脲基苯乙炔4＇-（对甲基苯基）-6-苯基-2,2＇-二联吡啶铂（Ⅱ）络合物的合成

本文通过异氰酸酰化反应合成了含有脲基的苯乙炔新型配体及以它作为辅助配体的4'-(对甲基苯基)-6-苯基-2,2'-二联吡啶铂(Ⅱ)络合物,初步研究了铂(Ⅱ)络合物的光物理性质,发现由于脲基的存在,当浓度大于3.32×10-5mol/L时铂(Ⅱ)络合物能够发生分子间簇集.     

4-(4-甲基苯基)-6-苯基-2,2′-二联吡啶芳炔铂(II)络合物的合成及光物理性质

设计合成以4-甲基苯基-6-苯基-2,2′-二联吡啶为主配体、芳炔为辅助配体的铂(II)络合物1-3.与苯乙炔、萘乙炔为辅助配体的络合物1,2相比,蒽乙炔4-(4-甲基苯基)-6-苯基-2,2′-二联吡啶铂(II)络合物MLCT激发态的能量升高.     

4-（4-甲基苯基）-6-苯基-2，2’-二联吡啶芳炔铂（Ⅱ）络合物的合成及光物理性质

设计合成以4-甲基苯基-6-苯基-2，2’-二联吡啶为主配体、芳炔为辅助配体的铂（Ⅱ）络合物1-3．与苯乙炔、萘乙炔为辅助配体的络合物1，2相比。蒽乙炔4-（4-甲基苯基）-6-苯基-2，2’-二联吡啶铂（Ⅱ）络合物MLCT激发态的能量升高．     

2-(苯乙炔基)烟碱醛的合成研究

以2-氯烟碱醛和苯乙炔为原料,在双三苯基膦二氯化钯催化作用下,发生Sonogashira偶联反应,得到目标化合物2-(苯乙炔基)烟碱醛,产物结构通过核磁共振氢谱和质谱表征.并研究该偶联反应最佳条件为:物料比n(苯乙炔)∶n(2-氯烟碱醛)=1.8∶1;钯催化剂用量为n(双三苯基膦二氯化钯)∶n(2-氯烟碱醛)=0.06...     

2-甲基-4-(4-(吡啶-4-乙炔基)苯基)-3-丁炔-2-醇的合成及结构表征

由1,4-二碘代苯出发,经过两步Sonogashira偶联反应合成标题化合物2-甲基-4-(4-(吡啶-4-乙炔基)苯基)-3-丁炔-2-醇。通过1 H NMR、13 C NMR核磁共振、X射线单晶衍射等手段对化合物的结构进行了表征。结果表明,该化合物属于单斜晶系,空间群为P2(1)2(1)2(1)。晶体学参数:a=0.060754(15)nm,b=0.081700(19)nm,c=0.32073(7)nm,α=90.00°,β=90.00°,γ=90.00°,V=15.920(7)nm3,Z=8。     

间／对混合二乙炔基苯的合成

混合二乙炔基苯在药物合成,液晶材料,航天航空材料等方面具有十分重要的用途,因而较大规模地合成二乙炔基苯受到广泛的关注.今从工业级二乙烯基苯(含间二乙烯基苯59.5%,对二乙烯基苯21.8%,间乙基苯乙烯11.3%,对乙基苯乙烯7.4%)出发,经溴化加成反应得到二(α,β-二溴乙基)苯(或相应的溴化物),冷却后分离出部分对二(α,β-二溴乙基)苯,残余物经减压蒸馏分离出沸点小于160℃ / 1～2 mmHg的间/对乙基-α,β-二溴乙基苯,使间/对二(α,β-二溴乙基)苯的含量达到98%以上.后者在乙醇钠/乙醇介质中脱去溴化氢,经纯化处理后得到含量98%的间/对混合二乙炔基苯.讨论了影响各步反应及分离的因素,给出了较佳的反应参数,使用上述条件实现了50kg/批规模的生产.     

