Structural Refinement of Carbimazole by NMR Crystallography

The characterization of the three-dimensional structure of solids is of major importance, especially in the pharmaceutical field. In the present work, NMR crystallography methods are applied with the aim to refine the crystal structure of carbimazole, an active pharmaceutical ingredient used for the treatment of hyperthyroidism and Grave’s disease. Starting from previously reported X-ray diffraction data, two refined structures were obtained by geometry optimization methods. Experimental ¹H and ¹³C isotropic chemical shift measured by the suitable ¹H and ¹³C high-resolution solid state NMR techniques were compared with DFT-GIPAW calculated values, allowing the quality of the obtained structure to be experimentally checked. The refined structure was further validated through the analysis of ¹H-¹H and ¹H-¹³C 2D NMR correlation experiments. The final structure differs from that previously obtained from X-ray diffraction data mostly for the position of hydrogen atoms.     

X射线晶体学结合电子晶体学在复杂无机晶体结构解析中的应用

自然界中的材料,比如无机材料,有机材料,生物材料等等,均有其独特的物理和化学性质。而材料的性能又与材料的结构息息相关,只有充分了解了材料的结构,才能更加深入的研究材料性质。因此,材料结构的确定在化学、物理、生物等学科中的显得尤为重要。X射线晶体学作为传统的结构解析技术仍然是目前最重要的结构解析手段,但是对于复杂结构,X射线衍射晶体学解析结构也存在一些不足,往往需要其他技术手段相补充才能完成复杂结构的结构解析。电子晶体学虽然起步比X射线晶体学晚,但是,经过近几十年的发展,已经是结构解析领域一个非常重要的手段。本文将主要介绍X射线晶体学结合电子晶体学在复杂无机晶体结构解析中的应用。     

Formation of Cyclodextrin Inclusion Complexes with Doxycyclin-Hyclate: NMR Investigation of Their Characterisation and Stability

The solubility of cyclodextrin (CD) can be notably improved when it is included in a polymeric structure. CD was reacted with citric acid, yielding a water-soluble polymer whose inclusion properties towards doxycyclin-hyclate (DOX) as guest molecule were investigated by NMR. The new DOSY (Diffusion Ordered SpectroscopY) method, based on diffusion coefficient measurements is convenient study complexes made of large molecules and it was applied to determine the association constants between DOX and parent β and γ-CD and their polymerised forms. The association constant obtained by DOSY was compared with that determined more classically by the chemical shift variation measurement using Scott's plot.     

Chirality Recognition of Selenium Compounds by NMR Spectroscopy in the Presence of a Chiral Dirhodium Complex

Abstract

Diastereomeric adducts of chiral soft-base selenium ligands with the enantiopure dirhodium complex Rh* allows stereodifferentiation by NMR spectroscopy of various nuclei (dirhodium method). The individual adduct species can be identified by low-temperature NMR spectroscopy.     

Synthesis and structural characterisation of redox-responsive N-ferrocenoyl amino acid esters; the X-ray crystal structure of N-ferrocenoyl alanine methyl ester; electrochemical anion recognition and H NMR complexation studies

The N-ferrocenoyl amino acid ester derivatives FcCOR {Fc=(η⁵-C₅H₅)Fe(η⁵-C₅H₄)} where R=Gly(OMe) 1, Gly(OEt) 2, Gly(OBn) 3, l-Ala(OMe) 4, l-Ala(OEt) 5, l-Leu(OMe) 6, l-Leu(OEt) 7, l-Leu(OBn) 8, l-Phe(OMe) 9 and l-Phe(OEt) 10, were prepared by coupling ferrocene carboxylic acid with the appropriate amino acid ester starting materials using the 1,3-dicyclohexylcarbodiimide (DCC), 1-hydroxybenzotriazole (HOBt) protocol and these have been characterised by spectroscopic techniques. The electrochemical anion sensing behaviour of compounds 1-10 with several anions using a platinum microdisk working electrode is described, together with ¹H NMR anion complexation studies. The X-ray single crystal structure of N-ferrocenoyl-l-alanine methyl ester 4 has been determined and contains two molecules which differ slightly in conformation in the asymmetric unit of space group P2₁ (No. 4); principal dimensions are amide N(H)CO 1.224(6) and 1.231(6) Å, ester CO 1.220(10) and 1.190(7) Å, with N-H?OC(amide) as the primary intermolecular hydrogen bond, N?O 2.992(6) and 2.971(6) Å and with graph set C(4).     

