基于N-羧甲基壳聚糖钆基磁共振造影剂的制备及性能

文通过在DTPA配体上修饰N-羧甲基壳聚糖（NCMCS）增加配体的分子量,构建配合物Gd-（DTPA-NCMCS）.测定了Gd-（DTPA-NCMCS）及对照组Gd-DTPA与Gd-（DTPA-CS）不同浓度的弛豫时间T₁,拟合了配合物的纵向弛豫率r₁,结果表明Gd-（DTPA-NCMCS）纵向弛豫能力明显强于Gd-DTPA,也高于配合物Gd-（DTPA-CS）,浓度梯度的体外加权成像图清晰地观察到配合物Gd-（DTPA-NCMCS）比Gd-DTPA、Gd-（DTPA-CS）对应水溶液的信号更强。MTT法测定了Gd-（DTPA-NCMCS）的IC₅₀值为568 μmol·L^-1,表现出良好的生物相容性。Gd-（DTPA-NCMCS）可作为潜在的磁共振造影剂。     

两亲性双核钆(Ⅲ)配合物的合成与肝选择MRI增强

通过二乙三胺五乙酸单环酸酐和乙二胺四乙酸单环酸酐分别与L-赖氨酸苄酯的双酰化反应,制得两种含有双胺羧螯合单元的配体.它们与GdCl₃·6H₂O反应得到相应的两亲性双核钆(Ⅲ)配合物.表征了配体和配合物的结构,测试了配合物的纵向弛豫效能(R1).进行了双DTPA酰(L-赖氨酸苄酯)钆(Gd₂-3_a)的急性毒性和与Gd-DTPA的动物T₁加权成像对比实验.结果表明,这两种新配合物的R1都高于Gd-DTPA.Gd₂-3_a无明显急性毒性,且比Gd-DTPA对肝区实质细胞有更长时间和更大程度的选择性增强.     

一种新型磁共振成像造影剂的制备及性能

通过酰化反应将窄分子量分布的低聚壳聚糖(CS_n, n＝6, 8, 11)引入到二乙三胺五乙酸(DTPA)中得到新型配体, 再与Mn²⁺配位得到3种顺磁性Mn(Ⅱ)基配合物, 其结构用IR、元素分析及电感耦合等离子体发射仪(ICP-AES)进行表征. 测定了配合物的纵向弛豫率(r₁), 结果表明, 这类造影剂的弛豫率高于商业化医用的磁共振成像对比剂Gd-DTPA. 通过等温滴定微量热法(ITC)测定了功能配合物与牛血清白蛋白(BSA)相互作用的热力学参数.     

酰胺衍生寡聚DTPA钆配合物的合成、表征及弛豫性能

以寡聚二乙撑三胺-N,N′-二(乙酰苯胺)-N,N′,N″-三乙酸([H₃L]_n)为配体, 与GdCl₃在二甲基甲酰胺-水混合溶剂中组装得到了寡聚金属螯合物. 采用傅里叶变换红外光谱(FTIR)、元素分析、核磁共振氢谱(¹H NMR)和热重及差热分析(TG-DTA)确定了寡聚金属螯合物的组成单元为[GdL(H₂O)]·4H₂O, 即寡聚配体的每个链节与1个金属离子配位. 采用反转恢复法测试了寡聚金属螯合物和小分子配合物Gd-DTPA(DTPA为二乙撑三胺五乙酸)的纵向弛豫时间T₁, 该寡聚金属螯合物体外弛豫率为8.526 mmol·L^-1·s^-1, 与配合物Gd-DTPA的弛豫率(4.370 mmol·L^-1·s^-1) 相比, 弛豫性能明显提高.     

二乙三胺五乙酸吡哆醇酯配体及其钆配合物的合成、弛豫率和肝靶向性研究

由维生素B₆族化合物吡哆醇及其衍生物与二乙三胺五乙酸(DTPA)双酸酐反应合成了一系列二乙三胺五乙酸吡哆醇酯配体.将这些配体与GdCl₃·6H₂O反应后得到了钆配合物.测定了这些配合物在水溶液中水质子的纵向弛豫率R₁.与母体配合物GdDTPA相比,R₁值略有提高.配体用放射性核素⁹⁹Tc标记,研究了其肝靶向性.结果表明,配体2和6的肝靶向性较为明显.动物核磁共振成像实验进一步证实由这两种配体合成的钆配合物对大鼠肝部的造影信号明显增强     

