Fullertubes: A 30-Year Story of Prediction, Experimental Validation, and Applications for a Long-Missing Family of Soluble Carbon Molecules.

ConspectusDuring the last 30 years, theoretical scientists imagined segmental families of monolayer carbon tubules with fullerene-based end-caps. These molecules would possess structural features of both enes (hemispherical end-caps) and tubular belts of single-walled carbon nano (SWCNTs). Yet, their experimental verification remained elusive for decades.

Colossal C Fullertubes: Soluble [5,5] C-D(1) Pristine Molecules with 70 Nanotube Carbons and Two 30-Atom Hemifullerene End-caps.

We report the seminal experimental isolation and DFT characterization of pristine [5,5] C-D(1) fullertubes. This achievement represents the largest soluble carbon molecule obtained in its pristine form. The [5,5] C species is the highest aspect ratio fullertube purified to date and now surpasses the recent gigantic [5,5] C-D(1).

Water-soluble endohedral metallofullerenes: new horizons for biomedical applications.

Endohedral metallofullerenes (EMFs) offer a safe avenue to manipulate metals important to biomedical applications such as MRI contrast, X-ray contrast, radiolabeling, radiotherapy, chemotherapy, and the control of inflammation by scavenging reactive oxygen species (ROS). Moreover, functionalizing the double bonds on the surface of EMFs modifies their solubility, supramolecular behaviour, binding, targeting characteristics, and physical properties. While most existing water-soluble derivatives possess a statistical mixture of appended functional groups, progress has been made in creating molecularly-precise derivatives with a defined number of surface functional groups, leading to potentially more nuanced control of their behaviour and properties.

Gigantic C Fullertubes: Prediction and Experimental Evidence for Isomerically Purified Metallic [5,5] C-D(1) and Nonmetallic [10,0] C-D(10766).

We report the first experimental characterization of isomerically pure and pristine C fullertubes, [5,5] C-D(1) and [10,0] C-D(10766). These new molecules represent the highest aspect ratio fullertubes isolated to date; for example, the prior largest empty cage fullertube was [5,5] C-D(1). This increase of 20 carbon atoms represents a gigantic leap in comparison to of C-C fullerene research.

Amine Functionalized Trimetallic Nitride Endohedral Fullerenes: A Class of Nanoparticle to Tackle Low Back/Leg Pain.

Low back pain is the most common health problem with a prevalence of over 80% worldwide and an estimated annual cost of $100 billion in the United States. Intervertebral disc degeneration accounts for a major cause of low back pain. However, there is still a lack of safe and effective treatment to tackle this devastating condition.

Semiconducting and Metallic [5,5] Fullertube Nanowires: Characterization of Pristine D(1)-C and D(1)-C.

Although fullerenes were discovered nearly 35 years ago, scientists still struggle to isolate "single molecule" tubular fullerenes larger than C. In similar fashion, there is a paucity of reports for pristine single-walled carbon nanotubes (SWNTs). In spite of Herculean efforts, the isolation and properties of pristine members of these carbonaceous classes remain largely unfulfilled.

A New Formyl Peptide Receptor-1 Antagonist Conjugated Fullerene Nanoparticle for Targeted Treatment of Degenerative Disc Diseases.

Intervertebral disc degeneration associated back pain is the most common cause of disability worldwide; however, no safe and effective treatments have been available. Here, we report a new functionalized nanofullerene conjugated with a peptide that binds specifically to a formyl peptide receptor-1 (FPR-1) expressed on activated macrophages. The new nanoparticle (aka FT-C) was synthesized by conjugating carboxyl-C with the primary amine group of the peptide with a fluorescence dye for easy detection.

Isolation and Crystallographic Characterization of Two, Nonisolated Pentagon Endohedral Fullerenes: Ho N@C (22010)-C and Tb N@C (22010)-C.

Purified samples of Ho N@C (22010)-C and Tb N@C (22010)-C have been isolated by two distinct processes from the rich array of fullerenes and endohedral fullerenes present in carbon soot from graphite rods doped with Ho O or Tb O . Crystallographic analysis of the endohedral fullerenes as cocrystals with Ni(OEP) (in which OEP is the dianion of octaethylporphyrin) shows that both molecules contain the chiral C (22010)-C cage. This cage does not obey the isolated pentagon rule (IPR) but has two sites where two pentagons share a common C-C bond.

High Blocking Temperature of Magnetization and Giant Coercivity in the Azafullerene Tb @C N with a Single-Electron Terbium-Terbium Bond.

