6-巯基嘌呤在HPMCAS包覆介孔分子筛SBA-15药物系统中的缓释行为研究

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[高分子材料] 南京大学朱俊杰团队《德国应化》：金属有机框架纳米材料用于癌症多模式治疗

南京大学朱俊杰团队《德国应化》：金属有机框架纳米材料用于癌症多模式治疗2019-05-07南京大学化学化工学院朱俊杰教授课题组近期在金属有机框架纳米材料用于癌症多模式治疗研究中取得重要进展，其研究论文“A Catalase-Like Metal‐Organic Framework Nanohybrid for O2‐Evolving Synergistic Chemoradiotherapy”于2019年5月2日在线发表于《德国应用化学》，这项工作是朱俊杰课题组和美国国立卫生研究院陈小元课题组合作完成的。

化学化工学院何智梅博士、生科院王晨博士和南昌大学黄小林博士为共同一作，朱俊杰教授、澳门大学代云路教授，美国国立卫生研究院喻国灿博士和陈小元教授为论文的共同通讯作者，南京大学为第一通讯单位。

近年来，朱俊杰教授与陈小元教授合作在生物标志物检测、纳米诊疗方面取得了系列进展（Theranostics 2018, 8, 3461–3473; Small 2019, 15, e1804131）。

在快速生长的肿瘤附近，畸形血管供氧不足，形成了肿瘤组织严重缺氧的特点。

进一步地，乏氧会诱导肿瘤的迁移、侵袭和转移，并制约光动力治疗、放疗等需氧治疗的疗效。

为了提高乏氧细胞对放疗的敏感性，可从以下两方面着手：1）提高肿瘤处氧气含量；2）基于高原子序数元素（如Au、Bi、Hf等）的材料具有较大的X射线能量衰减系数，可以有效地将X射线能量沉积在肿瘤处，从而最佳地利用放疗辐射。

在临床上，放疗通常与其他治疗手段如手术或化疗联用以有效铲除肿瘤，防止肿瘤的复发。

目前，尽管关于协同治疗已有大量研究报道，但是由于肿瘤对治疗的抗性，大多数的抗肿瘤效果欠佳。

为了克服这一难题，两个课题组密切合作，提出原位催化产氧策略，基于卟啉金属有机框架材料（MOF）@金纳米颗粒（AuNP）纳米复合物（MOF-Au），实现氧气增强的放疗和化疗联合治疗。

在这个工作中，金纳米颗粒修饰具有以下优点：1）增敏乏氧癌细胞对X射线的响应性；2）赋予MOF相对稳定性，防止在递送过程中的过早降解；3）使得MOF具有类过氧化氢酶的活性，有效催化肿瘤代谢产物H2O2生成氧气，提高氧气依赖的放疗疗效。

pH响应型药物缓释纳米载体制备及其性能

pH响应型药物缓释纳米载体制备及其性能季梦婷;王新敬;边思梦;尚宏周;于德红;温立坤;杜思琪【期刊名称】《华北理工大学学报:自然科学版》【年(卷),期】2023(45)1【摘要】以介孔二氧化硅纳米为内核,氨基和苯硼酸基团为功能单体,修饰在介孔二氧化硅表面,制备出pH响应型药物载体MSNs-PBA。

通过SEM、TEM、FT-IR和UV-vis等仪器进行结构和性能分析,结果表明氨基和苯硼酸基成功修饰在介孔二氧化硅表面。

以盐酸阿霉素(DOX)为药物模型,考察纳米粒的吸附和释放能力,吸附性能测试表明,MSNs-PBA的载药率为46.05%,包封率为85.40%。

体外释药结果显示,在pH=7.4的环境下,MSNs-PBA-DOX的药物累积释放率为17.56%,在pH=6.8的环境下,该药物的累积释放率明显增加达到35.69%,在pH=5.5的环境下,该药物累积释放率达到42.07%,说明该纳米药物载体具有pH缓释性。

【总页数】8页(P58-65)【作者】季梦婷;王新敬;边思梦;尚宏周;于德红;温立坤;杜思琪【作者单位】华北理工大学化学工程学院;北京化工大学化学工程学院;华北理工大学材料科学与工程学院;华北理工大学药学院【正文语种】中文【中图分类】TQ460.4;TB383【相关文献】1.温度/pH双重响应型壳聚糖纳米药物载体的制备及性能2.反相微乳液制备pH响应型纳米水凝胶及其作为药物载体的研究3.pH响应型纳米药物载体的释药机制及性能研究进展4.pH响应性树枝状聚合物-金纳米粒子复合药物载体的制备5.pH/酶/光热多重响应的金纳米笼/透明质酸核壳结构纳米载体的制备与性能因版权原因，仅展示原文概要，查看原文内容请购买。

2010化学科学部国家自然科学基金项目

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基于肟类桥连配体的单分子磁体的合成与性质研究周爱菊21081220312/B060104 第四届中美“能源与环境：化学工程师的机遇与挑战”化工研讨会仲崇立21064004/B0403 壳聚糖新型衍生物作为农业杀菌剂研究钟志梅21002104/B020203 基于共轭环状金属配合物的线型分子导线的合成与研究钟羽武21076195/B0608 大肠杆菌K5产肝素前体heparosan代谢控制研究钟卫鸿21076194/B060409 基于Baylis-Hillman反应的手性膦杯芳烃的合成及催化性能研究钟为慧21006103/B060903 燃料电池用掺杂型非铂催化剂制备及其构效关系研究钟和香21074012/B0402 基于聚对苯撑乙炔分子链内环化反应构筑新型共轭高分子支俊格21073110/B030204 量子相空间动力学：轨线——密度函数方法郑雨军21072067/B020506 基于有机分子聚集诱导发光特性的手性识别研究郑炎松21073095/B030106 离子液体对TiO2的成核、物相及形貌的影响研究郑文君21071062/B010403 新型有机硒化合物协同TRAIL诱导肿瘤细胞凋亡的分子机制研究郑文杰21003053/B0301 螺旋体为前体的配位聚合物的组装与动态组合化学库的建立郑盛润21077011/B070302 苯二氮类镇静催眠药物在A2/O工艺中的强化净化郑少奎21037003/B07 典型工业过程中持久性有机污染物生成机制与控制原理郑明辉21006073/B060407 基于扩散层原位生长纳米碳纤维的燃料电池膜电极组件研究郑俊生21073129/B030608 锂离子电池中正负电极间的相互作用与机理研究郑洪河91022011/B0103 含[MCuxSy] (M = Mo, W)功能基元的簇合物的合成及高阶非线性光学性能研究郑和根21071033/B0111 枝状结构硅纳米线的合成与高灵敏度生物传感器的制备郑耿锋21075085/B0503 多模式薄膜化学蒸气发生：装置、反应体系及应用郑成斌21073228/B030105 硼掺杂TiO2光催化活性增强机制的固体NMR和量子化学计算研究郑安民21007062/B0701 近海海洋环境中PBDEs迁移转化机制研究赵宗山21073235/B030301 FCC汽油选择性加氢脱硫新型L沸石基催化剂及反应机理研究赵震21006031/B060306 新型的ZIFs晶体膜的制备及其分离CO2/N2机理赵祯霞21062024/B020102 DNA聚合酶抑制剂(+)-Aphidicolin全合成研究赵元鸿21074081/B040101 多组分星形和接枝聚合物的合成及性能研究赵优良21073114/B030301 氧化铝载体在含水加氢体系中的水合脱结构研究赵永祥21005059/B050105 基于多功能免疫磁珠和微流控芯片的痕量循环肿瘤细胞检测赵永席91022022/B0211 低维有机微晶材料的设计、合成与光电性能研究赵永生21074091/B040308 分子印迹中空纤维膜的制备及其对手性分子吸附与拆分性能的智能化调控赵义平21073146/B030203 具有多桥的复杂分子体系中的电子转移理论和应用赵仪21075101/B0503 以纳米颗粒为载体的分子药物控制释放和监测体系研究赵一兵21003039/B030802 离子液体与有机分子的相互作用及其对若干化学反应选择性的影响赵扬21062030/B020506 新型桥联环糊精/DABO类HIV逆转录酶抑制剂包结配合物的超分子体系研究赵焱21066005/B060903 新型稀土/金属离子掺杂Ta2O5纳米电极材料的制备及在燃料电池中的应用赵彦宏21073216/B030503 氢/氘分子在微孔碳材料上的动力学量子筛分离机理的研究赵学波21076059/B061103 基于甘油氢解和CO2醇解反应过程集成的碳酸丙烯酯新绿色合成反应研究赵新强21005060/B050102 固定化功能蛋白质取向及构象表征和调控色谱新方法赵新锋21076040/B060905 锌离子调节酵母菌乙醇耐性的分子机制和胁迫耐受酵母的构建赵心清21007063/B0701 有机基团修饰的磁性纳米材料在复杂环境水样品分析中的应用研究赵晓丽21005091/B050206 分子印迹阵列传感器的研制及其在食品安全快速检测中的应用赵晓娟21073033/B0305 基于光子晶体编码微球的蛋白质SERS检测及其应用赵祥伟21001043/B010101 具有超顺磁性的小粒径大孔径介孔药物载体的制备及性能研究赵文茹21075065/B050206 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基于单分子转动产生铁电性的有机铁电体的合成与性能测试赵海霞21077077/B0703 电吸附调控-光催化氧化降解不透光污染体系的方法与协同机制赵国华21072115/B0206 以AKT为靶标的新型三取代吲哚衍生物的设计、合成及抗肿瘤活性研究赵桂森21005087/B0501 卷烟烟气中主要杂环胺类化合物的体内代谢研究赵阁21032006/B02 含氟有机化合物的合成、反应规律及应用研究赵刚21003071/B030301 纳米-亚纳米复合结构贵金属催化剂的合成与表征赵丹21072117/B021101 新型硼桥联梯形pi-共轭分子材料的设计合成及性能研究赵翠华21075122/B0501 基于代谢组学的转基因植物的安全性评价研究赵春霞21076093/B060804 中国红豆杉细胞合成多乙酰基紫杉烷的代谢规律及调控机制赵春芳21076219/B061103 高纯纳米Al13溶胶制备大孔拟薄水铝石及其转化机制研究赵长伟21073035/B030201 负载型前过渡金属氧化物团簇模型催化剂构效关系的理论研究章永凡21072096/B020901 新型烯丙基香豆素类分子的设计与合成及其抗菌活性研究章维华21076052/B060702 糖分子内P、N手性配体的设计、制备及在不对称合成中的应用章鹏飞21072173/B020706 基于双AAO酶的手性汇聚法研究张子张21073224/B0305 基于金属纳米颗粒－氧化石墨烯复合体系的表面增强拉曼基底的构筑及其用于细胞与药物相互作用研究张智军21002051/B0201 炔丙基全碳1,3-偶极子在构建呋喃并杂环衍生物中的应用张志国21076126/B060301 强极性流体的气液相平衡行为及其应用张志刚21077043/B070301 基于转化频率的碳烟催化燃烧机制张昭良21073162/B030602 纳米结构CeO2薄膜的光助阳极电沉积机制及其腐蚀电化学行为研究张昭21072042/B020101 新型环状过氧化物的合成方法研究张占辉21006075/B0603 微波辅助离子液体提取天然产物有效成分的传质机理研究张越非21076143/B060306 磷酸促进型掺锆二氧化硅/聚合物杂化膜及性能的研究张裕卿21071096/B010303 配合物嫁接的具有"二合一"功能的纳米复合材料张玉良21072169/B0202 过渡金属催化的C-O键活化反应研究张玉红21074020/B040101 聚丙烯腈基碳纳米微球的可控制备及其基础问题研究张幼维21075102/B050303 金银纳米粒子增强室温磷光机理及其应用研究张勇21001097/B010701 陀螺状磷酸亚铁锂/碳纳米管复合材料的结构调控及电化学特性研究张勇21066009/B061201 富氧增强褐煤燃烧性能及其在水泥熟料煅烧中的应用研究张永锋21005020/B0505 介孔纳米材料富集质谱鉴定糖肽新方法用于大肠癌血清糖肽组的研究张莹21076207/B060806 细胞间质体外模拟系统的构建及物质传递基本规律的研究张英21002092/B020405 白蚁共生放线菌的抗菌成分研究张应烙21073003/B030106 石墨烯表面化学修饰以及量子尺寸效应研究张艳锋21005086/B050202 环介岛等温基因扩增过程的电化学信息研究张旭志21075132/B0504 14N核磁共振研究赖氨酸三甲基化蛋白质的相互作用动力学张许21074141/B040607 烯烃嵌段共聚物及其与聚烯烃共混体系的结构与性能关系研究张秀芹21010402027/B030201 过渡金属二茂夹心卤化物的国际合作研究张秀辉21075029/B0502 基于分子印迹聚合物固相微萃取β-兴奋剂电化学传感器的研究张修华21001103/B0107 电沉积制备石墨烯/导电聚合物复合薄膜电极材料及其电容特性张熊21076030/B060306 优先渗透分离CO2的ZIF型金属有机骨架结构类分子筛膜的设计制备研究张雄福21076188/B061102 低温氮等离子体改性碳纳米管吸附二氧化碳的基础研究张兴旺21002117/B020601 靶向Mcl-1蛋白的抗肿瘤药物先导化合物的优化改造张兴龙21074106/B0401 基于CO2/环氧化物可控共聚技术合成可降解的聚合物分子刷张兴宏21002070/B0201 钯催化多组分环化反应合成含硫杂环化合物的研究张兴国21005010/B050304 LED诱导化学发光适配体传感器张信凤21077070/B070701 丁二烯代谢产物1-氯-3-丁烯-2-醇和1-氯-3-丁烯-2-酮与DNA碱基反应的研究张新宇21073061/B030606 纳米碳纤维的微结构及表面性质与其电催化活性的内在规律研究张新胜21027013/B0505 小型质谱仪器关键技术研究张新荣21072002/B020401植物甾醇单体氧化物的制备及其细胞毒性的研究张欣21007025/B070403 从芳香烃受体（AhR）的基因型研究卤代芳烃污染物的鸟类种间敏感差异性张效伟21010302032/B0509 2010 年第四届生物分析、生物医学工程与纳米技术国际会议(ISBBN 2010)张晓兵21072025/B0211 新型甲基酮桥连的给体-共轭-受体类分子电子开关的研究张晓安21003079/B0306 染料敏化太阳能电池中染料的分子设计、合成与光电性能研究张晓21073001/B030607 金属基复合材料电极的构建及其在肼类化合物中的检测应用张小俊21036007/B061201 离子液体及其在清洁化工中的应用基础研究张香平21007066/B070403 六溴环十二烷3种异构体在鱼体内代谢过程研究张娴21071030/B01 介电可调的有机-无机杂化包合物张闻21076130/B060805 皮胶原-有机交联剂反应机理的计算化学研究张文华21075041/B0502 半导体复合纳米材料光电分析方法在乙酰胆碱酯酶活性检测中的应用研究张文21076012/B060306 膜吸收近膜壁面处的传质行为及其传质强化手段研究张卫东21007023/B070302 树脂基纳米M/Fe(0)的研制及其催化脱除硝酸根的研究张炜铭21003097/B030106 高效可控制备微/纳米条形码的新方法研究张伟明21074035/B040501 新型特定结构功能性β－环糊精包结络合超分子聚合物的构建、形态和应用张伟安21075039/B050106 磁性纳米固定相毛细管电色谱分离系统研究张维冰21074059/B040106 疏水单体在水中的RAFT聚合：壳-冠型空心微球反应器中的RAFT聚合研究张望清21003119/B030301 IrMOx双活性位催化剂CO选择氧化微观动力学研究张万生21077134/B070201 城市大气碳质颗粒物综合测定及七组分来源研究张烃21071007/B010404 钙化结节中钙磷酸盐的结构及其转变——内、外源性金属离子的作用张天蓝21081260197/B06 第三届两岸化学工程与产品工程高峰研讨会张锁江21072143/B020101 低价稀土金属试剂在合成多烯及多官能团化合物中的应用研究张松林21075021/B050901 微流控体系下DNA-蛋白质相互作用的单分子检测技术研究张松21077095/B070101 环境水体中超痕量溴酸根的在线富集、聚焦和毛细管电泳分离分析研究张书胜21007006/B070302 膜曝气分离单级自养脱氮生物反应器过程控制和功能菌群研究张寿通21004048/B040309 聚丁二酸丁二醇酯的仿生改性及其仿细胞外层膜结构纳米胶束的研究张世平21001036/B010701 具有多种聚阴离子基团的锂离子电池正极材料的结构调控及脱嵌锂性能研究张森21072156/B020601 新型激酶抑制剂：8-羟基-2-芳基-1-异喹啉酮类的合成和抗肿瘤活性研究张三奇21004021/B040308 利用非氟嵌段聚合物和超临界二氧化碳制备纳米孔径的高分子功能化薄膜张锐21003144/B030204 汽车尾气催化剂Pt掺杂CaTiO3的自再生机理的计算研究张秋菊21006108/B060402 转鼓式生物浸出反应器的传递特性和放大规律研究张庆华21002107/B021102 新型“类离子液体”软功能材料制备与性能研究张庆华21003081/B030802 离子液体与极性溶剂间相互作用规律研究张庆国21001061/B010303 具有化学传感功能的多孔发光MOFs材料的设计构筑及其检测大气中POPs的研究张庆富21074123/B0403 单个偶氮聚合物囊泡的光致可逆形变的放大研究张其锦21062013/B0210 四氯化硅催化氢化制备三氯氢硅工艺及机理研究张宁21006023/B060304 扩张床吸附原位提取中药有效成分的方法研究张敏21007083/B0705 环境渐变过程实验模拟及初始浓度效应研究张美一21005006/B0502 基于扫描电化学显微镜的指纹采集技术的研究张美芹21006069/B060802 “智能”溶栓策略探索——多尺度分子动力学模拟张麟21076176/B060306 含无机纳米水通道反渗透复合膜的结构设计与制备张林21076107/B061202 微小空间反应器中生物激发合成沸石与纳米金属粒子的研究张利雄21071032/B010303 新型季铵盐功能化的金属有机骨架材料的合成、结构与性能研究张丽娟21027002/B0501 蛋白质样品多级预处理系统的研制张丽华21073177/B0307 甲醛分子离子电子激发态的振动分辨光解离动力学研究张立敏21073069/B030304 自掺杂光催化剂的设计、制备及其可见光光催化性能研究张礼知21074152/B0404 含树枝化结构基元的新型聚多糖衍生物研究张黎明21001004/B0107 功能氧化物/碳纳米纤维复合材料的制备和电催化性能研究张莉21075016/B0501 多维毛细管液相色谱－质谱联用新技术用于甲型Ｈ１Ｎ１流感病毒的研究张兰21002115/B0203 环状手性含氟亚砜亚胺、亚磺酰胺和磺酰胺的立体专一性合成及应用研究张来俊21003050/B030301 限域纳米空间内酸碱有机官能团分子的可控组装及其协同催化机理的研究张坤21076162/B0608 油包水乳化体系中新型交联酶聚集体的构建及其结构与性能张峻21074048/B040605 具有不对称构筑基元的微结构阵列及其各向异性光学性质张俊虎21076063/B061201 基于离子液体的氯硅烷催化反应-相控耦合分离研究张军21006110/B060901 炭黑和气体组分在煤气化过程中的作用机理研究张聚伟21004001/B040601 停流光谱技术研究阳离子聚合物/DNA络合与解络合动力学张璟焱21076144/B060404 气液固三相高剪切反应器性能与模型放大研究张金利21001120/B010303 多孔金属多氮唑框架张杰鹏21073191/B0301 基于非手性源的单手性材料的催化不对称结晶张健21002062/B020601 STAT3选择性抑制剂的设计、优化及其功能研究张健21004077/B040303 基于主-客体相互作用的三重化学响应性聚合物组装体：设计、构建及其药物传输性能研究张建祥21074063/B040401 微量填充生物可降解高分子共混体系的微结构与性能研究张建明21073053/B030803 桥联型双核稀土多取代芳香羧酸配合物结构与热分解反应机理及性能研究张建军21071025/B010303 异金属团簇化合物的合成和性能研究张建军21071019/B010601 二元金属氨硼烷的制备、释氢机理及其在推进剂中应用研究张建国21061004/B010701 含Fe钨青铜结构化合物的结构调控与电磁特性研究张辉21071021/B010902 锝-99m、氟-18、碘-125-VEGF多肽肿瘤显像剂的制备、体外评价及生物分布研究张华北21073055/B030802 溶液中无机阴离子在纳米晶表面上的复合与稳定化作用研究张虎成21073077/B0304 有机光电材料激子态动力学研究张厚玉21071140/B0105 新型稀土纳米复合材料的合成、发光和磁性能的研究张洪杰21074071/B040609 透明质酸多糖自聚集物理水凝胶的形成机理和流变学研究张洪斌21071027/B0101 功能化的多金属氧酸盐组装分子磁性晶态材料的可控合成与性能研究张宏21007069/B0704 T-2毒素生物转化及毒性的分子机制研究张红霞21005067/B050105 集成化多功能可控细胞操纵及分析微流控芯片的研制张何21073079/B030702 高双光子吸收截面有机半导体材料的设计与性质研究张浩力21004032/B040102 新型烯烃复分解催化剂的设计、合成以及在制备结构可控的高性能聚合物材料中的应用张浩21077030/B0704 固氮蓝藻修复多氯联苯污染水稻土的机理研究张杭君21077102/B0706 大辽河流域代表性卤代阻燃剂的污染特征与演变趋势张海军21006066/B060409 CH4/CO2重整高抗积碳金属/炭材料催化剂的制备及机理研究张国杰21007002/B070301 三维有序大孔-介孔复合氧化物原位担载贵金属纳米粒子的可控制备及同时消除NOx和碳烟的催化性能研究张桂臻21081260019/B020402 中国西北部中药资源开发国际研讨会张桂珍21076215/B060802 层析过程中界面上蛋白质结构及动态变化张贵锋21071146/B0107 多酸基多元复合光电催化材料的设计,制备及其性能研究张光晋21075126/B0509 基于聚集荧光增强机理的化学/生物传感的研究张关心21076095/B0608 慢消化淀粉与茶多酚对餐后血糖反应的协同作用张根义21073105/B030505 基于alpha-烷氧基锌酞菁J聚集机理的酞菁光控自组装张复实21077120/B070304 含溴电子废物在超临界甲醇中的催化脱溴机制研究张付申21064002/B040705 介孔材料环境下原位乳液聚合稳定性及其聚合物复合材料热学和力学性能研究张发爱21072226/B020601 基于小檗碱抗耐药真菌作用的小分子探针研究张大志21003077/B030301 以废轮胎热解炭为载体的脱氢催化剂在有机液体储氢中的研究张翠21075129/B050901 病原体的超灵敏高通量单分子检测研究张春阳21027007/B0506 电化学发光成像分析仪的研制张成孝21005030/B0511 基于碳纳米管表面印迹技术的猕猴桃根中抗肿瘤活性成分分离及活性研究张朝晖21004080/B040303 组织诱导型可生物降解聚谷氨酸水凝胶支架材料制备及其在骨组织工程中的应用研究张超21077117/B070301 Pt/TiO2催化剂室温氧化甲醛的高活性机制研究及非贵金属化探索张长斌21005065/B050102 基于液滴技术的蛋白质组分离分析新方法张博21077126/B070502 典型羟基多溴联苯醚拟/抗激素效应的H12定位选择机制及构效关系研究张爱茜21073087/B0303 多壁碳纳米管的结构缺陷及其自发氧化还原性能在催化反应中的作用研究张爱民21034004/B040101 大尺度螺旋聚合物的可控合成及其结构分析张阿方21075077/B0503 痕量多溴联苯醚的表面增强拉曼光谱检测占金华21072159/B0201 过渡金属催化下各类杂环化合物的新合成方法研究詹庄平21076184/B060702 持久低表面能、环境友好含短氟碳链聚合物的分子设计与合成詹晓力。

