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Antioxidant studies of fullerene and metallofullerene derivatives and fluorescence studies of terbium-containing metallofullerene derivativesHuang, Rong 10 February 2022 (has links)
Fullerenes and metallofullerenes have been discovered to have a lot of applications in the biomedical area, for instance, they have been shown to have antioxidant, anti-virus, anti-cancer, immunological properties, etc. However, the hydrophobicity nature of fullerenes and metallofullerenes raises the need for functionalized hydrophilic fullerenes and metallofullerenes. Also, the advancement of the purification techniques of fullerenes and metallofullerenes makes the isolation of new fullerenes and metallofullerenes possible. Therefore, discovering the biomedical applications of these newly found fullerenes and metallofullerenes is also of vital importance.
In Chapter 1, we provided a comprehensive background on the history of fullerenes and metallofullerenes, synthesis and purification methods of fullerenes and metallofullerenes, and some of their biological applications, including antioxidant applications and fluorescence applications. Some important fullerene and metallofullerenes and milestones in this area were also discussed.
In Chapter 2, we demonstrated the antioxidant and anti-inflammation ability of a conjugate, FIFIFK(Cy5)PEG24K(NH2)CONH2-C60, that consisted of a peptide that binds specifically to a formyl peptide receptor-1 (FPR-1), which expresses on activated macrophages, and a carboxyl-group-functionalized C60, which is the first discovered and most used fullerene is history. We showed that the fullerene-peptide conjugate had great ability as a radical scavenger and to reduce the volume of inflammatory tissue.
In Chapter 3, we demonstrated the antioxidant and anti-inflammation ability of several metallofullerene derivatives, including amino-Gd3N@C80, amino-Sc3N@C80, carboxy-Gd3N@C80, and carboxyl-Sc3N@C80. Amino-group-functionalized metallofullerenes were found to have higher radical scavenging ability and anti-inflammation ability.
In Chapter 4, we developed fluorescent metallofullerene derivatives, including Tb3N@C80(NH2)9(OH)4NO2 and Tb3N@C80(CH2CH2COOH)21(OH)18. The fluorescence properties of the derivatives of fullerenes or metallofullerenes were normally realized by the addition of fluorescent moieties on the carbon cage of fullerenes or metallofullerenes. However, the fluorescence of our newly developed metallofullerene derivative was realized by the tri-terbium nitride cluster inside the carbon cage. This saved the multi-step synthesis of the fluorescence probe and maintained the simplicity of the structure of the metallofullerene derivative. These derivatives of terbium-containing metallofullerene also showed radical scavenging ability towards hydroxyl radicals.
In Chapter 5, we developed another fluorescent Tb3N@C80 derivative, Tb3N@C80[DiPEG2000]. The advantage of this fluorescent metallofullerene derivative was that it was easier to purify compared to small-functional-groups-functionalized Tb3N@C80 derivatives. This newly developed fluorescent Tb3N@C80 derivative also showed great fluorescent ability and radical scavenging ability.
In Chapter 6, we provided a summary of the studies on the antioxidant and fluorescent properties of fullerenes and metallofullerenes' derivatives that were discussed in this dissertation. / Doctor of Philosophy / Fullerenes and metallofullerenes' have large carbonaceous outer structures that give them possibilities for a lot of chemical reactions. The conjugated carbonaceous outer structures also endow them with exceptional antioxidant ability by reacting with the oxidant species. Therefore, fullerenes and metallofullerenes can be considered as great antioxidants, which are substances that can prevent or slow damage to cells caused by oxidants, in most cases free radicals or other unstable oxidant molecules that the body produces as reactions to environmental and other pressures. Fullerenes and metallofullerenes are sometimes called "free-radical scavengers". However, fullerenes and metallofullerenes are not soluble in biological systems, therefore, it's necessary to attach functional groups onto the outer cage-like structures of fullerenes and metallofullerenes to make them water-soluble, while maintaining their great antioxidant properties. Fullerenes and metallofullerenes are not limited to antioxidant applications, and with the attachment of specialized moieties, for instance, short peptides, they can be made of additional applications. Different metals in these metallofullerenes also provide them with specialized applications. Herein, we have developed a series of water-soluble fullerenes and metallofullerenes and compared their antioxidant properties. We have also developed a water-soluble C60-peptide conjugate that can specifically bind to inflammatory cells and ease the inflammatory condition. We also synthesized a series of metallofullerene derivatives that had dual modalities fluorescent properties and antioxidant properties.