Study on Inclusion Complexes of Cyclodextrin with Sodium Dodecyl Polyoxyethylenated Sulfonate Using Microcalorimetry and 1H NMR

The association of α‐, β‐ and γ‐cyclodextrin (α‐CD, β‐CD and γ‐CD) with sodium dodecyl polyoxyethylenated sulfonate (C₁₂E_nS n=1, 3) was studied by means of isothermal titration calorimetry and ¹H NMR measurements in aqueous solution at T=298.15 K. The results indicate that the binding processes of β‐CD with the surfactants are characterized by both enthalpy favorable and entropy favorable, while those of α‐CD or γ‐CD with the surfactants are mainly entropy driven. The stoichiometry of β‐CD binding with the surfactants is different with different numbers of oxyethyl groups in surfactant molecules, while that of α‐CD or γ‐CD binding with the surfactants makes no difference. The ¹H NMR spectra reveal that chemical shift data of all protons in α‐CD, β‐CD and γ‐CD molecules move to high field in the presence of C₁₂E_nS, which can be regarded as a microscopic evidence of the occurrence of inclusion interaction.     

Structural Assignment of Side Chain Liquid Crystalline Monomer and Polymer by 1-D and 2-D Solution NMR Studies

In the present study, the synthesis and characterization of a methacrylic-based side chain liquid crystalline monomer and its polymer were investigated with the aid of both 1-D and 2-D nuclear magnetic resonance (NMR) techniques. The mesophase characteristics of the monomer and polymer were determined by hot-stage optical polarized microscopy (HOPM). The nematic and smectic phases were observed for the monomer and polymer. Furthermore, ¹³C spin-lattice relaxation time measurements were performed on the above systems in order to monitor molecular dynamics. The present study provides an opportunity to carry out a systematic comparison of the evolution of structural as well as dynamical changes of the monomer and the polymer.     

核磁共振研究二茂铁硒铂配合物构象交换热焓

The intramolecular conformational exchange thermodynamics of cis-PtCl[1,1'bis(undecenylseleno)ferrocene](B11SeFcPt) in CDCl3 solution was studied by one dimensional proton NMR． The chemical equilibrium constants were obtained directly from the integration of the 1H NMR spectra and the enthalpy as a function of temperature for the conformational exchange of B11SeFcPt was calculated from the equilibrium constant.     

Investigation of the inclusion of the herbicide cycluron in native cyclodextrins by X-ray diffraction,nuclear magnetic resonance spectroscopy and isothermal titration calorimetry

The formation of inclusion complexes between the native cyclodextrins (CDs) and the urea herbicide cycluron has been investigated both in solution and in the solid state. Single-crystal X-ray structures of both the uncomplexed guest and the β-CD·cycluron complex were determined while powder X-ray diffraction was used to confirm complexation between γ-CD and cycluron in the solid state. Solution-state complexation between the herbicide and α-, β- and γ-CD was established using ¹H NMR spectroscopy and isothermal titration calorimetry (ITC). From the ¹H NMR spectroscopic studies 1:1 complex stoichiometry was indicated in all cases and association constant values (K) were determined as 228, 3254 and 155 for the complexes α-CD·cycluron, β-CD·cycluron and γ-CD·cycluron, respectively. Assigning a 1:1 host–guest ratio, the ITC technique produced K values of the same order as those determined using the spectroscopic method. The thermodynamic parameters ΔH, ΔS and ΔG obtained using ITC provide insights into the driving forces involved during complex formation.     

Styryl dyes. Synthesis and study of the solid-state [2+2] autophotocycloaddition by NMR spectroscopy and X-ray diffraction

New styryl dyes of the pyridine and benzothiazole series were synthesized with the aim of investigating the solid-state [2+2] autophotocycloaddition (PCA) reaction. The ¹H NMR spectroscopy showed that for most of the compounds under study, the visible light irradiation of thin polycrystalline films of the dyes affords cyclobutane derivatives. The rate of the photoreaction depends on the structure of the dye and is higher for compounds, which contain a short N-substituent in the heterocyclic moiety and have strong absorption in the visible region. Dyes bearing electron-releasing substituents in the benzene ring undergo the stereospecific PCA in the syn-head-to-tail dimeric pair to give the only rctt isomer of cyclobutane derivatives. Electron-withdrawing and bulky substituents in the benzene fragment of styryl dyes extend the range of the mutual orientations of the molecules in the dimeric pairs, resulting in the formation of two or even four isomeric cyclobutanes in the PCA reactions. The structures of some dyes were established by X-ray diffraction. In the overwhelming majority of the structures, one of two packing modes, either syn-head-to-tail or syn-head-to-head, with extensive stacking interactions is observed. A rare example of the anti-head-to-head stacking mode was found for the dicationic dye containing the bulky N⁺(Et)Me₂ substituent in the benzene ring. The syn-head-to-tail and anti-head-to-head stacking modes can facilitate the PCA reaction due to the close spatial proximity of the ethylenic bonds and their parallel orientation in the dimeric pairs of the dye molecules. Dedicated to Academician G. A. Abakumov on the occasion of his 70th birthday. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1797–1819, September, 2007.     

