Solid‐State NMR Studies of Pharmaceutical Systems

Abstract

High‐and low‐resolution solid‐state nuclear magnetic resonance (SSNMR) applications to the study of pharmaceuticals are reviewed. Examples are shown involving the use of mono‐and bidimensional SSNMR techniques based on different nuclear interactions and the measurement of several nuclear parameters, such as chemical shifts, line widths, and relaxation times (T₁, T₂, T_1ρ). The systems investigated include pure active pharmaceutical ingredients (APIs), substances used as drug excipients, and solid dispersions formed by APIs and excipients, up to final drug formulations. The most important aspects treated concern structural, dynamic, and morphological properties, and, in particular, identification, characterization, and quantitation of polymorphs and related forms, conformational and crystalline packing behavior, amorphous phase properties and stability, effects of drug processing, molecular motions, API‐excipient and excipient‐excipient chemical and physical interactions, and phase mixing in heterophasic systems.     

Studies on the Formation of β-Cyclodextrin/Alkylcobaloxime Inclusion Complexes by Using NMR Methods

Abstract

It has been established that alkylcobaloxime(R=i-C₄H₉, n-C₄H₉, n-C_sH₁₁, c-C₆H₁₁, PhCH₂) and β-cyclodextrin form a kind of 1: 1 inclusion complexes in aqueous solution by ¹H NMR spectroscopy. Ka and ?ΔG^θ were calculated according to chemical shift changes of different probe protons. The stability constant(Ka) has been found increasing in the order: PhCH₂ > n-C₅H₁₁ > c-C₆H₁₁ > i-C₄H₉ > n-C₄H₉.     

Triangle Geometry of the Qubit State in the Probability Representation Expressed in Terms of the Triada of Malevich’s Squares

We map the density matrix of the qubit (spin-1/2) state associated with the Bloch sphere and given in the tomographic probability representation onto vertices of a triangle determining Triada of Malevich’s squares. The three triangle vertices are located on three sides of another equilateral triangle with the sides equal to\( \sqrt{2} \). We demonstrate that the triangle vertices are in one-to-one correspondence with the points inside the Bloch sphere and show that the uncertainty relation for the three probabilities of spin projections +1/2 onto three orthogonal directions has the bound determined by the triangle area introduced. This bound is related to the sum of three Malevich’s square areas where the squares have sides coinciding with the sides of the triangle. We express any evolution of the qubit state as the motion of the three vertices of the triangle introduced and interpret the gates of qubit states as the semigroup symmetry of the Triada of Malevich’s squares. In view of the dynamical semigroup of the qubit-state evolution, we constructed nonlinear representation of the group U(2).     

Zero-Magnetic-Field Spin Splitting of Polaron‘s Ground State Energy Induced by Rashba Spin-Orbit Interaction

We study theoretically the ground state energy of a polaron near the interface of a polar-polar semiconductor by considering the Rashba spin-orbit (SO) coupling with the Lee-Low-Pines intermediate coupling method. Our numerical results show that the Rashba SO interaction originating from the inversion asymmetry in the heterostructure splits the ground state energy of the polaron. The electron arealdensity and vector dependence of the ratio of the SO interaction to the total ground state energy or other energy composition are obvious. One can see that even without any external magnetic field, the ground state energy can be split by the Rashba SO interaction, and this split is not a single but a complex one. Since the presents of the phonons, whose energy gives negative contribution to the polaron‘s,the spin-splitting states of the polaron are more stable than electron‘s.     

Spin splittings in the ν3 band of NO2

Spin splittings for several important atmospheric lines in the ν₃ band of NO₂ have been measured by diode laser. An improved spin-splitting program has been developed which takes into account the asymmetry effects in the lower K_a splittings. The measured spin splittings and the derived spin-rotational constants are reported in this study to a much higher accuracy than previously achieved.     

Characterization of Porous Materials by Magnetic Relaxometry in the Earth’s Field

In this paper, it is shown how free induction decay signals recorded in the Earth’s magnetic field from water protons confined in porous media can be used to derive transversal relaxation times (T ₂) and their distributions. After T ₂ determination of six sintered glass samples with various pore sizes, the common theoretical model can be fitted to the data set. The T ₂ distribution of water protons in a bimodal porous system is analyzed and compared to mercury porosimetry results. The implications for the calculation of pore sizes and pore size distributions of porous media by this method are discussed.     

