溶液pH对硫堇与DNA相互作用方式的影响

用电化学和光谱方法研究了溶液pH对硫堇(TH)与小牛胸腺脱氧核糖核酸(CT-DNA)相互作用方式的影响.电化学测量结果表明，在pH 7.2的磷酸盐缓冲溶液中, TH与CT-DNA之间的作用方式以嵌入结合为主，在pH 6.5的磷酸盐缓冲溶液中， TH与CT-DNA之间的作用方式既存在嵌入结合也存在静电作用.荧光光谱测量结果表明，TH与DNA结合后其荧光发生猝灭，通过Stern-Volmer方程计算得到pH 6.5时TH-DNA体系的猝灭常数高于pH 7.2时的值，表明在pH 6.5的溶液中两者相互作用更强.圆二色谱(CD)实验结果也证实了这一结论.     

单核锇配合物的合成、晶体结构及其与DNA的作用

使用溶剂热合成法,以p-bitmb配体(1,4-二(1-咪唑基-亚甲基)-2,3,5,6-四甲基苯)与[(η6-cymene)Os(μ-Cl)Cl]2或[(η6-bip)Os(μ-Cl)Cl]2为原料,合成了2种单核芳基锇配合物,并利用核磁、质谱、元素分析和X射线单晶衍射等手段对配合物进行了表征。配合物1属于单斜晶系,P21/c空间群,为一个单核锇的结构。中心锇原子与2个配体p-bitmb上的氮原子以及氯原子进行配位,2个配体的另一个咪唑基团通过一个亚甲基碳原子进行连接形成咪唑嗡离子,形成一个类似"碗"状的结构。一个氯离子通过氢键装载在结构的空腔内。利用核磁共振氢谱研究了结构中亚甲基的来源,并研究了配合物在缓冲溶液中的稳定性。用紫外吸收光谱、圆二色谱以及粘度法研究了配合物与DNA的相互作用,结果表明,配合物中的亚甲基来自于溶剂二氯甲烷。配合物以嵌入的方式与CT-DNA相互作用,结合常数分别为3.222×10~4 L·mol-1 (1)和1.53×10~4 L·mol-1 (2),同时配合物会减弱DNA的碱基堆积作用并可以使DNA发生解旋。     

季铵盐联吡啶-钌(Ⅱ)配合物的合成及其与小牛胸腺DNA的相互作用

利用紫外-可见吸收光谱、荧光光谱、圆二色谱等光谱手段,以及黏度测定等流体力学方法在三羟甲基氨基甲烷(tris)缓冲溶液和磷酸缓冲溶液中研究了含季铵盐联吡啶配体的钌(Ⅱ)配合物[Ru(L)(phen)2](PF6)4(L=5,5′-二(三甲铵基甲基)-2,2′-联吡啶离子,phen=邻菲咯啉)与小牛胸腺DNA(CT-DNA)的相互作用.结果表明,合成的配合物与CT-DNA之间存在一定的亲和作用,拟合得到的结合常数可达105;与此同时,该配合物能够稳定CT-DNA的结构,并对CT-DNA有较好的立体选择性(右旋异构体优先与DNA结合).     

水溶性铜卟啉配合物的合成、与DNA的相互作用及抗肿瘤活性

合成了3种水溶性铜卟啉配合物,分别为水溶性含溴铜卟啉(CuP-1)及其溴取代衍生物(CuP-2、CuP-3),并采用核磁氢谱、元素分析、质谱等手段进行了结构表征。利用紫外光谱法、EB-DNA荧光淬灭法、粘度法以及圆二色谱法等光谱法研究了CuP-1、CuP-2和CuP-3与小牛胸腺DNA(CT-DNA)的相互作用。采用噻唑兰(MTT)法,以体外培养的宫颈癌细胞(Hela)和乳腺癌细胞(MDA)为测试细胞株对CuP-1~CuP-3的抗肿瘤活性进行检测。人成纤维细胞(L929)作为正常细胞系。光谱法实验结果表明,CuP-1以插入的方式与CT-DNA相互作用,而CuP-2和CuP-3与CT-DNA以沟面结合的方式相互作用,且CuP-1与CT-DNA的结合能力优于CuP-2和CuP-3。体外抗癌活性实验结果表明,CuP-1~CuP-3对Hela和MDA均有体外抑制细胞增殖作用,呈时间、剂量依赖关系,并且CuP-1的体外抗肿瘤活性明显优于CuP-2、CuP-3。     

二芳基乙烯衍生物与DNA结合的分子动力学研究

基于分子动力学方法, 对2种旋转异构的二芳基乙烯(DTE, dithienylethene)衍生物(DTE1和DTE2)与不同分子结构DNA结合过程的热力学与动力学特征进行模拟, 结果发现, DTE1, DTE2与DNA分子采用小凹槽结合(MiGB)的模式结合时所需能量最低, 存在的分子间库仑能与范德华相互作用能最小, 说明该结合模式最稳定; 由于空间位阻作用, 互为旋转异构体的2个DTE衍生物与DNA作用表现出截然不同的结合行为, DNA对DTE衍生物具有明显的对映异构体选择性; DTE衍生物与DNA分子作用位点的选择性直接与构成位点的碱基对相关.     

