A General Method for Growing Two‐Dimensional Crystals of Organic Semiconductors by “Solution Epitaxy”

Two‐dimensional (2D) crystals of organic semiconductors (2DCOS) have attracted attention for large‐area and low‐cost flexible optoelectronics. However, growing large 2DCOS in controllable ways and transferring them onto technologically important substrates, remain key challenges. Herein we report a facile, general, and effective method to grow 2DCOS up to centimeter size which can be transferred to any substrate efficiently. The method named “solution epitaxy” involves two steps. The first is to self‐assemble micrometer‐sized 2DCOS on water surface. The second is epitaxial growth of them into millimeter or centimeter sized 2DCOS with thickness of several molecular layers. The general applicability of this method for the growth of 2DCOS is demonstrated by nine organic semiconductors with different molecular structures. Organic field‐effect transistors (OFETs) based on the 2DCOS demonstrated high performance, confirming the high quality of the 2DCOS.     

Creation of “Rose Petal” and “Lotus Leaf” Effects on Alumina by Surface Functionalization and Metal‐Ion Coordination

Functional differences between superhydrophobic surfaces, such as lotus leaf and rose petals, are due to the subtle architectural features created by nature. Mimicry of these surfaces with synthetic molecules continues to be fascinating as well as challenging. Herein, we demonstrate how inherently hydrophilic alumina surface can be modified to give two distinct superhydrophobic behaviors. Functionalization of alumina with an organic ligand resulted in a rose‐petal‐like surface (water pinning) with a contact angle of 145° and a high contact angle hysteresis (±69°). Subsequent interaction of the ligand with Zn²⁺ resulted in a lotus‐leaf‐like surface with water rolling behavior owing to high contact angle (165°) and low‐contact‐angle‐hysteresis (±2°). In both cases, coating of an aromatic bis‐aldehyde with alkoxy chain substituents was necessary to emulate the nanowaxy cuticular feature of natural superhydrophobic materials.     

An Allosteric Receptor by Simultaneous “Casting” and “Molding” in a Dynamic Combinatorial Library

Allosteric synthetic receptors are difficult to access by design. Herein we report a dynamic combinatorial strategy towards such systems based on the simultaneous use of two different templates. Through a process of simultaneous casting (the assembly of a library member around a template) and molding (the assembly of a library member inside the binding pocket of a template), a Russian‐doll‐like termolecular complex was obtained with remarkable selectivity. Analysis of the stepwise formation of the complex indicates that binding of the two partners by the central macrocycle exhibits significant positive cooperativity. Such allosteric systems represent hubs that may have considerable potential in systems chemistry.     

Photochemical Internalization of Tamoxifens Transported by a “Trojan‐Horse” Nanoconjugate into Breast‐Cancer Cell Lines

Photochemical internalization (PCI) has shown great promise as a therapeutic alternative for targeted drug delivery by light‐harnessed activation. However, it has only been applicable to therapeutic macromolecules or medium‐sized molecules. Herein we describe the use of an amphiphilic, water‐soluble porphyrin–β‐cyclodextrin conjugate (mTHPP‐βCD) as a “Trojan horse” to facilitate the endocytosis of CD‐guest tamoxifens into breast‐cancer cells. Upon irradiation, the porphyrin core of mTHPP‐βCD expedited endosomal membrane rupture and tamoxifen release into the cytosol, as documented by confocal microscopy. The sustained complexation of mTHPP‐βCD with tamoxifen was corroborated by 2D NMR spectroscopy and FRET studies. Following the application of PCI protocols with 4‐hydroxytamoxifen (4‐OHT), estrogen‐receptor β‐positive (Erβ+, but not ERβ?) cell groups exhibited extensive cytotoxicity and/or growth suspension even at 72 h after irradiation.     