端氨基聚(醚-氨酯-酰胺)配体及磁共振成像造影剂研究

设计合成了一种端氨基聚(醚-氨酯)PEU-((CH2)6NH2)2(Ⅱ),以Ⅱ为原料制备端氨基聚(醚-氨酯-酰胺)PEU/DTPA共聚物造影剂配体(Ⅲ).Ⅲ的特点为(1)大分子配体的端基为—(CH2)6—NH2,柔性间隔基较长,可克服较大的空间位阻,与靶向性物质(如靶向多肽、蛋白质)反应;(2)原料Ⅱ为采用聚氨酯反应制备,亲水亲油链段长短、种类可控性好,实验条件简单;(3)端氨基可以在温和条件下与多肽等反应.大分子配体Ⅲ与Gd3+络合制备了相应的Gd3+配合物(Ⅳ),研究了Ⅳ的弛豫性能,磁共振成像(MRI)结果表明,合成的造影剂Ⅳ纵向弛豫速率(R1)与医用造影剂钆喷酸葡胺Gd-DTPA相比提高了38.40%,在裸鼠肝脏内信号增强率在0.1、6、12、24 h分别是Gd-DTPA最大信号增强的1.5、3、1.8和1.3倍,在体内的半衰期明显延长.用IR、NMR、GPC、官能团滴定、ICP等方法表征产物.     

含磺胺嘧啶基团的葡聚糖钆配合物的研究

将具有肿瘤靶向性的磺胺嘧啶(SD)、二乙三胺五乙酸(DTPA)与葡聚糖(dextran)大分子侧链羟基偶联,合成葡聚糖大分子配体(SD-Dextran-DTPA),再与金属钆离子Gd3+配合,从而制备肿瘤靶向性葡聚糖大分子钆配合物(SD-Dextran-DTPA-Gd).对所合成的配体及钆配合物进行FTIR、UV和1H-NMR等结构表征,测试了配体及钆配合物在水溶液中的粒径分布和zeta电位、钆配合物的体外弛豫率、细胞摄取与T1加权磁共振成像性能.与小分子钆-二乙三胺五乙酸(Gd-DTPA)相比,SD-Dextran-DTPA-Gd具有较高的弛豫率,对肺癌细胞系H460、乳腺癌细胞系MDA-MB-231和T40D均有较好的亲和性,可被肿瘤细胞较好地摄取,并能获得较好的肿瘤细胞磁共振成像.     

钆(Ⅲ)仿叶绿素配合物的合成、表征以及作为光磁双模式诊疗探针的应用

模拟自然界对四吡咯染料的β位调节方式,结合卟吩内酯近红外吸收和三线态能级可调、且易于修饰的优点,设计并合成了Gd(Ⅲ)卟吩内半缩醛配合物,并通过水溶性铵基修饰,使之具有两亲性质。该类配合物能较好地敏化O_2,单线态氧量子产率约0.75,且可应用于光毒性治疗,即使在红光(600~700 nm)激发下,其对He La细胞的半数致死浓度(IC50)仍低至1.5μmol·L~(-1)。同时,Gd-4的纵向弛豫率(r1)为1.1 mmol·L~(-1)·s~(-1)(0.5 T,37℃),表明配合物具有磁共振成像造影能力。因此,这类化合物具有光、磁双功能诊疗的潜在应用价值。     

肝靶向性聚天冬酰胺磁共振成像造影剂

用吡哆胺(PM)作为肝靶向基团,先与DTPA双N-羟基琥珀酰亚胺活性酯(SuO-DTPA-OSu)反应生成含一个吡哆胺的DTPA单N-羟基琥珀酰亚胺活性酯(SuO-DTPA-PM),再分别与α,β-聚(2-羟乙基)-L-天冬酰胺和α,β-聚(2-胺乙基)-L-天冬酰胺反应,合成了2类肝靶向性大分子配体,并制备了它们的Gd(Ⅲ)配合物.对所合成的大分子配体以及钆配合物进行了表征.测试了配合物的弛豫率.初步测试大分子载体PHEA和PAEA及其钆配合物的细胞毒性.研究了大分子配体在小白鼠体内分布和大分子钆配合物对大白鼠肝脏造影成像性能.结果表明,与临床广泛应用的小分子磁共振成像造影剂Gd-DTPA相比,以上2类大分子造影剂的弛豫率有明显的提高,并且具有较好的肝靶向性和肝脏成像对比度及清晰度.     

一种新的稀土配合物结构分析方法-无顺磁位移混合三稀土法

提出无顺磁位移混合三稀土配合物结构分析方法, 并以丙氨酸稀土为例, 选取Eu-Yb-Pr和Er-Yb-Pr体系从实验上予以验证。研究发现, 通过选择适当的三种顺磁性稀土离子以一定比例混合, 可以抵消顺磁诱导位移, 仅保留顺磁弛豫增强效应, 因而可直观地从谱线半高宽(W1/2)看出稀土配合位点, 从纵向弛豫时间(T1)或谱线半高宽计算稀土与配体磁核间的相对距离。     

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.     

