CL-20/TATB共晶的分子动力学模拟

基于CL-20的晶胞参数和主要生长面及共晶的形成原理,构建了6种CL-20/TATB共晶结构模型。运用Forcite及在MD下达到平衡后,基于平衡结构进行径向分布函数考察、X射线粉末衍射图谱计算及模型能量计算。结果表明:6种共晶模型中分子间均存在较强的氢键作用力;随机取代模型的XRD衍射峰与纯组分CL-20相近,主要生长面模型的XRD衍射峰较纯组分CL-20和TATB有很大不同,且均有新峰出现;共晶模型在生长速率最慢的(10-1)晶面上取代后的能量最低,结构最稳定。基于能量计算、径向分布函数研究,TATB取代CL-20(10-1)晶面的共晶模型更容易形成。     

A Novel Method to Prepare Nano‐sized CL‐20/NQ Co‐crystal: Vacuum Freeze Drying

Nano‐sized energetic co‐crystal consisting of the most powerful used military explosive 2,4,6,8,10,12‐hexanitro‐2,4,6,8,10,12‐hexaazaisowurtzitane (CL‐20) and a typical insensitive explosive used in propellants nitroguanidine (NQ) was prepared by vacuum freeze drying method. Material studio 6.1 was used to simulate the hydrogen bonds between CL‐20 and NQ molecules. Scanning electron microscopy (SEM) was used to reveal the morphology and size of the product. Fourier Transform infrared spectroscopy (FT‐IR) and X‐ray diffraction spectrum (XRD) proved the formation of the co‐crystal at the molecular level. Differential scanning calorimetry (DSC) was employed to characterize the thermal behavior of the co‐crystal. The result of mechanical sensitivity test indicated the sensitivity was effectively reduced compared to neat CL‐20.     

Enhancing the Physiochemical Properties of Puerarin via L-Proline Co-Crystallization: Synthesis,Characterization, and Dissolution Studies of Two Phases of Pharmaceutical Co-Crystals

Puerarin (PUE) is a Chinese traditional medicine known to enhance glucose uptake into the insulin cells to downregulate the blood glucose levels in the treatment of type II diabetes. Nevertheless, the bioavailability of pristine PUE is limited due to its poor solubility and low intestinal permeability. In this work, we demonstrate that the solubility of PUE can be significantly enhanced via its co-crystallization with L-Proline (PRO). Two crystalline phases, namely, the solvate-free form [PUE][PRO] (I) and the solvated form [PUE]₂[PRO]∙EtOH∙(H₂O)₂ (II) are isolated. These two phases are characterized by single-crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), Fourier-transformed infrared (FT-IR) spectra, nuclear magnetic resonance (NMR), and thermogravimetric analysis in association with differential scanning calorimetry (TGA-DSC). The solubility and dissolution rate of both I and II in water, gastrointestinal tract at pH 1.2, and phosphate buffer at pH 6.8 indicates a nearly doubled increase as compared to the pristine PUE. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay of pristine PUE, I and II against murine colon cancer cell lines CT-26 and human kidney cell lines HEK-293 indicated that neither compound exhibits obvious cytotoxicity after 24 h. This work showcases that the readily available and biocompatible PRO can be a promising adjuvant to enhance the physicochemical properties of PUE toward orally administered drug formulation with improved pharmacokinetics.     

CL-20/HMX无规作用及共晶作用的理论计算

为了对比六硝基六氮杂异戊兹烷(CL-20)/环四亚甲基四硝铵(HMX)炸药分子间的无规作用及共晶作用,基于密度泛函理论(DFT),在B3LYP方法上使用6-311++G(d,p)基组优化得到了4种CL-20/HMX无规构型(Ⅰ、Ⅱ、Ⅲ和Ⅳ),对4种无规构型的几何结构、静电势、能量及电子密度拓扑进行了分析;利用分子动力学方法计算了共晶结构中H原子和O原子的径向分布函数;计算了不同摩尔比CL-20/HMX共晶的密度及爆速。结果表明,4种CL-20/HMX的无规构型存在氢键相互作用,氢键键长在0.274 2~0.296 4nm之间;4种无规构型的稳定性排序为:ⅣⅢⅡⅠ,构型的稳定性主要取决于氢键的数量和键长;4种无规构型在键临界点BCP处的电子密度ρ(r)大小排序为:ⅣⅢⅡⅠ,CL-20和HMX分子之间不仅存在H…O以及H…N形式的氢键相互作用,还存在N…O和C…O形式的范德华作用;共晶结构中CL-20与HMX的相互作用主要有氢键和强范德华力,氢键键长为0.22nm;CL-20/HMX共晶(摩尔比2∶1)的理论密度为2.003g/cm~3,理论爆速为9 608m/s。     

