- Photophysics of Perylene Diimide Dianions and Their Application in Photoredox Catalysis
-
The two-electron reduced forms of perylene diimides (PDIs) are luminescent closed-shell species whose photochemical properties seem underexplored. Our proof-of-concept study demonstrates that straightforward (single) excitation of PDI dianions with green
- Li, Han,Wenger, Oliver S.
-
supporting information
(2021/12/23)
-
- Novel method for preparing tris (3,6 -dioxo-heptyl) amine
-
The invention relates to a new method for preparing tris(3,6-dioxaheptyl)amine. The new method is characterized in that ammonia water, diethylene glycol monomethyl ether and thionyl chloride are takenas raw materials, and the tris(3,6-dioxaheptyl)amine is synthesized through three steps. The new method provided by the invention has the following advantages that reaction conditions are mild, the operation is safe, and the danger of using high-risk chemicals such as hydrogen and Raney nickel is avoided; the reaction conversion rate is high, and the product yield is high; only products, sodium chloride and a very small amount of pre-distillation fractions are produced in the process, excess materials can be recycled after treatment, three wastes are very few, and the production process is green and environmentally friendly.
- -
-
-
- Hybrids of Small-Molecule CD4 Mimics with Polyethylene Glycol Units as HIV Entry Inhibitors
-
CD4 mimics are small molecules that inhibit the interaction of gp120 with CD4. We have developed several CD4 mimics. Herein, hybrid molecules consisting of CD4 mimics with a long alkyl chain or a PEG unit attached through a self-cleavable linker were synthesized. In anti-HIV activity, modification with a PEG unit appeared to be more suitable than modification with a long alkyl chain. Thus, hybrid molecules of CD4 mimics, with PEG units attached through an uncleavable linker, were developed and showed high anti-HIV activity and low cytotoxicity. In investigation of pharmacokinetics in a rhesus macaque, a hybrid compound had a more effective PK profile than that of the parent compound, and intramuscular injection was a more useful administration route to maintain the high blood concentration of the CD4 mimic than intravenous injection. The presented hybrid molecules of CD4 mimics with a PEG unit would be practically useful when combined with a neutralizing antibody.
- Kobayakawa, Takuya,Tsuji, Kohei,Konno, Kiju,Himeno, Ai,Masuda, Ami,Yang, Tingting,Takahashi, Kohei,Ishida, Yusuke,Ohashi, Nami,Kuwata, Takeo,Matsumoto, Kaho,Yoshimura, Kazuhisa,Sakawaki, Hiromi,Miura, Tomoyuki,Harada, Shigeyoshi,Matsushita, Shuzo,Tamamura, Hirokazu
-
supporting information
p. 1481 - 1496
(2021/02/27)
-
- Self-Assembly and Molecular Recognition in Water: Tubular Stacking and Guest-Templated Discrete Assembly of Water-Soluble, Shape-Persistent Macrocycles
-
Supramolecular chemistry in aqueous media is an area with great fundamental and practical significance. To examine the role of multiple noncovalent interactions in controlled assembling and binding behavior in water, the self-association of five water-soluble hexakis(m-phenylene ethynylene) (m-PE) macrocycles, along with the molecular recognition behavior of the resultant assemblies, is investigated with UV-vis, fluorescence, CD, and NMR spectroscopy, mass spectrometry, and computational studies. In contrast to their different extents of self-aggregation in organic solvents, all five macrocycles remain aggregated in water at concentrations down to the micromolar (μM) range. CD spectroscopy reveals that 1-F6 and 1-H6, two macrocycles carrying chiral side chains and capable of H-bonded self-association, assemble into tubular stacks. The tubular stacks serve as supramolecular hosts in water, as exemplified by the interaction of macrocycles 1-H6 and 2-H6 and guests G1 through G4, each having a rod-like oligo(p-phenylene ethynylene) (p-PE) segment flanked by two hydrophilic chains. Fluorescence and 1H NMR spectroscopy revealed the formation of kinetically stable, discrete assemblies upon mixing 2-H6 and a guest. The binding stoichiometry, determined with fluorescence, 1H NMR, and ESI-MS, reveals that the discrete assemblies are novel pseudorotaxanes, each containing a pair of identical guest molecules encased by a tubular stack. The two guest molecules define the number of macrocyclic molecules that comprise the host, which curbs the "infinite" stack growth, resulting in a tubular stack with a cylindrical pore tailoring the length of the p-PE segment of the bound guests. Each complex is stabilized by the action of multiple noncovalent forces including aromatic stacking, side-chain H-bonding, and van der Waals interactions. Thus, the interplay of multiple noncovalent forces aligns the molecules of macrocycles 1 and 2 into tubular stacks with cylindrical inner pores that, upon binding rod-like guests, lead to tight, discrete, and well-ordered tubular assemblies that are unprecedented in water.
- Wang, Qiuhua,Zhong, Yulong,Miller, Daniel P.,Lu, Xiaoxing,Tang, Quan,Lu, Zhong-Lin,Zurek, Eva,Liu, Rui,Gong, Bing
-
p. 2915 - 2924
(2020/02/04)
-
- Targeting G Protein-Coupled Receptors with Magnetic Carbon Nanotubes: The Case of the A3 Adenosine Receptor
-
The A3 adenosine receptor (AR) is a G protein-coupled receptor (GPCR) overexpressed in the membrane of specific cancer cells. Thus, the development of nanosystems targeting this receptor could be a strategy to both treat and diagnose cancer. Iron-filled carbon nanotubes (CNTs) are an optimal platform for theranostic purposes, and the use of a magnetic field can be exploited for cancer magnetic cell sorting and thermal therapy. In this work, we have conjugated an A3AR ligand on the surface of iron-filled CNTs with the aim of targeting cells overexpressing A3ARs. In particular, two conjugates bearing PEG linkers of different length were designed. A docking analysis of A3AR showed that neither CNT nor linker interferes with ligand binding to the receptor; this was confirmed by in vitro preliminary radioligand competition assays on A3AR. Encouraged by this result, magnetic cell sorting was applied to a mixture of cells overexpressing or not the A3AR in which our compound displayed indiscriminate binding to all cells. Despite this, it is the first time that a GPCR ligand has been anchored to a magnetic nanosystem, thus it opens the door to new applications for cancer treatment.
