Characterization of the solid phases of paracetamol and fenamates at equilibrium in saturated solutions

Differential scanning calorimetry (DSC), supported by hot stage microscopy, IR spectroscopy and X-ray powder diffractometry, was used to investigate the characteristics of the solid phases of mefenamic, niflumic, and flufenamic acids and of paracetamol, before and after equilibration with saturated solutions in different solvents. Mixtures of Lewis base (dioxane and ethyl acetate) and amphiprotic solvents (ethanol and water) were prepared for evaluating the influence of both nature and polarity of the solvents. Solid-state analysis performed on the original samples (commercial products) made it possible to establish that paracetamol, mefenamic acid and flufenamic acid were in their respective Form I. No polymorphic modifications are known for niflumic acid. Paracetamol, niflumic and mefenamic acids did not show any change after equilibration with the various solvents or solvent mixtures, regardless of their different chemical nature. In contrast, DSC, IR and X-ray analyses revealed the partial recrystallization of flufenamic acid into its polymorphic Form III in solid phases at equilibrium with ethanol, ethyl acetate and their blends, as well as in dioxane-water mixtures containing 30 to 100% dioxane and in ethanol-water mixtures with a water content less than 50%. This revised version was published online in July 2006 with corrections to the Cover Date.     

Theoretical and spectroscopic study of 2-substituted indan-1,3-diones: a coherent picture of the tautomeric equilibrium

The structures of some 2-substituted indan-1,3-diones are investigated in the gas phase and solution using quantum chemical calculations and spectral (NMR, IR, and UV) measurements. The influence of the substituent at the 2-position on the tautomeric equilibrium of 2-substituted indan-1,3-diones in solvents with different polarity is evaluated. It is shown that the equilibrium in 2-formyl-indan-1,3-dione and 2-acetyl-indan-1,3-dione is shifted to the 2-hydroxyalkylidene-indan-1,3-dione tautomer, while 2-carboxyamide-indan-1,3-dione exists as a mixture of two tautomers, 2-(hydroxyaminomethylidene)-indan-1,3-dione and 2-carboamide-1-hydroxy-3-oxo-indan, with extremely fast proton transfer between them. The situation for 2-carboxy-indan-1,3-dione is quite different - on the basis of the analysis of the obtained results, the possible existence of an anionic form of 2-carboxy-indan-1,3-dione in solution can be inferred.     

Structural study of tropane-3-spiro-4'-imidazol-5'-one

Tropane-3-spiro-4'-imidazol-5'-one has been synthesized and its crystal and molecular structures determined by X-ray diffraction, IR, Raman, ¹H-NMR and ¹³C-NMR methods. The tautomeric equilibrium between this structure and the corresponding conjugated form in different solvents is also studied from IR and UV data. The imidazoline ring, the spiranic C(3, 4'), the N(8) and the methyl C(9) atoms are situated in a plane. The piperidine ring adopts a distorted chair conformation in the crystalline form and in solution. The flattening of the C(1), C(2), C(3, 4'), C(4), C(5) part of the chair and the opposite puckering are noticeably large. In order to complete the results, some spectroscopic measurements have also been made for the tropane-3-spiro-4'-imidazol-5'-one hydrochloride.     

Conformational preferences of N-acetyl-L-leucine-N'-methylamide. Gas-phase and solution calculations on the model dipeptide

A DFT study of N-acetyl-l-leucine-N'-methylamide conformers in the gas phase and in solution was carried out. The theoretical computational analysis revealed 43 different conformations at the B3LYP/6-31G(d) level of theory in the gas phase. In addition, the effects of three solvents (water, acetonitrile, and chloroform) were included in the calculations using the isodensity polarizable continuum model (IPCM) and the Poisson-Boltzmann self-consistent reaction field (PB-SCRF) method. The stability order of the different conformers in solution has been analyzed. The theoretical results were compared with some experimental data (X-ray, IR, and NMR).     

