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We developed a voltage-sensitive artificial transmembrane channel by mimicking the dipolar structure of natural alamethicin channel. The artificial channel featured a zwitterionic structure and could undergo voltage-driven flipping in the lipid bilayers. Importantly, this flipping of the channel could lead to their directional alignment in the bilayers and rectifying behavior for ion transport.

Artificial aquaporins are synthetic molecules that mimic the structure and function of natural aquaporins (AQPs) in cell membranes. The development of artificial aquaporins would provide an alternative strategy for treatment of AQP-related diseases. In this report, an artificial aquaporin has been constructed from an amino-terminated tubular molecule, which operates in a unimolecular mechanism. The artificial channel can work in cell membranes with high water permeability and selectivity rivaling those of AQPs. Importantly, the channel can restore wound healing of the cells that contain function-lost AQPs.

A novel one-pot relay glycosylation has been established. The protocol is characterized by the construction of two glycosidic bonds with only one equivalent of triflic anhydride. This method capitalizes on the in situ generated cyclic-thiosulfonium ion as the relay activator, which directly activates the newly formed thioglycoside in one pot. A wide range of substrates are well-accommodated to furnish both linear and branched oligosaccharides. The synthetic utility and advantage of this method have been demonstrated by rapid access to naturally occurring phenylethanoid glycoside kankanoside F and resin glycoside merremoside D.

RNAi approaches have been widely combined with platinum-based anticancer agents to elucidate cellular responses and to target gene products that mediate acquired resistance. Recent work has demonstrated that platination of siRNA prior to transfection may negatively influence RNAi efficiency based on the position and sequence of its guanosine nucleosides. Here, we used detailed spectroscopic characterization to demonstrate rapid formation of Pt-guanosine adducts within 30 min after coincubation of oxaliplatin [OxaPt(II)] or cisplatin [CisPt(II)] with either guanosine monophosphate or B-cell lymphoma 2 (BCL-2) siRNA. After 3 h of exposure to these platinum(II) agents,50% of BCL-2 siRNA transcripts were platinated and unable to effectively suppress mRNA levels. Platinum(IV) analogues [OxaPt(IV) or CisPt(IV)] did not form Pt-siRNA adducts but did display decreased in vitro uptake and reduced potency. To overcome these challenges, we utilized biodegradable methoxyl-poly(ethylene glycol)-block-poly(ε-caprolactone)-block-poly(l-lysine) (mPEG-b-PCL-b-PLL) to generate self-assembled micelles that covalently conjugated OxaPt(IV) and/or electrostatically complexed siRNA. We then compared multiple strategies by which to combine BCL-2 siRNA with either OxaPt(II) or OxaPt(IV). Overall, we determined that the concentrations of siRNA (nM) and platinum(II)-based anticancer agents (μM) that are typically used for in vitro experiments led to rapid Pt-siRNA adduct formation and ineffective RNAi. Coincorporation of BCL-2 siRNA and platinum(IV) analogues in a single micelle enabled maximal suppression of BCL-2 mRNA levels (to10% of baseline), augmented the intracellular levels of platinum (by ∼4×) and the numbers of resultant Pt-DNA adducts (by5×), increased the cellular fractions that underwent apoptosis (by ∼4×), and enhanced the in vitro antiproliferative activity of the corresponding platinum(II) agent (by 10-100×, depending on the cancer cell line). When combining RNAi and platinum-based anticancer agents, this generalizable strategy may be adopted to maximize synergy during screening or for therapeutic delivery.

Chemodynamic therapy (CDT) has demonstrated new possibilities for selective and logical cancer intervention by specific manipulation of dysregulated tumorous free radical homeostasis. Current CDT methods largely rely on conversion of endogenous hydrogen peroxide (H2O2) into highly toxic hydroxyl radicals via classical Fenton or Haber-Weiss chemistry. However, their anticancer efficacies are greatly limited by the requirement of strong acidity for efficient chemical reactions, insufficient tumorous H2O2, and upregulated antioxidant defense to counteract free radical-caused oxidative damage. Here, we present a new concept whereby bioorthogonal chemistry and prodrug are combined to create a new type of aptamer drug conjugate (ApDC): aptamer-prodrug conjugate (ApPdC) micelle for improved and cancer-targeted CDT. The hydrophobic prodrug bases can not only promote self-assembly of aptamers but also act as free radical generators via bioorthogonal chemistry. In depth mechanistic studies reveal that, unlike traditional CDT systems, ApPdC micelles enable in situ activation and self-cycling generation of toxic C-centered free radicals in cancer cells through cascading bioorthogonal reactions, with no dependence on either H2O2 or pH, yet concurrently with diminished cancerous antioxidation by GSH depletion for a synergistic CDT effect. We expect this work to provide new insights into the design of targeted cancer therapies and studies of free radical-related molecular mechanisms.

