载有5-氟脲嘧啶高分子药物的合成、结构及性能的研究

用可溶性淀粉或羧甲基纤维素作载体,合成了侧链连有5-氟脲嘧啶的四个系列的高分子载体药物;用分子筛作催化剂合成了两种新的5-氟脲嘧啶衍生物,利用IR、¹HNMR和质谱确定了它们的结构;研究了高分子药物含氮量随反应条件的变化规律及对其特性粘度的影响;并模拟生理条件在不同pH的缓冲溶液中对5-氟脲嘧啶的水解释放率进行了系统考查,对个别淀粉衍生物进行了生物活性测定。     

Synthesis, Characterization, and Spectroelectrochemistry of Cobalt Porphyrins Containing Axially Bound Nitric Oxide

Several cobalt nitrosyl porphyrins of the form (T(p/m-X)PP)Co(NO) (p/m-X = p-OCH(3) (1), p-CH(3) (2), m-CH(3) (3), p-H (4), m-OCH(3) (5), p-OCF(3) (6), p-CF(3) (7), p-CN (8)) have been synthesized in 30-85% yields by reaction of the precursor cobalt porphyrin with nitric oxide. Compounds 1-7 were also prepared by reaction of the precursor cobalt porphyrin with nitrosonium tetrafluoroborate followed by reduction with cobaltocene. Compounds 1-8 have been characterized by elemental analysis, IR and (1)H NMR spectroscopy, mass spectrometry, and UV-vis spectrophotometry. They are diamagnetic and display nu(NO) bands in CH(2)Cl(2) between 1681 and 1695 cm(-)(1). The molecular structure of 1, determined by a single-crystal X-ray crystallographic analysis, reveals a Co-N-O angle of 119.6(4) degrees. Crystals of 1 are monoclinic, P2/c, with a = 15.052(1) ?, b = 9.390(1) ?, c = 16.274(2) ?, beta = 111.04(1) degrees, V = 2146.8(4) ?(3), Z = 2, T = 228(2) K, D(calcd) = 1.271 g cm(-)(3), and final R1 = 0.0599 (wR2 = 0.1567, GOF = 1.054) for 3330 "observed" reflections with I >/= 2sigma(I). Cyclic voltammetry studies in CH(2)Cl(2) reveal that compounds 1-7 undergo two reversible oxidations and two reversible reductions at low temperature. This is not the case for compound 8, which undergoes two reversible reductions but an irreversible oxidation due to adsorption of the oxidized product onto the electrode surface. Combined electrochemistry-infrared studies demonstrate that each of the compounds 1-7 undergoes a first oxidation at the porphyrin pi ring system and a first reduction at either the metal center or the nitrosyl axial ligand. The formulation for the singly oxidized products of compounds 1-7 as porphyrin pi-cation radicals was confirmed by the presence of bands in the 1289-1294 cm(-)(1) region (for compounds 1-5), which are diagnostic IR bands for generation of tetraarylporphyrin pi-cation radicals.     

哌嗪取代卟啉的合成、表征及其抗癌活性

设计并合成了6个具有抗癌活性的哌嗪取代卟啉化合物,分别为5,10,15,20-四[4-(4'-乙基哌嗪基)苯基]卟啉(TEPPH2,8a),5,10,15,20-四[4-(4'-丁基哌嗪基)苯基]卟啉(TBPPH2,8b),5,10,15,20-四[4-(4'-庚基哌嗪基)苯基]卟啉(THPPH2,8c),5,10,15,20-四[4-(4'-苯基哌嗪基)苯基]卟啉(TPhPPH2,8d),5-[4-(4'-乙基哌嗪基)苯基]-10,15,20-三苯基卟啉(EPTPPH2,8e)和5-[4-(4'-丁基哌嗪基)苯基]-10,15,20-三苯基卟啉(BPTPPH2,8f).这些卟啉化合物都由取代苯甲醛与吡咯缩合而成,每一个卟啉分子中含有一个或四个具有抗癌活性的取代哌嗪结构,结构经元素分析,MS,1H NMR,IR和UV-vis等表征.初步的生物活性研究表明,这些化合物具有一定的抗癌活性,因而在医学上可能具有潜在应用前景.     

