反应控制相转移催化剂催化丙烯环氧化反应的影响因素

 以H2O2为氧化剂,以磷酸氢盐或磷酸二氢盐为添加剂,研究了反应控制相转移催化剂(磷钨杂多酸季铵盐)催化丙烯环氧化的反应性能. 结果表明,当体系中不存在添加剂时,产物环氧丙烷的水解情况严重; 加入适量的添加剂可有效抑制环氧丙烷的水解. 作为抑制环氧丙烷水解的添加剂,磷酸氢盐比磷酸二氢盐具有更优异的性能,且磷酸氢钾比磷酸氢钠效果更佳. 在没有丙烯的情况下,随着温度的升高,环氧丙烷水解反应加剧; 在相同的温度下,环氧丙烷浓度越低,其水解率越高; 当环氧丙烷浓度较低时,催化剂的存在促进其水解,但在较高的浓度下,催化剂的存在则可抑制其水解. 随着温度的升高, H2O2分解反应加剧,当温度超过60 ℃时,分解速度显著加快. 催化剂在油/水二相中的分配实验结果表明,在H2O2存在的情况下,于50 ℃达到平衡时, 85.0%以上的催化剂被转移至有机相.     

温敏性乙二醇壳聚糖水凝胶的制备及药物缓释性能

以乙二醇壳聚糖为原料, 乙酸酐为酰化剂, 通过N-乙酰化反应, 制得了新型温敏性高分子乙酰化乙二醇壳聚糖. 通过核磁共振氢谱(¹H NMR)、 傅里叶变换红外光谱(FTIR)及试管倒置法对乙酰化乙二醇壳聚糖的结构及温敏性进行了表征, 通过扫描电子显微镜(SEM)和紫外-可见分光光度计(UV-Vis)对水凝胶的微观形貌和体外药物释放性能进行了研究. 结果表明, 随着反应时间和乙酸酐与乙二醇壳聚糖氨基摩尔比的增加, 产物的乙酰度逐渐增加; 乙酰化乙二醇壳聚糖溶液具有热可逆温敏性溶胶-凝胶转变行为, 可以通过控制乙酰化乙二醇壳聚糖的乙酰度和溶液浓度, 使溶胶-凝胶转变温度处于室温至体温(25~37 ℃)之间; 乙酰化乙二醇壳聚糖水凝胶具有“高度孔隙化且孔隙之间相互连通”的结构特点, 通过控制乙酰度和溶液浓度, 可使其孔径大小处于1~40 μm范围内; 乙酰化乙二醇壳聚糖水凝胶的乙酰度为89.90%时, 质量分数为5%~7%的水凝胶对抗癌药物吉西他滨具有缓释作用, 载药凝胶的释药时间可达3~5 d. 乙酰化乙二醇壳聚糖有望在药物释放及组织工程等领域得到广泛应用.     

载万古霉素PLGA-PEG-PLGA温度敏感水凝胶的体外抗菌性能

利用聚乙二醇（PEG 1500）引发乙交酯和D,L-丙交酯开环共聚合制备聚丙交酯乙交酯（PLGA）三嵌段共聚物（PLGA-PEG-PLGA）温敏水凝胶材料,并通过核磁共振氢谱（¹H NMR）确定产物的结构及组成.应用倒置小瓶法测量得到不同浓度下PLGA-PEG-PLGA水凝胶的溶胶-凝胶相变温度为27~32℃.此外,体外降解实验及细胞毒性实验结果表明,质量分数为25%的水凝胶有满意的降解速度及良好的生物相容性.同时,利用紫外-可见光谱分析了载万古霉素水凝胶的体外药物释放行为,结果表明,万古霉素可以持续释放12 d.抗菌实验结果表明,载万古霉素水凝胶具有良好的抗菌效果.表明PLGA-PEG-PLGA三嵌段温敏水凝胶是一种较理想的万古霉素缓释载体,具有良好的临床应用前景.     