Determination of components of the order parameter tensor of cholesteryl myristate by1H NMR data

The order parameter and orientation of the long axis of a cholesteryl myristate molecule have been determined by the second, fourth, and sixth moments of the¹H NMR line of a polycrystalline sample in the smectic phase. The effects of molecular diffusion in the cholesteric phase are discussed.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1269–1272, July, 1995.     

顺磁性镧系金属有机配合物的1H核磁共振研究

顺磁类的核磁共振研究大多是简单化合物,偏重理论方面的研究,对镧系配合物曾有报道。由于这类样品对空气和湿气极为敏感,在国内外研究顺磁性¹H谱甚少。本文研究了含氯桥的醚基取代环戊二烯镧系配合物二聚体的¹H化学位移,线宽,弛豫时间T₁和磁化率,从中找出了顺磁类有机镧系配合物¹H NMR的规律。     

Synthesis and Structural Characterization of a Ruthenium Complex： trans-RuCle（COD）Py2

A new ruthenium complex trans-RuCl2（COD）Py2 has been synthesized and characterized by elemental analysis, IR, IH NMR and single-crystal X-ray diffraction. Crystal data： trans- RuCl2（COD）Py2, Mr = 438.35, monoclinic, space group P21/c, a = 8.9116（9）, b = 14.6175（15）, c = 13.7582（14）A, β = 101.994（1）°, V= 1753.1（3）A^3, Z= 4, Dc= 1.661 g/cm^3, F（000）= 888,μ = 1.199 mm^-1, R = 0.0376 and wR = 0.0789 for 2492 observed reflections with I 〉 2σ（I）.     

Inclusion of the Niflumic Acid Anion in β-cyclodextrin: A Solution NMR and X-ray Structural Investigation

We report parallel solution and solid state studies of the inclusion of the anionic form of the non-steroidal anti-inflammatory drug niflumic acid (2-[[3-(trifluoromethyl)phenyl]-amino]-3-pyridinecarboxylic acid) in the host g -cyclodextrin ( g -CD). 1 H NMR data for the interaction between host and guest in aqueous solution recorded at 300 MHz indicated a strong preference for insertion of the trifluoromethylphenyl residue, rather than the pyridinecarboxylate moiety, in the host cavity. A 1:1 complex stoichiometry was determined by the continuous variation method utilising chemical shifts of both host and guest protons. Analysis of the data using a new flexible program developed for this purpose yielded an overall association constant K of 336 M m 1 at 298 K. The NMR data indicate a dynamic equilibrium between complexed and uncomplexed species but do not distinguish guest entry from the primary and secondary sides of the host. Reaction between the Cs + salt of niflumic acid and g -CD yielded the crystalline complex ( g -CD) 2 ·(Cs + niflumate m ) 4 ·22H 2 O whose single crystal X-ray structure was determined. A novel inclusion mode for this host, namely entry of guest trifluoromethylphenyl residues from both the primary and secondary sides, was revealed by the X-ray analysis.     

Synthesis and Structural Characterization of a Ruthenium Complex:trans-RuCl_2(COD)Py_2

A new ruthenium complex trans-RuCl2(COD)Py2 has been synthesized and charac- terized by elemental analysis, IR, 1H NMR and single-crystal X-ray diffraction. Crystal data: trans- RuCl2(COD)Py2, Mr = 438.35, monoclinic, space group P21/c, a = 8.9116(9), b = 14.6175(15), c = 13.7582(14) , β = 101.994(1)°, V = 1753.1(3) 3, Z = 4, Dc = 1.661 g/cm3 , F(000) = 888, μ = 1.199 mm-1, R = 0.0376 and wR = 0.0789 for 2492 observed reflections with I > 2σ(I).     

