表面改性聚丙烯的血液相容性研究进展

聚丙烯具有价格低廉、无毒、易于加工等优点,使其在许多领域得到广泛的应用。但是聚丙烯自身有较强的疏水性,与血液相接触时,血浆蛋白会在材料表面大量吸附,诱发血小板的粘附和聚集,从而造成凝血和溶血的发生。在生物医用材料的应用过程中,血液相容性是限制材料能否长期应用的关键因素。本文综述了表面改性法提高聚丙烯血液相容性的研究现状、表面改性方法和常用的大分子单体,并分析了当前聚丙烯表面改性研究存在的问题,展望了具有良好血液相容性聚丙烯的发展前景。     

2-甲基丙烯酰氧基乙基磷酰胆碱单体及其聚合物的合成与应用

近年来,生物医用高分子材料的生物相容性研究备受关注。基于仿细胞膜外层结构设计合成的2-甲基丙烯酰氧基乙基磷酰胆碱（MPC）及其聚合物研究已成为一个新热点。大量研究结果表明,用MPC聚合物修饰生物材料表面,可获得良好的血液相容性和组织相容性。本文综述了MPC单体及其聚合物的合成以及其在人造器官、组织工程、血液净化、药物控释与基因治疗、固定化酶、生物传感器等方面的应用,探讨了MPC聚合物研究应用的发展趋势。     

生物医用材料表面仿细胞膜结构改性

细胞膜因其固有的生物相容性,可以作为体内植入材料及器件表面生物相容化改性的范例。大量研究结果表明,用细胞外层膜的亲水官能团－磷酰胆碱基团修饰材料表面,可显著提高材料的生物相容性,具有广阔的应用前景。本文综述了用含磷酰胆碱基团小分子及聚合物进行仿细胞膜结构改性的各种方法及其代表性工作;讨论了不同方法得到的仿细胞膜结构表面的性能;总结了几种有影响的生物相容性机理;对仿细胞膜结构表面改性研究及应用的前景做了展望。     

磷酰胆碱基共聚物的合成及其稳定聚合物涂层表面的构筑

设计并合成了侧基分别含有磷酰胆碱(PC)亲水基团和胆固醇(Chol)疏水基团的两亲性二元无规共聚物PMC,用其对疏水基材聚丙烯中空纤维膜(PPHF)表面进行亲水改性,并以疏水基团为十二烷基柔性烷烃的磷酰胆碱基两亲性二元无规共聚物PML为参照聚合物,研究了聚合物涂层加热处理及空气中久置后涂层表面的稳定性.用1H-NMR和DSC对二元随机共聚物PMC和PML的结构和熔点(Tm)进行测定,用ARTR和XPS表征磷酰胆碱基共聚物构筑的两性离子表面的化学成分,用接触角研究其表面亲水性,并用水的动态接触角(DCA)评价涂层表面功能基团重新迁移取向的能力.结果发现,所得二元无规共聚物PMC和PML中组成与投料比相近且PMC的熔点Tm(190.5℃)远高于PML的(90.3℃);与PML改性PPHF表面相比,PMC-PPHF表面亲水性提高,而且经100℃高温处理2 h和空气中放置8个月后,接触角和表面磷元素相对含量基本不发生变化,说明表面功能基团基本不发生重新迁移取向,表面结构稳定性好.     

2-甲基丙烯酰氧基乙基磷酰胆碱单全及其聚合物的合成与应用

近年来,生物医用高分子材料的生物相容性研究备受关注.基于仿细胞膜外层结构设计合成的2-甲基丙烯酰氧基乙基磷酰胆碱(MPC)及其聚合物研究已成为一个新热点.大量研究结果表明,用MPC聚合物修饰生物材料表面,可获得良好的血液相容性和组织相容性.本文综述了MPC单体及其聚合物的合成以及其在人造器官、组织工程、血液净化、药物控释与基因治疗、固定化酶、生物传感器等方面的应用,探讨了MPC聚合物研究应用的发展趋势.     

还原胺化反应的新进展

综述了近几年来各种还原胺化方法的研究进展及其在合成中的应用, 尤其对高效和高选择性的还原胺化进行了重点介绍.     

细胞内转运载体超支化聚砜胺及其生物相容性

通过制备超支化聚砜胺-异硫氰酸荧光素聚合物(PSA-FITC), 研究其生物相容性、肿瘤细胞对其内吞作用和在正常小鼠体内的生物分布, 以探讨PSA作为载体进行药物和基因体内输送的可行性. 在碱性条件下共价结合PSA与FITC, 形成荧光标记聚合物(PSA-FITC)后测定聚合物中FITC含量. 在不同时间点, 通过流式细胞术检测细胞对聚合物的内吞作用; 正常balb/c裸鼠尾静脉注射PSA-FITC 24 h后, 用小动物活体荧光成像系统研究各脏器聚合物分布. 不同浓度PSA与3T3小鼠成纤维细胞及KB人口腔上皮肿瘤细胞分别孵育24, 48, 72 h后, 通过MTT法测得其生物相容性. 结果表明, PSA生物相容性良好, 72 h的细胞半抑制浓度大于1 mg/mL. 细胞摄入PSA-FITC高效快速, 3 h阳性细胞百分含量为99.24%±1.03%, 且具有时间依赖性. 在正常小鼠体内, PSA在各主要脏器或组织中无明显特异性浓聚. 超支化聚砜胺具有明显生物低毒性和高效细胞内转运特点. 由于其表面功能基团容易改性, 作为载体, 通过连接结合配体或抗体, 在肿瘤的主动靶向治疗中具有广阔的应用前景.     