有机胺高氯酸盐共晶化合物的单晶制备与表征

用核磁共振波谱和X射线单晶衍射法对乙二胺·三乙烯二胺高氯酸盐（ST）的结构进行了表征。结构分析表明,化合物ST的乙二胺和三乙烯二胺的比例为1：1,晶体属单斜晶正交系,空间群：Cme21,晶胞参数：a=0．8103（16）nm;b=2．4725（5）nm;c=1．0195（2）nm;V=2．0425（7）nm3;Z=8;密度计算值Dc=1．828g·cm^-3,μ=0．67mm^-1,乙二胺分子参与分子间氢键的形成,形成锯齿形的链状结构,高氯酸根和三乙烯二胺分子填充在锯齿结构的齿缝里,共同形成孔状的超分子结构。     

Economic Separations of Organic Acidic or Basic Enantiomeric Mixtures—A Protocol Suggestion

In this review, we aim to present new concepts for the revisited separation of enantiomers from racemic compounds and a protocol worth to be followed in designing the preparation of pure enantiomers. We have taken into account not only the influence of the properties (eutectic composition) and characteristics of the reactants (racemic compound, resolving agent), but also the behavior of the resulting diastereomers and the different conditions (e.g., crystallization time, solvents used, solvate-forming compounds, achiral additives, etc.). The examples discussed are resolutions developed by our research team, through which we will try to illustrate the impact of all these considerations, presenting the methodological investigations interpreting recent discoveries and observations. Some special solid-state analytical and structural investigations assisting us in the elucidation and invention design of the resolution processes of some active pharmaceutical ingredients, such as Tetramisole, tofisopam, and Amlodipine, are also shown.     

Rational Design and Synthesis of Selective PRMT4 Inhibitors: A New Chemotype for Development of Cancer Therapeutics**

Protein arginine N-methyl transferase 4 (PRMT4) asymmetrically dimethylates the arginine residues of histone H3 and nonhistone proteins. The overexpression of PRMT4 in several cancers has stimulated interest in the discovery of inhibitors as biological tools and, potentially, therapeutics. Although several PRMT4 inhibitors have been reported, most display poor selectivity against other members of the PRMT family of methyl transferases. Herein, we report the structure-based design of a new class of alanine-containing 3-arylindoles as potent and selective PRMT4 inhibitors, and describe key structure–activity relationships for this class of compounds.     

基于溶剂/非溶剂法的微通道结晶制备CL-20/HMX共晶

为了发展易放大、可连续化的共晶制备方法,采用溶剂/非溶剂法的微通道结晶技术制备了六硝基六氮杂异伍兹烷/奥克托今(CL-20/HMX)共晶.采用场发射扫描电子显微镜(FE-SEM)、X射线粉末衍射(XRD)、拉曼光谱(Raman)、傅里叶红外光谱(FT-IR)、热分析和感度测试,对样品的形貌、结构、热性能和感度进行了表征分析.结果表明,该方法成功制备了CL-20/HMX共晶,其表观形貌部分呈花簇状,直径为20～30μm,由厚度为200～600 nm的片状晶体组装而成,部分呈单独的片状结晶(厚度为200～600 nm);所制备的CL-20/HMX共晶在放热过程中仅有一个尖锐的放热分解峰,放热峰温位于243.4℃,低于原料CL-20(250.2℃)和HMX(284.7℃).放热区间仅为242.7～246.0℃,比原料CL-20(230.0～254.6℃)和HMX(281.0～290.7℃)窄,具有较高的能量释放效率;表观活化能470.75 kJ·mol-1,介于CL-20(175.04 kJ·mol-1)和HMX(481.45 kJ·mol-1)之间,比CL-20提高了295.71 kJ·mol-1,具有较好的热稳定性;撞击感度为18 J,较原料CL-20(10 J)和HMX(14.4 J)分别提高8 J和3.6 J,摩擦感度比CL-20原料降低了20％,安全性有所提高.     

干燥法制备聚丙烯腈初生纤维样品的研究

采用湿法纺丝得到聚丙烯腈(PAN)初生纤维,干燥后得到PAN初生纤维样品.利用电阻法确定初生纤维的共晶温度;获得初生纤维的冻干曲线;通过压汞法对初生纤维孔结构进行表征,并对比考察了鼓风干燥、自然风干和冷冻干燥对样品截面形貌的影响.结果表明:初生纤维的共晶温度为-55℃;鼓风干燥会使样品收缩,纤维间发生粘连,原有形貌被破坏;自然风干使样品的截面积和周长分别收缩了20.66%、10.67%,形状系数变化率为3.52%.而冷冻干燥时样品的截面积和周长仅收缩了1.21%、1.15%,形状系数变化率为1.13%.冷冻干燥有效地保留了PAN初生纤维的固有原始结构,可用于制备各种分析的样品.     

冻干海蓬子粉加工工艺研究

通过电阻法测定了海蓬子的共晶点和共熔点,确定了海蓬子粉真空冷冻干燥的条件,冷冻产品呈黄绿色,有胡桃样清香味,产品的含水量为5.0%,维生素C的含量为182.3mg/100g。