胶体马达

胶体马达亦称微纳米马达、微纳米泳体或游动纳米机器人,是研究复杂系统的绝佳非平衡态物理模型,同时因其具有额外的自推进力、自主导航等独特优势,有望为靶向药物递送等生物医学应用带来颠覆性变革.作为一个新兴的多学科交叉领域,胶体马达拓展了胶体与界面化学的研究范畴,带来了新的现象、理论与应用,是以胶体科学为核心的国际前沿交叉学科研究的热点领域.本文系统地阐述了胶体马达以及基于胶体马达的超分子胶体马达和游动纳米机器人的新概念,同时以本课题组在胶体马达领域取得的研究成果为例,详细综述了胶体马达的结构设计与可控制备、驱动机理及运动行为的界面调控策略、集群行为规律与重构方法以及突破各种生物屏障实现药物主动靶向递送等方面的最新进展,在此基础上展望了胶体马达对于胶体科学发展所带来的新机遇与新挑战.     

纳米粒子在药物传递中的应用

目前,利用纳米粒子传递药物并用于恶性肿瘤组织的靶向识别,进一步提高肿瘤的诊断和治疗水平是一个比较热点的领域,人们期望用制备容易、价格便宜、毒性小的纳米技术来提高肿瘤的治疗效率。然而,由近年的报道来看,所摄入的纳米粒子仅有约0.7%能够到达肿瘤部位,传递效率较低,这无疑加大了治疗应用的难度。本综述中,我们分析了造成纳米粒子靶向药物转运效率较低的原因,包括纳米粒子的转运途径,纳米粒子转运过程中所遇到的屏障,纳米粒子在体内的清除途径等;随后我们介绍了较早应用的聚合物纳米粒子、磁性氧化铁纳米粒子以及目前广泛研究的介孔二氧化硅纳米粒子在药物传递系统构建中的应用情况,还介绍了细胞膜仿生纳米粒子在药物传递系统中的应用;最后,对纳米粒子在药物传递中的研究进行总结和展望。我们希望通过对纳米粒子传递药物的系统研究,进一步促进纳米粒子在药物传递上的研究,加速纳米药物的临床应用。     

磁应答型药物递送载体的设计与构建

复合磁性生物材料的发展和应用已引起生物医学领域的极大关注。磁性纳米粒子因其易功能化而具有靶向药物传递、可控药物释放及磁成像特性逐渐成为药物传递和新型诊疗领域最有前途的材料之一。基于磁性纳米粒子或掺杂的铁氧化物构建的远程触发磁性载药递送系统,有望实现在运输过程中携载药物不泄露的情况下,提高药物递送效率且对病灶周围的健康细胞无毒或低毒性。为构建理想的可控靶向磁性药物递送系统,多种材料或配体可以与磁性纳米粒子复合来构建更安全有效的磁性药物递送系统。一些生物分子、聚合物及天然产物等通过与磁性纳米粒子相结合,构建出可用于药物传递且具有独特性质的磁性复合新材料。迄今为止,具有磁场应答能力的磁性药物递送载体已经在远程控制药物释放领域得到了长足发展。本文总结了近年来磁性药物递送载体作为远程控制治疗体系在设计与构建上的研究进展。重点关注了磷脂分子、聚合物、多孔微纳米材料以及天然产物等与其构建的复合材料,并对当前磁性复合特定给药载体的优点、局限及发展前景等做了简要阐述。     

苯硼酸功能化聚合物纳米载体用于蛋白质药物胞内递送

蛋白质药物在疾病治疗方面具有广泛应用,但它们的低细胞膜穿透性往往导致生物利用度较低.近年来,人们开发了一系列纳米载体用于提高蛋白质药物的胞内递送效率,其中基于苯硼酸及其衍生物的聚合物纳米载体显示出良好的应用前景.本文综述了苯硼酸功能化聚合物纳米载体在蛋白质药物胞内递送方面的最新研究进展.首先,简要介绍了苯硼酸的化学性质及其二醇、pH和活性氧(ROS)响应性.其次,从苯硼酸与蛋白质药物的结合方式不同出发,重点综述了通过动态共价作用和N→B配位等非共价作用构筑的苯硼酸功能化聚合物纳米载体在蛋白质药物胞内递送方面的典型研究实例,并对这些载体的组成、构筑方式和响应性释放机制进行了分析、总结.最后,介绍了利用苯硼酸增强细胞摄取和促进药物透过血脑屏障方面的研究进展.希望能为设计制备基于苯硼酸的新型蛋白质药物胞内递送体系提供借鉴.     

