紫杉醇对柔红霉素与DNA作用影响的研究

采用紫外-可见光谱、荧光光谱、微分脉冲伏安法以及紫外-可见光谱电化学法等多种手段, 从分子水平研究了紫杉醇对柔红霉素与DNA作用的影响. 紫杉醇可以和柔红霉素形成分子间氢键; 紫杉醇的长链对柔红霉素糖环以及柔红霉素和DNA所形成加合物的外围有一定程度的缠绕作用, 最终使柔红霉素的药效增加毒副作用减小.     

柔红霉素与DNA作用的序列特异性研究

采用紫外-可见光谱法和紫外-可见光谱电化学法研究了柔红霉素(DNR)与不同寡聚核苷酸之间的相互作用.结果表明,DNR优先作用于寡聚核苷酸的CpG位点,然后是ApG和ApC.因为DNR可与鸟嘌呤之间形成3个氢键.与双链寡聚核苷酸作用时,DNR最先插入的位点是(CpG)₂碱基对之间,其次是(TpG)(CpA)和(GpC)(ApC)碱基对之间.当DNR与存在未配对G碱基的DNA链作用时,因游离的DNR量增加使其电化学活性增加,导致DNA构象和构型的变化,使DNA生理功能受到损伤,DNA碱基增色效应显著上升.此法可用于G碱基未配对DNA链的检测.     

碳纳米管/纳米金修饰金电极上柔红霉素电化学行为的研究

将碳纳米管与纳米金结合修饰在金电极上制成修饰电极,并用于柔红霉素(DNR)的电化学行为研究和检测.在4.4 mmol/L磷酸盐缓冲溶液(pH=5.81)中,DNR在碳纳米管-纳米金/Au电极上有一对灵敏的氧化还原峰.还原峰电流与DNR的浓度在3.2×10-8～1.0×10-6mol/L和1.0× 10-6～2.2× 1...     

蒽环类抗肿瘤抗生素与DNA作用差异性的光谱电化学研究

利用在线紫外一可见光谱电化学技术、微分脉冲伏安法及琼脂糖凝胶电泳技术考察了柔红霉素、表阿霉素、阿克拉霉素、伊达比星与DNA的作用。实验表明,药物与DNA形成复合物的稳定性主要取决于药物的糖环与DNA之问的作用,糖苷配基上取代基与DNA形成氢键也有一定影响。另外,DNR在还原代谢过程中最易产生半醌自由基。     

2—氨基—9,10—蒽醌及其衍生物的光谱电化学研究

用循环伏安法研究了２－氨基－９，１０－蒽醌及其衍生物在ＤＭＦ－０．１ｍｏｌ／ＬＴＢＡＰ溶液中的电化学行为，结果表明它们在铂电极上均发生两步连续的单电子还原过程，取代基Ｒ及水和苯甲酸等质子性试剂的加对伏安曲线有很大的影响。     

阿霉素的光谱电化学研究

利用循环伏安、紫外可见光谱电化学、荧光光谱电化学、圆二色光谱电化学等方法研究了阿霉素(ADM)在石墨电极上的电化学行为.结果发现,阿霉素在+0.2～+0.7V和-0.2～-0.7V范围内分别出现一对氧化还原峰.正电位下,蒽环上的酚羟基发生单电子氧化,并伴随后续化学反应.负电位范围内,阿霉素经历ECE电极反应过程,即蒽醌经单电子还原生成半醌自由基,半醌可发生不可逆的化学反应,脱去配氧糖基,转变为7-去氧柔毛霉醌(7-deoxyadriamycinone),后者在更负的电位下形成一对可逆的新的氧化还原峰.     

银盘电极盐酸柔红霉素电化学行为及其与BSA的相互作用

应用线性扫描伏安法和循环伏安法研究盐酸柔红霉素在银盘电极上的电化学行为及其与牛血清白蛋白(BSA)的相互作用.结果表明,在pH6.50的Britton-Robinson缓冲溶液中,盐酸柔红霉素有一灵敏的还原峰,峰电位Ep-0.64V(vs.SCE),缓冲液加入BSA后盐酸柔红霉素的还原峰峰电流下降,据此建立了BSA的电化学测定方法.在优化条件下,峰电流与BSA浓度于1.0×10-8～1.0×10-4mol·L-1(r=0.9965)范围内呈线性关系,检出限为5.0×10-9mol·L-1.同时还测定了盐酸柔红霉素与BSA的结合比和结合常数.     