Semiconductor-based photocathodes with high light-absorption capability are of interest in the production of solar fuels, but many of them are limited by low efficiencies due to rapid interfacial back electron transfer. We demonstrate here that a nanowire-structured p-type Si (p-Si) electrode, surface-modified with a perylene-diimide derivative (PDI'), can undergo photoreduction of a surface-bound, water reduction catalyst toward efficient H

Light-harvesting inorganic nanocrystals play an important role in emerging solar energy conversion and optoelectronic devices. We describe here a strategy for a new family of photoelectrodes with upconverting nanocrystal assemblies as the photosensitizer. The assemblies consist of oleic acid-capped cadmium selenide (CdSe) nanocrystals that coordinate directly onto a layer of surface-bound, carboxylic acid-derivatized anthracenes through displacement of the oleic acid capping ligands. Steady-state emission and transient absorption measurements show that the upconverting nanocrystal assemblies, selectively excited by green light, generate singlet excitons that enable efficient charge injection into both the conduction band of TiO

Despite extensive studies in gold catalysis, σ-allenylgold species have not been invoked as catalytic intermediates and their reactivities not studied. This work reports for the first time they are generated in situ and undergo nucleophilic addition to activated aldehydes in a bifunctional phosphine ligand-enabled gold catalysis. This development reveals a broad range of opportunities to achieve propargylic C-H functionalization for the first time under catalytic and mild conditions. The homopropargylic alcohols generated undergo ligand-enabled cycloisomerizations involving an unexpected silyl migration.

For two-dimensional transition metal dichalcogenides (TMD) materials, achieving large size with high quality to provide a basis for the next generation of electronic device geometries has been a long-term need. Here, we demonstrate that, by only manual shaking within several seconds, very large-sized TMD monolayers that cover a wide range of group IVB-VIB transition metal sulfides and selenides can be efficiently harvested from intercalated single-crystal counterparts. Taking TaS2 as examples, monolayers up to unprecedented size (>100 μm) are obtained while maintaining high crystalline quality and the phase structure of the starting materials. Furthermore, benefiting from the gentle manual shaking, we unraveled the atomic-level correlation between the intercalated lattice-strain effects and exfoliated nanosheets, and that strong tensile strain usually led to very large sizes. This work helps to deepen the understanding of exfoliation mechanism and provides a powerful tool for producing large-sized and hig...

Here we report for the first time that ion current rectification (ICR) can be observed at the micrometer scale in symmetric electrolyte solution with polyimidazolium brush (PimB)-modified micropipets, which we call micrometer-scale ion current rectification (MICR). To qualitatively understand MICR, a three-layer model including a charged layer, an electrical double layer, and a bulk layer is proposed, which could also be extended to understanding ICR at the nanoscale. Based on this model, we propose that when charges in the charged layer are comparable with those in the bulk layer, ICR would occur regardless of whether the electrical double layers are overlapped. Finite element simulations based on the solution of Poisson and Nernst-Planck equations and in situ confocal laser scanning microscopy results qualitatively validate the experimental observations and the proposed three-layer model. Moreover, possible factors influencing MICR, including the length of PimB, electrolyte concentration, and the radius of the pipet, are investigated and discussed. This study successfully extends ICR to the micrometer scale and thus opens a new door to the development of ICR-based devices by taking advantage of ease-in-manipulation and designable surface chemistry of micropipets.