Reaction between alkyl isocyanides and isopropylidene Meldrum’s acid in the presence of bidentate nucleophiles

Summary The reaction between alkyl isocyanides and isopropylidene Meldrum’s acid in the presence of 1,2-ethanediol leads to N ¹-(alkyl)-2-(5,7-dioxo-1,4-dioxepane-6-yl)-2-methylpropanamides. 1,3-Propanediol or 1,4-butanediol produce hydroxyalkyl 1-(tert-butyl)-4,4-dimethyl-2,5-dioxo-3-pyrrolidinecarboxylates. When the reaction was performed in the presence of catechol, bis(2-hydroxyphenyl) 2-[2-(tert-butylamino)-1,1-dimethyl-2-oxoethyl]malonate was obtained. 2-Aminophenols react with alkyl isocyanides in the presence of isopropylidene Meldrum’s acid to produce 1-alkyl-N ³-(2-hydroxyaryl)-4,4-dimethyl-2,5-dioxo-3-pyrrolidinecarboxamides in good yields.     

Development of the Earth’s Field NMR Spectrometer for Liquid Screening

Earth??s field nuclear magnetic resonance (NMR) can be used for non-destructive in-bottle liquid screening by evaluating the spin?Clattice relaxation times of protons in various liquids. An Earth??s field NMR apparatus has been developed and optimized to measure the spin?Clattice relaxation times of various liquids contained in 500?ml PET bottles. Two methods to generate 90-degree readout pulses using transient oscillating signals generated in a resonator are reported. The lower detection limit of pure water was 1?ml. The minimum measurable spin?Clattice relaxation time was 50?ms.     

First Experimental Synthesis of Mg Orthocarbonate by the MgCO3 + MgO = Mg2CO4 Reaction at Pressures of the Earth’s Lower Mantle

JETP Letters - Mg-carbonate is one of the main carbonates subducting from the Earth’s surface into the mantle and possible reactions of this compound with the main mantle minerals determine...     

Modulation of the Acher’s limit by medium thickness in [FeCoB/ZnO]50 multilayers

This work investigates the high frequency characteristics of [FeCoB/ZnO]₅₀ multilayers with different ZnO thickness. The results reveal that the Acher’s limit of [FeCoB/ZnO]₅₀ multilayers can be modulated by medium thickness. Increasing medium layer thickness is favorable for breaking through the Acher’s limit. It is found that the differences of Acher’s limit between multilayers and single layers are caused by magnetic interface anisotropy related to interface roughness and some unknown factor.     

Nuclear g-Factor Measurement of the 9/2− Isomeric State in 171Ta

The nuclear g-factor of 9/2⁻ isomeric state in ¹⁷¹Ta at 184 keV has been measured as g(9/2⁻)=+0.515(3) using the TDPAD method following pulsed heavy-ion reaction and recoil implantation. Pulsed ¹⁶O ion beam (84 MeV) from the 15UD pelletron accelerator facility of Nuclear Science Centre at New Delhi was used in the reaction ¹⁵⁹Tb(¹⁶O, 4nγ)¹⁷¹Ta. This revised version was published online in September 2006 with corrections to the Cover Date.     

Soliton Lattice State of Spin—1／2 Antiferromagnetic Chain in an External Magnetic Field

One-dimensional spin-1-2 anisotropic Heisenberg antiferromagnet in a longitudinal external magnetic field is studied using bosonization method and Gaussian wave functional techniques which take account of the spatial structure.The magnetization and the energy of the ground state which depend on the external magnetic field are calculated.For the case of anisotropic parameter △＞△0,increasing of the external magnetic field above the threshold value leads to the appearance of the soliton lattice state in the ground state,until to an another critical field where the ground state changes to the canted state phase.Therefore,with increasing external magnetic field,the ground state experiences four different phases successively,namely,antiferromagnetic Ising,soliton lattice state canted state,and magnetization saturated phases.When △＜△0,the soliton lattice state phase does not appear,with increasing external field,the paramagnetic phase smoothly evolves into the canted state phase,finally reaches magnetization saturated phase.     