玻璃表面铜-胺氧化还原引发自由基接枝聚合

将3-氨基丙基三乙氧基硅烷(KH-550)固定于玻璃片表面,利用铜-胺氧化还原反应在水溶液中引发缺电子乙烯基单体,如N,N-二甲基丙烯酰胺(DMAAm)进行自由基接枝聚合.通过衰减全反射红外分析(ATR-FTIR)、接触角、原子力显微镜(AFM)和X射线光电子能谱(XPS)等方法进行表征,证明玻璃表面已接枝上功能性聚合物链,且不会产生游离均聚物.当原料配比为m(CuSO4):m(DMAAm):m(H2O) ＝5:1000:1000,反应温度为80℃,反应时间为4h时,所得样品GlassKH-550-g-PDMAAm的接枝率与单位面积接枝量分别达到了0.342％和0.47 mg/cm2.接枝后玻璃表面化学组成和形貌都发生了显著变化.本方法操作简单、效果明显,具有一定普适性.     

聚丙烯微孔膜表面修饰的葡聚糖固定化研究

糖以各种形式广泛存在于自然界,在人类的许多生理过程中起着不可或缺的重要作用．它具有优良的亲水性和生物特异性．研究表日月,将含糖单体接枝到聚丙烯微孔膜表面或通过共聚引入聚丙烯腈超滤膜,能显著提高常规高分子分离膜的抗污染能力和表面生物相容性,从而扩大其应用范围．     

一种基于巯基化聚丙烯胺自组装膜的免疫传感器固定方法

提出了一种基于巯基自组装的新型蛋白质固定化方法。应用偶联试剂碳二亚胺(EDC)和N-羟基琥珀酰亚胺(NHS)使聚丙烯胺盐酸盐(PAH)与3-巯基丙酸(MPA)偶合，在石英晶振表面自组装，形成一带多氨基的巯基自组装膜。应用该方法成功地固定了羊抗人IgM抗体，并用于人血清免疫球蛋白M(IgM)的测定。详细考察了自组装条件、抗体包被和免疫反应的主要实验条件以及传感器的响应性能。与MPA法比较，应用该方法可在传感器表面固定更多的抗体分子，传感器的响应灵敏度亦更好。在优化的实验条件下，反应的线性范围0．66-26．4mg／L；回归方程Y=92．44 12．40X；相关系数r=0．9920。     

Synthesis of Primary Amines by One-Pot Reductive Amination of Aldehydes

We report here a novel, one-pot, two-step reductive amination of aldehydes for the atom-economical synthesis of primary amines. The amination step has been carried out with hydroxylammonium chloride and does not require the use of a base. In the subsequent reduction step, a metal zinc/hydrochloride acid system has been used. This method is applicable to both aliphatic and aromatic aldehydes. The operational simplicity, the short reaction times, and the mild reaction conditions add to the value of this method as a practical alternative to the reductive amination of aldehydes.

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.     

Asymmetric Reductive Amination in Organocatalysis and Biocatalysis

This review summarizes the recent progress of organocatalytic and biocatalytic asymmetric reductive amination (ARA), a challenging but important topic for drug discovery and the pharmaceutical industry. At present, ARA can be divided into three categories: metal catalysis, organic catalysis, and biocatalysis. In the past decade, transition metal-catalysed ARA has been well established. Organocatalytic ARA has emerged as a powerful alternative to metal-catalysed ARA, the hydrogen sources used in organocatalytic ARA are usually Hantzsch esters, benzothiazolines, boranes, and hydrosilanes, which require Lewis base or phosphoric acid catalysts to activate them to give secondary chiral amines. It is worth mentioning that biocatalytic ARA has made remarkable progress in the last decade, amino acid dehydrogenases, amine dehydrogenases, opine dehydrogenases and imine reductases have been successfully used in ARA.     

Catalytic One-Pot Reductive Amination of Carboxylic Acids

The broad applications of primary alkyl amines in various fields have spurred extensive interests in synthetic organic chemistry. Recently, the reductive amination of carboxylic acids has become an attractive and practical strategy for synthesizing primary alkyl amines, due to their wide availability and bench stability. However, the inherent stability and higher oxidation state of carboxylic acids render this new strategy with new challenges. This Concept provides a summary of the recent advancements in the reductive aminations of carboxylic acids, specifically focusing on the catalytic tactics, underlying mechanisms, and applications in the synthesis of valuable products.     

