Synthesis and applications of materials and polymers containing graphenic and/or triptycene moities

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, February 2013."November 2012." Cataloged from PDF version of thesis.Includes bibliographical references.In this thesis, molecular design is used to synthesize novel materials with specific properties. The materials presented herein are based on two motifs. In part I, new methods of functionalizing graphenic materials and the applications of those materials are presented. In part II, new triptycene-based polymers are synthesized and their performance is explored. Part I: Graphenic Materials Chapter 1: Three different types of epoxy-functionalized multiwalled carbon nanotubes (EpCNTs) were prepared via multiple covalent functionalizaton methods. The effect of the different chemistries on the adhesive properties of a nanocomposite prepared from commercial epoxy at 0.5, 1, 2, 3, 5, and 10 weight % CNT was studied. It was found that a covalently functionalized EpCNT (EpCNT2) at 1 weight % increased the lap shear strength, by 36 % over the unfilled epoxy formulation and by 27 % over a 1 weight % unmodified MWNT control sample. SEM images revealed a fracture surface morphology change with the incorporation of EpCNT and a deflection of the crack fronts at the site of embedded CNTs, as the mechanism accounting for increased adhesive strength. Chapter 2: In this chapter, the hydroxyl functionalities in graphene oxide (GO, a highly oxidized analogue of graphite), the vast majority that must be allylic alcohols, are subjected to Johnson-Claisen rearrangement conditions. In these conditions, a [3, 3] sigmatropic rearrangement after reaction with triethyl orthoacetate gives rise to an ester functional group, attached to the graphitic framework via a robust C-C bond. The resultant functional groups were found to withstand reductive treatments for the deoxygenation of graphene sheets and a resumption of electronic conductivity is observed. The chemical versatility of the ester groups allows for a variety of functional graphenes to be synthesized, and several of these have been used to successfully build layer-by-layer (LBL) constructs. Chapter 3: The effects of quantity of graphene and carbon nanotube-based fillers and their pendant functional groups on the shear properties of a thermoset epoxy were investigated. Two novel functionalized graphenes, one with epoxy functionality and the other with an amine, are synthesized for this purpose. The properties of the epoxy nanocomposites containing epoxy- and amine-functionalized graphene are compared with those containing GO, Claisen-functionalized graphene, MWNT, the EpCNTs, and the unfilled epoxy. One of the EpCNT (EpCNT3) was found to increase the plateau shear storage modulus by 136 % (1.67 MPa to 3.94 MPa) and the corresponding loss modulus by almost 400 % at a concentration of 10 weight %. A hybrid system of EpCNT3 and graphite was also studied, which improved the storage modulus by up to 51 %. Part II: Triptycene-Based Polymers Chapter 4: A series of soluble, thermally stable aromatic polyimides were synthesized using commercially available five and six membered ring anhydrides and 2, 6- diaminotriptycene derivatives. All of these triptycene polyimides (TPIs) were soluble in common organic solvents despite their completely aromatic structure, due to the threedimensional triptycene structure that prevents strong interchain interactions. Nanoporosity in the solid state gives rise to high surface areas (up to 430 m2/g) and low refractive indices (1.19- 1.79 at 633 nm), which suggest very low dielectric constants at optical frequencies. The decomposition temperature (Td) for all of the polymers is above 500 'C, indicating excellent prospects for high temperature applications. Chapter 5: Several new triptycene-containing polyetherolefins were synthesized via acyclic diene metathesis (ADMET) polymerization. Two types of triptycene-based monomer with varying connectivities were used in the synthesis of homopolymers, block copolymers, and random copolymers. In this way, the influence of the triptycene architecture and concentration in the polymer backbone on the thermal behavior of the polymers was studied. Inclusion of increasing amounts of triptycene were found to increase the glass transition temperature, from -44 °C in polyoctenamer to 59 °C in one of the hydrogenated triptycene homopolymers (H-PT2). Varying the amounts and orientations of triptycene was found to increase the stiffness (H-PT1), toughness (PT1₁- b-PO₁) and ductility (PT1₁-ran-PO₃) of the polymer at room temperature. Chapter 6: A novel all-hard block polyurea containing triptycene units was synthesized from N,N-carbonyldiimidizole and 2,6-diaminotriptycene. The incorporation of triptycene along the backbone prohibits the polymer from hydrogen-bonding with itself and leave the sites of the urea open for the capture of H-bond accepting analytes. Targeted analytes include cyclohexanone, a signature of the powerful explosive RDX (1 ,3,5-trinitro- 1,3,5- triazacyclohexane) and organophosphate nerve agents. This triptycene-polyurea (TPU) was found to be fluorescent in solution in the presence of H-bonding solvents. TPU was cast into thin films and a 12% increase in the fluorescent emission at 443 nm was observed in the presence of saturated cyclohexanone vapor. The sensitivity and selectivity of this response is enhanced by creating a hybrid system with squaraine (Hbond acceptor) and a HFIP-dypyrrin based dye (H-bond donor).by Stefanie A. Sydlik.Ph.D

