黄芩苷与人血清白蛋白的相互作用研究

利用紫外光谱、荧光光谱、傅立叶红外谱、圆二色谱及分子模型等技术,在生理pH条件下,研究了黄芩苷与人血清白蛋白(HSA)的相互作用,并计算了其结合常数和热力学参数.分子模型研究表明,黄芩苷与HSA在亚结构域ⅡA结合,二者间的作用主要为静电作用和疏水作用,与荧光光谱结果基本一致.红外光谱和圆二色谱显示黄芩苷与HSA结合后未...     

土贝母皂苷II与人血清白蛋白相互作用机制的光谱研究

人血清白蛋白多种结合位点的存在使其成为许多药物可能的结合靶点. 土贝母皂苷具有广泛的生理和药理活性, 它与蛋白质相互作用机制的研究对于深入了解其药理药效具有重要的意义. 采用荧光光谱法研究了土贝母皂苷II (TBMSⅡ)与人血清白蛋白(HSA)之间的相互作用, 根据Stern-Volmer荧光淬灭方程计算得293, 298, 303, 308 K时TBMSⅡ与HSA相互作用的结合常数分别为1.002×10⁵, 0.701×10⁵, 0.514×10⁵, 0.411×10⁵ L•mol^－1. 由实验计算出热力学参数焓变ΔH为－44.829 kJ•mol^－1, 熵变ΔS为－57.497 J•mol^－1•K^－1, 表明分子间的氢键及疏水作用是TBMSⅡ-HSA复合物的主要作用力, 结合位点位于HSA的亚结构ⅡA, 这与分子模拟方法的结果相一致. 依据能量转移原理求得TBMSⅡ与HSA间的距离为4.95 nm|三维、同步荧光光谱及圆二色谱的结果表明TBMSⅡ的加入使HSA构象发生变化, α-螺旋结构有所下降.     

水溶性阳离子型吡啶基咔咯镓配合物与人血清蛋白的相互作用

利用紫外吸收光谱、荧光光谱、圆二色(CD)光谱和分子对接计算探究了5,10,15-三[4-(N-甲基-吡啶)]咔咯镓配合物(1-Ga)与人血清蛋白(HSA)的相互作用.结果表明,HSA的荧光能被1-Ga静态猝灭,两者的结合常数为2.82×104L/mol,作用距离为3.342 nm.热力学参数显示1-Ga主要通过氢键和疏水作用与HSA结合,位点标记竞争实验表明1-Ga优先结合HSA的布洛芬位点Ⅱ.此外,紫外吸收光谱和CD光谱显示二者的相互作用会导致HSAα-螺旋结构的减少.分子对接计算结果表明1-Ga优先结合在HSA亚结构域ⅢA的位点Ⅱ疏水袋中.     

吡虫啉与人血清白蛋白相互作用热力学行为

在模拟人体生理条件下,综合利用荧光光谱、紫外吸收光谱、圆二色谱和分子模拟等方法,研究了吡虫啉(IMI)和人血清白蛋白(HSA)相互作用的热力学行为。荧光光谱和紫外吸收光谱的分析表明：吡虫啉能有效猝灭HSA的内源荧光,猝灭机制为静态猝灭;通过所获取的相互作用热力学参数,可知两者之间的相互作用是一个吉布斯自由能降低的自发过程,且二者之间的主要作用力为氢键和范德华力。位点竞争实验和分子模拟的结果表明：吡虫啉在HSA的主要结合位置为位点?。圆二色谱、同步荧光光谱和三维荧光的分析发现：吡虫啉引起HSA的构象发生改变,其α-螺旋含量降低,无规卷曲含量升高,肽链结构在吡虫啉的作用下有所伸展。     

