- An array-based nanosensor for detecting cellular responses in macrophages induced by femtomolar levels of pesticides
-
Environmental agents can induce cellular responses at concentrations far below the limits of detection for current viability and biomarker-based cell sensing platforms. Hypothesis-free cell sensor platforms can be engineered to maximize sensitivity to phenotypic changes, providing a tool for lowering the threshold for detecting cellular changes. Pesticides are one of the most prevalent sources of chemical exposure due to their use in food and agriculture fields. We report here a FRET-based nanosensor array engineered to maximize responses to changes at cell surfaces after pesticide exposure. This sensor array robustly detected macrophage responses to femtomolar concentrations of common pesticides-orders of magnitude lower concentrations than traditional toxicological and biomarker-based strategies. Significantly, this platform was able to classify these responses by pesticide class, demonstrating the ability to distinguish between changes induced by these different agents. Taken together, hypothesis-free cell surface sensing is a promising tool for detecting the effects of ultra-trace environmental chemicals on human health, as well as detecting threshold responses for use in drug discovery and diagnostics.
- Chattopadhyay, Aritra Nath,Geng, Yingying,Jiang, Mingdi,Rotello, Vincent M.
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supporting information
p. 2890 - 2893
(2022/03/09)
-
- Synthesis and bioactivity evaluation of 5,6-epoxynorcantharidin mono-amide and imide derivatives
-
A series of 5,6-epoxynorcantharidin mono-amide and imide derivatives were designed and synthesized. MTT cell inhibition experiment shows that 5,6-epoxy compounds have good biological activity compared with the corresponding 5,6-olefin compounds and their hydrogenated products. Graphical abstract: [Figure not available: see fulltext.]
- Chen, Guangliang,Gao, Jiyu,Huang, Wencai,Li, Zicheng,Zhao, Yinglan
-
-
- Erratum: Direct cytosolic delivery of proteins through coengineering of proteins and polymeric delivery vehicles (Journal of the American Chemical Society (2020) 142:9 (4349-4355) DOI: 10.1021/jacs.9b12759)
-
In this revised Supporting Information file, Figure S15 was misplaced in the text. The corrected figure is shown in the corrected Supporting Information file. This change does not affect any conclusions of the article, but this correction of the record is important.
- Clark, Vincent,Elia, James,Gopalakrishnan, Sanjana,Goswami, Ritabrita,Jeon, Taewon,Lee, Yi-Wei,Luther, David C.,Rotello, Vincent M.
-
supporting information
p. 6702 - 6702
(2021/05/31)
-
- Spherical Nucleic Acids for Topical Treatment of Hyperpigmentation
-
Oligonucleotide-based materials such as spherical nucleic acid (SNA) have been reported to exhibit improved penetration through the epidermis and the dermis of the skin upon topical application. Herein, we report a self-assembled, skin-depigmenting SNA structure, which is based upon a bifunctional oligonucleotide amphiphile containing an antisense oligonucleotide and a tyrosinase inhibitor prodrug. The two components work synergistically to increase oligonucleotide cellular uptake, enhance drug solubility, and promote skin penetration. The particles were shown to reduce melanin content in B16F10 melanoma cells and exhibited a potent antimelanogenic effect in an ultraviolet B-induced hyperpigmentation mouse model.
- Fang, Yang,Lu, Xueguang,Wang, Dali,Cai, Jiansong,Wang, Yuyan,Chen, Peiru,Ren, Mengqi,Lu, Hao,Union, Jennifer,Zhang, Lei,Sun, Yehui,Jia, Fei,Kang, Xi,Tan, Xuyu,Zhang, Ke
-
supporting information
p. 1296 - 1300
(2021/02/01)
-
- Aiming at the tumor-specific accumulation of MGMT-inhibitors: First description of a synthetic strategy towards inhibitor-peptide conjugates
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In the therapy of cancer, alkylating agents are an efficient and often-used substance class. However, cells can repair the resulting alkyl modifications in the O6-position of guanine using the repair protein methylguanine methyltransferase (MGM
- W?ngler, Bj?rn,Schirrmacher, Ralf,W?ngler, Carmen
-
supporting information
(2020/03/23)
-
- Cysteine-Targeted Insecticides against A. gambiae Acetylcholinesterase Are Neither Selective nor Reversible Inhibitors
-
Acetylcholinesterase cysteine-targeted insecticides against malaria vector Anopheles gambia and other mosquitos have already been introduced. We have applied the olefin metathesis for the preparation of cysteine-targeted insecticides in high yields. The prepared compounds with either a succinimide or maleimide moiety were evaluated on Anopheles gambiae and human acetylcholinesterase with relatively high irreversible inhibition of both enzymes but poor selectivity. The concept of cysteine binding was not proved by several methods, and poor stability was observed of the chosen most potent/selective compounds in a water/buffer environment. Thus, our findings do not support the proposed concept of cysteine-targeted selective insecticides for the prepared series of succinimide or maleimide compounds.
