Co-reporter:José E. Báez, Ruobing Zhao, and Kenneth J. Shea
Industrial & Engineering Chemistry Research September 20, 2017 Volume 56(Issue 37) pp:10366-10366
Publication Date(Web):August 15, 2017
DOI:10.1021/acs.iecr.7b02596
Diblock copolymers of poly(methylene-b-ε-caprolactone) (PM-b-PCL) were synthesized in two steps: (a) polyhomologation, to obtain, following oxidative cleavage of the carbon–boron (PM, block1), an α-hydroxyl-ω-methyl polymethylene (PMOH, CH3–[CH2]m–OH) and, following the transfer reaction to the ring-opening polymerization catalyst, (b) ring-opening polymerization (ROP) of ε-caprolactone (CL) (PCL, block2). In addition, a series of homopolymers derived from poly(ε-caprolactone) (PCL) oligoesters containing an end group of docosyl (CH3–[CH2]21– or C22; C22–PCL) were obtained as a model to compare their physical properties by DSC with those of PM-b-PCL. The oligomers derived from PM-b-PCL and C22–PCL were characterized by 1H and 13C NMR, AFM, DSC, GPC, and MALDI-TOF. PM-b-PCL and C22–PCL were evaluated as compatibilizers for PE/PCL polymer blends. Identification and analysis of optimized blocks of PM-b-PCL by POM and SEM showed improved mixing of PE/PCL blends.
Co-reporter:Jeffrey O’Brien and Kenneth J. Shea
Accounts of Chemical Research 2016 Volume 49(Issue 6) pp:1200
Publication Date(Web):June 2, 2016
DOI:10.1021/acs.accounts.6b00125
Nanomaterials, when introduced into a complex, protein-rich environment, rapidly acquire a protein corona. The type and amount of proteins that constitute the corona depend significantly on the synthetic identity of the nanomaterial. For example, hydrogel nanoparticles (NPs) such as poly(N-isopropylacrylamide) (NIPAm) have little affinity for plasma proteins; in contrast, carboxylated poly(styrene) NPs acquire a dense protein corona. This range of protein adsorption suggests that the protein corona might be “tuned” by controlling the chemical composition of the NP.In this Account, we demonstrate that small libraries of synthetic polymer NPs incorporating a diverse pool of functional monomers can be screened for candidates with high affinity and selectivity to targeted biomacromolecules. Through directed synthetic evolution of NP compositions, one can tailor the protein corona to create synthetic organic hydrogel polymer NPs with high affinity and specificity to peptide toxins, enzymes, and other functional proteins, as well as to specific domains of large proteins. In addition, many NIPAm NPs undergo a change in morphology as a function of temperature. This transformation often correlates with a significant change in NP–biomacromolecule affinity, resulting in a temperature-dependent protein corona. This temperature dependence has been used to develop NP hydrogels with autonomous affinity switching for the protection of proteins from thermal stress and as a method of biomacromolecule purification through a selective thermally induced catch and release. In addition to temperature, changes in pH or buffer can also alter a NP protein corona composition, a property that has been exploited for protein purification. Finally, synthetic polymer nanoparticles with low nanomolar affinity for a peptide toxin were shown to capture and neutralize the toxin in the bloodstream of living mice.While the development of synthetic polymer alternatives to protein affinity reagents is in its early stages, these recent successes using only small libraries of functional monomers are most encouraging. It is likely that by expanding the chemical diversity of functional hydrogels and other polymers, a much broader range of NP–biomacromolecule affinity pairs will result. Since these robust, nontoxic polymers are readily synthesized in the chemistry laboratory, we believe the results presented in this Account offer a promising future for the development of low cost alternatives to more traditional protein affinity reagents such as antibodies.
Co-reporter:Jeffrey O’Brien, Shih-Hui Lee, Shunsuke Onogi, and Kenneth J. Shea
Journal of the American Chemical Society 2016 Volume 138(Issue 51) pp:16604-16607
Publication Date(Web):December 14, 2016
DOI:10.1021/jacs.6b10950
Biochemical diversity of venom extracts often occurs within a small number of shared protein families. Developing a sequestrant capable of broad-spectrum neutralization across various protein isoforms within these protein families is a necessary step in creating broad-spectrum antivenom. Using directed synthetic evolution to optimize a nanoparticle (NP) formulation capable of sequestering and neutralizing venomous phospholipase A2 (PLA2), we demonstrate that broad-spectrum neutralization and sequestration of venomous biomacromolecules is possible via a single optimized NP formulation. Furthermore, this optimized NP showed selectivity for venomous PLA2 over abundant serum proteins, was not cytotoxic, and showed substantially long dissociation rates from PLA2. These findings suggest that it may show efficacy as an in vivo venom sequestrant and may serve as a generalized lipid-mediated toxin sequestrant.
Co-reporter:Ruobing Zhao, Yan Zhang, Jaeyoon Chung, and Kenneth J. Shea
ACS Macro Letters 2016 Volume 5(Issue 7) pp:854
Publication Date(Web):July 1, 2016
DOI:10.1021/acsmacrolett.6b00427
The insertion of long hydrocarbon chains between ester groups in polyester allows for introduction and modulation of crystallinity, which can result in enhanced performance approaching high-density polyethylene. We report a convenient synthesis of building blocks for long-chain aliphatic polyesters via an aqueous C1 polymerization. The macromonomers include ω-hydroxyacid esters, α,ω-diols and α,ω-diacids. The length of hydrocarbon chain segment (C20–C60) can be controlled by the ratio of monomer/initiator in the C1 polymerization. The obtained polyesters from condensation of the long-chain ω-hydroxyacid esters have thermal and mechanical properties indistinguishable from related materials derived from biomass.