光谱技术结合分子模拟测定塑化剂邻苯二甲酸二正辛酯与人血清白蛋白相互作用模式

在生理酸度(pH 7.4)条件下,采用荧光光谱、紫外-可见吸收光谱、圆二色谱(CD)和红外光谱(FT-IR)等多种光谱方法并结合分子模拟技术,测定了塑化剂邻苯二甲酸二正辛酯(DnOP)与人血清白蛋白(HSA)的相互作用模式。荧光滴定结果表明,DnOP对HSA内源荧光的猝灭机制为形成HSA-DnOP复合物的静态猝灭,其在不同温度下的熵变(ΔS°)和焓变(ΔH°)分别为35.32 J·mol-1·K-1和-9.13 kJ·mol-1,表明结合反应主要由疏水作用和氢键驱动。位点竞争实验表明DnOP与曙红Y发生了置换反应,揭示DnOP主要结合在HSA亚结构域ⅡA(SiteⅠ位),分子模拟结果显示,DnOP插入亚结构域ⅡA的疏水空腔,通过疏水作用以及DnOP的羰基氧与His242氨基酸残基间形成的氢键与蛋白结合,实验结果与荧光光谱及位点竞争实验一致。紫外-可见光谱、CD及FT-IR光谱的分析结果表明,DnOP与HSA结合导致了HSA二级结构发生变化,降低了HSA中α-螺旋的含量,并诱导HSA的多肽链发生部分伸展。     

利福布汀与人血清白蛋白相互作用的光谱研究

用荧光光谱法和圆二色谱法研究了利福布汀(RB)与人血清白蛋白(HSA)的相互作用. 结果表明, RB与HSA之间的相互作用主要是疏水作用, 作用机制是静态猝灭与动态猝灭的结合. 其结合常数(Ka)在106数量级, 说明RB和HSA有很强的结合. 此外, 探讨了金属离子(Cu2+, Zn2+, Mg2+ 和Ca2+)对RB与HSA结合常数的影响. 同步荧光光谱和圆二色谱数据表明, RB可导致HSA的构象改变.     

多光谱法结合分子模拟技术研究多西他赛与人血清白蛋白的作用

利用荧光光谱、紫外光谱、三维荧光光谱、红外光谱、圆二色谱和分子对接技术研究了多西他赛(DT)与人血清白蛋白(HSA)的相互作用机理,探讨了 7种辅酶对HSA及DT-HSA体系的影响.结果表明,DT对HSA的猝灭机制为静态猝灭且伴随非辐射能量的转移,二者通过疏水力、氢键和范德华力共同作用形成1∶1的配合物.HSA的主要结...     

光谱法结合原子力显微镜和分子对接技术研究金丝桃苷与人血清白蛋白的相互作用

在模拟生理条件下,采用荧光、共振散射、圆二色谱(CD)等光谱法和原子力显微镜及分子对接技术,研究了金丝桃苷与人血清白蛋白(HSA)的相互作用。应用分子对接技术预测金丝桃苷结合在HSA的SiteⅠ位,预测结果与位点探针竞争实验结果吻合。原子力显微镜(AFM)图像和共振散射光谱表明,与金丝桃苷结合后HSA的分子直径变大,产生相互聚集。金丝桃苷对HSA内源荧光的猝灭机制属于形成基态复合物所引起的静态猝灭。测得的热力学参数表明,金丝桃苷与HSA作用主要由疏水作用和氢键驱动。根据Frster非辐射能量转移理论求得两者间的结合距离为3.52nm。CD谱显示金丝桃苷诱导HSA的二级结构产生稍许的变化。     

白杨素与不同构型人血清白蛋白的作用机制

采用多种光谱学手段研究了白杨素(CHR)和不同构型人血清白蛋白(HSA)相互作用的分子机制.研究表明,白杨素能使蛋白质荧光发射峰发生静态淬灭,同时,白杨素的紫外吸收谱带也发生了明显的位移,说明与蛋白质的结合可使白杨素分子中的酚羟基发生解离.蛋白质还可以引起白杨素荧光发射峰强度的明显增强.利用荧光淬灭和荧光增强两种模式计算得到的白杨素和人血清白蛋白在生理条件下(pH 7.4)的结合常数(KA)分别为(9.97±0.24)×104和(9.75±0.11)×104L mol-1,其结合比例为1:1.随着pH值的降低,蛋白质与白杨素的结合常数逐渐减小,这与蛋白质的构型变化有关.根据不同异构体血清蛋白质的结构特征,判定白杨素在蛋白质分子上的结合位置位于IIA亚域的Site I活性位点.结合分子模拟,讨论了白杨素与蛋白质分子的结合机制.     