温敏性水凝胶在抗菌领域应用的研究进展

智能水凝胶是一种能在水中溶胀而不溶于水的高分子聚合物,且能对外界刺激而作出应答的一类凝胶体系。温敏水凝胶是智能水凝胶的一种,它能根据环境温度的变化而产生体积相转变现象,与抗菌剂复合可使其具有抗菌活性。温敏水凝胶可以根据环境温度的变化间断式地释放抗菌剂,提高抗菌剂的效用时间,可应用于生物、医药、纺织等领域。本文介绍了温敏水凝胶的温敏机理,重点综述了近年来与抗菌剂相结合的丙烯酰胺、泊洛沙姆、壳聚糖及聚乙二醇-b-聚酯类共聚物等温敏性复合水凝胶在抗菌应用方面的研究进展,并探讨了近年来抗菌复合水凝胶研究存在的问题及未来的研究方向。     

甲基纤维素硬脂酸酯/γ-聚谷氨酸复合温敏水凝胶的制备及其性能研究

为解决慢性创伤修复过程中机体因氧化还原反应失衡造成的延迟愈合问题,本研究以甲基纤维素(MC)和γ-聚谷氨酸(γ–PGA)为原料,制备温敏性水凝胶;该体系最低凝胶化温度为37℃左右;MC/γ-PGA水凝胶具有较高的吸水率和保水性,其吸水率随着γ-PGA含量的增加而增大;通过负载超氧化物歧化酶(SOD)使得其具有SOD的可控缓慢释放作用,能够有效地清除超氧自由基;而且该凝胶体系具有良好的细胞相容性。本研究为实现负载SOD的温敏性水凝胶创伤修复材料的应用奠定了实验基础。     

P123重水溶液的物理凝胶化及凝胶结构

利用 1H NMR方法, 研究了高浓度的P123(PEO20PPO70PEO20)在重水溶液中的溶胶-凝胶转变过程. 升高温度使得体系发生溶胶-凝胶转变, 进一步升高温度, 体系发生凝胶-溶胶转变. 通过对不同质子基团的谱线宽度和化学位移偏移的分析, 同时结合流变学频率扫描和同步辐射(SR)研究, 发现质量分数为30%的P123的重水溶液在凝胶化过程中, 结构经历了由立方相(cubic)-六角柱状相(hcp)-层状相(lamellar)的转变过程, 其中立方相为面心立方(fcc)和六角密堆积球状相(hcps)的混合相. 高温时从凝胶到溶胶的转变主要体现为P123形成富集区与水发生相分离的过程.     

温度和pH双敏性PVME/CMCS水凝胶辐射交联制备及其性能

以聚甲基乙烯基醚(PVME)和羧甲基壳聚糖(CMCS)为原料, 采用电子束辐照交联方法制备聚甲基乙烯基醚/羧甲基壳聚糖(PVME/CMCS)水凝胶, 研究了温度、pH值、CMCS含量等对PVME/CMCS水凝胶溶胀度的影响, 同时以5-氟尿嘧啶(5-Fu)作模型药物, 初步探讨了凝胶药物释放性能. 结果表明, 辐射剂量在20—40 kGy时, 凝胶分数随辐射剂量的增加而快速增加, 辐射40 kGy以后趋于平衡. 在相同辐射剂量下, 随着体系中CMCS含量的增加, 凝胶分数反而减少. 该水凝胶具有一定的温度和pH敏感性, 其低临界溶解温度(LCST)在35 ℃左右, 并且在相同时间内和25及37 ℃下的溶胀反复可逆, 表现出较快的响应性. pH<3.0和pH>5.0时, 溶胀度较大; pH值为3.0~5.0时, 凝胶网络由于静电力收缩, 溶胀度较小. CMCS含量的增加和辐射剂量的减小均可提高凝胶载药量. 药物释放时间可通过改变体系中CMCS的含量和辐射剂量来调节.     

丙烯酸β-羟丙酯/乙烯基吡咯烷酮水凝胶的合成和热敏行为的研究

用自由基共聚法合成了一系列 β -羟丙酯 ( β -HPAT)和乙烯基吡咯烷酮 (NVP)的共聚物及其水凝胶。发现共聚物的水溶液有敏锐的温敏行为 ,最低汇溶温度 (LCST)随NVP含量的增加而升高 ,随着反应单体总浓度的增加 ,相变敏锐性下降且LCST也随之下降。通过考察水凝胶的溶胀率 (SR) ,发现共聚凝胶在适当的单体浓度 ,交联剂浓度和较宽的单体浓度配比范围内 ,有较灵敏的温敏行为。     