Co-reporter:Mingming Liu, Jiangyan Pi, Xiaojie Wang, Rong Huang, Yamei Du, Xiaoyang Yu, Wenfeng Tan, Fan Liu, Kenneth J. Shea
Analytica Chimica Acta 2016 Volume 932() pp:29-40
Publication Date(Web):17 August 2016
DOI:10.1016/j.aca.2016.05.020
•An alkyl-functionalized ionic liquid was used as monomer, stabilizer and catalyst to prepare MIPs.•The MWCNTs@BSA-MIPIL was prepared via a multi-step sol-gel route.•The imprinting conditions were optimized by investigating molecular interactions between templates and monomers.•The MWCNTs@BSA-MIPIL was found to be pH-responsive.•The MWCNTs@BSA-MIPIL demonstrated high adsorption capacity, good imprinting effect and strong shape selectivity to BSA.A pH-responsive surface molecularly imprinted poly(ionic liquids) (MIPILs) was prepared on the surface of multiwall carbon nanotubes (MWCNTs) by a sol-gel technique. The material was synthesized using a 3-aminopropyl triethoxysilane modified multiwall carbon nanotube (MWCNT-APTES) as the substrate, bovine serum albumin (BSA) as the template molecule, an alkoxy-functionalized IL 1-(3-trimethoxysilyl propyl)-3-methyl imidazolium chloride ([TMSPMIM]Cl) as both the functional monomer and the sol-gel catalyst, and tetraethoxysilane (TEOS) as the crosslinking agent. The molecular interaction between BSA and [TMSPMIM]Cl was quantitatively evaluated by UV–vis spectroscopy prior to polymerization so as to identify an optimal template/monomer ratio and the most suitable pH value for the preparation of the MWCNTs@BSA-MIPILs. This strategy was found to be effective to overcome the problems of trial-and-error protocol in molecular imprinting. The optimum synthesis conditions were as follows: template/monomer ratio 7:20, crosslinking agent content 2.0–2.5 mL, temperature 4 °C and pH 8.9 Tris–HCl buffer. The influence of incubation pH on adsorption was also studied. The result showed that the imprinting effect and selectivity improved significantly with increasing incubation pH from 7.7 to 9.9. This is mainly because the non-specific binding from electrostatic and hydrogen bonding interactions decreased greatly with the increase of pH value, which made the specific binding affinity from shape selectivity strengthened instead. The polymers synthesized under the optimal conditions were then characterized by BET surface area measurement, FTIR, thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). The adsorption capacity, imprinting effect, selective recognition and reusability were also evaluated. The as-prepared MWCNTs@BSA-MIPILs were also found to have a number of advantages including high surface area (134.2 m2 g−1), high adsorption capacity (55.52 mg g−1), excellent imprinting effect (imprinting factor of up to 5.84), strong selectivity (selectivity factor of 2.61 and 5.63 for human serum albumin and bovine hemoglobin, respectively), and good reusability.A pH-responsive bovine serum albumin molecularly imprinted poly(ionic liquids) was prepared on the surface of multiwall carbon nanotubes via a sol-gel route. The specific binding from shape selectivity was significantly strengthened by controlling the non-specific binding by adjusting the incubation pH value to 9.9. The use of ionic liquids as stabilizers, functional monomers and sol-gel catalysts was found to be a promising strategy for the preparation of water compatible molecularly imprinted polymers for protein molecules.
Co-reporter:Beverly Chou, Peter Mirau, Tian Jiang, Szu-Wen Wang, and Kenneth J. Shea
Biomacromolecules 2016 Volume 17(Issue 5) pp:
Publication Date(Web):April 11, 2016
DOI:10.1021/acs.biomac.6b00296
Hydrophobic interactions often dominate the associative forces between biomacromolecules. A synthetic affinity reagent must be able to exploit and optimize these interactions. We describe synthesis of abiotic affinity reagents that sequester biomacromolecules with lipid-like domains. NIPAm-based copolymer nanoparticles (NPs) containing C4–C8 hydrophobic groups were evaluated for their affinity for lipopolysaccharides (LPS), the lipophilic component of the outer membrane of Gram-negative bacteria. Optimal affinity was found for NPs incorporating a linear C4 hydrocarbon group. 1D and 2D 1H NMR studies revealed that in water, the longer chain (C6 and C8) alkyl groups in the hydrogel NPs were engaged in intrachain association, rendering them less available to interact with LPS. Optimal LPS–NP interaction requires maximizing hydrophobicity, while avoiding side chain aggregation. Polymer compositions with high LPS binding were grafted onto agarose beads and evaluated for LPS clearance from solution; samples containing linear C4 groups also showed the highest LPS clearance capacity.
Co-reporter:Ruobing Zhao and Kenneth J. Shea
ACS Macro Letters 2015 Volume 4(Issue 5) pp:584
Publication Date(Web):May 6, 2015
DOI:10.1021/acsmacrolett.5b00218
We report the first synthesis of a gradient methylidene-ethylidene copolymer via a living C1 polymerization. The copolymer has a similar chemical structure as the corresponding ethylene-propylene copolymer. To achieve this goal a new and convenient source of the ethylide monomer, diethylsulfoxonium ethylide, was developed for the introduction of the methyl branch in the polymer backbone. The gradient copolymer contains a gradual change of instantaneous methyl branch content from 0% on one end of the polymer chain to 63% on the other end. Thermal analysis revealed that the gradient copolymers have a narrow glass transition temperature range with values intermediate between those of linear polyethylene and atactic polypropylene.
Co-reporter:Xilun Weng;Dr. José E. Baez;Dr. Mariya Khiterer;Madelene Y. Hoe;Dr. Zongbi Bao;Dr. Kenneth J. Shea
Angewandte Chemie International Edition 2015 Volume 54( Issue 38) pp:11214-11218
Publication Date(Web):
DOI:10.1002/anie.201504934
Abstract
Following its resolution by diastereomeric complexation, 5,5′,6,6′-tetrahydroxy-3,3,3′,3′-tetramethyl-1,1′-spirobisindane (TTSBI) was used to synthesize a chiral ladder polymer, (+)-PIM-CN. (+)-PIM-COOH was also synthesized by the acid hydrolysis of (+)-PIM-CN. Following characterization, both (+)-PIM-CN and (+)-PIM-COOH were solvent cast directly into semipermeable membranes and evaluated for their ability to enable the selective permeation of a range of racemates, including mandelic acid (Man), Fmoc-phenylalanine, 1,1′-bi-2-naphthol (binol), and TTSBI. High ee values were observed for a number of analytes, and both materials exhibited high permeation rates. A selective diffusion–permeation mechanism was consistent with the results obtained with these materials. Their high permeability, processability, and ease of chemical modification offer considerable potential for liquid-phase membrane separations and related separation applications.
Co-reporter:Xilun Weng;Dr. José E. Baez;Dr. Mariya Khiterer;Madelene Y. Hoe;Dr. Zongbi Bao;Dr. Kenneth J. Shea
Angewandte Chemie 2015 Volume 127( Issue 38) pp:11366-11370
Publication Date(Web):
DOI:10.1002/ange.201504934
Abstract
Following its resolution by diastereomeric complexation, 5,5′,6,6′-tetrahydroxy-3,3,3′,3′-tetramethyl-1,1′-spirobisindane (TTSBI) was used to synthesize a chiral ladder polymer, (+)-PIM-CN. (+)-PIM-COOH was also synthesized by the acid hydrolysis of (+)-PIM-CN. Following characterization, both (+)-PIM-CN and (+)-PIM-COOH were solvent cast directly into semipermeable membranes and evaluated for their ability to enable the selective permeation of a range of racemates, including mandelic acid (Man), Fmoc-phenylalanine, 1,1′-bi-2-naphthol (binol), and TTSBI. High ee values were observed for a number of analytes, and both materials exhibited high permeation rates. A selective diffusion–permeation mechanism was consistent with the results obtained with these materials. Their high permeability, processability, and ease of chemical modification offer considerable potential for liquid-phase membrane separations and related separation applications.