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Exohedral Functionalization and Applications of the Trimetallic Nitride Endohedral MetallofullerenesIezzi, Erick B. 24 October 2003 (has links)
This dissertation addresses the exohedral cage functionalization and potential applications of the Sc₃N@C₈₀ and Sc₃N@C₇₈ trimetallic nitride endohedral metallofullerenes. In addition, this dissertation discusses miscellaneous research that is relevant to the aformentioned metallofullerenes and their applications, such as the discovery of a new cage isomer <i>(D<sub>5h</sub>)</i> of Sc₃N@C₈₀, the synthesis of Lu₃N@C₈₀ as a novel X-ray contrasting agent, and the synthesis of Sc₃¹⁵N@C₈₀ with ¹⁵N₂ gas.
The first derivative of Sc₃N@C₈₀ was synthesized by functionalizing the exterior of the cage via a [4 + 2] cycloaddition reaction with a ¹³C-labeled intermediate. Addition occurred across the [5,6] ring-juncture of the cage to form a mono-adduct, which has a mirror plane of symmetry as observed from the time-averaged ¹³C NMR spectrum. The structure of the mono-adduct was confirmed by X-ray crystallography. Diethyl and dibenzyl malonate adducts of Sc₃N@C₈₀ were synthesized, in addition to a ¹⁵N-labeled terminal amine derivative. Water-soluble metallofullerenols, Sc₃N@C₈₀(OH)<sub>~10</sub>(O)<sub>~10</sub>, were synthesized from polyanionic intermediates.
The Sc₃N@C₇₈ metallofullerene was derivatized with a ¹³C-labeled reagent to afford mono-, di- and tri-adducts. A single structural isomer of the mono-adduct was found, while several isomers of the di- and tri-adducts were observed by HPLC. ¹³C and ¹H NMR data of the mono-adduct support a structure that results from addend addition to an asymmetric site on the C₇₈ carbon cage.
The HPLC isolation and characterization of Lu₃N@C₈₀ is discussed. When irradiated with X-rays, Lu₃N@C₈₀ provided a small level of contrast that can only be attributed to the large atomic number (Z) of the lutetium atoms. Mixed-metal species that contains gadolinium and lutetium or holmium and lutetium could be employed as multifunctional contrasting agents for X-ray, MRI and radiopharmaceuticals, thereby eliminating the need for three separate agents.
A new cage isomer of the Sc₃N@C₈₀ metallofullerene was synthesized and partially isolated by HPLC. This carbon cage possesses <i>D<sub>5h</sub></i> symmetry, as indicated by the time-averaged six line ¹³C NMR spectrum with a 1:2:2:1:1:1 ratio.
The internal metal-nitride cluster of Sc₃N@C₈₀ was synthesized with a ¹⁵N-label for studying the motion(s) of the cluster (within the carbon cage) at various temperatures using ¹⁵N NMR spectroscopy. / Ph. D.
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Chemical Reactivity and Regioselectivity of Trimetallic Nitride Endohedral MetallofullerenesCai, Ting 21 April 2008 (has links)
Endohedral metallofullerenes (EMF) have attracted increasing attention during past decades for their potential applications in the fields of biomedicine and nanomaterials. Trimetallic nitride template endohedral metallofullerenes (TNT EMFs) are some of the most promising fullerene-based materials (e.g., as MRI and X-ray contrast agents) because of their high yields compared to classic endohedral metallofullerenes. This dissertation addresses the chemical reactivity and regioselectivity of TNT EMFs.
Based on the extraordinarily high stability of TNT EMFs relative to empty cage fullerenes and classic endohedral metallofullerenes, macroscopic quantities of high purity TNT EMFs were obtained directly from crude soot in a single facile step by using a cyclopentadiene-functionalized resin to trap the more reactive species via Diels-Alder reactions, allowing the TNT EMFs to pass through. We also developed a support-free chemical separation method of TNT EMFs from Sc- and Lu-based soot extract that makes use of the differing solubilities of unreacted TNT EMFs versus 9-methylanthracene-derivatized empty cage fullerenes.