Structural rationalisation of co-crystals formed between trithiocyanuric acid and molecules containing hydrogen bonding functionality

Crystallisation of trithiocyanuric acid (TTCA) from various organic solvents that have hydrogen bonding capability (acetone, 2-butanone, dimethylformamide, dimethyl sulfoxide, methanol and acetonitrile) leads to the formation of co-crystals in which the solvent molecules are incorporated together with TTCA in the crystal structure. Structure determination by single-crystal X-ray diffraction reveals that these co-crystals can be classified into different groups depending upon the topological arrangement of the TTCA molecules in the crystal structure. Thus, three different types of single-tape arrangements of TTCA molecules and one type of double-tape arrangement of TTCA molecules are identified. In all co-crystals, hydrogen-bonding interactions are formed through the involvement of N-H bonds of TTCA molecules in these tapes and the other molecule in the co-crystal. Detailed rationalisation of the structural properties of these co-crystals is presented.     

Dipeptide structure determination by vibrational circular dichroism combined with quantum chemistry calculations.

The solution structure and the local solvation environments of alanine dipeptide (AD, 1 a) and its isotopomer (AD*, 1 b, 13C on the acetyl end C==O) are studied by using infrared (IR) spectroscopy and vibrational circular dichroism (VCD). From the amide I IR spectra of AD* in various protic solvents, it is found that each of the two carbonyl groups is fully H-bonded to two water molecules. However, the number of alcohol molecules H-bonded to each C==O varies from one to two, and the local solvation environments are asymmetric around the two peptides of AD* in alcohol solutions. The amide I VCD spectra of AD and AD* in D2O are also measured, and a series of density functional theory (DFT, B3LYP/6-311++G**) calculations are performed to obtain the amide I normal-mode rotational strengths of AD and the intrinsic rotational strengths of its two peptide fragments. By combining the VCD-measurement and DFT-calculation results and employing a coupled oscillator theory, we show that the aqueous-solution structure of the dipeptide can be determined. We believe that the present method will be of use in building up a library of dipeptide solution structures in water.     

四苯基卟啉锌J-聚集体的光谱与晶体结构分析

四苯基卟啉锌在完全无水的乙氰中发生自聚现象, 聚集体的形成可以通过稳态光谱来证实. 吸收光谱和荧光发射光谱的红移表明四苯基卟啉锌的聚集体是卟啉之间以头对头的方式排列, 即J-聚集体. 进一步研究表明聚集体的形成还依赖于溶剂. 光谱和激发态寿命的测定结果表明聚集体的辐射跃迁速率比单体快两倍, 这表明形成的J-聚集体存在超辐射. 四苯基卟啉锌的晶体呈现出杆状的结构. 通过X射线的结构分析, 提出了一个四苯基卟啉锌J-聚集体的结构模型. 四苯基卟啉锌中的一个苯基和相邻的四苯基卟啉锌中的吡咯垂直并通过C—H…π键相互作用. 最后讨论了乙氰配位后对四苯基卟啉锌中Zn—N键的影响.     

Conformation equilibrium of 3-(hydroxymethyl)piperidine in solvents with different polarity

Quantum-chemical calculations of the 3-(hydroxymethyl)piperidine molecule conformers were performed at the B3LYP/6-31+G** level of theory, and four most stable conformations with different relative orientation of CH₂OH and N–H groups were determined. The optimized structures, vibration frequencies, and band intensities in the spectra of the conformers were obtained. The conformational equilibria of the most stable rotational isomers in solvents of different polarity was studied within the polarizable continuum model. According to the results of calculations, the conformational equilibrium in solution is substantially changed on varying the solvent polarity. This conclusion was confirmed by comparison with IR absorption spectra of 3-(hydroxymethyl)piperidine solutions in carbon tetrachloride in the region of ОН-stretchings.