Co-reporter:Keiichi Yoshimatsu ; Tomohiko Yamazaki ; Yu Hoshino ; Paul E. Rose ; Linda F. Epstein ; Les P. Miranda ; Philip Tagari ; John M. Beierle ; Yusuke Yonamine
Journal of the American Chemical Society 2014 Volume 136(Issue 4) pp:1194-1197
Publication Date(Web):January 10, 2014
DOI:10.1021/ja410817p
We describe a novel epitope discovery strategy for creating an affinity agent/peptide tag pair. A synthetic polymer nanoparticle (NP) was used as the “bait” to catch an affinity peptide tag. Biotinylated peptide tag candidates of varied sequence and length were attached to an avidin platform and screened for affinity against the polymer NP. NP affinity for the avidin/peptide tag complexes was used to provide insight into factors that contribute NP/tag binding. The identified epitope sequence with an optimized length (tMel-tag) was fused to two recombinant proteins. The tagged proteins exhibited higher NP affinity than proteins without tags. The results establish that a fusion peptide tag consisting of optimized 15 amino acid residues can provide strong affinity to an abiotic polymer NP. The affinity and selectivity of NP/tMel-tag interactions were exploited for protein purification in conjunction with immobilized metal ion/His6-tag interactions to prepare highly purified recombinant proteins. This strategy makes available inexpensive, abiotic synthetic polymers as affinity agents for peptide tags and provides alternatives for important applications where more costly affinity agents are used.
Co-reporter:Leah Cleary, Jennifer Pitzen, John A. Brailsford, and Kenneth J. Shea
Organic Letters 2014 Volume 16(Issue 17) pp:4460-4463
Publication Date(Web):August 15, 2014
DOI:10.1021/ol5020043
Progress toward the welwitindolinone alkaloid N-methylwelwitindolinone B isothiocyanate is reported. A key reaction to synthesize the [4.3.1] bicycle embedded in the core of the molecule is a furan type 2 intramolecular Diels–Alder reaction with a tetrasubstituted dienophile, which sets the two vicinal quaternary centers present in the natural product. The sterically encumbered cycloaddition precursor was synthesized using a Horner–Wadsworth–Emmons reaction followed by a Suzuki cross-coupling reaction. Finally, introduction of the secondary alkyl chloride was achieved by a regio- and diastereoselective opening of a [2.2.1] oxobicycloheptane functionality.
Co-reporter:Dr. John M. Beierle;Dr. Keiichi Yoshimatsu;Beverly Chou;Dr. Michael A. A. Mathews;Benjamin K. Lesel; Kenneth J. Shea
Angewandte Chemie International Edition 2014 Volume 53( Issue 35) pp:9275-9279
Publication Date(Web):
DOI:10.1002/anie.201404881
Abstract
We report a new material design concept for synthetic, thermally responsive poly(N-isopropylacrylamide)-based copolymer nanoparticle (NP) hydrogels, which protect proteins from thermal stress. The NP hydrogels bind and protect a target enzyme from irreversible activity loss upon exposure to heat but “autonomously” release the enzyme upon subsequent cooling of the solution. Incorporation of the optimized amount of negatively charged and hydrophobic comonomers to the NP hydrogels was key to achieve these desired functions. As the NP hydrogels do not show a strong affinity for the enzyme at room temperature, they can remain in solution without adversely affecting enzymatic activity or they can be removed by filtration to leave the enzyme in solution. The results demonstrate the promise of this approach for improving the thermal tolerance of proteins.
Co-reporter:Jun Luo, Ruobing Zhao, and Kenneth J. Shea
Macromolecules 2014 Volume 47(Issue 16) pp:5484-5491
Publication Date(Web):August 5, 2014
DOI:10.1021/ma501206a
The living C1 polymerization of sulfoxide ylides initiated by organoborane is one of the few methods for controlling the molecular weight, polydispersity, and topology of simple hydrocarbon polymers. However, the synthesis of linear hydrocarbon polymers (polymethylene) with molecular weights >50 kDa via this method often results in some erosion of polymer polydispersity (PDI 1.3–2.0). In the absence of known chain transfer or termination steps, the origin of the PDI erosion remained a mystery. Here, we report that the PDI erosion can be attributed to small quantities of a borinic ester (R2BOR) impurity that arises from the oxidation of the trialkylborane initiator/catalyst (R3B) by trace oxygen. The propagation rate of R2BOR is substantially lower than that of R3B. Since the oxidized initiator/catalyst would produce very little polymer during the course of polymerization, the low reactivity of R2BOR alone could not account for the increased PDI. However, we have found that during the course of the polymerization (10 min) R2BOR will complex with ylide and undergo 1,2-oxygen migration. The resulting species R2BCH2OR is a more reactive initiator/catalyst than its borinic ester precursor R2BOR. The catalyst transformation introduces reactive growing polymer chains into the system after initiation and throughout the remaining polymerization, contributing to the formation of lower MW polymer. These results are supported by a computational study of the activation energies of the rate-limiting steps. The introduction of a less oxygen-sensitive amine–borane complex initiator/catalyst minimizes this complication and provides a method for synthesizing high-MW, low-PDI polymethylene.
Co-reporter:Adam Weisman, Yingyao Allie Chen, Yu Hoshino, Huiting Zhang, and Kenneth Shea
Biomacromolecules 2014 Volume 15(Issue 9) pp:
Publication Date(Web):June 29, 2014
DOI:10.1021/bm500666j
Methicillin resistant Staphylococcus aureus (MRSA) is a highly virulent bacterium capable of inflicting severe infections. This pathogen has a long history of developing resistance to antibacterial drugs, and many phenotypes are capable of disabling the host immune response by releasing peptide and protein toxins with the capacity to lyse human polymorphonuclear neutrophils. The peptide phenol-soluble modulin α3 (PSMα3) has been identified as an important toxin released by the most virulent strains of MRSA. A library of polymer nonaparticles was synthesized by precipitation polymerization and screened for their ability to bind and neutralize this toxin. To generate high affinity, monomers were chosen to compliment the functional groups of PSMα3. Nanoparticles incorporating aromatic monomers provided a high affinity for the peptide and were effective at neutralizing its toxicity in vitro.
