A Novel Hybrid of Chloroquine and Primaquine Linked by Gold(I): Multitarget and Multiphase Antiplasmodial Agent

Plasmodium parasites kill 435 000 people around the world every year due to unavailable vaccines, a limited arsenal of antimalarial drugs, delayed treatment, and the reduced clinical effectiveness of current practices caused by drug resistance. Therefore, there is an urgent need to discover and develop new antiplasmodial candidates. In this work, we present a novel strategy to develop a multitarget metallic hybrid antimalarial agent with possible dual efficacy in both sexual and asexual erythrocytic stages. A hybrid of antimalarial drugs (chloroquine and primaquine) linked by gold(I) was synthesized and characterized by spectroscopic and analytical techniques. The CQPQ-gold(I) hybrid molecule affects essential parasite targets, it inhibits β-hematin formation and interacts moderately with the DNA minor groove. Its interaction with PfTrxR was also examined in computational modeling studies. The CQPQ-gold(I) hybrid displayed an excellent in vitro antimalarial activity against the blood-stage of Plasmodium falciparum and liver-stage of Plasmodium berghei and efficacy in vivo against P. berghei, thereby demonstrating its multiple-stage antiplasmodial activity. This metallic hybrid is a promising chemotherapeutic agent that could act in the treatment, prevention, and transmission of malaria.     

含羧酸基的功能化离子液体催化合成氯乙酸异丙酯

将合成的羧酸基功能化离子液体用于氯乙酸和异丙醇的酯化反应,考察了不同功能化离子液体的催化性能、不同的反应条件、反应结束后产物的分离和离子液体的循环使用。结果表明,以[C1imCH2COOH]HSO4为催化剂,n(氯乙酸)∶n(异丙醇)∶n(离子液体)=5∶5∶1,反应温度为60℃,反应时间为3 h的条件下,异丙醇的转化率为90.6%,氯乙酸异丙酯的选择性达到100%。反应结束后产物和离子液体分层明显,通过简单的倾倒就可以分离产物。分离后的催化剂重复使用5次,催化剂活性基本不变。     

Synthesis and application of Br?nsted-Lewis acidic ionic liquids

Br?nsted-Lewis双酸性离子液体同时具备B酸性和L酸性,是融合双酸性固体酸与离子液体的特征发展起来的一类新型催化剂。本文综述了近年来B-L双酸性离子液体的合成、表征及催化剂应用等方面的进展,在此基础上,总结出B-L双酸性离子液体的三个特征。其一,利用一种催化剂就可以催化分别需要B酸和L酸催化的分步反应,使反应一锅化,简洁可控。其二,B酸性和L酸性之间存在相互增强的协同作用,使其具有更好的催化性能,或可提高反应转化率或产物选择性。其三,液体催化剂在传质和扩散等方面均优于双酸性固体酸。上述特征使B-L双酸性离子液体替代并超越传统酸性催化剂成为可能,在工业应用中显示良好的发展前景。     

离子液体催化二氧化碳合成环状碳酸酯的研究进展

概述了以离子液体作为催化剂或作为反应介质,用CO2合成环状碳酸酯的研究进展。离子液体是固定CO2产生环状碳酸酯的适宜催化剂和溶剂,离子液体的话性可以通过添加本身并无活性或低活性的Lewis酸性金属卤化物或金属配合物得到改善。使用离子液体使得合成过程变得更加绿色和简单,因为产品易分离,催化剂可以循环利用,而且不必使用挥发性有害的有机溶剂。     

绿色溶剂离子液体在化学反应中的应用

离子液体用作化学反应的溶剂，对提高化学反应速率、选择性，或实现催化剂的循环利用及产物分离都具有明显的优势，而且对许多化学反应，离子液体还具有催化功能。这对于开发新的化学工艺，实现绿色化学过程具有重要的意义。本文主要介绍离子液体在化学反应中的应用最新进展及其工业化前景。     

