In addition, evidence was accumulated that indicates an outer sphere coordination is significant for effective reduction of spin-lattice relaxation times (T₁'s). Finally, the magnitude of the magnetic moment, as pertains to Gd⁺³ and Fe⁺³, was examined and related to effective reduction of T₁'s.     

Separation of Anisotropy and Exchange Broadening Using N CSA–N–H Dipole–Dipole Relaxation Cross-Correlation Experiments

Based on the measurement of cross-correlation rates between ¹⁵N CSA and ¹⁵N–¹H dipole–dipole relaxation we propose a procedure for separating exchange contributions to transverse relaxation rates (R₂ = 1/T₂) from effects caused by anisotropic rotational diffusion of the protein molecule. This approach determines the influence of anisotropy and chemical exchange processes independently and therefore circumvents difficulties associated with the currently standard use of T₁/T₂ ratios to determine the rotational diffusion tensor. We find from computer simulations that, in the presence of even small amounts of internal flexibility, fitting T₁/T₂ ratios tends to underestimate the anisotropy of overall tumbling. An additional problem exists when the N–H bond vector directions are not distributed homogeneously over the surface of a unit sphere, such as in helix bundles or β-sheets. Such a case was found in segment 4 of the gelation factor (ABP 120), an F-actin cross-linking protein, in which the diffusion tensor cannot be calculated from T₁/T₂ ratios. The ¹⁵N CSA tensor of the residues for this β-sheet protein was found to vary even within secondary structure elements. The use of a common value for the whole protein molecule therefore might be an oversimplification. Using our approach it is immediately apparent that no exchange broadening exists for segment 4 although strongly reduced T₂ relaxation times for several residues could be mistaken as indications for exchange processes.     

NMR STRUCTURAL INVESTIGATION OF THE BIOTIN-AVIDIN COMPLEX: A 13C NMR PARAMAGNETIC RELAXATION STUDY

The paramagnetic contributions to the spin-lattice relaxation rates of biotin ¹³C nuclei, induced by the presence in the water/DMSO solution of the TEMPOL nitroxide, have been analysed in the interaction with avidin. The paramagnetic relaxation data, obtained at different temperatures, indicate that the average solvent/spin-label exposure of biotin carbons is consistent with the conformational features previously observed for the complex in the crystal. The analysis of the paramagnetic perturbation profiles, derived from ¹³C spin lattice relaxation measurements, seems to be highly informative of the sterical aspects of interaction processes of large biopolymers with their ligands.     

Nuclear magnetic resonance study of the relaxation mechanisms of the Be, Al, and Si nuclei in Cr-doped Be3Al2Si6O18 crystals

The variations with temperature of the relaxation mechanisms of the ⁹Be, ²⁷Al, and ²⁹Si nuclei in emerald (Be₃Al₂Si₆O₁₈:Cr³⁺) single crystals were investigated by using a pulse NMR spectrometer. The values of the spin-lattice relaxation rates for the three nuclei are different, and these differences are attributed to the differences between their Larmor frequencies and their local nuclear environments. The relaxation rates of the ⁹Be and ²⁷Al nuclei undergo no abrupt changes within the temperature range 180-400 K, which indicates that there are no phase transitions within this temperature range. The spin-lattice relaxation rates of ⁹Be and ²⁷Al were found to be proportional to temperature. Therefore, the nuclear spin-lattice relaxation processes of these two nuclei proceed via single-phonon processes.     

Mössbauer Spectrometer with Novel Moving System and Resonant Detection of Gamma Rays

Temperature-dependent ⁵⁷Fe Mössbauer spectroscopy has been used to elucidate the hyperfine parameters and dynamical behavior of the metal atom in several organo-iron complexes which have one or more η⁵ P₅ ring structures as ligated groups. The spin-lattice relaxation of the (paramagnetic) one-electron oxidation products occurs on a time scale fast compared to τ_1/2 (ME) at temperatures in the range 85 < T < 320 K.     