The exohedral functionalization of metallofullerenes can fine-tune their chemical and physical properties. The first N-methylpyrrolidino derivatives of TNT EMFs (Ih Sc3N@C80 and Ih Er3N@C80) were synthesized via 1,3-dipolar cycloaddition of N-methylazomethine ylides (Prato reaction). The demonstration of planar symmetry in the N-methylpyrrolidino derivatives by 13C NMR spectroscopy suggested that the reaction exclusively took place at the 5,6-ring junction. However, both 5,6-ring and 6,6 ring junction adducts were obtained when Ih Sc3N@C80 reacted with N-triphenylmethyl-5-oxazolidinone, as characterized by NMR spectroscopy and X-ray crystallography. The kinetically favored 6,6-ring junction adduct was converted to the thermodynamic product, the 5,6-ring junction adduct, upon thermal equilibration. The synthesis of pyrrolidino derivatives was also extended to two other Sc-based TNT EMFs, D5h Sc3N@C80 and Sc3N@C78. The reactivity and regioselectivity of D5h Sc3N@C80 and Sc3N@C78 were demonstrated by NMR spectroscopy, X-ray crystallography and theoretical calculations.
Another type of reaction, the Bingel-Hirsch cyclopropanation was carried out with D3h Sc3N@C78 for the first time, yielding a single Cs-symmetric monoadduct and a dominant C2v-symmetric diadduct for the first time. The symmetric diadduct clearly demonstrates the remarkable regioselectivity control exerted by the encapsulated Sc3N cluster. We employed a LUMO electron density surface computational approach to predict multiadduct docking sites on the ellipsoidal fullerene cage surface. We also successfully synthesized the first derivative of a non-IPR fullerene, the diethyl malonate derivative of Sc3N@C68 by a Bingel-Hirsch reaction. The reactivity and regioselectivity of Sc3N@C68 were investigated by NMR spectroscopy and theoretical calculations. / Ph. D.
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Synthesis and Functionalizations of Trimetallic Nitride Template Endohedral Metallofullerenes (TNT-EMFs)Wang, Xuelei 29 September 2006 (has links)
This thesis addresses the synthesis of a new mix-metal trimetallic nitride template endohedral metallofullerene (TNT-EMF) and the functionalizations of M3N@C80 (M = Sc, Gd, Ho) under the high-speed vibration milling (HSVM) condition. In addition, this thesis discusses the internal motion of the cluster, Sc3N inside three different carbon cages, C68, C78 and C80.
Water-soluble derivatives of endohedral metallofullerenes possess a unique potential for medical applications, such as magnetic resonance imaging (MRI) contrast agents, X-ray contrast agents and nuclear medicine. The TNT-EMFs have inherent advantages over other endohedral metallofullerenes, such as M@C60 and M@C82, due to the encapsulation of up to three metal atoms inside the carbon cages. M3N@C80(OH)m(O)n (M = Sc, Gd, Ho) were synthesized under the HSVM condition and characterized by FT-IR, MALDI-TOF and XPS. The relaxivity studies on these water-soluble derivatives have shown that Gd-based metallofullerols have significantly higher relaxivities than commercially used MRI contrast agents (e.g. OmniscanTM) and can be the next generation MRI contrast agent. The Ho containing species has a high R2/R1 ratio compared to other samples showing the potential to be a T2 agent.
In contrast to homonuclear M3N clusters, there is a paucity of mixed-metal cluster cases of TNT-EMFs reported to date because the mixed-metal metallofullerenes are difficult to be separated and purified. In this thesis, CeSc2N@C80 was synthesized, separated in pure form and fully characterized. Single-crystal X-ray diffraction shows that CeSc2N@C80 consists of a four atom asymmetric top (CeSc2N) inside a C80 (Ih ) carbon cage and the nitride ion is not located at the center of the carbon cage but is offset by 0.36 Å. The NMR studies, together with the XPS results, show that CeSc2N@C80 is a weakly paramagnetic system with a single buried f electron spin. A new cage isomer of the Sc3N@C80 (D5h) metallofullerene was also isolated from the Ce-Sc mixture and the cage symmetry was confirmed by single-crystal X-ray diffraction.
The internal motion of the metal-nitride cluster, Sc3N within the carbon cages (C68, C78 and C80) was studied at various temperatures using 45Sc NMR spectroscopy. The reorientation barriers (presumably dominated by motion internal to the cage) were calculated for these three TNT-EMFs. The preliminary results show that the quadrupole coupling constant of Sc3N@C80 (Ih) is quite close to that of Sc3N@C68. / Master of Science
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Preparation, Separation, Characterization and Hydrogenation of Endohedral MetallofullerenesFu, Wujun 26 January 2010 (has links)
Endohedral metallofullerenes (EMFs) have attracted increasing attention during past decades due to their novel structures and potential applications in a variety of fields such as biomedical applications and molecular electronics. This dissertation addresses the structural characterization and hydrogenation of EMFs.