中药小分子阿魏酸和丹皮酚与人血清白蛋白的竞争结合作用研究

用亲和色谱研究了两种中药小分子阿魏酸(FA)、丹皮酚(PAE)在人体生理条件缓冲溶液(pH7.4)条件下与人血清白蛋白(HSA)的相互作用.从药物分子在蛋白质分子上有多种类型相互独立的结合位点的假定出发,应用Langmuir吸附模型和竞争置换分析研究了FA,PAE与HSA的竞争性相互作用.结果表明,FA,PAE与HSA之间存在一类位点,且FA与PAE竞争HSA上的indole位点(siteⅡ).根据热力学参数推测出FA,PAE与HSA之间的作用力主要为氢键作用.从FA,PAE竞争HSA上同一位点的角度,对中医用药中常将含有FA与含有PAE的中药配伍使用,以提高疗效的临床用药现象进行了解释.     

二氧化碳和丙烯直接合成甲基丙烯酸的NiPMo/TiO2催化剂的研究

用溶胶-凝胶法以磷钼酸(MPA)的镍盐溶液水解钛酸四丁酯制备了NiPMo/TiO2催化剂.使用ICP、 XRD、 TG-DTA、 IR、 TPD-MS和微反应技术研究了催化剂的化学组成、热稳定性、化学吸附性质和催化反应性能.杂多钼酸盐与TiO2通过O2-在TiO2表面发生了键合.在623 K下,杂多阴离子仍保持原有的Keggin结构.CO2在Lewis酸位Ni(Ⅱ)和Lewis碱位Ni-O-Mo的桥氧协同作用下生成CO2卧式吸附态Ni(Ⅱ)←O-(CO)←(O--Ni).丙烯有多种吸附态在催化剂上吸附.在563 K、 1 MPa和空速1500 h-1的反应条件下,丙烯的摩尔转化率为3.2%,产物MAA选择性为95%.     

Synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives

Different approaches for the synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives from simple amino acids have been investigated. A library of 33 precursors for the preparation of N-hydroxy pyrazinones was obtained in moderate to good yields.     

Toward new camptothecins. Part 6: Synthesis of crucial ketones and their use in Friedländer reaction

In the context of the preparation of camptothecin and luotonin A analogs, the synthesis of some key keto-precursors and their use in Friedländer condensation are described. This paper also focuses on the stability of these keto intermediates and emphasizes the major differences between indolizinones and pyrroloquinazolinones series. Noteworthy is also the report of some original structures isolated as by-products of some experiments.     

CoFe2O4自形成磁性液体场致结构化对磁化的影响

The Langevin paramagnetic theory can’t describe the relation between magnetization of ferrofluids and applied magnetic field. The structuralization of ferrofluids, which is considered the main influence factor of the magnetization, is regarded. The part of magnetization works is deposited when the structure is forming. This action influences the magnetization of ferrofluids directly or indirectly. On the base of the “compressing” model, the Langevin function that usually describes the magnetization of ferrofluid is modified, and a well-fitted curve is obtained. An equation of the relation between the equivalent volume fraction after being “compressed” and the intensity of magnetic field is discovered, which approximately describes the process of magnetization. The relation between the approximate initial susceptibility and the volume fraction can be obtained from modified formula.     