In Vivo Compatibility of Graphene Oxide with Differing Oxidation States

Graphene oxide (GO) is suggested to have great potential as a component of biomedical devices. Although this nanomaterial has been demonstrated to be cytocompatible in vitro, its compatibility in vivo in tissue sites relevant for biomedical device application is yet to be fully understood. Here, we evaluate the compatibility of GO with two different oxidation levels following implantation in subcutaneous and intraperitoneal tissue sites, which are of broad relevance for application to medical devices. We demonstrate GO to be moderately compatible in vivo in both tissue sites, with the inflammatory reaction in response to implantation consistent with a typical foreign body reaction. A reduction in the degree of GO oxidation results in faster immune cell infiltration, uptake, and clearance following both subcutaneous and peritoneal implantation. Future work toward surface modification or coating strategies could be useful to reduce the inflammatory response and improve compatibility of GO as a component of medical devices.National Institutes of Health (U.S.). Centers of Cancer and Nanotechnology Excellence (1U54CA151884-01)National Institutes of Health (U.S.). Ruth L. Kirschstein National Research Service Award (F32EB018155)David H. Koch Institute for Integrative Cancer Research at MIT (Mazumdar-Shaw International Oncology Fellowship)National Institutes of Health (U.S.). Ruth L. Kirschstein National Research Service Award (F32DK101335)National Institutes of Health (U.S.) (R01- DE016516-06

Hypercalcaemia after treatment with denosumab in children: bisphosphonates as an option for therapy and prevention?

BACKGROUND Pharmacologic options for treatment of osteolytic diseases especially in children are limited. Although not licensed for use, denosumab, a fully humanized antibody to RANKL, is used in children with good effects. Among others, one possible indication are giant cell tumors and aneurysmatic bone cysts. However, there are reports of severe hypercalcemia during weeks to months after termination of denosumab, that are rarely seen in adults. METHODS We collected~data of four patients, aged 6-17~years, who~experienced severe hypercalcemia after completion of treatment with denosumab for unresectable giant cell tumors of bone or aneurysmal bone cysts and methods of their treatment. The detailed case information were described. RESULTS One patient was treated with long-term, high-dose steroid therapy, leading to typical Cushing's syndrome. Another patient was restarted on denosumab repeatedly due to relapses of hypercalcemia after every stop. Finally, in two patients, hypercalcemia ceased definitely after treatment with bisphosphonates. However, several applications were necessary to stabilize calcium levels. CONCLUSIONS There is a considerable risk of hypercalcemia as an adverse effect after denosumab treatment in children. Therapeutic and, preferably, preventive strategies are needed. Bisphosphonates seem to be an option for both, but effective proceedings still remain to be established

Preventing carbon nanoparticle-induced lung inflammation reduces antigen-specific sensitization and subsequent allergic reactions in a mouse model

Background Exposure of the airways to carbonaceous nanoparticles can contribute to the development of immune diseases both via the aggravation of the allergic immune response in sensitized individuals and by adjuvant mechanisms during the sensitization against allergens. The cellular and molecular mechanisms involved in these adverse pathways are not completely understood. We recently described that the reduction of carbon nanoparticle-induced lung inflammation by the application of the compatible solute ectoine reduced the aggravation of the allergic response in an animal system. In the current study we investigated the influence of carbon nanoparticles on the sensitization of animals to ovalbumin via the airways. Ectoine was used as a preventive strategy against nanoparticle-induced neutrophilic lung inflammation. Methods Balb/c mice were repetitively exposed to the antigen ovalbumin after induction of airway inflammation by carbon nanoparticles, either in the presence or in the absence of ectoine. Allergic sensitization was monitored by measurement of immunoglobulin levels and immune responses in lung and lung draining lymph nodes after challenge. Furthermore the role of dendritic cells in the effect of carbon nanoparticles was studied in vivo in the lymph nodes but also in vitro using bone marrow derived dendritic cells. Results Animals exposed to antigen in the presence of carbon nanoparticles showed increased effects with respect to ovalbumin sensitization, to the allergic airway inflammation after challenge, and to the specific TH2 response in the lymph nodes. The presence of ectoine during the sensitization significantly reduced these parameters. The number of antigen-loaded dendritic cells in the draining lymph nodes was identified as a possible cause for the adjuvant effect of the nanoparticles. In vitro assays indicate that the direct interaction of the particles with dendritic cells is not able to trigger CCR7 expression, while this endpoint is achieved by lung lavage fluid from nanoparticle-exposed animals. Conclusions Using the intervention strategy of applying ectoine into the airways of animals we were able to demonstrate the relevance of neutrophilic lung inflammation for the adjuvant effect of carbon nanoparticles on allergic sensitization.n