Co-reporter:Dr. John M. Beierle;Dr. Keiichi Yoshimatsu;Beverly Chou;Dr. Michael A. A. Mathews;Benjamin K. Lesel; Kenneth J. Shea
Angewandte Chemie 2014 Volume 126( Issue 35) pp:9429-9433
Publication Date(Web):
DOI:10.1002/ange.201404881
Abstract
We report a new material design concept for synthetic, thermally responsive poly(N-isopropylacrylamide)-based copolymer nanoparticle (NP) hydrogels, which protect proteins from thermal stress. The NP hydrogels bind and protect a target enzyme from irreversible activity loss upon exposure to heat but “autonomously” release the enzyme upon subsequent cooling of the solution. Incorporation of the optimized amount of negatively charged and hydrophobic comonomers to the NP hydrogels was key to achieve these desired functions. As the NP hydrogels do not show a strong affinity for the enzyme at room temperature, they can remain in solution without adversely affecting enzymatic activity or they can be removed by filtration to leave the enzyme in solution. The results demonstrate the promise of this approach for improving the thermal tolerance of proteins.
Co-reporter:Yusuke Yonamine, Keiichi Yoshimatsu, Shih-Hui Lee, Yu Hoshino, Yoshio Okahata, and Kenneth J. Shea
ACS Applied Materials & Interfaces 2013 Volume 5(Issue 2) pp:374
Publication Date(Web):December 21, 2012
DOI:10.1021/am302404q
Cationic-functionalized polymer nanoparticles (NPs) show strikingly distinct affinities to proteins depending on the nature of the cationic functional group. N-Isopropylacrylamide (NIPAm) polymer NPs incorporating three types of positively charged functional groups (guanidinium, primary amino, and quaternary ammonium groups) were prepared by precipitation polymerization. The affinities to fibrinogen, a protein with an isoelectric point (pI) of 5.5, were compared using UV–vis spectrometry and a quartz crystal microbalance (QCM). Guanidinium-containing NPs showed the highest affinity to fibrinogen. The observation is attributed to strong, specific interactions with carboxylate groups on the protein surface. The affinity of the positively charged NPs to proteins with a range of pIs revealed that protein-NP affinity is due to a combination of ionic, hydrogen bonding, and hydrophobic interactions. Protein affinity can be modulated by varying the composition of these functional monomers in the acrylamide NPs. Engineered NPs containing the guanidinium group with hydrophobic and hydrogen bonding functional groups were used in an affinity precipitation for the selective separation of fibrinogen from a plasma protein mixture. Circular dichroism (CD) revealed that the protein was not denatured in the process of binding or release.Keywords: affinity precipitation; fibrinogen; guanidinium; plastic antibodies; polymer nanoparticles; protein interaction;
Co-reporter:Leah Cleary, Victor W. Mak, Scott D. Rychnovsky, Kenneth J. Shea, and Nicholas Sizemore
The Journal of Organic Chemistry 2013 Volume 78(Issue 8) pp:4090-4098
Publication Date(Web):March 11, 2013
DOI:10.1021/jo4004025
Quantum mechanical calculations have been used to investigate type 2 intramolecular N-acylnitroso Diels–Alder reactions. Experimentally observed regioselectivities and diastereoselectivities of these reactions have been reproduced using B3LYP/6-31+G(d) DFT calculations. The factors that govern selectivity (i.e., tether length, tether substitution and diene substitution) were systematically investigated. Tethers less than 6 carbon atoms lead to 1,3-regioisomers due to conformational restrictions. Substituents on the tether lead to diastereoselective outcomes dictated by transannular interactions in the transition states. The modest diastereoselectivity of diene-substituted substrates is rationalized as arising from reduction of eclipsing interactions in the flattened diene transition states. This method should prove valuable for planning syntheses involving type 2 intramolecular Diels–Alder reactions.
Co-reporter:Zhiyang Zeng ; Jiten Patel ; Shih-Hui Lee ; Monica McCallum ; Anuradha Tyagi ; Mingdi Yan
Journal of the American Chemical Society 2012 Volume 134(Issue 5) pp:2681-2690
Publication Date(Web):January 9, 2012
DOI:10.1021/ja209959t
The interaction between synthetic polymer nanoparticles (NPs) and biomacromolecules (e.g., proteins, lipids, and polysaccharides) can profoundly influence the NPs fate and function. Polysaccharides (e.g., heparin/heparin sulfate) are a key component of cell surfaces and the extracelluar matrix and play critical roles in many biological processes. We report a systematic investigation of the interaction between synthetic polymer nanoparticles and polysaccharides by ITC, SPR, and an anticoagulant assay to provide guidelines to engineer nanoparticles for biomedical applications. The interaction between acrylamide nanoparticles (∼30 nm) and heparin is mainly enthalpy driven with submicromolar affinity. Hydrogen bonding, ionic interactions, and dehydration of polar groups are identified to be key contributions to the affinity. It has been found that high charge density and cross-linking of the NP can contribute to high affinity. The affinity and binding capacity of heparin can be significantly diminished by an increase in salt concentration while only slightly decreased with an increase of temperature. A striking difference in binding thermodynamics has been observed when the main component of a polymer nanoparticle is changed from acrylamide (enthalpy driven) to N-isopropylacryalmide (entropy driven). This change in thermodynamics leads to different responses of these two types of polymer NPs to salt concentration and temperature. Select synthetic polymer nanoparticles have also been shown to inhibit protein–heparin interactions and thus offer the potential for therapeutic applications.
Co-reporter:Li-Chih Hu ; Yusuke Yonamine ; Shih-Hui Lee ; Wytze E. van der Veer
Journal of the American Chemical Society 2012 Volume 134(Issue 27) pp:11072-11075
Publication Date(Web):June 25, 2012
DOI:10.1021/ja303118w
A functional nanoparticle with light-triggered charge reversal based on a protected amine-bridged polysilsesquioxane was designed. An emulsion- and amine-free sol–gel synthesis was developed to prepare uniform nanospheres. Photolysis of suspensions of these nanoparticles results in a reversal of the ζ potential. This behavior has been used to trigger nanoparticle self-assembly, nanocomposite hydrogel formation, and nanoparticle release, showing the potential of this material in nanoscale manipulation and nanoparticle therapy.