Globo H-based therapeutic cancer vaccines have been tested in clinical trials for the treatment of late stage breast, ovarian, and prostate cancers. In this study, we explored Globo H analogue antigens with an attempt to enhance the antigenic properties in vaccine design. The Globo H analogues with modification at the reducing or nonreducing end were synthesized using chemoenzymatic methods, and these modified Globo H antigens were then conjugated with the carrier protein diphtheria toxoid cross-reactive material (CRM) 197 (DT), and combined with a glycolipid C34 as an adjuvant designed to induce a class switch to form the vaccine candidates. After Balb/c mice injection, the immune response was studied by a glycan array and the results showed that modification at the C-6 position of reducing end glucose of Globo H with the fluoro, azido, or phenyl group elicited IgG antibody response to specifically recognize Globo H (GH) and the GH-related epitopes, stage-specific embryonic antigen 3 (SSEA3) (also called Gb5) and stage-specific embryonic antigen 4 (SSEA4). However, only the modification of Globo H with the azido group at the C-6 position of the nonreducing end fucose could elicit a strong IgG immune response. Moreover, the antibodies induced by these vaccines were shown to recognize GH expressing tumor cells (MCF-7) and mediate the complement-dependent cell cytotoxicity against tumor cells. Our data suggest a new potential approach to cancer vaccine development.

A new series of hydrogen-bonded helical aromatic hydrazide oligomers and polymer that bear phenylalanine tripeptide chains have been designed and synthesized. It was revealed that the helical structures could insert into lipid bilayers to form unimolecular channels. The longest oligomeric and polymeric helical channels exhibited an NH4(+)/K(+) selectivity that was higher than that of natural gramicidin A, whereas the transport of a short helical channel for Tl(+) could achieve an efficiency as high as that of gramicidin A.

The self-assembly of well-defined 2D supramolecular polymers in solution has been a challenge in supramolecular chemistry. We have designed and synthesized a rigid stacking-forbidden 1,3,5-triphenylbenzene compound that bears three 4,4'-bipyridin-1-ium (BP) units on the peripheral benzene rings. Three hydrophilic bis(2-hydroxyethyl)carbamoyl groups are introduced to the central benzene ring to suppress 1D stacking of the triangular backbone and to ensure solubility in water. Mixing the triangular preorganized molecule with cucurbit[8]uril (CB[8]) in a 2:3 molar ratio in water leads to the formation of the first solution-phase single-layer 2D supramolecular organic framework, which is stabilized by the strong complexation of CB[8] with two BP units of adjacent molecules. The periodic honeycomb 2D framework has been characterized by various (1)H NMR spectroscopy, dynamic light scattering, X-ray diffraction and scattering, scanning probe and electron microscope techniques and by comparing with the self-assembled structures of the control systems.

The structural diversity of glycoproteins often comes from post-translational glycosylation with heterogeneous N-glycans. Understanding the complexity of glycans related to various biochemical processes demands a well-defined synthetic sugar library. We report herein a unified convergent strategy for the rapid production of bi-, tri-, and tetra-antennary complex type N-glycans with and without terminal N-acetylneuraminic acid residues connected via the α-2,6 or α-2,3 linkages. Moreover, using sialyltransferases to install sialic acid can minimize synthetic steps through the use of shared intermediates to simplify the complicated procedures associated with conventional sialic acid chemistry. Furthermore, these synthetic complex oligosaccharides were compiled to create a glycan array for the profiling of HIV-1 broadly neutralizing antibodies PG9 and PG16 that were isolated from HIV infected donors. From the study of antibody PG16, we identified potential natural and unnatural glycan ligands, which may facilitate the design of carbohydrate-based immunogens and hasten the HIV vaccine development.

Peptide-appended pillar[n]arene (n = 5, 6) derivatives have been synthesized. (1)H NMR and IR studies revealed that the molecules adopt a tubular conformation in solution and lipid bilayer membranes. Kinetic measurements using the fluorescent labeling method with lipid vesicles revealed that these molecules can efficiently mediate the transport of amino acids across lipid membranes at a very low channel-to-lipid ratio (EC(50) = 0.002 mol %). In several cases, chiral selectivity for amino acid enantiomers was achieved, which is one of the key functions of natural amino acid channels.