Applied Catalysis A_ General 2009

Ce-promoted Ru/SBA-15catalysts prepared by a‘‘two solvents’’impregnation method for selective hydrogenation of benzene to cyclohexeneJian-Liang Liu a,Ling-Jun Zhu a,Yan Pei a,Ji-Hua Zhuang a,*,Hui Li b,He-Xing Li b,Ming-Hua Qiao a,*, Kang-Nian Fan aa Department of Chemistry and Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials,Fudan University,No.220Handan Road,Shanghai200433,PR Chinab Department of Chemistry,Shanghai Normal University,Shanghai200234,PR China1.IntroductionThe selective hydrogenation of benzene to cyclohexene is ofgreat industrial interest,because cyclohexene can be facilelyconverted to value-added cyclohexanol,caprolactam,and adipicacid by typical oleﬁn pared to traditional methodsfor the manufacture of cyclohexene by dehydrogenation ofcyclohexane,dehydration of cyclohexanol,and the Birch reduction,selective hydrogenation of benzene is superior in terms ofinexpensive starting feedstock,energy-saving,lower amounts ofundesirable products,and simpliﬁed operation[1,2].However,thermodynamically it is difﬁcult to obtain cyclohexene frombenzene,since the standard free energy change for cyclohexeneformation from benzene hydrogenation isÀ23kJ molÀ1,while thatfor cyclohexane formation isÀ98kJ molÀ1.So,for a long period,only cyclohexane was obtained during the hydrogenation ofbenzene[3].Theﬁrst encouraging result was reported by Drinkard[4],whofound that in the presence of water and employing Ru as thecatalyst in a tetra-phase reactor at403–453K and7MPa of H2pressure,a yield of cyclohexene of30%was obtained,showing theprospect of the industrial application of the catalytic hydrogena-tion of benzene to cyclohexene.Up to now,methods for thecatalytic hydrogenation of benzene to cyclohexene have includedgas-phase[5,6]and liquid-phase[7–11]hydrogenations.The mainadvantage of the liquid-phase hydrogenation method is that it ispossible to achieve much higher selectivity to cyclohexene at highconversion of benzene[4,7–10].Among various metals investi-gated,Ru gives the highest selectivity to cyclohexene[4–7].AsahiChemical has industrialized the process for the selective hydro-genation of benzene to cyclohexene using a proprietary Ru catalyst[12].The performance is80%selectivity to cyclohexene at50%conversion of benzene or70%selectivity to cyclohexene at62%conversion of benzene.However,they have not presented thedetails of this process,and hence scientiﬁc studies especially oncatalyst preparation and modiﬁcation are needed.It was found that the catalyst preparation method and thepromoter have great impacts on the yield of cyclohexene.Mizukami et al.[13]and Niwa et al.[14]prepared a supportedRu catalyst doped with a small amount of Cu by the sol–gelmethod,and obtained a cyclohexene yield of31%at a benzeneconversion of83%.Deng and co-workers[15–17]reported that RuBcatalysts prepared by the chemical reduction method were moreselective to cyclohexene than Ru catalysts reduced by H2,giving acyclohexene yield of33%.Liu et al.[18]performed the reactionwith a RuLaB/ZrO2catalyst,and found that the selectivity tocyclohexene could reach66%at the conversion of81%by furtheradding ZrO2as disperser and byﬁnely tuning the acidity of theApplied Catalysis A:General353(2009)282–287A R T I C L E I N F OArticle history:Received21July2008Received in revised form31October2008Accepted31October2008Available online12November2008Keywords:BenzeneA B S T R A C TCe-promoted Ru/SBA-15catalysts were prepared by a‘‘two solvents’’impregnation method.In liquid-phase hydrogenation of benzene,the Ce-promoted Ru/SBA-15catalysts exhibited superior catalyticperformance to the un-promoted catalyst.The optimum bulk Ce/Ru molar ratio was determined to be0.25,at which a cyclohexene yield of53.8%was obtained.Based on characterizations,the beneﬁcialeffect of the Ce promoter on the selectivity to cyclohexene was ascribed to the enhancement of thehydrophilicity of the catalyst and to the electron transfer between the Ce(III)species and metallic Ru.ß2008Elsevier B.V.All rights reserved.*Corresponding author.Tel.:+862155664679;fax:+862165641740.E-mail address:mhqiao@(M.-H.Qiao).Contents lists available at ScienceDirectApplied Catalysis A:Generalj o u r n a l h o m e p a g e:w w w.e l s e v i e r.c o m/l o c at e/a p c a t a0926-860X/$–see front matterß2008Elsevier B.V.All rights reserved.doi:10.1016/j.apcata.2008.10.056aqueous solution of ZnSO4.Hu and Chen[19]doped the Ru/SiO2 catalyst with Zn by the co-precipitation method,and found that the yield of cyclohexene increased from17%to32%.On the other hand,Ce has been frequently used as promoter for hydrogenation catalysts.For example,Li et al.[20]prepared Ce-doped PdB catalysts for the selective hydrogenation of phenol to cyclohexanone,on which the maximum yield of cyclohexanone increased from33.1%to83.0%after the promotion with Ce.The promoting effect of the Ce dopant was ascribed to the improve-ment of the dispersion of Pd,the increment of the electron density of Pd,and the enhancement of the surface basicity.Bachiller-Baeza et al.[21]tested the un-promoted and Ce-promoted Ru/AC catalysts in gas-phase crotonaldehyde and liquid-phase citral hydrogenations,and found that CeO2alone and CeO2supported on AC showed low activity but very high selectivity to unsaturated alcohols(93%and100%,respectively).It is suggested that the defect sites on the Ce promoter were highly selective sites for the formation of unsaturated alcohols due to the positive effects on C O bond activation.Regular mesoporous molecular sieves have shown great potential in catalysis,which is closely related to their high surface area,uniform pore structure and narrow pore size distribution [22–24].These unique features of mesoporous molecular sieves offer new possibilities for obtaining highly dispersed metal catalysts with deﬁned particle sizes.However,the traditional incipient wetness impregnation method is not good at dispersing homogeneously the active components in the mesopores;thus we are unable to fully utilize the advantages of the mesoporous structure.The‘‘two solvents’’impregnation method,a derivative of the traditional incipient wetness impregnation technique using a combination of a hydrophobic solvent and water to impregnate the porous materials,has been successfully employed by Huu et al.[25]to disperse uniform CoFe2O4nanoparticles into the pores of carbon nanotubes and by Clerc et al.[26]to synthesize MnO2 nanowires patterned by SBA-15under mild condition.In our preliminary work,we have prepared a series of Ru catalysts supported on different siliceous materials including commercial amorphous SiO2,HMS,MCM-41,SBA-15,and MCF by the‘‘two solvents’’impregnation method,and we have found that the SBA-15-supported catalyst exhibited the highest selectivity and yield in liquid-phase hydrogenation of benzene to cyclohex-ene.Motivated by these results,in this work we prepared the Ce-promoted Ru/SBA-15catalysts by the‘‘two solvents’’impregnation method for liquid-phase hydrogenation of benzene to cyclohexene. It is expected that using this method Ce and Ru could be homogeneously distributed in the channels of the mesoporous SBA-15.The physicochemical properties of the catalysts were characterized and the promoting effect of Ce was discussed.2.Experimental2.1.Catalyst preparationThe mesoporous siliceous SBA-15with hexagonal structure was prepared according to the procedure reported by Zhao et al.[22].The catalysts were prepared by the‘‘two solvents’’impregnation method ly,30ml of cyclohexane was added to1.0g of SBA-15while stirring until all SBA-15was well dispersed.Then3.0ml of0.04g Ru/ml of RuCl3aqueous solution with different amounts of Ce(NO3)3was added dropwise under stirring.After the supernatant was decanted,the solid was dried at373K overnight,then reduced by5vol.%H2in Ar at573K for4h at a ramping rate of2K minÀ1.The loading of Ru was kept at 12wt%relative to the weight of SBA-15.Measurements revealed that the concentration of Ru ions in the supernatant was below the detection limit,showing that the‘‘two solvents’’impregnation method is very efﬁcient in transferring Ru ions from the liquid phase to the channels of SBA-15.The catalyst without Ce was denoted as Ru/SBA-15,while RuCe/SBA-15-x is used for the Ce-promoted catalyst,where x denotes the nominal molar ratio between Ce and Ru.2.2.Catalyst characterizationThe bulk compositions of the catalysts were analyzed by inductively coupled plasma-atomic emission spectroscopy(ICP-AES;Thermo Elemental IRIS Intrepid).N2physisorption was performed on a Micromeritics TriStar3000apparatus at77K.The sample was transferred to the adsorption glass tube and heated at 383K under N2for2h before measurement.The pore size distribution was calculated from the desorption branch of the isotherm by the Barrett–Joyner–Halenda(BJH)method.Temperature programmed reduction(TPR)was carried out on a home-made apparatus.After being heated at473K for1h under Ar,the sample was cooled down,and then raised to$700K at a heating rate of10K minÀ1in5%H2in Ar.The active surface area (S Ru)was determined by temperature-programmed desorption of H2(H2-TPD).After being heated at473K for1h under Ar,the catalyst was cooled to273K.Then H2was introduced by the pulse method at273K until saturation,followed by purging with Ar to remove the gaseous and/or physisorbed H2until that the TCD signal returned to the baseline.The H2desorption curve was acquired at a heating rate of20K minÀ1.The active surface area was calculated based on the desorption area with the assumption of a H:Ru stoichiometry of1:1and a Ru surface atomic density of 1.63Â1019atoms mÀ2[27,28].Powder X-ray diffraction(XRD)patterns were acquired on a Bruker AXS D8Advance X-ray diffractometer using Ni-ﬁltered Cu K a radiation(l=0.15418nm).The tube voltage was40kV,and the current was40mA.The surface morphology and particle size were observed by transmission electron microscopy(TEM;JEOL JEM2011)operating at200kV.X-ray photoelectron spectroscopy (XPS)was performed on a Perkin Elmer PHI5000C instrument with Mg K a radiation as the excitation source(h n=1253.6eV).Spectra were recorded after Ar+sputtering for15min.Because the Ru3d3/2 peak partly overlaps with the C1s line of contaminant carbon,all binding energy(BE)values were referenced to the Si2p peak of SBA-15at103.3eV.2.3.Activity testThe selective hydrogenation of benzene was carried out in a 500ml stainless steel autoclave with a mechanical stirrer.After the desired amount of ZnSO4was dissolved in100ml of distilled water,1.0g of the reduced catalyst and50ml of benzene were introduced.Then the autoclave was sealed and purged with H2 at leastﬁve times to expel air.The reaction conditions were: reaction temperature of413K,H2pressure of 4.0MPa,and stirring rate of1000rpm to exclude the diffusion effect.The reaction process was monitored by taking a small amount of the reaction mixture at intervals,followed by gas chromatographic analysis with a PEG-20M packed column and a thermal conductivity detector(TCD).3.Results and discussion3.1.Structural and electronic propertiesN2physisorption isotherms(Fig.1)were recorded to assess the textural properties of the as-prepared catalysts.The isotherms of the Ru/SBA-15and RuCe/SBA-15-0.4catalysts are of type IV and are almost identical to that of SBA-15[22],but the speciﬁc surfaceJ.-L.Liu et al./Applied Catalysis A:General353(2009)282–287283area and pore volume were decreased due to the incorporation of Ru and Ce to the channels,while the average pore diameter was slightly increased from 6.4to 7.4nm.As seen in the inset of Fig.1,the BJH pore size distributions of the SBA-15,Ru/SBA-15,and RuCe/SBA-15-0.4samples were similar,signifying the preservation of the regular pore structure.Fig.2shows the XRD patterns of the SBA-15,Ru/SBA-15,and RuCe/SBA-15samples.The small-angle XRD patterns (Fig.2a)exhibited three well-resolved reﬂections in the 2u range of 0.5–3.08,which can be indexed to the ordered hexagonal lattice (p6mm)of SBA-15[22].The hexagonal structure was present after the incorporation of Ru and Ce,although the intensity was attenuated.In the wide-angle XRD patterns (Fig.2b),besides the broad feature at 2u of ca.228ascribable to amorphous silica,there was only a broad diffraction peak at $43.08attributable to the (101)diffraction of hcp Ru [29].From the X-ray line-broadening analysis,the Ru crystallite size of ca.2nm was estimated.Fig.3shows the TEM images of the Ru/SBA-15catalyst and the RuCe/SBA-15-0.4catalyst as a representative of the Ce-promoted catalysts.Fig.3a and c revealed that the Ru nanoparticles imaged as dark dots were uniformly dispersed in the mesopores of SBA-15,with the Ru particle sizes mainly ranging from 4to 5nm.Fig.3b shows the HRTEM image of Ru nanoparticles with a diameter of around 5nm taken from the Ru/ttice fringes with an average spacing of 0.21nm were identiﬁed,corresponding well to the (101)plane of hcp Ru [29].But for the RuCe/SBA-15-0.4catalyst,the lattice fringes of Ru were blurred (Fig.3d),possibly due to the coverage of the Ru nanoparticles by the Ce bined with the Ru crystallite size derived from XRD,it can be deduced that the Ru nanoparticles observed by TEM were mainly polycrystalline.The catalysts before reduction were characterized by H 2-TPR to investigate the interactions between Ru and Ce (Fig.4).The appearance of two reduction peaks for the Ru/SBA-15catalyst is in good agreement with the literature descriptions [30–32].The ﬁrst one,in the range of 320–410K,is attributed to the reduction of RuCl 3.The second peak,in the range of 410–515K,is related to the reduction of ruthenium oxide arising from the hydrolysis of RuCl 3during the impregnation or the drying process.After being doped with Ce,both reduction peaks shifted continuously to higher temperatures below the nominal Ce/Ru ratio of 0.6,indicating the stronger interaction between Ce and Ru.However,when further increasing the nominal Ce/Ru ratio,both reduction peaks shifted backwards,implying that the interaction between Ce and Ru was weakened at higher Ce/Ru ratio.Fig.5displays the Ru 3d and Ce 3d spectra of the Ru/SBA-15and RuCe/SBA-15catalysts.It is found that Ru was in the metallic state with the Ru 3d 5/2BE of 280.0eV [32].The complex spectrum of Ce 3d can be resolved into four components,with the assignments being labeled in the ﬁgure.The band labeled v 0at 880.5eV is ascribed to the Ce 3d 5/2level,and the band labeled u 0at 899.2eV represents the Ce 3d 3/2level.The band labeled v 0at 885.1eV is the satellite arising from the Ce 3d 5/2level,while the band u 0at 903.8eV is the satellite arising from the Ce 3d 3/2level [33,34].If one compares the XPS spectrum of pure cerium(III)nitrate hexahydrate and the literature values [35–37],one can conclude that the surface Ce species in RuCe/SBA-15catalysts was present in the three-valence state.Moreover,the Ce 3d BEs of the Ce(III)species were 0.3eV higher than the standard values (880.2,884.8,898.9,and 903.5eV for v 0,v 0,u 0,and u 0,respectively)[36],inferring the electronic interaction between Ru and the Ce(III)species,in which the latter donated electrons to the former.It is noted that only Ru ions were reduced under the present reduction condition,as no metallic Ce was identiﬁed in (Fig.5).The surface compositions were determined by analysis of relative peak areas in the XPS spectra.As listed in Table 1,together with the bulk compositions,the Ce-promoted catalysts showed a signiﬁcant surface segregation of Ce.However,when the nominal Ce/Ru ratio was increased to 0.6,the surface Ce/Ru ratio became lower than the bulk value,which can be interpreted as the aggregation of the Ce(III)species to larger particles at higher doping amounts,thus reducing the intensity of the Ce 3d spectrum.The aggregation of the Ce(III)species is expected to weakenitsFig.1.Nitrogen adsorption–desorption isotherms and pore size distributions (inset)of the SBA-15,Ru/SBA-15,and RuCe/SBA-15-0.4samples.Fig.2.(a)Small-and (b)wide-angle XRD patterns of the SBA-15,Ru/SBA-15,RuCe/SBA-15-0.2,RuCe/SBA-15-0.4,and RuCe/SBA-15-0.6samples.J.-L.Liu et al./Applied Catalysis A:General 353(2009)282–287284interaction with Ru,which rationalizes the lower reduction temperatures of the RuCe/SBA-15-0.6catalyst shown in (Fig.4).3.2.Catalytic performanceFig.6shows the courses of the hydrogenation of benzene over the as-prepared catalysts at 413K and H 2pressure of 4.0MPa in the presence of 0.14M ZnSO 4.The products obtained under the present reaction condition were exclusively cyclohexane and cyclohexene.In Fig.6,both the conversion of benzene and the concentration of cyclohexane increased monotonically with thereaction time.On the Ru/SBA-15catalyst,the reaction rate was so fast that within only 15min the benzene was totally consumed.However,the maximum yield of cyclohexene was only 25.0%at 65.5%conversion of benzene.On the RuCe/SBA-15-0.4catalyst,in contrast,the concentration of cyclohexene increased much faster than that of cyclohexane at the beginning of the reaction,and reached a maximum yield of cyclohexene of 44.8%at 80.0%conversion of benzene with a reaction time of about 20min.The yield of cyclohexene then declined gradually following the known behavior of such consecutive reactions.As can be seen from Table 1,the higher the Ce/Ru ratio,the lower is the active surface area.From the XPS analysis,the Ce(III)species was enriched on the surface of the RuCe/SBA-15catalysts.Those facts indicate the physical blocking of the Ru active sites by the Ce promoter,which decreased the number of the exposed Ru atoms and consequently lowered the hydrogenation activity of the catalysts.Table 2also shows that the maximum yield of cyclohexene increased with the increment of the Ce/Ru ratio,and then declined at higher doping amounts of Ce,with the optimal bulk Ce/Ru molar ratio being 0.25.The mechanism of selective hydrogenation of benzene to cyclohexene over Ru-based catalysts has been studied;results demonstrated that the existence of a layer of water over the catalyst surface was one of the most important factors responsible for the high selectivity towards cyclohexene [38,39].The roles of water played in selective hydrogenation of benzene can be understood based on the following considerations:(1)Water readily occupies active sites where cyclohexane ispreferentially formed [38];(2)water promotes the desorption of cyclohexene from thecatalyst surface by competitive adsorption,and inhibitstheFig.3.TEM and HRTEM images of the Ru/SBA-15(a)and (b),and RuCe/SBA-15-0.4(c)and (d)catalysts.Fig.4.TPR proﬁles of the Ru/SBA-15,RuCe/SBA-15-0.2,RuCe/SBA-15-0.4,and RuCe/SBA-15-0.6catalysts.J.-L.Liu et al./Applied Catalysis A:General 353(2009)282–287285readsorption of cyclohexene for further hydrogenation to cyclohexane [39].It is expected that the existence of the Ce(III)species on the Ru crystallites in the RuCe/SBA-15catalysts,as inferred by the HRTEM image,could enhance the hydrophilicity of the catalysts,which is beneﬁcial to the selectivity to cyclohexene.Hronec et al.[40]prepared charcoal and anionic cross-linked polymer-supported Ru catalysts for liquid-phase hydrogenation of benzene.The selectiv-ity to cyclohexene was much higher for Ru catalysts supported on a strongly hydrophilic microporous resin than that for those supported on charcoal.Ronchin and Toniolo [41]conducted the reaction on Ru catalysts supported on different oxides (TiO 2,ZrO 2,Yb 2O 3,and Fe 2O 3),and found that the hydrophilicity of the support was related to the selectivity to cyclohexene.In fact,if the organic phase (benzene)surrounds the catalyst,the consecutive hydro-genation of cyclohexene is so fast that the selectivity to cyclohexene is nearly zero [39].Our experiment showed that,for the RuCe/SBA-15-0.4catalyst,only a small amount of cyclohexene (selectivity to cyclohexene less than 7%)was detected during the hydrogenation of benzene under the present condition when absolute ethanol instead of water was used as the solvent,regardless of the addition of ZnSO 4.In addition,according to the XPS spectra in Fig.5,electron transfer occurred between the Ce(III)species and Ru for RuCe/SBA-15catalysts,making the Ce(III)species electron-deﬁcient.Since the electron-deﬁcient Ce(III)species can more easily accept the lone electron pair on the oxygen atom of water,itFig.5.XPS spectra of the Ru 3d and Ce 3d levels of the Ru/SBA-15,RuCe/SBA-15-0.2,RuCe/SBA-15-0.4,and RuCe/SBA-15-0.6catalysts.Table 2Results of the hydrogenation of benzene over the Ru/SBA-15and RuCe/SBA-15catalysts a .CatalystCon.b (%)Sel.b (%)Yield b (%)Time b (min)Ru/SBA-1565.538.125.05RuCe/SBA-15-0.278.150.039.115RuCe/SBA-15-0.480.056.444.820RuCe/SBA-15-0.675.257.742.930aReaction conditions: 1.0g of catalyst,50ml of benzene,100ml of H 2O,temperature of 413K,H 2pressure of 4.0MPa,stirring rate of 1000rpm,and C znso 4of 0.14M.bValues recorded at the maximum yield ofcyclohexene.Fig.6.The courses of benzene hydrogenation over the Ru/SBA-15and RuCe/SBA-15-0.4catalysts.Reaction conditions:1.0g of catalyst,50ml of benzene,100ml of H 2O,temperature of 413K,H 2pressure of 4.0MPa,stirring rate of 1000rpm,and 0.14M of ZnSO 4.Table 1Physiochemical properties of SBA-15,Ru/SBA-15,and RuCe/SBA-15samples.SampleCe/Ru ratio(bulk a /surface b )S Ru(m 2g À1Ru)S BET(m 2g À1)V p(cm 3g À1)d p (nm)SBA-15––5330.96 6.4Ru/SBA-15–794080.757.1RuCe/SBA-15-0.20.13/0.45263710.737.2RuCe/SBA-15-0.40.25/0.38163600.707.4RuCe/SBA-15-0.60.35/0.29113200.687.6a Determined by ICP-AES.bDetermined by XPS.J.-L.Liu et al./Applied Catalysis A:General 353(2009)282–287286would promote the adsorption of water on the catalyst surface.Moreover,the electron-enriched Ru is not favorable for the overlap of the p -electrons of cyclohexene with the empty d-orbitals of Ru,thus promoting the desorption of cyclohexene [38].For the RuCe/SBA-15-0.4catalyst exhibiting the best perfor-mance in selective hydrogenation of benzene,we further explored the effect of the concentration of the ZnSO 4additive on the selectivity to cyclohexene.As seen from Fig.7,with the increase of the concentration of ZnSO 4,the yield of cyclohexene increased greatly,with a maximum yield of 53.8%being obtained at the ZnSO 4concentration of 0.42M.As far as we are aware,this value represents the highest yield of cyclohexene in selective hydrogenation of benzene over heterogeneous Ru catalysts reported in the open literature [18].The positive effect of the zinc salts,according to Fukuoka et al.[42],can be interpreted partly by the stabilization of hydrogenated inter-mediates by forming adducts between cyclohexene and Zn cations,and partly by the hindering of the readsorption of cyclohexene,which both suppress the rapid consecutive hydrogenation of cyclohexene.4.ConclusionsThe RuCe/SBA-15catalysts prepared by the ‘‘two solvents’’impregnation method exhibited better selectivity towards cyclo-hexene than the Ru/SBA-15catalyst in liquid-phase hydrogenation of benzene.The existence of the Ce(III)species decreased the number of exposed Ru atoms,increased the number of electrons on metallic Ru,and enhanced the hydrophilicity of the catalyst.As a result,these improvements generated a high selectivity towards cyclohexene.After the concentration of ZnSO 4was optimized,the maximum yield of cyclohexene of 53.8%was obtained on the RuCe/SBA-15-0.4catalyst.AcknowledgementsThis work was supported by the National Basic Research Program of China (2006CB202502),Shanghai Science and Tech-nology Committee (06JC14009),the Fok Ying Tong Education Foundation (104022),the NSF of China (20673025),and State Key Laboratory of Catalytic Material and Reaction Engineering (RIPP,SINOPEC).References[1]E.Dietzsch,U.Rymsa,D.Honicke,Chem.Eng.Technol.22(1999)130–133.[2]S.C.Hu,Y.W.Chen,J.Chin.Inst.Chem.Eng.29(1996)387–396.[3]P.T.Suryawanshi,V.V.Mahajani,J.Chem.Technol.Biotechnol.69(1997)154–160.[4]W.L.Drinkard,NL Patent 7,205,832(1972)to Dupont de 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cyclohexene over the RuCe/SBA-15-0.4catalyst against the concentration of ZnSO 4.Reaction conditions:1.0g of catalyst,50ml of benzene,100ml of H 2O,temperature of 413K,H 2pressure of 4.0MPa,and stirring rate of 1000rpm.J.-L.Liu et al./Applied Catalysis A:General 353(2009)282–287287。