Co-reporter:Shih-Hui Lee ; Yu Hoshino ; Arlo Randall ; Zhiyang Zeng ; Piere Baldi ; Ruey-an Doong
Journal of the American Chemical Society 2012 Volume 134(Issue 38) pp:15765-15772
Publication Date(Web):August 27, 2012
DOI:10.1021/ja303612d
A process for the preparation of an abiotic protein affinity ligand is described. The affinity ligand, a synthetic polymer hydrogel nanoparticle (NP), is formulated with functional groups complementary to the surface presentation of the target protein. An iterative process is used to improve affinity by optimizing the composition and proportion of functional monomers. Since the polymer NPs are formed by a kinetically driven process, the sequence of functional monomers in the polymer chain is not controlled; only the average composition can be adjusted by the stoichiometry of the monomers in the feed. To compensate for this the hydrogel NP is lightly cross-linked resulting in chain flexibility that takes place on a submillisecond time scale allowing the polymer to “map” onto a protein surface with complementary functionality. In this study, we report a lightly cross-linked (2%) N-isopropyl acrylamide (NIPAm) synthetic polymer NP (50–65 nm) incorporating hydrophobic and carboxylate groups that binds with high affinity to the Fc fragment of IgG. The affinity and amount of NP bound to IgG is pH dependent. The hydrogel NP inhibits protein A binding to the Fc domain at pH 5.5, but not at pH 7.3. A computational analysis was used to identify potential NP–protein interaction sites. Candidates include a NP binding domain that overlaps with the protein A–Fc binding domain at pH 5.5. The computational analysis supports the inhibition experimental results and is attributed to the difference in the charged state of histidine residues. Affinity of the NP (3.5–8.5 nM) to the Fc domain at pH 5.5 is comparable to protein A at pH 7. These results establish that engineered synthetic polymer NPs can be formulated with an intrinsic affinity to a specific domain of a large biomacromolecule.
Co-reporter:Jun Luo, Fangfang Lu, and Kenneth J. Shea
ACS Macro Letters 2012 Volume 1(Issue 5) pp:560
Publication Date(Web):April 12, 2012
DOI:10.1021/mz300140x
We report the synthesis of polymethylene waxes, a surrogate of PE waxes, by a controlled polymerization reaction in water at or near r.t. and under atmospheric pressure. The monomer, dimethylsulfoxonium methylide, is generated in situ from a salt, trimethylsulfoxonium halide. The carbon sources for the polymerizations are C1 molecules, which can be derived from nonpetroleum feedstock. DMSO serves as the C1 carrier and is not consumed. The reaction is initiated and catalyzed by trialkylboranes, compounds that are stable in water. A certain degree of molecular weight control is achieved by adjusting the stoichiometry of “salt” to organoborane. Polymethylene, the simplest hydrocarbon polymer, is a semicrystalline material. The room temperature polymerization produces a linear polymer approximately 100 °C below its melting temperature (Tm). The supercooled polymers rapidly crystallize into flat nanoparticles comprised of stacked lamellae.
Co-reporter:Yusuke Yonamine, Yu Hoshino, and Kenneth J. Shea
Biomacromolecules 2012 Volume 13(Issue 9) pp:
Publication Date(Web):July 19, 2012
DOI:10.1021/bm300986j
Synthetic polymer nanoparticles (NPs) that display high affinity to protein targets have significant potential for medical and biotechnological applications as protein capture agents or functional replacements of antibodies (“plastic antibodies”). In this study, we modified an immunological assay (enzyme-linked immunosorbent assay: ELISA) into a high-throughput screening method to select nanoparticles with high affinity to target proteins. Histone and fibrinogen were chosen as target proteins to demonstrate this concept. The selection process utilized a biotinylated NP library constructed with combinations of functional monomers. The screen identified NPs with distinctive functional group compositions that exhibited high affinity to either histone or fibrinogen. The variation of protein affinity with changes in the nature and amount of functional groups in the NP provided chemical insight into the principle determinants of protein-NP binding. The NP affinity was semiquantified using the ELISA-mimic assay by varying the NP concentrations. The screening results were found to correlate with solution-based assay results. This screening system utilizing a biotinylated NP is a general approach to optimize functional monomer compositions and can be used to rapidly search for synthetic polymers with high (or low) affinity for target biological macromolecules.
Co-reporter:Dr. Keiichi Yoshimatsu;Benjamin K. Lesel;Dr. Yusuke Yonamine;Dr. John M. Beierle;Dr. Yu Hoshino; Kenneth J. Shea
Angewandte Chemie 2012 Volume 124( Issue 10) pp:2455-2458
Publication Date(Web):
DOI:10.1002/ange.201107797
Co-reporter:Dr. Keiichi Yoshimatsu;Benjamin K. Lesel;Dr. Yusuke Yonamine;Dr. John M. Beierle;Dr. Yu Hoshino; Kenneth J. Shea
Angewandte Chemie International Edition 2012 Volume 51( Issue 10) pp:2405-2408
Publication Date(Web):
DOI:10.1002/anie.201107797
Co-reporter:Yu Hoshino;Hiroyuki Koide;Keiichi Furuya;Walter W. Haberaecker III;Takashi Kodama;Hiroaki Kanazawa;Naoto Oku;Shih-Hui Lee
PNAS 2012 Volume 109 (Issue 1 ) pp:
Publication Date(Web):2012-01-03
DOI:10.1073/pnas.1112828109
Synthetic polymer nanoparticles (NPs) that bind venomous molecules and neutralize their function in vivo are of significant
interest as “plastic antidotes.” Recently, procedures to synthesize polymer NPs with affinity for target peptides have been
reported. However, the performance of synthetic materials in vivo is a far greater challenge. Particle size, surface charge,
and hydrophobicity affect not only the binding affinity and capacity to the target toxin but also the toxicity of NPs and
the creation of a “corona” of proteins around NPs that can alter and or suppress the intended performance. Here, we report
the design rationale of a plastic antidote for in vivo applications. Optimizing the choice and ratio of functional monomers
incorporated in the NP maximized the binding affinity and capacity toward a target peptide. Biocompatibility tests of the
NPs in vitro and in vivo revealed the importance of tuning surface charge and hydrophobicity to minimize NP toxicity and prevent
aggregation induced by nonspecific interactions with plasma proteins. The toxin neutralization capacity of NPs in vivo showed
a strong correlation with binding affinity and capacity in vitro. Furthermore, in vivo imaging experiments established the
NPs accelerate clearance of the toxic peptide and eventually accumulate in macrophages in the liver. These results provide
a platform to design plastic antidotes and reveal the potential and possible limitations of using synthetic polymer nanoparticles
as plastic antidotes.
Co-reporter:Li-Chih Hu and Kenneth J. Shea
Chemical Society Reviews 2011 vol. 40(Issue 2) pp:688-695
Publication Date(Web):12 Jan 2011
DOI:10.1039/C0CS00219D
Bridged polysilsesquioxanes (BPS) are a class of versatile functional hybrid materials with tunable chemical, physical and mechanical properties. This tutorial review describes recent advances of these functional hybrid nanomaterials. The review includes control of factors affecting nanometre scale morphology, the preparation of spherical hybrid nanoparticles, along with applications in fields including energy, optics and electronics. Special emphasis will be made regarding the synergy between the organic component of the hybrid material and the polysilsesquioxane moieties.