The azafullerene Tb @C N is found to be a single-molecule magnet with a high 100-s blocking temperature of magnetization of 24 K and large coercivity. Tb magnetic moments with an easy-axis single-ion magnetic anisotropy are strongly coupled by the unpaired spin of the single-electron Tb-Tb bond. Relaxation of magnetization in Tb @C N below 15 K proceeds via quantum tunneling of magnetization with the characteristic time τ =16 462±1230 s.

Giant exchange coupling and field-induced slow relaxation of magnetization in Gd@CN with a single-electron Gd-Gd bond.

Magnetic properties of the azafullerene Gd@CN are studied by SQUID magnetometry. The effective exchange coupling constant j between the Gd spins and the spin of unpaired electron residing on the single-electron Gd-Gd bond is determined to be 170 ± 10 cm. Low temperature AC measurements revealed field-induced millisecond-long relaxation of magnetization.

Gadolinium based endohedral metallofullerene Gd@CN as a relaxation boosting agent for dissolution DNP at high fields.

We show increased dynamic nuclear polarization by adding a low dosage of a S = 15/2 Gd based endohedral metallofullerene (EMF) to DNP samples. By adding 60 μM Gd@CN, the nuclear polarization of H and C spins from 40 mM 4-oxo-TEMPO increases by approximately 40% and 50%, respectively, at 5 T and 1.2 K.

Trimetallic Nitride Endohedral Fullerenes Carboxyl-GdN@C: A New Theranostic Agent for Combating Oxidative Stress and Resolving Inflammation.

Antioxidative and anti-inflammatory effects of trimetallic nitride endohedral fullerenes carboxyl-GdN@C, a newly developed magnetic resonance imaging (MRI) contrast agent, were investigated. All hydrochalarone and carboxyl-functionalized fullerenes showed effective radical (hydroxyl and superoxide anion) scavenging, whereas the carboxyl-GdN@C more efficiently attenuated lipopolysaccharide (LPS) induced oxidative stress in macrophages. Carboxyl-GdN@C also suppressed LPS-elicited mRNA expression of pro-inflammatory inducible nitric oxide synthase and tumor necrosis factor-alpha, and upregulated antioxidative enzyme axis Nrf2 and heme oxygenase-1, possibly via ERK but not AKT signaling pathways.

Detecting Chronic Post-Traumatic Osteomyelitis of Mouse Tibia via an IL-13Rα2 Targeted Metallofullerene Magnetic Resonance Imaging Probe.

Differential diagnosis of chronic post-traumatic osteomyelitis (CPO) from aseptic inflammation remains challenging, since both pathological processes share similar clinical symptoms. Here we utilized a novel targeted metallofullerene nanoparticle based magnetic resonance imaging (MRI) probe IL-13-TAMRA-GdN@C(OH)(CHCHCOOH) to detect CPO in mouse tibia via overexpressed IL-13Rα2 receptors. The functionalized metallofullerene was characterized by X-ray photoelectron spectroscopy.

Biomedical Applications of Metal-Encapsulated Fullerene Nanoparticles.

The carbonaceous nanomaterials known as metallofullerenes have attracted considerable attention due to their attractive properties. The robust nature of the "Trojan Horse" fullerene cage provides an important structural component, which isolates the metal cluster from the bioenvironment. The large carbon surface area is ideally suited for multiple exo-functionalization approaches to modify the hydrophobic cage for a more hydrophilic bioenvironment.

Optimization and prediction of the electron-nuclear dipolar and scalar interaction in H and C liquid state dynamic nuclear polarization.

During the last 10-15 years, dynamic nuclear polarization (DNP) has evolved as a powerful tool for hyperpolarization of NMR and MRI nuclides. However, it is not as well appreciated that solution-state dynamic nuclear polarization is a powerful approach to study intermolecular interactions in solution. For solutions and fluids, the H nuclide is usually dominated by an Overhauser dipolar enhancement and can be significantly increased by decreasing the correlation time () of the substrate/nitroxide interaction by utilizing supercritical fluids (SF CO).

A New Interleukin-13 Amino-Coated Gadolinium Metallofullerene Nanoparticle for Targeted MRI Detection of Glioblastoma Tumor Cells.