Synthesis Structure and Behavbr of Polymeric Drugs Covalently Linked 5-Fluorouracil

Four series of polymeric drugs with 5-Fluorouracil(5-FU) cova-lently linked in side chain were synthesized by the use of starch and carboxylmethylcellulose and two new 5-FU derivatives were also synthesized by using molecular sieve as a catalyst.Their structures were determined by IR,1H NMR and mass spectra.The changes in the Nitrogen content of polymeric drugs with reaction conditions and the influences of the N content on their limiting viscosity were studied.The hydrolysis of 5-FU from starch and carboxylmethylcellulose derivatives in various of buffer were researched by simulating physiologically acid-alkali enviroment.In addition,anticancer activity(in vivo and in vitro) of some starch derivative has been preliminaryly observed.     

几种对称镍卟啉配合物的合成、表征和电化学性质

卟啉试剂是一类重要的离子配位显色剂,在生物体中具有重要作用．作为自然界存在的金属卟啉之一,镍卟啉的电化学研究具有化学和生物学意义．四对羟基苯基卟啉合成已有不少报道［１,２］,但产率较低,只有１０％左右．Ｌｉｎｄｓｅｙ等发现用ＢＦ３作催化剂,在ＣＨ２Ｃ...     

Synthesis of Lactosylated Piperazinyl Porphyrins and Their Biological Activity

The aim of this work is to synthesize of a new family of lactosylated piperazinly porphyrins, in which the galactoside piperazine moieties are linked to the tetra‐ and mono‐phenyl rings of tetraphenylporphyrin (TPP). 5,10,15,20‐Tetrakis[4‐(4‐lactobionylpiperazin‐1‐yl)phenyl]porphyrin (TLPP) and 5‐mono[4‐(4‐lactobionylpiperazin‐1‐yl)phenyl]‐10,15,20‐triphenylporphyrin (MLPP) have been synthesized. A detailed ¹H NMR study gave their complete structural elucidation. The UV‐Visible, mass spectra and elemental analysis are also presented. The biological activity on cancer cells and the pharmacokinetics have also been evaluated, showing a better biological activity, a very high liver to skin ratio and short retention time in tissues. It was suggested that such novel lactosylated piperazinly porphyrins, as potential hepatocyte‐selective targeting drugs, exhibit a promising activity in photodynamic therapy (PDT).     

Blocking Behavior of Covalently Attached Anthraquinone Towards Solution‐Based Redox Probes

The electrochemical properties of glassy carbon (GC) electrodes modified with 9,10‐anthraquinone (AQ) have been investigated. Electrografting of GC surface was carried out from the solution of the AQ diazonium derivative. The blocking action of GC/AQ electrodes for Fe(CN)$\rm{{_{6}^{3-}}}$ and Ru(NH₃)$\rm{{_{6}^{3+}}}$ redox probes was studied using cyclic voltammetry (CV) and the rotating disk electrode (RDE) method. It was established that the extent of blocking was a function of AQ surface concentration. A peculiar behavior was observed at the potentials of AQ reduction.     

Studies on Synthesis and Chromatographic Properties of NAD Covalently Bound onto Phospholipid-Coated Aminated Silica

Abstract

Recently affinity chromatography with a biospecific stationary phase was widely used in separation and purification processes of all kinds of enzymes. In this paper, a series of synthetic reactions of solid-liquid phase on a silica surface are described. By using a wide-pore (30μm). microspheric silica (8μm) as the matrix and γ-aminopropyltriethoxy-silane as the activating agent, the nicotinamide adenine dinucleotide (NAD) was bonded through its amino groups with carboxylic groups of linked phospholipid by a covalent bond on the aminated supports. This bonded stationary phase provided high thermal stability which could be used for separating nucleotides with good resolution. At the same time, the effects of pH, organic modifier and ionic strength on the retention properties of nucleotides were also investigated.     

