马来酰肼多形态的太赫兹光谱研究

分子的多形态(多晶型)是指化学组成相同但存在不止一种晶体形式的物质.这些多形态广泛存在于自然界中,其中药物的多形态尤其普遍.这些药物多形态虽然具有相同的化学分子组成,但其理化性质却存在差异,最终会导致药物作用功能的不同.近年来,随着太赫兹(THz)辐射源的产生方式成为一种常规技术后,太赫兹时域光谱技术(THz-TDS)...     

Correlation of monomer structures of tripalmitin with the spectroscopic fingerprint of polymorphs: infrared,Raman, and DFT study

In the light of application of vibrational spectroscopy in medical diagnosis, it is necessary to have a tool to distinguish between different lipids that may be present in biochemical samples such as cells and tissues. One of the most common lipids in the human body are triglycerides. Therefore, the aim of this work was to investigate the model triglyceride, namely tripalmitin in order to find the differences between the vibrational signatures of its polymorphs and interpret them with the help of quantum‐chemical computations. Although monomeric models are not sufficient to reproduce polymorphs structure, analysis of these models is very helpful in understanding of relations between the structure and changes in vibrational spectra. Copyright © 2012 John Wiley & Sons, Ltd.     

Raman microspectroscopic mapping or thermal system used to investigate milling‐induced solid‐state conversion of famotidine polymorphs

Confocal Raman microspectroscopy was used to nondestructively determine the polymorphic conversion of famotidine in the course of the milling process. A mapping system was applied to assess the blending uniformity of each polymorphic component in the milled mixture. Raman microspectroscopy combined with a thermal analyzer was also used to investigate the synergistic co‐effects of milling and heating on the polymorphic conversion of famotidine polymorphs. Famotidine has two polymorphs, forms A and B, the raw material of famotidine used was proved to be of form B. The Raman peak intensity ratio of the 2920 cm⁻¹ band for form A and 2897 cm⁻¹ band for form B was used to act as an indicator to evaluate the polymorphic conversion of famotidine form B to form A after different milling courses. The results indicate that the peak intensity at 2897 cm⁻¹ gradually decreased with the milling time, whereas the peak intensity at 2920 cm⁻¹ slowly enlarged, suggesting the polymorphic conversion of famotidine from form B to form A. The longer milling process might strongly induce and promote this polymorphic conversion of famotidine. Both polymorphic forms of famotidine were found to be well uniformly distributed within the milled samples due to their smaller varieties by using the Raman microscopic mapping system. The temperature effect could synergistically accelerate the polymorphic conversion of famotidine from form B to form A in the milled sample. The thermal‐dependent critical temperature for sharply enhancing the content of famotidine form A in each milled sample was also identified. Copyright © 2007 John Wiley & Sons, Ltd.     

Shock-Induced Phase Transformations in Melt Pockets within Martian Meteorite NWA 4468

Northwest Africa (NWA) 4468 is a 675 g Martian meteorite recovered from the Western Sahara in 2006. It is an olivine basaltic shergottite, comprising clinopyroxene, olivine, maskelynite, chromite, ilmenite, Ca-phosphate polymorphs, troilite, and pyrrhotite. The sample shows both bulk (maskelynite formation) and localized shock effects (pressure-temperature excursions in veins and melt pockets). Here we report the presence of high-pressure polymorphs in melt pockets. We have discovered three phosphate polymorphs in the melt pockets (chlorapatite, merrillite, and tuite). Their crystal structure has been confirmed by Raman analysis. The mineral assemblages of the melt pockets are indicative of solid-state transformations, nucleation, and recrystallization at high temperatures and pressures. The stability fields of these minerals are used to infer the pressure and temperature conditions reached locally in the melt pockets as 23 GPa and 2000°C.     

Near-Infrared Spectroscopy: Effective Tool for Screening of Polymorphs in Pharmaceuticals

Abstract

Near-infrared (NIR) spectroscopy has emerged as an important technique for the screening and characterization of polymorphs in pharmaceuticals. Polymorphism, the ability of a substance to exist in two or more crystalline phases having different physicochemical and biopharmaceutical parameters, has attracted pharmaceutical scientists due to the patentability of new forms. Transformation of the solid phase due to polymorphic changes during manufacturing and storage may lead to formulation hurdles. Vibrational spectroscopy, particularly NIR spectroscopy, is a widely used technique for polymorphs screening in drug development processes and has emerged as a process analytical technology tool. In this review, a brief overview of NIR spectroscopy, chemometric tools, and polymorphs screening of pharmaceuticals using NIR spectroscopy is presented. Recent developments in NIR spectroscopy instrumentation are also discussed.     