A family of novel large cage yttrium-based TNT EMFs Y₃N@C₂ₙ (n=40-44) was prepared, separated, and structurally characterized for the first time. The structure of Y₃N@C₂ₙ (n=40-44) is proposed by the experimental and computational ¹³C NMR studies. The first ⁸⁹Y NMR results for Y₃N@<I>Iₕ</i>-C₈₀, Y₃N@<I>Cₛ</i>-C₈₄ and Y₃N@<I>D₃</i>-C₈₆ reveal a progression from isotropic to restricted (Y₃N)⁶⁺</sup> cluster motional processes.
The di-metallic EMF Y₂C₉₄ is distinguished as a metal-carbide based EMF, Y₂C₂@<I>D₃</i>-C₉₂. The carbide within the cage is successfully detected by ¹³C NMR. The scalar J<sub>Y-C</sub> coupling between the yttrium atoms and the C₂ unit within the C₉₂ cage is successfully observed, suggesting the C₂ unit rotates rapidly around the yttrium atoms.
Two paramagnetic endohedral metalloheterofullerenes, Y₂@C₇₉N and Gd₂@C₇₉N, were also synthesized and characterized. The EPR study demonstrated that the spin density is mainly localized between the two metallic ions. A spin-site exchange system could be constructed between Y₂@C₇₉N and the organic donor TMPD. Being a unique paramagnetic material, Gd₂@C₇₉N displays an unusual stability over a wide temperature range, which could be very useful in optical and magnetic areas.
Functionalization of EMFs is another point of interest in this dissertation. Hydrogenated Sc₃N@C₈₀ was synthesized and characterized. Our study demonstrated that the Sc₃N@C₈₀ can be fully hydrogenated and the pristine Sc₃N@C₈₀ can be recovered from Sc₃N@C₈₀H₈₀ after being heated in vacuum. The hydrogenated EMFs could be potential hydrogen storage materials. / Ph. D.
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Studies of Solution Paramagnetic-Substrate Nuclear and Electron Intermolecular InteractionsRuss, Jennifer Lynn 26 April 2006 (has links)
Advanced nuclear and electron magnetic resonance techniques (i.e. nuclear magnetic resonance (NMR), dynamic nuclear polarization (DNP), and magnetic resonance imaging (MRI)) were used to study the attitude and dynamics of TEMPO (2,2,6,6-tetramethylpiperidinyloxy)-substrate systems and the relaxivity properties of water-soluble trimetallic nitride template functionalized endohedral metallofullerenes (TNT-fMF). The attitude and average distance of interaction for each TEMPO-substrate system was determined from comparing density functional theory (DFT) calculation results with experimental hyperfine coupling constants leading to an improved understanding of solution dynamics. The short-lived solvent-solute interactions of the TEMPO-substrate molecules, such as transient complex formation, are governed by weak hydrogen-bonding interactions. The collisions in solution were explained by determining the favored orientations of the two molecules interacting using calculated relative energy minima and reproducibility of the experimental results by the calculated coupling constants.
Water-soluble TNT-fMFs are studied as candidates for the next generation MRI contrast agents as diagnostic agents and also as possible therapeutic agents to kill cancer cells and decrease tumors. The TNT-fMFs are being studied as part of a multi-modal platform dependent upon which metal atoms are encapsulated inside: Gd — MRI contrast agent (diagnostic), Lu and Ho — radio labeled for use as a therapeutic agent, Tb – fluorescence, and Lu – x-ray contrast. The current commercial MRI contrast agent, OmniscanTM, contains one gadolinium atom; however, the metal is complexed to, not encapsulated in, the molecule. TNT-fMFs fully encapsulate three metal atoms to ensure the patient does not run the risk of metal poisoning. The r1 and r2 relaxivities of TNT-fMFs containing either Gd, Lu, Ho, or Sc metals were measured at 0.35T. The data for the Gd containing TNT-fMFs indicated the metallofullerene has significantly higher relaxivities than OmniscanTM, and can be the next generation MRI contrast agent. The Ho containing species has a high r2/r1 ratio compared to the other samples showing it is a potential T2 agent, and has therapeutic capabilities. / Ph. D.