Improved quantification of alite and belite in anhydrous Portland cements by Si MAS NMR: Effects of paramagnetic ions

The applicability, reliability, and repeatability of ²⁹Si MAS NMR for determination of the quantities of alite (Ca₃SiO₅) and belite (Ca₂SiO₄) in anhydrous Portland cement was investigated in detail for 11 commercial Portland cements and the results compared with phase quantifications based on powder X-ray diffraction combined with Rietveld analysis and with Taylor–Bogue calculations. The effects from paramagnetic ions (Fe³⁺) on the spinning sideband intensities, originating from dipolar couplings between ²⁹Si and the spins of the paramagnetic electrons, were considered and analyzed in spectra recorded at four magnetic fields (4.7–14.1 T) and this has led to an improved quantification of alite and belite from ²⁹Si MAS NMR spectra recorded at “high” spinning speeds of ν_R=12.0–13.0 kHz using 4 or 5 mm rotors. Furthermore, the impact of Fe³⁺ ions on the spin-lattice relaxation was studied by inversion-recovery experiments and it was found that the relaxation is overwhelmingly dominated by the Fe³⁺ ions incorporated as guest-ions in alite and belite rather than the Fe³⁺ sites present in the intimately mixed ferrite phase (Ca₂Al_xFe_2−xO₅).     

1H and 13C NMR Conformational Analysis of Adrenergic Drugs. III. Dichloroisoproterenol,A Nonselective β-Blocking Agent

¹³C and ¹H NMR parameters were measured for dichloroisoproterenol in solution. Spin-lattice relaxation rates, nuclear Overhauser effects and J couplings were determined and compared to those obtained from isoproterenol. The t rotamer was shown to occur with a much higher probability than the two g rotamers. Dynamics in solution were interpreted in terms of a nearly isotropic motion of an extended molecular backbone. Some interesting differences were given evidence between the ‘preferred’ conformations in solution of dichloroisoproterenol and isoproterenol.     

嵌段共聚物溶致液晶相中水的2H-NMR动力学分析

采用D₂O 的²H-NMR线型和弛豫分析了PEO-PPO-PEO/D₂O/对二甲苯体系的层状和六角液晶相的动力学行为. 通过实验测得了两个不同体系的自旋 晶格弛豫时间T₁、自旋-自旋弛豫时间T₂和²H-NMR 谱. ²H-NMR 谱均为具有四极劈裂的粉末谱线型，且在谱图的中心，β_LD=54.7°时存在一个倒峰. 倒峰的出现直接表明引起体系中弛豫的主要动力学过程处于极窄化区域. 采用NMR弛豫模型，通过调节动力学参数，使理论模拟的²H-NMR谱、弛豫时间、倒峰的大小与实验的对应量相吻合，求得了体系的动力学参数.     

19F nuclear spin relaxation and spin diffusion effects in the single-ion magnet LiYF4:Ho3+

Temperature and magnetic field dependences of the ¹⁹F nuclear spin-lattice relaxation in a single crystal of LiYF₄ doped with holmium are described by an approach based on a detailed consideration of the magnetic dipole-dipole interactions between nuclei and impurity paramagnetic ions and nuclear spin diffusion processes. The observed non-exponential long time recovery of the nuclear magnetization after saturation at intermediate temperatures is in agreement with predictions of the spin-diffusion theory in a case of the diffusion limited relaxation. At avoided level crossings in the spectrum of electron-nuclear states of Ho^{3 +} ions, rates of nuclear spin-lattice relaxation increase due to quasi-resonant energy exchange between nuclei and paramagnetic ions in contrast to the predominant role played by electronic cross-relaxation processes in the low-frequency ac-susceptibility.     

Dynamical structure of α-Ag0.99Cu0.01I crystal by Cu NMR chemical shift, spin-lattice relaxation time and molecular dynamics simulation

Solid ⁶³Cu NMR and Molecular Dynamics (MD) methods have been used to investigate the dynamical structure of Ag_0.99Cu_0.01I crystal, through the viewpoint of the chemical shift and the spin-lattice relaxation. In the superionic phase (α-phase), we obtained the temperature variation of the chemical shift as −0.2 ppm/K, and the activation energy of the Cu⁺ ion diffusion as 11 kJ/mol. The temperature dependence of the chemical shift was explained by the calculated chemical shielding surface based on ab initio MO calculation, and by the probability density of Cu⁺ ion estimated by MD simulation. The spin-lattice relaxation was also analyzed by using the MD method in which we assumed two jumping models as the diffusion process of the mobile cations. It is concluded that the temperature dependence of the chemical shift is dominated by the shielding in the vicinity of the 24(h) site, and the observed activation energy is due to the diffusion process of the mobile cations jumping from the 6(b) intrasub-lattice to the nearest-neighbor 6(b) sub-lattice.     