A novel Raman spectroscopic approach to identify polymorphism in leflunomide: a combined experimental and theoretical study

Polymorphism is an important characteristic which affects the activity, solubility and other physical properties of a compound and can be induced by varying temperature, pressure and solvent. The presence and conversion of α to β polymorphic forms of an anti‐rheumatic drug leflunomide have been studied by temperature‐dependent and in situ Raman observations. Both α and β polymorphs were found to co‐exist in the temperature interval 367–372 K. The α form alone exists below 367 K and the β form alone above 373 K. The CO stretching band clearly demonstrates the α → β conversion because of breaking of N–H···O bond and formation of N–H···N bond. On cooling the Raman spectra suggest the irreversibility of this conversion. Thermodynamic stability, crystal parameters and surface morphology of both forms in the leflunomide powder used for the present study have been verified by differential scanning calorimetry, X‐ray powder diffraction and scanning electron microscopy. Copyright © 2015 John Wiley & Sons, Ltd.     

Insight into thermally induced solid‐state polymorphic transformation of sulfathiazole using simultaneous in situ Raman spectroscopy and differential scanning calorimetry

Pharmaceutical solids exposed to thermal stress during manufacturing processes undergo various phase transformations in bulk drug substances or excipients, resulting in altered dosage form performance. Due to its relatively rapid spectral acquisition rate, as well as the possibility of incorporation into in‐line monitoring, Raman spectroscopy is ideally suited to monitoring the transformation between different solid‐state forms. In this study, we demonstrate that the transition temperature for polymorphs can be estimated from the transformation profiles obtained from real‐time, in situ, simultaneous Raman spectroscopic, and differential scanning calorimetric data. Using this method, we have estimated the transition temperature of the solid‐state transformation of the enantiotropically related sulfathiazole polymorphs III and I. These results suggest that this method is a useful approach to determine transition temperatures in systems that are not amenable to accessing other methods. Copyright © 2009 John Wiley & Sons, Ltd.     

Temperature-accelerated method for exploring polymorphism in molecular crystals based on free energy

The ability of certain organic molecules to form multiple crystal structures, known as polymorphism, has important ramifications for pharmaceuticals and high energy materials. Here, we introduce an efficient molecular dynamics method for rapidly identifying and thermodynamically ranking polymorphs. The new method employs high temperature and adiabatic decoupling to the simulation cell parameters in order to sample the Gibbs free energy of the polymorphs. Polymorphism in solid benzene is revisited, and a resolution to a long-standing controversy concerning the benzene II structure is proposed.     

三维光谱学--二维红外光谱和时间分辨光谱

本文介绍了一类重要的光谱学分析方法-三维光谱学方法,对其中的时间分辨光谱和二维红外光谱作了详细的介绍,包括它们的基本原理、获取谱图的方法、谱图的性质等.介绍了二维红外光谱方法在光谱学分析中的一些应用领域.三维光谱分析方法已经成为光谱分析中重要的研究方法之一.     

铁基超导体Li0.8Fe0.2ODFeSe的红外光谱研究

测量和研究了铁基超导体Li_0.8Fe_0.2ODFeSe单晶的红外光学响应,发现室温下光电导率谱不存在Drude分量,载流子具有非相干输运行为.随着温度降低,Drude分量形成并不断变窄,同时在相应的反射率谱上出现清晰的等离子体边,表明散射率急剧降低.在最低温度,观察到超导能隙形成导致的光谱变化,光电导率谱在160 cm^-1以下受到显著压制.对比FeSe单晶的光谱数据,发现整体的光电导率谱型很相似,但自由载流子的谱重更低,揭示出样品具有更低的载流子浓度.另外还观察到温度变化诱导的谱重由低频向高频区域转移的现象,表明其存在强关联效应.     