Hydrazide-appended pillar[5]arene derivatives have been synthesized. X-ray crystal structure analysis and (1)H NMR studies revealed that the molecules adopt unique tubular conformations. Inserting the molecules into the lipid membranes of vesicles leads to the transport of water through the channels produced by single molecules, as supported by dynamic light scattering and cryo-SEM experiments. The channels exhibit the transport activity at a very low channel to lipid ratio (0.027 mol %), and a water permeability of 8.6 × 10(-10) cm s(-1) is realized. In addition, like natural water channel proteins, the artificial systems also block the transport of protons.

A novel type of chiral layered supramolecular copolymer with high molecular weight has been assembled from a hydrogen bonded C(6)-symmetric zinc porphyrin hexamer and chiral C(3)-symmetric pyridine hexadentate linkers driven by multivalent zinc porphyrin-pyridine coordination. UV-vis, circular dichroism, and static light scattering experiments revealed that the formation of the layered supramolecular copolymers is at first dynamically controlled and then becomes thermodynamically controlled.

The photochemical reaction of (C(5)Me(5))Rh(PMe(3))H(2) (1) in neat acetonitrile leads to formation of the C-H activation product, (C(5)Me(5))Rh(PMe(3))(CH(2)CN)H (2). Thermolysis of this product in acetonitrile or benzene leads to thermal rearrangement to the C-C activation product, (C(5)Me(5))Rh(PMe(3))(CH(3))(CN) (4). Similar results were observed for the reaction of 1 with benzonitrile. The photolysis of 1 in neat benzonitrile results in C-H activation at the ortho, meta, and para positions. Thermolysis of the mixture in neat benzonitrile results in clean conversion to the C-C activation product, (C(5)Me(5))Rh(PMe(3))(C(6)H(5))(CN) (5). DFT calculations on the acetonitrile system show the barrier to C-H activation to be 4.3 kcal mol(-1) lower than the barrier to C-C activation. A high-energy intermediate was also located and found to connect the transition states leading to C-H and C-C activation. This intermediate has an agostic hydrogen interaction with the rhodium center. Reactions of acetonitrile and benzonitrile with the fragment [Tp'Rh(CNneopentyl)] show only C-H and no C-C activation. These reactions with rhodium are compared and contrasted to related reactions with [Ni(dippe)H](2), which show only C-CN bond cleavage.

The processes of C-C and C-S bond cleavage have been studied with the homogeneous organometallic compound [Ni(dippe)H](2) (1). When 1 is reacted with 2-cyanothiophene at room temperature, cleavage of the nitrile-substituted C-S bond occurs, forming the Ni-metallacycle complex (dippe)Ni(kappa(2)-S,C-SCH=CHCH=C(CN)) (2a), which has been fully characterized by NMR spectroscopy and X-ray diffraction. 2a was converted to the C-CN cleavage product (dippe)Ni(CN)(2-thiophenyl) (3) when heated in solution. On closer inspection, four other intermediates were observed by (31)P NMR spectroscopy at low temperature. Structures for the intermediates were elucidated through a combination of independent synthesis, theoretical calculations, chemical characterization, and experimental precedent. A kinetic product (dippe)Ni(kappa(2)-S,C-SC(CN)=CHCH=CH) (2b) was formed from cleavage of the nonsubstituted C-S bond, as well as a Ni(0) eta(2)-nitrile intermediate, (dippe)Ni(eta(2)-C,N-2-cyanothiophene) (4), and a dinuclear mixed Ni(0)-Ni(II) product (6b). A complete DFT analysis of this system has been carried out to reveal comparative details about the two bond cleavage transition states.

This paper reports a systematic study of the dynamic process for the self-assembly of chiral organogels from achiral hydrogen bonded hydrazide foldamers by induction of chiral glucose. Six foldamers incorporated with six decyl chains and two benzene, naphthalene, anthracene, or pyrene units at the ends are revealed to strongly gelate apolar and polar solvents, including alkanes, arenes, esters, alcohols, and 1,4-dioxane. The gels are characterized by UV-vis, fluorescent, XRD, SEM, and AFM methods, based on which a dislocated "tail-to-tail" stacking pattern is proposed. Addition of octylated glucose considerably enhances the capacity of the foldamers to gelate apolar solvents due to strong complexation. The complexation also causes unique dynamic helicity induction in the gels, which is studied systematically by circular dichroism. The results are treated with the Avrami theory according to a reported method (J. Am. Chem. Soc. 2005, 127, 4336), which suggests that the gelation involves a nucleation-elongation mechanism. In addition, the "Sergeants and Soldiers" effect in the gel phase is also revealed.