CPPαFP缩糠胺席夫碱铜配合物的合成及其与DNA相互作用

合成出一种新型酰基吡唑啉酮席夫碱试剂(HL):1-对氯苯基-3-苯基-4-(α-呋喃甲酰基)-吡唑啉酮-5缩糠胺席夫碱及其铜配合物。由元素分析、络合滴定法、红外光谱、热重谱、质谱和核磁共振氢谱对配体和配合物的结构进行了表征并推测出配合物组成为CuL2,同时对该配合物与小牛胸腺DNA之间的相互作用进行了研究。结果表明:在测试条件下,配体以酮式和烯醇式共存。配位时酮式结构可能转化为烯醇式结构,按去质子的方式以羟基上的氧负离子和亚胺基上的氮原子双齿形式与铜中心离子成键;与小牛胸腺DNA作用实验结果显示:配合物主要以插入方式与CT-DNA相互作用,嵌入CT-DNA的碱基对中。     

氧钒配合物[VO（o-Van-Asn）（Phen）]·1.5CH3OH的合成、晶体结构及与DNA和BSA的相互作用

合成了一种新的L-天冬酰胺邻香草醛席夫碱和1,10-邻菲咯啉的氧钒配合物[VO(o-Van-L-Asn)(Phen)]1.5CH3OH(o-Van-L-Asn=邻香草醛与L-天冬酰胺形成的席夫碱,Phen=1,10-邻菲咯啉).利用红外光谱对其进行了表征,并通过X射线单晶衍射测定了其晶体结构.该晶体属于三斜晶系,P-1空间群,晶胞参数为:a=0.98990(10)nm,b=1.21591(11)nm,c=1.28349(12)nm,α=66.8180(10)°,β=83.816(2)o,γ=66.4150(10)o,V=1.2992(2)nm3,Dc=1.430 g cm-3,Z=1,F(000)=580,R1=0.0626,wR2=0.1631.通过紫外吸收光谱、荧光光谱、圆二色光谱(CD)和粘度测定等方法研究了该配合物与小牛胸腺DNA(CT-DNA)的相互作用.结果表明,配合物以插入方式与CT-DNA结合.光谱法研究该配合物与牛血清白蛋白(BSA)的相互作用表明,它主要以静态猝灭方式使BSA的内源性荧光发生猝灭,可引起蛋白构象的变化.计算得到了其结合常数Kb和结合位点数n.     

不对称大环双核Ni(Ⅱ)配合物的DNA切割性能研究

本文利用模板导向的方式合成了一种含有不对称侧链的大环双核金属Ni(Ⅱ)配合物(大环配体由3-溴甲基-5-甲基水杨醛,乙二胺,N,N-二(氨丙基)-2呋喃甲胺分步合成得到),其结构通过红外光谱、元素分析、X-射线单晶衍射进行了表征。利用紫外光谱、分子荧光和粘度试验对配合物与DNA的相互作用进行了研究,结果表明配合物与CT-DNA的结合常数K=4.8×104mol-1.L荧光淬灭常数Ksv=7.12×103mol-1.L;同时机理研究表明配合物与CT-DNA结合方式为插入模式。     

4-硫醚喹啉类化合物的合成与抗菌活性研究

基于4-取代喹啉是一类重要的喹啉衍生物,采用活性亚结构拼接方法设计合成了24个4-硫醚取代喹啉化合物,通过多种谱学方法确证其结构,并初步评价了它们的抗真菌活性.结果表明,绝大多数目标化合物对每种供试真菌均表现出一定程度的抗菌活性,其中2-苯基-4-乙硫基喹啉(4a)、2-苯基-4-(异丙基硫基)-喹啉(4c)与2-苯基-4-(烯丙基硫基)-喹啉(4h)的活性相对较好的活性相对较好,对部分病原菌抑制作用等同或接近阳性药物嘧菌酯.初步构效分析表明:4-位不同硫醚取代能显著影响该类化合物的活性,一般脂肪族取代活性强于芳香族取代,空间位阻较小的取代基化合物活性强于位阻较大者,而芳香族取代中苯环的不同取代模式对活性的影响不大甚至是不利的.     

