2＇，3＇－O－异亚丙基－5＇－O－［N，N－二（2－氯乙基）磷酰胺基］核苷的合成

２＇，３＇－Ｏ－异亚丙基－５＇－Ｏ－［Ｎ，Ｎ－二（２－氯乙基）磷酰胺基］核苷的合成陈茹玉，迟国臣，陈小茹（南开大学元素有机化学研究所，天津，３０００７１）关键词核苷，亚磷酰化，抗肿瘤活性很多核苷类化合物具有很好的抗肿瘤、抗病毒等生物活性，某些化合物已...     

Protease sensors for bioimaging

Optical imaging of specific molecular targets and pathways in vivo has recently become possible through continued developments in imaging equipment, reconstruction algorithms, and more importantly the availability of imaging reporter molecules. These reporter molecules encompass photoproteins expressed in vivo and exogenously administered probes detectable by fluorescence and/or bioluminescence imaging. One particularly enticing aspect of optical imaging is the ability to design activatible probes with inherent amplification. This review summarizes our experience in developing novel near-infrared fluorescent (NIRF) imaging agents that report on protease activities. These agents are designed to be biocompatible, highly activatible, and able to produce bright NIRF following protease cleavage.     

Synthesis, crystal structure and in vitro antitumor activity of di-n-butyltin 4′-(7-oxabicyclo [2,2,1]-5-heptane-2,3-dicarboximide) benzoates

Dibutyltin(IV) oxide reacts with the cantharidin analogue, 4′-(7-oxabicyclo [2,2,1]-5-heptane-2,3-dicarboximide) benzoic acid, A, to give the complexes [(p-C₈H₈NO₃-C₆H₄-COOBu₂Sn)₂O]₂ (1) and (p-C₈H₈NO₃-C₆H₄-COO)₂SnBu₂ (2) which had been characterized by IR and ¹H, ¹³C, ¹¹⁹Sn NMR. Single X-ray crystal structure analysis has been determined for compound (1), which was analogue to most other [(RCOOBu₂Sn)₂O]₂. The dimer features central of Bu₄Sn₂O₂ unit with the two Bu₂Sn groups being linked via bridging oxygen atom. Each tin atom adopts distorted trigonal bipyramidal structures via two carbons from a dibutyl moiety and three oxygen atoms from cantharidin derivative and bridging oxygen atom. In vitro tests show compounds 1 and 2 exhibit high cytotoxicity against P388 and HL-60.     

符合经典构效关系的抗肿瘤铂类药物

综述了自顺铂、卡铂后符合经典构效关系的铂类抗肿瘤药物的发展概况，按载体配基和离去基团的结构特征进行了分类，总结了各类配合物的构效关系和临床进展，其中重点对手性二胺配体的铂(Ⅱ)配合物进行了介绍。并讨论了顺铂、卡铂、奥沙利铂的作用机理。     

Direct capillary electrophoretic determination of three chemotherapeutic drugs in human urine

Summary Capillary zone electrophoresis (CZE) has been used for direct determination of 6-thioguanine, methotrexate, and 5-fluorouracil in human urine, by use of a fused-silica capillary (60.2 cm×75 μm i.d.). Separation was performed after hydrodynamic injection for 7 s; the separation potential and capillary temperature were 25 kV and 35°C, respectively. A 45mm borate buffer solution (pH 9.2) was used as separation electrolyte. Under these conditions the analysis takes approximately 10 min and interday precision of migration times and corrected peak areas is satisfactory. A linear response over the concentration range 3.0–20.0 mg L¹ was observed for the three chemotherapeutic drugs in diluted human urine. Detection limits (s/n=3) for 6-thioguanine and methotrexate were approximately 1.60 mg L¹ in diluted human urine; that for fluorouracil was 2.60 mg L¹. A 2-ml volume of human urine was diluted with 2-mL of water and introduced directly into the electrophoresis system. CZE was shown to be a good method with regard to simplicity, satisfactory precision, and sensitivity. This method resulted in especially excellent recoveries for determination of methotrexate in all the different urine samples analysed (n=10).     

