高效液相色谱-电喷雾质谱(HPLC-ESI-MS/MS)测定新型抗癌铂配合物

采用高效液相色谱-电喷雾-多级质谱法(HPLC-ESI-MS/MS), 研究了cis-3,5-diisopropylsalylic cyclohexanodiaminoplatinum(Ⅱ)的电喷雾质谱行为, 鉴定了其杂质, 并测定了其纯度.     

氮杂环卡宾-钯配合物催化Buchwald-Hartwig偶联反应最新研究进展*

钯催化的Buchwald-Hartwig偶联反应是用于构建C-N键非常直接有效的方法。氮杂环卡宾-钯配合物具有性能稳定、催化活性高等优点,是Buchwald-Hartwig偶联反应的高效催化剂。对这一领域近3年的研究进展作简要介绍。     

铜铝尖晶石“缓释催化”*

催化化学是物理化学中的重要内容,有着较强的实践意义。催化剂寿命是催化剂的主要指标之一,关系工业催化的经济成本。常用的负载型催化剂常由于反应温度高导致活性金属聚集长大而失活,采取增加载体表面积、提高负载量、增强金属/载体的相互作用等方法可以在一定程度上提高催化剂的稳定性和寿命,却无法从根本上阻止活性金属聚集长大的热力学趋势。近年来笔者将活性铜组分均匀分散到氧化铝体相中形成尖晶石型缓释催化剂,从而有效增加了催化剂的稳定性,有望充实物理化学中关于催化化学的内容。     

“聚沙成塔”——硅元素及其化合物*

硅是地壳中丰度较高的元素之一,也是生活中当之无愧的主角元素之一。针对当今社会最关心的信息、能源和健康等领域,着重介绍硅单质、硅酸盐和氧化硅,以及有机硅在这些领域中所起的重要作用和背后的化学基本原理,并简单展望其未来的发展方向。     

基于一氧化氮性质的几个探究性实验*

通过一系列实验探究进一步认识一氧化氮的性质,结果发现一氧化氮能在不同条件下表现出氧化性,且一氧化氮与Cu⁺会形成一种未知的较稳定配合物;此外,从环境保护的角度,基于一氧化氮在不同条件下的氧化性提出对汽车尾气以及工业废气进行转化处理的可能方案。     

非金属元素硒的同素异形体*

结合史实文献和最新研究成果,汇总了硒的同素异形体,可分为气态硒、液态硒、固体硒、纳米硒和硒团簇等5类,重点介绍了固体硒、纳米硒和硒团簇的种类、结构、性质、制备和应用等。完善了硒同素异形体在教学中的深入介绍,有助于体现科学研究对本科教学内容改革的推进作用。     

化学元素与新型食品包装材料*

随着人们消费观念的升级,食品包装材料备受关注。从化学元素的视角介绍了新型食品外包装材料和食品表面可食性涂膜包装材料的组成、特点及发展趋势。食品外包装制品材料中的纳米材料和生物基材料因机械性能好、绿色环保等特点,深受消费者欢迎。而食品表面可食性涂膜材料,在“即时消费”兴起的今天,也因操作简便、投资低、安全性高等特点赢得了大众的喜爱。从新型食品包装材料的研制开发过程来看,其创新发展与化学元素的性质密切相关,未来食品包装材料性能的提升也必须依靠特征性化学元素的组合与利用。     

金属配合物显色原理的课堂教学软件研发*

有关金属配合物颜色的形成原理是现行无机化学教学中的一大难点,基于深度学习理论,以六水合氯化镍为例,研发了一款金属配合物显色原理的教学软件。该软件以宏观问题引入教学,创设探究情境,展示了金属配合物的结构、d-轨道分裂的原因、金属配合物显色的原理,软件能帮助学生从金属配合物的结构上去认知其显色原理,拓展学生的视野,进而达成深度学习的目标。     

顺铂:从意外合成到抗癌应用

19世纪中叶,顺铂在实验室意外合成。18世纪末到19世纪80年代,以原子-分子论为基础的配合物理论,对顺铂结构的探索从依赖宏观现象和经验归纳发展为微观层面的假说演绎。19世纪末,电子的发现使得配合物理论进入电子时代,并因此对顺铂结构有了新的解释。20世纪60年代,顺铂的抗癌价值得以发现,至今仍不断改良顺铂以减弱其副作用。顺铂的合成和抗癌应用过程,包含着对物质由表及里的认识过程,展现了化学家认识物质、改造物质的动态发展过程,对化学研究和化学教育均有重要的启示。     

