Quantitative determination of mebeverine HCl by NMR chemical shift migration

Quantitative ¹H NMR spectroscopic methods are not frequently reported, but current NMR instrumentation allows ready access to such data. Mebeverine HCl is an attractive molecule for NMR spectroscopy teaching purposes as it possesses a variety of simple but significant functional groups; we fully assign its ¹H and ¹³C NMR spectra. Using mebeverine HCl, we show that concentration changes, in water as a solvent, can lead to significant changes in the ¹H chemical shifts of non-exchangeable aromatic protons and to a lesser extent to aromatic methoxy protons. An important observation is that different protons migrate to different extents as the concentration of the solute is varied, and thus the ¹H NMR spectra are concentration-dependent across a useful range. This chemical shift variation of selected protons was therefore analyzed and applied in the quantitative determination of mebeverine HCl in a medicine (Colofac IBS) formulated as a tablet. Self-association phenomena in water could account for these observed chemical shift migration effects as shown by determining the hydrodynamic radius from the modified form of the Stokes-Einstein equation, and thence the apparent hydrodynamic volume, V_H, for mebeverine HCl in D₂O solution which is 10-fold greater than that seen in either CDCl₃ or CD₃OD.     

In and F MAS NMR study of (NH4)3InF6 phases

This study presents for the first time an NMR spectroscopic characterization of the room and high temperature phases of (NH₄)₃InF₆ using ¹⁹F and ¹¹⁵In as probe nuclei. The reversible phase transition to the cubic phase at 353 K was followed by MAS NMR in situ. Static NMR experiments of the room temperature phase and MAS NMR experiments of the high temperature phase allowed the determination of the NMR parameters of both nuclei. Finally, the scalar In-F coupling, rarely observed in solid state NMR, is evidenced in both room and high temperature phases of (NH₄)₃InF₆, and measured in the high temperature phase.     

Synthesis and Spectroscopic Characterization of Silver(I) Complexes of Selenones

Silver(I) complexes of selenones, [LAgNO₃] and [AgL₂]NO₃ (where L is imidazolidine-2-selenone or diazinane-2-selenone and their derivatives) have been prepared and characterized by elemental analysis, IR and NMR (¹H, ¹³C and ¹⁰⁷Ag) spectroscopy. An upfield shift in the C=Se resonance of selenones in ¹³C NMR and a downfield shift in N-H resonance in ¹H NMR are consistent with selenium coordination to silver(I). In ¹⁰⁷Ag NMR, the AgNO₃signal is deshielded by 450-650 ppm on coordination to selenones. Greater upfield shifts in ¹³C NMR were observed for [LAgNO₃] compared to [AgL₂]NO₃complexes, whereas the opposite trend was observed for ¹H and¹⁰⁷Ag NMR chemical shifts.     

Modification Study of Aluminum sec-Butoxide by Acrylic Acid

A new way of modifying aluminum sec-butoxide (Al(OBu^s)₃) is proposed. This synthesis is carried out by reacting Al(OBu^s)₃ dissolved in tetrahydrofuran with an unsaturated acid, viz. acrylic acid.The structure evolution of Al(OBu^s)₃ with increasing acrylic acid amounts is investigated by infrared, ¹H NMR, ¹³ C NMR, and ²⁷Al NMR spectroscopies and viscosity measurements. Information obtained suggests that the exchange reaction occurring between butoxy groups and acrylate ligands is stopped for an acid/alkoxide molar ratio within the range 1.6–1.7. This value leads us to assume that the dominant trimeric species of precursor is preserved after modification. Moreover, ²⁷Al NMR analysis only reveals the presence of hexacoordinated Al sites in the structure of the modified Al(OBu^s)₃.Evidence of the acrylic acid reaction with sec-butanol released during the alkoxide modification is also proved by the infrared and ¹³ C NMR data. However the produced ester amount can be considered as negligible.     