Primary Amines by Transfer Hydrogenative Reductive Amination of Ketones by Using Cyclometalated IrIII Catalysts

Cyclometalated iridium complexes are found to be versatile catalysts for the direct reductive amination (DRA) of carbonyls to give primary amines under transfer‐hydrogenation conditions with ammonium formate as both the nitrogen and hydrogen source. These complexes are easy to synthesise and their ligands can be easily tuned. The activity and chemoselectivity of the catalyst towards primary amines is excellent, with a substrate to catalyst ratio (S/C) of 1000 being feasible. Both aromatic and aliphatic primary amines were obtained in high yields. Moreover, a first example of homogeneously catalysed transfer‐hydrogenative DRA has been realised for β‐keto ethers, leading to the corresponding β‐amino ethers. In addition, non‐natural α‐amino acids could also be obtained in excellent yields with this method.     

General Reductive Amination of Aldehydes and Ketones with Amines and Nitroaromatics under H2 by Recyclable Iridium Catalysts

Heterogeneous iridium catalysts were prepared and applied for the reductive amination of aldehydes and ketones with nitroaromatics and amines using H₂ . The iridium catalysts were prepared by pyrolysis of ionic liquid 1‐methyl‐3‐cyanomethylimidazoulium chloride ([MCNI ]Cl) with iridium chloride (IrCl₃ ) in activated carbons. Iridium particles were well dispersed and stable in the N‐doped carbon materials from [MCNI ]Cl with activated carbon. The Ir@NC (600‐2h) catalyst was found to be highly active and selective for the reductive amination of aldehydes and ketones using H₂ and a variety of nitrobenzenes and amines were selectively converted into the corresponding secondary and tertiary amines. The Ir@NC (600‐2h) catalyst can be reusable several times without evident deactivation.     

Reductive Amination of Aldehydes and Ketones with Primary Amines by Using Lithium Amidoborane as Reducing Reagent

A variety of secondary amines were obtained in high isolated yields in the reductive amination of aldehydes and ketones by using lithium amidoborane as reducing agent. Compared to ammonia borane, lithium amidoborane has higher reducibility, and thus, exhibits faster reaction rate.     

Earth-abundant Metal-catalyzed Reductive Amination: Recent Advances and Prospect for Future Catalysis

Nitrogen-containing compounds, as an important class of chemicals, have been used widely in pharmaceuticals, materials synthesis. Transition metal-catalyzed reductive amination of an aldehyde or a ketone with ammonia or an amine has been proved to be an efficient and practical method for the preparation of nitrogen-containing compounds in academia and industry for a century. Given the above, several effective methods using transition metals have been developed in recent years. Noble transition metals like Pd, Pt, and Au-based catalysts have been predominately used in reductive amination. Because of their high prices, strict official regulations of residues in pharmaceuticals, and deleterious effects on the biological system, their industrial applications are severely hampered. With the increasing sustainable and environmental problems, the Earth-abundant transition metals including Ti, Fe, Co, Ni, and Zr have also been investigated for the reductive amination reaction and showed great potential to the advancement of sustainable and cost-effective reductive amination processes. This critical review will mainly summarize the work using Earth-abundant metals. The effects of different transition metals used in catalytic reduction amination were discussed and compared, and some suggestions were given. The last section highlights the catalytic activities of bi- and tri-metallic catalysts. Indeed, this latter family is very promising and simultaneously benefits from increased stability, and selectivity, compared to monometallic NPs, due to synergistic substrate activation. Few comprehensive reviews focusing on Earth-abundant transition metals catalyst has been published since 1948, although several authors reported some summaries dealing with one or the other part of this aspect. It is hoped that this critical review will inspire researchers to develop new efficient and selective earth-abundant metal catalysts for highly, environmentally sustainable reductive amination methods, as well as improve the pharmaceutical industry and related chemical synthesis company traditional method with the utilization of the green method widely.     

Asymmetric Stepwise Reductive Amination of Sulfonamides,Sulfamates, and a Phosphinamide by Nickel Catalysis

Asymmetric reductive amination of poorly nucleophilic sulfonamides was realized in the presence of nickel catalysts and titanium alkoxide. A wide range of ketones, including enolizable ketones and some biaryl ones, were converted into sulfonamides in excellent enantiomeric excess. The cyclization of sulfamates and intermolecular reductive amination of a diarylphosphinamide were also successful. Formic acid was used as a safe and economic surrogate of high‐pressure hydrogen gas.     

Nickel‐Catalyzed Enantioselective Reductive Amination of Ketones with Both Arylamines and Benzhydrazide

An asymmetric reductive amination of ketones using both arylamines and benzhydrazide in the presence of nickel catalysts was developed. A one‐pot synthesis of tetrahydroquinoxalines was also developed starting directly from α‐ketoaldehydes and 1,2‐diaminobenzene. Formic acid was used as a safe and economic surrogate for high‐pressure hydrogen gas. Strongly σ‐donating bis(alkylphosphine)s are crucial ancillary ligands for both stereoselective hydride insertion and decarboxylation of the formate.