     

Solution and solid state studies of a triangle-square equilibrium: anion-induced selective crystallization in supramolecular self-assembly

We report that an equilibrium mixture of triangular and square supramolecular species results when the flexible, ditopic donor unit, trans-bis(4-pyridyl)ethylene, is reacted with the ditopic acceptor unit, cis-(Me(3)P)(2)Pt(OTf)(2), in a one-to-one ratio. Both products are characterized in solution, by way of multinuclear NMR, and in the solid state, via X-ray crystallography. The effects of water and anions, cobalticarborane versus triflate, on the equilibrium are probed. The selective crystallization of either of the two species can be accomplished via the appropriate choice of solvents and ratio of anions present in the system. The dominant species in solution is not always consistent with the most prevalent species in the solid state.     

Molecular and computational structure characterizations of (E)-2-ethoxy-6-[(4-fluorophenylimino)methyl]phenol

The (E)-2-ethoxy-6-[(4-fluorophenylimino)methyl]phenol compound was synthesized and characterized by X-ray Diffraction, IR and Electronic spectroscopy. X-Ray and IR results showed that the title compound preferred the enol form in solid state. UV-Vis absorption spectra of the title compound were recorded in different solvents. The results showed that the molecule existed only in enol form even in the solvent media. Electronic structure and spectroscopic properties of the title compound were investigated from calculative point of view. The gas phase geometry optimization was obtained based on X-ray geometry by DFT method with B3LYP applying 6-311G(d,p) basis set. Geometry optimizations in the solvent media were obtained with the same level of theory by the polarizable continuum model (PCM). TD-DFT calculations starting from the optimized geometry were made in both gas and solution phase to measure the excitation energies of enol and keto tautomers. Vibrational frequency and natural bond orbital analysis (NBO) were performed and the thermodynamic properties of the title compound were obtained at the optimized geometry with the same level of theory.     

Interactions between metal ions and carbohydrates. Coordination behavior of neutral erythritol to Ca(II) and lanthanide ions

The study of the sugar-metal ion interactions remains one of the main objectives of carbohydrate coordination chemistry because the interactions between metal ions and carbohydrates are involved in many biochemical processes. This paper presents a comparison of coordination structures of erythritol with alkaline-earth-metal and lanthanide chloride and nitrate in the solid state using FT-IR and X-ray diffraction. Neutral, nondeprotonated erythritol (E) reacts with CaCl(2) to give three CaCl(2)(-)erythritol (CaE(I), CaE(II), CaE(III)) complexes, showing that three of the five general features of calcium-carbohydrate complexes deduced in the reference encounter contrary examples. Different coordination structures have been observed for calcium and lanthanide chloride and nitrates. The coordination of carbohydrates to metal ions is complicated, and erythritol, chloride ions, nitrates, water molecules, and ethanol (crystallization medium and reaction solvents) have the chance to coordinate to metal ions. IR spectral results show that different lanthanide ions, from LaCl(3) to TbCl(3), have similar coordination structures with erythritol. The results show that erythritol can act as two bidentate neutral ligands (CaE(I), CaE(II), CaE(III), CaEN, PrE, NdE) or as a three-hydroxyl donor (NdEN). The IR results are consistent with the crystal structures.     

Microhydration of NO3(-): a theoretical study on structure, stability and IR spectra

A systematic study on the structure and stability of nitrate anion hydrated clusters, NO3(-) x n H2O (n = 1-8) are carried out by applying first principle electronic structure methods. Several possible initial structures are considered for each size cluster to locate equilibrium geometry by applying a correlated hybrid density functional with 6-311++G(d,p) basis function. Three different types of arrangements, namely, symmetrical double hydrogen bonding, single hydrogen bonding and inter-water hydrogen bonding are obtained in these hydrated clusters. A structure having inter-water hydrogen bonding is more stable compared to other arrangements. Surface structures are predicted to be more stable over interior structures. Up to five solvent H2O molecules can stay around solute NO3(-) anion in structures having an inter-water hydrogen-bonded cyclic network. A linear correlation is obtained for weighted average solvent stabilization energy with the size (n) of the hydrated cluster. Distinctly different shifts of IR bands are observed in these hydrated clusters for different kinds of bonding environments of O-H and N=O stretching modes compared to isolated H2O and NO3(-) anion. Weighted average IR spectra are calculated on the basis of statistical population of individual configurations of each size cluster at 150 K.     