Unveiling the “Three‐Finger Pharmacophore” Required for p53–MDM2 Inhibition by Saturation‐Transfer Difference (STD) NMR Initial Growth‐Rates Approach

Inhibitors of the p53‐MDM2 protein–protein interaction are emerging as a new and validated approach to treating cancer. Herein, we describe the synthesis and inhibitory evaluation of a series of isoquinolin‐1‐one analogues, and highlight the utility of an initial growth‐rates saturation‐transfer difference (STD) NMR approach supported by protein–ligand docking to investigate p53‐MDM2 inhibition. The approach is illustrated by the study of compound 1 , providing key insights into the binding mode of this kind of MDM2 ligands and, more importantly, readily unveiling the previously proposed three‐finger pharmacophore requirement for p53‐MDM2 inhibition.     

From Packed “Sandwich” to “Russian Doll”: Assembly by Charge‐Transfer Interactions in Cucurbit[10]uril

As the host possessing the largest cavity in the cucurbit[n]uril (CB[n]) family, CB[10] has previously displayed unusual recognition and assembly properties with guests but much remains to be explored. Herein, we present the recognition properties of CB[10] toward a series of bipyridinium guests including the tetracationic cyclophane known as blue box along with electron‐rich guests and detail the influence of encapsulation on the charge‐transfer interactions between guests. For the mono‐bipyridinium guest (methylviologen, MV ²⁺), CB[10] not only forms 1:1 and 1:2 inclusion complexes, but also enhances the charge‐transfer interactions between methylviologen and dihydroxynaphthalene ( HN ) by mainly forming the 1:2:1 packed “sandwich” complex (CB[10] ? 2 MV ²⁺ ?HN ). For guest 1 with two bipyridinium units, an interesting conformational switching from linear to “U” shape is observed by adding catechol to the solution of CB[10] and the guest. For the tetracationic cyclophane‐blue box, CB[10] forms a stable 1:1 inclusion complex; the two bipyridinium units tilt inside the cavity of CB[10] according to the X‐ray crystal structure. Finally, a supramolecular “Russian doll” was built up by threading a guest through the cavities of both blue box and CB[10].     

Computational design of S‐nitrosothiol “click” reactions

To address a long‐standing problem of finding efficient reactions for chemical labeling of protein‐based S‐nitrosothiols (RSNOs), we computationally explored hitherto unknown (3+2) cycloaddition RSNO reactions with alkynes and alkenes. Nonactivated RSNO cycloaddition reactions have high activation enthalpy (>20 kcal/mol at the CBS‐QB3 level) and compete with alternative S—N bond insertion pathway. However, the (3+2) cycloaddition reaction barriers can be dramatically lowered by coordination of a Lewis acid to the N atom of the —SNO group. To exploit this effect, we propose to use reagents with Lewis acid and a strain‐activated carbon–carbon multiple bond linked by a rigid scaffold, which can react with RSNOs with small activation enthalpies (～5 kcal/mol) and high reaction exothermicities (～40 kcal/mol). The proposed efficient RSNO cycloaddition reactions can be used for future development of practical RSNO labeling reactions. © 2013 Wiley Periodicals, Inc.     

Synthesis of Chlamydia Lipopolysaccharide Haptens through the use of α‐Specific 3‐Iodo‐Kdo Fluoride Glycosyl Donors

A scalable approach towards high‐yielding and (stereo)selective glycosyl donors of the 2‐ulosonic acid Kdo (3‐deoxy‐D ‐manno‐oct‐2‐ulosonic acid) is a fundamental requirement for the development of vaccines against Gram‐negative bacteria. Herein, we disclose a short synthetic route to 3‐iodo Kdo fluoride donors from Kdo glycal esters that enable efficient α‐specific glycosylations and significantly suppress the elimination side reaction. The potency of these donors is demonstrated in a straightforward, six‐step synthesis of a branched Chlamydia‐related Kdo‐trisaccharide ligand without the need for protecting groups at the Kdo glycosyl acceptor. The approach was further extended to include sequential iteration of the basic concept to produce the linear Chlamydia‐specific α‐Kdo‐(2→8)‐α‐Kdo‐(2→4)‐α‐Kdo trisaccharide in a good overall yield.     