Co-reporter:Yu Hoshino and Kenneth J. Shea
Journal of Materials Chemistry A 2011 vol. 21(Issue 11) pp:3517-3521
Publication Date(Web):20 Dec 2010
DOI:10.1039/C0JM03122D
Plastic antibodies, synthetic polymer nanoparticles with antibody-like functions, have emerged as potential alternatives to protein antibodies. This paper focuses on recent developments of plastic antibodies for biomacromolecules and their application as antitoxins.
Co-reporter:Leah Cleary, Hoseong Yoo, and Kenneth J. Shea
Organic Letters 2011 Volume 13(Issue 7) pp:1781-1783
Publication Date(Web):March 8, 2011
DOI:10.1021/ol200244p
A new, concise method to synthesize triene precursors for the type 2 intramolecular Diels−Alder reaction has been developed. Microwave irradiation of the trienes provides a convenient method for the synthesis of bridgehead alkenes. Higher yields, shorter reaction times, and lower reaction temperatures provide a general and efficient route to this interesting class of molecules.
Co-reporter:Duangduan Chaiyaveij, Leah Cleary, Andrei S. Batsanov, Todd B. Marder, Kenneth J. Shea, and Andrew Whiting
Organic Letters 2011 Volume 13(Issue 13) pp:3442-3445
Publication Date(Web):June 6, 2011
DOI:10.1021/ol201188d
CuCl2, in the presence of a 2-ethyl-2-oxazoline ligand, is an effective catalyst for the room temperature, aerobic oxidation of hydroxamic acids and hydrazides, to acyl-nitroso and azo dienophiles respectively, which are efficiently trapped in situ via both inter- and intramolecular hetero-Diels–Alder reactions with dienes. Both inter- and intramolecular variants of the Diels–Alder reaction are suitable under the reaction conditions using a variety of solvents. Under the same conditions, an acyl hydrazide was also oxidized to give an acyl-azo dienophile which was trapped intramolecularly by a diene.
Co-reporter:Jun Luo and Kenneth J. Shea
Accounts of Chemical Research 2010 Volume 43(Issue 11) pp:1420
Publication Date(Web):September 8, 2010
DOI:10.1021/ar100062a
The physical properties of synthetic macromolecules are strongly coupled to their molecular weight (MW), topology, and polydispersity index (PDI). Factors that contribute to their utility include the control of functionality at the macromolecule termini and copolymer composition. Conventional polymerization reactions that produce carbon backbone polymers (ionic, free radical, and coordination) provide little opportunity for controlling these variables. Living polymerizations, sometimes referred to as controlled polymerizations, have provided the means for achieving these goals. Not surprisingly, these reactions have had a profound impact on polymer and materials science. Three basic reaction types are used for the synthesis of most carbon backbone polymers. The first examples of “living” polymerizations were developed for ionic polymerizations (cationic and anionic). These reactions, which can be technically challenging to perform, can yield excellent control of molecular weight with very low polydispersity. The second reaction type, free radical polymerization, is one of the most widely used polymerizations for the commercial production of high molecular weight carbon backbone polymers. Nitroxide mediated polymerization (NMP), reversible addition−fragmentation chain transfer polymerization (RAFT), and atom transfer radical polymerization (ATRP) have emerged as three of the more successful approaches for controlling these reactions. The third type, transition metal mediated coordination polymerization, is the most important method for large-scale commercial polyolefin production. Simple nonfunctional hydrocarbon polymers such as polyethylene (PE), polypropylene, poly-α-olefins, and their copolymers are synthesized by high pressure-high temperature free radical polymerization, Ziegler−Natta or metallocene catalysts. Although these catalysts of exceptional efficiency that produce polymers on a huge scale are in common use, control that approaches a “living polymerization” is rare. Although the controlled synthesis of linear “polyethylene” described in this Account is not competitive with existing commercial processes for bulk polymer production, they can provide quantities of specialized materials for the study of structure−property relationships. This information can guide the production of polymers for new commercial applications. We initiated a search for novel polymerization reactions that would produce simple hydrocarbon polymers with the potential for molecular weight and topological control. Our research focused on polymerization reactions that employ nonolefin monomers, more specifically the polymerization of ylides and diazoalkanes. In this reaction, the carbon backbone is built one carbon at a time (C1 polymerization). These studies draw upon earlier investigations of the Lewis acid catalyzed polymerization of diazoalkanes and build upon our discovery of the trialkylborane initiated living polymerization of dimethylsulfoxonium methylide 1.
Co-reporter:Yu Hoshino ; Hiroyuki Koide ; Takeo Urakami ; Hiroaki Kanazawa ; Takashi Kodama ; Naoto Oku
Journal of the American Chemical Society 2010 Volume 132(Issue 19) pp:6644-6645
Publication Date(Web):April 26, 2010
DOI:10.1021/ja102148f
We report that simple, synthetic organic polymer nanoparticles (NPs) can capture and clear a target peptide toxin in the bloodstream of living mice. The protein-sized polymer nanoparticles, with a binding affinity and selectivity comparable to those of natural antibodies, were prepared by combining a functional monomer optimization strategy with molecular-imprinting nanoparticle synthesis. As a result of binding and removal of melittin by NPs in vivo, the mortality and peripheral toxic symptoms due to melittin were significantly diminished. In vivo imaging of the polymer nanoparticles (or “plastic antibodies”) established that the NPs accelerate clearance of the peptide from blood and accumulate in the liver. Coupled with their biocompatibility and nontoxic characteristics, plastic antibodies offer the potential for neutralizing a wide range of biomacromolecules in vivo.
Co-reporter:Yu Hoshino ; Walter W. Haberaecker III ; Takashi Kodama ; Zhiyang Zeng ; Yoshio Okahata
Journal of the American Chemical Society 2010 Volume 132(Issue 39) pp:13648-13650
Publication Date(Web):September 9, 2010
DOI:10.1021/ja1058982
We report that multifunctional polymer nanoparticles approximately the size of a large protein can be “purified”, on the basis of peptide affinity just as antibodies, using an affinity chromatography strategy. The selection process takes advantage of the thermoresponsiveness of the nanoparticles allowing “catch and release” of the target peptide by adjusting the temperature. Purified particles show much stronger affinity (Kdapp ≈ nM) and a narrower affinity distribution than the average of particles before purification (Kdapp > μM) at room temperature but can release the peptide just by changing the temperature. We anticipate this affinity selection will be general and become an integral step for the preparation of “plastic antibodies” with near-homogeneous and tailored affinity for target biomacromolecules.