Rotaxane Probes for the Detection of Hydrogen Peroxide by 129Xe HyperCEST NMR Spectroscopy

The development of sensitive and chemically selective MRI contrast agents is imperative for the early detection and diagnosis of many diseases. Conventional responsive contrast agents used in ¹H MRI are impaired by the high abundance of protons in the body. ¹²⁹Xe hyperCEST NMR/MRI comprises a highly sensitive complement to traditional ¹H MRI because of its ability to report specific chemical environments. To date, the scope of responsive ¹²⁹Xe NMR contrast agents lacks breadth in the specific detection of small molecules, which are often important markers of disease. Herein, we report the synthesis and characterization of a rotaxane‐based ¹²⁹Xe hyperCEST NMR contrast agent that can be turned on in response to H₂O₂, which is upregulated in several disease states. Added H₂O₂ was detected by ¹²⁹Xe hyperCEST NMR spectroscopy in the low micromolar range, as well as H₂O₂ produced by HEK 293T cells activated with tumor necrosis factor.     

1H AND 31P NMR Spectroscopy of Agrocinopine

The ¹H NMR data of agrocinopine in D₂O solution as extracted from standard 2D NMR experiments, along with 1D ³¹P and ¹³C NMR experiments allow to support the trisaccharide structure originally proposed on basis of comparative ¹³C NMR measurements.     

New hyperbranched carbosiloxane–carbosilane polymers with aromatic units in the backbone

New hyperbranched polymers based on a carbosiloxane–carbosilane skeleton with aromatic units in the backbone have been prepared via one-pot hydrosilylation reaction using HSi(Me)₂–O–CH₂–C₆H₄–OSiMe–(CH₂)₄(C₃H₅)₂ as a novel AB₂ monomer. These polymers are easy to prepare, have narrow polydispersity values and present allyl groups on the surface which can be used as synthetic platforms for the introduction of different terminal groups like amine groups through hydrosilylation reactions, opening the door to functionalized polymers. The polymerization process was monitored using real-time ¹H NMR spectroscopy and the resulting hyperbranched polymers were characterized using ¹H NMR, ¹³C NMR, ²⁹Si NMR and SEC/MALLS. The degree of branching in these polymers was determined by quantitative ²⁹Si NMR spectroscopy and found to be very close to the theoretical value of 0.50 for AB₂ systems. The hydrolytic degradation of these polymers in protic solvents has been studied by ²⁹Si NMR.     

Reactions of silicon-, germanium- and tin-containing carbene complexes of tungsten Ph3E-CW(OBu)3 (E=Si, Ge, Sn) with hydrogen chloride: crystal structures of carbene complexes Ph3E-CHWCl2(OBu)2 (E=Si, Ge)

The novel organosilicon, -germanium and -tin-containing carbene complexes of tungsten of the type Ph₃E-CHWCl₂(OBu^t)₂ (E=Si, Ge, Sn) have been prepared by the reaction of heteroelement-containing carbene complexes of tungsten Ph₃E-CW(OBu^t)₃ (E=Si, Ge, Sn) with hydrogen chloride. The tin-containing carbene complex was identified in solution by ¹H NMR spectroscopy. Silicon- and germanium-containing carbene complexes were isolated in high yields as crystalline solids and characterized by elemental analysis, IR, ¹H NMR, ¹³C NMR and ²⁹Si NMR spectroscopy and X-ray diffraction studies. The geometry of the W atoms in the compounds can be described as a distorted square pyramid.     

On the use of the Bayliss-McRae dispersion model in NMR solvent effects

The use of the Bayliss-McRae theory on the solvent induced electronic frequency shifts for NMR dispersion shifts is criticized. It is suggested that the NMR shifts should actually be proportional to the square of the Bayliss-McRae function. It is shown that the methane gas-to-liquid shifts in eleven halo-methanes as solvents are indeed proportional to this squared function; ?σ_m(CH₄) = 9.62 (n₂²?1)²/(2n₂²+1)² ppm, where n₂ is the refractive index of the solvent. The relation between this solvent factor and several existing continuum models for NMR medium shifts is discussed.     