新实验药物合成实验报告

实验一TLC铺板、干燥、活化、色谱用硅胶柱的填装1．硅胶薄层色谱板的制备、干燥和活化薄层色谱中的吸附剂是铺在玻璃、塑料或金属片或薄板上的较薄的、均匀的一层细粉状物质，因支持剂的种类、制备方法和选用溶剂的不同，可按吸附、分配或二者结合的方式达到分离化合物的目的。

可以通过比较斑点的R f值，或将未知样品与对照品在同一板上展开至同样高度，对样品进行初步的鉴定。

还可通过比较可见斑点的大小进行半定量的判断。

还可以通过光密度测量法实现定量测定。

TLC中涂布的物质与柱色谱用的吸附剂非常相似，如硅胶、氧化铝、聚酰胺等，只是它们的颗粒更细一些，一般直径为5～40μm。

有些还含有石膏、淀粉等粘合剂以增强涂层与薄板的粘合力。

有时里面还含有荧光指示剂(如硅酸锌等)，在254或365nm的紫外光下能显示荧光，可借此对分离的斑点进行检测。

到目前为止，硅胶是最常用的薄层色谱吸附剂。

在涂布吸附剂时，用于排列和放置薄板的排列盘和具有平整表面的薄板是必需的。

而涂布器也很常用，当它从玻璃板上移过时，会在板的表面均匀铺上所需厚度的吸附剂涂层。

（1）实验目的掌握硅胶薄层色谱板的制备方法。

（2）仪器和试剂①玻璃板(5×10cm或10×20cm，洁净且干燥)；②薄层色谱用硅胶G；③％羧甲基纤维素钠水溶液；（3）实验步骤①把玻璃板在排列盘中依次相邻放好，置涂布器于其中一端。

②在具塞锥形瓶中把一份硅胶G和2～3份CMC-Na溶液混合，并用力振摇30秒。

③把混好的糊倒入涂布器中，均匀地移动涂布器至排列盘的另一端后，移开涂布器。

④铺好的板静置5分钟，然后把它们面朝上移至一个水平的平面上，阴干。

⑤把阴干后的板在105℃的烘箱中烘30分钟。

⑥待板凉至室温后，置干燥器中保存。

2．色谱用硅胶柱的填装液相柱色谱可以是液-固色谱或液一液色谱。

如果固定相是吸附剂，也称为液相吸附色谱.若为离子交换物质，就称为离子交换色谱；若为非离子的聚合物，如聚苯乙烯或hadex,则称为凝胶渗透色谱、凝胶过滤色谱或分子排阻色谱。

RSC Adv-2015

a
College of Material Chemistry and Chemical Engineering, Hangzhou Normal University, Hangzhou, 310036, China. E-mail: jinhua6903@; Fax: +86-57128866903; Tel: +86-571-28866903 Institute of Analytical and Applied Chemistry, Department of Chemistry, Zhejiang University, Hangzhou, 310027, China Qianjiang College, Hangzhou Normal University, Hangzhou, 310036, China information (ESI) available. See DOI:
RSC Advances
PAPER Thiol-functionalized silica microspheres for online preconcentration and determination of mercury species in seawater by high performance liquid chromatography and inductively coupled plasma mass spectrometry†
1. Introduction
Mercury has become a global environmental concern, especially in the form of methylmercury (MeHg), by virtue of global transport and the biogeochemical cycle.1 The toxicity and bioavailability of mercury are species-specic. It was reported that organomercuric compounds are generally more toxic than inorganic mercuric species and elemental mercury.2 The earth's oceans supply human beings with hundreds and thousands of diﬀerent kinds of seafood. Considering their high bioaccumulation and biomagnication in the food chain, the amounts of mercury species in seawater are vital to the quality of seafood. Besides, mercury speciation analysis in seawater is benecial to further understand the biogeochemical cycling of mercury.2 The development of accurate and sensitive analytical

纳米药物分析

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总之，纳米药物具有缓释特性，能够延长药物作用时间，靶向输送药物，保证药物作用前提下减少给药剂量，减轻或避免药物毒副作用，提高药物作用稳定性，利于药物储存。能够建立一些新的给药途径，通过修饰实现药物的智能化。而且能够实现药物向高产、自动化、大规模、低成本、携带储存方便、服用方便、小剂量和低副作用方面发展。
研究了胰岛素聚氰基丙烯酸酯（ <*,=’>=,
?=’+*’?7=,’(0，@ABA ）纳米粒。由于在强酸性条件下，胰岛素和 @ABA 纳米粒之间存在强烈的静电吸引作用，因此胰岛素分子可牢固吸附于 @ABA 纳米粒表面。体外研究表明，胰岛素吸附于纳米粒表面后，胃蛋白酶、胰蛋白酶等蛋白水解酶对其的降解作万方数据用显著降低，纳米粒表现出良好的保护胰岛素活性
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分子间作用力构筑的具有柔性结构的_省略_定性_溶解度和DFT计算_英文_孙盼盼