A study of molecular motion and Raman processes in K3H(SO4)2 and KHSO4 single crystals by observation of H and K spin-lattice relaxation

The spin-lattice relaxation rates for ¹H and ³⁹K nuclei in K₃H(SO₄)₂ and KHSO₄ single crystals, which are potential candidate materials for use in fuel cells, were determined as a function of temperature. The spin-lattice relaxation recovery of ¹H can be represented for both crystals with a single exponential function, but cannot be represented by the Bloembergen-Purcell-Pound (BPP) function, so is not related to HSO₄ motion. The recovery traces of ³⁹K, which predominantly undergoes quadrupole relaxation, can be represented by a linear combination of two exponential functions. The temperature dependences of the relaxation rates for ³⁹K can be described with a simple power law T₁⁻¹=αT². The spin-lattice relaxation rates for the ³⁹K nucleus in K₃H(SO₄)₂ and KHSO₄ crystals are in accordance with a Raman process dominated by a phonon mechanism.     

Solid-state NMR investigations of Si-29 and N-15 enriched silicon nitride

We compare ²⁹Si magic-angle spinning (MAS) nuclear magnetic resonance (NMR) spectra from the two modifications of silicon nitride, α-Si₃N₄ and β-Si₃N₄, with that of a fully (²⁹Si, ¹⁵N)-enriched sample ²⁹Si₃¹⁵N₄, as well as ¹⁵N NMR spectra of Si₃¹⁵N₄ (having ²⁹Si at natural abundance) and ²⁹Si₃¹⁵N₄. We show that the ¹⁵N NMR peak-widths from the latter are dominated by J(²⁹Si–¹⁵N) through-bond interactions, leading to significantly broader NMR signals compared to those of Si₃¹⁵N₄. By fitting calculated ²⁹Si NMR spectra to experimental ones, we obtained an estimated coupling constant J(²⁹Si–¹⁵N) of 20 Hz. We provide ²⁹Si spin-lattice (T₁) relaxation data for the ²⁹Si₃¹⁵N₄ sample and chemical shift anisotropy results for the ²⁹Si site of β-Si₃N₄. Various factors potentially contributing to the ²⁹Si and ¹⁵N NMR peak-widths of the various silicon nitride specimens are discussed. We also provide powder X-ray diffraction (XRD) and mass spectrometry data of the samples.     

13C NMR Chemical Shift of β-Alkoxyvinylketones: II. Empirical Substituent Effects in β-Aryl-β-Methoxyvinyltrihalomethylketones

Evaluation by empirically derived equations for the substituent effect (α,β,γ,δ) on the ¹³C NMR chemical shifts for C-1, C-2, C-3 and C-4 in β-aryl-β-methoxyvinylhalomethylketones 1a-g to 2a-g [R³C(O)-CH=C(Ar)-OMe, where R³ = CCl₃, CF₃ and Ar = p-YC₆H₄ (Y = H, Me, MeO, F, Cl, Br, NO₂)], taking as reference the β-ethoxyvinyltrichloromethylketone (3), is reported. From the calculated values for the α,β,γ,δ effects for each substituent it was possible to estimate the chemical shift of each carbon of the compounds 1,2. The ¹³C chemical shifts of the C-1, C-2, C-3, C-4 of these compounds, can be estimated with good to rasoable precision: 84% of the calculated chemical shifts are found to be within ±1.0ppm, and 100% are found to be within ±1.5ppm. The Y-Effects on C-3 and C-4 are compared with carbon charge densities (qr).     