用核磁共振技术研究[C4mim][BF4]在重水和氘代氯仿中的聚集行为

运用核磁共振技术, 研究了室温离子液体1-丁基-3-甲基咪唑四氟硼酸盐([C4mim][BF4])在重水和氘代氯仿中的聚集行为. 实验结果表明, 随着混合体系中离子液体摩尔分数的增加, 在重水中, 离子液体阳离子上各氢原子的化学位移向低场移动, 且呈现了先急剧变化, 后趋于平缓的变化趋势; 在氘代氯仿中, 离子液体阳离子上H2的化学位移向高场移动, H4和H5以及与氮原子直接相连的甲基和亚甲基上的氢原子的化学位移都向低场移动, 且各氢原子的核磁共振信号发生了变化. 根据质量作用定律及1H NMR化学位移随浓度的变化关系计算了[C4mim][BF4]在重水中的临界聚集浓度和聚集数, 并在离子液体阴、阳离子缔合以及离子液体与溶剂相互作用的基础上对实验结果进行了讨论.     

用核磁共振技术研究[C4mim][BF4]在重水和氘代氯仿中的聚集行为

运用核磁共振技术,研究了室温离子液体1-丁基-3-甲基咪唑四氟硼酸盐([C4mim[BF4])在重水和氘代氯仿中的聚集行为.实验结果表明,随着混合体系中离子液体摩尔分数的增加,在重水中,离子液体阳离子上各氢原子的化学位移向低场移动,且呈现了先急剧变化,后趋于平缓的变化趋势;在氘代氯仿中,离子液体阳离子上H2的化学位移向高场移动,H4和H5以及与氮原子直接相连的甲基和亚甲基上的氢原子的化学位移都向低场移动,且各氢原子的核磁共振信号发生了变化.根据质量作用定律及1H NMR化学位移随浓度的变化关系计算了[C4mim][BF4]在重水中的临界聚集浓度和聚集数,并在离子液体阴、阳离子缔合以及离子液体与溶剂相互作用的基础上对实验结果进行了讨论.     

Preparation of alginate coated chitosan hydrogel beads by thermosensitive internal gelation technique

Chitosan hydrogel beads were successfully prepared by the method of thermosensitive internal gelation technique. The prepared beads were spherical, smooth-surfaced and non-aggregated with a diameter of 1.7–2.1 mm. The diameters of beads can be controlled and have a correlation with the initial drop size, the concentration of CaCl₂, alginate and the time of solidification. The bead is comprised of three parts, which are chitosan/glycerophosphate (CS/GP) hydrogel core, chitosan-alginate (CS/SA) gel layer in the middle and calcium-alginate gelatin capsules in outer layer. Swelling studies indicate that the beads can be stable in simulated gastric fluid. But the beads shrink sharply when removed to simulated intestinal fluid. Drug release behavior showed that release of ornidazole in the beads is much slower than in the CS/GP hydrogel.     

Complete NMR data assignments for novel pterocarpans from Harpalyce brasiliana

A NMR study of two new pterocarpans isolated from the roots of Harpalyce brasiliana is described. In addition to 1D NMR, 2D shift-correlated NMR pulse sequences ((1)H-(1)H-COSY, HSQC and HMBC) were used to establish the structures, and unambiguously perform the (1)H and (13)C chemical shift assignments.     

表面活性剂胶束形状随浓度转变的核磁共振研究

运用核磁共振一维氢谱和自扩散实验方法研究了聚乙烯乙二醇异辛酚醚(TX-100)、十二烷基苯磺酸钠(SDBS)和十四烷基三甲基溴化铵(TTAB)三种不同类型的表面活性剂在重水溶液中的胶束形状转变, 发现它们在临界胶束浓度以上的各自相应浓度都有胶束形状的变化(由球状转变为椭球状或棒状). 在常温常压和没有其他添加剂的情况下, 表面活性剂溶液浓度高于其临界胶束浓度时, 球状胶束开始形成. 核磁共振一维氢谱和自扩散实验的结果显示, 当溶液浓度继续增加到一定程度时, 溶液中表面活性剂分子的化学位移和自扩散系数的变化速率都有明显的转折, 这说明溶液中球状胶束开始发生转变. 进一步通过仔细分析对比核磁共振一维氢谱中各基团谱峰, 发现表面活性剂胶束亲水表面上的质子的化学位移变化速率要远高于其疏水内核中的质子, 据此推测胶束形状很可能由球状转变为椭球状或棒状.     