Anisotropic nuclear spin interactions for the morphology analysis of proteins in solution by NMR spectroscopy.

Determining the relative orientation of domains within a protein is an important problem in structural biology, which has been difficult to address by either X-ray crystallography or NMR. The structure of a multidomain protein in a crystal lattice can be altered by crystal packing forces, resulting in different domain arrangements from those in solution. On the other hand, conventional NMR primarily provides short-range structural information, including proton-proton distances derived from nuclear Overhauser effects (NOEs) and torsion angles through vicinal spin couplings. Thus, NMR cannot always determine the precise interdomain arrangements due to the sparsely observed spin interactions between domains. However, the weak alignment of proteins in solution has enabled a new NMR technique to determine the domain arrangement based on the different structural information, which defines the orientation of a structural unit in protein against the magnetic field. This technique relies on the anisotropic nuclear spin interactions that only occur for a molecule in a weakly aligned state. In this review, the basics of the new NMR approach are described with focusing on its application to domain orientation analysis. We also describe our recently established NMR approach using the same spin interactions, which expands the domain arrangement analysis to higher-molecular weight proteins over 100 kDa.     

Singlet excited-state interactions in naphthalene-thymine dyads.

Two thymidine-derived nucleosides 1 and 2 were prepared by attaching a chiral naphthalene to the positions 5' and 3' of the sugar. The resulting dyads, which contain key substructures present in drugs and nucleic acids, exhibit different spatial arrangements (transoid or cisoid) of the fluorophore relative to the thymine unit. Emission measurements on these compounds in the presence of ROH molecules revealed a remarkable intramolecular prescence quenching for dyad 1. The obtained results are consistent with quenching of the singlet excited state of 1 by hydrogen-bond donor solvents. Thus, a physical deactivation process (vibronically induced internal conversion) would be the pathway responsible for the accelerated decay of 1*, favorably competing with fluorescence and intersystem crossing to the triplet. This effect appears to be strongly dependent on the relative spatial arrangement between the naphthalene and thymine units, together with the hydrogen-bonding ability of the employed ROH.     

Chromatographic resolution, solution and crystal phase conformations, and absolute configuration of tert-butyl(dimethylamino)phenylphosphine-borane complex

The enantiomers of tert-butyl(dimethylamino)phenylphosphine-borane complex 2 have been separated by HPLC using cellulose tris-p-methylbenzoate as chiral stationary phase. The borane protection could be removed without racemization and the P-configuration of the free aminophosphine 1 has shown to be stable in solution. Infrared (IR) and vibrational circular dichroism (VCD) spectra have been measured in CD2Cl2 solution for both enantiomers. B3LYP/6-31+G(d) DFT calculations allowed a prediction that complex (S)-2 exists as three conformers in equilibrium and computed population-weighted IR and VCD spectra. Predicted and experimental IR and VCD spectra compared very well and indicate that enantiomer (+)-2 has the S absolute configuration. This assignment has been confirmed by an X-ray diffraction study on a single crystal of (+)-2. The crystal structure of enantiomerically pure 2 appears to be very close to the most stable computed conformer which proved to be predominant in solution.     