N-磷酰化肽酯及小肽与溶菌酶相互作用的ESI-MS研究

用ESI-MS研究了一系列结构具有可比性的N-磷酰化肽酯及小肽和溶菌酶的非共价相互作用, 比较了磷酰化肽酯及小肽分子中的不同基团对相互作用的影响. 结果表明—OH对其与溶菌酶的相互作用有较大贡献; 芳香环由于位阻原因, 对相互作用有促进和阻碍双重效应; 当—OH与芳香环相连时会发生协同效应, 可使相互作用显著增强. 磷酰化肽酯及小肽的体积大小、空间位阻对相互作用亦有显著影响. 磷酰化二肽中氨基酸残基的构型、顺序、碳链长短的变化(增加1～2个C)对其与蛋白溶菌酶之间的相互作用在质谱中没有表现出影响. 分子结构较为伸展、分子柔顺性好、空间位阻较小的磷酰化小肽更容易使蛋白在溶液中的构象趋于收缩, 而构象较为收缩的蛋白分子更易结合空间位阻较小的磷酰化小肽分子.     

Reaction of derivatives of 1,4-dihydropyridine with the peroxynitrite anion

The reaction of derivatives of 1,4-dihydropyridine (1,4-DHP) with peroxynitrite anion is an oxidation reaction; no products of nitration were detected. It was found that some 1,4-DHP increase the lifetime of the peroxynitrite anion and the yield of hydroxyl radical in decomposition of the peroxynitrite anion.Latvian Institute of Organic Synthesis, Riga LV-1006. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 355–357, March, 1998.     

1,4-Dihydropyridine derivatives as deactivators of singlet oxygen

The constants of deactivation (k_q) of ¹O₂ by 1,4-dihydropyridine (1,4-DHP) derivatives were determined by quenching of the luminescence of singlet oxygen (¹O₂). The k_q values for 1,4-DHP derivatives range from 10⁶ to 10⁷ litersmole^–1-sec^–1 and depend to a considerable extent on the nature of the substituents in the 1,4-DHP ring. The presence of a substituent in the 4 position decreases k_q, while conversion of the 1,4-DHP system to the corresponding pyridine system deprives the compound of its ability to deactivate ¹O₂. As a result of tests of 12 1,4-DHP derivatives it was found that 2,6-dimethyl-3,5-di (phenylcarbamoyl)-1,4-dihydropyridine deactivates ¹O₂ most effectively.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 924–926, July, 1981.     

Fluorescence of 3,5-diethoxycarbonyl-1,4-dihydropyridine derivatives and their anions

The fluorescence spectra of a group of 3,5-diethoxycarbonyl-1,4-dihydropyridine (1,4-DHP) derivatives were investigated. The introduction of electron-acceptor N-substituents and 2,6-methyl groups decreases Q markedly. The fluorescence spectra of 1,4-DHP anions are shifted bathofluorically, and the Q values are higher than for the corresponding 1,4-DHP. The fluorescence spectra have large Stokesian shifts, which are decreased for 1,4-DHP anions. A good correlation exists between the _max values of the fluorescence bands of 1,4-DHP anions and the Hammett _p ⁺ constants of the 4-R-aryl substituents.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 67–70, January, 1988.     

Reductive ability of 1,4-dihydropyridine derivatives in relation to ions of trivalent iron

3,5-Dicarbonyl derivatives of 2,6-dimethyl-1,4-dihydropyridine (1,4-DHP) can reduce Fe³⁺ to Fe²⁺ depending on the nature of the substituents at position 4 and in the 3,5-ester group. This ability is less pronounced for the 1,4-DHP derivatives investigated than for ascorbic acid, but among derivatives possessing antioxidant activity it is less than that of the known antioxidants ionol (BOT) and trolox. Latvian Institute of Organic Synthesis, Riga, LV-1006, Latvia Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 661–663, May, 1999.     

Influence of 1,4-dihydropyridine derivatives on the generation of hydroxyl radicals

It was shown that a series of 1,4-dihydropyridine (1,4-DHP) derivatives in the NAD-H-Cu²⁺ -H₂O₂ system inhibit the formation of the hydroxyl radical (HO), while derivatives of 1,4-DHP with electron-donor substituents in the molecule are themselves capable of generating HO in the presence of Cu²⁺ and H₂O₂.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 519–521, April, 1992.     