- Gorecki, Lukas,Andrys, Rudolf,Schmidt, Monika,Kucera, Tomas,Psotka, Miroslav,Svobodova, Barbora,Hrabcova, Veronika,Hepnarova, Vendula,Bzonek, Petr,Jun, Daniel,Kuca, Kamil,Korabecny, Jan,Musilek, Kamil
-
supporting information
p. 65 - 71
(2019/12/25)
-
- Direct Cytosolic Delivery of Proteins through Coengineering of Proteins and Polymeric Delivery Vehicles
-
Nanocarrier-mediated protein delivery is a promising strategy for fundamental research and therapeutic applications. However, the efficacy of the current platforms for delivery into cells is limited by endosomal entrapment of delivered protein cargo with concomitantly inefficient access to the cytosol and other organelles, including the nucleus. We report here a robust, versatile polymeric-protein nanocomposite (PPNC) platform capable of efficient (≥90%) delivery of proteins to the cytosol. We synthesized a library of guanidinium-functionalized poly(oxanorborneneimide) (PONI) homopolymers with varying molecular weights to stabilize and deliver engineered proteins featuring terminal oligoglutamate "E-tags". The polymers were screened for cytosolic delivery efficiency using imaging flow cytometry with cytosolic delivery validated using confocal microscopy and activity of the delivered proteins demonstrated through functional assays. These studies indicate that the PPNC platform provides highly effective and tunable cytosolic delivery over a wide range of formulations, making them robust agents for therapeutic protein delivery.
- Lee, Yi-Wei,Luther, David C.,Goswami, Ritabrita,Jeon, Taewon,Clark, Vincent,Elia, James,Gopalakrishnan, Sanjana,Rotello, Vincent M.
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supporting information
p. 4349 - 4355
(2020/03/05)
-
- Inverse electron-demand Diels-Alder (iEDDA) bioorthogonal conjugation of half-sandwich transition metallocarbonyl entities to a model protein
-
Novel transition metallocarbonyl complexes carrying a norbornene or an oxanorbornene group were synthesized by [4 + 2] cycloaddition between the organometallic maleimide dienophiles and cyclopentadiene or furan, respectively. The oxanorbornene adduct was obtained as a mixture of endo and exo isomers as confirmed by X-ray diffraction and NMR spectroscopy. The (oxa)norbornene groups further provided convenient chemical reporters to carry out inverse electron demand Diels-Alder (iEDDA) reactions with tetrazine derivatives. Detailed kinetic studies with a model tetrazine revealed that faster rates of reaction were determined with both isomers of the oxanorbornene complex with respect to the norbornene complexes. Eventually, incorporation of metallocarbonyl entities into bovine serum albumin equipped with tetrazine handles was achieved as shown by IR spectroscopy of the protein conjugates.
- Fischer-Durand, Nathalie,Jamroz, Daria,Jarzyński, Szymon,Palusiak, Marcin,Rudolf, Bogna,Salmain, Michèle,St?pniewska, Marlena,Wojtulewski, S?awomir
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-
- Dendritic architectures by orthogonal thiol-maleimide "click" and furan-maleimide dynamic covalent chemistries
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A set of dendrons and dendrimers is synthesized divergently using an orthogonal combination of kinetically-driven thiol-maleimide "click" chemistry and thermodynamically reversible furan-maleimide cycloaddition/retrocycloaddition reactions. Growth is controlled by taking advantage of the selective thiol-ene addition of thiols to the electron withdrawn alkene of maleimide in the presence of electron rich alkene of oxanorbornene. Subsequent activation of growing dendrons/dendrimers requires only heat to induce the dynamic covalent liberation of peripheral furan protecting groups. The methodology introduced provides a new route to multifunctional dendrimers that could, in principle, be synthesized by introducing different branched monomers at any stage of dendrimer growth, allowing dendrimer architectures and properties to be better tailored to their intended applications.
- Frayne, Stephen H.,Stolz, Robert M.,Northrop, Brian H.
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supporting information
p. 7878 - 7883
(2019/09/06)
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- “Dial-In” Emission from a Unique Flexible Material with Polarization Tuneable Spectral Intensity
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The development of organic photoluminescent materials, which show promising roles as catalysts, sensors, organic light-emitting diodes, logic gates, etc., is a major demand and challenge for the global scientific community. In this context, a photoclick polymerization method is adopted for the growth of a unique photoluminescent three-dimensional (3D) polymer film, E, as a model system that shows emission tunability over the range 350–650 nm against the excitation range 295–425 nm. The DFT analysis of energy calculations and π-stacking supports the spectroscopic observations for the material exhibiting a broad range of emission owing to newly formed chromophoric units within the film. Full polarization spectroscopic Mueller matrix studies were employed to extract and quantify the molecular orientational order of both the ground (excitation) and excited (emission) state anisotropies through a set of newly defined parameters, namely the fluorescence diattenuation and fluorescence polarizance. The information contained in the recorded fluorescence Mueller matrix of the organic polymer material provided a useful way to control the spectral intensity of emission by using pre- and post-selection of polarization states. The observation was based on the assumption that the longer lifetime of the excited dipolar orientation is attributed to the compactness of the film.