Catalytic applications of immobilized ionic liquids for synthesis of cyclic carbonates from carbon dioxide and epoxides

The catalytic applicability of ionic liquids immobilized on various support materials such as silica, polystyrene and biopolymers in the cycloaddition of carbon dioxide with epoxides is reviewed in this work. Comparisons of the catalytic efficiency of these various catalysts have been done from the aspect of turnover number and reusability. The studies revealed that ionic liquids or support materials possessing hydrogen bonding capable groups exhibited enhanced catalytic activity towards cyclic carbonate synthesis. Moreover, the increased quest towards environmentally benign materials has renewed the search for biocompatible materials as support for ionic liquids.     

4,9-Diaminoacridines and 4-Aminoacridines as Dual-Stage Antiplasmodial Hits

Multi-stage drugs have been prioritized in antimalarial drug discovery, as targeting more than one process in the Plasmodium life cycle is likely to increase efficiency, while decreasing the chances of emergence of resistance by the parasite. Herein, we disclose two novel acridine-based families of compounds that combine the structural features of primaquine and chloroquine. Compounds prepared and studied thus far retained the in vitro activity displayed by the parent drugs against the erythrocytic stages of chloroquine-sensitive and -resistant Plasmodium falciparum strains, and against the hepatic stages of Plasmodium berghei, hence acting as dual-stage antiplasmodial hits.     

Amino acid ionic liquids

The preparation of ionic liquids derived from amino acids, and their properties, are outlined. Since amino acids have both a carboxylic acid residue and an amino group in a single molecule, they can be used as either anions or cations. These groups are also useful in their ability to introduce functional group(s). Twenty different natural amino acids were used as anions, to couple with the 1-ethyl-3-methylimidazolium cation. The salts obtained were all liquid at room temperature. The properties of the resulting ionic liquids (AAILs) depend on the side groups of the amino acids involved. These AAILs, composed of an amino acid with some functional groups such as a hydrogen bonding group, a charged group, or an aromatic ring, had an increased glass transition (or melting) temperature and/or higher viscosity as a result of additional interactions among the ions. Viscosity is reduced and the decomposition temperature of imidazolium-type salts is improved by using the tetrabutylphosphonium cation. The chirality of AAILs was maintained even upon heating to 150 degrees C after acetylation of the free amino group. The amino group was also modified to introduce a strong acid group so as to form hydrophobic and chiral ionic liquids. Unique phase behavior of the resulting hydrophobic ionic liquids and water mixture is found; the mixture is clearly phase separated at room temperature, but the solubility of water in this IL increases upon cooling, to give a homogeneous solution. This phase change is reversible, and separation occurs again by raising the temperature a few degrees. It is extraordinary for an IL/water mixture to display such behavior with a lower critical solution temperature. Some likely applications are proposed for these amino acid derived ionic liquids.     

The influence of the monomer and the ionic liquid on the electrochemical preparation of polythiophene

Thiophene, bithiophene and terthiophene have been electropolymerised using ionic liquids as the growth medium and the supporting electrolyte. Both imidazolium and pyrrolidinium-based ionic liquids were used to assess the influence of the nature of the ionic liquid on the morphology and electrochemical activity of the conducting polymers. The pyrrolidinium-based ionic liquid produced slightly smoother films for all the thiophene species studied. A number of the polymers displayed multiple redox peaks, the possible origins of which are discussed. Both the ionic liquid and the choice of monomer had a significant influence on the polymer produced.     

Solvent-free synthesis of benzoic esters and benzyl esters in novel Brønsted acidic ionic liquids under microwave irradiation

Fischer esterifications of benzoic acid with a variety of alcohols and a variety of acids with benzyl alcohol could be promoted by four novel Brønsted acidic ionic liquids a–d that bear a benzyl on the imidazolium or pyridinium cation. The reactions were carried out smoothly without the need of added catalyst with good to excellent isolated yields (77–98.5%) under solvent-free microwave irradiation conditions in the presence of 50 mol% ionic liquids. These ionic liquids could be recovered easily and recycled three times without any significant loss in their catalytic activity.     