- Pineux, Florent,Federico, Stephanie,Klotz, Karl-Norbert,Kachler, Sonja,Michiels, Carine,Sturlese, Mattia,Prato, Maurizio,Spalluto, Giampiero,Moro, Stefano,Bonifazi, Davide
-
supporting information
p. 1909 - 1920
(2020/09/11)
-
- MULTI-ELECTRON REDOX-ACTIVE ORGANIC MOLECULES FOR HIGH-ENERGY-DENSITY NONAQUEOUS REDOX FLOW BATTERIES
-
The invention relates to 1,4-diaminoanthraquinones and an electrolyte, and their use in batteries.
- -
-
Page/Page column 10-13
(2020/12/11)
-
- A halogen-bonding foldamer molecular film for selective reagentless anion sensing in water
-
We describe self-assembled monolayers of novel halogen-bonding and hydrogen-bonding foldamer receptors capable of selectively recruiting perrhenate, iodide and thiocyanate in water. Unprecedented anion sensing via impedance-derived capacitance spectroscopy enables subsequent sensitive and selective anion detection without the need for a redox probe. Importantly, the sensing of any anion should be possible using this novel electrochemical approach.
- Hein, Robert,Borissov, Arseni,Smith, Martin D.,Beer, Paul D.,Davis, Jason J.
-
supporting information
p. 4849 - 4852
(2019/05/02)
-
- Anion Recognition in Water by Charge-Neutral Halogen and Chalcogen Bonding Foldamer Receptors
-
A novel strategy for the recognition of anions in water using charge-neutral σ-hole halogen and chalcogen bonding acyclic hosts is demonstrated for the first time. Exploiting the intrinsic hydrophobicity of halogen and chalcogen bond donor atoms integrated into a foldamer structural molecular framework containing hydrophilic functionalities, a series of water-soluble receptors was constructed for an anion recognition investigation. Isothermal titration calorimetry (ITC) binding studies with a range of anions revealed the receptors to display very strong and selective binding of large, weakly hydrated anions such as I- and ReO4-. This is achieved through the formation of 2:1 host-guest stoichiometric complex assemblies, resulting in an encapsulated anion stabilized by cooperative, multidentate, convergent σ-hole donors, as shown by molecular dynamics simulations carried out in water. Importantly, the combination of multiple σ-hole-anion interactions and hydrophobic collapse results in I- affinities in water that exceed all known σ-hole receptors, including cationic systems (β2 up to 1.68 × 1011 M-2). Furthermore, the anion binding affinities and selectivity trends of the first example of an all-chalcogen bonding anion receptor in pure water are compared with halogen bonding and hydrogen bonding receptor analogues. These results further advance and establish halogen and chalcogen bond donor functions as new tools for overcoming the challenging goal of anion recognition in pure water.
- Borissov, Arseni,Marques, Igor,Lim, Jason Y.C.,Félix, Vítor,Smith, Martin D.,Beer, Paul D.
-
supporting information
p. 4119 - 4129
(2019/03/07)
-
- Cell-Penetrating Dynamic-Covalent Benzopolysulfane Networks
-
Cyclic oligochalcogenides (COCs) are emerging as promising systems to penetrate cells. Clearly better than and different to the reported diselenolanes and epidithiodiketopiperazines, we introduce the benzopolysulfanes (BPS), which show efficient delivery, insensitivity to inhibitors of endocytosis, and compatibility with substrates as large as proteins. This high activity coincides with high reactivity, selectively toward thiols, exceeding exchange rates of disulfides under tension. The result is a dynamic-covalent network of extreme sulfur species, including cyclic oligomers, from dimers to heptamers, with up to nineteen sulfurs in the ring. Selection from this unfolding adaptive network then yields the reactivities and selectivities needed to access new uptake pathways. Contrary to other COCs, BPS show high retention on thiol affinity columns. The identification of new modes of cell penetration is important because they promise new solutions to challenges in delivery and beyond.
- Cheng, Yangyang,Zong, Lili,López-Andarias, Javier,Bartolami, Eline,Okamoto, Yasunori,Ward, Thomas R.,Sakai, Naomi,Matile, Stefan
-
p. 9522 - 9526
(2019/06/24)
-
- Curcumin derivative and uses thereof
-
The present invention relates to a curcumin derivative represented by a general formula (I) or a pharmaceutically acceptable salt thereof, and a preparation method thereof, a composition containing aneffective amount of the compound represented by the general formula (I) or the pharmaceutically acceptable salt thereof, and applications of the compound represented by the general formula (I) or thepharmaceutically acceptable salt thereof in preparation of drugs for treatment of cancers, fatty liver, inflammations and the like, wherein R and R are defined in the specification.
- -
-
-
- AMYLOID TARGETING AGENTS AND METHODS OF USING THE SAME
-
Provided herein is the design and synthesis of novel molecular rotor fluorophores useful for detection of amyloid or amyloid like proteins. The fluorophores are designed to exhibit enhanced fluorescence emission upon associating with amyloid or amyloid like proteins as compared to unbound compound. Also disclosed herein are methods for treating diseases associated with amyloid or amyloid like proteins.
- -
-
-
- Thermodynamics of Halide Binding to a Neutral Bambusuril in Water and Organic Solvents
-
Driving forces of anion binding in water in contrast to nonpolar environments are of high interest because of their relevance to biology and medicine. Here we report a neutral bambusuril macrocycle (1), soluble in both water and nonpolar solvents due to decoration with 12 polyethylene glycol-based substituents. The new bambusuril has the highest affinity for I- in pure water ever reported for a synthetic macrocycle relying on hydrogen bonding interactions rather than metal coordination or Coulombic forces. Isothermal titration calorimetry (ITC) experiments in nine different solvents, ranging from polar water to nonpolar carbon tetrachloride, provided insight into the forces responsible for halide binding by bambusurils. The different importance of anion solvation and solvent expulsion from the cavity of the macrocycle in various solvents is illustrated by the fact that halide binding in water and chloroform is exclusively driven by favorable enthalpy with an entropic penalty, while in alcohols and nonpolar solvents, both favorable enthalpy and entropy contribute to anion encapsulation. DFT calculations and correlation of thermodynamic data with the solvent Swain acity parameter further underscore the importance of solvent effects on anion binding by bambusurils.