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The Studies of Fullerenes and Metallofullerenes in Geometry, Electron Transfer, Chromatography and CharacterizationLiu, Xiaoyang 14 August 2019 (has links)
Since their discovery, fullerenes and metallofullerenes have been investigated regarding their structures, synthesis, isolations, and applications. The highly symmetric structures of fullerenes and metallofullerenes lead to extraordinary physical properties, such as electron transfers, and attract major attention from the science community. It has been well established that the stabilities of fullerenes and metallofullerenes can be estimated by recognizing structural patterns. Recently, we developed a generalized spiral program and additional codes and believe they are useful for fullerene/metallofullerene researchers. The higher fullerenes, those with more than 90 carbon atoms, also follow certain structural patterns. In our studies, we have shown that the higher fullerenes with tubular structures are stable in thermodynamics and can survive the aminopropanol reaction, but other spherical fullerenes cannot. For the past three decades, great efforts have been devoted to applying fullerenes and metallofullerenes as electronic materials. In our studies, we find the ground state electron transfer properties endow metallofullerenes as an ideal material for perovskite solar cells to enhance the stabilities. It has been shown in our investigations that common metallofullerenes, such as Sc3N@C80, are capable to be as the electron transfer layers in perovskite solar cells, and the test demonstrates that our novel perovskite solar cells may achieve high stability and high efficiency. The electron transfer abilities of metallofullerenes are studied with the M2@C79N since electron densities located in between the two metal atoms convert between a single electron bond and a double electron bond. The huge spherical electron delocalized structures of fullerenes and metallofullerenes lead to strong interactions with other delocalized systems, such as graphene. Previous studies have shown that graphene has a unique ability in molecular adsorptions. However, the graphene surface is not always flat and the rippled areas have effects on the packing styles. Therefore, we examined the behavior of fullerenes on the rippled graphene surface and then compared with another flat molecule, PTCDA. The results show that the effect of rippled areas varies due to molecular structures. This study gives instructions for electronic device manufacturing using graphene and fullerenes. In our studies, polarizability is a key factor of fullerenes and metallofullerenes. It has been shown that the chromatographic retention behavior has a strong relationship with the average polarizability of a molecule. Based on the experimental data, we built a model for the prediction of chromatographic retention times using computational polarizabilities. After that, we validated the model by two series of chromatographic data. The characterization of carbon-based materials has been long investigated. In the last chapter, we introduce a dynamic nuclear polarization-based method to characterize the structures of chars and studied the adsorption of oxygen on the activated radical sites. Overall, the dissertation reports my Ph. D. studies in the areas including theoretical studies of fullerene geometries, chromatographic models, applications and also experimental studies of the applications of fullerenes/metallofullerenes and characterization. / Doctor of Philosophy / Fullerenes and metallofullerenes are important materials for engineering and science. In general, a fullerene cage contains only carbon atoms and has a closed spherical structure. Theoretically, for a given number of carbon atoms, there are thousands of different ways to assemble a fullerene structure, just like assembling Lego. However, just a limited number of fullerene molecules have been discovered. In the past four decades, several theories have been proposed to explain the fact. For example, an isolated pentagon rule shows that the fullerene structures should not have any conjugated pentagons, which will decrease the stabilities of fullerene molecules. In this dissertation, I would like to show our results, which demonstrate fullerenes that can be synthesized follow certain patterns. We apply experimental and theoretical methods to discover the patterns and explain the reason. The application of fullerenes/metallofullerenes is another hot topic. We consider the structures of fullerenes endow them extraordinary abilities of electron transfers. Therefore, we use metallofullerenes as electron transfer material in a solar cell, and we have a good solar cell with high efficiency. We also inspect the interactions between fullerenes and rippled graphene surface. The results are also extended to understand the chromatographic behavior of fullerenes. By considering the physical properties of fullerenes, we build up simple models to simulate the chromatographic retention behaviors of fullerene inside the chromatographic column. The characterization of carbon-based material is a big challenge and in this dissertation, we demonstrate our contributions of a novel method for characterization, which can detect activated carbons.
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The Chemistry of Fullerenes, Polymers, and Host/Guest InteractionsSchoonover, Daniel Vernon 03 March 2015 (has links)
The exploitation of the relationship between the chemical and physical properties of materials is the hallmark of advancing science throughout the world. The basic understanding of how and why molecules react and interact with each other in different environments allows for the discovery and implementation of new materials and devices that not only advance the state of human life but continually change the planet. The work described in this dissertation generally falls under three diverse categories: functionalization of fullerenes, investigation of host/guest interactions in solution, and the synthesis and characterization of ion containing polymers.