- Kumar, Rajan,Ray, Subir Kumar,Mukherjee, Saikat,Saha, Sudipta,Bag, Arijit,Ghorai, Pradip Kr.,Ghosh, Nirmalya,Shunmugam, Raja
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supporting information
p. 13514 - 13522
(2019/10/28)
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- DIBENZO[D,B]SILOLE-BASED REACTIVE MESOGENS
-
The present invention provides a compound of Formula (I) D-S1-A-S2 B1, Formula (I) wherein a represents a conjugated chain of from 1 to 20 aromatic moieties independently selected from the group consisting of aromatic moieties, heteroaromatic moieties and E moieties, provided that A includes at least one E moiety, wherein E is selected from the group consisting of E1 being a dibenzo[d,b]silole moiety of the structure, E2 being a moiety of the structure and E3 being a moiety of the structure wherein E is connected in the conjugated chain of A and optionally to S1 or to S2 through covalent bonds at Y and Z; wherein each R is independently selected from the group consisting of straight chain or branched C1-C20 alkyl and C2-C20 alkenyl, optionally wherein from 1 to 5 CH2 groups are each replaced by an oxygen, provided that no acetal, ketal, peroxide or vinyl ether is present in the R group, and optionally wherein each H bonded to a C in each R group may independently be replaced by a halogen; wherein the X moieties are the same and are selected from the group consisting of hydrogen, straight chain or branched C1-C8 alkyl, straight chain or branched C1-C8 alkoxyl and a halogen, wherein each E moiety may have the same or different X moieties, wherein W is either an oxygen or sulfur atom, D represents a moiety having one or more cross-linkable functionalities, S1 and S2 are flexible linker groups; and B1 represents a moiety having one or more cross-linkable functionalities or a hydrogen atom, with the proviso that when B1 represents a hydrogen atom, D represents a moiety having at least two cross-linkable functionalities.
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Page/Page column 64; 65
(2018/04/21)
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- Facially Amphipathic Glycopolymers Inhibit Ice Recrystallization
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Antifreeze glycoproteins (AFGPs) from polar fish are the most potent ice recrystallization (growth) inhibitors known, and synthetic mimics are required for low-temperature applications such as cell cryopreservation. Here we introduce facially amphipathic glycopolymers that mimic the three-dimensional structure of AFGPs. Glycopolymers featuring segregated hydrophilic and hydrophobic faces were prepared by ring-opening metathesis polymerization, and their rigid conformation was confirmed by small-angle neutron scattering. Ice recrystallization inhibition (IRI) activity was reduced when a hydrophilic oxo-ether was installed on the glycan-opposing face, but significant activity was restored by incorporating a hydrophobic dimethylfulvene residue. This biomimetic strategy demonstrates that segregated domains of distinct hydrophilicity/hydrophobicity are a crucial motif to introduce IRI activity, which increases our understanding of the complex ice crystal inhibition processes.
- Graham, Ben,Fayter, Alice E. R.,Houston, Judith E.,Evans, Rachel C.,Gibson, Matthew I.
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supporting information
p. 5682 - 5685
(2018/05/09)
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- N-PHENYLMALEIMIDE DERIVATIVE AND MANUFACTURING METHOD THEREFOR, PRECURSOR OF N-PHENYLMALEIMIDE DERIVATIVE, POLYMER, PROTEIN ADHESION PREVENTION AGENT AND MEDICAL DEVICE
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PROBLEM TO BE SOLVED: To provide a polymer and a protein adhesion prevention agent that protein is less likely to adhere to a surface of a substrate or the like and a coating layer excellent in water resistance and heat resistance can be formed, and a med
- -
-
Paragraph 0106-0107
(2018/02/22)
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- Combining Orthogonal Chain-End Deprotections and Thiol–Maleimide Michael Coupling: Engineering Discrete Oligomers by an Iterative Growth Strategy
-
Orthogonal maleimide and thiol deprotections were combined with thiol–maleimide coupling to synthesize discrete oligomers/macromolecules on a gram scale with molecular weights up to 27.4 kDa (128mer, 7.9 g) using an iterative exponential growth strategy with a degree of polymerization (DP) of 2n?1. Using the same chemistry, a “readable” sequence-defined oligomer and a discrete cyclic topology were also created. Furthermore, uniform dendrons were fabricated using sequential growth (DP=2n?1) or double exponential dendrimer growth approaches (DP=2 22n ?1) with significantly accelerated growth rates. A versatile, efficient, and metal-free method for construction of discrete oligomers with tailored structures and a high growth rate would greatly facilitate research into the structure–property relationships of sophisticated polymeric materials.
- Huang, Zhihao,Zhao, Junfei,Wang, Zimu,Meng, Fanying,Ding, Kunshan,Pan, Xiangqiang,Zhou, Nianchen,Li, Xiaopeng,Zhang, Zhengbiao,Zhu, Xiulin
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supporting information
p. 13612 - 13617
(2017/10/24)
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- STABILIZED POLYMERIC NANOCAPSULES, DISPERSIONS COMPRISING THE NANOCAPSULES, AND METHODS FOR THE TREATMENT OF BACTERIAL BIOFILMS
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A nanocapsule includes a liquid hydrophobic core including an essential oil, and a shell encapsulating the core. The shell includes a copolymer having repeating units of Formula (I) and (II) wherein X, L1, R1, R2, y, and p are as described herein. A dispersion is also disclosed, wherein the dispersion includes a plurality of nanocapsules. The nanocapsules described herein are particularly useful for the treatment of bacterial biofilms.