- Fiala, Tomas,Sleziakova, Kristina,Marsalek, Kamil,Salvadori, Karolina,Sindelar, Vladimir
-
p. 1903 - 1912
(2018/02/23)
-
- Self-Assembly Can Direct Dynamic Covalent Bond Formation toward Diversity or Specificity
-
With the advent of reversible covalent chemistry the study of the interplay between covalent bond formation and noncovalent interactions has become increasingly relevant. Here we report that the interplay between reversible disulfide chemistry and self-assembly can give rise either to molecular diversity, i.e., the emergence of a unprecedentedly large range of macrocycles or to molecular specificity, i.e., the autocatalytic emergence of a single species. The two phenomena are the result of two different modes of self-assembly, demonstrating that control over self-assembly pathways can enable control over covalent bond formation.
- Komáromy, Dávid,Stuart, Marc C. A.,Monreal Santiago, Guillermo,Tezcan, Meniz,Krasnikov, Victor V.,Otto, Sijbren
-
supporting information
p. 6234 - 6241
(2017/05/09)
-
- Tuneable Transient Thermogels Mediated by a pH- and Redox-Regulated Supramolecular Polymerization
-
A multistimuli-responsive transient supramolecular polymerization of β-sheet-encoded dendritic peptide monomers in water is presented. The amphiphiles, which contain glutamic acid and methionine, undergo a glucose oxidase catalyzed, glucose-fueled transient hydrogelation in response to an interplay of pH and oxidation stimuli, promoted by the production of reactive oxygen species (ROS). Adjusting the enzyme and glucose concentration allows tuning of the assembly and the disassembly rates of the supramolecular polymers, which dictate the stiffness and transient stability of the hydrogels. The incorporation of triethylene glycol chains introduces thermoresponsive properties to the materials. We further show that repair enzymes are able to reverse the oxidative damage in the methionine-based thioether side chains. Since ROS play an important role in signal transduction cascades, our strategy offers great potential for applications of these dynamic biomaterials in redox microenvironments.
- Spitzer, Daniel,Rodrigues, Leona Lucas,Stra?burger, David,Mezger, Markus,Besenius, Pol
-
supporting information
p. 15461 - 15465
(2017/11/13)
-
- ALKYNYL INDAZOLE DERIVATIVE AND USE THEREOF
-
The main object of the present invention is to provide a novel compound which has a VEGF receptor tyrosine kinase inhibitory activity and is useful as an active ingredient for the treatment of diseases accompanying angiogenesis or edema, for example, age-related macular degeneration or the like. The present invention includes, for example, an alkynyl indazole derivative represented by the following general formula (I), a pharmaceutical acceptable salt thereof, and a medicine containing thereof.
- -
-
Paragraph 0142; 0143
(2017/02/24)
-
- Design, synthesis and cytotoxic activity of water-soluble quinones with dibromo-p-benzoquinone cores and amino oligo(ethylene glycol) side chains against MCF-7 breast cancer cells
-
A series of novel quinones was synthesized by reacting tetrabromo-p-benzoquinone with amino oligo(ethylene glycol) dendrons of generation numbers g = 0-2. According to the performed shake-flask experiments, their aqueous solubility (S = 18 mg l?1-1.6 g ml?1) and partition coefficients (log?Poct/wat = 2.53-0.21) can be tuned in a wide range as a function of g. In vitro cytotoxicity assays of tetrabromo-p-benzoquinone and its derivatives against MCF-7 human breast cancer cells showed a concentration- and generation-specific biological activity with IC50-values as low as 0.8 μM. Further investigations revealed a considerable selectivity against cancer cells, as indicated by a weak cytotoxicity against human skin fibroblast cells (>80% survival) within the studied range of concentrations. The results demonstrate that these novel amino oligo(ethylene glycol) dendrons depict versatile tools to ameliorate physical and pharmacological characteristics of extremely hydrophobic molecules and make them susceptible to biological applications.
- Scherz, Leon F.,Abdel-Rahman, Engy A.,Ali, Sameh S.,Schlüter, A. Dieter,Abdel-Rahman, Mona A.
-
p. 662 - 672
(2017/03/30)
-
- POLYMERIZABLE DENTAL MATERIAL
-
The invention relates to a dental material, which contains: at least one monomer, containing at least one radically polymerizable ehtylenically unsaturated group and at least one acid group; at least one monomer, which contains no acid groups and at least one radically polymerizable ethylenically unsaturated group; at least one photoinitiator; and at least one tertiary aromatic amine as a coinitiator, which amine has a benzene ring, to which at least one dialkylamine group and at least one further group are directly bonded. According to the invention, the further group is selected from carboxylic acid ester groups containing at least one polyoxyalkylene group having at least 2 oxyethylene and/or oxypropylene units; and amide groups.
- -
-
Paragraph 0077
(2017/03/28)
-
- Monitoring Fluorinated Dendrimer-Based Self-Assembled Drug-Delivery Systems with 19F Magnetic Resonance
-
Monitoring a drug-delivery system with an imaging modality is of great importance for detailed understanding of drug-delivery processes and for achieving optimal therapeutic effects. Here, novel fluorinated self-assembled dendrimers with a single 19
- Liu, Xin,Yuan, Yaping,Bo, Shaowei,Li, Yu,Yang, Zhigang,Zhou, Xin,Chen, Shizhen,Jiang, Zhong-Xing
-
p. 4461 - 4468
(2017/08/23)
-
- Potential for minimal self-replicating systems in a dynamic combinatorial library of equilibrating imines
-
The presence of a self-replicator in a dynamic combinatorial library (DCL) offers function above and beyond libraries under thermodynamic control, moving towards out-of-equilibrium systems which mimic biological networks. In this work, we examine a previously reported DCL based on reversible imine formation to give amphiphilic structures. The amphiphilic imines were readily produced in organic solvents, and were found to aggregate to micelles in water as judged by diffusion-ordered NMR spectroscopy, dynamic light scattering and interferometric scattering microscopy. Unfortunately, the autocatalytic formation of products was not observed in water, and preformed imines slowly hydrolysed to aldehyde and amine components at neutral pD.
- Morrow, Sarah M.,Bissette, Andrew J.,Fletcher, Stephen P.