Co-reporter:Li-Chih Hu, Mariya Khiterer, Shing-Jong Huang, Jerry Chun Chung Chan, Joseph R. Davey, and Kenneth J. Shea
Chemistry of Materials 2010 Volume 22(Issue 18) pp:5244
Publication Date(Web):August 11, 2010
DOI:10.1021/cm101243m
A nonemulsion method to prepare spherical, monodisperse nanoparticles of bridged polysilsesquioxanes was developed. This is the first method to fabricate uniform spherical bridged polysilsesquioxanes from monomers with low to moderate hydrophilicity. The average particle size can be systematically controlled from ∼20 nm to ∼1.5 μm. These particles have distinctive properties that include porosity without templating and buffering capacity. A mechanism for particle growth is proposed.
Co-reporter:Zhiyang Zeng, Yu Hoshino, Andy Rodriguez, Hoseong Yoo and Kenneth J. Shea
ACS Nano 2010 Volume 4(Issue 1) pp:199
Publication Date(Web):December 16, 2009
DOI:10.1021/nn901256s
Synthetic polymer nanoparticles with antibody-like affinity for a hydrophilic peptide have been prepared by inverse microemulsion polymerization. Peptide affinity was achieved in part by incorporating the target (imprint) peptide in the polymerization reaction mixture. Incorporation of the imprint peptide assists in the creation of complementary binding sites in the resulting polymer nanoparticle (NP). To orient the imprint peptide at the interface of the water and oil domains during polymerization, the peptide target was coupled with fatty acid chains of varying length. The peptide−NP binding affinities (ca. 90−900 nM) were quantitatively evaluated by a quartz crystal microbalance (QCM). The optimal chain length was established that created high affinity peptide binding sites on the surface of the nanoparticles. This method can be used for the preparation of nanosized synthetic polymers with antibody-like affinity for hydrophilic peptides and proteins (“plastic antibodies”).Keywords: inverse microemulsion polymerization; molecular imprinting; plastic antibodies; QCM; selective peptide capture; synthetic nanoparticles
Co-reporter:John A. Brailsford, Ryan Lauchli and Kenneth J. Shea
Organic Letters 2009 Volume 11(Issue 22) pp:5330-5333
Publication Date(Web):October 27, 2009
DOI:10.1021/ol902173g
Synthesis of an advanced welwitindolinone intermediate via an alkylation/cyclization reaction is reported. The key step involves a one pot Lewis acid-mediated alkylation of a silylketene aminal with a furan alcohol followed by an intramolecular cyclization. The reaction is stereoselective and takes place at low temperature. The cycloadduct was highly functionalized and contains the welwitindolinone core structure.
Co-reporter:Andrew A. Rodriguez, Hoseong Yoo, Joseph W. Ziller, Kenneth J. Shea
Tetrahedron Letters 2009 50(49) pp: 6830-6833
Publication Date(Web):
DOI:10.1016/j.tetlet.2009.09.129
Co-reporter:Lihua Zhao, Matthias Vaupel, Douglas A. Loy and Kenneth J. Shea
Chemistry of Materials 2008 Volume 20(Issue 5) pp:1870
Publication Date(Web):February 1, 2008
DOI:10.1021/cm702804r
A chemically stable photodimer of 7-allyloxycoumarin (1) has been identified. An efficient synthesis of the syn-ht photodimer (2) was developed, and the compound was subsequently elaborated to the bis(triethoxysilyl) derivative (7). Sol–gel polymerization produced a robust hybrid glass (7X) that could be fabricated as monoliths or cast as transparent colorless thin films. Photopatterning of thin films with UV light (254 nm) produces fluorescent and refractive index patterns which are revealed by fluorescence microscopy (λex = 330 nm, λem = 392 nm) and imaging ellipsometry. At short irradiation times the photoinduced cleavage produces a slight collapse of the silsesquioxane network (∼3%) that is attributed to rupture of the coumarin photodimer cross-links. The topological patterns are also observed by imaging ellipsometry. This material provides a new robust matrix for producing “hidden” fluorescent images, refractive index gratings, and topographical features in dense, hybrid glassy materials. Prolonged irradiation at short wavelengths results in a hard → soft transformation that deforms and “melts” the hard brittle thermoset.
Co-reporter:Kenneth J. Shea;Jie Bai
Macromolecular Rapid Communications 2006 Volume 27(Issue 15) pp:1223-1228
Publication Date(Web):25 JUL 2006
DOI:10.1002/marc.200600252
Summary: Borane reacts with TDM by a sequence of insertion and disproportionation reactions to yield tris-(trimethylsilylmethyl)borane. No further addition of TDM occurs. Triallylborane and tris-(4-methoxyphenylethyl)borane initiate the copolymerization of TDM and dimethylsulfoxonium methylide. The reactions afford TMS-substituted polymethylene oligomers. The resultant poly(methylidene-co-TMSmethylidene) random copolymers arise from incorporation of TMSmethylidene (CHSiMe3) and methylidene (CH2) groups into the growing polymer chain one carbon at a time.
Co-reporter:Hidekazu Nishino Dr.;Chin-Shiou Huang Dr. Dr.
Angewandte Chemie 2006 Volume 118(Issue 15) pp:
Publication Date(Web):9 MAR 2006
DOI:10.1002/ange.200503760
Auf den Film gebannt: Ein molekular geprägter Polymerfilm (MIP-Film) mit der Peptidsequenz des C-Terminus von Cytochrom c (Cyt c) als Prägung kann Cyt c selektiv aus einer Lösung von fünf verschiedenen Proteinen einfangen. Mit einer solchen Methode lassen sich Zielproteine ausschließlich auf der Grundlage von Genominformationen fassen.
Co-reporter:Hidekazu Nishino, Chin-Shiou Huang,Kenneth J. Shea
Angewandte Chemie International Edition 2006 45(15) pp:2392-2396
Publication Date(Web):
DOI:10.1002/anie.200503760
Co-reporter:Jonathan M. Stoddard and Kenneth J. Shea
Chemical Communications 2004 (Issue 7) pp:830-831
Publication Date(Web):27 Feb 2004
DOI:10.1039/B311292F
Dimethylsulfoxonium methylide reacts with dicyclohexyl(α-thiophenylmethyl)methylborane via 1,2-alkyl migration and alkyldithiaborolane via 1,2-sulfur migration.
