药物化学中的大分子效应※

药物种类按照分子量来划分可以分为小分子药物(自然提取或化学合成的)和大分子药物(生物制剂). 尽管目前小分子药物仍然是市场的主流, 但其研发增速趋缓, 而大分子药物在药物研发中的地位日渐突显, 并被预期在未来药物市场中占据越来越高的份额. 除了生物制剂大分子药物, 将小分子药物与天然或合成大分子结合制备得到的化学合成大分子药物, 近年来受到药物研究者们越来越多的关注. 由于大分子具有丰富的骨架结构及空间构架, 其所特有的骨架效应、多价效应, 以及通过分子组装而产生的聚集效应和靶向效应等, 能够为药物化学的设计带来更多新的可能. 有鉴于此, 本综述将简略介绍药物化学设计中的大分子效应, 重点讨论合成大分子的骨架效应、多价效应、聚集效应和靶向效应等为药物化学设计所带来的新性能. 通过对药物化学中大分子效应所带来的优势、问题和重要研究进展的探讨, 以期能够推动化学合成大分子药物的发展, 为药物化学设计提供新的思路.     

电子效应对单取代苯定位效应和反应活性的影响

单取代苯的定位效应和反应活性主要受取代基的电子效应控制,列表总结了取代基的电子效应与定位效应和反应活性的关系,分析了烃基电子效应的特殊性,取代基具有-Ⅰ效应的普遍性。除卤素取代基外,探讨了共轭效应的方向对定位效应和反应活性的决定作用。     

Thorpe-Ingold效应及其在有机成环反应中的应用

本文首先介绍了Thorpe-Ingold效应及其相关理论和实验研究进展,然后综述了近年来Thorpe-Ingold效应在形成三、四、五和六元环产物的环化反应中的应用。Thorpe-Ingold效应可以有效地促进分子内和分子间环化,提高环化的产率和速率。该效应主要通过空间效应、电子效应或者两者协同起作用,在某些情况下,该效应还会受催化剂和溶剂等影响。利用该效应可以促使一些难以发生的环化反应顺利进行,并能获得较好的产率。     

Kinetic Studies of Solvent and Pressure Effects on the Thermal Isomerization of Palladium Dithizonate

IntroductionThe photo-and thermo-chromisms of organometallic compounds have been intensivelystudied during thelast1 0 years.Meriwetheretal.[1 ,2 ] examined the chromic behaviorofmet-al-dithizone(phenyldiazenecarbothionic acid2 -phenylhydrazide) complexesin detail.From thekinetic and infrared studies,they showed thatthe central metal of a dithizonate complex de-termined the photochemical stability,the rate of the thermal return reaction,and the colorofthe dithizonate complex.As reported by Mer…     

α，ω－双香豆素长链化合物光二聚反应的影响因素

对α，ω－双香豆素长链化合物光二聚反应中盐效应、溶剂效应、粘度效应及连接体的长度和柔顺性等因素的影响进行了研究。借助１ＨＮＭＲ谱、ＵＶ吸收谱、荧光光谱分别对α，ω－双香豆素长链化合物在不同条件下的构象进行了分析，并解释了不同条件下的光二聚行为     

PdCONaOH体系中NaOH助催化作用的理论研究

用Gaussian94程序，HF和MP2方法，LANL2DZ基组，研究了模型化合物PdCONaOH的电子结构，讨论了碱的助催化作用。结果表明碱NaOH对PdCO的助催化作用是通过Na⁺和OH^-协同作用而完成，并且其助催化效果与Na⁺和OH^-相对于PdCO的位置(距离和方向)以及Na⁺和OH^-之间的距离有关。     

Heavy Atom Effect on the First Hyperpolarizabilities of Squaric Acid Homologues Studied by Ab Initio and DFT Methods

1 INTRODUCTION In the past decades, there have been great efforts to research on the molecules nonlinear opti- cal (NLO) properties in which theoretical calcu- lation[1～3] became a powerful tool because it not only explains the micro-mechanism of the mo…     