-
supporting information
p. 5005 - 5010
(2017/07/27)
-
- Synthesis and pH-dependent hydrolysis profiles of mono- and dialkyl substituted maleamic acids
-
Maleamic acid derivatives as weakly acid-sensitive linkers or caging groups have been used widely in smart delivery systems. Here we report on the controlled synthetic methods to mono- and dialkyl substituted maleamic acids and their pH-dependent hydrolysis behaviors. Firstly, we studied the reaction between n-butylamine and citraconic anhydride, and found that the ratio of the two n-butyl citraconamic acid isomers (α and β) could be finely tuned by controlling the reaction temperature and time. Secondly, we investigated the effects of solvent, basic catalyst, and temperature on the reaction of n-butylamine with 2,3-dimethylmaleic anhydride, and optimized the reaction conditions to efficiently synthesize the dimethylmaleamic acids. Finally, we compared the pH-dependent hydrolysis profiles of four OEG-NH2 derived water-soluble maleamic acid derivatives. The results reveal that the number, structure, and position of the substituents on the cis-double bond exhibit a significant effect on the pH-related hydrolysis kinetics and selectivity of the maleamic acid derivatives. Interestingly, for the mono-substituted citraconamic acids (α-/β-isomer), we found that their hydrolyses are accompanied by the isomerization between the two isomers.
- Su, Shan,Du, Fu-Sheng,Li, Zi-Chen
-
supporting information
p. 8384 - 8392
(2017/10/19)
-
- IN VITRO COMPOSITIONS COMPRISING HUMAN SAMPLE AND AMYLOID TARGETING AGENT
-
Provided herein are compositions and methods useful for detection of amyloid related disorders in samples, such as human tissue, cell or body fluid. Use of the compositions and methods herein allows for the rapid, in vitro detection of amyloid accumulation, often before amyloid disorder symptoms are manifest or without introduction of foreign fluorophore molecules into a subject.
- -
-
-
- Tuning the DNA binding and cleavage of bpa Cu(II) complexes by ether tethers with hydroxyl and methoxy groups
-
Five bpa (bis(2-picolyl)amine) derivatives (1b, 2e, 3f, 4c, 5d) carrying ether tethers with hydroxyl and methoxy groups, have been synthesized from pyridine aldehyde and the respective amines by reductive amination. Their Cu(II) complexes carrying additio
- Sudarga Tjakraatmadja, Airlangga Arya Janitra,Lüdtke, Carsten,Kulak, Nora
-
p. 159 - 169
(2016/10/03)
-
- Polyacrylamide pseudo crown ethers via hydrogen bond-assisted cyclopolymerization
-
Polyacrylamide pseudo crown ethers with large in-chain rings (15–24 membered) were synthesized by hydrogen bond-mediated cyclopolymerization of bisacrylamides comprising poly(ethylene oxide) spacers (PEGnDAAm, ethylene oxide units: n = 3–6). The monomers undergo the intramolecular hydrogen bonding of the bisacrylamide units in halogenated solvents to dynamically place the two olefins adjacently. As a result, the bisacrylamides homogeneously allowed controlled radical cyclopolymerization without any macroscopic gelation in 1,2-dichloroethane, even at relatively high concentration of monomers (200 mM), to directly provide precision cyclopolyacrylamides and the related copolymers with high cyclization efficiency (84–98%). Owing to the in-chain ring pendants, a cyclopolyacrylamide had glass transition temperature higher than a corresponding polyacrylamide with linear pendants.
- Kimura, Yoshihiko,Miyabara, Yuichiro,Terashima, Takaya,Sawamoto, Mitsuo
-
p. 3294 - 3302
(2016/09/09)
-
- Antioxidants Having Aromatic Structures Reacting with Superoxide
-
Disclosed is a method of treating diseases which are: reactive oxygen species mediated, ischemic or reperfusion-related, or T-cell mediated, including autoimmune diseases. The method is administering a therapeutically effective amount of a formulation wherein the active ingredient includes non-phenolic aromatic structures that are electron deficient and are capable of converting the superoxide radical to O2; and/or of converting superoxide radical to oxygen and hydrogen peroxide, or pharmaceutically acceptable salts of said structures. Also disclosed is a method of diagnosing and treating such diseases and conditions.
- -
-
-
- AMYLOID TARGETING AGENTS AND METHODS OF USING THE SAME
-
Provided herein is the design and synthesis of novel molecular rotor fluorophores useful for detection of amyloid or amyloid like proteins. The fluorophores are designed to exhibit enhanced fluorescence emission upon associating with amyloid or amyloid like proteins as compared to unbound compound. Also disclosed herein are the methods for treating of diseases associated with an amyloid or amyloid like proteins.
- -
-
-
- N-monosubstituted methoxy-oligo(ethylene glycol) carbamate ester prodrugs of resveratrol
-
Resveratrol is a natural polyphenol with many interesting biological activities. Its pharmacological exploitation in vivo is, however, hindered by its rapid elimination via phase II conjugative metabolism at the intestinal and, most importantly, hepatic levels. One approach to bypass this problem relies on prodrugs. We report here the synthesis, characterization, hydrolysis, and in vivo pharmacokinetic behavior of resveratrol prodrugs in which the OH groups are engaged in an N-monosubstituted carbamate ester linkage. As promoiety, methoxy-oligo(ethylene glycol) groups (m-OEG) (CH3-[OCH2CH2]n-) of defined chain length (n = 3, 4, 6) were used. These are expected to modulate the chemico-physical properties of the resulting derivatives, much like longer poly(ethylene glycol) (PEG) chains, while retaining a relatively low MW and, thus, a favorable drug loading capacity. Intragastric administration to rats resulted in the appearance in the bloodstream of the prodrug and of the products of its partial hydrolysis, confirming protection from first-pass metabolism during absorption.
- Mattarei, Andrea,Azzolini, Michele,Zoratti, Mario,Biasutto, Lucia,Paradisi, Cristina
-
p. 16085 - 16102
(2015/12/01)
-
- SHORT CHAIN PEGYLATION OF AMINO ACID MONOMERS GLUTAMINE AND LYSINE AND PEPTIDES FORMED THEREBY
-
Novel synthesized amino acids of glutamine and lysine that are directly PEGylated with small, monodisperse PEGs, and a novel process for creating novel amino acid monomers using PEGylation. These amino acids are readily incorporated into peptides for a range of different applications.