Highly regioselective Buchwald–Hartwig amination at C-2 of 2,4-dichloropyridine enabling a novel approach to 2,4-bisanilinopyridine (BAPyd) libraries

The highly regioselective Buchwald–Hartwig amination at C-2 of the cheap and readily accessible reagent, 2,4-dichloropyridine with a range of anilines and heterocyclic amines is described. This new methodology is robust and provides a facile access to 4-chloro-N-phenylpyridin-2-amines on 0.25 mol scale. These intermediates undergo a further Buchwald–Hartwig amination at higher temperature to enable rapid exploration of the chemical space at C-4 and to provide a library of 2,4-bisaminopyridines.     

KMnO4-mediated oxidative CN bond cleavage of tertiary amines: Synthesis of amides and sulfonamides

KMnO₄-mediated oxidative CN bond cleavage of tertiary amines producing secondary amine was introduced, which was trapped by electrophiles (acyl chloride and sulfonyl chloride) to form amides and sulfonamides. The reaction could take place at mild condition, tolerating a wide range of function groups and affording products in moderate to excellent yields.     

Chemistry of heterocyclic compounds at the A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, over 50 years (Review)

The review contains a concise historical account and information on the most significant researches undertaken by the staff at the A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences on the Chemistry of Heterocyclic Compounds. Dedicated to Academician of the Russian Academy of Sciences B. A. Trofimov on his 70th jubilee. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1443–1502, October, 2008.     

A general and convenient synthesis of 4-(tosylmethyl)semicarbazones and their use in amidoalkylation of hydrogen,heteroatom, and carbon nucleophiles

A general synthesis of previously unknown semicarbazone-based α-amidoalkylating reagents, 4-(tosylmethyl)semicarbazones, has been developed. The synthesis involved three-component condensation of semicarbazones of aliphatic or aromatic aldehydes with the same or other aldehydes and p-toluenesulfinic acid. The scope and limitations of this reaction were investigated. The compounds obtained were demonstrated to be an efficient α-(4-semicarbazono)alkylating agents. They were reacted with H- (sodium borohydride), O- (sodium methylate), S- (sodium phenylthiolate), N- (pyrrolidine, sodium succinimide), P- (trialkyl phosphites), and C-nucleophiles (sodium diethyl malonate) to give the corresponding products of the tosyl group substitution, 4-substituted semicarbazones, including analogues of nitrofurazone. Among the prepared compounds tested in vitro for antibacterial and antifungal activity, three nitrofuryl-containing semicarbazones exhibited high biological activities with minimum inhibitory concentration (MIC) values of 8–32 μg/mL.     

Sulfur-directed metal-free and regiospecific methyl C(sp3)–H imidation of thioanisoles

Regiospecific and direct imidation of the methyl C(sp³)–H bond of thioanisoles is realized under mild and metal-free conditions with N-fluorobis(benzenesulfonyl)imide as an oxidant and nitrogen source. Proposed mechanism suggests that thionium ion intermediates and a Pummerer-type reaction are involved. The imidation has advantages such as high step-economy, excellent functionality tolerance, and regiospecificity, giving structurally diverse imidation products.     

Synthesis of novel chiral bidentate hydroxyalkyl-N-heterocyclic carbene ligands and their application in palladium-catalyzed Mizoroki–Heck couplings and asymmetric addition of diethylzinc to benzaldehyde

A small library of new chiral bidentate hydroxyalkyl-imidazolium salts 1 is conveniently synthesized on multi-gram scale from inexpensive and commercially available chiral pool amino acids. The corresponding carbenes, generated by deprotonation of imidazolium salts 1, in combination with palladium(II) chloride were tested in the Mizoroki–Heck coupling reaction. The most significant results in terms of yields and reactivities were achieved with low catalyst loading. The catalytic activities of these imidazolium salts were also investigated in the asymmetric addition of diethylzinc to benzaldehyde. The use of MgO nanoparticles as an additive in conjunction with these ligands played a crucial role in increasing the efficiency of these reactions.