Structure-acidity-IR spectra correlations for p-substituted N-phenylsulfonylbenzamides

The wavenumbers of the IR absorption bands of the C=O, S=O and N-H stretching vibrations for a series of p-substituted N-phenylsulfonylbenzamides were measured in trichloromethane. The bond orders, Mulliken charges, charge densities and heats of formation were calculated using the PM3 method. Fifty significant mutual mono parameter (MP) and six dual parameter (DP) correlations were found for the IR spectral, theoretical structural data, substituent constants and previously reported dissociation constants in five polar organic solvents. The transmission of the substituent effects has been discussed and the solvent effect on the slopes of some linear correlations was evaluated using different solvent parameters. The results showed that the factors describing the electronic structure and controlling the dissociation equilibrium and the IR spectra properties of p-substituted N-phenylsulfonylbenzamides must be the same.     

Aggregation of 2‐Aminobenzimidazole—A Combined Experimental and Theoretical Investigation

An investigation of 2‐aminobenzimidazole was carried out by calculations at HF, MP2, and DFT levels of theory and also by UV and IR spectroscopy. The quantum chemical calculations predict a full shift of the equilibrium towards the amino form, but the absorption spectra in different solvents distinctly show a two‐component equilibrium system. Examination of possible equilibria in solution shows that an equilibrium between two dimeric forms of the amino tautomer of 2‐aminobenzimidazole explains the spectral observations.     

含聚1,3-二氧戊环链段可降解pH敏感性水凝胶的合成与表征

制备了含聚 1,3 二氧戊环链段具有pH敏感性的可解体聚合物凝胶网络 ,网络可在水中及有机溶剂中溶胀 ,且由聚 1,3 二氧戊环构成的水凝胶成分可以在酸性介质中降解 ,使网络解体 .利用红外光谱、色 质联谱等分析手段对聚合物凝胶网络进行了表征 .通过对降解产物的分析 ,一方面证实了降解现象的存在 ,另一方面证实了聚合反应机理     

Rigid Arrangements of Ionic Charge in Zeolite Frameworks Conferred by Specific Aluminum Distributions Preferentially Stabilize Alkanol Dehydration Transition States

Zeolite reactivity depends on the solvating environments of their micropores and the proximity of their Brønsted acid sites. Turnover rates (per H⁺) for methanol and ethanol dehydration increase with the fraction of H⁺ sites sharing six-membered rings of chabazite (CHA) zeolites. Density functional theory (DFT) shows that activation barriers vary widely with the number and arrangement of Al (1–5 per 36 T-site unit cell), but cannot be described solely by Al–Al distance or density. Certain Al distributions yield rigid arrangements of anionic charge that stabilize cationic intermediates and transition states via H-bonding to decrease barriers. This is a key feature of acid catalysis in zeolite solvents, which lack the isotropy of liquid solvents. The sensitivity of polar transition states to specific arrangements of charge in their solvating environments and the ability to position such charges in zeolite lattices with increasing precision herald rich catalytic diversity among zeolites of varying Al arrangement.     

Site-specific hydrogen-bonding interaction between N-acetylproline amide and protic solvent molecules: comparisons of IR and VCD measurements with MD simulations

The effects of solute-solvent interactions on solution structures of small peptides have been paid a great deal of attention. To study the effect of hydrogen-bonding interactions on peptide solution structures, we measured the amide I IR and VCD spectra of N-acetylproline amide (AP) in various protic solvents, i.e., D2O, MeOD, EtOD, and PrOD, and directly compared them with theoretically simulated ones. The numbers of protic solvent molecules hydrogen-bonded to the two peptide bonds in the AP were quantitatively determined by carrying out the molecular dynamics (MD) simulations and then compared with the spectral analyses of the experimentally measured amide I bands. The two peptides in the AP have different propensities of forming H-bonds with protic solvent molecules, and the H-bond population distribution is found to be strongly site-specific and solvent-dependent. However, it is found that adoption of the polyproline II (PII) conformation by AP in protic solvents does not strongly depend on the hydrogen bond network-forming ability of protic solvents nor on the solvent polarity. We present a brief discussion on the validity as well as limitation of the currently available force field parameters used for the present MD simulation study.