- -
-
Paragraph 0041
(2016/01/01)
-
- Dynamic Covalent Assembly of Peptoid-Based Ladder Oligomers by Vernier Templating
-
Dynamic covalent chemistry, in conjunction with template-directed assembly, enables the fabrication of extended nanostructures that are both precise and tough. Here we demonstrate the dynamic covalent assembly of peptoid-based molecular ladders with up to 12 rungs via scandium(III)-catalyzed imine metathesis by employing the principle of Vernier templating, where small precursor units with mismatched numbers of complementary functional groups are coreacted to yield larger structures with sizes determined by the respective precursor functionalities. Owing to their monomer diversity and synthetic accessibility, sequence-specific oligopeptoids bearing dynamic covalent pendant groups were employed as precursors for molecular ladder fabrication. The generated structures were characterized using matrix-assisted laser desorption/ionization mass spectrometry and gel permeation chromatography, confirming successful molecular ladder fabrication.
- Wei, Tao,Jung, Jae Hwan,Scott, Timothy F.
-
supporting information
p. 16196 - 16202
(2016/01/15)
-
- Protein-Induced Supramolecular Disassembly of Amphiphilic Polypeptide Nanoassemblies
-
Mimicking noncovalent interaction based processes in nature has been an important goal of supramolecular chemistry. Here, we report on amphiphilic polypeptides that self-assemble to form nanoscale supramolecular assemblies and are programmed to disassemble in response to a specific protein. Benzenesulfonamide and carbonic anhydrase have been chosen as the ligand and protein, respectively, to demonstrate this possibility. Since the amphiphilic nanoassembly sequesters hydrophobic guest molecules, the protein-specific disassembly event provides a protein-sensitive molecular release as well. We envision that the binding induced disassembly and guest release might open up new opportunities for the next generation of supramolecular assemblies for protein-specific delivery and diagnostics.
- Molla, Mijanur Rahaman,Prasad, Priyaa,Thayumanavan
-
supporting information
p. 7286 - 7289
(2015/06/30)
-
- Designed Intercalators for Modification of DNA Origami Surface Properties
-
The modification of the backbone properties of DNA origami nanostructures through noncovalent interactions with designed intercalators, based on acridine derivatized with side chains containing esterified fatty acids or oligo(ethylene glycol) residues is reported. Spectroscopic analyses indicate that these intercalators bind to DNA origami structures. Atomic force microscopy studies reveal that intercalator binding does not affect the structural intactness but leads to altered surface properties of the highly negatively charged nanostructures, as demonstrated by their interaction with solid mica or graphite supports. Moreover, the noncovalent interaction between the intercalators and the origami structures leads to alteration in cellular uptake, as shown by confocal microscopy studies using two different eukaryotic cell lines. Hence, the intercalator approach offers a potential means for tailoring the surface properties of DNA nanostructures. Into the fold: Designed acridine derivatives bearing esterified fatty acids or oligo-ethyleneglycol side chains (see figure) can be used to alter the surface properties of DNA origami nanostructures. Noncovalent binding of the intercalators changes the interaction of the origami with solid supports and the membrane of living cells. HOPG=highly oriented pyrolytic graphite.
- Brglez, Josipa,Nikolov, Pavel,Angelin, Alessandro,Niemeyer, Christof M.
-
p. 9440 - 9446
(2015/06/30)
-
- Non-invasive, real-time reporting drug release in vitro and in vivo
-
We developed a real-time drug-reporting conjugate (CPT-SS-CyN) composed of a near-infrared (NIR) fluorescent cyanine-amine dye (CyN), a disulfide linker, and a model therapeutic drug (camptothecin, CPT). Treatment with dithiothreitol (DTT) induces cleavage of the disulfide bond, followed by two simultaneous intramolecular cyclization reactions with identical kinetics, one to cleave the urethane linkage to release the NIR dye and the other to cleave the carbonate linkage to release CPT. The released CyN has an emission wavelength (760 nm) that is significantly different from CPT-SS-CyN (820 nm), enabling easy detection and monitoring of drug release. A linear relationship between the NIR fluorescence intensity at 760 nm and the amount of CPT released was observed, substantiating the use of this drug-reporting conjugate to enable precise, real-time, and non-invasive quantitative monitoring of drug release in live cells and semi-quantitative monitoring in live animals. This journal is
- Zhang, Yanfeng,Yin, Qian,Yen, Jonathan,Li, Joanne,Ying, Hanze,Wang, Hua,Hua, Yuyan,Chaney, Eric J.,Boppart, Stephen A.,Cheng, Jianjun
-
p. 6948 - 6951
(2015/04/22)
-
- Fluorous 1,2,3-Triazol-4-ylmethyl Amines and Amine Derivatives for Novel Surfactant Applications
-
A series of fluorous surfactants with additional functionality were generated through the attachment of substituents at the amino nitrogen atom of the surfactant moiety. Examples of molecules containing one and two triazole ring systems were synthesized through N-alkylation and N-acylation strategies.
- Francis, Dominic V.,Harper, Jason B.,Read, Roger W.
-
-
- Living ring-opening metathesis-polymerization synthesis and redox-sensing properties of norbornene polymers and copolymers containing ferrocenyl and tetraethylene glycol groups
-
The controlled synthesis of monodisperse, redox-active metallopolymers and their redox properties and functions, including robust electrode derivatization and sensing, remains a challenge. Here a series of polynorbornene homopolymers and block copolymers containing side-chain amidoferrocenyl groups and tetraethylene glycol linkers were prepared via living ring-opening metathesis polymerization initiated by Grubbs' third-generation catalyst (1). Their molecular weights were determined using MALDI-TOF mass spectra, size exclusion chromatography (SEC), end-group analysis, and the empirical Bard-Anson electrochemical equation. All polymerizations followed a living and controlled manner, and the number of amidoferrocenyl units varied from 5 to 332. These homopolymers and block copolymers were successfully used to prepare modified Pt electrodes that showed excellent stability. The modified Pt electrodes show excellent qualitative sensing of ATP2- anions, in particular those prepared with the block copolymers. The quantitative recognition and titration of [n-Bu4N]2[ATP] was carried out using the CH 2Cl2 solution of the homopolymers, showing that two amidoferrocenyl groups of the homopolymers interacted with each ATP2- molecule. This stoichiometry led us to propose the H-bonding modes in the supramolecular polymeric network.
- Gu, Haibin,Rapakousiou, Amalia,Castel, Patricia,Guidolin, Nicolas,Pinaud, Noeel,Ruiz, Jaime,Astruc, Didier
-
supporting information
p. 4323 - 4335
(2014/12/09)
-
- Aryloxymaleimides for cysteine modification, disulfide bridging and the dual functionalization of disulfide bonds
-
Tuning the properties of maleimide reagents holds significant promise in expanding the toolbox of available methods for bioconjugation. Herein we describe aryloxymaleimides which represent 'next generation maleimides' of attenuated reactivity, and demonstrate their ability to enable new methods for protein modification at disulfide bonds.
