嘧啶衍生物与人血清白蛋白的相互作用

在模拟生理条件下,运用荧光光谱、激光闪光光解(LFP)和分子对接等技术研究了8种具有抗肿瘤活性的嘧啶衍生物(PDs,其中PDs A 5-FU为成药,PDs B-H为实验室自制)与人血清白蛋白(HSA)的相互作用.利用Stern-Volmer方程和激光闪光光解技术分析了PDs对HSA的荧光猝灭机制,PDs A和B为静态猝灭,PDs G和H为动态猝灭.用双倒数曲线法得出5种PDs与HSA的结合常数Ka和结合位点数n,在测定条件下5种PDs与载体结合位点数均为1,且均以弱结合力结合,通过热力学参数ΔH,ΔS和ΔG推测出PDs B,C和E与HSA之间的作用力为静电作用力和疏水作用力,PDs A和D与HSA之间的作用力是氢键和范德华力,分子对接结果与其一致.根据F9rster非辐射能量转移理论(FRET)分析了HSA和PDs之间的结合距离(r),其结果均小于4 nm,符合能量转移理论.进一步利用同步荧光、三维荧光和圆二色光谱考察了PDs与HSA结合过程中HSA空间构象的变化,结果显示,仅PDs A和C对HSA的芳香族氨基酸周围的疏水性略有增强作用.体外实验结果表明,HSA可以作为优良的载体来运输和储存PDs A~E,这为嘧啶衍生物的后续研究提供了可参考的实验数据.     

低温制冷机冷头焊接工艺研究

冷头是低温制冷机的关键零部件,是制冷机的重要结构件,同时也是制冷机与热载荷的接口部位。文中对冷头的焊接工艺进行研究,提出一种爆炸焊复合材料与激光焊结合的冷头焊接工艺。     

滚珠花键支撑斯特林制冷机研制

针对整体式斯特林制冷机"侧向力"的问题,提出一种滚珠花键支撑结构,并设计加工了样机。对采用滚珠花键支撑结构斯特林制冷机结构设计的要点进行了详尽的分析,指出采用滚珠花键支撑结构改善了整体式斯特林制冷机的可靠性。文中还对样机性能调试的相关情况进行了介绍。     

A new efficient method for the preparation of intermediate aromatic ketones by Friedel–Crafts acylation

Research on Chemical Intermediates - As the most important method to prepare pharmaceutical and chemical intermediate aromatic ketones, Friedel–Crafts (F–C) acylation is used to seek a...     

Kinetics of hydrogen atom transfer from (eta(5)-C(5)H(5))Cr(CO)(3)H to various olefins: influence of olefin structure

Treating (etha(5)-C(5)H(5))Cr(CO)3H (1) or (etha(5)-C(5)H(5))Cr(CO)3D (1-d(1)) with an excess of olefin containing the opposite isotope generally leads to H/D exchange, although hydrogenation is also observed in some cases. Application of an appropriate statistical correction to the observed exchange rate gives kH and kD, the rate constants for H* (D*) transfer from (etha(5)-C(5)H(5))Cr(CO)(3)H (D) to various olefins. The values of kH and kD vary appreciably with the substituents on the double bond. Phenyl-substituted olefins accept H* more readily than do carbomethoxy-substituted olefins, although the latter accept H* more readily than do alkyl-substituted olefins. A methyl substituent on the incipient radical site increases k(H) at 323 K by a factor between 5 and 50. A methyl substituent on the carbon to which the H* is being transferred decreases kH substantially. On the whole, the rate constants for H* transfer reflect steric effects as well as the stability of the resulting carbon-centered radicals.     

Adaptive dynamic programming-based stabilization of nonlinear systems with unknown actuator saturation

This paper addresses the stabilizing control problem for nonlinear systems subject to unknown actuator saturation by using adaptive dynamic programming algorithm. The control strategy is composed of an online nominal optimal control and a neural network (NN)-based feed-forward saturation compensator. For nominal systems without actuator saturation, a critic NN is established to deal with the Hamilton–Jacobi–Bellman equation. Thus, the online approximate nominal optimal control policy can be obtained without action NN. Then, the unknown actuator saturation, which is considered as saturation nonlinearity by simple transformation, is compensated by employing a NN-based feed-forward control loop. The stability of the closed-loop nonlinear system is analyzed to be ultimately uniformly bounded via Lyapunov’s direct method. Finally, the effectiveness of the presented control method is demonstrated by two simulation examples.     

Kinetics and thermodynamics of H. transfer from (eta5-C5R5)Cr(CO)3H (R = Ph,Me, H) to methyl methacrylate and styrene

The rates of H/D exchange have been measured between (a) the activated olefins methyl methacrylate-d(5) and styrene-d(8), and (b) the Cr hydrides (eta(5)-C(5)Ph(5))Cr(CO)(3)H (2a), (eta(5)-C(5)Me(5))Cr(CO)(3)H (2b), and (eta(5)-C(5)H(5))Cr(CO)(3)H (2c). With a large excess of the deuterated olefin the first exchange goes to completion before subsequent exchanges begin, at a rate first order in olefin and in hydride. (Hydrogenation is insignificant except with styrene and CpCr(CO)(3)H; in most cases, the radicals arising from the first H. transfer are too hindered to abstract another H. .) Statistical corrections give the rate constants k(reinit) for H. transfer to the olefin from the hydride. With MMA, k(reinit) decreases substantially as the steric bulk of the hydride increases; with styrene, the steric bulk of the hydride has little effect. At longer times, the reaction of MMA or styrene with 2a gives the corresponding metalloradical 1a as termination depletes the concentration of the methyl isobutyryl radical 3 or the alpha-methylbenzyl radical 4; computer simulation of [1a] as f(t) gives an estimate of k(tr), the rate constant for H. transfer from 3 or 4 back to Cr. These rate constants imply a DeltaG (50 degrees C) of +11 kcal/mol for H. transfer from 2a to MMA, and a DeltaG (50 degrees C) of +10 kcal/mol for H. transfer from 2a to styrene. The CH(3)CN pK(a) of 2a, 11.7, implies a BDE for its Cr-H bond of 59.6 kcal/mol, and DFT calculations give 58.2 kcal/mol for the Cr-H bond in 2c. In combination the kinetic DeltaG values, the experimental BDE for 2a, and the calculated DeltaS values for H. transfer imply a C-H BDE of 45.6 kcal/mol for the methyl isobutyryl radical 3 (close to the DFT-calculated 49.5 kcal/mol), and a C-H BDE of 47.9 kcal/mol for the alpha-methylbenzyl radical 4 (close to the DFT-calculated 49.9 kcal/mol). A solvent cage model suggests 46.1 kcal/mol as the C-H BDE for the chain-carrying radical in MMA polymerization.     

D60K Mb定点突变对肌红蛋白结构及荧光量子产率的影响

为了探究肌红蛋白表面60位的Asp突变为Lys后对蛋白荧光强度的影响,在模拟生理条件下,利用荧光法和圆二色法对WT Mb及D60K Mb的结构及荧光光谱特性进行了对照研究,结果表明D60K Mb的荧光量子产率远大于WT Mb。通过研究pH值和结构对荧光量子产率的影响,发现Mb 60位天冬氨酸(Asp)突变为赖氨酸(Lys)后,蛋白表面电荷发生改变,导致蛋白的荧光量子产率明显增强;同时使蛋白内部的芳香族氨基酸较原来更暴露,极性增强,激发态分子的去激发过程由原来的无辐射能量转移为主转变为辐射能量转移为主,最终导致荧光强度增强。