分子间作用力构筑的具有柔性结构的_省略_定性_溶解度和DFT计算_英文_孙盼盼[Article]/doc/4d13421908.html物理化学学报(Wuli Huaxue Xuebao )Acta Phys.-Chim.Sin .2015,31(2),211-220February Received:October 30,2014;Revised:December 22,2014;Published on Web:December 23,2014.?Corresponding authors.CHEN San-Ping,Email:sanpingchen@/doc/4d134219 08.html;sanpingchen312@/doc/4d13421908. html.WEIQing,Email:weiqq@/doc/4d13421908.htm l;Tel/Fax:+86-29-88302604.#These authors contributed equally to this work.The project was supported by the National Natural Science Foundation of China (21373162,21463020,21073142,21173168)and Natural Science Foundation of Shaanxi Province,China (11JS110,2013JM2002,SJ08B09).国家自然科学基金(21373162,21463020,21073142,21173168)和陕西自然科学基金(11JS110,2013JM2002,SJ08B09)资助项目Editorial office of Acta Physico -Chimica Sinicadoi:10.3866/PKU.WHXB 201412231分子间作用力构筑的具有柔性结构的醋氯芬酸多聚物:晶体结构,热稳定性,溶解度和DFT 计算孙盼盼1,#刘翔宇1,2,#孙琳2张盛1魏青1,*尹琰1杨奇1陈三平1,*(1西北大学化学与材料科学学院,合成与天然功能分子化学教育部重点实验室,西安710069;2宁夏大学化学化工学院,银川750021)摘要:非甾体类抗炎药物醋氯芬酸(ACF)的水溶性差,导致其生物利用度较低.本文制备了三种多聚物,分别是醋氯芬酸与4,4?-联吡啶(BIPY)共晶(1),与3-氨基苯甲酸(3-ABA)盐(2)和与二甲基亚砜(DMSO)的溶剂化物(3),利用红外光谱、粉末X 射线衍射和单晶X 射线衍射对它们的结构进行了表征.结果表明,化合物1-3的超分子结构是通过氢键、C ―H …π和π…π堆积作用构筑而成,三个多聚物具有良好的热稳定性.从热力学角度分析和密度泛函理论(DFT)计算说明ACF 在化合物3中的构象比其在化合物1和2中更稳定.此外,ACF 形成共晶、盐和溶剂化物后有效提高了其溶解度.关键词: 醋氯芬酸;多聚物;热稳定性;密度泛函理论;溶解度中图分类号:O641Intermolecular Interaction Induced Multi-Polymers of Aceclofenac with Flexible Conformation:Crystal Structure,Thermostability,Solubility andDFT CalculationsSUN Pan-Pan 1,#LIU Xiang-Yu 1,2,#SUN Lin 2ZHANG Sheng 1WEI Qing 1,*YIN Yan 1YANG Qi 1CHEN San-Ping 1,*(1Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education,College of Chemistry and Materials Science,Northwest University,Xi ?an 710069,P .R.China ;2School of Chemistry and Chemical Engineering,Ningxia University,Yinchuan 750021,P .R.China )Abstract:The non-steroidal anti-inflammatory drug aceclofenac (ACF)has low bioavailability because of its poor water solubility.To enhance its water solubility we synthesized three compounds:a co-crystal of ACF-0.5BIPY (4,4'-bipyridine)(1),a salt of ACF-3-ABA (3-aminobenzoic acid)(2),and a solvate of ACF-DMSO (dimethyl sulfoxide)(3).These compounds were characterized by infrared spectroscopy,powder and single crystal X-ray diffractions.The supramolecular structures of 1-3are sustained by hydrogen bonding C ―H …πand π…πstacking interactions and they have favorable thermal stabilities.Thermodynamically,DFT calculations revealed that the most stable conformation of ACF exists in compound 3and this structure is more stable than 1and 2.Furthermore,upon the formations of the co-crystal,the salt or the solvate the solubility of ACF improves significantly.211Acta Phys.-Chim.Sin.2015V ol.311IntroductionThe solubility and bioavailability of drugs are the critical factors for the development of pharmaceutical industry.1-3In many cases,some active pharmaceutical ingredients(APIs)cannot be used as drug candidates due to their poor solubility and,conse-quently,inefficient bioavailability.4Thus,it is a great challenge to enhance the solubility without compromising thestability and other performance characteristics in the product development of drugs.5-11A number of crystallized solid-state forms improve physicochemical properties of drug substances,including poly-morphs,12amorphous,13hydrates,14solvates,15and salts16.For ex-ample,salts are the most preferred formulation for improving the solubility of APIs,17which can only be formed for acidic or basic APIs.18Compared with the method above,cocrystals have been recently performed as a pharmaceutical development for neutral drug19and have gotten extensive attention in pharmaceutical science.20Pharmaceutical cocrystals are defined as structurally homogeneous crystalline materials comprising API and phar-maceutically acceptable cocrystal formers which are solids at room temperature.21The components of cocrystal are connected by noncovalent intermolecular interactions,such as hydrogen bonding,22,23halogen bonding,24π…πstacking,25,26and other no-ncovalent interactions.27-29Moreover,cocrystals have also been documented to be effective for improving the physicochemical properties of API,such as melting point,30photosensitivity,31dis-solution behavior,and bioavailability.32Aceclofenac(ACF,Scheme1)performs diverse conformations in multiple component compounds,33which is the nonsteroidal anti-inflammatory drug(NSAID)derived from N-phenylanthra-nilic acid.It has remarkable anti-inflammatory,analgesic,anti-pyretic properties and a reduced level of gastrointestinal damage compared to some other anti-inflammatory drugs.34,35However, ACF is a biopharmaceutics classification system(BCS)class II drug with poor water solubility of0.058μg?mL-1.36Therefore,it is very necessary to improve the solubility and bioavailability of ACFthrough the method of multi-component forms in the de-velopment of new dosage forms.In2008,Mutalik et al.37reported the chitosan-based solvent change approach to enhance the dis-solution rate and bioavailability of aceclofenac.In2011,Maulvi et al.38reported the solid dispersion technique to improve the dissolution rate of ACF.In2013,Nangia et al.33reported four salts of ACF with piperazine,cytosine,L-lysine,andγ-aminobutyric acid,a salt hydrate with piperazine and a cocrystal hydrate with 4,4'-bipyridine.The same year,Saxena and Kuchekar39published three aceclofenac sodium saccharin PVPK-30cocrystals.The research results show that ACF molecule integrating with ap-propriate coformers forming multi-components would effectively improve the solubility and bioavailability of the drug target. Pharmaceutically,dimethyl sulfoxide(DMSO)has anti-inflam-matory analgesic effect and strong permeability,4,4'-bipyridine (BIPY)and3-aminobenzoic acid(3-ABA)are acceptable co-formers31,33(Scheme1).With this in mind,we report the preparation of three multi-component forms,cocrystal of ACF with BIPY(1),salt of ACF with3-ABA(2),and solvate of ACF with DMSO(3).The structures of the three compounds are investigated by single-crystal X-ray diffraction(XRD)and density functional theory(DFT)calcula-tion.The different conformations of ACF are also proved by DFT calculation.Additionally,the dissolutions of compounds1-3and ACF are investigated and compared as well.2Experimental2.1ChemicalsAll solvents and chemicals were obtained from commercial sources and used without further purification unless otherwise stated.Aceclofenac(99.9%)was purchased from Xi'an HaixinPharmaceutical Co.,Ltd.4,4'-Bipyridine(99.2%)and3-amino-benzoic acid(99%)were purchased from Sigma-Aldrich.Di-methyl sulfoxide(99.5%),absolute ethanol(99.7%),methanol (99.5%),and acetonitrile(99.9%)were purchased from Xi'an Chemblossom Pharmaceutical Technology Co.,Ltd.2.2Preparation of compounds1-32.2.1ACF-0.5BIPY cocrystal(1)A mixture of ACF(35.4mg,0.1mmol)and BIPY(15.6mg,0.1 mmol)was dissolved in7mL of absolute ethanol and allowed to stir for1h at room temperature,and then the resulting solution was left to evaporate at room temperature.After7days,block-shaped yellow crystals of1were obtained in70%yield.Anal.(%) Calcd.for C21H17Cl2N2O4(432.27):C,58.35;H,3.96;N,6.48. Found:C,58.37;H,3.99;N,6.51.2.2.2ACF-3-ABA salt(2)ACF(35.4mg,0.1mmol)and3-ABA(13.7mg,0.1mmol) were dissolved in7mL of a1:1mixture of methanol and aceto-nitrile and left to slowly evaporate at room temperature.15days later,colorless crystals of2were harvested in85%yield.Anal.Key Words:Aceclofenac;Multi-polymer;Thermostability;Density functional theory;SolubilityScheme1Structural formulae of aceclofenacand cocrystal formers212SUN Pan-Pan et al.:Intermolecular Interaction Induced Multi-Polymers of Aceclofenac with Flexible Conformation No.2 (%)Calcd.for C23H20Cl2N2O6(491.31):C,56.23;H,4.10;N,5.70. Found:C,56.25;H,4.13;N,5.73.2.2.3ACF-DMSO solvate(3)ACF(35.4mg,0.1mmol)was dissolved in5mL of a3:1 mixture of DMSO and water and left to slowly evaporate at room temperature.7days later,plate-shaped colorless crystals of3were harvested in90%yield.Anal.(%)Calcd.for C18H19Cl2NO5S (432.30):C,50.01;H,4.43;N,3.24.Found:C,50.04;H,4,46;N, 3.27.2.3Single crystal X-ray diffractionThe single-crystal X-ray diffraction data of the crystals were collected on a Bruker Smart Apex charge-coupled-device(CCD) diffractometer equipped with graphite monochromatized Mo Kαradiation(λ=0.071073nm)usingωandφscan modes.The structures were solved by the direct methods using the SHELXS-9740and refined by means of full-matrix least-squares proce-dures on F2with SHELXL-97program41.All non-hydrogen at-oms were refined with anisotropic displacement parameters,and hydrogen atoms were placed in calculated positions and con-strained to ride on their parent atoms.Selected crystallographic data and structural refinement details of1-3are summarized in Table1.The hydrogen bonding distances and angles are listed in Table S1(in Supporting Information).Oak ridge thermal ellipsoid plot(ORTEP)diagrams at50%probability level for the com-pounds1-3are displayed in Fig.S1(in Supporting Information).2.4Dissolution studyThe solubility studies for ACF and compounds1-3in25%(φ) ethanol-water medium were carried out with a Shimadzu UV-2450 spectrophotometer,and the absorbance values were related to solution concentrations using a calibration curve.The solids were milled to powders and sieved using standard mesh sieves to provide samples with approximate particle size ranges of75-150μm.Then,excess amounts(50mg)of the samples were dippedinto5mL of25%ethanol-w ater medium in a10mL vial at37°C, and the slurries were stirred continuously with magnetic stirrer (RCT,Germany IKA company)at a rate of600r?min-1.At each time interval an aliquot of the slurry was withdrawn from the vial and filtered through a0.2μm nylon filter.And appropriate dilu-tions were made to maintain absorbance readings within the standard curve.The resulting solution was measured with a UV/ V is spectrophotometer.After the dissolution experiment,the remaining solids were collected by filtration,dried and analyzed by powder X-ray diffraction(PXRD).2.5Physical measurementsPXRD data were collected on a Bruker D8ADV ANCE dif-fractometer(Germany).Experimental conditions:Cu-Kαradiation (λ=0.15406nm),40kV,40mA,scanning interval5°-50°(2θ)at a scan rate of1(°)?min-1.Fourier transform infrared(FTIR) spectroscopy was performed on a Bruker Vector-33Fourier transform infrared spectrometer(Bruker Spectrospin,Karlsruhe, Germany)with spectrum range of4000-500cm-1.IR spectra were recorded on samples dispersed in KBr pellets.Differential scanning calorimetry(DSC)and thermogravimetric analysis (TGA)were performed on a Netzsch STA449C instrument (Germany)and a CDR-4P thermal analyzer of Shanghai Balance Instrument factory,respectively.The temperature range for the heating curve was30-600°C,and the sample was heated at a rate of10°C?min-1under a dry oxygen-free nitrogen atmosphere. Elemental analyses were performed on a V ario EL III fully au-tomated trace element analyzer(USA).2.6DFT calculationDFT calculation was carried out using X-ray crystallographic parameters of compounds1-3.A Gaussian03W package42was runon a personal computer.The geometric optimization and the frequency analyses were carried out using B3LYP43functional analyses with the6-31+G(d)44basis set without any restraints.All of the optimized structures were characterized to be true local energy minima on the potential energy surface without imaginary frequencies.3Results and discussion3.1Structure description3.1.1ACF-0.5BIPY cocrystal(1)The crystal structure of compound1crystallizes in the triclinic space group P1with one molecule of ACF and a half molecule of BIPY in the asymmetric unit(Fig.1(a)).The ACF and BIPY molecules are linked together by O4―H4…N2(D O4…N2=0.25963 (25)nm)hydrogen bond to form a three component adduct ob-served in known ACF-BIPY-hydrate as reported in Ref.33,which Table1Crystal data and structure refinementfor compounds1-3ParameterEmpirical formula Formula weight Crystal system Space groupT/Ka/nmb/nmc/nmα/(°)β/(°)γ/(°)V/nm3ZD calc/(mg?cm-3)μ/mm-1θrange/(°)R indices(all data) R1 wR2Final R indicesR1wR2GOF on F2 CCDC No. Value1C21H17Cl2N2O4 432.27triclinicP1296(2)0.71724(19)1.0477(3)1.3724(4)79.187(4)81.958(4)77.483(4)0.9836(4)21.4600.3611.52-25.000.05600.14520.04960.13681.0682C23H20Cl2N2O6 491.31triclinicP1296(2)0.4874(2)1.0801(5)2.1273(10)91.761(12)95.806(8)96.887(8)1.1050(8)21.4770.3380.96-25.350.17440.24760.07710.18430.9159885143C18H19Cl2NO5S 432.30 monoclinicP2(1)/c296(2)0.9680(3)0.9721(3)9095.991(5)901.9919(10)41.4420.4600.96-25.530.11760.19990.06200.14900.963988511213Acta Phys.