- -
-
Paragraph 0069
(2017/03/21)
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- POLYMER NANOCAPSULES FOR PROTEIN DELIVERY
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A nanocapsule includes a shell including a polymer and a protein, a nucleic acid, or a combination thereof. The polymer has repeating units of Formula (I) (I) wherein X, L1, R1, and y are as described herein. The nanocapsule further includes a core comprising an oil. A composition is also disclosed including a plurality of the nanocapsules dispersed in an aqueous solution. The nanocapsules prepared according to the methods described herein are particularly useful for the delivery of proteins and nucleic acids into cells.
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Paragraph 0054
(2016/12/01)
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- NOVEL LIPOPHILIC N-SUBSTITUTED NORCANTHARIMIDE DERIVATIVES AND USE THEREOF
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PROBLEM TO BE SOLVED: To provide novel N-substituted norcantharimide derivatives that exhibit excellent selective cytotoxicity to cancerous cells. SOLUTION: The N-substituted norcantharimide derivatives are represented by formula (I). EFFECT: The N-substituted norcantharimide derivatives are useful as lead compounds for producing pharmaceutical compositions for treating cancer, particularly leukemia. SELECTED DRAWING: None COPYRIGHT: (C)2016,JPO&INPIT
- -
-
Paragraph 0070; 0071
(2017/04/03)
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- NOVEL LIPOPHILIC N-SUBSTITUTED NORCANTHARIMIDE DERIVATIVES AND USES THEREO
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Novel N-substituted norcantharimide derivatives are disclosed herein. The novel N-substituted norcantharimide derivatives are useful as lead compounds for manufacturing a medicament or a pharmaceutical composition for treating cancer, particularly for treating leukemia.
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-
Paragraph 0093-0095; 0096; 0097
(2017/04/28)
-
- Protein transduction domains mimics
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The invention generally relates to synthetic mimics of cell penetrating peptides. More particularly, the invention relates to certain novel monomers, oligomers and polymers (e.g., co-polymers) that are useful for the preparation of synthetic mimics of cell penetrating peptides, their compositions, preparations and use.
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Page/Page column 40
(2016/08/07)
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- CHARGED LINKERS AND THEIR USES FOR CONJUGATION
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Cell binding agent-drug conjugates comprising phosphinate-based charged linkers and methods of using such linkers and conjugates are provided.
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Page/Page column 52
(2015/10/05)
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- Site-Specific Amphiphilic Magnetic Copolymer Nanoaggregates for Dual Imaging
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Molecular imaging along with combinations of imaging modalities can provide a thorough understanding of disease, in particular, tumors. Magnetic resonance imaging (MRI) offers exceptional tissue contrast and resolution; whereas optical imaging provides high sensitivity. Hence a norbornene based copolymer (Nor-Cob-Py-Fol) is reported in this paper as a dual-imaging agent. Nor-Cob-Py-Fol having Co2+ complex, pyrene and poly(ethylene glycol) derived folate, have been synthesized using ring-opening metathesis polymerization (ROMP). All the monomers and polymers are characterized by 1H NMR, IR, GPC, and TGA techniques. The morphology of the copolymer nanoaggregates has been evaluated with DLS, TEM, and SEM techniques. The functionalization of Co2+ to the polymer is monitored by FTIR, 1H NMR, and 13C NMR spectroscopy. Furthermore, the presence of Co2+ in the nanoaggregates is confirmed by the EDX (SEM) technique. To prove the MRI capabilities nature of copolymer nanoaggregates, NMR experiment is performed at room temperature. Cell viability studies suggest the biocompatibility nature of the copolymer. Flow cytometry as well as epifluoroscence microscope experiments clearly demonstrate the dual-imaging ability of the newly designed copolymer. The much higher relaxivity ratio (r2/r1) of the present method clearly establishes the superiority of our system as one of the best contrast agents known to the practitioners of magnetic resonance imaging.
- Mukherjee, Saikat,Dinda, Himadri,Shashank, Litesh,Chakraborty, Ipsita,Bhattacharyya, Rangeet,Das Sarma, Jayasri,Shunmugam, Raja
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p. 6791 - 6800
(2015/10/28)
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- Design of aromatic-containing cell-penetrating peptide mimics with structurally modified π electronics
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Cell-penetrating peptides (CPPs) and their synthetic mimics (CPPMs) represent a class of molecules that facilitate the intracellular delivery of various cargo. Previous studies indicated that the presence of aromatic functionalities improved CPPM activity. Given that aromatic functionalities play prominent roles in membrane biology and participate in various π interactions, we explored whether these interactions could be optimized for improved CPPM activity. CPPMs were synthesized by ring-opening metathesis polymerization by using monomers that contained aromatic rings substituted with electron-donating and electron-withdrawing groups and covered an electrostatic potential range from -29.69 to + 15.57 kcalmol-1. These groups altered the quadrupole moments of the aromatic systems and were used to test if such structural modifications changed CPPM activity. CPPMs were added to dye-loaded vesicles and the release of carboxyfluorescein was monitored as a function of polymer concentration. Changes in the effective polymer concentration to release 50% of the dye (effective concentration, EC50) were monitored. Results from this assay showed that the strength of the electron-donating and electron-withdrawing groups incorporated in the CPPMs did not alter polymer EC50 values or activity. This suggests that other design parameters may have a stronger impact on CPPM activity. In addition, these results indicate that a wide range of aromatic groups can be incorporated without negatively impacting polymer activity.