1-甲氧基-9,10-双(苯乙炔基)蒽的合成

由１－硝基蒽醌与甲酸钠作用生成１－甲氧基蒽醌,收率７５％。１．甲氧基蒽醌与苯乙炔基溴化镁在ＴＨＦ中回流２４ｈ,水解后的混合物不经分离直接与氯化亚锡的乙酸溶液反应３０ｍｉｎ,一步法合成了题示化合物,收率４６％。     

1-(5-(4-氯苯基)-1-(2,4-二氯苯基)-4-甲基-1H-吡唑-3-基)-3-(吡啶-3-基甲基)脲的合成

以5-(4-氯苯基)-1-(2,4-二氯苯基)-4-甲基-1H-吡唑-3-甲酸与二氯亚砜为起始原料,经酰氯化反应、酰胺反应、霍夫曼重排以及水解反应生成中间体5-(4-氯苯基)-1-(2,4-二氯苯基)-3-氨基-4-甲基-1H-吡唑,再经过与氯甲酸苯酯反应、胺酯交换反应得到标题化合物,其结构经1HNMR、MS谱确证,总收率26.9%。     

高纯度对二乙炔基苯的合成(偶合法)和表征

以对二溴苯、甲基丁炔醇为原料,PdCl2(PPh3)2和CuI为催化剂,四氢呋喃/三乙胺做混合溶剂,60℃反应6 h得到偶合中间体,并在NaOH作用下发生水解反应,得到对二乙炔基苯.分别用1HNMR、气相色谱(GC)、熔点仪对其结构和纯度进行表征.最终产物为白色晶状对二乙炔基苯,总产率为92.6%,纯度>99.9%.     

1,3-二(3′-溴苯基)-5-(4′-氯苯基)苯的合成

以苯乙酮、溴素为原料 ,无水三氯化铝为催化剂 ,按n (苯乙酮 )∶n (溴素 )∶n (AlCl3) =1.8∶2 .3∶4.2制得间溴苯乙酮 ,产率为 6 5 % ;间溴苯乙酮与催化剂四氯化硅按n(间溴苯乙酮 )∶n(四氯化硅 ) =1∶1在无水乙醇中经缩合反应制得 1,3 二 (3′ 溴苯基 )丁烯 2 酮 1(A) ,产率为5 2 % ,以此为中间体与对氯苯乙酮在四氯化硅催化下按n(A)∶n (对氯苯乙酮 )∶n (四氯化硅 )=1.0∶1.0∶2 .5经缩合反应 ,合成了 1,3 二 (3′ 溴苯基 ) 5 (4′ 氯苯基 )苯 (B) ,产率为 43%。     

二苯氨基修饰的阳离子型环金属铂(II)配合物的合成及性能

以1,10-邻菲罗啉为辅助配体，设计合成了三个二苯氨基修饰的阳离子型环金属铂(II)配合物Ⅰ-Ⅲ。系统研究了配合物的光物理、电化学及氧传感性能。结果表明，在2-(4-二苯氨基)苯基吡啶的吡啶环的5位引入不同基团，可实现铂(II)配合物的发光波长在544 nm - 583 nm之间调控。其中，在吡啶环的5位引入三氟甲基的配合物Ⅲ的最大发射波长为583 nm。氧传感性能测试结果表明，在吡啶环的5位引入三氟甲基的配合物Ⅲ的氧敏感性能显著提升，其在DMF溶液中的I0/I2.17值为6.4。     

抗肿瘤潜在药物―酰肼类铂配合物合成路线简介

介绍了包括苯磺酰肼和苯甲酰肼等酰肼类铂配合物的一些合成方法,并对其中一些物质所具有的潜在生物活性作了简单评价。     

A Comparative Study of the Effects of Platinum (II) Complexes on β-Amyloid Aggregation: Potential Neurodrug Applications