The development of new nanoparticles as next-generation diagnostic and therapeutic ("theranostic") drug platforms is an active area of both chemistry and cancer research. Although numerous gadolinium (Gd) containing metallofullerenes as diagnostic magnetic resonance imaging (MRI) contrast agents have been reported, the metallofullerene cage surface, in most cases, consists of negatively charged carboxyl or hydroxyl groups that limit attractive forces with the cellular surface. It has been reported that nanoparticles with a positive charge will bind more efficiently to negatively charged phospholipid bilayer cellular surfaces, and will more readily undergo endocytosis.

Gd3N@C84(OH)x: a new egg-shaped metallofullerene magnetic resonance imaging contrast agent.

Water-soluble derivatives of gadolinium-containing metallofullerenes have been considered to be excellent candidates for new magnetic resonance imaging (MRI) contrast agents because of their high relaxivity and characteristic encapsulation of the lanthanide ions (Gd(3+)), preventing their release into the bioenvironment. The trimetallic nitride template endohedral metallofullerenes (TNT EMFs) have further advantages of high stability, high relative yield, and encapsulation of three Gd(3+) ions per molecule as illustrated by the previously reported nearly spherical, Gd3N@I(h)-C80. In this study, we report the preparation and functionalization of a lower-symmetry EMF, Gd3N@C(s)-C84, with a pentalene (fused pentagons) motif and an egg-shaped structure.

Single-walled carbon nanohorns decorated with semiconductor quantum dots to evaluate intracellular transport.

Single-walled carbon nanohorns (SWNHs) have great potential to enhance thermal and chemotherapeutic drug efficiencies for cancer therapies. Despite their diverse capabilities, minimal research has been conducted so far to study nanoparticle intracellular transport, which is an important step in designing efficient therapies. SWNHs, like many other carbon nanomaterials, do not have inherent fluorescence properties making intracellular transport information difficult to obtain.

A missing link in the transformation from asymmetric to symmetric metallofullerene cages implies a top-down fullerene formation mechanism.

Although fullerenes were discovered nearly three decades ago, the mechanism of their formation remains a mystery. Many versions of the classic 'bottom-up' formation mechanism have been advanced, starting with C2 units that build up to form chains and rings of carbon atoms and ultimately form those well-known isolated fullerenes (for example, I(h)-C60). In recent years, evidence from laboratory and interstellar observations has emerged to suggest a 'top-down' mechanism, whereby small isolated fullerenes are formed via shrinkage of giant fullerenes generated from graphene sheets.

Assembly of bio-nanoparticles for double controlled drug release.

A critical limiting factor of chemotherapy is the unacceptably high toxicity. The use of nanoparticle based drug carriers has significantly reduced the side effects and facilitated the delivery of drugs. Source of the remaining side effect includes (1) the broad final in vivo distribution of the administrated nanoparticles, and (2) strong basal drug release from nanoparticles before they could reach the tumor.

Trimetallic nitride template endohedral metallofullerenes: discovery, structural characterization, reactivity, and applications.

Shortly after the discovery of the carbon fullerene allotrope, C₆₀, researchers recognized that the hollow spheroidal shape could accommodate metal atoms, or clusters, which quickly led to the discovery of endohedral metallofullerenes (EMFs). In the past 2 decades, the unique features of EMFs have attracted broad interest in many fields, including inorganic chemistry, organic chemistry, materials chemistry, and biomedical chemistry. Some EMFs produce new metallic clusters that do not exist outside of a fullerene cage, and some other EMFs can boost the efficiency of magnetic resonance (MR) imaging 10-50-fold, in comparison with commercial contrast agents.

Enhanced dipole moments in trimetallic nitride template endohedral metallofullerenes with the pentalene motif.

Although not found to date in empty-cage fullerenes, the fused pentagon motifs (pentalenes) are allowed in endohedral metallofullerenes (EMFs). We have found that members of the trimetallic nitride template (TNT) EMF Y3N@C2n (n = 39-44) family that contain pentalene motifs exhibit significant dipole moments. This finding is predicted to be significant for other EMFs with a metal atom orientated toward the pentalene motif.

Metallofullerene-nanoplatform-delivered interstitial brachytherapy improved survival in a murine model of glioblastoma multiforme.

Fullerenes are used across scientific disciplines because of their diverse properties gained by altering encapsulated or surface-bound components. In this study, the recently developed theranostic agent based on a radiolabeled functionalized metallofullerene ((177)Lu-DOTA-f-Gd(3)N@C(80)) was synthesized with high radiochemical yield and purity. The efficacy of this agent was demonstrated in two orthotopic xenograft brain tumor models of glioblastoma multiforme (GBM).