Plasma hydrogenated cationic detonation nanodiamonds efficiently deliver to human cells in culture functional siRNA targeting the Ewing sarcoma junction oncogene

The expression of a defective gene can lead to major cell dysfunctions among which cell proliferation and tumor formation. One promising therapeutic strategy consists in silencing the defective gene using small interfering RNA (siRNA). In previous publications we showed that diamond nanocrystals (ND) of primary size 35 nm, rendered cationic by polyethyleneimine-coating, can efficiently deliver siRNA into cell, which further block the expression of EWS/FLI-1 oncogene in a Ewing sarcoma disease model. However, a therapeutic application of such nanodiamonds requires their elimination by the organism, particularly in urine, which is impossible for 35 nm particles. Here, we report that hydrogenated cationic nanodiamonds of primary size 7 nm (ND-H) have also a high affinity for siRNA and are capable of delivering them in cells. With siRNA/ND-H complexes, we measured a high inhibition efficacy of EWS/FLI-1 gene expression in Ewing sarcoma cell line. Electron microscopy investigations showed ND-H in endocytosis compartments, and especially in macropinosomes from which they can escape before siRNA degradation occurred. In addition, the association of EWS/FLI-1 silencing by the siRNA/ND-H complex with a vincristine treatment yielded a potentiation of the toxic effect of this chemotherapeutic drug. Therefore ND-H appears as a promising delivery agent in anti-tumoral gene therapy.     

化工工艺设计过程中几种决策方法的应用

催化裂化汽油通过加氢处理可有效降低硫含量,是清洁汽油或清洁汽油调和油生产的重要过程。随着环保标准的日益严格,汽油加氢技术的研发和使用正日益受到重视,在技术开发、工艺设计、项目投资的过程中要面临诸多决策问题,从管理学角度对不同级别决策问题适用的决策方法和模型进行了介绍,并对定量决策方法、定性决策方法以及定量与定性相结合的决策方法使用场合提出了一些建议。     

缓和加氢裂化动力学模型

参考缓和加氢裂化（ＭＨＣ）反应机理，开发了一种既能预测产品产率，又能预测产品性质的ＭＨＣ动力学网络模型。以文献上发表的ＭＨＣ实验数据为例，进行了参数估计，确定了动力学参数，给出了模型的标准差。本模型所预测的ＭＨＣ结果，与文献数据吻合良好，具有良好的预测性能。     

煤加氢液化和苯加压萃取所得沥青质组成结构的研究

借助~1H-NMR、IR、分子量测定和元素分析,采用Brown-Ladner方法,研究了煤加氢沥青质(Ⅰ)和苯加压萃取沥青质(Ⅱ)的组成结构,计算了碳原子分布、芳香度、芳环和脂环数等结构参数,推测了它们的化学结构模型,并与煤的化学结构模型进行了比较。Ⅰ随反应温度增加,芳香度急剧提高。390℃、430℃和470℃时,其芳香度分别为0.78、0.85和0.91,说明在高温下发生了脱氢反应。Ⅱ的芳香度随煤的变质程度增加而提高,其组成结构与煤本体没有根本的差别,是分散在高分子结构中的低分子化合物。     

茂钛络合物—纳米NaH体系催化苯乙烯氢化

茂钛络合物，以纳米ＮａＨ为助催化剂催化苯乙烯氢化，初速率为３．７×１０＾３－８．３×１０＾３ｍｏｌ／（ｍｏｌ．ｍｉｎ）（Ｈ２／Ｔｉ），催化效率为６．４×１０＾３－１８．５×１０＾３ｍｏｌ／ｍｏｌ（Ｈ２／Ｔｉ），均高于文献的其他２茂钛催化体系，考察了不同温度对催化反应的影响，反应温度在２７５－３１５Ｋ时，活化能为２０．３ｋＪ／ｍｏｌ，与催化体系活性高一致。     

美替诺龙醋酸酯的合成

目的　由 17β 乙酰氧基 5α雄甾 1 烯 3 酮 (1)经 5步反应合成蛋白同化激素美替诺龙醋酸酯 (17β 乙酰氧基 1 甲基 5α雄甾 1 烯 3 酮 ,6 )。方法　 17β 乙酰氧基 5α雄甾 1 烯 3 酮 (1)在酸的存在下与NBS反应 ,得2 β 溴 1α ,17β 二羟基 5α 雄甾烷 3 酮 17 醋酸酯 (2 ) ,化合物 (2 )用H2 /活性镍催化氢解 ,得 1α ,17β 二羟基 5α 雄甾烷 3 酮 17 醋酸酯 (3) ,然后在对甲苯磺酸的催化下化合物 (3)与甲醇作用 ,得 3,3 二甲氧基 5α 雄甾烷 1α ,17β 二醇 17 醋酸酯 (4 )。化合物 (4 )经铬酐 硫酸氧化 ,得 17β 乙酰氧基 3,3 二甲氧基 5α 雄甾烷 1 酮 (5 ) ,再经格氏反应和乙酰化反应 ,制得 17β 乙酰氧基 1 甲基 5α 雄甾 1 烯 3 酮 (美替诺龙醋酸酯 ,6 )。由化合物 1到 6的总收率为 48.7%。结果　此法以较高收率合成了美替诺龙醋酸酯。结论　该合成法有适用于工业化生产的前景     

Isolation,identification, and characterization of a palladium complex in the catalytic deprotection of a protected peptide

The final catalytic deprotection in the large scale synthesis of thymopentin (Arg-Lys-Asp-Val-Tyr) produced an impurity which had not previously been observed. Isolation by preparative HPLC and spectroscopic characterization led to a postulated structure of the impurity as the 1: 1 thymopentin-palladium complex. A complex corresponding to the proposed structure was independently synthesized and shown to have identical chromatographic and spectroscopic properties with the isolated material. Proton and carbon (13) NMR were used to determine the coordination sites of the peptide with palladium. The susceptibility of the complex to hydrogenation indicated a possible source for its formation.     

2-酰氨基-3-芳基丙烯酸甲酯的不对称氢化反应

以单齿磷配体(S)-MonoPHOS和［Rh(COD)₂］BF₄作为催化剂,研究2-酰氨基-3-芳基丙烯酸甲酯类化合物中的氨基保护基对其不对称催化氢化反应的影响。最终经水解等操作,2-酰氨基-3-芳基丙烯酸甲酯类化合物的不对称氢化反应以63%~92%的收率得到相应的D-苯丙氨酸及其衍生物。     

Side reactions in peptide synthesis

During the hydrogenolytic removal of the benzyl ester from the pentapeptide Boc-Asp(OBzl)-Ala-Phe-Ile-Gly-OEt, either with hydrogen gas or ammonium formate in the presence of palladium-on-charcoal as catalyst, variable amounts (5–30%) of an unexpected by-product were always obtained. The compound was eventually identified as Boc-Asc-Ala-Phe-Ile-Gly-OEt (Asc = aminosuccinyl). The application of field desorption mass spectrometry as a diagnostic tool is reported. The study of this side reaction, carried out on the pentapeptide and two other dipeptide models, showed that: 1) palladium-on-charcoal may induce Asc formation; 2) the contemporary presence of the catalyst and a base (even in trace amounts) greatly increases the by-product formation; 3) the side reaction is sequence and solvent dependent; 4) the Asc formation is completely prevented by adding a few equivalents of acetic or formic acid. Some mechanistic considerations are also reported.