N-Heterocyclic carbene-palladacyclic complexes: synthesis,characterization and their applications in the C-N coupling and α-arylation of ketones using aryl chlorides

N-Heterocyclic carbene-palladacyclic complexes 3 were successfully achieved in a one-pot procedure under mild conditions. The structure of 3a was unambiguously confirmed by X-ray single crystal diffraction and it was an active catalyst in the Buchwald-Hartwig amination and α-arylation of ketones even at very low catalyst loadings (0.01?mol%).     

Iodine-mediated oxidative Pictet-Spengler reaction using terminal alkyne as the 2-oxoaldehyde surrogate for the synthesis of 1-aroyl-β-carbolines and fused-nitrogen heterocycles

An efficient iodine-mediated oxidative Pictet-Spengler reaction in dimethyl sulphoxide (DMSO) using terminal alkynes as the 2-oxoaldehyde surrogate for the synthesis of aryl (9H-pyrido[3,4-b]indol-1-yl)methanones is described. The scope of the protocol includes the total synthesis of Fascaplysin, Eudistomins Y₁ and Y₂. The methodology is extended for preparing pyrrolo[1,2-a]-quinoxaline and indolo[1,5-a]quinoxaline derivatives. The utility of 1-aroyl-β-carbolines was demonstrated by performing palladium-catalyzed β-carboline directed ortho-C(sp2)-H functionalization of the phenyl ring with thiomethyl (SMe) group using DMSO as source and for accessing 4-aryl-canthin-6-ones.     

Facile synthesis of bicyclic 1-arylpyrazol-5-ones

In this Letter, we described a facile method for constructing fused bicyclic 1-arylpyrazol-5-one ring system. We employed various methylene-containing carboxylic acids as the substrates and proved that the pyrazolone ring closure requires activated methylene group in intermediate II. Accordingly, a series of structurally diversified, fused bicyclic 1-arylpyrazol-5-ones was prepared in moderate to high yields using the requisite substrates.     

Synthesis of pyrrolo[1,2-a]pyrazines and pyrazino[1,2-a]indoles by Curtius reaction in Morita-Baylis-Hillman derivatives

Synthesis of substituted pyrrolo[1,2-a]pyrazines and pyrazino[1,2-a]indoles from the Morita-Baylis-Hillman derivatives of acrylates via saponification followed by Curtius reaction is described.     

正丁胺对激光染料荧光谱影响的研究

用正丁胺作为碳源,采用射频辉光放电制备碳膜,选用激光染料R6G和聚乙二醇混合液作为蒸气源,采用单源热蒸发,在蒸发室与染料同时沉积得到混合膜,用拉曼光谱和红外光谱分析了碳膜的结构和键合方式,分析表明:碳膜中存在胺基团和氢原子.混合膜的荧光谱测量结果表明,认为正丁胺对染料荧光谱的影响是因为胺基和氢原子的存在.     

Cu0-catalysed 1,3-dipolar cycloadditions of α-amino acid derived N,N-cyclic azomethine imines to ynones

A series of 20 CuAIAC reactions between eight 4-acylamino substituted pyrazolidine-3-one-1-azomethine imines and four terminal ynones were performed using Cu⁰ as catalyst. The corresponding fluorescent cycloadducts were obtained in very high yields upon simple workup. Thus, Cu-metal turned out to be a better catalyst than Cu^I in terms of yield and ease of isolation. Availability of azomethine imines, mild reaction conditions, and simple workup enable a “click” access to libraries of densely substituted 2,3-dihydro-1H,5H-pyrazolo[1,2-a]pyrazol-1-ones. Reactivity of differently substituted dipoles was evaluated experimentally and by quantum chemical methods (DFT).     

Synthesis and antioxidative/anti-inflammatory activity of novel fullerene–polyamine conjugates

(E)-4-(Fullerenopyrrolidin-1-yl)-3-methylbut-2-enoic acid and its corresponding succinimidyl ester, readily obtained through Prato-type modification of C₆₀, were used for the selective N-acylation of polyamines. The thus obtained conjugates were evaluated for their antioxidative and anti-inflammatory activity and their cytotoxicity was determined. Members of this family of compounds showed interesting anti-lipid peroxidation, anti-lipoxygenase and anti-inflammatory activity and comparable cytocompatibility to spermidine.