Al nuclear magnetic resonance study of synthetic and natural corundum (α-Al2O3) Some experimental aspects of quantitative Al nuclear magnetic resonance spectroscopy

The ²⁷Al nuclear magnetic resonance (NMR) response of a series of natural and synthetic corundum (α-Al₂O₃) samples is studied quantitatively by short-pulse excitation and frequency-stepped adiabatic half-passage (FSAHP). Using on- and off-resonance nutation NMR, it was established that the quadrupole coupling parameters of visible Al is identical in all samples. Remarkably, the relaxation behavior for the aluminum is very different in the various samples and has a marked effect on the quantitative response. In natural corundum samples the ²⁷Al spin-lattice relaxation is very efficient as these samples contain paramagnetic impurities. As a result, however, the full signal could not be recovered, which is attributed to relaxation broadening of spins in the vicinity of these impurities. In synthetic samples, containing no impurities, the full signal could be recovered, although the relaxation behaviour appeared to depend strongly on the preparation method. We observed differences in the spin-lattice relaxation by a factor 20; the longest T₁ was observed in a crushed single crystal. This implies that α-Al₂O₃ can only be used as a standard in quantitative analyses if it has been characterized thoroughly. Furthermore, the effective relaxation behaviour for different types of excitation is studied. Finally, a method to measure the spin-lattice relaxation of half-integer quadrupole nuclei is introduced, using a frequency-stepped adiabatic passage (FSAP) to invert the spin system.     

NMR and quantum chemistry study of mesoscopic structuring in 3-methylpyridine/water/NaBr mixture in the vicinity of the phase separation boundary

²³Na and ⁸¹Br NMR spin-lattice relaxation times and signal half widths (Δ_1/2) have been measured in 3-methylpyridine (3MP)/H₂O/NaBr mixture along T?=?294 and 301 K isotherms gradually increasing the mass fractions of salt (X) up to the phase separation boundary. The extreme narrowing condition and thus 1/T ₁?=?1/T ₂?=?πΔ _1/2 was found to be valid in all cases. Discontinuous changes in slope of 1/T _1,2?=?f(X) were detected, and then corresponding points on the phase diagram (X, T) were attributed to the borderline between the molecular-ionic solution and the area of enhanced mesoscopic structuring. A very strong relaxation effect was observed for ⁸¹Br nuclei reaching relaxation rates of 14,000 s^–1. ²³Na and ⁸¹Br NMR relaxation data together with calculations of quantum chemistry model of electrical field gradient tensor evidence the migration of 3-methylpyridinium at increasing X from the anions hydration shells towards cations. An interchange from migration to steady distribution regimes is observed for anions and vice versa for cations at the borderline of the structured phase.     

Effect of the frequency of intramolecular motions on the NMR relaxation in liquid state temperature regime

Equations for the spectral densities of complex motion of a spin pair undergoing internal motion and isotropic/anisotropic overall rotation have been considered. The fluctuations of the interproton distances, caused by internal motion, have been taken into account in the theoretical equations. A method allowing a distinction between the isotropic and the anisotropic overall rotation of molecules has been proposed. The effect of the activation parameters of internal motions (known from the solid state study) on the measured T ₁ relaxation of the ¹³C and ¹H–¹H cross-relaxation rates has been analysed for methyl-β-D-galactopyranoside in DMSO-d6 solution. The conformational trans-gauche jumps of the methylene group are not fast enough to affect the T ₁ value of carbon C6 in the liquid state temperatures regime. Only the methyl group rotation is a very fast internal motion. This motion influences the carbon C7 relaxation and methyl protons–anomeric proton cross-relaxation. The values of interatomic distances between anomeric H(C1) and H(C5) as well as the three methyl protons H(C7) have been calculated from the cross-relaxation rates. The distance H(C1)–H(C7) fluctuates due to the rotation of methyl group. The application of the ‘model-free approach’ to study molecular dynamics in solutions is discussed.     

Quadrupole relaxation enhancement and polarisation transfer in DMSO solution of [Bi(NO3)3(H2O)3]*18-crown-6 in solid state

ABSTRACT

¹H spin-lattice relaxation studies have been performed for pure [Bi(NO₃)₃(H₂O)₃]*18-crown-6 in powder and its solution in dimethyl sulfoxide (DMSO). The experiments have been carried out in the frequency range of 10?kHz–30?MHz and the temperature range of 240–277?K; at 277?K the solution is already frozen. The ¹H relaxation of pure [Bi(NO₃)₃(H₂O)₃]*18-crown-6 has been interpreted in terms of three dynamical processes. Quadrupole Relaxation Enhancement effects have been observed in the frozen DMSO solution of [Bi(NO₃)₃(H₂O)₃]*18-crown-6. The specific mechanisms of the ¹H spin-lattice relaxation enhancement have been discussed distinguishing between effects caused by time independent (residual) and fluctuating ¹H-²⁰⁹Bi dipole-dipole interactions.