This paper describes the synthesis and characterization of the first series of hydrogen bonding-driven hydrazide foldamers and their recognition for alkyl saccharides in chloroform. Oligomers 1, 2-4, 5, 6, and 7, which contain one, two, four, six, or twelve repeated dibenzoyl hydrazide residues, respectively, have been prepared. The rigid and planar conformations of 1 and 2 or 4 have been established with X-ray analysis and (1)H NMR spectroscopy, whereas the folding and helical conformations of 5-7 have been evidenced by the 1D and 2D (1)H NMR and IR spectroscopy and molecular mechanics calculations. Molecular mechanics calculations also revealed that 5, 6, and 7 possess a rigid cavity with size of ca. 10.6 to 11.1 A, and half of the carbonyl groups in the folding conformations are orientated inwardly inside the cavity. (1)H NMR and CD experiments revealed that 5-7 efficiently complex alkylated mono- and disaccharides 32-35 in chloroform. The association constants (K(assoc)) of the complexes have been determined with the (1)H NMR and fluorescent titration methods. The energy-minimized conformation of 6.34 has been obtained with molecular mechanics calculation. The hydrazide-based folding structures described here represent novel examples of hydrogen bonding-driven foldamers that act as artificial receptors for selective molecular recognition.

Experimental and density functional theory show that the reaction of acetonitrile with a zerovalent nickel bis(dialkylphosphino)ethane fragment (alkyl = methyl, isopropyl) proceeds via initial exothermic formation of an eta(2)-nitrile complex. Three well-defined transition states have been found on the potential energy surface between the eta(2)-nitrile complex and the activation products. The lowest energy transition state is an eta(3)-acetonitrile complex, which connects the eta(2)-nitrile to a higher energy eta(3)-acetonitrile intermediate with an agostic C-H bond, while the other two lead to cleavage of either the C-H or the C-CN bonds. Gas-phase calculations show C-CN bond activation to be endothermic, which contradicts the observation of thermal C-CN activation in THF. Therefore, the effect of solvent was taken into consideration by using the polarizable continuum model (PCM), whereupon the activation of the C-CN bond was found to be exothermic. Furthermore the C-CN bond activation was found to be favored exclusively over C-H bond activation due to the strong thermodynamic driving force and slightly lower kinetic barrier.

This paper describes the self-assembly of a new class of foldamer-based molecular tweezers, whose rigid folded conformations are stabilized by intramolecular hydrogen bonding. Two zinc porphyrin units are introduced to the ends of molecular tweezers Zn(2)1 and Zn(2)2, while three zinc porphyrin units are incorporated to the S-shaped bi-tweezers Zn(3)3, which may be regarded as a combination of two Zn(2)1 molecules. Due to the preorganized U-shaped feature, Zn(2)1 and Zn(2)2 are able to strongly complex C60, C70, and C60 derivative 25 in chloroform or toluene in a 1:1 binding stoichiometry, whereas Zn(3)3, which possesses two tweezer units, complexes the guests in a 1:2 stoichiometry. More stable complex Zn(3)3.24 is formed between Zn(3)3 and 24, a linear molecule bearing two C60 moieties at the ends, as a result of the cooperative interaction of two binding sites. Chiral induction is observed for all the three receptors upon complexation with C60-incoporated chiral phenylalanine derivative 29, although the complexation of 29 by the folding receptors is pronouncedly weaker than that of C60 and 25 due to increased steric hindrance. The driving force for the formation of the complexes is the well established pi-pi stacking between the zinc porphyrin and fullerene units. The 1H and 13C NMR, UV-vis, fluorescent, and circular dichroism spectroscopy have been used to investigate the complexing behavior of the folding receptors and the fullerene guests. The association constants of the corresponding complexes in toluene and chloroform (if possible) have been evaluated with the UV-vis and fluorescent titration experiments.