The separation and functionalization of fullerenes is a recent and exciting area of research. The separation methods outlined are intended to increase the availability of endohedral metallofullerenes by decreasing their cost of production. Functionalized fullerene species were achieved through Bingel and Prato reactions to provide materials with novel functional groups. These materials may be further utilized in photovoltaic or other organic electronic devices.
The characterization of noncovalent interactions between different molecules in solution is the focus of supramolecular chemistry. Isothermal Titration Calorimetry stands out as one of the best, among the many methods used to elucidate the characteristics of these systems. The binding of bis- imidazolium and paraquat guests with macrocyclic host molecules has been explored in this work. The measurements of the association constants for these systems will aid in the ongoing synthesis of new host/guest systems.
Ion containing polymers were synthesized and characterized for their use in electroactive devices. Imidazolium containing polymers with bulky anions were synthesized on low glass transition polymer chains. These materials had enhanced ion conductivity and may eventually be used in electronic actuator materials. / Ph. D.
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Fullerene Based Nanomaterials for Biomedical ApplicationsLi, Tinghui 18 January 2018 (has links)
Trimetallic nitride endohedral fullerenes (TNT-EMF) have been recognized for their multifunctional capabilities in biomedical applications. Functionalized gadolinium-loaded fullerenes attracted much attention as a potential new nanoplatform for next-generation magnetic resonance imaging (MRI) contrast agents, given their inherent higher 1H relaxivity than most commercial contrast agents. The fullerene cage is an extraordinarily stable species which makes it extremely unlikely to break and release the toxic Gd metal ions into the bioenvironment. In addition, radiolabeled metals could be encapsulated in this robust carbon cage to deliver therapeutic irradiation. In this dissertation, we aim to develop a series of functionalized TNT-EMFs for MRI detection of various pathological conditions, such as brain cancer, chronic osteomyelitis, and gastrointestinal (GI) tract.
As a general introduction, Chapter 1 briefly introduces recent progress in developing metallofullerenes for next-generation biomedical applications. Of special interest are MRI contrast agents. Other potential biomedical applications, toxicity, stability and biodistribution of metallofullerenes are also discussed. Finally, the challenges and future outlook of using fullerene in biomedical and diagnosis applications are summarized at the end of this chapter.
The large carbon surface area is ideally suited for multiple exo-functionalization approaches to modify the hydrophobic fullerene cage for a more hydrophilic bio-environment. Additionally, peptides and other agents are readily covalently attached to this nanoprobe for targeting applications. Chapter 2 presents the functionalized metallofullerenes conjugated with interleukin-13 peptide exhibits enhanced targeting of U-251 glioblastoma multiforme (GBM) cell lines and can be effectively delivered intravenously in an orthotopic GBM mouse model. Chapter 3 shows, with the specific targeting moiety, the functionalized metallofullerenes can be applied as a non-invasive imaging approach to detect and differentiate chronic post-traumatic osteomyelitis from aseptic inflammation.
Fullerene is a powerful antioxidant due to delocalization of the π-electrons over the carbon cage, which can readily react with free radicals and subsequently delivers a cascade of downstream possessions in numerous biomedical applications. Chapter 4 investigates the antioxidative and anti-inflammatory properties of functionalized Gd3N@C80. This nanoplatform would hold great promise as a novel class of theranostic agent in combating oxidative stress and resolving inflammation, given their inherent MRI applications.
In chapter 5, Gd3N@C80 is modified with polyethylene glycol (PEG) for working as MRI contrast agents for GI tract. The high molecular weight can prevent any appreciable absorption through the skin or mucosal tissue, and offer considerable advantages for localized agents in the GI tract. Besides the excellent contrast capability, the PEGylated-Gd3N@C80 exhibits outstanding radical scavenging ability, which can potentially eliminate the reactive oxygen species in GI tract. The biodistribution result suggests this nanoplatform can be worked as the potential contrast agent for GI tract at least for 6 hours.
A novel amphiphilic Gd3N@C80 derivative is discussed in Chapter 6. It has been noticed for a long time the functionalization Gd3N@C80 contrast agents have higher relaxivity at lower concentrations. The explanation for the concentration dependency is not fully understood. In this work, the amphiphilic Gd3N@C80 derivative is used as the model to investigate the relationship between the relaxivity and concentration of the Gd-based fullerenes.
