Polymers in medicine

The problems encountered in the use of artificial materials in the body are discussed, using as example the artificial heart. In the quest for suitable materials, numerous investigations have been carried out, including, inter alia, studies on the adsorption of proteins on polymer surfaces and on the passivation of such surfaces by coating with proteins or by the growth of cell cultures. The development of passive artificial substances is also discussed.     

The Crystalline State of Macromolecular Substances

Unlike low molecular weight substances, high polymers do not crystallize completely. However long the crystallization process is continued, they still consist of a mixture of crystalline and non crystalline regions. In the undrawn material, these regions form larger units which are known as spherulites. Questions that are of special interest concern the arrangement of the chains in the noncrystalline regions, the causes of chain folding, and the imperfections in the crystals. The incomplete crystallization is a consequence of kinetic inhibitions. This can be deduced from the fact that the crystalline fraction increases with rising crystallization temperature. If polymerization is carried out in the solid crystalline state, one obtains a completely crystalline polymeric material.     

Nuclear medicine and radiochemistry

Nuclear-medical diagnostic methods are widely used at present, examples being localization diagnosis e.g. of the thyroid, the kidney, and the spleen and function tests, e.g. on the thyroid and on the liver. For these tests it is essential to have organ-specific vehicle substances that can be labeled with suitable radionuclides. For in-vivo investigations, the exposure of the patient to radiation should be kept as small as possible, but the radiation must nevertheless be sufficient to allow the detection of the nuclide. Today, the therapeutic use of radionuclides is only small in comparison with their use in diagnosis.     

Combination of click chemistry and sulfonamides to develop three-armed triazole compounds

Fragment-based drug discovery is a valuable tool in hit identification, as well as the combination of different small fragments showing a minimal binding activity against biological receptors or enzymes to give merged hits. A high number of fragments on the same scaffold improve the probability to find a candidate showing single- or multi-target affinities. A rapid and versatile approach for synthesizing libraries of densely fragment-functionalized scaffolds is reported. Many fragments were assembled in few steps around a triazole ring starting from amino alcohols and other readily available building blocks. A binding assay against integrin α_vβ₃ was used as a test-bed in order to demonstrate the potential of such an approach in hit discovery strategies.     

Macromolecular polyyne-containing benzoxazines for cross-linked polymerization

A Mannich condensation of 2,4-di-tert-butylphenol, p-bromophenethylamine, and formaldehyde followed by a Sonogashira coupling of the resulting 3-(4-bromophenethyl)-6,8-di-tert-butyl-3,4-dihydro-2H-benz[1,3]oxazine (1-Br) with TMSCCH gave acetylenic benzoxazine 1-C₂TMS which was a precursor for polyynic derivatives. Firstly, it was deprotected with K₂CO₃ in iPrOH/MeOH to give the terminal acetylene 1-C₂H, which was subsequently dimerized to the symmetrical diyne 1-C₄-1. Next, 1-C₂H was transformed to 1-C₄TMS via a Cadiot-Chodkiewicz coupling, and then 1-C₄TMS was homocoupled with in situ deprotection to give octatetrayne 1-C₈-1. X-ray diffraction studies of 1-C₈-1 showed distinctive chain bending and a packing analysis revealed the potential for 1,n-topochemical polymerization that implies a cross-linking opportunity.     

Applications of heteronuclear NMR spectroscopy in biological and medicinal inorganic chemistry

There is a wide range of potential applications of inorganic compounds, and metal coordination complexes in particular, in medicine but progress is hampered by a lack of methods to study their speciation. The biological activity of metal complexes is determined by the metal itself, its oxidation state, the types and number of coordinated ligands and their strength of binding, the geometry of the complex, redox potential and ligand exchange rates. For organic drugs a variety of readily observed spin I = 1/2 nuclei can be used (¹H, ¹³C, ¹⁵N, ¹⁹F, ³¹P), but only a few metals fall into this category. Most are quadrupolar nuclei giving rise to broad lines with low detection sensitivity (for biological systems). However we show that, in some cases, heteronuclear NMR studies can provide new insights into the biological and medicinal chemistry of a range of elements and these data will stimulate further advances in this area.     

Pharmaceutical Chemistry Today—Changes,Problems, and Opportunities

Dissatisfaction with empirical methods, high expectations of the public, poorly harmonized international regulations, and rising costs have induced pharmaceutical research to search for new approaches. As a consequence, the medicinal chemist's professional activity is in a state of change. His synthetic strategy is being increasingly influenced by the reasoning of molecular biology. Novel classes of biologically active compounds demand the development of new synthetic methods beyond the scope of modern preparative organic chemistry: enzymes and microorganisms, cell cultures, and genetic engineering are harnessed to supply highly complex structures. Major efforts are devoted to the development of reliable structure-activity relationships to rationalize his work. Thus the field of medicinal chemistry stretches from physical and physical organic chemistry far into the realm of biosciences, and the interdisciplinary character of this research is rapidly increasing. The author endeavors to convey an impression of this complex subject with the aid of selected examples.     