Herein the effects of three platinum complexes, namely (SP-4-2)-(2,2′-bipyridine)dichloridoplatinum(II), Pt-bpy, (SP-4-2)-dichlorido(1,10-phenanthroline) platinum(II), Pt-phen, and (SP-4-2)-chlorido(2,2′:6′,2′′-terpyridine)platinum(II) chloride, Pt-terpy, on the aggregation of an amyloid model system derived from the C-terminal domain of Aβ peptide (Aβ_21–40) were investigated. Thioflavin T (ThT) binding assays revealed the ability of Pt(II) compounds to repress amyloid aggregation in a dose-dependent way, whereas the ability of Aβ_21–40 peptide to interfere with ligand field of metal complexes was analyzed through UV-Vis absorption spectroscopy and electrospray ionization mass spectrometry. Spectroscopic data provided micromolar EC₅₀ values and allowed to assess that the observed inhibition of amyloid aggregation is due to the formation of adducts between Aβ_21–40 peptide and complexes upon the release of labile ligands as chloride and that they can explore different modes of coordination toward Aβ_21–40 with respect to the entire Aβ_1–40 polypeptide. In addition, conformational studies through circular dichroism (CD) spectroscopy suggested that Pt-terpy induces soluble β-structures of monomeric Aβ_21–40, thus limiting self-recognition. Noticeably, Pt-terpy demonstrated the ability to reduce the cytotoxicity of amyloid peptide in human SH-SY5Y neuroblastoma cells. Presented data corroborate the hypothesis to enlarge the application field of already known metal-based agents to neurodegenerative diseases, as potential neurodrugs.     

Synthesis, Spectral and Antibacterial Studies of Copper(II) Tetraaza Macrocyclic Complexes

A novel family of tetraaza macrocyclic Cu(II) complexes [CuLX(2)] (where L = N(4) donor macrocyclic ligands) and (X = Cl(-), NO(3) (-)) have been synthesized and characterized by elemental analysis, magnetic moments, IR, EPR, mass, electronic spectra and thermal studies. The magnetic moments and electronic spectral studies suggest square planar geometry for [Cu(DBACDT)]Cl(2) and [Cu(DBACDT)](NO(3))(2) complexes and distorted octahedral geometry to the rest of the ten complexes. The biological activity of all these complexes against gram-positive and gram-negative bacteria was compared with the activity of existing commercial antibacterial compounds like Linezolid and Cefaclor. Six complexes out of twelve were found to be most potent against both gram-positive as well as gram-negative bacteria due to the presence of thio group in the coordinated ligands.     

Lewis Acid Behavior of Cationic Complexes of Palladium(II) and Platinum(II): Some Examples of Catalytic Applications

The behavior of a variety of cationic diphosphine complexes of Pd(II) and Pt(II) as Lewis acid catalysts is reviewed. The reactions considered are the Baeyer–Villiger oxidation of ketones, the acetalization of aldehydes and ketones and the Diels–Alder reaction in both their regular and enantioselective version.     

新型多吡啶铂(Ⅱ)络合物的设计、合成及性能研究

由于特殊的分子构型及电子排布,具有平面四边形构型的多吡啶Pt(Ⅱ)络合物能够产生许多特殊的、具有潜在应用价值的激发态性质．本论文设计、合成了一系列以三联吡啶、6-苯基-2,2’-二联吡啶、菲啰啉为主配体,取代苯乙炔为辅助配体的多吡啶Pt(Ⅱ)络合物,系统地研究了它们的光物理性质,取得如下有意义的研究结果:     

Reduction of nitroaromatics with poly(vinylpyridine) complexes of palladium(II) and platinum(II)

Palladium(II) and platinum(II) anchored to 2- and 4-vinylpyridine polymers of different molecular weights were used for the dihydrogen reduction of various nitroaromatics and benzaldehyde in ethanol at 50°C. Palladium(II) complexes were far more effective than their platinum(II) analogues and the activity decreased with increasing molecular weights of the polymers. The nitroaromatics were selectively and almost completely reduced to the corresponding anilines. During reduction, the orange palladium(II) complexes changed to voluminous green precipitates, which could be used repeatedly and preserved for a long time without any loss of activity. A rate equation of the type: rate = K[Cat] [H₂] has been derived and a reduction mechanism has been proposed on the basis of experimental results and kinetic data.     