Gold(I) Complexation with Trialkyl/Triaryl Phosphine Selenide Ligands

Abstract

A number of phosphine selenide ligands and their gold(I) complexes of general formula R₃P?Se?Au?X (where X is Cl^?, Br^? and CN^? and R = phenyl, cyclohexyl and tolyl) were prepared. The complexes were characterized by elemental analysis, IR and ³¹P NMR spectroscopic methods. In the IR spectra of all complexes a decrease in frequency of P?Se bond upon coordination was observed, indicating a decrease in P?Se bond order. ³¹P NMR showed that the electronegativity of the substituents is the most important factor determining the ³¹P NMR chemical shift. It was observed that phosphorus resonance is more downfield in alkyl substituted phosphine selenides, as compared to the aryl substituted ones. Ligand disproportionation in the complex Cy₃P?SeAuCN in solution to form [Au(CN)₂]^? and [(Cy₃P?Se)₂Au]⁺ was investigated by ¹³C and ¹⁵N NMR spectroscopy.     

The Silicides M4Si4 with M = Na,K, Rb,Cs, and Ba2Si4 – NMR Spectroscopy and Quantum Mechanical Calculations

The Zintl phases M₄Si₄ with M = Na, K, Rb, Cs, and Ba₂Si₄ feature a common structural unit, the Si₄^4– anion. The coordination of the anions by the cations varies significantly. This allows a systematic investigation of the bonding situation of the anions by ²⁹Si NMR spectroscopy. The compounds were characterized by powder X‐ray diffraction, differential thermal analysis, magnetic susceptibility measurements, ²³Na, ²⁹Si, ⁸⁷Rb, ¹³³Cs NMR spectroscopy, and quantum mechanical calculation of the NMR coupling parameter. The chemical bonding was investigated by quantum mechanical calculations of the electron localizability indicator (ELI). Synthesis of the compounds results for all of them in single phase material. A systematic increase of the isotropic ²⁹Si NMR signal shift with increasing atomic number of the cations is observed by NMR experiments and quantum mechanical calculation of the NMR coupling parameter. The agreement of experimental and theoretical results is very good allowing an unambiguous assignment of the NMR signals to the atomic sites. Quantum mechanical modelling of the NMR shift parameter indicates a dominant influence of the cations on the isotropic ²⁹Si NMR signal shift. In contrast to this a negligible influence of the geometry of the anions on the NMR signal shift is obtained by these model calculations. The origin of the systematic variation of the isotropic NMR signal shift is not yet clear although an influence of the charge transfer estimated by calculation using the QTAIM approach is indicated.     

Molecular motion in solid ammonia trimethylalane

Solid state ²H NMR has been used to study molecular motion in deuterated ammonia trimethylalane (CH₃)₃AlND₃. From analysis of the ²H NMR lineshape between 123 and 298 K, reorientation of the -ND₃ group about the molecular Al-N axis is shown to occur at a rate higher than 10⁸ s^-1, and simulation of partially relaxed ²H NMR lineshapes shows that the reorientation can be described as a 3-site 120° jump motion. From the temperature dependence of the ²H spin-lattice relaxation time, the activation energy for this motion is estimated to be 9.3±0.3 kJ mol^-1. There is no evidence from either ²H or ²⁷Al NMR data for any site-exchange between the sites occupied by the -ND₃ and -CH₃ groups. The anisotropy of the dynamics of (CH₃)₃AlND₃ indicates that the orientation of the Al-N bond is highly constrained, presumably by a strong interaction between the electric dipoles of neighboring molecules.     