光控释药型药物递送系统的研究进展

释药可控的药物递送系统能够在特定刺激条件下,在时间和空间上精确实现在病灶处释放包载的药物分子,具有药物利用率高、毒副作用低等诸多优点,为各种重大疾病,如肿瘤的精准治疗提供了新思路.在众多的可控释药递送系统中,利用特定光照控制药物释放的光控释药型药物递送系统展现出广阔的应用潜力,受到研究者的广泛关注.近年来,基于不同光响应机理的光控释药型药物递送系统被设计开发用于药物的精确可控释放,本文介绍了四种光敏感基团的不同光响应机理,对基于不同光响应机理的光控释药型药物递送系统的研究进展进行了综述,指出现有光控释药型药物递送系统存在的问题及对未来的研究方向进行了展望.     

预置粒子对均匀胶体粒子形成的影响

研究预置粒子对于均匀胶体粒子形成的影响,对深入了解均匀粒子的形成机理以及开拓覆盖技术的应用具有重要意义.所谓预置粒子就是在经升温陈化能够生成均匀胶体粒子的溶液中,于陈化前加入的具有一定形态(组成、形状和大小),一定浓度的胶体粒子,新形成的沉淀物因预置粒子的表面性质、形态和浓度的不同而变化.据文献报导,新沉淀的形成过程有:①新粒子的形成与预置粒子的存在无关,新沉淀物独立成核并成长为独立的稳定     

Lennard-Jones流体中胶体粒子间耗尽势的密度泛函理论研究

基于Roth, Evans和Dietrich有关耗尽势的密度泛函理论研究了Lennard-Jones (L-J)流体中胶体粒子间的耗尽势. 通过计算胶体稀溶液中两个胶体粒子在不同条件下的耗尽势, 进一步分析了L-J流体的相关因素对耗尽势的影响. 结果表明, L-J流体分子的体积分数、胶体粒子与溶剂分子的尺寸比率、L-J流体分子间的相互作用以及胶体粒子与流体分子之间的弱相互作用等因素均可对胶体粒子间耗尽势产生显著影响. 研究结果可为实验上调控胶体粒子间的相互作用提供可能的线索.     

AaDd型氢键流体的统计理论（Ⅳ）：胶体粒子间的耗尽势

基于耗尽势的密度泛函理论研究了AaDd型氢键流体中胶体粒子间的耗尽势.针对胶体稀溶液,通过计算在不同条件下两个胶体粒子间的耗尽势和耗尽力,进一步分析了氢键流体中相关因素对二者的影响.结果表明,胶体粒子与流体分子的尺寸比率、氢键流体的体相密度、氢键键能、质子给体和受体数目以及胶体粒子与流体之间的弱相互作用等因素均可对胶体粒子间耗尽势产生显著影响.     

刺激响应性水凝胶在肿瘤治疗中的研究进展

恶性肿瘤的治疗在临床中一直备受关注，由于肿瘤细胞的浸润性和顽固性，常规治疗通常会产生严重的毒副作用。相较于全身化疗，局部载药水凝胶的使用显著降低了全身毒性并可实现药物在肿瘤部位的持续递送。此外，经物理掺杂或化学修饰的刺激响应性水凝胶，还可响应环境条件变化(如温度、pH、光等),实现原位交联和药物可控释放，大大提高了临床顺应性和药物递送效率。本综述分类讨论了用于肿瘤治疗的刺激响应性水凝胶的设计策略；汇总了近年来此类水凝胶的研究进展及其药物递送方案；并针对该领域存在的实际问题提出了可能的发展方向。     