环糊精聚合物的高分子效应

环糊精以其独特的包络性能而引人注目, 现已广泛应用于色谱分离、选择性合成的催化剂、食品、医药及农药等多种领域。环糊精聚合物被证实亦具有包络、缓释及催化的能力, 以及较好的机械强度和化学稳定性。目前环糊精聚合物主要应用在色谱分离、空气净化和食品工业等方面。本文综述了环糊精高分子化后所表现出的高分子效应, 为环糊精聚合物的合成和应用提供参考。     

Ab Initio and Density Functional Study on the First Hyperpolarizabilities of Squaric Acid Homologues

The first hyperpolarizabilities of four squaric acid homologues: squaric acid, 1,2-dithiosquaric acid,1,2-diselenosquaric acid and 1,2-ditellurosquaric acid have been calculated using ab initio and DFT methods. The effects of equilibrium geometries, basis set and electron correlation on the first hyperpolarizabilties of these molecules were investigated. The frequency dispersion effect and solvent effect, which are essential to get reliable outputs in comparison to the experimental results, have also been explored. On the basis of these investigations, it is worthy to point out that the heavy atom effect takes effect for these squaric acid homologues.     

若干有机合成反应的构象效应

通过分析竞争反应的过渡态在构象上能量的高低,探讨构象效应(立体电子效应和位阻效应)对一些有机反应的立体性的影响;而立体电子效应和位阻效应与反应机制,反应物的结构-构象和反应条件等都有关系,最终能影响反应产物的立体结构。阐明其中的缘由可有助于正确预测产物的结构及选择可行的合成线路。     

包覆效应与压片法X射线荧光光谱分析

提出了在压片法X射线荧光光谱分析中存在包覆效应。用粉末压片X射线荧光光谱法测定刚玉镁砂浇注料的成分时,氧化镁的测定结果偏高,氧化铝的测定结果偏低,且偏低量、偏高量相近。用玛瑙研钵将样品不断研磨至更小的粒径时,上述现象没有明显的改变,表明此现象不属于粒度效应。用分别研磨至0.096mm的刚玉和镁砂粉末,按氧化铝和氧化镁含量与浇注料相近的比例混合均匀后,分别用压片法和熔片法测定,发现两种制片方法测定结果相近,表明上述现象也不是矿物效应。因此,提出了包覆效应的概念。用已有的报道证实了包覆效应,并指出了粒度效应、矿物效应和包覆效应的区别。     

Substituent effect on N?H bond dissociation enthalpies of amines and amides: A theoretical study

N? H bond dissociation enthalpies for the substituted ammonia, amine, amides, and their thio‐ and seleno‐analogs have been studied employing ab initio and density functional methods. The orbital interactions involving lone pair of electrons on nitrogen and substituent, electrostatic interactions, spin delocalization, and hydrogen bonding are the important factors affecting the stability of the molecule and the radical. The molecule stabilization effect and radical stabilization effect have been calculated using isodesmic reactions in order to analyze the effect of substituent on the stabilization of the molecule and the radical. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2009     

有机化学中的异头效应

1955年Edward 首次发现吡喃糖C(1)位的电负性强的取代基处于a键上, 随后被Lemieux和Chü定义为异头效应. 它是有机化学中最重要的立体电子效应之一, 通常存在于有Lp-X-A-Y结构单元的分子中, 其中X是带有孤对电子的电负性强的元素, A是一般元素, Y 也是电负性强的元素, Lp是X的孤对电子, 其轨道与A—Y键反平行. 异头效应对分子的结构和反应活性有重要影响. 综述了各类化合物中存在的异头效应、广义异头效应、反异头效应及在有机化学中的应用.     