Cu-catalyzed one-pot multicomponent approach for the synthesis of symmetric and asymmetric 1,4-dihydropyridine (1,4-DHP) linked 1,2,3-triazole derivatives

Abstract

Synthesis of various symmetric and asymmetric 1,4-DHP linked 1,2,3-triazole derivatives from economical and readily available starting materials via a convenient methodology in a single-pot method using CuSO₄·5H₂O as an efficient catalyst has been reported. The reaction proceeded efficiently under the optimized reaction conditions with excellent functional group compatibility providing the desired products in good yields. The method appears to be an efficient combinatorial strategy for the synthesis of new 1,4-DHP linked triazole derivatives.     

Molecular level model for the agonist/antagonist selectivity of the 1,4-dihydropyridine calcium channel receptor

Summary Crystal structures of the 1,4-dihydropyridine (1,4-DHP) calcium channel activators Bay K 8643 [methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(3-nitrophenyl)-pyridine-5-carboxylate], Bay O 8495 [methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(3-trifluoromethylphenyl)-pyridine-5-carboxylate], and Bay O 9507 [methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(4-nitrophenyl)-pyridine-5-carboxylate] were determined. The conformations of the 1,4-DHP rings of these activator analogues of Bay K 8644 [methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine-5- carboxylate] do not suggest that their activator properties are as strongly correlated with the degree of 1,4-DHP ring flattening as was indicated for members of the corresponding antagonist series. The solid state hydrogen bonding of the N(1)-H groups of the activators is not, unlike that of their antagonist counterparts, to acceptors that are directly in line with the donor. Rather, acceptor groups are positioned within ± 60 degrees of the N(1)-H bond in the vertical plane of the 1,4-DHP ring. Previously determined structure-activity relationships have indicated the importance of this N(1)-H group to the activity of the 1,4-DHP antagonists. Based on these observations, a model is advanced to describe the 1,4-DHP binding site of the voltage-gated Ca²⁺ channel and its ability to accommodate both antagonist and activator ligands.     

N-alkylation of 1,4-dihydropyridine-3,5-dicarboxylic acid esters

Alkylation of the anions of 1,4-dihydropyridines (1,4-DHP) formed by treatment of sodium hydride in aprotic solvents gave 1-alkyl(up to C₆H₁₃)-3,5-bis(ethoxycarbonyl)- and 1-alkyl-3,5-bis(aryloxycarbonyl)-1,4-DHP. The presence of a substituent in the 4 position increases the reactivity of the 1,4-DHP anion in the alkylation reaction. The absorption maximum in the UV spectra of the 1,4-DHP anion is shifted 100 nm bathochromically as compared with the neutral molecule. The longwave absorption maximum in the UV spectra of 1-alkyl-1,4-DHP is shifted hypsochromically as compared with the 1-unsubstituted compounds; this is explained by steric hindrance of the conjugation of the C=O groups with the -electron system of the ring. The introduction of an alkyl group at the nitrogen atom facilitates the electrical oxidation of 1,4-DHP.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1508–1513, November, 1978.     

Organocatalyzed regioselective and enantioselective synthesis of 1,4- and 1,2-dihydropyridines

Abstract

Herein, we introduce one of the first examples of asymmetric organocatalyzed synthesis of 1,2-dihydropyridines, affording enantioselective access to and partially solving regioselectivity challenges in the synthesis of dihydropyridines. We demonstrate that through modification of organocatalysts both 1,2- and 1,4-dihydropyridines (1,2- and 1,4-DHPs) can be obtained with high regioselectivity (ratio of 1,2-DHP/1,4-DHP from 95/5 to 0/100) and enantioselectivity (33% ee for 1,2-DHPs and up to 98% ee for 1,4-DHPs) in good yields (up to 87%).     

Multispectroscopic studies of the interaction of calf thymus DNA with the anti-viral drug, valacyclovir

The present study investigated the binding interaction between an antiviral drug, valacyclovir and calf thymus DNA (CT-DNA) using emission, absorption, circular dichroism, viscosity and DNA melting studies. In fluorimetric studies, thermodynamic enhancement constant (K(D)) and bimolecular enhancement constant (K(B)) were calculated at different temperatures and demonstrated that fluorescence enhancement is not initiated by a dynamic process, but instead by a static process that involves complex DNA formation in the ground state. Further, the enthalpy and entropy of the reaction between the drug and CT-DNA showed that the reaction is exothermic and enthalpy-favored. In addition, detectable changes in the circular dichroism spectrum of CT-DNA in the presence of valacyclovir indicated conformational changes in the DNA double helix following interaction with the drug. All these results prove that this antiviral drug interacts with CT-DNA via an intercalative mode of binding.