Click chemistry has been extensively used in functionalization due to the high efficiency and technical simplicity of the reaction. Appendix A describes a new type of Sc3N@C80 derivative conducted by employing the click reaction. The structure of Sc3N@C80-alkynyl and Sc3N@C80- alkynyl-benzyl azide are characterized by NMR, MALDI-TOF, UV-Vis, and HPLC. The high yield of the click reaction can provide access to various derivatives which have great potential for application in medical and materials science.
The functionalization and characterizations of Ho3N@C80 derivatives are reported in Appendix B. The contrast ability of Ho3N@C80 is directly compared with Gd3N@C80. The Ho-based fullerenes can be performed as the radiotherapeutic agents; the leaching study is performed to test the stability of carbon cage after irradiation.
Appendix C briefly shows a new method to develop Gd3N@C80 based targeting platform, which can be used as the probe for chronic post-traumatic osteomyelitis. / PHD
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The Preparation, Functionalization and Biomedical Applications of Carbonaceous NanomaterialsZhang, Jianfei 06 May 2011 (has links)
Carbon nanomaterials have attracted significant attention in the past decades for their unique properties and potential applications in many areas. This dissertation addresses the preparation, functionalization and potential biomedical applications of various carbonaceous nanomaterials.
Trimetallic nitride template endohedral metallofullerenes (TNT-EMFs, M₃N@C₈₀, M = Gd, Lu, etc.) are some of the most promising materials for biomedical applications. Water-soluble Gd₃N@C₈₀ was prepared by the functionalization with poly(ethylene glycol) (PEG) and hydroxyl groups (Gd₃N@C₈₀[DiPEG(OH)ₓ]). The length of the PEG chain was tuned by changing the molecular weight of the PEG from 350 to 5000. The 1H magnetic resonance relaxivities of the materials were studied at 0.35 T, 2.4 T and 9.4 T. Their relaxivities were found to increase as the molecular weight of the PEG decreased, which is attributed to the increasing aggregate size. The aggregate sizes were confirmed by dynamic light scattering. In vivo study suggested that Gd3N@C₈₀[DiPEG(OH)x] was a good candidate for magnetic resonance imaging (MRI) contrast agents. Another facile method was also developed to functinalize Gd₃N@C₈₀ with both carboxyl and hydroxyl groups by reaction with succinic acyl peroxide and sodium hydroxide thereafter. The product was determined to be Gd₃N@C₈₀(OH)~₂₆(CH₂CH₂COOM)~₁₆ (M = Na, H) by X-ray photoelectron spectrometry. The Gd₃N@C₈₀(OH)~₂₆(CH₂CH₂COOM)~₁₆ also exhibited high relaxivity, and aggregates in water. The research on both pegylated and carboxylated Gd₃N@C₈₀ suggests that aggregation and rotational correlation time plays an important role in relaxation, and the relaxivities and aggregation of the water-soluble metallofullerenes can be tuned by varying the molecular weight of the functionality.
TNT-EMFs can be encapsulated inside single-walled carbon nanotubes (SWNTs) to form "peapod" structures by heating the mixture of TNT-EMFs and SWNTs in a vacuum. The peapods were characterized by Raman spectrometry and transmission electron microscopy (TEM). The peapods were then functionalized with hydroxyl groups by a high speed vibration milling (HSVM) method in the presence of KOH. The functionalized Gd-doped peapods exhibited high relaxivites and had an additional advantage of "double carbon wall" protection of the toxic Gd atoms from possible leaking.
The HSVM method was modified by using succinic acyl peroxide. The modified HSVM method could functionalize multi-walled carbon nanotubes (MWNT) and single-walled carbon nanohorns (SWNHs) with carboxyl groups. In the presence of N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC), carboxylate MWNTs and SWNHs could be conjugated with CdSe/ZnS quantum dots (QDs).
TNT-EMFs were also encapsulated inside SWNHs to form SWNH peapods. SWNH peapods were functionalized by the modified HSVM method and then were conjugated with CdSe/ZnS QDs. The peapods were characterized by TEM. In vitro and in vivo studies indicated that SWNH peapods could serve as a multimodal diagnostic agent: MRI contrast agent (Gd₃N@C₈₀ encapsulated), radio-active therapeutic agent (Lu₃N@C₈₀ encapsulated) and optical imaging agent (QDs). / Ph. D.
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