Hydrogen bonding in nitrofurantoin polymorphs: a computation‐assisted spectroscopic study

The importance of hydrogen‐bond formation in the molecular packing arrangements of two anhydrous forms of nitrofurantoin is investigated, combining computational methods and spectroscopic data. The overall results indicate, as expected, that the vibrational modes related to the CO, N H and C H groups are strongly affected by intermolecular hydrogen‐bond formation. Moreover, the importance of weak C‐H···O interactions in conferring additional stability to molecular associations in biological systems is evidenced in this study. The complete assignment of the Raman and infrared spectra of both polymorphs is accomplished by means of a computationally based methodology, which accounts for the effects of intermolecular interactions in the crystal. The vibrational shifts due to crystal packing interactions are evaluated from DFT calculations for a set of suitable molecular pairs, using the B3LYP/6‐31G* approach. This methodology provides an answer to the current demand for a reliable and complete assignment of the vibrational spectra of pharmaceutically active compounds such as nitrofurantoin. Copyright © 2009 John Wiley & Sons, Ltd.     

利用太赫兹光谱检测萘啶酸的同质多晶

太赫兹光谱可以反映与固体中晶格振动有关的信息，特别适合于检测相同分子形成的不同晶体，因此利用太赫兹光谱对检测并控制药物的不同晶型具有重要的意义。而药物分子的晶型会影响药物在存储中的稳定性等性质。选取最早使用的喹诺酮类抗生素萘啶酸作为研究对象，首先合成了萘啶酸的两种晶型NA-Ⅰ和NA-Ⅱ。通过X射线粉末衍射确认了两种晶型。使用太赫兹时域光谱技术在室温下对合成的两种萘啶酸不同晶型NA-Ⅰ和NA-Ⅱ在0.2～2.4 THz范围内进行检测，NA-Ⅰ和NA-Ⅱ在太赫兹光谱中表现出明显的差异。NA-Ⅰ在0.94，1.41，1.88，2.05和2.17THz处有五处特征峰，而NA-Ⅱ在0.72，0.96，1.38，1.80，2.04和2.16 THz处有六处特征峰。二者最明显的差异是NA-Ⅱ在2.04 THz处的峰为肩峰，而NA-Ⅰ在2.05 THz处的吸收强度要大得多。不同于其他光谱，如红外光谱，太赫兹光谱中的特征峰不对应特定的官能团，因此对光谱峰的指认尤为重要。利用密度泛函理论对两种晶型进行理论计算，理论峰与实验特征峰基本对应，得出萘啶酸两种晶型在此低频范围的振动模式主要是分子的骨架运动，并从两种晶体堆积方式的不同阐述了光谱显著差异的原因。该研究为利用太赫兹光谱检测药物的同质多晶提供了依据。     

Comparison of the thermal stability of the α, β and γ phases in poly(vinylidene fluoride) based on in situ thermal Fourier transform infrared spectroscopy

The electroactive β phase of poly(vinylidene fluoride) (PVDF) is induced due to the aging time of PVDF solutions. The feasibility of the combination of the three crystalline polymorphs (α, β and γ) is demonstrated where their relative proportion within the PVDF film can be tailored by the simple monitoring of the preparation conditions. To identify all these phases, Fourier transform infrared (FT-IR) spectroscopy is carried out and it is spotlighted that the vibrational bands at 510 and 841 cm^?1 are not sufficient to state the formation of the β phase. The main aim of this work is devoted to develop a better understanding on the thermal stability of these several phases of PVDF, which has a longstanding ambiguity persisting in this area. It has been found that the in situ thermal FT-IR spectroscopy is one of the best alternatives to understand this important issue. It is ascertained that the β phase is the least thermally stable phase among α, β and γ phases, whereas the γ phase is the most thermally stable phase.     

硫代巴比妥酸多晶型的太赫兹光谱和DFT理论分析

硫代巴比妥酸是目前多晶型种类较丰富的一类固体药物。利用太赫兹时域光谱(THz-TDS)技术对硫代巴比妥酸晶型Ⅰ,Ⅱ,Ⅲ,Ⅳ和水合晶型进行表征分析,得到明显不同的太赫兹光谱,表明THz光谱技术可以有效鉴别硫代巴比妥酸不同类多晶型。硫代巴比妥酸晶型Ⅳ为异构多晶型,它在0.65 THz处的宽峰以及1.02,1.41 THz处的吸收峰明显区别于晶型Ⅰ和Ⅱ简单的物理混合。运用密度泛函理论(DFT)对硫代巴比妥酸晶型Ⅳ的两种可能结构进行了分子结构优化和光谱模拟,模拟结果显示其中的结构a在0.41/0.47,0.89和1.35 THz处具有吸收峰,与实验结果较吻合。由此推断晶型Ⅳ由硫代巴比妥酸异构体A的硫酮键中的S7和异构体B酰胺中的H23构成第一处氢键,异构体B硫酮键中的S20和异构体A酰胺中的H13形成第二处氢键。本文还结合理论模拟结果对硫代巴比妥酸晶型Ⅳ的振动模式进行归属。     