-Chim.Sin .2015V ol.31is further stabilized through numerous π…π(distance of 0.39236(9)nm)interactions to form an infinite one-dimensional (1D)chain (Fig.1(b)).The adjacent chains are further connected by the interchain C ―H …π(distance of 0.38939(8)nm)interactions from pyridine C ―H and chlorophenyl ring,generating a two-dimen-sional (2D)layer (Fig.1(c)).Finally,the three-dimensional (3D)supramolecular structure of 1is stacked by several 2D layers (Fig.1(d)).While in ACF-BIPY-hydrate,Cl …O hydrogen bonds exist in ACF molecules and water molecules,acting as bridges toconnect ACF molecules between adjacent layers.3.1.2ACF-3-ABA salt (2)The compound crystallizes in the triclinic space group P 1,the asymmetric unit contains one ACF molecule and one 3-ABA molecule (Fig.2(a)).As shown in Fig.2(a),the proton transfer occurs in the compound from carboxyl group of ACF to the N ―H base of 3-ABA,and each ACF molecule interacts with five 3-ABA cations via four types of hydrogen bonds of N1―H1B …O6#1(D N1…O6=0.2921(6)nm),N1―H1B …O6#2(D N1…O6=0.2822(6)nm),N1―H1C …O5(D N1…O5=0.2924(7)nm),O2―H2A …O5(D O2…O5=0.2647(6)nm)(Fig.2(b)).The combination of two 3-ABA cations produces one dimer through N1―H1A …O1(D N1…O1=0.2924(7)nm)hydrogen bonds in the R 22(14)ring motif (Fig.2(c)).Adjacent dimers are bridged by ACF molecules with the inter-molecular hydrogen bonds of O2―H2A …O5and N1―H1B …O6to generate the 2D layer (Fig.2(d)).Adjacent layers are further linked through interchain hydrogen bonds N1―H1C …O5to form the 3D supramolecular network of 2(Fig.2(e)).3.1.3ACF-DMSO solvate (3)The asymmetric unit of compound 3contains one ACF mole- cule and one DMSO molecule.As shown in Fig.3(a),the hy-drogen bonds of O4―H4…O5(D O4…O5=0.2608(5)nm)and O4―H4…S1(D O4…S1=0.3616(4)nm)connect ACF molecule and DMSO molecule.The molecular units connect to each other by means of C ―H …πinteractions (distance of 0.34913(1)nm),presenting an infinite one-dimensional (1D)chain (Fig.3(b)).The interchain C ―H …πinteractions (distance of 0.35561(7)nm)integrate the 1D chains to yield 2D layer-like structure (Fig.3(c)).Finally,the 3D supramolecular network of 3isformed by the combination of countless 2D layers (Fig.3(d)).3.1.4Summaries of structuresAccording to reported previously,the carboxylate anion in salt displays two close D (C ―O)values (ΔD (C ―O)≤0.003nm),while the neutral carboxyl group in cocrystal exhibits two different D (C ―O)values (ΔD (C ―O)>0.008nm).41,45-47The ΔD (C ―O)values are 0.0126nm for 1and 0.0125nm for 3,conforming that 1is cocrystal and 3is solvate (Table S2,in Supporting Informa-tion).A relatively small ΔD (C ―O)value of 0.0043nm suggests that compound 2is salt.As shown in Figs.1-3,the ACF mole-cules in the three compounds display intramolecular hydrogen bonds of N ―H …O (C ＝O of ester group)or N ―H …O (C ―O of ester group)for compounds 1-3,the distances of O …N are 0.2935,0.3063,and 0.2946nm,and the angles of N ―H …O are 150°,140°,and 130°,respectively.ACF m olecules connect with BIPY and DMSO through O ―H …N and O ―H …S hydrogen bonds in compounds 1and 3,respectively,while connect with 3-ABA through O ―H …O and N ―H …O hydrogen bonds in compound 2.In addition,the weak C ―H …πinteraction exists in compounds 1and 3.Fig.1(a)Asymmetric unit of compound 1showing the part of atom-numbering scheme and intermolecular hydrogen bonds (shown as dashed lines);(b)1D chain of 1;(c)2D layer of 1;(d)3D structure of 1214SUN Pan-Pan et al .:Intermolecular Interaction Induced Multi-Polymers of Aceclofenac with Flexible ConformationNo.23.2Optimized structure with DFTThe isolated molecules of the compounds are selected as the initial structure,the DFT-B3LYP/6-31+G(d )method is used to optimize the structure of the compounds and compute their fre-quencies.Vibration analysis indicates that the optimized structures are in accordance with the minimum points on the potentialen-Fig.2(a)Asymmetric unit of compound 2showing the part of atom-numbering scheme and intermolecular hydrogen bonds (shown asdashed lines);(b)the hydrogen bond modes of ACF;(c)dimer R 22(14)ring motif between two 3-ABA cations;(d)2D layer of 2;(e)3D structure of2Fig.3(a)Asymmetric unit of compound 3showing the part of atom-numbering scheme and intermolecular hydrogen bonds (shown as dashed lines);(b)1D chain of 3;(c)2D structure of 3;(d)3D structure of 3215Acta Phys.-Chim.Sin .2015V ol.31ergy planes,which means no virtual frequencies,confirming that the optimized structures are stable,as shown in Fig.4.Obviously,the optimized structures have a good agreement with the measured one.Besides,the calculated distances of intramolecular hydrogen bond O …N are 0.2956,0.2971,and0.2958nm,and the angles of N ―H …O are 146.77°,146.60°,and 142.23°for 1-3,respec-tively,which match with the measured value.This indicates that the method of DFT-B3LYP/6-31+G(d )is appropriate to carry out relevant study.The energies of compounds 1-3are calculated as -2388.601080,-2369.372531,and -2446.491928hartree,re-spectively.Thermodynamically,it is obvious that compound 3is more stable than the other two compounds,as shown in Fig.5.3.3Conformational analysis with DFT for ACFAccording to the structural analysis above,it is demonstrated that ACF consists of N -2,6-dichlorophenyl and N -phenylacety-loxyacetic acid groups,and is conformationally flexible molecule stems from the rotation at C ―N and CH 2―COO moieties (Fig.6(a)round box).The flexible conformation in ACF is determined by the following four torsion angles (atoms numbering corre-sponds to Fig.6(b)),(i)C(3)N(1)C(7)C(8),the angle characterizes the flip of the N -2,6-dichlorophenyl ring along the axis of the N(1)―C(7)bond;(ii)C(4)C(13)C(14)O(4),the angle charac-terizes the rotation of the CO 2CH 2COOH fragment along the C(13)―C(14)bond;(iii)C(15)O(3)C(14)O(4),the angle char-acterizes the twist of the OCH 2COOH fragment along the O(3)―C(14)bond;(iv)O(3)C(15)C(16)O(1),the angle characterizes the twist of the carboxyl group along the C(15)―C(16)bond.The selected torsion angles for compounds 1-3are listed in Table S3 (in Supporting Information).First,the aryl rings are twisted at certain angle to relieve steric hindrance of ortho-substituted phenyls at the secondary amine,the dihedral angles between the two ring planes are 74.18°,73.18°,and 58.86°separately for compounds 1-3,as indicated in Fig.6(a).Noteworthily,the CO 2CH2COOH fragment of ACF in compound 2rotates a larger angle along the C(13)―C(14)bond than the angles in other two compounds,thereby,ACF molecules with various conformations show two types of intramolecular hydrogen bonds of N ―H …O in the three compounds.In order to analyze the conformations of ACF definitely,DFT method has been used to optimize the conformations of ACF and calculate the frequencies.Vibrational analysis indicates that the optimized conformations are in accordance with the minimum points on the potential energy planes,proving that the three conformations of ACF are reliable.Thermodynamically,the en-ergies of the three conformations of ACF in 1-3are calculated to be -1893.365358,-1893.365644,and -1893.366412hartree,respectively.It indicates that the third conformation of ACF istheFig.4Optimized structures of compounds (a)1,(b)2,and (c)3using DFTcalculationFig.5Energies of compounds 1-3Fig.6(a)Overlaid conformations of ACF molecule in the compounds 1-3and (b)numbering scheme used for the analysis of torsion angles216SUN Pan-Pan et al .:Intermolecular Interaction Induced Multi-Polymers of Aceclofenac with Flexible Conformation No.2most stable form,corresponding to the compound 3with the most stable structures.3.4Powder X-ray diffraction analysesPowder X-ray diffraction is introduced to demonstrate the formation of new phases and the purity of the bulk phase.As a result,the patterns of the products are different from the starting materials and match with the PXRD patterns simulated from the crystal structure data,indicating the formation of new phases and qualified purity of the bulk phase (Fig.7).3.5FTIR analysisVibrational spectroscopy is a reliable technique to characterize hydrogen bonding and crystal packing in the solid state.48IR spectra of compounds 1-3show clear differences compared to the pure component,as shown in Fig.S2(in Supporting Information).The IR spectrum of ACF exhibits peaks at 1768cm -1for the carboxylic carbonyl stretching vibration,at 1715cm -1for the esterfunction,and at 3324cm -1for vibrations of the amine functional.The stretches of C ―O bond and bend of O ―H bond appear at 1259and 1431cm -1,respectively.33In compounds 1and 3,the N ―H stretching frequencies red shift to 3302and 3293cm -1,re-spectively.Due to the hydrogen bonding between BIPY molecule and the acid group in ACF,the C ＝N stretching in BIPY shifts from 1409to 1416cm -1in compound 1.Similarly,the S ＝O stretching in DMSO shifts from 1663to 1715cm -1in compound 3.In compound 2,two strong peaks at 3368and 3218cm -1cor-respond to amine group and a broad peak around 2900cm -1be-longs to hydroxyl /doc/4d13421908.html paring with the 3-ABA monomer,a red shift emerges in the curve of compound 2resulting from the formations of hydrogen bonds between 3-ABA and ACF.Addi-tionally,the carboxylate anions in compound 2show two sym-metric stretching vibrationsat 1452and 1267cm -1.3.6Thermal analysisThe first information about the existence of new solid phases is obtained from the change of the melting points between com-pounds and the start materials.As shown in Fig.8,the first en-dothermic peaks in the DSC curves of compounds 1-3correspond to the processes of melt,the melting points of 1-3and the starting materials are listed in Table 2.The specific melting or decom-position tendencies are shown as endothermic or exothermic peaks in the DSC curves.We do not notice any relationship be-tween the melting points of the coformers and corresponding multi-component forms,similar to previous cocrystal systems.33,49The TGA measurements indicate that the ACF decomposes at the temperature of 155°C (Fig.8(a)).The weight losses for compounds 1and 2initiate at app roximately 171and 159°C (Fig.8(b,c)),respectively,while compound 3starts from about 134°C due to the release of DMSO molecule and the carboxylate group in ACF molecule (Fig.8(d)).3.7Solubility and dissolution studyDissolution rate and apparent solubility of solids are of crucial factor in pharmaceutical development and quality control,and shorter dissolution times and higher apparent solubility may lead to more absorption.The solubility of compounds 1-3was per-formed in 25%ethanol-water medium because the concentration of ACF in pure water is very low,33the powder dissolution curves are shown in Fig.9.It can be found that the three compounds display an increase in the dissolution rates and solubility values compared to/doc/4d13421908.htmlpound 1appears the maximum solubility after 90min,while compound 2,3and ACF reach the maximum solubility within 30min,and then decrease over the time.This particular model of the solubility is a product derived from the “spring and parachute effect ”w hich has been exhibited in a number of pharmaceutical cocrystals.15,50The maximum solubility values of compounds 1-3are approximately 2.9,2.4,and 3.4times as large as that of ACF,respectively,which is close to that of ACF-PIP-hydrate reported in Nangia ?s group work 33,and it follws othe order of 3>1>2>ACF,demonstrating that the solubility of API can be increased through the multi-component forms.After the dissolution experiments,the undissolved solids arefiltered,Fig.7PXRD patterns of ACF,BIPY,as-synthesized,and simulated from the single-crystal data for (a)1,(b)2,and (c)3 217Acta Phys.-Chim.Sin .2015V ol.31dried,and characterized by PXRD analysis.It is observed that compound 1maintains the original component,while the residues of compounds 2and 3are determined as ACF due to the disso-lution of 2and 3(Fig.S3,in Supporting Information).4ConclusionsThe cocrystal,salt,and solvate of ACF are obtained,of which the supramolecular structures are constructed through a numerousof intermolecular interactions.Three types of conformationsof ACF exist in 1-3,respectively,and the most stable conformation locates in 3which possesses the most stable structure in the three compounds,which is verified by DFT calculation.The results of DSC-TGA indicate that the compounds 1-3exhibit good ther-molstabilities,and the melting points of 1-3are different from those of starting materials.In addition,the solubility of ACF has been increased after the formation of compounds 1-3,indicating that the solubility and bioavailability of ACF can be improved via cocrystal,salt,and solvate.Obviously,the construction of multi-component forms can be a viable strategy for improving the physicochemical properties of API.Supporting Information : Hydrogen bonding distancesand angles (Table S1),ΔD (C ―O)of the C ―O bond lengths (Table S2),torsion angles (Table S3),ORTEP diagrams (Fig.S1),IR spectra (Fig.S2),PXRD patterns before and after disso-lution experiments (Fig.S3),and X-ray crystallographic datafor 1-3in CIF format have been included.This information is available free of charge via the internet at /doc/4d13421908.htmlDC numbers for 1-3are 1000083,988514,and 988511,respectively.These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via /doc/4d13421908.html/data_request/cif.References(1)Schultheiss,N.;Bethune,S.CrystEngComm 2010,12,2436.Fig.8DSC and TGA curves of (a)ACF,(b)1,(c)2,(d)3Table 2Melting points for compounds 1-3and thestarting materialsMelt pointOnset decompositionT /°C1136.5171.52144.1159.9386.5134.1ACF 152.3155.4BIPY 110-112-3-ABA 170-171-Fig.9Powder dissolution profiles for ACF and compounds 1-3218SUN Pan-Pan et al.:Intermolecular Interaction Induced Multi-Polymers of Aceclofenac with Flexible Conformation No.2 doi:10.1039/c002045a(2)Chadha,R.;Saini,A.;Jain,D.S.;Venugopalan,P.Cryst.Growth Des.2012,12,4211.doi:10.1021/cg3007102(3)Moradiya,H.;Islam,M.T.;Woollam,G.R.;Slipper,I.J.;Halsey,S.;Snowden,M.J.;Douroumis,D.Cryst.Growth Des.2013,14,189.(4)Luo,Y.H.;B.Sun,W.Cryst.Growth Des.2013,13,2098.doi:10.1021/cg400167w(5)Chen,J.M.;Wang,Z.Z.;Wu,C.B.;Li,S.;Lu,T.B.CrystEngComm2012,14,6221.doi:10.1039/c2ce25724f (6)Kawabata,Y.;Wada,K.;Nakatani,M.;Yamada,S.;Onoue,S.Int.J.Pharm.2011,420,1.doi:10.1016/j.ijpharm.2011.08.032(7)Torchilin,V.P.Pharm.Res.2007,24,1.(8)Brewster,M.E.;Loftsson,T.Adv.Drug Delivery Rev.2007,59,645.doi:10.1016/j.addr.2007.05.012。

