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 fullertube molecules would possess structural features of both fullerenes (hemispherical end-caps) and tubular belts of single-walled carbon nanotubes (SWCNTs). Yet, their experimental verification remained elusive for decades. It was not until 2020-2023 that segmental families of fullertubes were finally confirmed in the lab. The shocking irony is that these fullertubes were unwittingly coproduced alongside fullerenes (e.g., C60, C70, C84) in both flame and electric arc soot since the 1990s. Yet, nobody knew these "hidden" families of fullertubes were experimentally present in their extracted soot due to their low abundance and the absence of isolation methodology.This eruption of fullertube discoveries in 2020-2023 was brought to fruition by structural data, both DFT and experimental. This "Treasure Trove" of new molecules during this four-year window occurred with only microgram quantities. Typically, milligram levels of purified samples are required for X-ray crystallography and 13C NMR structural analysis. The breakthrough for experimentally verifying the missing fullertubes was an aminopropanol reagent to selectively react with and remove spheroidal carbon (e.g., C60, C70, C84) as hydrophilic derivatives. In contrast, there was suppressed reaction with fullertubes, which remained in organic solvent. It is well established that high symmetry (3-, 5-, and 6-fold) hemispheres for C60-Ih and other fullerenes and metallofullerenes are prerequisite end-caps for fullertubes. For the case of [5,5] C130 fullertubes, this requirement results in only eight 3-, 5-, and 6-fold symmetry structural isomers possible from a total of 39,393 possible isolated pentagon rule (IPR) isomers. From this C130 list of 8 candidate isolated pentagon rule (IPR) high symmetry isomers, surprisingly only one structure matched the DFT polarizability versus chromatographic retention parameter (a new gold standard for isomer identification). The simultaneous emergence of DFT computations of other properties (e.g., total energy, HOMO-LUMO gap, UV-vis) for large carbon molecules provided support for structural determination. Experimental approaches (e.g., mass spectrometry, UV-vis, XPS, Raman, and STEM) provided additional layers of structural elucidation at the microgram level. For the first time, we developed a chemical isolation protocol that would allow the preparation and isolation of soluble pristine fullertubes in the range of C90-C200. To date, applications of SWCNTs for use in nanoscale computer applications requires purities greater than 99.999%. Although this stringent mandate has not yet been demonstrated using SWCNT samples, this high level of purity appears achievable for metallic [5,5] D5d-C120 and semiconductor [10,0] D5h-C120 [10,766] fullertubes. Moreover, commercial production of pristine fullertubes should easily be feasible by the flame method due to its continuous operation and inexpensive feedstock. For application development, theoretical and electrochemical experimental data show that fullertubes exhibit high catalytic activity in oxygen reduction reactions. In the medical sector, pristine fullertube dispersions exhibit antimicrobial effects on Mycobacterium smegmatis and M. abscessus.

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. Further elucidation of the structure-function relationships of these materials is expected to enhance their utility in biomedical applications and possibly broaden their use in diverse areas of science and technology.

Colossal C130 Fullertubes: Soluble [5,5] C130-D5h(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] C130-D5h(1) fullertubes. This achievement represents the largest soluble carbon molecule obtained in its pristine form. The [5,5] C130 species is the highest aspect ratio fullertube purified to date and now surpasses the recent gigantic [5,5] C120-D5d(1). In contrast to C90, C100, and C120 fullertubes, the longer C130-D5h has more nanotubular carbons (70) than end-cap fullerenyl atoms (60). Starting from 39,393 possible C130 isolated pentagon rule (IPR) structures and after analyzing polarizability, retention time, and UV-vis spectra, these three layers of data remarkably predict a single candidate isomer and fullertube, [5,5] C130-D5h(1). This structural assignment is augmented by atomic resolution STEM data showing distinctive and tubular "pill-like" structures with diameters and aspect ratios consistent with [5,5] C130-D5h(1) fullertubes. The high selectivity of the aminopropanol reaction with spheroidal fullerenes permits facile separation and removal of fullertubes from soot extracts. Experimental analyses (HPLC retention time, UV-vis, and STEM) were synergistically used (with polarizability and DFT property calculations) to down select and confirm the C130 fullertube structure. Achieving the isolation of a new [5,5] C130-D5h fullertube opens the door to application development and fundamental studies of electron confinement, fluorescence, and metallic character for a fullertube series of molecules with systematic tubular elongation. This [5,5] fullertube family also invites comparative studies with single-walled carbon nanotubes (SWCNTs), nanohorns (SWCNHs), and fullerenes.