- DeRonde, Brittany M.,Birke, Alexander,Tew, Gregory N.
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supporting information
p. 3013 - 3019
(2015/02/05)
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- Polyethylene as a Cosolvent and Catalyst Support in Ring-Opening Metathesis Polymerization
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Polyethylene oligomers (PEOlig) can be used as cosolvents and sometimes soluble catalyst supports in ring-opening metathesis polymerization (ROMP) reactions. As a catalyst support, this polyolefin serves as an N-heterocyclic carbene ligand for a ROMP catalyst, making it soluble at 70 °C and insoluble at room temperature. As a cosolvent, unfunctionalized PE oligomers facilitate quantitative separation of PEOlig-bound Ru-catalyst residues from polymer products. In these cases, the insolubility of the unfunctionalized polyethylene (Polywax) and its entrapment of the PEOlig-supported Ru residue in the product phase at room temperature afford ROMP products with Ru contamination lower than other procedures that use soluble catalysts. These separations require only physical processes to separate the product and catalyst residues - no additional solvents are necessary. Control experiments suggest that most (ca. 90%) of the Ru leaching that is seen results from Ru byproducts formed in the vinyl ether quenching step and not from the polymerization processes involving the PEOlig-supported Ru complex. (Chemical Equation Presented).
- Suriboot, Jakkrit,Hobbs, Christopher E.,Guzman, William,Bazzi, Hassan S.,Bergbreiter, David E.
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p. 5511 - 5516
(2015/09/02)
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- FLUOROALKYLFLUORENE DERIVATIVES
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There are provided compounds of the formula D-S1-A-S2-B1 wherein A comprises a 2,7- disubstituted 9,9-fluoroalkyl fluorene diradical of the formula wherein S1, S2, D and B1 have meanings given in the description that are useful as charge transport and emissive materials for the fabrication of electronic devices such as diodes, transistors, and photovoltaic devices.
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Page/Page column 50
(2015/11/09)
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- Cyclopolymerization of α,ω-heterodifunctional monomers containing styrene and maleimide moieties
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A series of α,ω-heterodifunctional monomers with styrene (St) and maleimide moieties bridged by a varied length of oligo-ethylene glycol (OEG) linkers were synthesized. Cyclopolymerizations of these monomers through reversible addition-fragmentation chain transfer-mediated alternating radical copolymerization between intramolecular St and maleimide moieties were investigated. For the monomers with three or more ethylene glycol (EG) units, their cyclopolymerizations can be realized properly in low monomer feeding concentrations, affording well-defined cyclopolymers with crown ether encircled in their main chains. Importantly, the cyclopolymerizations of monomers with six or seven EG units in the presence of KPF6 could be enhanced by the supramolecular effects between the OEG linkers and the potassium metal ion. Thus, the monomer feeding concentration could be largely improved, which may benefit preparation of the cyclopolymers with high degrees of copolymerization. 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 330-338 The cyclopolymerizations of α,ω-heterodifunctional monomers with styrene and maleimide moieties bridged by oligo-ethylene glycol linkers can be realized in low monomer feeding concentrations. The cyclopolymerizations of monomers with six or seven ethylene glycol units in high concentrations could be enhanced by the supramolecular effects between the linkers and the potassium metal ion, both of which afford well-defined cyclopolymers with crown ether encircled in their main chains. Copyright
- Zou, Lei,Liu, Jian'An,Zhang, Ke,Chen, Yongming,Xi, Fu
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p. 330 - 338
(2014/01/06)
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- HYDROPHILIC LINKERS AND THEIR USES FOR CONJUGATION OF DRUGS TO CELL BINDING MOLECULES
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Cell binding agent-drug conjugates comprising hydrophilic linkers, and methods of using such linkers and conjugates are provided.
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Page/Page column 53; 54
(2014/06/11)
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- Synthesis of novel lipophilic N-Substituted norcantharimide derivatives and evaluation of their anticancer activities
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This research attempted to study the effect of lipophilicity on the anticancer activity of N-substituted norcantharimide derivatives. Twenty-three compounds were synthesized and their cytotoxicities against five human cancer cell lines studied. The lipophilicity of each derivative was altered by its substituent, an alkyl, alkyloxy, terpenyl or terpenyloxy group at the N-position of norcantharimide. Further, among all synthesized derivatives studied, the compounds N-farnesyloxy-7-oxabicyclo[2.2.1]heptane-2,3- dicarboximide (9), and N-farnesyl-7-oxabicyclo[2.2.1]heptane-2,3-dicarboximide (18), have shown the highest cytotoxicity, anti-proliferative and apoptotic effect against human liver carcinoma HepG2 cell lines, yet displayed no significant cytotoxic effect on normal murine embryonic liver BNL CL.2 cells. Their overall performance led us to believe that these two compounds might be potential candidates for anticancer drugs development.
