(Iso)Quinoline–Artemisinin Hybrids Prepared through Click Chemistry: Highly Potent Agents against Viruses

Viral infections cause life-threatening diseases in millions of people worldwide every year and there is an urgent need for new, effective antiviral drugs. Hybridization of two chemically diverse compounds into a new bioactive effector product is a successful concept to improve the properties of a hybrid drug relative to the parent compounds. In this study, (iso)quinoline–artemisinin hybrids, obtained through copper-catalyzed azide–alkyne cycloaddition or metal-free click reactions (in organic solvents or in the presence of water), were analyzed in vitro, for the first time, for their inhibitory activity against human cytomegalovirus (HCMV), relative to their parent compounds and the reference drug ganciclovir. EC₅₀ (HCMV) values were obtained in a range 0.22–1.20 μm , which indicated highly potent antiviral properties in the absence of cytotoxic effects on normal cells (CC₅₀>100 μm ). The most active hybrid, 1 (EC₅₀=0.22 μm ), is 25 times more potent than its parent compound artesunic acid (EC₅₀=5.41 μm ) and 12 times more efficient than the standard drug ganciclovir (EC₅₀=2.6 μm ). Interestingly, hybrid 1 also shows inhibitory activity against hepatitis B virus in vitro (EC₅₀ (HBeAg)=2.57 μm ).     

可见光诱导的烯炔和多氟烷基卤环化合成含氟异喹啉酮

发展了一种可见光诱导的1,7-烯炔与全氟烷基卤串联原子转移自由基加成(ATRA)/环化合成含氟2,4-二氢异喹啉-2(1H)-酮的反应。以多氟烷基碘或溴为自由基前体,面式-三( 2-苯基吡啶)合铱(摩尔分数1%)为光敏剂,在5 W蓝光发光二极管(LED)照射下,多种苯桥联1,7-烯炔顺利发生串联(ATRA)/环化反应,以中等到优秀(62%~84%)的产率合成了一系列多氟化异喹啉酮衍生物。 此合成方法反应条件温和、清洁、高效且底物适用范围广,为具有潜在药用价值的多氟化2,4-二氢异喹啉-2(1H)-酮的合成提供新的途径。     

Palladium‐Catalzyed Atroposelective 16‐Membered Macrocyclization: Total Synthesis of Isoplagiochin D†

Isoplagiochin D is a ring‐strained macrocyclic bisbibenzylis, which showed stable axial chirality in one biaryl structure, and semistable axial chirality in the other biaryl moiety. We reported here an unprecedented example for the catalytically asymmetric synthesis of ring‐strained atropisomers via Pd‐catalyzed macrocyclization between benzyl halides and carbenes. This newly developed Pd‐catalyzed asymmetric macrocyclization protocol enabled us a quick synthesis of isoplagiochin D in a highly enantioselective manner.     

Bioresponsive Hyaluronic Acid‐Capped Mesoporous Silica Nanoparticles for Targeted Drug Delivery

In this paper, we present a facile strategy to synthesize hyaluronic acid (HA) conjugated mesoporous silica nanoparticles (MSP) for targeted enzyme responsive drug delivery, in which the anchored HA polysaccharides not only act as capping agents but also as targeting ligands without the need of additional modification. The nanoconjugates possess many attractive features including chemical simplicity, high colloidal stability, good biocompatibility, cell‐targeting ability, and precise cargo release, making them promising agents for biomedical applications. As a proof‐of‐concept demonstration, the nanoconjugates are shown to release cargoes from the interior pores of MSPs upon HA degradation in response to hyaluronidase‐1 (Hyal‐1). Moreover, after receptor‐mediated endocytosis into cancer cells, the anchored HA was degraded into small fragments, facilitating the release of drugs to kill the cancer cells. Overall, we envision that this system might open the door to a new generation of carrier system for site‐selective, controlled‐release delivery of anticancer drugs.     