Tb2O@C2(13333)-C74: A Non-Isolated Pentagon Endohedral Fullerene Containing a Nearly Linear Tb-O-Tb Unit.

Terbium has been added to the list of elements that form oxide clusters inside fullerene cages. Tb2O@C2(13333)-C74 has been isolated as a byproduct of the electric arc synthesis of the azafullerene Tb2@C79N. Cocrystallization of Tb2O@C2(13333)-C74 with Ni(OEP) (where OEP is the dianion of octaethylporphyrin) in toluene yielded black needles of Tb2O@C2(13333)-C74·NiII(OEP)·1.5C7H8 that have been examined by single-crystal X-ray diffraction. The resulting structure shows that a nearly linear Tb-O-Tb unit is contained in a C2(13333)-C74, which has two sites where pentagons share an edge to form pentalene units at opposite ends of the fullerene. Unlike the usual situations where metal atoms in fullerenes that do not obey the isolated pentagon rule are situated within the folds of the pentalene units, the Tb atoms in Tb2O@C2(13333)-C74 are positioned to the side of the pentalene units and near-neighboring hexagons. The magnetic properties of Tb2O@C2(13333)-C74 have been examined starting from the experimental geometry, using ab-initio multiconfigurational methods. The computations predict that Tb2O@C2(13333)-C74 will show strong axiality, which would make it a single-molecule magnet with a large magnetic anisotropy barrier.

Gigantic C120 Fullertubes: Prediction and Experimental Evidence for Isomerically Purified Metallic [5,5] C120-D5d(1) and Nonmetallic [10,0] C120-D5h(10766).

We report the first experimental characterization of isomerically pure and pristine C120 fullertubes, [5,5] C120-D5d(1) and [10,0] C120-D5h(10766). These new molecules represent the highest aspect ratio fullertubes isolated to date; for example, the prior largest empty cage fullertube was [5,5] C100-D5d(1). This increase of 20 carbon atoms represents a gigantic leap in comparison to three decades of C60-C90 fullerene research. Moreover, the [10,0] C120-D5d(10766) fullertube has an end-cap derived from C80-Ih and is a new fullertube whose C40 end-cap has not yet been isolated experimentally. Theoretical and experimental analyses of anisotropic polarizability and UV-vis assign C120 isomer I as a [5,5] C120-D5d(1) fullertube. C120 isomer II matches a [10,0] C120-D5h(10766) fullertube. These structural assignments are further supported by Raman data showing metallic character for [5,5] C120-D5d(1) and nonmetallic character for C120-D5h(10766). STM imaging reveals a tubular structure with an aspect ratio consistent with a [5,5] C120-D5d(1) fullertube. With microgram quantities not amenable to crystallography, we demonstrate that DFT anisotropic polarizability, augmented by long-accepted experimental analyses (HPLC retention time, UV-vis, Raman, and STM) can be synergistically used (with DFT) to down select, predict, and assign C120 fullertube candidate structures. From 10 774 mathematically possible IPR C120 structures, this anisotropic polarizability paradigm is quite favorable to distinguish tubular structures from carbon soot. Identification of isomers I and II was surprisingly facile, i.e., two purified isomers for two possible structures of widely distinguishing features. These metallic and nonmetallic C120 fullertube isomers open the door to both fundamental research and application development.

Metamagnetic transition and a loss of magnetic hysteresis caused by electron trapping in monolayers of single-molecule magnet Tb2@C79N.