β-环糊精修饰电极对柔红霉素的电化学定量测定

柔红霉素(DNR)是强效的抗白血病制剂,但具有心脏毒性,基因毒性和生殖器官毒性。因此,研究柔红霉素的用量,建立多种微量检测方法,在临床医学方面具有积极的和现实的意义。本文研究了DNR在β-环糊精（β-CD）修饰金电极上的电化学行为,发现DNR能在β-CD俢饰电极上发生包络反应,其包络常数为6.1×104 L•mol-1。而且,只有包络的DNR能进行不可逆的电化学反应。其速率常数为28.03 s-1。在3-30 μmol• L-1的浓度范围内,DNR还原峰峰电流与DNR浓度成线性关系,因此,β-CD修饰电极可用于DNR的定量检测。在pH=7.0的中性电解液和温度接近40℃时,DNR在β-CD修饰电极上有最好的电化学活性。此时,β-CD修饰电极对DNR有较低的检出极限。     

抗癌药物阿克拉霉素-A的氧化还原代谢机理研究

大多数化疗药物因很强的毒副作用在临床应用中受到很大的限制,阿克拉霉素为蒽环药物家族新成员,因其抗癌活性高和毒副作用低在抗肿瘤药物中占有重要地位．本论文将药物置于代谢模型内,以光谱技术现场监测药物的代谢过程,研究了阿克拉霉素-A的氧化还原代谢机理．阿克拉霉素．A在体内的代谢过程为先通过一步二电子过程还原生成阿克拉氢醌．A,再脱去糖．其脱糖反应与介质的pH密切相关．脱糖、异构化后的产物7-去氧阿克拉霉醌经缔合后可生成双分子缔合物．整个代谢过程中并不产生半醌自由基,因而对心脏和细胞的毒性较小．研究结果同时也表明药物分子中的糖环结构与药物代谢及药物的毒副作用密切相关．研究成果有助于深入探讨药物的构效关系,对药物的临床应用有着重要的实际意义．     

中性配体存在下(OEP)Co的电化学和光谱电化学研究

本文以循环伏安跟踪的电化学滴定,结合现场紫外-可见薄层光谱电化学方法,研究了丙烯腈、乙醇、二甲基甲酰胺和二甲基亚砜等电中性轴向配体的配位反应及其对(OEP)Co三步单电子氧化步骤的影响,计算了(OEP)Co(Ⅲ)与四种配体的配合常数,表明配位能力的大小顺序为丙烯腈<乙醇<二甲基甲酰胺<二甲基亚砜。(OEP)Co(Ⅲ)可以和一个或两个丙烯腈或乙醇分子形成五配位或六配位的化合物,但是只出现和两个二甲基甲酰胺或二甲基亚砜分子形成六配位化合物;发现(OEP)Co(Ⅱ)并不与这些配体在轴向配位。在环阳离子自由基状态下,钴中心的配位性依然存在但强度减小。讨论了这些体系的电化学-配位反应机理。     

Rapid Prototyped Optically Transparent Thin‐Layer Electrode Holder for Spectroelectrochemistry in Bench‐Top Spectrophotometers

A new optically transparent thin layer electrode (OTTLE) cell and holder have been designed to facilitate spectroelectrochemical measurements in standard bench‐top absorbance and fluorescence spectrophotometers. The use of rapid prototyping for the OTTLE cell holder combined with the selection of inexpensive OTE materials results in a practical, low‐cost spectroelectrochemical cell. The cell was characterized by thin‐layer cyclic voltammetry and coulometry of ferricyanide/ferrocyanide. Spectroelectrochemistry of tris‐(2,2′‐bipyridine) ruthenium(II) chloride (Ru(bpy)₃Cl₂) and 1‐hydroxypyrene (1‐pyOH) was done with commercially available bench‐top absorbance and fluorescence spectrophotometers. The good correlation between the results obtained and the known properties of each compound demonstrate that the OTTLE cell and holder provide an effective means for making spectroelectrochemical measurements in bench‐top absorbance and fluorescence spectrophotometers.     

钼和稀土的二乙基二硫代甲酸盐配合物的电化学研究

研究了N,N-二乙基二硫代甲酸根(dtc)作配体的双核配位化合物[Mo(dtc)₄][Ln(dtc)₄](Ln=La,Pr,Nd,Sm,Eu,Gd,Tb,Dy,Ho和Er)的氧化还原性质及其在电极过程中的电化学特性.     