“Design” of Boron‐Based Compounds as Pro‐Nucleophiles and Co‐Catalysts for Indium(I)‐Catalyzed Allyl Transfer to Various Csp3‐Type Electrophiles

We have recently uncovered a general indium(I)‐catalyzed method for allylations and propargylation of acetals and ketals with a water‐ and air‐stable allyl boronate. By using a more reactive allyl borane, we have successfully extended this methodology to the more challenging C C coupling with ethers. Herein, we report an improved methodology for the indium(I)‐catalyzed allylation of acetals and ethers, through combination of the allyl boronate with a commercially available “hard” Lewis acid, B‐methoxy‐9‐BBN (BBN=borabicyclo[3.3.1]nonane), as an effective co‐catalyst. Significantly, our work highlights for the first time the correlation between the Lewis acidity of “electrophilic” boron‐based compounds and their “nucleophilic” reactivity in Csp³–Csp³ couplings, catalyzed by a “soft” low‐oxidation main group metal. In addition, we also report several applications of these methodologies to the selective synthesis of various carbohydrate derivatives.     

Quantitative and in situ Detection of Oxidatively Generated DNA Damage 8,5′‐Cyclo‐2′‐Deoxyadenosine Using an Immunoassay with a Novel Monoclonal Antibody

Xeroderma pigmentosum (XP) is a genetic disorder associated with defects in nucleotide excision repair, which eliminates a wide variety of helix‐distorting types of DNA damage including sunlight‐induced pyrimidine dimers. In addition to skin disease, approximately 30% of XP patients develop progressive neurological disease, which has been hypothesized to be associated with the accumulation of a particular type of oxidatively generated DNA damage called purine 8,5′‐cyclo‐2′‐deoxynucleosides (purine cyclonucleosides). However, there are no currently available methods to detect purine cyclonucleosides in DNA without the need for DNA hydrolysis. In this study, we generated a novel monoclonal antibody (CdA‐1) specific for purine cyclonucleosides in single‐stranded DNA that recognizes 8,5′‐cyclo‐2′‐deoxyadenosine (cyclo‐dA). An immunoassay using CdA‐1 revealed a linear dose response between known amounts of cyclo‐dA in oligonucleotides and the antibody binding to them. The quantitative immunoassay revealed that treatment with Fenton‐type reagents (CuCl₂/H₂O₂/ascorbate) efficiently produces cyclo‐dA in DNA in a dose‐dependent manner. Moreover, immunofluorescent analysis using CdA‐1 enabled the visualization of cyclo‐dA in human osteosarcoma cells, which had been transfected with oligonucleotides containing cyclo‐dA. Thus, the CdA‐1 antibody is a valuable tool for the detection and quantification of cyclo‐dA in DNA, and may be useful for characterizing the mechanism(s) underlying the development of XP neurological disease.     

Using “Threading Followed by Shrinking” to Synthesize Highly Stable Dialkylammonium‐Ion‐Based Rotaxanes

Herein, we report a “threading followed by shrinking” approach for the synthesis of rotaxanes by using an “oxygen‐deficient” macrocycle that contained two arylmethyl sulfone units and the dumbbell‐shaped salt bis(3,5‐dimethylbenzyl)ammonium tetrakis(3,5‐trifluoromethylphenyl)borate as the host and guest components, respectively. The extrusion of SO₂ from both of the arylmethyl sulfone units of the macrocyclic component in the corresponding [2]pseudorotaxane resulted in a [2]rotaxane that was sufficiently stable to maintain its molecular integrity in CD₃SOCD₃ at 393 K for at least 5 h.     