多肽介导的肿瘤靶向纳米递药系统

肿瘤靶向纳米递药系统是指利用肿瘤组织特殊的生理病理特点,由纳米载体包载肿瘤诊疗药物构建而成的对肿瘤组织具有靶向定位功能的药物递送系统。多肽介导的肿瘤靶向纳米递药系统是肿瘤靶向递药领域较新的一个研究方向,本文综述了该研究方向的四个重要发展历程——单功能靶向、双功能靶向、肿瘤穿透和环境响应型靶向纳米递药系统,并介绍了各类递药系统的设计原理和典型研究案例。此外,对目前多肽介导的纳米递药系统存在的优势与不足进行了分析。最后,针对当前主动靶向肿瘤递药系统存在的研究困境,提出了一种新型肿瘤靶向递药策略——"系统性靶向"策略。随着相关学科和多学科交叉的发展,多肽介导的肿瘤靶向纳米递药系统将在肿瘤治疗中扮演更为重要的角色。     

二氧化碳和丙烯直接合成甲基丙烯酸的NiPMo/TiO2催化剂的研究

用溶胶-凝胶法以磷钼酸(MPA)的镍盐溶液水解钛酸四丁酯制备了NiPMo/TiO2催化剂.使用ICP、 XRD、 TG-DTA、 IR、 TPD-MS和微反应技术研究了催化剂的化学组成、热稳定性、化学吸附性质和催化反应性能.杂多钼酸盐与TiO2通过O2-在TiO2表面发生了键合.在623 K下,杂多阴离子仍保持原有的Keggin结构.CO2在Lewis酸位Ni(Ⅱ)和Lewis碱位Ni-O-Mo的桥氧协同作用下生成CO2卧式吸附态Ni(Ⅱ)←O-(CO)←(O--Ni).丙烯有多种吸附态在催化剂上吸附.在563 K、 1 MPa和空速1500 h-1的反应条件下,丙烯的摩尔转化率为3.2%,产物MAA选择性为95%.     

Synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives

Different approaches for the synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives from simple amino acids have been investigated. A library of 33 precursors for the preparation of N-hydroxy pyrazinones was obtained in moderate to good yields.     

A general and convenient synthesis of 4-(tosylmethyl)semicarbazones and their use in amidoalkylation of hydrogen,heteroatom, and carbon nucleophiles

A general synthesis of previously unknown semicarbazone-based α-amidoalkylating reagents, 4-(tosylmethyl)semicarbazones, has been developed. The synthesis involved three-component condensation of semicarbazones of aliphatic or aromatic aldehydes with the same or other aldehydes and p-toluenesulfinic acid. The scope and limitations of this reaction were investigated. The compounds obtained were demonstrated to be an efficient α-(4-semicarbazono)alkylating agents. They were reacted with H- (sodium borohydride), O- (sodium methylate), S- (sodium phenylthiolate), N- (pyrrolidine, sodium succinimide), P- (trialkyl phosphites), and C-nucleophiles (sodium diethyl malonate) to give the corresponding products of the tosyl group substitution, 4-substituted semicarbazones, including analogues of nitrofurazone. Among the prepared compounds tested in vitro for antibacterial and antifungal activity, three nitrofuryl-containing semicarbazones exhibited high biological activities with minimum inhibitory concentration (MIC) values of 8–32 μg/mL.     

Toward new camptothecins. Part 6: Synthesis of crucial ketones and their use in Friedländer reaction

In the context of the preparation of camptothecin and luotonin A analogs, the synthesis of some key keto-precursors and their use in Friedländer condensation are described. This paper also focuses on the stability of these keto intermediates and emphasizes the major differences between indolizinones and pyrroloquinazolinones series. Noteworthy is also the report of some original structures isolated as by-products of some experiments.     

Synthesis of novel chiral bidentate hydroxyalkyl-N-heterocyclic carbene ligands and their application in palladium-catalyzed Mizoroki–Heck couplings and asymmetric addition of diethylzinc to benzaldehyde

A small library of new chiral bidentate hydroxyalkyl-imidazolium salts 1 is conveniently synthesized on multi-gram scale from inexpensive and commercially available chiral pool amino acids. The corresponding carbenes, generated by deprotonation of imidazolium salts 1, in combination with palladium(II) chloride were tested in the Mizoroki–Heck coupling reaction. The most significant results in terms of yields and reactivities were achieved with low catalyst loading. The catalytic activities of these imidazolium salts were also investigated in the asymmetric addition of diethylzinc to benzaldehyde. The use of MgO nanoparticles as an additive in conjunction with these ligands played a crucial role in increasing the efficiency of these reactions.     