- Wu, Jin-Yi,Kuo, Cheng-Deng,Chu, Chien-Yu,Chen, Min-Shin,Lin, Jia-Hua,Chen, Yu-Jen,Liao, Hui-Fen
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p. 6911 - 6928
(2014/07/08)
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- Synthesis of 3′-allylindoline spirobenzopyrans derived from 3-allyl-3H-indoles
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In this study, 8 new spirobenzopyrans were synthesized. A novel, three-step, facile route for the synthesis of 3′-allylindoline spirobenzopyrans via 3-allyl-3H-indoles was developed. The newly synthesized spirobenzopyrans were evaluated for their photochr
- Kagawa, Natsuko,Takabatake, Hiroki,Masuda, Yoshitake
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supporting information
p. 6427 - 6431
(2014/12/10)
-
- Experimental and theoretical studies of selective thiol-ene and thiol-yne click reactions involving N -substituted maleimides
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A combination of experimental and computational methods has been used to understand the reactivity and selectivity of orthogonal thiol-ene and thiol-yne ″click″ reactions involving N-allyl maleimide (1) and N-propargyl maleimide (2). Representative thiols methyl-3-mercaptopropionate and β-mercaptoethanol are shown to add exclusively and quantitatively to the electron poor maleimide alkene of 1 and 2 under base (Et3N) initiated thiol-Michael conditions. Subsequent radical-mediated thiol-ene or thiol-yne reactions can be carried out to further functionalize the remaining allyl or propargyl moieties in near quantitative yields (>95%). Selectivity, however, can only be achieved when base-initiated thiol-Michael reactions are carried out first, as radical-mediated reactions between equimolar amounts of thiol and N-substituted maleimides give complex mixtures of products. CBS-QB3 calculations have been used to investigate the energetics and kinetics of reactions between a representative thiol (methyl mercaptan) with N-allyl and N-propargyl maleimide under both base-initiated and radical-mediated conditions. Calculations help elucidate the factors that underlie the selective base-initiated and nonselective radical-mediated thiol-ene/yne reactions. The results provide additional insights into how to design selective radical-mediated thiol-ene/yne reactions.
- Stolz, Robert M.,Northrop, Brian H.
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supporting information
p. 8105 - 8116
(2013/09/12)
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- Investigation of the Diels-Alder reaction as a cross-linking mechanism for degradable poly(ethylene glycol) based hydrogels
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The Diels-Alder (DA) reaction was investigated as a cross-linking mechanism for poly(ethylene glycol) (PEG) based hydrogels. Two complementary macromonomers were synthesized by functionalizing star-shaped PEG with furyl and maleimide groups. Gel formation occurred in water at 37 °C; the gelation time ranged between 171 ± 25 min and 14 ± 1 min depending on the used hydrogel formulation. The complex shear modulus was dependent on the concentration, branching factor and molecular weight of the macromonomers; values between 2821 ± 1479 Pa and 37097 ± 6698 Pa were observed. Hydrogel swelling and degradation were influenced by the same parameters; the degradation time varied between a few days and several weeks. Gel dissolution was found to occur by retro-DA reaction and subsequent hydrolysis of maleimide groups. Calculations of the network mesh size revealed that the prepared hydrogels would be suitable for the controlled release of therapeutic proteins.
- Kirchhof, Susanne,Brandl, Ferdinand P.,Hammer, Nadine,Goepferich, Achim M.
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p. 4855 - 4864
(2013/09/23)
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- Intermediates Useful in the Preparation of Maleimide Functionalized Polymers
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Methods for forming maleimide functionalized polymers are provided. In one such embodiment, a maleimide functionalized polymer is prepared in a method that includes a step of carrying out a reverse Diels-Alder reaction. Intermediates useful in the methods, as well as methods for preparing the intermediates, are also provided. Also provided are polymeric reagents, methods of using polymeric reagents, compounds and conjugates.
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Page/Page column 20
(2012/01/14)
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- Synthesis of a bridging ligand with a non-denatured protein pendant: Toward protein encapsulation in a coordination cage
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Toward protein encapsulation by a synthetic host, we synthesized an ubiquitin-dangled ligand, a potential precursor of a nanoscale coordination cage. The key step is the addition of a C-terminal Cys76 SH group, which was introduced by Gly76Cys mutation, to a maleimide acceptor on the ligand. The C-terminal mutation and the SH addition to the ligand did not damage the ubiquitin moiety at all, neither structurally nor conformationally.