A study of the hydrolysis of ZrF<Stack><Subscript>6</Subscript><Superscript>2−</Superscript></Stack> and the structure of intermediate hydrolysis products by <Superscript>19</Superscript>F and <Superscript>91</Superscript>Zr NMR in the 9.4 T field

The high-field ¹⁹F and ⁹¹Zr NMR method is used to study the hydrolysis and polycondensation of hexafluorozirconate ZrF₆²⁻ in aqueous and water-peroxide solutions. During hydrolysis in aqueous solutions only ZrF₆²⁻ and F⁻ ions were observed by NMR, however, in the water-peroxide medium, an intermediate product of hydrolysis ([F₅Zr-OO-ZrF₅]⁴⁻ dimer) was detected. The dimer structure is confirmed by ¹⁹F and ⁹¹Zr NMR. In high fields (¹⁹F NMR frequency > 200 MHz), the fluorine exchange between ZrF₆²⁻ and F⁻ is slow in the ¹⁹F NMR scale and has a multisite character.     

Substitution effects in the 15N NMR chemical shifts of heterocyclic azines evaluated at the GIAO‐DFT level

A systematic study of the accuracy factors for the computation of ¹⁵N NMR chemical shifts in comparison with available experiment in the series of 72 diverse heterocyclic azines substituted with a classical series of substituents (CH₃, F, Cl, Br, NH₂, OCH₃, SCH₃, COCH₃, CONH₂, COOH, and CN) providing marked electronic σ‐ and π‐electronic effects and strongly affecting ¹⁵N NMR chemical shifts is performed. The best computational scheme for heterocyclic azines at the DFT level was found to be KT3/pcS‐3//pc‐2 (IEF‐PCM). A vast amount of unknown ¹⁵N NMR chemical shifts was predicted using the best computational protocol for substituted heterocyclic azines, especially for trizine, tetrazine, and pentazine where experimental ¹⁵N NMR chemical shifts are almost totally unknown throughout the series. It was found that substitution effects in the classical series of substituents providing typical σ‐ and π‐electronic effects followed the expected trends, as derived from the correlations of experimental and calculated ¹⁵N NMR chemical shifts with Swain–Lupton's F and R constants.     

Laser-induced NMR shift of a paramagnetic system

Perturbation theory on optical ac Stark effect is applied to study the NMR spectroscopy in paramagnetic systems. Application of the circularly or linearly polarized optical field would lead to shifts in the NMR lines, which is proportional to the laser intensity and the induced polarizability tensors by hyperfine interaction. The induced shift for 193Ir NMR spectrum of [IrBrg]2- is expected to be of the order of 1-10 Hz as resonance is approached with light intensity 10 W·cm-2. For the supersonic molecular beam samples 193IrC, the laser-induced NMR shift is estimated to be as large as 1-10 MHz near resonance.     

Computational and dynamic NMR investigation of 2,2-dimesityl-1,1,1,3,3,3-hexamethyltrisilane

The structure and rotational barrier for the mesityl-silicon bond of 2,2-dimesityl-1,1,1,3,3,3-hexamethyltrisilane have been investigated by ¹H- and ¹³C-variable temperature nuclear magnetic resonance (NMR) as well as by density functional theory structural calculations. The calculations show that the lowest energy structure has C₂ symmetry with nonequivalent ortho methyl groups, consistent with the crystal structure and solution NMR. The nonequivalent ortho methyl groups exchange through a C_s transition state with a calculated relative free energy of 11.0 kcal mol⁻¹. The barrier for this rotation found by dynamic NMR is 13.4 ± 0.2 kcal mol⁻¹ at 298 K.     

Solid‐State NMR Investigations on the Amorphous Network of Precursor‐Derived Si2B2N5C4 Ceramics

Employing a multitude of modern solid state NMR techniques including ¹³C{¹⁵N}REDOR NMR, ¹H–¹³C CP NMR, ¹¹B MQMAS NMR spectroscopic experiments, the structural organization of Si₂B₂N₅C₄ ceramic has been studied. The experiments were executed on double isotope enriched (¹³C, ¹⁵N) and natural isotope abundance Si₂B₂N₅C₄ ceramics. The materials were synthesized by aminolysis and subsequent pyrolysis of intermediate pre‐ceramic polymers that were obtained from the single source precursor TSDE, 1‐(trichlorosilyl)‐1‐(dichloroboryl)ethane (Cl₃Si–CH(CH₃)–BCl₂). The result of the ¹³C{¹⁵N} REDOR NMR spectroscopic experiment shows that carbon atoms are incorporated into the network by bridging to nitrogen, which already occurs during the polymerization step. Furthermore, the combined results of ¹¹B NMR and ¹¹B MQMAS NMR indicate that boron atoms may also be connected to carbon in addition to nitrogen.     