α-Amino acid derived enaminones and their application in the synthesis of N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates and other heterocycles

A new and simple synthesis of novel N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates, which exist in equilibrium with their 4-oxo tautomers, has been developed in two steps starting from N-protected α-amino acids. The key intermediates are enaminones, which can also be isolated, characterized, and used for the construction of other functionalized heterocycles, before they spontaneously decompose to pyrrole products. 4-Hydroxypyrroles are prone to partial aerial oxidation but can be efficiently alkylated or reduced to stable polysubstituted pyrrolidine derivatives.     

Specific intramolecular aromatic CH insertion of diazosulfonamides

The chemoselectivity in the intramolecular CH insertion of various diazosulfonamides has been experimentally studied. The results reveal that the aliphatic 1,4-, 1,5-, or 1,6-C(sp³)?H insertions of diazosulfonamides are not accessible, while the aromatic 1,5-C(sp²)?H insertion can be realized specifically by adjusting the diazo-adjacent group. In addition, the general chemoselectivities in the intramolecular CH insertions of diazosulfonyl compounds are summarized. Generally, diazosulfones undergo both aromatic 1,5-C(sp²)?H and aliphatic 1,5- and 1,6-C(sp³)?H insertions, while diazosulfonates undergo aliphatic 1,5- and 1,6-C(sp³)?H insertions. However, diazosulfonamides only undergo aromatic 1,5-C(sp²)?H insertion.     

CoFe2O4自形成磁性液体场致结构化对磁化的影响

The Langevin paramagnetic theory can’t describe the relation between magnetization of ferrofluids and applied magnetic field. The structuralization of ferrofluids, which is considered the main influence factor of the magnetization, is regarded. The part of magnetization works is deposited when the structure is forming. This action influences the magnetization of ferrofluids directly or indirectly. On the base of the “compressing” model, the Langevin function that usually describes the magnetization of ferrofluid is modified, and a well-fitted curve is obtained. An equation of the relation between the equivalent volume fraction after being “compressed” and the intensity of magnetic field is discovered, which approximately describes the process of magnetization. The relation between the approximate initial susceptibility and the volume fraction can be obtained from modified formula.     

Microwave-assisted copper-catalyzed stereoselective ring expansion of three-membered heterocycles with α-diazo-β-dicarbonyl compounds

Microwave-assisted copper-catalyzed ring expansions of three-membered heterocycles with α-diazo-β-dicarbonyl compounds were investigated. Thiiranes generated 3-acyl-5,6-dihydro-1,4-oxathiines in the presence of copper sulfate and trans-3-acyl-5,6-dihydro-1,4-oxathiines as stereospecific products for 1,2-disubstituted cis-thiiranes through an intramolecular S_N2 process. Oxiranes gave rise to 2-acyl-5,6-dihydro-1,4-dioxines under the catalysis of copper hexafluoroacetylacetonate and cis-3-acyl-5,6-dihydro-1,4-dioxines as stereospecific products for 1,2-disubstituted cis-oxiranes via an intimate ion-pair mechanism. The current method provides a direct and simple strategy in efficient preparation of 3-acyl-5,6-dihydro-1,4-oxathiines and 2-acyl-5,6-dihydro-1,4-dioxines, important agents in medicinal and agricultural chemistry, from readily available thiiranes and oxiranes, respectively.     

KMnO4-mediated oxidative CN bond cleavage of tertiary amines: Synthesis of amides and sulfonamides

KMnO₄-mediated oxidative CN bond cleavage of tertiary amines producing secondary amine was introduced, which was trapped by electrophiles (acyl chloride and sulfonyl chloride) to form amides and sulfonamides. The reaction could take place at mild condition, tolerating a wide range of function groups and affording products in moderate to excellent yields.