前沿科研引导下的纳米材料教学改革*

针对纳米材料课程知识点繁杂、实践性强的特点,提出在纳米材料课程教学中积极融入前沿科研实例。通过前沿科研成果、校企医教研结合、教学实验室建设和综合性课程考核等举措,促进本课程与实际应用结合,为创新课程的开展引入硬件条件,提升学生的课程参与度,提升学生解决问题的综合素质。引导学生主动学习、积极学习,从而达到纳米材料课程教研一体化、校企实践一体化,教学质量提高的良好效果。     

基于天然产物的铂类和芳基金属抗癌药物研究进展

临床使用的现代药物超过50%都来自于天然产物,它们不仅能够通过阻止细胞周期进程、抑制癌细胞存活信号通路以及调节免疫细胞等多种生物途径来阻止肿瘤生长及其进程,而且对正常组织表现出较低的毒性。虽然以顺铂为代表的金属抗肿瘤药物广泛用于临床,但是它们存在严重的耐药性和毒副作用,包括肾毒性、神经毒性等。因此,利用天然产物中的优势来改造铂类配合物,有望开发出新型铂类抗癌药物以克服铂药的缺陷。另一方面,芳基金属配合物因其良好的水溶性和对正常组织的低毒性受到了广泛关注,将天然产物与芳基金属配合物相结合,也为开发高效低毒的新型抗癌药物提供了更多可能。结合天然产物和金属各自优势开发基于天然产物的金属配合物作为抗癌剂已成为研究热点,开辟了抗癌的新途径。本文对已经报道的有关天然产物的铂类和芳基金属配合物的研究及作用机理进行了较为全面的综述,并对该领域的未来发展进行了展望。     

抗肿瘤多核铂配合物的研究

多核铂配合物作为非经典铂抗肿瘤药物,其抗肿瘤机制与现有铂类抗肿瘤药物不同,因而在克服现有铂类抗肿瘤药物耐药性方面有着巨大的潜力。本文综述了多核铂类抗肿瘤药物的研究进展,以连接铂原子的桥配体结构的不同,可分为六大类:以烷基二胺及其衍生物为桥的多核铂配合物、以含氮杂环为桥的多核铂配合物、以羧酸根为桥的多核铂配合物、以卤素离子为桥的多核铂配合物、以含硫配体为桥的多核铂配合物及以其他配体为桥的多核铂配合物。本文还介绍了这几类多核铂配合物的抗肿瘤机理及在克服顺铂耐药性机理方面的研究进展。     

铂抗癌药物研究进展

综述了铂抗癌药物作用机理及合成进展状况，并对该类药物的发展趋势进行了展望，参考文献31篇。     

DNA-Intercalative Platinum Anticancer Complexes Photoactivated by Visible Light

Photoactivatable agents offer the prospect of highly selective cancer therapy with low side effects and novel mechanisms of action that can combat current drug resistance. 1,8-Naphthalimides with their extended π system can behave as light-harvesting groups, fluorescent probes and DNA intercalators. We conjugated N-(carboxymethyl)-1,8-naphthalimide (gly-R-Nap) with an R substituent on the naphthyl group to photoactive diazido Pt^IV complexes to form t,t,t-[Pt(py)₂(N₃)₂(OH)(gly-R-Nap)], R=H ( 1 ), 3-NO₂ ( 2 ) or 4-NMe₂ ( 3 ). They show enhanced photo-oxidation, cellular accumulation and promising photo-cytotoxicity in human A2780 ovarian, A549 lung and PC3 prostate cancer cells with visible light activation, and low dark cytotoxicity. Complexes 1 and 2 exhibit pre-intercalation into DNA, resulting in enhanced photo-induced DNA crosslinking. Complex 3 has a red-shifted absorption band at 450 nm, allowing photoactivation and photo-cytotoxicity with green light.     

Substitution‐Inert Polynuclear Platinum Complexes That Inhibit the Activity of DNA Polymerase in Triplex‐Forming Templates

The formation of triple‐helical DNA is implicated in the regulation of gene expression. The triplexes are, however, unstable under physiological conditions so that effective stabilizers for the triplex formation are needed. Herein, we describe a new strategy for the stabilization of such triplexes that is based on antitumor substitution‐inert polynuclear platinum complexes (SI‐PPCs). These compounds were previously shown to bind to DNA through the phosphate clamp—a discrete mode of DNA–ligand recognition distinct from the canonical intercalation and minor‐groove binding. We have found that SI‐PPCs efficiently inhibit DNA synthesis by DNA polymerase in sequences prone to the formation of pyrimidine‐ and purine‐motif triplex DNAs. Moreover, the results suggest that SI‐PPCs are able to induce the formation of triple‐helical DNA between duplexes and strands that are not completely complementary to each other. Collectively, these data provide evidence that SI‐PPCs are very efficient stabilizers of triple‐stranded DNA that might exert their action by stabilizing higher‐order structures such as triple‐helical DNA.     