- Fujita, Daishi,Suzuki, Kosuke,Sato, Sota,Yagi-Utsumi, Maho,Kurimoto, Eiji,Yamaguchi, Yoshiki,Kato, Koichi,Fujita, Makoto
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supporting information; scheme or table
p. 313 - 315
(2012/06/01)
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- Functionalized phosphonated half-cage molecules as ligands for metal complexes
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Phosphonated molecules, featuring a half-cage structure and a N-lateral chain with additional metal coordinating groups were designed as ligands of metal cations. These compounds were synthesized by a Diels-Alder (DA) strategy, using 1-diethoxyphosphoryl-1,3-butadiene and a series of N-substituted maleimides as dienophiles. Two cycloadducts, bearing a terminal primary alcohol and a terminal iodide, respectively, were used as key intermediates for further functionalizations. Metal coordination properties of the ligands equipped with functionalized N-lateral chains were proven by an ESI-HRMS study. The stoichiometry of one selected EuIII complex with a diphosphonated ligand was determined by photoluminescence spectroscopy in emission mode.
- Villemin, Elise,Herent, Marie-France,Marchand-Brynaert, Jacqueline
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supporting information
p. 6165 - 6178
(2013/01/15)
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- Protein transduction domain mimics: The role of aromatic functionality
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For better or worse: Protein transduction domain mimics built from synthetic polymers demonstrate that aromatic side chains provide better transduction than aliphatic groups at the same relative hydrophobicity. Similarly, a less hydrophobic aromatic side chain is more active than the corresponding aliphatic one containing the same number of carbon atoms (see picture). Copyright
- Som, Abhigyan,Reuter, Anika,Tew, Gregory N.
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supporting information; experimental part
p. 980 - 983
(2012/02/16)
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- Self-activation in de novo designed mimics of cell-penetrating peptides
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DIY transduction: Cell-penetrating peptides (CPPs) efficiently cross the nonpolar biological membrane, but activation by hydrophobic counterions is essential for transport activity. Polymeric mimics of CPPs are coupled with hydrophobic side chains; the "self-activation" in these species is demonstrated by transport of the fluorescent probe CF out of bilayer vesicles. Copyright
- Som, Abhigyan,Tezgel, A. Ozgul,Gabriel, Gregory J.,Tew, Gregory N.
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supporting information; experimental part
p. 6147 - 6150
(2011/08/03)
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- Efficient synthesis of isoxazolidine-tethered monolayer-protected gold nanoparticles (MPGNs) via 1,3-dipolar cycloadditions under high-pressure conditions
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(Chemical Equation Presented) A maleimide-modified 2.5 ± 0.5 nm mixed monolayer protected gold nanoparticle (2-C12MPGN) containing approximately 30% maleimide-terminated dodecanethiolate/dodecanethiolate ligands was prepared. The 2-C12MPGN was reacted with a series of nitrones (a-i) at both atmospheric and hyperbaric (11 000 atm) conditions to form the corresponding isoxazolidine-modified nanoparticles (3-C12MPGN) via an interfacial 1,3-dipolar cycloaddition. At atmospheric pressures, the reaction proceeds slowly (if at all) and makes this reaction impractical for the synthetic modification of the nanoparticles. However, by performing the reaction under the high-pressure conditions, the reaction proceeds efficiently and quantitatively. TEM shows that the use of high pressure does not affect the size of the gold nanoparticle core. The 3-C12MPGNs were characterized by 1H NMR spectroscopy by comparing the spectra obtained with those of model reactions utilizing N-dodecylmaleimide (4) with the same nitrones (a-i) to form 5. Additionally, the cycloaddition reaction also occurs more readily with 4 than with 2-C12MPGN with all nitrones, indicating that the environment of the latter affects the cycloaddition reaction.
- Zhu, Jun,Lines, Brandon M.,Ganton, Michael D.,Kerr, Michael A.,Workentin, Mark S.
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p. 1099 - 1105
(2008/09/18)
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- Chemical modification of monolayer-protected gold nanoparticles using hyperbaric conditions
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Sluggish or impractical Diels-Alder reactions of a maleimide modified-MPN with a series of dienes of varying electronic and steric demands at ambient pressure and temperature proceed under hyperbaric conditions in less than 10 min without altering the gold core of the nanoparticle or its inherent physical properties. Copyright
- Zhu, Jun,Ganton, Michael D.,Kerr, Michael A.,Workentin, Mark S.
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p. 4904 - 4905
(2008/02/01)
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- Phthalocyanines and related compounds: XLI. Synthesis of 9,10-diphenylanthracene-2,3-dicarboxylic acid derivatives
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Derivatives of 9,10-diphenylanthracene-2,3-dicarboxylic acid were synthesized by the Diels-Alder reaction of 1,3-diphenylisobenzofuran with adducts of furan (or silvan) and the corresponding maleic (fumaric) acid derivative or with trans-cyclohex-4-ene-1,2-dicarbonitrile, followed by aromatization. Pleiades Publishing, Inc., 2006.
- Donyagina,Kovshev,Luk'yanets
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p. 654 - 658
(2008/02/07)
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- Synthesis of a homotrifunctional conjugation reagent based on maleimide chemistry
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A novel homotrifunctional conjugation reagent, 1,3,5-tris-(N- maleimidomethyl)benzene has been synthesized in high yield with minimum purification. The reactivity of this compound was examined by using l-cysteine as a nucleophile.