The effect of mixing methods on the dispersion of carbon nanotubes during the solvent-free processing of multiwalled carbon nanotube/epoxy composites

The article of record as published may be found at: http://dx.doi.org/10.1002/polb.23225Several solvent-free processing methods to disperse multiwalled carbon nanotubes (MWCNTs) in bisphenol F-based epoxy resin were investigated, including the use of a microfluidizer (MF), planetary shear mixer (PSM), ultrasonication (US) and combinations. The processed mixture was cured with diethyl toluene diamine. Three complimentary techniques were used to characterize the dispersion of the MWCNTs in cured composite samples: optical microscopy, micro Raman spectroscopy, and scanning electron microscopy (SEM). For sample MF þ PSM, optical micrographs and Raman images showed reduced agglomeration and a homogeneous distribution of MWCNTs in the epoxy matrix. SEM analysis of fractured specimen after tensile testing revealed breakage of nanotubes along the fracture surface of the composite. A comparison of the MWCNT dispersion in the epoxy samples processed using different methods showed that a combination of MF and PSM processing yields a more homogeneous sample than the PSM or US þ PSM processed samples. Mechanical testing of the composites showed about 15% improvement in the tensile strength of samples processed by the MF þ PSM method over other methods. Thermogravimetric analysis (TGA) results showed a small decrease in the onset degradation temperature for poorly dispersed samples produced by PSM compared with the well-mixed samples (MF þ PSM). These results strongly suggest that the MF þ PSM processing method yield better-dispersed and stronger MWCNT/epoxy composites

Preventing carbon nanoparticle-induced lung inflammation reduces antigen-specific sensitization and subsequent allergic reactions in a mouse model

BACKGROUND: Exposure of the airways to carbonaceous nanoparticles can contribute to the development of immune diseases both via the aggravation of the allergic immune response in sensitized individuals and by adjuvant mechanisms during the sensitization against allergens. The cellular and molecular mechanisms involved in these adverse pathways are not completely understood. We recently described that the reduction of carbon nanoparticle-induced lung inflammation by the application of the compatible solute ectoine reduced the aggravation of the allergic response in an animal system. In the current study we investigated the influence of carbon nanoparticles on the sensitization of animals to ovalbumin via the airways. Ectoine was used as a preventive strategy against nanoparticle-induced neutrophilic lung inflammation. METHODS: Balb/c mice were repetitively exposed to the antigen ovalbumin after induction of airway inflammation by carbon nanoparticles, either in the presence or in the absence of ectoine. Allergic sensitization was monitored by measurement of immunoglobulin levels and immune responses in lung and lung draining lymph nodes after challenge. Furthermore the role of dendritic cells in the effect of carbon nanoparticles was studied in vivo in the lymph nodes but also in vitro using bone marrow derived dendritic cells. RESULTS: Animals exposed to antigen in the presence of carbon nanoparticles showed increased effects with respect to ovalbumin sensitization, to the allergic airway inflammation after challenge, and to the specific T(H)2 response in the lymph nodes. The presence of ectoine during the sensitization significantly reduced these parameters. The number of antigen-loaded dendritic cells in the draining lymph nodes was identified as a possible cause for the adjuvant effect of the nanoparticles. In vitro assays indicate that the direct interaction of the particles with dendritic cells is not able to trigger CCR7 expression, while this endpoint is achieved by lung lavage fluid from nanoparticle-exposed animals. CONCLUSIONS: Using the intervention strategy of applying ectoine into the airways of animals we were able to demonstrate the relevance of neutrophilic lung inflammation for the adjuvant effect of carbon nanoparticles on allergic sensitization. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12989-015-0093-5) contains supplementary material, which is available to authorized users

In Situ Loading of Basic Fibroblast Growth Factor Within Porous Silica Nanoparticles for a Prolonged Release

Basic fibroblast growth factor (bFGF), a protein, plays a key role in wound healing and blood vessel regeneration. However, bFGF is easily degraded in biologic systems. Mesoporous silica nanoparticles (MSNs) with well-tailored porous structure have been used for hosting guest molecules for drug delivery. Here, we report an in situ route to load bFGF in MSNs for a prolonged release. The average diameter (d) of bFGF-loaded MSNs is 57 ± 8 nm produced by a water-in-oil microemulsion method. The in vitro releasing profile of bFGF from MSNs in phosphate buffer saline has been monitored for 20 days through a colorimetric enzyme linked immunosorbent assay. The loading efficiency of bFGF in MSNs is estimated at 72.5 ± 3%. In addition, the cytotoxicity test indicates that the MSNs are not toxic, even at a concentration of 50 μg/mL. It is expected that the in situ loading method makes the MSNs a new delivery system to deliver protein drugs, e.g. growth factors, to help blood vessel regeneration and potentiate greater angiogenesis