铂络合物的反相离子对色谱

在反相离子对色谱中,研究了四种离子对试剂对铂络合物保留值的影响。用流动相中离子-偶极作用物和铂络合物的结构说明了保留机理。用NaCl作内标测定了顺式-二氨-1,1-环丁二羧酸铂(Ⅱ)(碳铂)和顺式二氯二氨合铂(Ⅱ)(顺铂)样品,七次配样测定得到满意的回收率,相对标准偏差分别为0.7%和0.5%,检出限为75ng/ml和0.23μg/ml。     

无机纳米稀土发光材料的制备方法*

无机纳米稀土发光材料作为一种重要的发光材料,由于具有独特的光、电和化学性质,使其在高性能磁体、发光器件、显示、生物标记、光学成像和光学治疗等方面得到了广泛的应用。稀土发光材料的这些性质与材料的尺寸和形状密切相关,近年来研究者已经利用多种合成方法制备了不同形状的纳米稀土发光材料,包括纳米线、纳米棒、纳米管、纳米纤维和纳米片等。本文综述了无机纳米稀土发光材料的几种常用的制备方法,包括水热/溶剂热法、有机/无机前驱体热分解法和超声辅助合成法等,评述了这些方法的优缺点,并结合课题组在无机纳米稀土发光材料制备方面的工作,对无机纳米稀土发光材料制备方法的发展进行了展望。     

Influence of Ligand and Nuclearity on the Cytotoxicity of Cyclometallated C^N^C Platinum(II) Complexes

A series of cyclometallated mono- and di-nuclear platinum(II) complexes and the parent organic ligand, 2,6-diphenylpyridine 1 (HC^N^CH), have been synthesized and characterized. This library of compounds includes [(C^N^C)Pt^II( L )] ( L =dimethylsulfoxide (DMSO) 2 and triphenylphosphine (PPh₃) 3 ) and [((C^N^C)Pt^II)₂( L‘ )] (where L‘ =N-heterocycles (pyrazine (pyr) 4 , 4,4‘-bipyridine (4,4‘-bipy) 5 or diphosphine (1,4-bis(diphenylphosphino)butane (dppb) 6 ). Their cytotoxicity was assessed against four cancerous cell lines and one normal cell line, with results highlighting significantly increased antiproliferative activity for the dinuclear complexes ( 4 – 6 ), when compared to the mononucleated species ( 2 and 3 ). Complex 6 is the most promising candidate, displaying very high selectivity towards cancerous cells, with selectivity index (SI) values >29.5 (A2780) and >11.2 (A2780cisR), and outperforming cisplatin by >4-fold and >18-fold, respectively.     

A Rationally Designed Bimetallic Platinum (II)-Ferrocene Antitumor Agent Induces Non-Apoptotic Cell Death and Exerts in Vivo Efficacy

Despite phenomenal clinical success, the efficacy of platinum anticancer drugs is often compromised due to inherent and acquired drug resistant phenotypes in cancers. To circumvent this issue, we designed two heterobimetallic platinum (II)-ferrocene hybrids that display multi-pronged anticancer action. In cancer cells, our best compound, 2 , platinates DNA, produces reactive oxygen species, and has nucleus, mitochondria, and endoplasmic reticulum as potential targets. The multi-modal mechanism of action of these hybrid agents lead to non-apoptotic cell death induction which enables circumventing apoptosis resistance and significant improvement in platinum cross resistance profile. Finally, in addition to describing detail mechanistic insights, we also assessed its stability in plasma and demonstrate anticancer efficacy in an in vivo A2780 xenograft model. Strikingly, compared to oxaliplatin, our compound displays better tolerability, safety profile and efficacy in vivo.     

Platinum and rhodium complexes with isoleucinol-based bi- and tricyclic hydrophosphoranes

The complex formation of bi- and tricyclic hydrophosphorane derivatives of isoleucinol with [Pt(COD)Cl₂], [Rh(CO)₂Cl]₂, and [Rh(THF)₂(COD)]⁺BF₄ ^– (COD is cycloocta-1,5-diene) was investigated. In all cases, bicyclic hydrospirophosphorane selectively forms the metal chelates [M(²-PN)(X)Cl] (M = Pt, X = Cl; M = Rh, X = CO) and [Rh(²-PN)(COD)]⁺BF₄ ^–. («» denotes the residue of the hydrospirophosphorane ligand, which does not contain the P and N atoms). In addition, tricyclic hydrophosphorane (L) generates the phosphoranide complexes [Pt(¹-L)(COD)Cl]⁺Y^– (Y = Cl or BF₄). The structures of the new compounds were established by IR spectroscopy, ³¹P, ¹³C, ¹H, ²H, ¹¹B, ¹⁹F, and ¹⁹⁵Pt NMR spectroscopy, and plasma-desorption and electrospray ionization mass spectrometry. The possible mechanism of coordination of hydrophosphoranes is discussed.