- Marculescu, Cristina,Kossen, Hanno,Morgan, Rachel E.,Mayer, Patrick,Fletcher, Sally A.,Tolner, Berend,Chester, Kerry A.,Jones, Lyn H.,Baker, James R.
-
supporting information
p. 7139 - 7142
(2014/07/07)
-
- New derivatives of resveratrol
-
A novel class of derivatives of resveratrol is provided which have favourable physico-chemical properties when compared with resveratrol itself. It is characterized by the presence of three carbamate functions, in which resveratrol is the oxygen-linked moiety, while the nitrogen atom carries a substituent conferring desirable characteristics to the molecule. These new compounds are especially suitable as precursors (prodrugs) and vehicles of resveratrol in preparations used as dietary integrators or in pharmaceutical compositions: they are stable towards oxidative degradation allowing for long shelf lifetimes and have suitable reactivity to regenerate and deliver resveratrol under physiological conditions.
- -
-
-
- Multivalent alteration of quorum sensing in Staphylococcus aureus
-
Virulence in Staphylococcus aureus is strongly and positively correlated with local cell density. Here we present an effective approach to modulate this group behaviour using multivalent peptide-polymer conjugates. Our results show that by attaching multiple AIP-4′ units to macromolecular scaffolds, the agr QS response in S. aureus was affected strongly, while displaying a clear multivalency effect.
- Melamed Yerushalmi, Sarit,Buck, Maren E.,Lynn, David M.,Lemcoff, N. Gabriel,Meijler, Michael M.
-
p. 5177 - 5179
(2013/06/27)
-
- Single-particle and ensemble diffusivitiesa-test of ergodicity
-
To prove the ergodic theorem experimentally the diffusivities of guest molecules inside a nanostructured porous glass were measured by using two conceptually different approaches under identical conditions. The data obtained through the direct observation of dye-molecule diffusion by single-molecule tracking experiments (red circles) was in perfect agreement with the ensemble value obtained in pulsed-field gradient NMR experiments (black squares). Copyright
- Feil, Florian,Naumov, Sergej,Michaelis, Jens,Valiullin, Rustem,Enke, Dirk,Kaerger, Joerg,Braeuchle, Christoph
-
p. 1152 - 1155
(2012/03/22)
-
- HETEROCYCLIC COMPOUND AND HEMATOPOIETIC STEM CELL AMPLIFIER
-
An expansion agent for hematopoietic stem cells and/or hematopoietic progenitor cells useful for improvement in the efficiency of gene transfer into hematopoietic stem cells for gene therapy useful for treatment of various disorders is provided. An expansion agent for hematopoietic stem cells and/or hematopoietic progenitor cells containing a compound represented by the formula (I) (wherein X, Y, Z, Ar1, R1, R2, R3, R4, R5, R6 and R7 are as defined in the description), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or a solvate thereof, which can expand hematopoietic stem cells and/or hematopoietic progenitor cells.
- -
-
-
- Structure-conductivity relationship for peptoid-based PEO-mimetic polymer electrolytes
-
Polymer electrolytes offer great potential for application in lithium batteries. In order to systematically optimize the performance of these materials, atomic level synthetic control over the polymer chemical structure is desired. In this study, we designed a series of chemically defined, monodisperse peptoid polymers to explore the impact of side-chain structure on the thermal and electrical properties. A series of comblike peptoid homopolymers with ethylene oxide (EO)n side chains of varying length were synthesized by a rapid solid phase synthetic method. The electrical properties of these materials with dissolved lithium salt were characterized by ac impedance. The temperature dependence of the ionic conductivity of the polypeptoid electrolytes is consistent with the Vogel-Tamman-Fulcher equation. The optimum ionic conductivity of 2.6 × 10-4 S/cm achieved for oligo-N-2-(2-(2-methoxyethoxy)ethoxy)ethylglycine-Li salt complex at 100 °C, is approximately 10-fold lower than the analogous PEO-salt complex. It is, however, nearly 2 orders of magnitude higher than previously reported comblike PEO-mimetic polypeptides. The ionic conductivities of these side chain analogs vary by 3 orders of magnitude, but this variation is entirely governed by the proximity of the system to the glass transition temperature. This investigation shows that polypeptoids provide a unique platform for examining the structure-property relationships of solid polymer electrolytes.
- Sun, Jing,Stone, Gregory M.,Balsara, Nitash P.,Zuckermann, Ronald N.
-
p. 5151 - 5156
(2012/09/25)
-
- Synthesis and thermoresponsive solution properties of poly[oligo(ethylene glycol) (meth)acrylamide]s: Biocompatible PEG analogues
-
A library of (meth)acrylamido (co)polymers was prepared by reacting poly(pentafluorophenyl (meth)acrylate) with α-amino, ω-methoxy functionalized di(ethylene glycol), tri(ethylene glycol), and poly(ethylene glycol) (PEG)-350, PEG-750, and PEG-5k, in combination with hexylamine or thyroxine. The resulting copolymers showed an improved solubility in water (higher or absent LCST values) and in alcohols (lower or absent UCST values) than the analogous common series of poly[oligo(ethylene glycol) methyl ether (meth)acrylates]. The polyacrylamido species showed a better solubility than the corresponding polymethacrylamido derivatives of similar molecular weight with all polyacrylamides investigated being water-soluble at temperatures exceeding 90.0 °C. Tunable thermosensitive behavior could be effected by the incorporation of the hydrophobic hexylamide comonomer. Similarly, an acrylamido backbone with grafted oligo(propylene glycol 600) amides exhibited a sharp LCST-type transition around 22.0 °C. The UCST-type transitions of the (meth)acrylamido homopolymers were evaluated in 2-propanol and 1-octanol and were found to increase with an increasing ethylene glycol side chain length, but were essentially independent of the alcohol chain length with polymers exhibiting higher UCST transitions in 2-propanol vs 1-octanol. Cytotoxicity tests on MRC5 fibroblast cells of the di- and tri(ethylene glycol) methyl ether acrylamido homopolymers revealed no toxicity up to concentrations of 10.0 g/L. By employing mixtures of di(ethylene glycol) methyl ether amine and the prohormone thyroxine (T4), water-soluble copolymers containing varying amounts of T4 could be easily synthesized. Because of enhanced solubility, low toxicity, and higher hydrolytic stability of amides versus ester linkages, activated ester polymers in combination with amino-functionalized ethylene glycol based side chains are presented as a versatile platform for highly soluble, biocompatible, bioconjugated materials.