Realization of stable spin states in surface-supported magnetic molecules is crucial for their applications in molecular spintronics, memory storage or quantum information processing. In this work, we studied the surface magnetism of dimetallo-azafullerene Tb2@C79N, showing a broad magnetic hysteresis in a bulk form. Surprisingly, monolayers of Tb2@C79N exhibited a completely different behavior, with the prevalence of a ground state with antiferromagnetic coupling at low magnetic field and a metamagnetic transition in the magnetic field of 2.5-4 T. Monolayers of Tb2@C79N were deposited onto Cu(111) and Au(111) by evaporation in ultra-high vacuum conditions, and their topography and electronic structure were characterized by scanning tunneling microscopy and spectroscopy (STM/STS). X-ray photoelectron spectroscopy (XPS), in combination with DFT studies, revealed that the nitrogen atom of the azafullerene cage tends to avoid metallic surfaces. Magnetic properties of the (sub)monolayers were then studied by X-ray magnetic circular dichroism (XMCD) at the Tb-M4,5 absorption edge. While in bulk powder samples Tb2@C79N behaves as a single-molecule magnet with ferromagnetically coupled magnetic moments and blocking of magnetization at 28 K, its monolayers exhibited a different ground state with antiferromagnetic coupling of Tb magnetic moments. To understand if this unexpected behavior is caused by a strong hybridization of fullerenes with metallic substrates, XMCD measurements were also performed for Tb2@C79N adsorbed on h-BN|Rh(111) and MgO|Ag(100). The co-existence of two forms of Tb2@C79N was found on these substrates as well, but magnetization curves showed narrow magnetic hysteresis detectable up to 25 K. The non-magnetic state of Tb2@C79N in monolayers is assigned to anionic Tb2@C79N- species with doubly-occupied Tb-Tb bonding orbital and antiferromagnetic coupling of the Tb moments. A charge transfer from the substrate or trapping of secondary electrons are discussed as a plausible origin of these species.

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. In this study, we synthesized four functionalized trimetallic nitride endohedral metallofullerenes (carboxyl-f-Sc3N@C80, carboxyl-f-Gd3N@C80, amino-f-Sc3N@C80, and amino-f-Gd3N@C80) and characterized them with X-ray photoelectron spectroscopy, matrix-assisted laser desorption/ionization-time of flight mass spectrometry, and UV-vis. Via electron paramagnetic resonance, all four metallofullerene derivatives possessed dose-dependent radical scavenging capabilities (hydroxyl radicals and superoxide anions), with the most promising radical scavenging properties shown in the amine functionalized C80 metallofullerenes. Both amino-f-Sc3N@C80 and amino-f-Gd3N@C80 at 1 µM significantly reduced lipopolysaccharide induced reactive oxygen species production and mRNA expressions of pro-inflammatory mediators (inos, tnf-α, il-1, and cox-2) in macrophages without apparent cytotoxicity through regulating activity of p38 MAPK, p65, and nuclear translocation of NF-κB. Furthermore, in an established mouse model of lumbar radiculopathy, amino-f-Sc3N@C80 and amino-f-Gd3N@C80 effectively alleviated ipsilateral mechanical hyperalgesia for up to 2 weeks. In dorsal root ganglia explant culture, we also showed that amino-f-Sc3N@C80 and amino-f-Gd3N@C80 ameliorated TNF-α elicited neuroinflammation. In summary, we presented results for a potent radical scavenging, anti-inflammatory and analgesic nanoparticle, amino-functionalized eighty-carbon metallofullerenes in vitro and in vivo. Our study provides important assets for developing pleiotropic treatment strategies to tackle the inflammation, a significant pathological hallmark in the intervertebral disc degeneration and associated pain.

Semiconducting and Metallic [5,5] Fullertube Nanowires: Characterization of Pristine D5h(1)-C90 and D5d(1)-C100.

Although fullerenes were discovered nearly 35 years ago, scientists still struggle to isolate "single molecule" tubular fullerenes larger than C90. 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. For example, the low abundance of spherical and tubular higher fullerenes in electric-arc extracts (<0.01-0.5%) and multiplicity of structural isomers remain a major challenge. Recently, a new isolation protocol for highly tubular fullerenes, also called f ullertubes, was reported. Herein, we describe spectroscopic characterization including 13C NMR, XPS, and Raman results for purified [5,5] fullertube family members, D5h-C90 and D5d-C100. In addition, DFT computational HOMO-LUMO gaps, polarizability indices, and electron density maps were also obtained. The Raman and 13C NMR results are consistent with semiconducting and metallic properties for D5h-C90 and D5d-C100, respectively. Our report suggests that short [5,5] fullertubes with aspect ratios of only ∼1.5-2 are metallic and could exhibit unique electronic properties.