This paper describes the synthesis, self-assembly, and characterization of a new class of highly stable hydrazide-based quadruply hydrogen-bonded heterodimers. All of the hydrazide-derived heterodimers possess the complementary ADDA-DAAD hydrogen-bonding sequences. Hydrazide derivatives 1, which has two intramolecular S(6) RO.H-N hydrogen bonds, and 2 complex to afford two fastly exchanging isomeric heterodimers 1.2 and 1.2' in chloroform, as a result of two different conformational arrangements of 2. An average binding constant K(assoc) of 4.7 x 10(4) M(-)(1) was determined for heterodimer 1.2 and 1.2' by (1)H NMR titration of 1 with changing 2 in chloroform-d. In contrast, 1 binds 11 and 12, both of which are introduced with two intramolecular S(6) hydrogen bonds, to exclusively afford heterodimers 1.11 and 1.12, with K(assoc) values of 1.8 x 10(4) and 5.0 x 10(2) M(-)(1), respectively. Fluorine-containing 19, which has a hydrazide skeleton identical to that of 1 but two intramolecular S(6) F.H-N hydrogen bonds, can also complex with 2, 11, and 12, to afford heterodimers 19.2, 19.2', 19.11, and 19.12, with K(assoc) values of of 1.2 x 10(4) (average value for 19.2 and 19.2'), 5.4 x 10(3), and 1.9 x 10(2) M(-)(1), respectively. The structures of the new heterodimers have been proven with NOESY, IR, and VPO (for some of the heterodimers) experiments. Moreover, 1 and 19 can also strongly bind 2,7-dilauroylamido-1,8-naphthyridine 23 to afford dimers 1.23 and 19.23 with K(assoc) values of 6.0 x 10(5) and 1.4 x 10(5) M(-)(1), respectively. Adding 1 to the 1:1 solution of 23 and 1-octyl-3-(4-oxo-3,4-dihydro-pyrido[2,3-d]pyrimidin-2-yl)urea 24 or 1-octyl-3-(4-oxo-1,4-dihydro-pyrimidin-2-yl)urea 25, which had been developed initially by Zimmerman and Meijer, respectively, induces dimers 23.24 and 23.25 to dissociate, leading to the formation of dimers 1.23 and 24.24 or 25.25, respectively. The new hydrazide-based hydrogen-bonding modules described are useful building blocks for self-assembly and open a new avenue to recognition between discrete supramolecular species.

Nonamphiphilic, hydrogen-bonded hydrazide foldamers appended with four or six long flexible chains were revealed to spontaneously assemble to form vesicles in methanol and organogels in aliphatic hydrocarbons. SEM, AFM, TEM, DLS, and fluorescence microscopy were all used to identify the structures of the vesicles. It was proposed that intermolecular pi stacking of the folded frameworks and hydrogen bonding of the amide units in the appended chains induced the molecules to produce cylindrical aggregates. In polar methanol, these aggregates packed together to generate one-layered vesicles owing to hydrophobically induced entanglement of the peripheral chains, while in nonpolar hydrocarbons, the peripheral chains entwined across stacked cylinders to form three-dimensional networks and thus immobilize the liquid molecules.

Colloidal metal halide perovskite (MHP) nanocrystals (NCs) are an emerging class of fluorescent quantum dots (QDs) for next-generation optoelectronics. A great hurdle hindering practical applications, however, is their high lead content, where most attempts addressing the challenge in the literature compromised the material's optical performance or colloidal stability. Here, we present a postsynthetic approach that stabilizes the lead-reduced MHP NCs through high-entropy alloying. Upon doping the NCs with multiple elements in considerably high concentrations, the resulting high-entropy perovskite (HEP) NCs remain to possess excellent colloidal stability and narrowband emission, with even higher photoluminescence (PL) quantum yields, ηPL, and shorter fluorescence lifetimes, τPL. The formation of multiple phases containing mixed interstitial and doping phases is suggested by X-ray crystallography. Importantly, the crystalline phases with higher degrees of lattice expansion and lattice contraction can be stabilized upon high-entropy alloying. We show that the lead content can be approximately reduced by up to 55% upon high-entropy alloying. The findings reported here make one big step closer to the commercialization of perovskite NCs. ISSN:0002-7863 ISSN:1520-5126