高分子链在微通道剪切流中的迁移机制及浓度的影响

提出了剪切流中高分子链在微通道内的迁移机制.该机制采用珠-簧链模型表示高分子链,高分子链受剪切作用而被拉伸,相邻珠子之间的流体力学相互作用产生了对称的扰动流场,由于在通道壁面附近对称的流场被破坏,壁面与高分子链间的流体力学相互作用使高分子远离壁面,在强受限时,这种壁面诱导的流体力学相互作用会被屏蔽掉.利用耗散粒子动力学数值模拟了高分子链在微通道压力流中的迁移行为.数值模拟结果表明,在受限较弱时,高分子链向远离壁面的方向迁移,并随着流场增强,远离壁面的趋势越强;在受限较强时,高分子链不会发生远离壁面的行为.实验研究了长链高分子λ-DNA在壁面附近的迁移行为,实验结果及模拟结果与迁移机制预测的结果相吻合,验证了迁移机制的正确性.高分子链浓度会影响高分子链的迁移行为,当高分子链浓度较大时,高分子链在通道宽度方向不会发生迁移现象,意味着随着浓度的增大,壁面与高分子链间的流体力学相互作用会逐渐被屏蔽.     

中医药现代化对分析化学的机遇与挑战

综述了多种分析方法在中医药现代化中的重要作用,内容包括中药面临的机遇与挑战,中药市场及所存在的问题,当前在中药鉴别、分离、提纯以及复方药效的研究常用的分析方法,中药指纹图谱以及残留农药的检测。引用文献183篇。     

A flow chemistry route to 2-phenyl-3-(1H-pyrrol-2-yl)propan-1-amines

The Knoevenagel condensation of pyrrole-2-carboxaldehyde (1) with a range of substituted benzyl nitriles (2a-e) afforded rapid access to a family of α,β-unsaturated nitriles (3a-e) in good yields (67-78%). Flow hydrogenation (ThalesNano H-cube™) at 60 °C, 50 bar H₂ pressure, 1.0 mL/min through a 10% Pd-C catalyst selectively, and quantitatively, hydrogenated the olefin double bond (4a-e). Use of a Raney Nickel catalyst at 70 °C, 70 bar H₂ pressure and flow rates of 0.5-1.0 mL/min afforded quantitative conversion into the corresponding saturated amines with the reduction of both the olefin and nitrile bonds (5a-e). The versatility of this approach was further exemplified by reaction of 5a and 5c with norcantharidin to afford acid amide norcantharidin analogues 7 and 8 as novel protein phosphatase 1 and 2A inhibitors.     

Two-Dimensional Chromatography as an Essential Means for Understanding Macromolecular Structure

Current liquid chromatography techniques allow to determine distributions of various properties for macromolecules. The polydisperse nature of macromolecules regulates the structure-property relationship and is responsible for the vast degree of fine-tuning of application properties. The understanding of macromolecular structure is fundamental for the use of polymers in increasingly specific applications. The coexistence of property distributions requires multi-dimensional (combined) chromatography methodologies. The use and implementation of two-dimensional (2D) separation methods and their benefits are described in this paper for synthetic polymers. Similar approaches have been used successfully for mapping complex natural and bio polymers.     

General synthetic strategies towards N-alkyl sulfoximine building blocks for medicinal chemistry and the use of dimethylsulfoximine as a versatile precursor

The sulfoximine group has great potential as a substituent in drug discovery, as evidenced by two new clinical candidates, and can be viewed as an isosteric alternative to the commonly used sulfone. Our aim was to improve the accessibility of this group by synthesising a diverse range of S-alkyl and N-alkyl sulfoximine building blocks with procedures that are applicable on a practical scale (>10 g). In particular, synthesis of the less well exploited N-alkyl sulfoximines and the use of dimethylsulfoximine as a versatile, commercially available precursor is discussed.     

High Pressure Kinetic Investigations in Organic and Macromolecular Chemistry

High pressure kinetics appears to be a valuable tool in investigating the mechanism of specific organic reactions. For instance, in pericyclic, Mentshutkin, cage, and polymerization reactions, such studies reveal various features of the transition state, in particular its localization along the reaction coordinate and its nature. However, precise conclusions require separation of the different effects (electrostatic, steric, orbital, etc.) which may contribute to the structure of the transition state.     

Preparation of 5-amino-6-oxo-1,6-dihydro[1,2,4]triazine-3-carboxylic acid derivatives and synthesis of compound libraries thereof

Treatment of [1,3,5]triazine-2,4,6-tricarboxylic acid triethyl ester (4) with arylhydrazines provided 5-amino-6-oxo-1,6-dihydro[1,2,4]triazine-3-carboxylic acid ethyl esters 5a-g in moderate to good yields. Hydrolysis under basic conditions gave the corresponding free carboxylic acids 6a-d. Despite the relatively high number of heteroatoms present the amido as-triazine compounds 6a-d showed good solubility in phosphate buffer as determined by a lyophilization solubility assay. Building block 5a served as starting point for the syntheses of two discrete exocyclic 5-amido and 3-amido compound libraries 7 and 8, respectively.     

充满生机和科学机遇的磷化学研究所

简要地综述了第十五届国际磷化学会议的报告内容，介绍了目前磷化学的主要 研究领域，包括不对称合成、配合化学，生物碱化学，药物化学，农业化学等相关 领域的研究动态及新进展。     

Synthesis of heterocycles from arylacetonitriles: Powerful tools for medicinal chemists

Arylacetonitriles are versatile building blocks for the construction of heterocyclic scaffolds in medicinal chemistry. These intermediates are able to engage in a variety of synthetic transformations, giving rise to diverse biologically active structures. This digest focuses on recent applications of this synthetic methodology by drug discovery teams across several disease areas, with an emphasis on different reaction types.