Synthesis and Investigation of 1,2,3,4-Thiatriazol-5-ylcarbamates

Methyl 1,2,3,4-thiatriazol-5-ylcarbamate (2a), ethyl 1,2,3,4-thiatriazol-5-ylcarbamate (2b), 2-butyl 1,2,3,4-thiatriazol-5-ylcarbamate (2c), allyl 1,2,3,4-thiatriazol-5-ylcarbamate (2d), and 3-(1,2,3,4-thiatriazol-5-yl)oxazolidin-2-one (2e) were synthesized with high yields by the reaction of the corresponding carbon(isothiocyanatidic) acid, alkyl esters, and sodium azide in aqueous solution. The compounds were characterized by ¹H, ¹³C, and ¹⁵N NMR, vibrational spectroscopy (IR), and single crystal X-ray diffraction. The thermal stability was investigated by differential scanning calorimetry.     

Comprehensive Characterisation of the Ketoprofen-β-Cyclodextrin Inclusion Complex Using X-ray Techniques and NMR Spectroscopy

Racemic ketoprofen (KP) and β-cyclodextrin (β-CD) powder samples from co-precipitation (1), evaporation (2), and heating-under-reflux (3) were analysed using X-ray techniques and nuclear magnetic resonance (NMR) spectroscopy. On the basis of NMR studies carried out in an aqueous solution, it was found that in the samples obtained by methods 1 and 2, there were large excesses of β-CD in relation to KP, 10 and 75 times, respectively, while the sample obtained by method 3 contained equimolar amounts of β-CD and KP. NMR results indicated that KP/β-CD inclusion complexes were formed and the estimated binding constants were approximately 2400 M⁻¹, showing that KP is quite strongly associated with β-CD. On the other hand, the X-ray single-crystal technique in the solid state revealed that the (S)-KP/β-CD inclusion complex with a stoichiometry of 2:2 was obtained as a result of heating-under-reflux, for which the crystal and molecular structure were examined. Among the methods used for the preparation of the KP/β-CD complex, only method 3 is suitable.     

Halide ion effect on the chloroform chemical shift in supramolecular complexation studies with tetra-n-butylammonium salts: a 1H NMR and X-ray study

A ¹H NMR spectroscopic study of tetra-n-butylammonium halides (TBAX: X = Cl^? , Br^?  or I^? ) in CDCl₃ solutions was conducted. Complexation studies of TBAX salts with different host molecules using ¹H NMR in CDCl₃ have previously revealed that the reference residual CHCl₃ proton signal had been shifted downfield. The aim of the study was to quantify the extent of these chemical shift changes with TBAX salts. Linear concentration–chemical shift relationships in each case were obtained from the resulting titration plots obtained from the addition of the TBAX salts alone to CDCl₃. Interactions in the solid state as determined by X-ray crystallography support the solution-state investigations indicating halide ion–chloroform proton interactions.     

A comparative study of NMR chemical shifts of sparteine thiolactams and lactams

The ¹³C and ¹H NMR spectra of the four possible thiolactams of sparteine (1) were recorded and the thiolactam group effects were determined. Most of the effects are greater than those of the lactam group in the oxo analogs. A good linear correlation between the ¹³C chemical shifts of CS and those of CO was found. The effects could help in assignment of the spectra and determination of conformation of thiolactams and related thiocarbonyl compounds.     

Solid State NMR Studies of the Bromocyclohexane/Thiourea Inclusion Compound

Solid state ¹³C-MAS and ²H-NMR investigationshave been performed on the bromo-cyclohexane/thiourea inclusion compound.The main objective of this study was the evaluation of the molecularfeatures of the guest molecules and their changes over a large temperaturerange (100 K < T < 350 K). Particular emphasis was placed on themolecular behaviour in the vicinity of a solid–solid phase transitionat T = 237 K and in the low temperature phase, which was hitherto unknown.The ²H-NMR lineshape and relaxation studies reveal that, inthe low temperature phase, restricted but fast overall motions (MHz to GHzregion) of the guest molecules are dominant and reflect the distortedsymmetry of the thiourea channels. On heating above the solid–solidphase transition almost unrestricted overall motions appear, together with alarge degree of orientational disorder at higher temperature. Furthermore,the ring interconversion process presents a major relaxation process in theMHz region. The conformational order is unusual in the sense that the axialconformational state of the guest molecules is stabilized in the thioureachannels. It turns out that this unique property is also preserved in thelow temperature phase.