卟啉多枝分子合成与分子内能量转移、双光子吸收性能研究

以三苯胺或硝基苯为端基, 合成了三个卟啉多枝分子: 5-(4-硝基苯甲酰氧基)苯基-10,15,20-三-(4-溴苯基)卟啉(TPP-NO₂)、5-(4-硝基苯甲酰氧基)苯基-10,15,20-三-(4-二苯胺基-1-苯乙烯基)苯基卟啉(TPP-X₃)和5,10,15,20-四-(4-二苯胺基-1-苯乙烯基)苯基卟啉(TPP-X₄), 进行了红外光谱、核磁共振光谱和质谱表征. 比较研究了分子“枝”、“核”不同键合方式与不同对称结构对分子的线性光谱、非线性光谱以及分子内能量转移行为的影响. 在钛宝石激光器(800 nm)和Nd∶YAG倍频光(532 nm)泵浦下, 样品溶液均发出卟啉环特有的红色荧光——前者系双光子吸收机制“上转换”荧光, 后者则为双光子吸收与分子内能量转移机制“下转换”荧光. 飞秒Z-scan技术测得样品双光子吸收截面最大可达130 GM, 与四苯基卟啉(TPP)同等测试条件下的双光子吸收截面相比增大了两个数量级.     

Fullerene C60 Bound to Insoluble Hydrophilic Polymer: Synthesis,Photophysical Behavior,and Generation of Singlet Oxygen in Water Suspensions

Fullerene C₆₀ has been covalently bound to an insoluble hydrophilic polymeric matrix: Sephadex ^® G‐200. The new polymeric equivalent of C₆₀ swells in H₂O to form gel‐like suspensions. The transient photochemical behavior of this polymeric fullerene has been studied in dry and H₂O‐suspended samples. Both samples show a transient absorption similar to the absorption of the parent C₆₀ solution. There is a lack of triplet‐triplet annihilation and of a O₂‐quenching process in the dry sample. On the contrary, the O₂‐quenching process is very efficient in the H₂O‐suspended samples (k_q(O₂)=(1.9±0.5)×10⁸ dm³ mol⁻¹ s⁻¹) and results in the formation of singlet oxygen, which is detected by its emission at 1270 nm. These results point to this hydrophilic polymeric equivalent of C₆₀ as a good candidate for use as a singlet‐oxygen solid sensitizer in H₂O suspensions.     

β-Diketonates of Cyclopalladated Arylazonaphthalenes: Synthesis, Characterization and Redox Activity

The synthesis of monomeric mixed species of the type [PdLK] (L = cyclopalladated arylazonaphthalenes) have been achieved by splitting the halogeno-bridge in [Pd₂L₂Cl₂] by β-diketones (HK). The compounds have been characterized on the basis of spectral (IR, UV–VIS, FAB mass, ¹H and ¹³C{¹H}NMR) and elemental analysis data. Some of the [PdLK] cyclometallates occur as isomeric mixtures whose composition have been established by ¹H-NMR data. Electron transfer properties of the cyclopalladates in DMF have been thoroughly examined using cyclic voltammetry.     

Synthesis and Steroidogenic Activity of Covalently Dimerized Corticotropin (ACTH) Fragments

The chemical synthesis by classical methods in solution of a dimer of the sequence 1 to 24 of adrenocorticotropin(ACTH) is described. The two monomers were covalently linked through their C-termini, using lysine amide as spacer. Dimerization did not improve significantly the potency of the agonist ACTH-(1–24), while it strongly potentiated the antagonistic effect of the fragments ACTH-(11–24) and ACTH-(7–24) in the stimulation of steroidogenesis in isolated adrenal cells. The results seem to imply a microaggregation of the receptors at the adrenal cell surface.     