Catalytic performance of sulfonic acid functionalized ionic liquids on preparation of biodiesel

通过1-烯丙基咪唑与1,4-丁基磺酸内酯反应制备的两性离子分别与硫酸、三氟甲基磺酸、磷钨酸、磷钼酸和硅钨酸直接反应制备了5种磺酸功能化离子液体。采用¹H NMR、FTIR、TG/DTA等技术手段对其结构及热稳定性进行了表征。最后通过催化油酸与甲醇酯化反应制生物柴油过程对催化剂的催化活性和重复使用性进行了评价。结果表明,5种离子液体均具有高催化活性（高于浓硫酸）,并且重复使用4次后,催化活性基本保持不变。3种杂多酸离子液体不溶于产物,以固态形式与产物混合,为其回收和重复利用提供了有利条件。     

离子液体对白炭黑填充SBR性能的影响

研究了两种离子液体对白炭黑填充丁苯橡胶性能的影响,并与未改性白炭黑填充丁苯橡胶进行了对比。实验结果表明,与空白样相比,离子液体的加入可以改善白炭黑的分散,抑制白炭黑填料网络的形成,增强白炭黑与丁苯胶的相互作用,促进硫化反应,使焦烧时间tc₁₀、正硫化时间tc₉₀大大缩短,提高硫化胶的交联密度,同时赋予硫化胶较高的拉伸强度、撕裂强度。且综合比较,两种离子液体中,BMI比AMI改性效果更好。     

Characteristics of protic ionic liquids based on triethanolammonium salts of biologically active carboxylic acids and their impact on the growth properties of the <Emphasis Type="Italic">Rhizopus oryzae</Emphasis> fungus

A series of protic alkanolammonium ionic liquids (ILs) based on triethanolammonium salts (protatranes) of biologically active carboxylic acids (cinnamic, benzoic, oxalic, malonic, succinic, salicylic, and citric acids) is synthesized and characterized. Their biological activity against the Rhizopus oryzae F-814 fungus is studied. The presence of ionic liquids in a culture medium gives rise to the biomass of the fungus growing by 8 to 24%, depending on the salt concentration and its composition.     

离子液体催化苯与苄氯的烷基化合成二苯甲烷

考察了离子液体催化Friedel-Crafts苄基化制备二苯甲烷,同时考察了AlCl3的摩尔分数、离子液体用量及不同离子液体等因素对苯与苄氯烷基化反应的影响。实验结果表明,离子液体的催化活性与其酸强度密切相关,酸性条件下离子液体才显示催化活性。AlCl3摩尔分数为66.7%,催化剂(离子液体)用量3.3g、反应温度80℃及常压反应条件下,1-丁基-3-甲基氯咪唑,N-丁基氯吡啶与AlCl3形成的离子液体具有较高的二苯甲烷选择性,分别为97.4%和92.1%。离子液体催化剂重复使用4次后,活性基本没有降低。     

离子液体萃取分离有机物研究进展

离子液体是一种结构可调的绿色溶剂,在催化、分离和电化学等领域具有广泛应用,特别是在有机物萃取分离方面,由于其低挥发性及功能可调,避免了传统有机溶剂可能导致的VOCs二次污染,有望成为绿色高效的新型萃取剂。本文系统地综述了离子液体在萃取分离烃类化合物、有机酸、醇类、酚类以及天然产物中的应用研究进展,详细论述了离子液体萃取分离有机物的萃取机理和影响因素,离子液体与溶质分子之间强的氢键、π-π、范德华力以及静电作用使其具有良好的萃取分离能力,表明离子液体是一类可替代有机溶剂实现高效萃取分离有机化合物的潜在溶剂。针对实际工作应用,还需解决其高黏度、高成本等问题,此外萃取后离子液体的回收仍是其大规模应用而需要亟待解决的难题。     