- Chua, Giles B. H.,Roth, Peter J.,Duong, Hien T. T.,Davis, Thomas P.,Lowe, Andrew B.
-
scheme or table
p. 1362 - 1374
(2012/06/29)
-
- Electrochemical "switching" of Si(100) modular assemblies
-
We report on a modular approach for producing well-defined and electrochemically switchable surfaces on Si(100). The switching of these surfaces is shown to change a Si(100) surface from resistant to cell adsorption to promoting cell adhesion. The electrochemical conversion of the modified electrode surface is demonstrated by X-ray photoelectron spectroscopy, X-ray reflectometry, contact angle and cell adhesion studies.
- Ciampi, Simone,James, Michael,Le Saux, Guillaume,Gaus, Katharina,Justin Gooding
-
supporting information; experimental part
p. 844 - 847
(2012/03/07)
-
- Rapid preparation of multifunctional surfaces for orthogonal ligation by microcontact chemistry
-
Microcontact chemistry has been applied to patterned glass and silicon substrates by successive reaction of unprotected and monoprotected heterobifunctional linkers with alkene-terminated self-assembled monolayers (SAMs) to produce bi-, tri-, and tetrafunctional surfaces. Photochemical microcontact printing of an azide thiol linker followed by immobilization of an acid thiol linker on an undecenyl-terminated SAM results in a well-defined, micropatterned surface with terminal azide, acid, and alkene groups. Biologically relevant molecules (biotin, carbohydrates) have been selectively attached to the surface by means of orthogonal ligation chemistry, and the resulting microarrays display selective binding to fluorescently labeled proteins. An orthogonally addressable, tetrafunctional surface (azide, acid, alkene, and amine) can be prepared by an additional printing step of a tert-butyloxycarbonyl (Boc)-protected alkyne amine linker on the azide structures by using the copper(I)-catalyzed azide-alkyne Huisgen cycloaddition and subsequent removal of the protective group. Copyright
- Wendeln, Christian,Rinnen, Stefan,Schulz, Christian,Kaufmann, Tobias,Arlinghaus, Heinrich F.,Ravoo, Bart Jan
-
supporting information; experimental part
p. 5880 - 5888
(2012/07/01)
-
- A Synthesis of acetamidines
-
The condensation of primary amine with N,N-dimethylacetamide dimethyl acetal yields amixture of acetamidine and imidate ester. The product distribution in this reaction depends on the temperature, solvent, and structure of the primary amine. It is possible to suppress the formation of imidate ester by performing the reaction in the presence of excess dimethyl amine, yielding acetamidine as the exclusive product. For acetamidines that cannot be purified either by crystallization or distillation, this new method is necessary for the generation of pure acetamidines in good yields.
- Harjani, Jitendra R.,Liang, Chen,Jessop, Philip G.
-
p. 1683 - 1691
(2011/05/12)
-
- Folding of a donor-containing ionene by intercalation with an acceptor
-
Cationic ionenes that bear electron-rich 1,5-dialkoxynaphthalene (DAN) units within the alkylene segment were allowed to interact with different types of electron-deficient, acceptor-containing molecules in an effort to realize intercalation-induced folding of the ionenes; the collapse of the chains was expected to occur in such a way that the donor and acceptor units become arranged in an alternating fashion. Several acceptor-bearing molecules were prepared by the derivatization of pyromellitic dianhydride and naphthalene tetracarboxylic dianhydride with two different oligoethylene glycol monomethyl ether monoamines. This yielded acceptor molecules with different water solubility and allowed the examination of solvophobic effects in the folding process. UV/Vis spectroscopic studies were carried out by using a 1:1 mixture of the DAN-ionenes and different acceptor molecules in water/DMSO solvent mixtures. The intensity of the charge-transfer (CT) band was seen to increase with the water content in the solvent mixture, thereby suggesting that the intercalation is indeed aided by solvophobic effects. The naphthalene diimide (NDI) bearing acceptor molecules consistently formed significantly stronger CT complexes when compared to the pyromellitic diimide (PDI) bearing acceptor molecules, which is a reflection of the stronger π-stacking tendency of the former. AFM studies of drop-cast films of different ionene-acceptor combinations revealed that compact folded structures are formed most effectively under conditions in which the strongest CT complex is formed. Know when to fold 'em: When coerced to collapse in a polar solvent in the presence of an electron-deficient amphiphilic folding agent, suitably modified ionenes with a symmetrically positioned electron-rich 1,5-dialkoxylnaphthalene (DAN) unit appear to form an accordion-type folded structure wherein the units are arranged in an alternating fashion (see picture). D=Donor; A=Acceptor. Copyright
- De, Swati,Ramakrishnan
-
supporting information; experimental part
p. 149 - 156
(2011/10/08)
-
- Supramolecular ribbons from amphiphilic trisamides self-assembly
-
Two amphiphilic C3-symmetric OPE-based trisamides have been synthesized and their self-assembling features investigated in solution and on surface. Variable-temperature UV-vis experiments demonstrate the cooperative supramolecular polymerization of these trisamides that self-assemble by the operation of triple C=O???H-N H-bonding arrays between the amide functional groups and π-π stacking between the aromatic units. The helical organization of the aggregates has been demonstrated by circular dichroism at a concentration as low as 1 × 10-4 M in acetonitrile. In the reported trisamides, the large hydrophobic aromatic core acts as a solvophobic module impeding the interaction between the polar TEG chains and the amide H-bonds. This strategy makes unnecessary the separation of the amide functional groups to the polar tri(ethylene glycol) chains by paraffinic fragments. Achiral trisamide 1 self-assembles into flat ribbon-like structures that experience an amplification of chirality by the addition of a small amount of chiral 2 that generates twisted stripes.
- Garcia, Fatima,Buendia, Julia,Sanchez, Luis
-
supporting information; experimental part
p. 6271 - 6276
(2011/10/01)
-
- Vesicular assembly and thermo-responsive vesicle-to-micelle transition from an amphiphilic random copolymer
-
Vesicular assembly from a thermo-responsive amphiphilic random copolymer is reported. Vesicle-to-micelle transition above a critical morphology transition temperature (CMTT) resulted in selective triggered release of encapsulated hydrophilic guests over hydrophobic ones. The aggregation pattern of a control polymer indicated a defined role of the methacrylamide groups in the polymer backbone for such unprecedented self-assembly from a simple polymer.