- Farha, Omar K.,Julius, Richard L.,Hawthorne, M. Frederick
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p. 2619 - 2622
(2007/10/03)
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- Improved synthesis of DCDHF fluorophores with maleimide functional groups
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A group of dicyanodihydrofuran (DCDHF) fluorophores with thiol-reactive maleimide functionality has been synthesized. One of the methods involves aromatic nucleophilic substitution reaction between an arylfluoride containing DCDHF and an amine containing
- Lu, Zhikuan,Weber, Ryan,Twieg, Robert J.
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p. 7213 - 7217
(2007/10/03)
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- Controlling RNA digestion by RNase H with a light-activated DNA hairpin
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(Figure Presented) Making sense: A DNA hairpin was synthesized by attaching a 20-mer antisense oligodeoxynucleotide (asODN) to a sense ODN through a bifunctional photocleavable linker. This conjugate became much less stable upon UV photoactivation (ΔTsub
- Tang, Xinjing,Dmochowski, Ivan J.
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p. 3523 - 3526
(2007/10/03)
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- A retro-Diels-Alder reaction to uncover maleimide-modified surfaces on monolayer-protected nanoparticles for reversible covalent assembly
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(Chemical Equation Presented) Maleimide-modified monolayer-protected gold nanoparticles (MPGN) are prepared from the protected furan-maleimide via the thermally reversible Diels-Adler reaction when required. These maleimide-MPGNs serve as a general platform allowing for a Diels-Alder reaction with furan-modified MPN to prepare larger 3D networks reversibly.
- Zhu, Jun,Kell, Arnold J.,Workentin, Mark S.
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p. 4993 - 4996
(2007/10/03)
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- Duplex strand formation using alternating copolymers
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The regular arrangement of complementary diaminopyridine-thymine (DAP-THY) on alternating copolymers permits cooperative binding events and the effective formation of well-controlled micrometre-scale aggregates. The Royal Society of Chemistry 2005.
- Nakade, Hiroshi,Ilker, M. Firat,Jordan, Brian J.,Uzun, Oktay,LaPointe, Nicholas L.,Coughlin, E. Bryan,Rotello, Vincent M.
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p. 3271 - 3273
(2007/10/03)
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- Maleimido-terminated self-assembled monolayers
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Four approaches have been explored for the preparation of maleimido-functionalized self-assembled monolayers (SAMs) on silicon. SAMs prepared by self-assembly of maleimido-functionalized alkyltrichlorosilanes (11-maleimido-undecyl-trichlorosilane) on oxide-covered silicon yield higher signals from maleimido functionalities in ATR-IR (attenuated total reflection IR) spectroscopy and XPS (X-ray photoelectron spectroscopy) than the other three methods. The surface composition of maleimido groups was tailored further by the formation of mixed monolayers with nonfunctionalized alkyltrichlorosilanes (decyltrichlorosilane). The order of the alkyl chains within the monolayers only slightly depends on the composition of the mixed monolayers. We utilized the maleimido-terminated SAMs to bind various nucleophilic compounds, alkylamines, alkylthiols, and thiol-tagged DNA oligonucleotides by means of conjugate addition.
- Wang, Yayun,Cai, Jun,Rauscher, Hubert,Behm, Rolf Juergen,Goedel, Werner A.
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p. 3968 - 3978
(2007/10/03)
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- An experimental and theoretical study of stereoselectivity of furan-maleic anhydride and furan-maleimide Diels-Alder reactions
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The stereoselectivity of the reaction of furan (1) with maleic anhydride (2) and maleimide (3) was studied experimentally and theoretically. Although the two reactions are highly similar with regard to their preference for endo and exo steroisomers, notab
- Rulisek, Lubomir,Sebek, Pavel,Havlas, Zdenek,Hrabal, Richard,Capek, Pavel,Svatos, Ales
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p. 6295 - 6302
(2007/10/03)
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- Anhydride modified cantharidin analogues useful in the treatment of cancer
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Anhydride modified cantharidin analogues useful in the treatment of certain forms of cancer also methods for the screening for anti-cancer activity of these analogues and/or their ability to sensitise cancer cells to cancer treatment. The modified cantharidin analogues have structure (I) or (II), wherein R1, R2, R3 and R4 are H, aryl or alkyl; X is O, N or S; Y is O, S, NH, NR; R is alkyl or aryl; A and B are H or CH3; W and Z are CHOH or C=O. These compounds inhibit protein phosphatase. 1
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Page/Page column 6
(2008/06/13)
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- Self-Complementary ABC Triblock Copolymers via Ring-Opening Metathesis Polymerization
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The synthesis of self-complementary triblock copolymers using controlled ring-opening metathesis polymerization was presented. It was shown that polymers possess ordered sequences of complementary molecular recognition blocks and could be synthesized efficiently. It was found that changing the triblock copolymer sequence resulted in materials with different self-assembly properties.
- Bazzi, Hassan S.,Bouffard, Jean,Sleiman, Hanadi F.
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p. 7899 - 7902
(2007/10/03)
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