A synthetic hydrogel with thermoreversible gelation,III: an NMR study of the sol–gel transition

The sol–gel transition mechanism of a thermoreversible hydrogel composed of a copolymer comprising poly(N-isopropylacrylamide) and poly(ethylene glycol) (PNIPAAm–PEG) was studied by NMR. The ¹H– and ¹³C–NMR spectra measured on a PNIPAAm–PEG solution in 99.9% D₂O showed a remarkable line width broadening of the PNIPAAm block of more than that of the PEG block, during thermally induced hydrogel formation. This result suggested that the mobility of the PNIPAAm block is more restricted than that of the PEG block during gelation. A crosslinked polymer network formation was ascertained by a sudden reduction in the spin-lattice relaxation time (T₁) of the residual HDO proton during gelation. The temperature dependency of the T₁ values for the PNIPAAm and PEG blocks revealed that the microscopic condition of the PNIPAAm block in water was drastically changed during gelation, while that of the PEG block was unchanged. The experimental results from NMR supported the following gelation mechanism; that an aggregation of PNIPAAm blocks in the separate copolymers caused by hydrophobic interaction forms crosslinking points to give an infinite three-dimensional network structure. The hydrated PEG chains in the copolymers provide the network with a swelling property in water, and prevent the aggregation from causing a macroscopic phase separation.     

Effect of organic and inorganic acids on chitosan/glycerophosphate thermosensitive hydrogel

The influence of organic and inorganic acids on chitosan/glycerophosphate (CS/GP) hydrogel has been investigated by dissolving chitosan in different acids. The results of gelation showed that all of the chitosan dissolved in monovalent acid solutions (i.e., formic, acetic, propionic, butyric, isobutyric, lactic, nitric, hydrochloric, and chloroacetic acid), when neutralized by GP solution, could transform into hydrogel after 2–5 min at 37 °C, while those dissolved in multivalent acids failed in gel formation. The inner structures of CS/GP hydrogels prepared with monovalent acids depended on the ionic strength and chain length of acids. Morphological examination by scanning electron microphotography demonstrated that large pores occurred during the gel-forming process, and the aperture size was also related to different acids. The cytotoxicity studies indicated that CS/GP systems prepared by dissolving chitosan in tested acids except chloroacetic acid were nontoxic to mouse embryonic fibroblasts and Hela cells.     

Investigation of the local delivery of an intelligent chitosan-based 188Re thermosensitive in situ-forming hydrogel in an orthotopic hepatoma-bearing rat model

In this study, in vitro and in vivo evaluations of the local delivery of ¹⁸⁸Re-Tin colloid and doxorubicin (Dox) through chitosan (C)-based thermosensitive in situ-forming hydrogels by intratumoral injection in an orthotopic hepatoma-bearing rat model were carried out. Selective internal radiation therapy has been increasingly used as an alternative therapy option for hepatocellular carcinoma (HCC) and combined with biodegradable drug carrier systems to improve drug delivery and systemic toxicity. The C-based thermosensitive hydrogel (C/GP), an injectable thermogelling solution crosslinked between C and β-glycerophosphate (GP), was induced as an implanted carrier to combine the ¹⁸⁸Re-Tin colloid and Dox as a novel treatment strategy. The compounded hydrogel characteristics, including the gelation time, controlled release of Dox, and morphology, were examined. In the animal study, the biodistribution, scintigraphy, therapeutic efficacy, and histopathology were also evaluated. The characterization results reveal that C/GP/Dox hydrogels have similar gelation times of 4–4.5 min and pore sizes of as small as 10 μm compared with C/GP hydrogels. The C/GP/Dox/¹⁸⁸Re-Tin colloids have the longest release time for Dox at 2–3 days. In the in vivo experiments, both the biodistribution and scintigraphy studies have the highest hydrogel uptakes in the tumor at different time points, as well as localized radioactivities for a certain time. The therapeutic evaluation indicates that C/GP/Dox/¹⁸⁸Re-Tin colloids can more significantly inhibit tumors compared with the control group at 2 and 4 weeks post-treatment. These results indicate that this novel treatment system is a promising option for inoperable HCC.     