A Biomimetic Nanoparticle to “Lure and Kill” Phospholipase A2

Inhibition of phospholipase A2 (PLA2) has long been considered for treating various diseases associated with an elevated PLA2 activity. However, safe and effective PLA2 inhibitors remain unavailable. Herein, we report a biomimetic nanoparticle design that enables a “lure and kill” mechanism designed for PLA2 inhibition (denoted “L&K‐NP”). The L&K‐NPs are made of polymeric cores wrapped with modified red blood cell membrane with two inserted key components: melittin and oleyloxyethyl phosphorylcholine (OOPC). Melittin acts as a PLA2 attractant that works together with the membrane lipids to “lure” in‐coming PLA2 for attack. Meanwhile, OOPC acts as inhibitor that “kills” PLA2 upon enzymatic attack. Both compounds are integrated into the L&K‐NP structure, which voids toxicity associated with free molecules. In the study, L&K‐NPs effectively inhibit PLA2‐induced hemolysis. In mice administered with a lethal dose of venomous PLA2, L&K‐NPs also inhibit hemolysis and confer a significant survival benefit. Furthermore, L&K‐NPs show no obvious toxicity in mice. and the design provides a platform technology for a safe and effective anti‐PLA2 approach.     

A Hydrolase‐Catalyzed Cyclization Forms the Fused Bicyclic β‐Lactone in Vibralactone

Vibralactone is isolated from the basidiomycete fungus Boreostereum vibrans as one of the strongest lipase inhibitors. Its unusual β‐lactone‐fused bicycle is derived from an aryl ring moiety by an oxidative ring‐expansion prior to an intramolecular cyclization. Herein, we report the discovery of the cyclase VibC which belongs to the α/β‐hydrolase superfamily and is involved in the vibralactone biosynthesis. Biochemical and crystal studies suggest that VibC may catalyze an aldol or an electrocyclic reaction initiated by the Ser‐His‐Asp catalytic triad. For the aldol and pericyclic chemistry in living cells, VibC is a unique hydrolase performing the carbocycle formation of an oxepinone to a fused bicyclic β‐lactone. This presents a naturally occurring, new enzymatic reaction in both aldol and hydrolase (bio)chemistry that will guide future exploitation of these enzymes in synthetic biology for chemical‐diversity expansion of natural products.     

Self‐Assembly of Chiral Propeller‐like Supermolecules with Unusual “Sergeants‐and‐Soldiers” and “Majority‐Rules” Effects

Chiral amplification is an interesting phenomenon in supramolecular chemistry mainly observed in complicated systems in which cooperative effect dominate. Herein, chiral, supramolecular, propeller‐like architectures have been constructed through coassembly of an achiral disk‐shaped molecule and chiral amino acid derivatives driven by intermolecular hydrogen bonding. Both the “sergeants‐and‐soldiers” principle and “majority‐rules” effect are applicable in these discrete four‐component supermolecules, which are the simplest supramolecular system ever reported that exhibit chiral amplification.     

Facile Synthesis of Hierarchical Nanosized Single‐Crystal Aluminophosphate Molecular Sieves from Highly Homogeneous and Concentrated Precursors

The synthesis of hierarchical nanosized zeolite materials without growth modifiers and mesoporogens remains a substantial challenge. Herein, we report a general synthetic approach to produce hierarchical nanosized single‐crystal aluminophosphate molecular sieves by preparing highly homogeneous and concentrated precursors and heating at elevated temperatures. Accordingly, aluminophosphate zeotypes of LTA (8‐rings), AEL (10‐rings), AFI (12‐rings), and ‐CLO (20‐rings) topologies, ranging from small to extra‐large pores, were synthesized. These materials show exceptional properties, including small crystallites (30–150 nm), good monodispersity, abundant mesopores, and excellent thermal stability. A time‐dependent study revealed a non‐classical crystallization pathway by particle attachment. This work opens a new avenue for the development of hierarchical nanosized zeolite materials and understanding their crystallization mechanism.     

“Armor‐Plating” Enzymes with Metal–Organic Frameworks (MOFs)

Cell‐free enzymatic catalysis (CFEC) is an emerging biotechnology that enable the biological transformations in complex natural networks to be imitated. This biomimetic approach allows industrial products such as biofuels and biochemical to be manufactured in a green manner. Nevertheless, the main challenge in CFEC is the poor stability, which restricts the effectiveness and lifetime of enzymes in sophisticated applications. Immobilization of the enzymes within solid carriers is considered an efficient strategy for addressing these obstacles. Specifically, putting an “armor‐like” porous metal–organic framework (MOF) exoskeleton tightly around the enzymes not only shields the enzymes against external stimulus, but also allows the selective transport of guests through the accessible porous network. Herein we present the concept of this biotechnology of MOF‐entrapped enzymes and its cutting‐edge applications.     