液体酸耦合体系催化C4烷基化研究进展

综述了近十年来液体酸耦合体系催化C₄烃烷基化反应的最新进展,包括液体超强酸、有机酸-杂多酸、离子液体-酸耦合体系,对比了不同催化体系催化C₄烃烷基化反应过程中的烯烃转化率、三甲基戊烷的选择性和烷基化汽油的研究法辛烷值,总结了不同催化体系的优缺点。重点论述了离子液体-酸耦合体系催化剂中组成离子液体的阴阳离子以及耦合酸类型对C₄烃烷基化反应的影响：有机胺类离子液体较咪唑类有着更为优异的烷基化效果,阴离子和改性离子液体通过形成特定的结构来维持反应体系的酸强度、减少副反应,从而延长催化剂的使用寿命,耦合酸为反应提供酸性位点并与离子液体协同催化。离子液体-酸耦合催化体系具有酸耗低、稳定性好、不易失活且可循环使用等优点,是C₄烷基化催化剂未来的发展方向之一。     

异丁烷与2-丁烯在含有抑制剂离子液体中的烷基化反应

含有AlCl^-₄和/或Al₂Cl^-₇阴离子的氯铝酸离子液体对异丁烷/2-丁烯烷基化反应具有很强的催化活性,但反应的选择性较差. 改变离子液体本身的阴、阳离子种类不能提高反应的选择性.在氯铝酸离子液体中引入CuCl等金属氯化物,能够有效地抑制烷基化过程中多聚、异构、歧化、氢转移、裂解等副反应的发生,大幅提高烷基化油中三甲基戊烷等高辛烷值组分含量. 相同反应条件下,CuCl+［Et₃NH］Cl-1.8AlCl₃烷基化反应中高辛烷值产物的含量远高于H₂SO₄烷基化油中相应组分含量.     

对甲酚烷基化反应催化剂的研究进展

主要从酸性催化剂的发展历程全面综述了分子筛、固体超强酸、离子交换树脂、杂多酸、离子液体等多种酸性催化剂的优点和缺点,并总结出对甲酚在不同催化剂作用下反应产物区域选择性的结果。通过对多种催化剂的特性和反应结果对比着重介绍了离子液体催化剂,离子液体同时拥有液体酸高密度酸性和固体酸易分离不挥发的优点,在保持着浓硫酸酸性强度的同时,还具有低蒸气压、热稳定性高、对环境无污染、功能化设计的优良特性,这为今后对甲酚烷基化反应绿色催化剂的发展提供了重要的研究方向,避免了目前工业上常用液体酸催化剂存在的污染环境设备和安全隐患等重大问题。     

改性氯铝酸盐酸性离子液体催化正癸烷异构化反应研究

分别采用添加ZnCl2和通入HCl的方法对盐酸三乙胺型氯铝酸盐(Et3NHCl-2AlCl3)酸性离子液体进行改性,用吡啶和乙腈红外光谱探针法以及紫外光谱测定了改性前后离子液体的酸性,并考察了这两种改性方法对Et3NHCl-2AlCl3催化正癸烷异构化反应性能的影响规律。结果表明,ZnCl2改性的Et3NHCl-2AlCl3离子液体酸性减弱,对正癸烷异构化反应的催化活性降低,但异构化选择性有所提高;而用HCl改性后离子液体的酸性增强,提高了正癸烷异构化反应的催化活性和异癸烷产物中二甲基辛烷的含量。     

合成双酚A催化剂研究新进展

介绍了用于合成双酚A催化剂离子交换树脂的改性、固体酸催化剂,包括分子筛、杂多酸、自主合成固体酸以及离子液体等新型催化剂;分析比较了它们的催化效果;评述了介孔分子筛、杂多酸、离子液体等催化剂的催化性能和存在的问题,并对未来催化剂的发展提出了建议。