Magnetic Field and Magnetic Isotope Effects upon Reactions of Heavy Atom-Centered Radicals

We present our recent studies on magnetic field effects (MFEs) observed in reactions of heavy atom-centered radicals such as Si-,P-, Ge-, and Sn-radicals with a ns-laser photolysis technique under magnetic fields of 0–10 T. Although the MFES of heavy atom-centered radicals are much smaller than those of C-radicals due to the spin-orbit interaction of heavy atoms, we have found appreciable MFEs in many reactions of such heavy atom-centered radicals. Comparing the MFES of C-radicals with those of heavy atom-centered ones, we have explained the MFEs of heavy atom-centered radicals in terms of the Δg and relaxation mechanisms. We have found that the separation between the MFES due to the Δg mechanism and those due to the relaxation one is possible with the enhancement of spin relaxation by the addition of a paramagnetic ion. We have also tried to enrich magnetic isotopes of heavy atoms with the magnetic isotope effect (MIE), using the reactions which show fairly large MFES. Recently, we have succeeded in enriching ⁷³Ge. This is the heaviest isotope which has so far been enriched with the MIE from samples of natural abundance.     

NQR parameters of complexes and polarizability effect

The literature data on substituent influence on the nuclear quadrupole resonance frequencies (ν), quadrupole coupling constants (e²Qq ? h^{? 1}), and asymmetry parameters (η) for 36 series of the H‐complexes, charge–transfer complexes, transition metal complexes and other donor–acceptor complexes have been considered, using the correlation analysis. Generally the ν, e²Qq ? h^{? 1}, and η values were first established to depend on the inductive, resonance, polarizability, and steric effects of substituents. The presence or otherwise of certain effects as well as relation between their contributions are determined by the type of series. The polarizability effect owes its existence to the appearance of an excess charge on the indicator centre as a result of the complexation. The contribution of this effect ranges up to 75%. Copyright © 2012 John Wiley & Sons, Ltd.     

DIAR成色剂的最新进展

本文分别从定时基团、抑制基团、成色母体和分子结构这4方面介绍了近十几年来DIAR成色剂的最新进展,特别介绍了一些具有新结构和新功能的DIAR成色剂的情况.抑制基团是这几年发展最快的,一些具有好的照相性能的抑制基团被合成;为了提高DIAR成色剂的层间效应,设计出了双定时的DIAR成色剂;溶出型的DIAR成色剂得到进一步的改进,从而能够被广泛地应用.     

微波化学中微波的热与非热效应研究进展

微波作为一种传输介质和加热能源已广泛应用于各学科领域,如食品加工、药物合成、橡胶和塑料固化等,但是对在反应过程中微波的非热效应学术界一直存在争议.本文在微观和宏观两方面详细地阐述了微波化学中的热效应和非热效应作用机理.并具体介绍了微波热效应与非热效应在化学领域的应用实例.     

水通道蛋白启发下的人工水通道研究进展

受水通道蛋白(AQP)结构与功能启发,含有生物水通道或人工水通道(AWC)的仿生膜近年来取得了显著进展.借鉴AQP的传输特性,所制备的AWC获得了高度的选择性及水快速运输能力.通过对AQP的结构原型进行分析,对标AWC中H2O分子选择性和渗透特性,尝试提出了"门控效应"、"润湿效应"和"排队效应"3种效应,并对现有嵌入...     

以毛细和蒸发作用为驱动力的微泵的研制

报道了一种简单、造价低、体积小、流速稳定、可长时间连续使用及流速易于调节的微泵的研制。它以吸水膜的毛细作用和大气蒸发相结合作为驱动力，由储液管、蓄水池、吸水膜和蒸发孔组成。工作中对微泵性能进行了测试并考察了温度、湿度、蒸发面积、空气流动状况对微泵流速的影响，结果表明：在同一工作日的一般温湿度波动范围内，微泵可在较长时间内提供稳定的μL/min级液体流速。通过改变蒸发孔的面积或使用风扇可调节微泵的流速。微泵的流速精度(RSD)一般优于3％。     

充分利用电子效应解释苯环定位规律

利用电子效应解释一元取代苯环上亲电取代反应的定位规律,不但解释了各类定位基定位效应的不同,而且解释了同一类定位基邻位和对位产物比例的不同,而后者用被普遍使用的共振论则难以解释。