Three 2‐amino­purine derivatives

The structure of 2‐amino‐6‐chloro­purine, C₅H₄ClN₅, (I), comprises a flat mol­ecule, with all possible strong hydrogen‐bond donors and acceptors involved in the hydrogen‐bonding network. The structures of 2‐amino‐6‐(4‐chloro­phenylsulfanyl)­purine hemihydrate, C₁₁H₈ClN₅S·0.5H₂O, (II), and 2‐amino‐6‐(4‐methylphenylsulfanyl)purine 0.33‐hydrate, C₁₂H₁₁N₅S·0.33H₂O, (III), have two and three unique mol­ecules, respectively, and one water mol­ecule in their asymmetric units. Both (II) and (III) exhibit elaborate hydrogen‐bonding networks that involve the S (for both) and Cl [for (II)] atoms in addition to the expected strong hydrogen‐bonding sites. Both structures also have offset‐stacking formations of the phenyl and purine rings.     

Silica Scaffold with Shifted “Plumber's Nightmare” Networks and their Interconversion into Diamond Networks

Bicontinuous structures with hyperbolic surfaces have been found in a variety of natural and synthetic systems. Herein, we present the synthesis and structural study of the shifted double‐primitive networks, which is known as the rare “plumber's nightmare”, and its interconversion into diamond networks. The scaffold was prepared by self‐assembly of an amphiphilic triblock terpolymer and silica precursors. Electron crystallography indicates that the structure consists of two sets of hollow primitive networks shifted along 0.75b and 0.25c axes ( 2pcu (38 63), space group Cmcm ). The “side‐by‐side” epitaxial relationship of the primitive and diamond networks with unit cell ratio of about 1.30 has been directly observed with the intermediate surface related to the rPD family. These results bring new insights to previous theoretical studies.     

A “Distorted‐BODIPY”‐Based Fluorescent Probe for Imaging of Cellular Viscosity in Live Cells

Cellular viscosity is a critical factor in governing diffusion‐mediated cellular processes and is linked to a number of diseases and pathologies. Fluorescent molecular rotors (FMRs) have recently been developed to determine viscosity in solutions or biological fluid. Herein, we report a “distorted‐BODIPY”‐based probe BV‐1 for cellular viscosity, which is different from the conventional “pure rotors”. In BV‐1 , the internal steric hindrance between the meso‐CHO group and the 1,7‐dimethyl group forced the boron–dipyrrin framework to be distorted, which mainly caused nonradiative deactivation in low‐viscosity environment. BV‐1 gave high sensitivity (x=0.62) together with stringent selectivity to viscosity, thus enabling viscosity mapping in live cells. Significantly, the increase of cytoplasmic viscosity during apoptosis was observed by BV‐1 in real time.     

Inhibition of HER2‐Positive Breast Cancer Growth by Blocking the HER2 Signaling Pathway with HER2‐Glycan‐Imprinted Nanoparticles

Blocking the HER2 signaling pathway has been an effective strategy in the treatment of HER2‐positive breast cancer. It mainly relies on the use of monoclonal antibodies and tyrosine‐kinase inhibitors. Herein, we present a new strategy, the nano molecularly imprinted polymer (nanoMIP). The nanoMIPs, imprinted using HER2 N‐glycans, could bind almost all HER2 glycans and suppress the dimerization of HER2 with other HER family members, blocking the downstream signaling pathways, thereby inhibiting HER2+ breast cancer growth. In vitro experiments demonstrated that the nanoMIPs specifically targeted HER2+ cells and inhibited cell proliferation by 30 %. In vivo experiments indicated that the mean tumor volume of the nanoMIP‐treated group was only about half of that of the non‐treated groups. This study provides not only a new possibility to treat of HER2+ breast cancer but also new evidence to boost further development of nanoMIPs for cancer therapy.