Proton Spin–Lattice Relaxation Study of the Setting Reaction in Conventional and Resin-Modified Glass-Ionomer Dental Cements

The setting processes in KetacCem, AquaCem and Fuji I glass-ionomer dental cements (GIC) as well as in the resin-modified glass-ionomer dental cement (RM-GIC) Fuji Plus have been studied by proton spin–lattice, T ₁, and spin–spin, T ₂, relaxation. The setting time dependence of the degree of hydration was studied as well. In contrast to zinc oxide dental cements, the changes in T ₁ and T ₂ are determined by the interactions of the water with the internal surface. Proton nuclear magnetic resonance relaxation is thus suitable to follow the setting of GIC and RM-GIC and gives valuable information on the GIC hardening dynamics. Authors' address: Tomaz Apih, J. Stefan Institute, Jamova 39, Ljubljana 1000, Slovenia     

Structure of the Gauge Invariant Quark Green’s Function in QCD2

We study, in two-dimensional QCD and in the large-N _c limit, the properties of the gauge invariant quark Green’s function, defined with a path-ordered phase factor along a straight line. The analysis is done by means of an exact integrodifferential equation. The Green’s function is found to be infrared finite, with singularities represented by an infinite number of threshold type branch points with a power ?3/2, starting at positive mass squared values. Its expression is analytically determined.     

Nonadiabatic Predissociation Studies of the (1-3)Πg System of Al2 by Means of a Complex Rotated Finite Element Method

A general numerical Runge-Kutta-Fehlberg based diabatization procedure for electronic states in diatomics was applied to the adiabatic (1-3)³Π_g system of Al₂ in order to obtain a strictly diabatic basis. Using an exterior complex rotated finite element method, adiabatic Born-Oppenheimer (BO) as well as diabatic rovibronic term energy values and predissociation widths for the (2)³Π_g; (v, N)=(0−50, 0−25) and (3)³Π_g; (v, N)=(0−17, 0−25) levels were computed. Comparing rotationless BO and diabatic energies, differences between 10 and 25 cm⁻¹ are found for the (2)³Π_g levels while the (3)³Π_g levels display an almost constant shift ∼12 cm⁻¹. From the widths, the nonradiative lifetime for each rovibronic level was calculated. Based on existing rotationless radiative lifetimes, an estimation of an upper limit of about 50 ns was used to determine a number of rovibronic (2, 3)³Π_g levels which may be experimentally observed.     

Fundamental Concepts of Electron Spin Resonance Technique in the Determination of the Crystal Field Structure of O− 2 Ions in TiO2

Abstract

The basic principles of Electron Spin Resonance (ESR) as applicable in crystal field characterization of paramagnetic species has been outlined. Fundamental concepts of the precessional motion of electrons and their magnetic moments at resonance were developed. The theory of ESR based on the response of unpaired electron(s) as they undergo spin-spin or spin-lattice relaxation when subjected to strong external magnetic fields was examined. Ions of the O^? ₂ group adsorbed on TiO₂ were studied using a Varian Spectrometer. The resulting spectral diagrams obtained were used in calculating the g-factors which gave results for orthorhombic crystal symmetry for O^? ₂ ions in TiO₂.     

A Study of Antiferromagnetic Ordering in β-FeF3·3H2O by the Use of the NMR Method

The present work cites the investigation results of local magnetic fields on ¹H and ¹⁹F nuclei and spin ordering in β-FeF₃·3H₂O. In the structure of this compound (space group P4₂/n, a=7.846 Å, c=7.754 Å, z=4^1,2) Fe atoms are bonded via bridged F atoms (1) in infinite chains along the /001/ axis. With such positioning, in which two paramagnetic atoms are separated by a diamagnetic atom (F, O, C1 and others) there is a possibility for indirect (superexchange) interaction. Linear chains … Fe - F - Fe - F - Fe - F … are separated from each other by F(2) atoms and water molecules H₂O (1) and H₂O (2), so that exchange between neighboring Fe atoms from various chains is ostensibly much encumbered.     

A study of non-extensivity in the Earth’s magnetosphere

Magnetic storms are undoubtedly among the most important phenomena in space physics and also a central subject of space weather. The non-extensive Tsallis entropy has been recently introduced, as an effective complexity measure for the analysis of the geomagnetic activity D _st index. Tsallis entropy has been shown to sensitively detect the complexity dissimilarity between pre-storm activity and intense magnetic storms in the Earth’s magnetosphere. Here, we show that the D _st time series obey a modified form of the Gutenberg-Richter law for the case of non-extensive statistics, thus providing evidence for universality in magnetic storm and earthquake occurrence.