国家自然科学基金委员会生命科学部2016年度青年基金项目_0a55ef92_a4

第28卷第12期2016年12月V ol. 28, No. 12Dec., 2016生命科学Chinese Bulletin of Life Sciences文章编号：1004-0374(2016)12-1493-54国家自然科学基金委员会生命科学部2016年度青年基金项目DOI: 10.13376/j.cbls/20161861微生物学细菌基因组歧化和遗传界限的产生：新物种形成的分子基础唐　乐哈尔滨医科大学我国沿海盐田嗜盐古菌胞外蛋白酶多样性研究侯　靖江苏大学反硝化细菌的鉴定及其与胆固醇降解相关蛋白、基因的初探丁　滨浙江中医药大学大连新港石油污染海域沉积物中厌氧微生物种群和功能基因多样性与氮源响应规律研究陈　超大连民族大学苏云金芽胞杆菌晶胞粘连表型菌株资源及形成机制的多样性研究王月莹华中农业大学粪产碱菌杀线虫活性物质挖掘及作用线虫方式研究鞠守勇华中农业大学冰川稀有低温细菌Cryobacterium物种多样性、分类学及冷适应性研究刘　庆中国科学院微生物研究所捕食青枯菌的粘细菌资源分离与功能评价李安章广东省微生物研究所环境因子对花生根瘤菌遗传多样性和分布的影响机制研究李　岩中国科学院烟台海岸带研究所家蚕病原细菌多样性、分布规律及其与蚕体共生菌关系研究周洪英湖北省农业科学院杏褪绿卷叶植原体宿主植物内生细菌的群落变化及与宿主抗/感病性的相关性研究韩　剑新疆农业大学竹虫肠道微生物群落结构及纤维素酶基因多样性分析王彦伟农业部沼气科学研究所木质纤维素水解残渣厌氧消化过程中微生物群落的组成与功能分析汤晓玉农业部沼气科学研究所海绵复杂共生体中放线菌新分类单元及新活性物质发现李　蕾上海交通大学贵州喀斯特洞穴放线菌多样性及生物活性菌株筛选房保柱中山大学放线菌中五角多酚类化合物的基因组挖掘刘力伟中国科学院微生物研究所疣孢菌CRISPR/Cas9基因组编辑技术的建立和评价谢　峰中国科学院微生物研究所3种黄连属濒危植物内生放线菌多样性及其抗菌消炎活性初探田守征云南中医学院中国丽赤壳属Calonectria种类及系统发育研究张云霞仲恺农业工程学院东北地区红菇真菌子实体及其地下菌根分子生态学研究冀瑞卿吉林农业大学山东苹果主产区红富士果面酵母菌多样性及对苹果炭疽病的生防潜能陈　汝山东省农业科学院中国毛霉属系统发育研究及DNA条形码筛选王亚宁中国科学院微生物研究所壳二胞属物种分类研究陈　倩中国科学院微生物研究所食药用菌真菌病害病原鉴定及系统分类研究孙敬祖中国科学院微生物研究所七种鞘翅目昆虫共生蛇口壳目真菌资源的分类与分子系统发育研究殷明亮广东省微生物研究所木兰科植物的丛枝菌根真菌多样性及协同进化特征杨安娜安徽师范大学我国海洋性冰川低温真菌多样性研究王曼曼河北大学云芝新颖苔色酸木糖苷衍生物的糖基化机制研究朱丽萍青岛农业大学中国芒果炭疽菌多样性及致病力变异分子机制的研究李其利广西壮族自治区农业科学院赤水河流域枯枝暗色丝孢菌Dematiaceous hyphomycetes多样性研究李小霞遵义师范学院鹅膏科系统发育框架构建及营养方式演化研究蔡　箐中国科学院昆明植物研究所西南地区葡萄座腔菌科四个重要属的分类和分子系统学发育研究刘建魁贵州省农业科学院严紧反应下乙酰化修饰对大肠埃希菌DnaA降解调控的研究张秋芬上海交通大学蓝细菌能量-还原力代谢重平衡新策略及其生理影响研究栾国栋中国科学院青岛生物能源与过程研究所海洋细菌胞外多糖 EPS273 抑制铜绿假单胞菌生物膜形成的分子机理研究吴仕梅中国科学院青岛生物能源与过程研究所1494生命科学第28卷里氏木霉sorbicillinoid类次级代谢产物生物合成机制的研究齐飞飞中国科学院青岛生物能源与过程研究所枯草芽胞杆菌产生羊毛硫细菌素subtilomycin促进其在植物体内定殖的机制邓　运华中农业大学沙雷氏菌属新种YD25中环脂肽类化合物与灵菌红素生物合成的共调控机制研究苏　春陕西师范大学青枯菌生物素合成途径中一种新型甲酯庚二酸单酰ACP酯酶的鉴定及其生物学功能研究贾　佳南京医科大学硫转移蛋白在嗜酸热硫氧化古菌Metallosphaera cuprina硫传递网络中的功能研究刘丽君西安医学院希瓦氏菌中D型β-内酰胺酶诱导表达及其耐药机制的研究音建华南昌大学酿酒酵母生物合成中长链二元酸的动态调控及其作用机制韩　丽郑州轻工业学院土壤杆菌胞外水溶性β-1,3-葡聚糖的生物合成机制研究程　瑞南京理工大学基于AFM力谱与SPR技术的启动子强度高效表征策略的研究张晓娟江南大学P450单加氧酶AveE催化阿维菌素呋喃环形成的机制研究马　莉中国科学院青岛生物能源与过程研究所丁香假单胞菌海藻糖合成与抗水分胁迫相关性研究余希岚湖北大学解脂耶氏酵母中蛋白激酶Snf1参与氮饥饿启动赤藓醇合成的调控机制刘晓燕淮阴师范学院转录因子RpoD调控运动发酵单胞菌乙醇耐受性的机制研究谭芙蓉农业部沼气科学研究所酮基合酶MarO催化maremycin中哌嗪二酮的酰胺键形成和成环释放机制黄婷婷上海交通大学多模块持续性内切纤维素酶CcCel9A的持续性驱动力研究张坤迪中国科学院青岛生物能源与过程研究所里氏木霉外切纤维素酶CBH I的水解机理研究和理性设计王业飞中国科学院青岛生物能源与过程研究所单酶催化多步连续反应中底物结合模式研究姚明东天津大学灰盖鬼伞胞外β葡聚糖苷酶BGL2不同变体产生机制和生理功能的研究刘中华南京师范大学蛹虫草隐花色素Cry-DASH功能及作用机制王　芬中国科学院微生物研究所酶分子对黄姜细胞壁降解及皂苷释放的影响机理研究魏　蜜湖北工程学院基因内置特征影响密码子偏好对重组蛋白表达调控的研究周　勉华东理工大学大肠杆菌脂多糖转运关键蛋白LptFG的功能研究向泉桔四川农业大学金黄色葡萄球菌七异戊二烯二磷酸合成酶SaHepPPs晶体结构和抗菌药物开发李　倩中国科学院天津工业生物技术研究所以产油微藻海洋微拟球藻为模式的二酰甘油酰基转移酶功能机制研究辛　一中国科学院青岛生物能源与过程研究所聚酮合酶pks7和pks11对海洋草酸青霉合成Oxalicumone A及其环境适应性的调控机制研究王　洁中国科学院南海海洋研究所大肠杆菌中galE转录暂停调控下游ρ依赖型转录终止的分子机制王　璕华中农业大学XsfP催化的膜内受控蛋白水解在黄单胞菌致病过程中的调控功能邓超颖中国科学院微生物研究所鞘脂合成调控因子Orm1在球孢白僵菌中的功能鉴定及其致病机理研究王娟娟济南大学糖多孢红霉菌中与红霉素合成相关调控因子间的干扰机制研究汪焰胜安徽大学特异腐质霉转录因子HiProA调控纤维素酶表达机制的研究徐欣欣中国农业科学院生物技术研究所利用代谢拨动开关调控大肠杆菌芳香型氨基酸的合成古鹏飞济南大学CRISPR/Cas9介导的基因组进化构建固态发酵耐热酵母及机理研究李鹏松清华大学代谢工程改造枯草芽孢杆菌合成N-乙酰神经氨酸关键问题的研究刘延峰江南大学米曲霉Sedolisin家族基因相关联的外源蛋白表达分泌机制的研究朱　琳江苏大学L-异亮氨酸合成途径基因在谷氨酸棒杆菌中的模块化协调表达和代谢调控机制研究尹良鸿浙江农林大学酿酒酵母合成灵芝酸类似物的研究肖　晗上海交通大学聚3-羟基丁酸-4-羟基丁酸酯的全新合成代谢通路的构建与优化尹　进清华大学二硫吡咯酮生物合成途径中N4甲基转移酶的表征及组合生物合成应用黄　胜湖北民族学院大肠杆菌中植物CPR:P450模块化自主共价连接系统的构建及其在咖啡酸合成中的应用李宜奎江苏省中国科学院植物研究所胆囊癌微环境菌群结构特征和功能学的初步研究吴文广上海交通大学国家自然科学基金委员会生命科学部2016年度资助项目第12期1495单细胞水平高产虾青素雨生红球藻高通量筛选新方法研究王喜先中国科学院青岛生物能源与过程研究所基于功能活性可视化追踪的芳烃降解微生物高通量筛选方法方　云广东省微生物研究所微生物漆酶数据挖掘及底物杂泛性分析张寅良安徽大学亚硝酸盐还原酶转录调控蛋白NsrR去阻遏机制研究令桢民兰州大学异丙甲草胺脱烷基酶基因的克隆及脱烷基酶特性和功能的研究陈　青枣庄学院面向人工定向重构纤维素菌群的共生分子机理研究杜　然清华大学迪茨氏菌转录调控蛋白AlkX对烷烃降解过程的全局调控研究梁洁良中山大学GDSL酯酶的定向进化与分子改造研究丁俊美云南师范大学整合宏组学方法研究番茄秸秆堆肥生境中的关键微生物及其功能张小梅青岛农业大学假单胞菌CNB-12分解代谢3-氯硝基苯的机理研究闵　军中国科学院烟台海岸带研究所假单胞菌LY1降解3-吲哚乙酸上游途径分子机理研究于　浩青岛农业大学一种二苯醚类污染物直接开环角度双加氧酶的分子机制研究蔡　舒江苏省农业科学院根际促生解淀粉芽孢杆菌SQR9组氨酸激酶KinA-E响应的根系分泌物信号鉴定刘云鹏中国农业科学院农业资源与农业区划研究所膜囊泡介导Geobacter sulfurreducens胞外电子传递过程及机制刘　星福建农林大学短短芽孢杆菌Spo0A蛋白介导的生物膜调控通路中阻遏基因的功能分析侯启会山东农业大学高盐环境下盐单胞菌(Halomonas)降解偶氮染料的机制研究郭　光南京工程学院纳米氧化铝促海洋枯草芽孢杆菌抗菌物质合成机理研究于秀霞山东大学红树林湿地生态系统中MCG古菌mcrA基因的时空变化规律和环境效应研究潘　杰深圳大学基于秀丽隐杆线虫模型的抗菌性海洋益生菌筛选及其机理研究李英秀山东大学滇池水华中控藻菌的杀藻相关基因及其功能研究杨彩云西南大学太湖蓝藻群体颗粒附生细菌的宏基因组学研究张军毅东南大学稻田藻-菌生物膜中胞外聚合物对水体营养水平变化的响应机制刘俊琢中国科学院南京土壤研究所高原藏族人特异性皮肤菌群与紫外辐射适应关系研究曾　博四川农业大学学龄前儿童“口腔菌群年龄”的遗传基础和过程机制滕　飞中国科学院青岛生物能源与过程研究所地衣共生系统中地衣细菌群落结构及其功能研究司红丽山东师范大学广东省凡口铅锌矿矿山酸性废水中古菌的多样性与功能研究陈林兴中山大学鸡肠道微生物代谢黄曲霉毒素B1的分子机制研究汪玲玲华南农业大学西藏热泉环境栖热菌类群多样性及其生理生态功能研究周恩民中山大学中华蟾蜍蝌蚪肠道菌群的结构及其影响因素研究宋晓威信阳师范学院转录激活因子PilR在σ54调控水稻白叶枯病菌毒性中的功能研究余　超中国农业科学院植物保护研究所TLR介导的ATP释放在副猪嗜血杆菌感染上调IL-1β中的作用研究于　江山东省农业科学院分枝杆菌aceE基因影响细胞壁合成代谢的机制研究陈素婷首都医科大学碳青霉烯耐药鲍曼不动杆菌新优势克隆ST208毒力因子鉴定及功能研究陈　燕浙江中医药大学沙门氏菌毒素效应蛋白SifA C-端结构域毒力功能机制的研究赵伟栋新乡医学院MexS调控铜绿假单胞菌III型分泌系统分子机制的研究靳永新南开大学基于炭疽芽孢杆菌S-层蛋白自组装的双抗高灵敏检测纳米材料的研究王旭颖武汉血液中心c-di-AMP信号通路在炭疽杆菌致病机制中的功能研究胡　葭中国科学院武汉病毒研究所生物被膜在沙门菌逃逸肠黏膜树突状细胞免疫监视中的作用和机制阴银燕扬州大学结核分枝杆菌广谱胁迫蛋白Rv1996介导的异烟肼耐药机制研究胡新玲中国科学院微生物研究所一种肺炎链球菌磷壁酸合成相关蛋白的功能鉴定吴凯峰遵义医学院NO调控鲍曼不动杆菌多重耐药的机制研究邓珊珊成都医学院禾谷镰刀菌FgPrp6调控剪接体激活的作用机制研究金巧军西北农林科技大学高渗胁迫下应激活性蛋白激酶afSakA对黄曲霉毒素合成的调控机制研究袁　军福建农林大学低铁环境下白色念珠菌核质转运受体Nmd5调控转录因子Sef1异常核输出的分子机制研究黄新华中国科学院上海巴斯德研究所Fasciclin-1结构蛋白在红色毛癣菌生长发育和侵袭宿主细胞中的作用机制研究占　萍南昌大学生命科学第28卷1496白念珠菌灰菌细胞的菌丝生长调控机制研究管国波中国科学院微生物研究所水稻条纹病毒Pc2蛋白在病毒侵染介体中的功能研究赵淑玲扬州大学南方水稻黑条矮缩病毒(SRBSDV) P7-1形成的管状结构进入细胞壁的机制及其在病毒运动网络中的功能谢　礼浙江省农业科学院反向长链非编码RNA调控NIA基因响应CMV侵染的机制研究赵建华中国科学院微生物研究所植物液泡脂质调控CMV病毒基因组复制的机制顾周杭浙江理工大学Dicer-2调控抗病毒Toll免疫通路的作用机制研究王赵玮武汉大学利用MDV载体递呈靶向ALV-J的CRISPR/Cas9系统预防MDV和ALV-J感染的研究李　凯中国农业科学院哈尔滨兽医研究所NS1蛋白与人核仁磷酸化蛋白1互作在A型流感病毒感染过程中的作用研究朱春玉辽宁大学乙型肝炎病毒HBx类泛素化Neddylation修饰的功能及生物学意义刘宁宁中国科学院微生物研究所Nrf2/ARE信号通路对RHDV感染中肝脏氧化应激的作用胡　波江苏省农业科学院汉滩病毒核衣壳蛋白核质转运信号的鉴定及其在病毒感染中功能的研究叶　伟中国人民解放军第四军医大学免疫缺陷病毒Vpx蛋白识别宿主CRL4 (DCAF1) E3泛素连接酶的作用机制研究魏　伟吉林大学新型EV71病毒抑制剂靶向病毒3D蛋白的作用机制及其抗病毒功能研究张　伟苏州大学乙型肝炎病毒C蛋白促进Src/PI3K/Akt通路介导的肝细胞周期进程及机制刘　伟三峡大学基于"HCV core-ZEB相互作用促进EMT"探讨HCV感染相关性肝癌的发生机制张利军重庆医科大学抗肿瘤化合物tyrphostin AG490抑制丙型肝炎病毒NS5B聚合酶活性的分子机理研究杨　娜中国科学院海洋研究所GADD45G蛋白通过组蛋白修饰调控HSV-1感染的分子机理研究陈晓庆广州医科大学新型H3N2人流感的进化及受体结合特性研究路希山中国科学院天津工业生物技术研究所用VLP表达HPIV3的HN和F蛋白及其介导的免疫应答对小鼠的保护作用研究张光媛重庆医科大学CCHFV囊膜蛋白Gc结构域III与病毒入侵相关位点研究张怀东中国科学院武汉病毒研究所乙型脑炎病毒RNA元件的宿主特异性研究刘思情中国科学院武汉病毒研究所HIV-1利用CypA躲避TRIM11加速脱衣壳作用的机制研究袁　婷中国科学院武汉病毒研究所ISlncRNA-23促进HIV-1复制的机制研究董银慧中国科学院生物物理研究所发热伴血小板减少综合征病毒对IL-10和IL-11抗炎信号的抑制机制宁云佳中国科学院武汉病毒研究所HCMV通过IE1调控神经干细胞中Hes1表达及节律的机制李小军中国科学院武汉病毒研究所柠檬酸铁的抗病毒作用与机制研究王洪斌中国科学院上海巴斯德研究所长链非编码RNA A VIRL在抗流感病毒感染中的作用机制研究陈玉海中国科学院微生物研究所噬菌体SWU1杀菌过程中ROS的作用及产生机制研究樊祥宇济南大学gp38蛋白决定大肠杆菌噬菌体Bp7宽宿主谱的机制张　灿青岛农业大学鹦鹉热嗜衣原体两个TMH家族蛋白结构与功能研究伍海英南华大学黑龙江立克次体表面蛋白与血管内皮细胞(宿主细胞)表面分子相互作用的研究齐　永中国人民解放军南京军区军事医学研究所2植物学NAC转录因子调控荔枝果柄离区细胞凋亡的机理研究李彩琴华南农业大学细胞壁组分与复合多层结构对小麦籽粒水分及品质调控机理的研究应瑞峰南京林业大学水稻极度矮化基因STD1的图位克隆与功能分析房静静中国农业科学院作物科学研究所复苏植物牛耳草DnaJ蛋白参与水分胁迫下叶绿体保护的作用机理刘　杰中国科学院植物研究所PRSL1通过蛋白磷酸酶PP1调控拟南芥植株形态的分子机理秦倩倩兰州大学拟南芥WUSCHEL互作因子WIC1调控茎端分生组织功能的机理研究周　超山东农业大学虎耳草科虎耳草属石荷叶组的分类学研究张卓欣华南农业大学国家自然科学基金委员会生命科学部2016年度资助项目第12期1497中国景天科山景天组的分类学研究孟世勇北京大学日本蛇根草和广州蛇根草及其近缘类群的系统分类学研究吴　磊中南林业科技大学万寿竹属的分类学和系统学研究朱鑫鑫信阳师范学院豆科甘草属分子系统发育与生物地理学研究段　磊中国科学院华南植物园苍山冷杉复合体的物种划分与气候响应模式研究邵毅贞河南农业大学泛喜马拉雅地区鼠尾草属的分类修订胡国雄贵州大学豆科长柄山蚂蝗属的分子系统学研究宋柱秋中国科学院华南植物园中国长篦藻属硅藻的分类修订及分子系统学研究刘　琪山西大学平叶多褶苔和变异多褶苔的物种界定以及洲际间断分布格局的形成原因师雪芹安徽师范大学绿藻门橘色藻目的系统分类学研究朱　欢中国科学院水生生物研究所北半球间断分布植物珊瑚菜的亲缘地理学和保护遗传学研究李密密江苏省中国科学院植物研究所东亚植物区系空间分化的分子机制——棣棠花和粉花绣线菊复合群的谱系地理学研究罗　冬中国科学院昆明植物研究所热带亚洲鞭苔属的系统分类学研究董珊珊华南农业大学溯祖方法在系统发育基因组学分析中的可靠性席祯翔四川大学基于ddRAD-seq技术的悬竹属时空演化格局研究张宪智西北农林科技大学银莲花属西南银莲花组和鹅掌草组的分子系统学研究张　煜湖南科技大学双盖蕨属(蹄盖蕨科)的系统发育和物种多样性分化研究卫　然中国科学院植物研究所小檗科(Berberidaceae)系统基因组学及叶绿体基因组进化研究孙延霞中国科学院武汉植物园鬼灯檠属的进化历史研究马祥光中国科学院昆明植物研究所浅苞橐吾、云南橐吾和大黄橐吾之间的自然杂交和基因渗入研究余姣君中国科学院昆明植物研究所芸薹属油菜类作物细胞质基因组单倍型的精细解析及其协同进化分析乔江伟中国农业科学院油料作物研究所荨麻科叶绿体系统发育基因组学研究吴增源中国科学院昆明植物研究所大豆脂肪酸脱氢酶FAD2家族酶活性差异的进化与功能研究赵　嫚浙江工业大学印度-西太平洋地区红树基因组渐渗与物种分化机制研究何子文中山大学青藏高原—蒙古高原—中亚地区砾玄参复合群的亲缘地理学研究王瑞红浙江理工大学小麦杀配子现象中存在的转录组变异及miRNAs在其中的调控作用研究白　琰哈尔滨师范大学水玉簪属(Burmannia L.)植物与丛枝菌根真菌协同进化研究赵中涛中国科学院华南植物园结合几何形态学方法探索泽泻科植物心皮的发育与进化黄岚杰湖北大学荠属种内叶形自然变异的研究杨　丽中国科学院植物研究所姜科唇瓣的发生、发育及其分子机理研究李秀梅广东省农业科学院农业生物基因研究中心同域分布老鹳草属植物花冠开口方向的分化机制王　慧华中农业大学Hlips在保护蓝藻光系统II免受氨损伤中的机制研究戴国政华中师范大学管藻黄素型LHCII参与的假根羽藻非光化学淬灭机制研究王文达中国科学院植物研究所D1蛋白周转过程的调控机制研究-以短命植物为例涂文凤中国科学院植物研究所糖基化调控水稻乙醇酸氧化酶与过氧化氢酶互作及过氧化氢信号发生的机理研究张智胜湖南农业大学水稻镉吸收和积累相关基因的发掘和功能鉴定杨　猛华中农业大学硫-TOR信号通路介导拟南芥生长的分子机理研究徐　萍中国科学院上海生命科学研究院木薯碱性/中性转化酶MeNINV1的酶活性调节机制研究姚　远中国热带农业科学院热带生物技术研究所拟南芥转录因子NAC103在逆境胁迫响应中的生物学功能及其调控机理孙　玲江苏大学基于ssRNA-seq的木薯抗旱lncRNA的挖掘及相关基因调控网络的研究丁泽红中国热带农业科学院热带生物技术研究所BHLH转录因子HBI1调控植物生长和免疫抗病动态平衡的分子机制研究樊　敏山东大学转录因子基因LbCPC参与二色补血草盐腺分化的功能研究袁　芳山东师范大学GSK3类蛋白激酶SGK1通过SOS2调节植物耐盐性的分子机制研究周华鹏四川大学生命科学第28卷1498拟南芥内质网膜蛋白ROOT HAIR DEFECTIVE 3 (RHD3)调控花青素代谢分子机理王　静北方民族大学大豆转录因子SNAC的无序序列区对耐盐相关基因表达调控的分子基础刘国宝深圳大学光周期下拟南芥CAT2蛋白降解的分子机制研究苏　彤山东师范大学拟南芥类受体蛋白激酶CRKN1在脱落酸信号转导中的功能研究梁　杉清华大学一氧化氮调控拟南芥体内硼含量稳态的分子机制研究夏金婵河南中医学院植物高温响应的表观记忆机制刘军钟中国科学院上海生命科学研究院拟南芥光信号转录因子FAR1与EDS1互作调控植物免疫的机理研究王晚晴北京联合大学非传统G蛋白及其激活蛋白的晶体结构与水稻应答盐胁迫机制的关系解析苗　锐福建农林大学拟南芥MYB102通过调控细胞壁扩展蛋白的表达增强植物耐旱的分子机理研究周　成安徽科技学院大豆高盐响应蛋白GmOSM的调控机理研究万　群江苏省农业科学院拟南芥新型液泡阴离子通道(VSAC1和VSAC2)介导细胞水势调控的分子机制研究张海纹北京市农林科学院野生番茄响应昆虫唾液中FAC诱导物的遗传基础研究申国境中国科学院昆明植物研究所膜结合转录因子NAC091调控植物内质网胁迫应答的分子机理研究杨正婷贵州师范大学拟南芥丝氨酸羧肽酶SCPL41基因在干旱胁迫中的作用及机制贾艳霞中国科学院昆明植物研究所小麦类钙调素调节植物耐盐性的功能研究周　硕河北省农林科学院遗传生理研究所拟南芥RopGEF7的互作蛋白eIF4E1参与生长素介导的植物发育的分子机制刘太波华南农业大学拟南芥CKRW1调节内源生长素水平稳态平衡的分子机理研究武　磊兰州大学拟南芥乙酰转移酶HLS1在BR与Auxin协同调控植物生长发育中的功能研究刘晓磊中国科学院上海生命科学研究院GA与BR共同调控拟南芥纤维素合成的分子机制研究王　昕沈阳大学独脚金内酯信号通路D53-like SMXLs下游转录因子的鉴定与功能分析王　冰中国科学院遗传与发育生物学研究所一氧化氮与细胞分裂素信号通路互作调节植物适应性生长的分子机制张燕香中国科学院遗传与发育生物学研究所转录因子GhKNOX1-1调控棉花叶片形态建成的分子机制研究肖光辉陕西师范大学拟南芥WRKY71转录因子调控叶片衰老的分子机制研究于延冲青岛农业大学RLF1亚硝基化介导生长素调控水稻侧根发育的分子机制孙爱珍中国科学院上海生命科学研究院油菜生长素合成相关基因BnaA.YUCCA6调控分枝角度的机理研究成洪涛中国农业科学院油料作物研究所类受体激酶SIT1调节水稻叶片衰老的分子机制王　耕河北师范大学拟南芥隐花色素CRY2在介导蓝光依赖的生物钟调控中的作用机理研究曹世江福建农林大学周质微丝在植物网格蛋白介导内吞中的功能研究范路生福建农林大学IDD5的O-GlcNAc糖基化修饰在赤霉素信号转导通路中的作用KihyeShin福建农林大学甲基茉莉酸响应的bHLH类转录因子在青蒿素生物合成中的调控机制研究沈　乾上海交通大学糖基转移酶UGT78H2的活性鉴定及在黑莓类黄酮代谢中的功能分析陈　清四川农业大学玉米糖基转移酶UFGT2调节黄酮合成与耐逆的功能研究李燕洁山东大学FtMYB2对荞麦类黄酮生物合成的代谢调控机制及抗逆功能研究李晓华华中农业大学金柑类黄酮糖基转移酶基因功能分析及其调控网络构建刘小刚西南大学何首乌中芪合酶、白藜芦醇羟化酶基因的功能研究生书晶广东第二师范学院拟南芥LMBD2基因突变回复mur3-3表型的分子机制丁安明中国农业科学院烟草研究所博落回根中苄基异喹啉生物碱合成、转运和积累的细胞类型特异性定位及分子机制研究郑亚杰湖南农业大学拟南芥核质反向信号参与表观遗传调控的分子机理沈　杰中国科学院植物研究所灵芝三萜酸下游合成路径关键CYP450s基因挖掘与功能分析陈方方中国科学院武汉植物园文冠果性别分化的内源激素与microRNA调控机制敖　妍北京林业大学一个CCCH锌指蛋白调控水稻雄性生殖发育中胼胝质代谢的研究方瑞秋华南农业大学转录因子TDF1对拟南芥分泌型绒毡层发育与功能的转录调控楼　悦上海师范大学。