<Superscript>1</Superscript>H and <Superscript>7</Superscript>Li NMR in defect cobaltite Li<Subscript>0.6</Subscript>CoO<Subscript>2</Subscript>

Within a temperature range of 120–330 K, ⁷Li NMR spectra in Li_0.6CoO₂ are obtained. It is shown that as the temperature increases, both smooth and stepwise variation of ⁷Li NMR contact shifts occurs. The observed effects are explained by the occupation of the excited levels of cobalt ions. The stepwise change of the resonance line width depending on the temperature is revealed. It is driven by the features of the diffusive motion of lithium ions. The calculation of the ¹H NMR line shape provides the determination of the ratio of one-, two-, and three-spin proton clusters in Li_0.6CoO₂·xH₂O.     

Permutational isomerization of caged polycyclic oxyphosphoranes

The reaction of 1-phospha-2,8,9-trioxaadamantane with hexafluoroacetone gives a crystal-line caged polycyclic pentaoxyphosphorane. The ambient temperature fourier transform ¹³C NMR spectrum of the phosphorane in CH₂Cl₂ solution, with proton noise-decoupling, shows one singlet for three equivalent methine carbons, and one singlet for three equivalent methylene carbons. Hence, the phosphorane undergoes a rapid permutational isomerization, which is confirmed by the observation of equivalency of the three methine protons and of the three groups of methylene protons in the ¹H NMR, and of equivalency of the four CF₃ groups in the ¹⁹F NMR. The variable temperature ¹⁹F NMR spectra in a vinyl chloride-CHFCl₂ solvent system disclose that the permutational isomerization of this phosphorane cannot be prevented even at ? 165°, although there is a progressive line-broadening indicative of a decrease in the exchange rate. The ³¹P NMR spectrum of the phosphorane has a signal at a higher magnetic field (?³¹P = +42·4 ppm) than H₃PO₄; the shift is nearly identical in CH₂Cl₂ and in the acidic (CF₃)₂CHOH. The remarkably low energy barrier (< ca 5 kcal/mole) for the permutational isomerization of a compound as constrained as the caged oxyphosphorane is attributed to: (1) A small deviation from the perfect trigonal bipyramidal configuration, which raises the ground state energy. (2) The existence of a barrier configuration which can accommodate the constrains of the caged molecule, and is therefore of relatively low energy. The barrier configuration is deduced from the turnstile rotation mechanism of permutational isomerization.     

Vinyl polymerization of norbornene catalyzed by 2‐Py‐amidine Ni(II) complex/methylaluminoxane systems

Two 2‐Py‐amidine ligands (2‐Py―NH―C(Ph)═N―Ar, Ar = 2,6‐Me₂C₆H₃ and 2,6‐ⁱPr₂C₆H₃) and the corresponding Ni(II) complexes ( 1 and 2 ) were synthesized and characterized using elemental analysis and FT‐IR, UV–visible, ¹H NMR and ¹³C NMR spectroscopies. X‐ray crystal structures indicate that the chelate ring conformation of the less bulky complex 1 is relatively planar compared with that of the bulky complex 2 . Paramagnetic ¹H NMR and ¹³C NMR studies show that, in solution, the time‐average structures of complexes 1 and 2 have mirror symmetry. Both complexes 1 and 2 were used as catalyst precursors for norbornene polymerization with methylaluminoxane as a co‐catalyst. The effects of Al/Ni ratio, temperature and structure of precursors on the catalytic performance were investigated. Copyright © 2014 John Wiley & Sons, Ltd.