Complete 1H and 119Sn NMR spectral assignment for an asymmetric di[dihydroxotin(IV)] bis-porphyrin supramolecular host and its corresponding tetraacetato complex

The full (1)H and (119)Sn NMR spectral assignments for a di[dihydroxotin(IV)] bis-porphyrin supramolecular host I and for the di[diacetatotin(IV)] complex II are presented. Despite the lack of varied chemical functionality in these molecules, all of their 64 proton environments are non-equivalent. This is due to the asymmetry afforded by the Tr?ger's base (methanodiazocine) bridge between the porphyrin and quinoxalinoporphyrin macrocycles. The methanodiazocine bridge imparts chirality and concavity on the host framework and the quinoxalino link to one porphyrin macrocycle results in a negation of C(2) symmetry. The anisotropy of the aromatic porphyrin and quinoxalinoporphyrin macrocycles results in good dispersion for all 60 signals of the host framework and for the four ligands bound in the axial positions of the tin(IV) centres. The full assignment of the (1)H NMR spectra for these systems was achieved using dqf-COSY, NOESY, ROESY, (1)H-(119)Sn HMQC, (1)H-(13)C HSQC and (1)H-(13)C HMBC spectroscopy at temperatures that optimised dispersion. The (1)H-(119)Sn HMQC was particularly useful in this assignment. The (119)Sn chemical shift is sensitive to the functionality of the porphyrin and to the nature of the axial ligation, and the (119)Sn centre couples to both the ligand protons and the beta-pyrrolic protons. This allows unequivocal identification of the spin systems associated with each metal centre.     

Differential protonation and dynamic structure of doxylamine succinate in solution using 1H and 13C NMR

A protonation and dynamic structural study of doxylamine succinate, a 1:1 salt of succinic acid with dimethyl-[2-(1-phenyl-1-pyridin-2-yl-ethoxy)ethyl]amine, in solution using one- and two-dimensional 1H and 13C NMR experiments at variable temperature and concentration is presented. The two acidic protons of the salt doxylamine succinate are in 'intermediate' exchange at room temperature, as evidenced by the appearance of a broad signal. This signal evolves into two distinct signals below about -30 degrees C. A two-dimensional 1H-1H double quantum filtered correlation experiment carried out at -55 degrees C shows protonation of one of the acidic protons to the dimethylamine nitrogen. A two-dimensional rotating frame 1H-1H NOE experiment at the same temperature reveals that the other proton remains with the succinate moiety. Comparison of the 1H and 13C chemical shifts and the 13C T1 relaxation times of the salt with those of the free base further substantiate the findings.     

Effects of protonation and co-anion on the 1H and 13C chemical shifts of 2r,6c- diphenylpiperidin-4-ones: evidence for the formation of ion pair

(1)H and (13)C NMR spectra have been recorded for 2r,6c-diphenylpiperidin-4-one (1a), 3t-alkyl-2r,6c-diphenylpiperidin-4-ones 1b-d, 3t-alkyl-2r,6c-diphenyl-4-oxopiperidinium nitrates 2b and 2d, 3t-alkyl-2r,6c-diphenylpiperidin-4-one hydrochlorides 3a-c and 3t-methyl-2r,6c-diphenyl-4-oxopiperidinium picrate 4b in DMSO-d(6). For 1b, 2b and 3b, (1)H and (13)C NMR spectra have been recorded in CH(3)OD also. For 1b, 1d, 2b, 2d, 3b and 4b, 2D spectra have also been recorded. In DMSO-d(6) the protons of the piperidine ring and the ortho protons of the phenyl groups are markedly deshielded due to protonation. Protonation shields all the carbons of the piperidine ring and the ipso carbons of the phenyl groups markedly but deshields the other aromatic carbons slightly. The deshieldings on H-3a, H-5a and the ortho protons of the phenyl groups are less in the nitrate and picrate than in the corresponding hydrochloride. The effects on (13)C chemical shifts are not influenced by the co-anion. These observations suggest that the nitrates and pictrate exist as ion pairs in DMSO-d(6) and the nitrate and picrate ions shield, H-3a, H-5a and the ortho protons by magnetic anistropic effect. In CH(3)OD for 2b and 3b in addition to the ion-pair containing free ions two ion-pairs containing solvated ions are also present. The effects of protonation in the ion pairs containing the solvated ions are significantly different from those in the ion-pair containing free ions.