Electrochemical studies on PVC/PVdF blend-based polymer electrolytes

In recent years, special attention has been focused on the development of gel polymer electrolytes consisting of host polymers such as poly (acrylonitrile), PVC, poly (methyl methacrylate), poly (vinylidene fluoride) (PVdF), etc., as they may be found to have unique applications in consumer electronic and electric vehicle products. In the present study, blend-based polymer electrolytes composed of PVC, PVdF, NaClO₄, and propylene carbonate is prepared using the solvent casting technique. The thermal behaviors of PVC/PVdF polyblend films have been examined using differential scanning calorimetry and scanning electron microscopy. Miscibility studies were performed using X-ray diffraction and Fourier transform infrared. The role of interaction between polymer hosts on conductivity is discussed using the results of AC impedance studies.     

多目标线性规划的一种交互式单纯形算法

本文基于分析有效极点解的有效变量的特点以及在有效点处各个目标函数的数值来得到改进的搜索方向的研究思想,提出了求解目标函数和约束均为线性的多目标线性规划问题的一种交互式算法。该方法可以保证每一步得到的解均为有效极点解,且根据决策者的偏好不断得到改进,直至最终得到满意的最终解。     

Existence, uniqueness and stability ofC m solutions of iterative functional equations

In this paper we discuss a relatively general kind of iterative functional equation G(x,f(x), ...,f ⁿ (x)) = 0 (for allx ∈J), whereJ is a connected closed subset of the real number axis ?,G∈C ^m (J ⁿ⁺¹, ?) andn ≥ 2. Using the method of approximating fixed points by small shift of maps, choosing suitable metrics on functional spaces and finding a relation between uniqueness and stability of fixed points of maps of general spaces, we prove the existence, uniqueness and stability ofCm solutions of the above equation for any integer m ≥ 0 under relatively weak conditions, and generalize related results in reference in different aspects.     

Micelle-like particles based on self-assembly of rod-like FPEEK and coil-like PVA

The self-assembly of a rod-like polymer [hydroxyl-terminated trifluoromethylphenyl-substituted fluorinated poly(ether ether ketone) (FPEEK)] and a coil-like polymer (polyvinyl alcohol, PVA) in water has been studied. It was found that this polymer pair could form micelle-like particles. Hydrogen bonding between the hydroxy groups of rod-like FPEEK and coil-like PVA, and parallel packing of the rod-like FPEEK are the main factors affecting the formation of micelle-like particles. Over a broad range, when the FPEEK/PVA mass ratio or the tetrahydrofolate/H₂O volume ratio is decreased, the diameter of micelle-like particles is decreased. The diameters (around 250 nm) of micelle-like particles measured by scanning electron microscopy and dynamic light scattering are similar, but are different from that measured by transmission electron microscopy (around 150 nm). Thus, it can be concluded that micelle-like particles have a core–shell structure and the cores of micelles are composed of FPEEK, and that the shells of micelles are composed of PVA. When polyethylene glycol was used instead of PVA, micelle-like particles were also formed, but the average diameter was bigger than that of the particles formed by PVA and FPEEK. This work was supported by the National Nature Science Foundation of China (50203004).     

A micromechanics-based Cosserat-type model for dense particulate solids

A two-dimensional continuum theory is presented for cohesionless granular media consisting of identical rigid disks. While the normal deformation of contacting particles is constrained, the tangential frictional contact is modelled by a line spring with a constant stiffness. To describe the static frictional system transmitting couples at contacts, a Cosserat-type continuum including rotational degrees of freedom is appropriate. Contrary to the classical elastic medium, movement of particles within a granular system in response to applied loads can give rise to localisations of force chains and large voids. In addition to relative displacement and rotation, a director governing the direction of interparticle forces and a phase field delineating density variation, are therefore introduced. Total work done involving these two order parameters for a particle is attained on an orientation average. Based on the formulation of free energy, a concentration- and anisotropy-dependent formulation for static quantities (stress and couple stress) in the rate form is derived in light of the principles of thermodynamics. It is consistent with the requirement of observer independence and material symmetry. The governing equations for two order parameters are derived, in which void concentration and stress anisotropy are related to relative displacement and rotation. As an example, the proposed model is applied to the hardening regime of deformation of a dense particle assembly with initial perfect lattice under simple shear. It is demonstrated that in the presence of dilatancy and director variation, there exists a linear relation between the shear stress and strain, in coincidence with experimental observations. Received: February 24, 2005