- Dan, Krishna,Bose, Nivedita,Ghosh, Suhrit
-
supporting information; experimental part
p. 12491 - 12493
(2012/02/02)
-
- Simple and efficient: Ethylene glycol isonitrile gold(I) chlorides for the formation and stabilization of gold nanoparticles
-
Ethylene glycol isonitriles C≡N(CH2CH2O) nCH3 (5a, n = 1; 5b, n = 3; 5c, n = 4) with different chain lengths were prepared by using straightforward synthesis methodologies including the Gabriel synthesis and an Appel-type reaction protocol. Upon treatment with [AuCl(SMe)2], compounds 5a-c gave the corresponding isocyanide gold(I) chlorides [AuCl{C≡N(CH2CH2O) nCH3}] (7a, n = 1; 7b, n = 3; 7c, n = 4). Single-crystal X-ray diffraction studies reveal a polymeric (7a) or dimeric (7c) structure with aurophilic interactions. Gold(I) complexes 7a-c were applied in the formation and stabilization of gold nanoparticles (AuNPs). The isonitriles with their ethylene glycol functionalities, which provide multiple donating capabilities, are able to stabilize the encapsulated gold colloids. The reduction of 7a-c by the addition of Na[BH4] in tetrahydrofuran or methanol produces AuNPs without the further addition of any stabilizer, since metal-organic 7a-c combine the stabilizing component and gold source in one molecule. The dependency of different solvents, concentrations, and varying ethylene glycol chain lengths on the NP size and size distribution is reported. Characterization by TEM, UV/Vis spectroscopy, and XRPD revealed that AuNPs are formed with a size between 6.4(±1.4) to 9.5(±2.3) nm in methanol and 18.2(±2.3) to 27.2(±3.5) nm in tetrahydrofuran. Copyright
- Tuchscherer, Andre,Schaarschmidt, Dieter,Schulze, Steffen,Hietschold, Michael,Lang, Heinrich
-
experimental part
p. 4421 - 4428
(2011/11/30)
-
- Substituted Fused Imidazole Derivatives, Pharmaceutical Compositions, and Methods of Use Thereof
-
Substituted fused imidazole derivatives, methods of their preparation, pharmaceutical compositions comprising a substituted fused imidazole derivative, and methods of use in treating inflammation are provided. The substituted fused imidazole derivatives may control the activity or the amount or both the activity and the amount of heme-oxygenase.
- -
-
Page/Page column 149
(2011/09/14)
-
- 1H, 13C NMR, FT-IR, ESI MS and PM5 studies of a new 3,6,9-trioxadecylamide of monensin A and its complexes with Li+, Na+ and K+ cations
-
A new 3,6,9-trioxadecylamide of monensin A (M-AM4) has been synthesised and its ability to form complexes with Li+, Na+ and K + cations has been studied by ESI mass spectrometry, 1H and 13C NMR, FT-IR spectroscopy and PM5 semiempirical method. The ESI MS data indicate that M-AM4 forms complexes with Li+, Na+ and K+ of exclusively 1:1 stoichiometry which are stable up to cv = 70 V. The formation of the M-AM4-Na+ is strongly favoured. Above cv = 70 the fragmentation process is observed. The spectroscopic studies show that the structures of the M-AM4 and its complexes with the cations of 1:1 stoichiometry are stabilized by intramolecular hydrogen bonds in which the OH groups are always involved. The CO amide group is engaged in the complexation process of each cation. The M-AM4-K+ complex can also assume a structure in which the CO amide group does not participate in the complexation but the complexes of such structure do not dominate.
- ?owicki, Daniel,Huczyński, Adam,Brzezinski, Bogumil,Bartl, Franz
-
p. 121 - 131
(2011/04/23)
-
- Water accessibility to the binding cleft as a major switching factor from entropy-driven to enthalpy-driven binding of an alkyl group by synthetic receptors
-
Free energy, enthalpy, and entropy changes in the binding of alkyl pyridines to water-soluble zinc porphyrin receptors with varying accessibility of water to the binding cleft were determined to explain why the driving force of hydrophobic effects is enthalp-ic in some occasions and entropic in others. Zinc porphyrins bearing four alkyl pillars with terminal solubilizing poly(oxyethylene) (POE) chains of molecular weight of 750 (1), with eight alkyl pillars with terminal solubilizing POE chains of molecular weight of 350 (3), and with eight alkyl pillars with POE of molecular weight of 750 (4) had a binding cleft with decreasing water accessibility in this order as revealed by binding selectivity of imidazole/pyridine. Although all these porphyrins showed that the free energy of binding (-ΔG°) increases linearly as the alkyl group of the guest is lengthened (-ΔG° per CH2 was 2.6, 2.8, and 2.6kJmol-1 for 1, 3, and 4, respectively), the origin of the free energy gain was much different. Receptor 1 with the most hydrophilic binding site bound the alkyl group by an enthalpic driving force (4-pentylpyridine favored over 4-methylpyridine by ΔΔH° = -16.4 kJmol-1), while receptor 4 with the most hydrophobic binding site by an entropic driving force (4-pentylpyridine favored over 4-methylpyridine by ΔΔ5° = 39.6 JK-1mol-1). Receptor 3 showed intermediate behavior: both enthalpic and entropic terms drove the binding of the alkyl group with the en-thalpic driving force being dominant. The binding site of the four-pillared receptor (1) is open and accessible to water molecules, and is more hydro-philic than that of the eight-pillared receptor (4). We propose that the alkyl chains of 1 are exposed to water to produce a room to accommodate the guest to result in enthalpy-driven hy-drophobic binding, whereas 4 can accommodate the guest without such structural changes to lead to entropy-driven hydrophobic binding. Therefore, accessibility of water or exposure of the binding site to the water phase switches the driving force of hydropho-bic effects from an entropic force to an enthalpic force. 2010 Wiley-VCH Verlag GmbH Co. KGaA, Weinheim.
- Matsumoto, Sayaka,Iwamoto, Hiroya,Mizutani, Tadashi
-
supporting information; experimental part
p. 1163 - 1170
(2011/07/07)
-