琥珀酰化壳聚糖-铜(Ⅱ)-苯并咪唑衍生物配合物的合成、表征及抗菌活性

文章利用琥珀酸酐对壳聚糖进行改性,并合成了两个新的配合物:sucts-Cu(Ⅱ)-hpb(1)和sucts-Cu(Ⅱ)-tbz(2)[sucts=琥珀酰化壳聚糖,hpb=2-(2’-吡啶)-苯并咪唑,tbz=2-(4′-噻唑基)苯并咪唑]。应用红外光谱,紫外-可见光谱,原子吸收光谱对配合物进行了表征,采用试管倍比稀释法研究了这些配合物对苏云金杆菌、枯草芽孢杆菌、大肠杆菌和金黄色葡萄球菌的抑制作用。结果表明,两种配合物对四种细菌均有较强的抑菌活性,配合物1、2,最小抑菌浓度(MIC)分别为62.5～125μg.mL-1和125～250μg.mL-1,抗菌效果明显强于自由配体。     

Reactions with Proteins of Three Novel Anticancer Platinum(II) Complexes Bearing N-Heterocyclic Ligands

Three novel platinum(II) complexes bearing N-heterocyclic ligands, i.e., Pt2c, Pt-IV and Pt-VIII, were previously prepared and characterized. They manifested promising in vitro anticancer properties associated with non-conventional modes of action. To gain further mechanistic insight, we have explored here the reactions of these Pt compounds with a few model proteins, i.e., hen egg white lysozyme (HEWL), bovine pancreatic ribonuclease (RNase A), horse heart cytochrome c (Cyt-c) and human serum albumin (HSA), primarily through ESI MS analysis. Characteristic and variegate patterns of reactivity were highlighted in the various cases that appear to depend both on the nature of the Pt complex and of the interacting protein. The protein-bound Pt fragments were identified. In the case of the complex Pt2c, the adducts formed upon reaction with HEWL and RNase A were further characterized by solving the respective crystal structures: this allowed us to determine the exact location of the various Pt binding sites. The implications of the obtained results are discussed in relation to the possible mechanisms of action of these innovative anticancer Pt complexes.     

Methyl 6‐Amino‐6‐deoxy‐d‐pyranoside‐Conjugated Platinum(II) Complexes for Glucose Transporter (GLUT)‐Mediated Tumor Targeting: Synthesis,Cytotoxicity, and Cellular Uptake Mechanism

Methyl 6‐aminodeoxy‐d ‐pyranoside‐derived platinum(II) glycoconjugates were designed and synthesized based on the clinical drug oxaliplatin for glucose transporter (GLUT)‐mediated tumor targeting. In addition to a substantial improvement in water solubility, the conjugates exhibited cytotoxicity similar to or higher than that of oxaliplatin in six different human cancer cell lines. GLUT‐mediated transport of the complexes was investigated with a cell‐based fluorescence competition assay and GLUT‐inhibitor‐mediated cytotoxicity analysis in a GLUT‐overexpressing human colorectal adenocarcinoma (HT29) cell line. The antitumor effect of the aminodeoxypyranoside‐conjugated platinum(II) complexes was found to depend significantly on the GLUT inhibitor, and the cellular uptake of the molecules was regulated by GLUT‐mediated transport. The results from this study demonstrate the potential advantages of aminodeoxypyranosides as sugar motifs for glycoconjugation for Warburg‐effect‐targeted drug design. These fundamental results also support the potential of aminodeoxypyranoside‐conjugated platinum(II) complexes as lead compounds for further preclinical evaluation.