分等级大微孔、介孔大孔

ARTICLEOPENReceived11Dec2012|Accepted16May2013|Published14Jun2013A solid with a hierarchical tetramodalmicro-meso-macro pore size distributionYu Ren1,Zhen Ma2,3,Russell E.Morris1,Zheng Liu1,Feng Jiao4,Sheng Dai3&Peter G.Bruce1Porous solids have an important role in addressing some of the major energy-related pro-blems facing society.Here we describe a porous solid,a-MnO2,with a hierarchical tetramodalpore size distribution spanning the micro-,meso-and macro pore range,centred at0.48,4.0,18and70nm.The hierarchical tetramodal structure is generated by the presence ofpotassium ions in the precursor solution within the channels of the porous silica template;thesize of the potassium ion templates the microporosity of a-MnO2,whereas theirreactivity with silica leads to larger mesopores and macroporosity,without destroying themesostructure of the template.The hierarchical tetramodal pore size distribution inﬂuencesthe properties of a-MnO2as a cathode in lithium batteries and as a catalyst,changingthe behaviour,compared with its counterparts with only micropores or bimodalmicro/mesopores.The approach has been extended to the preparation of LiMn2O4with ahierarchical pore structure.1EaStCHEM,School of Chemistry,University of St Andrews,St Andrews KY169ST,UK.2Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention(LAP3),Department of Environmental Science and Engineering,Fudan University,Shanghai200433,China.3Chemical Sciences Division,Oak Ridge National Laboratory,Oak Ridge,T ennessee37831,USA.4Department of Chemical and Biomolecular Engineering,University of Delaware,Newark,Delaware19716,USA.Correspondence and requests for materials should be addressed to P.G.B.(email:p.g.bruce@).P orous solids have an important role in addressing some of the major problems facing society in the twenty-ﬁrst century,such as energy storage,CO2sequestration,H2 storage,therapeutics(for example,drug delivery)and catalysis1–8. The size of the pores and their distribution directly affect their ability to function in a particular application2.For example, zeolites are used as acid catalysts in industry,but their micropores impose severe diffusion limitations on the ingress and egress of the reactants and the catalysed products9.To address such issues, great effort is being expended in preparing porous materials with a bimodal(micro and meso)pore structure by synthesizing zeolites or silicas containing micropores and mesopores10–17,or microporous metal–organic frameworks with ordered mesopores18.Among porous solids,porous transition metal oxides are particularly important,because they exhibit many unique properties due to their d-electrons and the variable redox state of their internal surfaces8,19–22.Here we describe theﬁrst solid(a-MnO2)possessing hierarchical pores spanning the micro,meso and macro range, centred at0.48,4.0,18and70nm.The synthesis method uses mesoporous silica as a hard template.Normally such a template generates a mesoporous solid with a unimodal23–31or,at most,a bimodal pore size distribution32–38.By incorporating Kþions in the precursor solution,within the silica template,the Kþions act bifunctionally:their size templates the formation of the micropores in a-MnO2,whereas their reactivity with silica destroys the microporous channels in KIT-6comprehensively, leading to the formation of a-MnO2containing large mesopores and,importantly,macropores,something that has not been possible by other methods.Signiﬁcantly,this is achieved without destroying the silica template by alkaline ions.The effect of the tetramodal pore structure on the properties of the material is exempliﬁed by considering their use as electrodes for lithium-ion batteries and as a catalyst for CO oxidation and N2O decomposition.The novel material offers new possibilities for combining the selectivity of small pores with the transport advantages of the large pores across a wide range of sizes.We also present results demonstrating the extension of the method to the synthesis of LiMn2O4with a hierarchical pore structure.ResultsComposition of tetramodal a-MnO2.The composition of the synthesized material was determined by atomic absorption ana-lysis and redox titration to be K0.08MnO2(the K/Mn ratio of the precursor solution was1/3).The material is commonly referred to as a-MnO2,because of the small content of Kþ19.N2sorption analysis of tetramodal a-MnO2.The tetramodal a-MnO2shows a type IV isotherm(Fig.1a).The pore size dis-tribution(Fig.1b)in the range of0.3–200nm was analysed using the density functional theory(DFT)method applied to the adsorption branch of the isotherm39–42,as this is more reliable than analysing the desorption branch43;note that this is not the DFT method used in ab initio electronic structure calculations. Plots were constructed with vertical axes representing ‘incremental pore volume’and‘incremental surface area’.Large (macro)pores can account for a signiﬁcant pore volume while representing a relatively smaller surface area and vice versa for small(micro)pores.Therefore,when investigating a porous material with a wide range of pore sizes,for example,micropore and macropore,the combination of surface area and pore volume is essential to determine the pore size distribution satisfactorily (Fig.1b).Considering both pore volume and surface area, signiﬁcant proportions of micro-,meso-and macropores are evident,with distinct maxima centred at0.70,4.0,18and70nm.To probe the size of the micropores more precisely than is possible with DFT,the Horvath–Kawazoe pore size distribution analysis was employed44.A single peak was obtained at0.48nm(Fig.1c),in good accord with the0.46-nm size of the2Â2channels of a-MnO2 (refs.19,21).The relatively small Brunauer–Emmett–Teller(BET) surface area of tetramodal a-MnO2(79–105m2gÀ1; Supplementary Table S1)compared with typical surface areas of mesoporous metal oxides(90–150m2gÀ1)45is due to the signiﬁcant proportion of macropores(which have small surface areas)and relatively large(18nm)mesopores—a typical mesoporous metal oxide has only3–4nm pores.TEM analysis of tetramodal a-MnO2.Transmission electron microscopic(TEM)data for tetramodal a-MnO2,Fig.2, demonstrates a three-dimensional pore structure with a sym-metry consistent with space group Ia3d.From the TEM data,an a0lattice parameter of23.0nm for the mesostructure could be extracted,which is in good agreement with the value obtained from the low-angle powder X-ray diffraction(PXRD)data, a0¼23.4nm(Supplementary Fig.S1a).High-resolution TEM images in Fig.2c–e demonstrate that the walls are crystalline with a typical wall thickness of10nm.The lattice spacings of0.69,0.31 and0.35nm agree well with the values of6.92,3.09and3.46Åfor the[110],[310]and[220]planes of a-MnO2(International Centre for Diffraction Data(ICDD)number00-044-0141), respectively.The wide-angle PXRD data matches well with the PXRD data of bulk cryptomelane a-MnO2(Supplementary Fig. S1b),conﬁrming the crystalline walls.The various pores in tetramodal a-MnO2can be observed by TEM directly:the0.48-nm micropores are seen in Fig.2e(2Â2 tunnels with dimensions of0.48Â0.48nm in the white box);the 4.0-nm pores are shown in Fig.2b–d;the18-nm pores are shown in Fig.2a;the70-nm pores are evident in Fig.2b(highlighted with white circles).Li intercalation.Li can be intercalated into bulk a-MnO2 (ref.46).Therefore,it is interesting to compare Li intercalation into bulk a-MnO2(micropores only)and bimodal a-MnO2 (micropores along with a single mesopore of diameter3.6nm,see Methods)with tetramodal a-MnO2(micro-,meso-and macropores).Each of the three a-MnO2materials was subjected to Li intercalation by incorporation as the positive electrode in a lithium battery,along with a lithium anode and a non-aqueous electrolyte(see Methods).The results of cycling(repeated intercalation/deintercalation of Li)the cells are shown in Fig.3. Although all exhibit good capacity to cycle Li at low rates of charge/discharge(30mA gÀ1),tetramodal a-MnO2shows sig-niﬁcantly higher capacity(Li storage)at a high rate of 6,000mA gÀ1(corresponding to charge and discharge in3min). The tetramodal a-MnO2can store three times the capacity(Li) compared with bimodal a-MnO2,and18times that of a-MnO2 with only micropores,at the high rate of intercalation/deinter-calation(Fig.3).The superior rate capability of tetramodal a-MnO2over microporous and bimodal forms may be assigned to better Liþtransport in the electrolyte within the hierarchical pore structure of tetramodal a-MnO2.The importance of elec-trolyte transport in porous electrodes has been discussed recently35,47,48and the results presented here reinforce the beneﬁcial effect of a hierarchical pore structure.Catalytic studies.CO oxidation and N2O decomposition were used as reactions to probe the three different forms of a-MnO2as catalysts(Supplementary Fig.S2).As shown in Supplementary Fig.S2a,tetramodal a-MnO2demonstrates better catalytic activity compared with only micropores or bimodal a-MnO2;thetemperature of half CO conversion (T 50)was 124°C for tetra-modal a -MnO 2,whereas microporous and bimodal a -MnO 2exhibited a T 50value of 275°C and 209°C,respectively.In the case of N 2O decomposition,a -MnO 2with only micropores demonstrated no catalytic activity in the range of 200–400°C,in accord with a previous report 49.Tetramodal and bimodal a -MnO 2showed catalytic activity and reached 32%and 20%of N 2O conversion,respectively,at a reaction temperature of 400°C.The differences in catalytic activity are related to the differences in the material.A detailed study focusing on the catalytic activity alonewould be necessary to demonstrate which speciﬁc features of the textural differences (pore size distribution,average manganese oxidation state,K þand so on)between the different MnO 2materials are responsible for the differences in behaviour.However,the preliminary results shown here do illustrate that such differences exist.Porous LiMn 2O 4.To demonstrate the wider applicability of the synthesis method,LiMn 2O 4with a hierarchical pore structurewas1801601401201008060402000.00.20.40.60.81.0V (c m 3 g –1)Pore diameter (nm)0.0120.0100.0080.0060.0040.0020.000I n c r e m e n t a l p o r e v o l u m e (c m 3 g –1)Pore width (nm)I n c r e m e n t a l s u r f a c e a r e a (m 2 g –1)I n c r e m e n t a l s u r f a c e a r e a (m 2 g –1)P /P 0Figure 1|N 2sorption analysis of tetramodal a -MnO 2.(a )N 2adsorption–desorption isotherms,(b )DFT pore size distribution and (c )Horvath–Kawazoe pore size distribution from N 2adsorption isotherm for tetramodal a -MnO 2.Figure 2|TEM images of tetramodal a -MnO 2.TEM images along (a )[100]direction,showing 18nm mesopores (scale bar,50nm);(b )4.0and 70nm pores (70nm pores are highlighted by white circles;scale bar,100nm);(c –e )high-resolution (HRTEM)images of tetramodal a -MnO 2showing 4.0and 0.48nm pores (scale bar,10nm).Inset is representation of a -MnO 2structure along the c axis,demonstrating the 2Â2micropores as shown in the HRTEM (white box)in e .Purple,octahedral MnO 6;red,oxygen;violet,potassium.synthesized in a way similar to that of tetramodal a -MnO 2.The main difference is the use of LiNO 3instead of KNO 3(see Methods).In this case,Li þreacts with the silica template col-lapsing/blocking the microporous channels in the KIT-6and resulting in the large mesopores and macropores (17and 50nm)in the LiMn 2O 4obtained.The use of Li þinstead of the larger K þdeters the formation of micropores because Li þis too small.TEM analysis illustrates the hierarchical pore structure of LiMn 2O 4(Supplementary Fig.S3):4.0nm pores are evident in Supplementary Fig.S3b;17nm pores in Supplementary Fig.S3a;and 50nm pores in Supplementary Fig.S3b (highlighted with white circles).The d-spacing of 0.47nm in the high-resolution TEM image (Supplementary Fig.S3c)is in good accordance with the values of 0.4655nm for the [111]planes of LiMn 2O 4(ICDD number 00-038-0789)and with the wide-angle PXRD data (Supplementary Fig.S4).The original DFT pore size distribution analysis from N 2sorption (adsorption branch)gives three pore sizes in the range of 1–100nm centred at 4.0,17and 50nm (Supplementary Fig.S5).A more in-depth presentation of the results for LiMn 2O 4will be given in a future paper;preliminary results presented here illustrate that the basic method can be applied beyond a -MnO 2.DiscussionTurning to the synthesis of the tetramodal a -MnO 2,the details are given in the Methods section.Hard templating using silica templates,such as KIT-6,normally gives rise to materials with unimodal or,at most,bimodal mesopore structures,and in the latter case the smaller mesopores dominate over the larger mesopores 8,32,35.Alkali ions are excellent templates for micropores in transition metal oxides 19,21,but they have been avoided in nanocasting from silica templates because of concerns that they would react with and,hence,destroy thesilica20018016014012010080604020D i s c h a r g e c a p a c i t y (m A h g –1)0Cycle numberx in Li x MnO 2Figure 3|Electrochemical behaviour of different a -MnO 2.Capacity retention for tetramodal a -MnO 2cycled at 30(empty blue circles)and 6,000mA g À1(ﬁlled blue circles);bulk a -MnO 2cycled at 30(empty red squares)and 6,000mA g À1(ﬁlled red squares);bimodal a -MnO 2cycled at 30(empty black triangle)and 6,000mA g À1(ﬁlled blacktriangles).18 nm pores70 nm poresTwo sets of mesoporeschannels connecting both sets of mesoporesEtching of silica Etching of silica Etching of silica template2discontinuously within one set of the KIT-6mesoporesFigure 4|Formation mechanism of meso and macropores in tetramodal a -MnO 2.When both KIT-6mesochannels are occupied by a -MnO 2and then the silica between them etched away,the remaining pore is 4nm (centre portion of ﬁgure).When a -MnO 2grows in only one set of mesochannels and then the KIT-6is dissolved away,the remaining metal oxide has 18nm pores (upper portion of ﬁgure).The comprehensive destruction of the microchannels in KIT-6by K þleads to a -MnO 2growing in only a proportion of one set of the KIT-6mesochannels,resulting in the formation of B 70nm pores (lower portion of ﬁgure).template50.Here,not only have alkali ions been used successfully in precursor solutions without destroying the template mesostructure but they give rise to macropores in the a-MnO2, thus permitting the synthesis of a tetramodal,micro-small,meso-large,meso-macro pore structure.Synthesis begins by impregnating the KIT-6silica template with a precursor solution containing Mn2þand Kþions.On heating,the Kþions template the formation of the micropores in a-MnO2,as the latter forms within the KIT-6template.KIT-6 consists of two interpenetrating mesoporous channels linked by microporous channels51–53.The branches of the two different sets of mesoporous channels in KIT-6are nearest neighbours separated by a silica wall of B4nm53;therefore,when both KIT-6mesochannels are occupied by a-MnO2and the silica between them etched away,the remaining pore is4nm(see centre portion of Fig.4).It has been shown previously,by a number of authors,that by varying the hydrothermal conditions used to prepare the KIT-6,the proportion of the microchannels can be decreased to some extent,thus making it difﬁcult to simultaneouslyﬁll the neighbouring KIT-6mesoporous channels by the precursor solution of the target mesoporous metal oxide33–35.As a result,the target metal oxide grows in only one set of mesochannels of the KIT-6host but not both.When the KIT-6is dissolved away,the remaining metal oxide has B18nm pores,because the distance between adjacent branches of the same KIT-6mesochannels is greater than between the two different mesochannels in KIT-6.Here we propose that the Kþions have a similar effect on the KIT-6to that of the hydrothermal synthesis,but by a completely different mechanism.Reaction between the Kþions in the precursor solution with the silica during calcination results in the formation of Kþ-silicates,which cause collapse or blocking of the microporous channels in KIT-6,such that the a-MnO2grows in one set of the KIT-6mesochannels,giving rise to18nm pores in a-MnO2when the silica is etched away,see top portion of Fig.4. However,the reaction between