1,4—二氢吡啶及其衍生物电化学反应机理的研究

研究了１１种１，４－二氢吡啶及其衍生物在乙腈溶剂中和铂盘电极上的电化学行为。实验结果表明：１，４－二氢吡啶及其衍生物在铂盘电极上的反应是受扩散和化学反应速率控制的两电子不可逆氧化过程，经连续两步失电子脱氢后形成相应的吡啶。用紫外吸收光谱电化学方法观测了电化学氧化过程。并与化学氧化产物的紫外光谱作了比较，证明１，４－二氢吡啶的电化学氧化产物与化学氧化产物一致。因此，电化学氧化是一种不需加化学试剂可使     

Spectroelectrochemical Study of N‐Substituted Phenoxazines as Electrochemical Labels of Biomolecules

The electrochemical conversion of N‐substituted phenoxazines (NSP's) bearing a CH₂CH₂? X substitute (where X?OH, COOH, CH₂NH₂, CH₂SO₃H, CH₂NHCOR) was investigated using cyclic voltammetry on a bulk gold electrode and a thin‐layer spectroelectrochemical cell. The electrochemical oxidation of NSP's on the gold electrode was quasi‐reversible and proceeded in a diffusion‐controlled regime. The formal redox potential of NSP's covered the range from 0.39 to 0.45 V vs. SCE. The electrochemical oxidation of NSP's in the thin‐layer spectroelectrochemical cell produced radical cations that showed absorbance at 385, 410 and 530 nm. Electrochemical conversion fitted the general voltammetric current‐potential equation of a reversible wave, whereas electrolysis at constant potential showed a typical Cottrell behavior. Combining of NSP's with a biologically‐relevant theophylline molecule did not change electrochemical and spectral properties of the phenoxazine core. Theophylline enlarged with NSP's demonstrated electrochemical and biocatalytic behavior similar to that of NSP's. The investigated NSP's possess electrochemical and spectral properties that are useful as biomolecular labels for electroanalysis.     

Synthesis and electrochemical characterisation of a near infrared absorbing oxo vanadium(IV) octapentylthio-phthalocyanine

The synthesis of an α-substituted phthalocyanine oxo vanadium(IV) 1,4,8,11,15,18,22,25-octapentathiophthalocyanine (4) which absorbs at 850 nm in dichloromethane is reported. The complex is purple in colour and becomes green on reduction. The cyclic and square wave voltammetries of the complex show five redox couples. The spectroelectrochemical data showed only ring based processes. The ring reduced species is observed at wavelengths greater than 680 nm rather than the usual 500–600 nm range typical of ring reduced phthalocyanine complexes.     

Electrochemistry and Spectroelectrochemistry of Luminescent Europium Complexes

Fast, cost effective, and robust means of detecting and quantifying lanthanides are needed to support more efficient tracking within the nuclear, medicinal, and industrial fields. Furthermore, methods for isolating lanthanide signal from spectroscopic interferents are also needed. Applying spectroelectrochemistry to the detection of these species can meet those needs. However, application of this technique is limited by the low molar absorptivities and quantum yields of the lanthanides. These limitations can be circumvented by complexing the lanthanides with sensitizing ligands that enhance fluorescence, thereby dropping the limits of detection. Complexation will also cause changes in the electrochemical behavior of the lanthanides. To demonstrate this concept, studies were completed using europium as a model lanthanide in complexes with four different sensitizing ligands, which included 2,2′‐bipyridine and related derivatives. Results indicate that all four studied complexes demonstrate quasi‐reversible redox couples and improvements in limits of detection where electrochemical and spectroscopic characteristics showed some dependence on attached ligand. All four complexes studied display the necessary characteristics for spectroelectrochemical analysis, which was successfully and reproducibly applied to all Eu complexes.     

Electrochemical and Spectroelectrochemical Analysis of 4‐(4‐(5‐Phenyl‐1,3,4‐oxadiazole‐2‐yl)phenoxy)‐Substituted Cobalt(II), Lead(II) and Metal‐Free Phthalocyanines

Electrochemical and spectroelectrochemical analyses of 4‐(4‐(5‐phenyl‐1,3,4‐oxadiazole‐2‐yl)phenoxy)‐substituted metal‐free phthalocyanine ( H₂Pc ( 1 )) and metallated phthalocyanines ( PbPc ( 2 ) and CoPc ( 3 )) were performed in solution. Voltammetric characterizations of the phthalocyanine complexes were investigated by using cyclic voltammetry and square wave voltammetry techniques. CoPc ( 3 ) gave common metal and ring based electron transfer reactions; however they split due to the aggregation. Although PbPc ( 2 ) illustrated reversible reduction processes during the voltammetric measurements, it was de‐metallized and thus turned to the metal free phthalocyanine during repetitive voltammetric cycles and in situ spectroelectrochemical measurements.