Flavin Derivatives with Tailored Redox Properties: Synthesis,Characterization, and Electrochemical Behavior

This study establishes structure–property relationships for four synthetic flavin molecules as bioinspired redox mediators in electro‐ and photocatalysis applications. The studied flavin compounds were disubstituted with polar substituents at the N1 and N3 positions (alloxazine) or at the N3 and N10 positions (isoalloxazines). The electrochemical behavior of one such synthetic flavin analogue was examined in detail in aqueous solutions of varying pH in the range from 1 to 10. Cyclic voltammetry, used in conjunction with hydrodynamic (rotating disk electrode) voltammetry, showed quasi‐reversible behavior consistent with freely diffusing molecules and an overall global 2e^?, 2H⁺ proton‐coupled electron transfer scheme. UV/Vis spectroelectrochemical data was also employed to study the pH‐dependent electrochemical behavior of this derivative. Substituent effects on the redox behavior were compared and contrasted for all the four compounds, and visualized within a scatter plot framework to afford comparison with prior knowledge on mostly natural flavins in aqueous media. Finally, a preliminary assessment of one of the synthetic flavins was performed of its electrocatalytic activity toward dioxygen reduction as a prelude to further (quantitative) studies of both freely diffusing and tethered molecules on various electrode surfaces.     

Ultralong π-Conjugated Bis(terpyridine)metal Polymer Wires Covalently Bound to a Carbon Electrode: Fast Redox Conduction and Redox Diode Characteristics

We developed an efficient and convenient electrochemical method to synthesize π-conjugated redox metal-complex linear polymer wires composed of azobenzene-bridged bis(terpyridine)metal (2-M, M = Fe, Ru) units covalently immobilized on glassy carbon (GC). Polymerization proceeds by electrochemical oxidation of bis(4′-(4-anilino)-2,2′:6′,2″-terpyridine)metal (1-M) in a water–acetonitrile–HClO₄ solution, affording ultralong wires up to 7400 mers (corresponding to ca. 15 μm). Both 2-Fe and 2-Ru undergo reversible redox reactions, and their redox behaviors indicate remarkably fast redox conduction. Anisotropic hetero-metal-complex polymer wires with Fe and Ru centers are constructed via stepwise electropolymerization. The cyclic voltammograms of two hetero-metal-complex polymer wires, GC/[2-Fe]–[2-Ru] (3) and GC/[2-Ru]–[2-Fe] (4), show irreversible redox reactions with opposite electron transfer characteristics, indicating redox diodelike behavior. In short, the present electrochemical method is useful to synthesize polymer wire arrays and to integrate functional molecules on carbon.     

Synthesis and Redox Behavior of Novel 9,10‐Diphenylphenanthrenes

The synthesis and electrochemical investigations of 9,10‐diphenylphenanthrene 2a and its derivatives 2b – 2e are reported. The cyclic voltammetry of derivatives 2a – 2c and 2e in different solvent/Bu₄NPF₆ electrolyte systems reveals that the redox properties are dependent on solvent, temperature, and sweep rate. The oxidation of 9,10‐diphenylphenanthrene 2a occurred as an irreversible process, while two fully reversible oxidation waves were observed for dimethoxy derivative 2c . The room‐temperature oxidation of brominated compound 2b is reversible, whereas AcO‐substituted phenanthrene 2e displayed a reversible oxidation peak only at low temperature. Furthermore, the electronic nature of the substituent affects the oxidation potentials. In the CH₂Cl₂‐based electrolyte system, the first oxidation potentials increase in the order 2c < 2e < 2b .     

CoC60(OH)的合成及氧化还原性能

富勒烯独特的电子及空间结构 ,使富勒烯及其衍生物具有特殊的物理化学性能[1 ,2 ] 。在富勒烯金属化合物方面 ,如碱金属原子可以与C60 键合成类“离子型”化合物而表现出十分良好的超导特性[3] 。过渡金属也能与富勒烯形成稳定的过渡金属富勒烯化合物[4] ,此类化合物可能具有与碱金属富勒烯化合物不同的性能 ,如Pd和C60 形成C60 Pdn后具有良好的催化性能[5] 。最近Chi等[6] 合成出稀土富勒烯化合物Sm3C70 ,并且认为Sm与C70 是以共价键的形式结合。研究的主要目的是通过研究富勒烯衍生物结构与性能之间的内在联系规律 ,以期在开发应用方…