Kþand the silica is more severe than the effect of varying the hydrothermal treatment.In the former case,the KIT-6microchannels are so comprehensively destroyed that the proportion of the large(18nm)to smaller (4nm)mesopores is greater than can be achieved by varying hydrothermal conditions.The comprehensive destruction of the microchannels in KIT-6by Kþ,perhaps augmented by some minor degradation of parts of the mesochannels,leads to a-MnO2 growing in only a proportion of one set of the KIT-6 mesochannels,resulting in the formation of B70nm pores in a-MnO2,see lower portion of Fig.4.In summary,the Kþreactivity with the silica goes beyond what can be achieved by varying the conditions of hydrothermal synthesis and is responsible for generating the tetramodal pore size distribution reported here. The mechanism of pore formation in a-MnO2by reaction between Kþand the silica template is supported by several ﬁndings.First,by the lower K/Mn molar ratio of theﬁnal tetramodal a-MnO2product(0.08)compared with the starting materials(0.33)implies that some of the Kþions in the impregnating solution have reacted with the silica.Second, support for collapse/blocking of the microporous channels in KIT-6due to reaction with Kþwas obtained by comparing the texture of KIT-6impregnated with an aqueous solution contain-ing only KNO3and calcined at300and500°C.The micropore volume in KIT-6is the greatest,with no KNO3in the solution;it then decreases continuously as the calcination temperature and calcination time is increased,such that after2and5h at500°C the micropore volume has decreased to zero(Supplementary Fig. S6).Third,we prepared tetramodal a-MnO2using a similar synthetic procedure to that described in the Methods section, except that this time we used a covered tall crucible for the calcination step.Sun et al.54have shown that using a covered,tall crucible when calcining results in porous metal oxides with much larger particle sizes.If the70-nm pores had arisen simply from the gaps between the particles,then the pore size would have changed;in contrast,it remained centred at70nm, Supplementary Fig.S7,consistent with the70-nm pores being intrinsic to the materials and arising from reaction with the Kþas described above.Fourth,if the synthesis of MnO2is carried out using the KIT-6template but in the absence Kþions,then the DFT pore size distribution shown in Supplementary Fig.S8is obtained.The0.48-and70-nm pores are now absent,but the4-and18-nm pores remain.This demonstrates the key role of Kþin the formation of the smallest and largest pores and,hence,in generating the tetramodal pore size distribution.The absence of Kþmeans that there is nothing to template the0.48nm pores and so a-MnO2is not formed;the b-polymorph is obtained instead.The absence of Kþalso means that the microchannels in the KIT-6template remain intact,resulting in no70nm pores and the dominance of the4-nm pores compared with the 18-nm pores.The hierarchical pore structure can be varied systematically by controlling the synthesis conditions,in particular the Kþ/Mn ratio of the precursor solution.A range of Kþ/Mn ratios,1/5,1/3and1/2,gave rise to a series of pore size distributions,in which the pore sizes remained the same but the relative proportions of the different pores varied (Supplementary Table S1).The higher the Kþ/Mn ratio,the greater the proportion of macropores and large mesopores.This is in accord with expectations,as the higher the Kþconcentra-tion in the precursor solution the greater the collapse/blocking of the microporous channels in the KIT-6(as noted above),and hence the greater the proportion of macropores and large mesopores.Indeed,these results offer further support for the mechanism of pore size distribution arising from reaction between Kþand the silica template.In conclusion,tetramodal a-MnO2,theﬁrst porous solid with a tetramodal pore size distribution,has been synthesized.Its hierarchical pore structure spans the micro,meso and macropore range between0.3and200nm,with pore dimensions centred at 0.48,4.0,18and70nm.Key to the synthesis is the use of Kþions that not only template the formation of micropores but also react with the silica template,therefore,breaking/blocking the micro-porous channels in the silica template far more comprehensively than is possible by varying the hydrothermal synthesis conditions, to the extent that macropores are formed,and without destroying the silica mesostructure by alkali ions,as might have been expected.The resulting hierarchical tetramodal structure demon-strates different behaviours compared with microporous and bimodal a-MnO2as a cathode material for Li-ion batteries,and when used as a catalyst for CO oxidation and N2O decomposi-tion.The method has been extended successfully to the preparation of hierarchical LiMn2O4.MethodsSynthesis.Tetramodal a-MnO2(surface area96m2gÀ1,K0.08MnO2)was pre-pared by two-solvent impregnation55using Kþand mesoporous silica KIT-6as the hard template.KIT-6was prepared according to a previous report (hydrothermal treatment at100°C)51.In a typical synthesis of tetramodal a-MnO2, 7.53g of Mn(NO3)2Á4H2O(98%,Aldrich)and1.01g of KNO3(99%,Aldrich)were dissolved in B10ml of water to form a solution with a molar ratio of Mn/K¼3.0. Next,5g of KIT-6was dispersed in200ml of n-hexane.After stirring at room temperature for3h,5ml of the Mn/K solution was added slowly with stirring.The mixture was stirred overnight,ﬁltered and dried at room temperature until a completely dried powder was obtained.The sample was heated slowly to500°C (1°C minÀ1),calcined at that temperature for5h with a cover in a normal crucible unless is speciﬁed54and the resulting material treated three times with a hot aqueous KOH solution(2.0M),to remove the silica template,followed by washing with water and ethanol several times,and then drying at60°C.Bimodal a-MnO2(surface area58m2gÀ1,K0.06MnO2)with micropore and a single mesopore size of3.6nm was prepared by using mesoporous silica SBA-15as a hard template.The SBA-15was prepared according to a previous report56.Bulk a-MnO2(surface area8m2gÀ1,K0MnO2)was prepared by the reaction between325mesh Mn2O3(99.0%,Aldrich)and6.0M H2SO4solution at80°C for 24h,resulting in the disproportionation of Mn2O3into a soluble Mn2þspecies and the desired a-MnO2product46.Treatment of KIT-6with KNO3was carried out as follows:1.01g of KNO3was dissolved in B15ml of water to form a KNO3solution.Five grams of mesoporous KIT-6was dispersed in200ml of n-hexane.After stirring at room temperature for 3h,5ml of KNO3solution was added slowly with stirring.The mixture was stirred overnight,ﬁltered and dried at room temperature until a completely dried powder was obtained.The sample was heated slowly to300or500°C(1°C minÀ1), calcined at that temperature for5h and the resulting material was washed with water and ethanol several times,and then dried at60°C overnight.The synthesis method for hierarchical porous LiMn2O4was similar to that of tetramodal a-MnO2.The main difference was to use1.01g of LiNO3instead of KNO3.After impregnation into KIT-6,calcination and silica etching,porous LiMn2O4was obtained.Characterization.TEM studies were carried out using a JEOL JEM-2011, employing a LaB6ﬁlament as the electron source,and an accelerating voltage of 200keV.TEM images were recorded by a Gatan charge-coupled device camera in a digital format.Wide-angle PXRD data were collected on a Stoe STADI/P powder diffractometer operating in transmission mode with Fe K a1source radiation(l¼1.936Å).Low-angle PXRD data were collected using a Rigaku/MSC,D/max-rB with Cu K a1radiation(l¼1.541Å)operating in reﬂection mode with a scintillation detector.N2adsorption–desorption analysis was carried out using a Micromeritics ASAP2020.The typical sample weight used was100–200mg. The outgas condition was set to300°C under vacuum for2h,and all adsorption–desorption measurements were carried out at liquid nitrogen tem-perature(À196°C).The original DFT method for the slit pore geometry was used to extract the pore size distribution from the adsorption branch usingthe Micromeritics software39–42.A Horvath–Kawazoe method was used to extract the microporosity44.Mn and K contents were determined by chemical analysis using a Philips PU9400X atomic adsorption spectrometer.The average oxidation state of framework manganese in a-MnO2samples was determined by a redoxtitration method57.Electrochemistry.First,the cathode was constructed by mixing the active material (a-MnO2),Kynar2801(a copolymer based on polyvinylideneﬂuoride),and Super S carbon(MMM)in the weight ratio80:10:10.The mixture was cast onto Al foil (99.5%,thickness0.050mm,Advent Research Materials,Ltd)from acetone using a Doctor-Blade technique.After solvent evaporation at room temperature and heating at80°C under vacuum for8h,the cathode was assembled into cells along with a Li metal anode and electrolyte(Merck LP30,1M LiPF6in1:1v/v ethylene carbonate/dimethyl carbonate).The cells were constructed and handled in anAr-ﬁlled MBraun glovebox(O2o0.1p.p.m.,H2O o0.1p.p.m.).Electrochemical measurements were carried out at30°C using a MACCOR Series4200cycler.Catalysis.Catalytic CO oxidation was tested in a plug-ﬂow microreactor(Alta-mira AMI200).Fifty milligrams of catalyst was loaded into a U-shaped quartz tube (4mm i.d.).After the catalyst was pretreated inﬂowing8%O2(balanced with He) at400°C for1h,the catalyst was then cooled down,the gas stream switched to1% CO(balanced with air)and the reaction temperature ramped using a furnace(at a rate of1°C minÀ1above ambient temperature)to record the light-off curve.The ﬂow rate of the reactant stream was37cm3minÀ1.A portion of the product stream was extracted periodically with an automatic sampling valve and was analysed using a dual column gas chromatograph with a thermal conductivity detector.To perform N2O decomposition reaction testing,0.5g catalyst was packed into a U-shaped glass tube(7mm i.d.)sealed by quartz wool,and pretreated inﬂowing 20%O2(balance He)at400°C for1h(ﬂow rate:50cm3minÀ1).After cooling to near-room temperature,a gas stream of0.5%N2O(balance He)ﬂowed through the catalyst at a rate of60cm3minÀ1,and the existing stream was analysed by a gas chromatograph(Agilent7890A)that separates N2O,O2and N2.The reaction temperature was varied using a furnace,and kept at100,150,200,250,300,350 and400°C for30min at each reaction temperature.The N2O conversion determined from GC analysis was denoted as X¼([N2O]in—[N2O]out)/[N2O]inÂ100%.References1.Corma,A.From microporous to mesoporous molecular sieve materials andtheir use in catalysis.Chem.Rev.97,2373–2419(1997).2.Davis,M.E.Ordered porous materials for emerging applications.Nature417,813–821(2002).3.Taguchi,A.&Schu¨th,F.Ordered mesoporous materials in catalysis.Micro.Meso.Mater.77,1–45(2005).4.Fe´rey,G.Hybrid porous solids:past,present,future.Chem.Soc.Rev.37,191–214(2008).5.Bruce,P.G.,Scrosati,B.&Tarascon,J.M.Nanomaterials for rechargeablelithium batteries.Angew.Chem.Int.Ed.47,2930–2946(2008).6.Zhai,Y.et al.Carbon materials for chemical capacitive energy storage.Adv.Mater.23,4828–4850(2011).7.Tu¨ysu¨z,H.&Schu¨th,F.in Advances in Catalysis.Chapter Two Vol.55pp127–239(Academic Press,2012).8.Ren,Y.,Ma,Z.&Bruce,P.G.Ordered mesoporous metal oxides:synthesis andapplications.Chem.Soc.Rev.41,4909–4927(2012).9.Corma,A.State of the art and future challenges of zeolites as catalysts.J.Catal.216,298–312(2003).10.Liu,Y.,Zhang,W.&Pinnavaia,T.J.Steam-stable aluminosilicatemesostructures assembled from zeolite type Y seeds.J.Am.Chem.Soc.122, 8791–8792(2000).11.Meng,X.J.,Nawaz,F.&Xiao,F.S.Templating route for synthesizingmesoporous zeolites with improved catalytic properties.Nano Today4,292–301(2009).12.Lopez-Orozco,S.,Inayat,A.,Schwab,A.,Selvam,T.&Schwieger,W.Zeoliticmaterials with hierarchical porous structures.Adv.Mater.23,2602–2615(2011).13.Na,K.et al.Directing zeolite structures into hierarchically nanoporousarchitectures.Science333,328–332(2011).14.Chen,L.-H.et al.Hierarchically structured zeolites:synthesis,mass transportproperties and applications.J.Mater.Chem.22,17381–17403(2012).15.Tsapatsis,M.Toward high-throughput zeolite membranes.Science334,767–768(2011).16.Zhang,X.et al.Synthesis of self-pillared zeolite nanosheets by repetitivebranching.Science336,1684–1687(2012).17.Jiang,J.et al.Synthesis and structure determination of the hierarchicalmeso-microporous zeolite ITQ-43.Science333,1131–1134(2011).18.Zhao,Y.et al.Metal–organic framework nanospheres with well-orderedmesopores synthesized in an ionic liquid/CO2/surfactant system.Angew.Chem.Int.Ed.50,636–639(2011).19.Feng,Q.,Kanoh,H.&Ooi,K.Manganese oxide porous crystals.J.Mater.Chem.9,319–333(1999).20.Tiemann,M.Repeated templating.Chem.Mater.20,961–971(2008).21.Suib,S.L.Structure,porosity,and redox in porous manganese oxide octahedrallayer and molecular sieve materials.J.Mater.Chem.18,1623–1631(2008).22.Zheng,H.et al.Nanostructured tungsten oxide–properties,synthesis,andapplications.Adv.Funct.Mater.21,2175–2196(2011).ha,S.C.&Ryoo,R.Synthesis of thermally stable mesoporous cerium oxidewith nanocrystalline frameworks using mesoporous silica templates.Chem.Commun.39,2138–2139(2003).24.Tian,B.Z.et al.General synthesis of ordered crystallized metal oxidenanoarrays replicated by microwave-digested mesoporous silica.Adv.Mater.15,1370–1374(2003).25.Zhu,K.K.,Yue,B.,Zhou,W.Z.&He,H.Y.Preparation of three-dimensionalchromium oxide porous single crystals templated by mun.39,98–99(2003).26.Tian,B.Z.et al.Facile synthesis and characterization of novel mesoporous andmesorelief oxides with gyroidal structures.J.Am.Chem.Soc.126,865–875 (2004).27.Jiao,F.,Shaju,K.M.&Bruce,P.G.Synthesis of nanowire and mesoporouslow-temperature LiCoO2by a post-templating reaction.Angew.Chem.Int.Ed.44,6550–6553(2005).28.Rossinyol,E.et al.Nanostructured metal oxides synthesized by hard templatemethod for gas sensing applications.Sens.Actuator B Chem.109,57–63(2005).29.Shen,W.H.,Dong,X.P.,Zhu,Y.F.,Chen,H.R.&Shi,J.L.MesoporousCeO2and CuO-loaded mesoporous CeO2:Synthesis,characterization,and CO catalytic oxidation property.Micro.Meso.Mater.85,157–162(2005).30.Wang,Y.Q.et al.Weakly ferromagnetic ordered mesoporous Co3O4synthesized by nanocasting from vinyl-functionalized cubic Ia3d mesoporous silica.Adv.Mater.17,53–56(2005).31.Ren,Y.et al.Ordered crystalline mesoporous oxides as catalysts for COoxidation.Catal.Lett.131,146–154(2009).32.Jiao,K.et al.Growth of porous single-crystal Cr2O3in a3-D mesopore system.mun.41,5618–5620(2005).33.Rumplecker,A.,Kleitz,F.,Salabas,E.L.&Schu¨th,F.Hard templating pathwaysfor the synthesis of nanostructured 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ＴｈｅｓｔｕｄｙｏｎｍｅｓｏｐｏｒｏｕｓｍｏｌｅｃｕｌａｒｓｉｅｖｅＳＢＡ－１５ｔａｂｌｅｔｃｏａｔｅｄｗｉｔｈＨＰＭＣＡＳａｓａｄｒｕｇｒｅｌｅａｓｅｃａｒｒｉｅｒｆｏｒ６－ｍｅｒｃａｐｔｏｐｕｒｉｎｅ
ｃｌｕｄｉｎｇｓｉｍｕｌａｔｅｄｉｎｔｅｓｔｉｎａｌｌｆｕｉｄ（ＳＩＦ，ｐＨ一７．４）ａｎｄｓｉｍｕｌａｔｅｄｇａｓｔｒｉｃｆｌｕｉｄ（ＳＧＦ，ｐＨ一１．２）ｗｅｒｅｕｓｅｄｔＯｉｎｖｅｓｔｉｇａｔｅｔｈｅｄｒｕｇｒｅ —
够迅速溶于肠液，对６－ＭＰ释放速度的影响较小。药物释放４ｈ后，释放率可达到８５．４。同时，发现膜的干燥温度影响６一ＭＰ的释放行为，干燥温度越高，药物系统在模拟胃液中的缓释效果越强。结论
所得产物过滤后用去离子水和无水乙醇反复冲洗直至滤液的ph为70然后样品在80下干燥最后将样品在索氏抽提器中用无水乙醇萃取48h80下烘干即得纯硅基介孔sba15122药物吸附分别取10gsba15粉末和15g6巯基嘌呤加入到250ml的去离子水和甲醇的等体积混合溶剂中
重庆医学２０１３年１月第４２卷第３期
释材料。
ＨＰＭＣＡＳ／ＳＢＡ－１５是一种良好的ｐＨ敏感型药物缓
关键词：６－巯基嘌呤；介孔分子筛；ｐＨ敏感；药物缓释；醋酸羟丙基甲基纤维素琥珀酸酯ｄｏｉ：１０．３９６９／ｊ．ｉｓｓｎ．１６７１ — ８３４８．２０１３．０３．００５文献标识码：Ａ文章编号：１６７１ — ８３４８（２０１３）０３ — ０２５１－０４
ＣｈｅｎＺｈｉ，Ｗ“Ｄｕｄｕ，ＨＹａｎｇｆｅｎ，ＣｈｅｎＷＭ＿，ｎｇ。（１．ＣｅｎｔｅｒｏｆＡｎａｌｙｓｉｓ；２．ＳｃｈｏｏｌｏｆＰｈａｒｍａｃｙ，ＧｕａｎｇｄｏｎｇＭｅｄｉｃａｌＣｏｌｌｅｇｅ，Ｄｏｎｇｇｕａｎ，Ｇｕａｎｇｄｏｎｇ５２３８０８，Ｃｈｉｎａ）Ａｂｓｔｒａｃｔ：ＯｂｊｅｃｔｉｖｅＴｏｐｒｅｐａｒｅａｐＨ— ｓｅｎｓｉｔｉｖｅｄｒｕｇｒｅｌｅａｓｅｓｙｓｔｅｍｈｙｄｒｏｘｙｐｒｏｐｙｌｍｅｔｈｙｌｃｅ１ｌｕｌｏｓｅａｃｅｔａｔｅｓｕｃｃｉｎａｔｅ（ＨＰＭ— ＣＡＳ）／ＳＢＡ－１５．ＭｅｔｈｏｄｓＨＰＭＣＡＳ／ＳＢＡ— ｌ５ｗａｓｓｙｎｔｈｅｓｉｚｅｄｂｙｃｏａｔｉｎｇＨＰＭＣＡＳｏｎ８ＳＢＡ一１５．Ｔｗｏｋｉｎｄｓｏｆｒｅｌｅａｓｅｆｌｕｉｄｓ。ｉｎ－
２５ｌ
・
论
著・
６一巯基嘌呤在ＨＰＭＣＡＳ包覆介孔分子筛ＳＢＡ一１５药物系统中的缓释行为研究
陈稚，吴都督，何仰芬。，陈文芳
（广东医学院：１．分析中心；２．药学院，广东东莞５２３８０８）
察ＨＰＭｃＡｓ／ｓＢＡ一１５系统在模拟胃液中（ｐＨ一１．２）和模拟肠液中（ｐＨ一７．５）的释放行为。结果在模拟胃液中（ｐＨ＝１．２），
ＨＰＭＣＡＳ能明显地延缓６－ＭＰ的释放速度。药物释放４ｈ后，其释放率仅为１２．５。而在模拟肠液中（ｐＨ一７．５），ＨＰＭＣＡＳ能
ｌｅａｓｅｂｅｈａｖｉｏｒｏｆｔｈｅＨＰＭＣＡＳ／ＳＢＡ：１５ｓｙｓｔｅｍ．ＲｅｓｕｌｔｓＩｎＳＧＦ（ｐＨ— １．２），ＨＰＭＣＡＳｃｏａｔｉｎｇｍａｔｅｒｉａｌｓｃｏｕｌｄｅｆｆｅｃｔｕａｌｌｙｄｅｌａｙ
摘要：目的制备ｐＨ敏感的药物控释系统醋酸羟丙基甲基纤维素琥珀酸酯（ＨＰＭＣＡＳ）／ＳＢＡ－１５。方法将肠溶性的
ＨＰＭＣＡＳ作为包覆材料，包覆于负载了抗癌药物６一巯基嘌呤（６－ＭＰ）的ＳＢＡ－１５介孔分子筛表面，制备ＨＰＭＣＡｓ／ｓＢＡ一１５，并考
ｔｈｅｒｅｌｅａｓｅｒａｔｅｏｆ６－ＭＰ．Ａｆｔｅｒ４ｈｏｕｒｓｏｆｄｒｕｇｒｅｌｅａｓｅ，ｔｈｅｒｅｌｅａｓｅｒａｔｅｗａｓ１２．５．Ｈｏｗｅｖｅｒ，ｉｎＳＩＦ（ＰＨ一７．５），ｎｏｄｉｓｔｉｎｃｔｉｎｆｌｕ～