Polymorphism of 4-Fluorophenylpyruvic Acid Studied by X-Ray Crystallography and Vibrational Spectroscopy

Two polymorphic forms (I and II) of 4-fluorophenylpyruvic acid (F-PPA) were obtained by crystallization from different solvents, showing a melting point at 163.2 and 171.0 °C. Crystal structures of polymorphs I and II were determined by X-ray crystallography. IR and Raman spectra of the two polymorphs were measured and the spectral characteristics were compared with those of phenylpyruvic acid. the two polymorphs show similar molecular and crystal structures to each other, except for the molecular geometries of the enol and the carboxylic acid moieties. Distinct IR spectral differences which result from the crystal field splitting were observed between the two polymorphs.     

pH-Induced Changes in the Secondary Structure of Cytochrome c: an Infrared Spectroscopic Study

The infrared spectra of 3mM solutions of horse heart cytochrome c were recorded as a function of pD(corresponding to acid high spin form, acidic low spin form, native form, lysine form, the so-termed “strained lysine form” as well as the so-termed “A state” of cytochrome c). An analysis of the pH-induced changes in the secondary structure was performed based on changes in the conformation-sensitive amide I bands of this protein. In lysine and strained lysine forms, the contents of random structure increase at the expense of α-helix. In acidic low. spin form (pH4–2.5), cytochrome c was almost unfolded. The proportion of α-helix had a substantial decrease while the contents of both random structure and 3₁₀-helices got a rise. In acidic high spin form (when pH is below 2.5), a further decrease of pD gave no rise to a continued unfolding in cytochrome c but made it refold to the “A state” with properties similar to those of a molten globular state. Adding enough KC1 to the cytochrome c solution(pD2.2 with 0.5MKC1 and pD3.0 with 1.5 MKCl) in which cytochrome c was nearly fully unfolded also led to the formation of A state of cytochrome c. The compositions of all types of secondary structures in A state were evaluated. The behavior of 3₁₀-helices in acidic high/low spin form indicated they might be intermediates between α-helices and random structure in acidic solution as proposed by Miick et al.     

Temperature dependence of the far infrared reflectivity spectra of a KD2PO4

Complete data on far infrared reflectivity spectra of a KD₂PO₄ single crystal in the temperature range 7–300 K, from the millimeter wave up to 400 cm^–1, for all crystallographic orientations of the crystal, in the ferro- and paraelectric phase, are given for the first time. The temperature dependence of the phonon spectra is similar to that we have observed and published for KH₂PO₄.     

New Methods for Detection of 14N NQR Frequencies

Nitrogen atoms are present in a number of solid explosives and illicit substances. The nuclear quadrupole resonance (NQR) spectra and spin?Clattice relaxation of the nitrogen atomic nucleus ¹⁴N can be used to characterize these compounds and to distinguish between possible crystal polymorphs. After the characteristic ¹⁴N NQR frequencies and spin?Clattice relaxation rates in a compound are determined, NQR can be used to detect this compounds and, in case of crystal polymorphs, also to determine the method of preparation. The ¹⁴N NQR frequencies and spin?Clattice relaxation rates are measured either by pulse NQR or by nuclear quadrupole double resonance (NQDR) based on magnetic field cycling. Here, we discuss several ¹H?C¹⁴N NQDR techniques which can be used to measure the ¹⁴N NQR frequencies and spin?Clattice relaxation rates under various experimental conditions. Some characteristic applications of these techniques are presented and discussed in details.     

并五苯同质异相体中分子间势能与能带计算

采用Born-Mayer-Haggins对势模型，分析了并五苯分子间势能及其相互作用. 用紧束缚模型计算了两种并五苯同质异相体结构的能带宽度. 计算带宽随温度升高减小8%—14%. 关键词： 并五苯 同质异相体 分子间势能 能带计算