Co-reporter:Jonathan M. Stoddard, Kenneth J. Shea
Thermochimica Acta 2004 Volume 424(1–2) pp:149-155
Publication Date(Web):15 December 2004
DOI:10.1016/j.tca.2004.05.024
Complexes of dimethylsulfoxonium methylide (1) and organoboranes are crystalline for ylide·BH3 (2), ylide·BPh3 (3), ylide·B(C6F5)3 (4), and ylide·BF3 (5). These complexes undergo exothermic rearrangement by 1,2-migration upon heating to produce homologated organoboranes and dimethylsulfoxide. Non-isothermal kinetic analysis of the differential scanning calorimetry (DSC) data for ylide·BPh3 (3) and ylide·B(C6F5)3 (4) complexes was applied using the Flynn–Wall–Ozawa and Kissinger methods. The calculated apparent activation energy for the reaction of ylide·BPh3 (3) yielded consistent results between the A1.5 model (Ea=120 kJ mol−1, A=4.79×1013 min−1) and Kissinger method (Ea=129 kJ mol−1, A=1.73×1017 min−1). The analysis for the reaction of ylide·B(C6F5)3 (4) gave consistent results between R2, R3, and F1 models with the average parameters, Ea=262 kJ mol−1, A=3.33×1033 min−1. The Kissinger analysis for the reaction of ylide·B(C6F5)3 (4) gave Arrhenius activation parameters (Ea=171 kJ mol−1, A=7.80×1019 min−1) that were higher than for the reaction of ylide·BPh3 (3). The kinetic data revealed that the C6F5 electron-deficient group has a higher activation energy for 1,2-migration and a higher entropy of activation for 1,2-migration than the C6H5 group. HF/6-31G(d) ab initio calculations agree with the kinetic data.
Co-reporter:Brian R. Bear;Steven M. Sparks
Angewandte Chemie 2001 Volume 113(Issue 5) pp:
Publication Date(Web):1 MAR 2001
DOI:10.1002/1521-3757(20010302)113:5<864::AID-ANGE864>3.0.CO;2-0
Anti-Bredt-Alkene, bicyclische Moleküle mit einer Brückenkopf-Doppelbindung, galten lange als chemische Kuriosität. Mit der intramolekularen Diels-Alder-Reaktion vom Typ 2 gelangt man in einem Reaktionsschritt zu dieser faszinierenden Klasse von Molekülen, und man erhielt so zahlreiche anti-Bredt-Alkene für Strukturuntersuchungen und chemische Studien. Kristallstrukturanalysen zeigten das Ausmaß der mit der Brückenkopf-Doppelbindung einhergehenden Deformationen auf, und die Messung von Reaktionsgeschwindigkeiten ermöglichte quantitative Aussagen zu kinetischen Konsequenzen der Verzerrungen. In neuerer Zeit wurden die intramolekulare Diels-Alder-Reaktion vom Typ 2 und die dabei entstehenden anti-Bredt-Alkene auch in der präparativen Organischen Chemie eingesetzt. Die aus der Art der Verknüpfungen in der Vorstufe resultierenden Einschränkungen bewirken im Cycloadditionsschritt eine starke regio- und stereochemische Präferenz mit dem Ergebnis einer stereoselektiven Synthese hochsubstituierter Sechsringe. Die Reaktion ermöglicht aber auch in einem Schritt eine einfache Synthese von Sieben- und Achtringen aus acyclischen Vorstufen. In letzter Zeit hat sich außerdem ihre Nützlichkeit bei der Totalsynthese komplexer Naturstoffe verwiesen.
Co-reporter:Kenneth J. Shea
Chemistry - A European Journal 2000 Volume 6(Issue 7) pp:
Publication Date(Web):3 APR 2000
DOI:10.1002/(SICI)1521-3765(20000403)6:7<1113::AID-CHEM1113>3.0.CO;2-V
The polymerization of dimethylsufoxonium methylide to produce linear polymethylene polymers is described. The reaction is catalyzed/initiated by trialkylboranes and gives organoboron star polymers as the primary product. The reaction is a living polymerization, providing control over molecular weight and functionality at the polymer chain ends. A variety of novel polymethylene architectures are available by this methodology.
Co-reporter:Kenneth J. Shea;Brett B. Busch;Manuel M. Paz
Angewandte Chemie International Edition 1998 Volume 37(Issue 10) pp:
Publication Date(Web):17 DEC 1998
DOI:10.1002/(SICI)1521-3773(19980605)37:10<1391::AID-ANIE1391>3.0.CO;2-0
Not conventional polymerization of ethylene, but rather the title reaction has allowed access to the ω-functionalized tertiary polymethylene alcohols 1. The ylide CH2SOMe2 is the methylene source in this living polymerization, and the chain length can be set by the initial ratio of ylide to organoborane.
Co-reporter:Adam Weisman, Beverly Chou, Jeffrey O'Brien, Kenneth J. Shea
Advanced Drug Delivery Reviews (1 August 2015) Volume 90() pp:81-100
Publication Date(Web):1 August 2015
DOI:10.1016/j.addr.2015.05.011
Toxins delivered by envenomation, secreted by microorganisms, or unintentionally ingested can pose an immediate threat to life. Rapid intervention coupled with the appropriate antidote is required to mitigate the threat. Many antidotes are biological products and their cost, methods of production, potential for eliciting immunogenic responses, the time needed to generate them, and stability issues contribute to their limited availability and effectiveness. These factors exacerbate a world-wide challenge for providing treatment. In this review we evaluate a number of polymer constructs that may serve as alternative antidotes. The range of toxins investigated includes those from sources such as plants, animals and bacteria. The development of polymeric heavy metal sequestrants for use as antidotes to heavy metal poisoning faces similar challenges, thus recent findings in this area have also been included. Two general strategies have emerged for the development of polymeric antidotes. In one, the polymer acts as a scaffold for the presentation of ligands with a known affinity for the toxin. A second strategy is to generate polymers with an intrinsic affinity, and in some cases selectivity, to a range of toxins. Importantly, in vivo efficacy has been demonstrated for each of these strategies, which suggests that these approaches hold promise as an alternative to biological or small molecule based treatments.Download high-res image (85KB)Download full-size image
Co-reporter:Li-Chih Hu and Kenneth J. Shea
Chemical Society Reviews 2011 - vol. 40(Issue 2) pp:NaN695-695
Publication Date(Web):2011/01/12
DOI:10.1039/C0CS00219D
Bridged polysilsesquioxanes (BPS) are a class of versatile functional hybrid materials with tunable chemical, physical and mechanical properties. This tutorial review describes recent advances of these functional hybrid nanomaterials. The review includes control of factors affecting nanometre scale morphology, the preparation of spherical hybrid nanoparticles, along with applications in fields including energy, optics and electronics. Special emphasis will be made regarding the synergy between the organic component of the hybrid material and the polysilsesquioxane moieties.
Co-reporter:Yu Hoshino and Kenneth J. Shea
Journal of Materials Chemistry A 2011 - vol. 21(Issue 11) pp:NaN3521-3521
Publication Date(Web):2010/12/20
DOI:10.1039/C0JM03122D
Plastic antibodies, synthetic polymer nanoparticles with antibody-like functions, have emerged as potential alternatives to protein antibodies. This paper focuses on recent developments of plastic antibodies for biomacromolecules and their application as antitoxins.
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