Surface modification of highly dispersed rubber fillers and pigments by titanate proadhesive and hydrophobic compounds

A method of modifying silicate and carbonate fillers with titanate coupling agents and proadhesive agents was worked out. The modification aimed at hydrophobization of filler surface by introduction to the surface of functional groups with chemical affinity to polymers. Optimum amounts of modifying substances and appropriate conditions for performing the modification process were established. The obtained fillers showed a high degree of hydrophobicity.The modified fillers were applied in rubber mixtures based on butadienestyrene or natural rubber, in polyurethanes, in PVC, and as pigments in oil dyes of high corossive resistance.     

New unsaturated polyesters as injectable drug carriers

New unsaturated polyesters of poly(fumaric acid-glycol-sebacic acid) copolymers and poly(maleic anhydride-glycol-sebacic acid) copolymers were prepared by melt polycondensation of the corresponding mixed monomers: sebacic anhydride, fumaric acid or maleic anhydride and glycol. Methyl-methacrylate (MMA) was used as crosslinker and dimer acid was used as thinner.In vitro studies showed that those copolymers are degradable in phosphate buffer at 37 °C and poly(fumaric acid-glycol-sebacic acid) has proper drug release rate as drug carriers. The biocompatibility of poly(fumaric acid-glycol-sebacic acid) copolymers under mice skin was also evaluated; macroscopic observation and microscopic analysis demonstrated that the copolymer is biocompatible and well tolerated in vivo. The injected poly(fumaric acid-glycol-sebacic acid) [molar ratio M_{fumaric acid}:M_glycol:M_{sebacic acid} = 1.75:2.20:0.25] containing 5% adriamycin hydrochloride (ADM) in the mice bearing Sarcoma-180 tumor exhibited a good antitumor efficacy. The volume doubling time (VDT) (18 ± 2.5 days) of the tumor growth by this treatment was longer than that (7 ± 0.9 days) by the subcutaneous injection of ADM.     

Synthesis of new 6-substituted purinyl-5′-nor-1′-homocarbanucleosides based on indanol

A series of new 6-substituted purinyl-5′-nor-1′-homocarbanucleosides based on indanol were synthesized from (±)-cis-3-hydroxymethyl-1-indanol, an appropriately functionalized derivative of which was reacted with 6-chloropurine in the presence of NaH and 18-crown-6 ether to prepare a key intermediate that gave access to the target molecules, purinylcarbanucleosides in which position 6 is occupied by a chloro, hydroxy, methoxy, amino or substituted phenyl group.     

Alginic acid–silica hydrogel coatings for the protection of osmotic distillation membranes against wet-out by surface-active agents

The formulation of organic–inorganic polymer composites can be used to enhance selected properties, such as susceptibility to microbial attack, thermal stability, mechanical strength and water sorption capability. Accordingly, a series of alginic acid–silica hydrogel films was prepared for testing as protective coating materials for PTFE osmotic distillation membranes. Unprotected hydrophobic membranes are subject to wet-out when contacted by surface-active agents, such as oils and detergents. Films containing 5, 10, 15 and 20 wt.% silica, with and without the addition of glycerol for plasticisation, moisturisation and silica dispersion, were characterised using scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, mechanical strength measurements, and water-swelling measurements. Composites prepared with glycerol addition had better thermal stability, mechanical strength and water sorption capability than those prepared without glycerol addition. Uncoated membranes and membranes coated with composites prepared with glycerol addition were tested for OD performance and resistance to surface-active agents using pure water, orange oil (limonene)–water mixtures, and sodium dodecylbenzene sulfonate detergent solutions. Uncoated membranes showed immediate hydrophobicity loss in the presence of orange oil and detergent. For coated membranes, no wet-out occurred over the 15 h duration of three consecutive 5 h OD trials using orange oil–water mixtures. In the case of detergent solutions, the coating afforded protection to the membrane for 4–5 h. In a separate trial, no wet-out occurred when the coated side of the membrane was placed in contact with 1.2 wt.% orange oil for 72 h.     

含己烷雌酚的聚磷酸酯的合成及其抗肿瘤活性研究

合成了３种主链含己烷雌酚的生物可降解的聚磷酸酯，结构经ＩＲ，＾１ＨＮＭＲ和元素分析鉴定，通过水接触角的测定研究了聚合物的亲水－疏水性能，以ｐＨ值变化表征了聚合物的体外水解速率。初步的体外实验表明，此类聚磷酸酯具有较好的体外抗艾氏腹水癌活性。