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-C60) was synthesized by conjugating carboxyl-C60 with the primary amine group of the peptide with a fluorescence dye for easy detection. The new nanoparticle was characterized by X-ray photoelectron spectroscopy, mass spectroscopy, and gel electrophoresis. It possessed effective radical (hydroxyl and superoxide anions) scavenging capabilities in electron paramagnetic resonance spectroscopy. In cultured cells, the nanoparticle FT-C60 demonstrated preferential binding to FPR-1 on activated macrophages and significantly attenuated mRNA expressions of proinflammatory factors including interleukin-6, interleukin-1, tumor necrosis factor-alpha, and cyclooxygenase-2. In vivo animal studies exhibited that a single intravenous injection of FT-C60 effectively alleviated pain in an established mouse model of radiculopathy for up to post-operation day (POD) 12. Ex vivo near-infrared fluorescence imaging of the mouse spine confirmed the targeting property of FT-C60 toward the injured disc on POD 14. Quantitative analysis of histological staining on spine sections showed that nanoparticle FT-C60 dramatically reduced inflammation at the local injury site compared to injury only on POD 7. In summary, we developed a novel targeted nanoparticle for treatment of lumbar radiculopathy by systemic delivery. This is a first-of-its-kind study for developing a novel class of targeted and systemic nanoparticle therapeutics to treat degenerative disc diseases.

Isolation and Crystallographic Characterization of Two, Nonisolated Pentagon Endohedral Fullerenes: Ho3 N@C2 (22010)-C78 and Tb3 N@C2 (22010)-C78.

Purified samples of Ho3 N@C2 (22010)-C78 and Tb3 N@C2 (22010)-C78 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 Ho2 O3 or Tb4 O7 . 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 C2 (22010)-C78 cage. This cage does not obey the isolated pentagon rule (IPR) but has two sites where two pentagons share a common C-C bond. These pentalene units bind two of the metal ions, whereas the third metal resides near a hexagon of the cage. Inside the cages, the Ho3 N or Tb3 N unit is planar. Ho3 N@C2 (22010)-C78 and Tb3 N@C2 (22010)-C78 use the same cage previously found for Gd3 N@C2 (22010)-C78 rather than the IPR-obeying cage found in Sc3 N@D3h -C78 .

High Blocking Temperature of Magnetization and Giant Coercivity in the Azafullerene Tb2 @C79 N with a Single-Electron Terbium-Terbium Bond.

The azafullerene Tb2 @C79 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 Tb2 @C79 N below 15 K proceeds via quantum tunneling of magnetization with the characteristic time τQTM =16 462±1230 s. At higher temperature, relaxation follows the Orbach mechanism with a barrier of 757±4 K, corresponding to the excited states, in which one of the Tb spins is flipped.

Gadolinium based endohedral metallofullerene Gd2@C79N 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 Gd2@C79N, the nuclear polarization of 1H and 13C spins from 40 mM 4-oxo-TEMPO increases by approximately 40% and 50%, respectively, at 5 T and 1.2 K. Electron-electron double resonance (ELDOR) measurements show that the high spin EMF shortens the electron relaxation times and increases electron spectral diffusion leading to the increased DNP enhancement.

Trimetallic Nitride Endohedral Fullerenes Carboxyl-Gd3N@C80: A New Theranostic Agent for Combating Oxidative Stress and Resolving Inflammation.

Antioxidative and anti-inflammatory effects of trimetallic nitride endohedral fullerenes carboxyl-Gd3N@C80, 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-Gd3N@C80 more efficiently attenuated lipopolysaccharide (LPS) induced oxidative stress in macrophages. Carboxyl-Gd3N@C80 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. Therefore, carboxyl-Gd3N@C80 held a great promise in becoming a novel theranostic nanoplatform for simultaneously deliver MRI contrast and therapeutic functions to inflammation-related diseases.

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-Gd3N@C80(OH)30(CH2CH2COOH)20 to detect CPO in mouse tibia via overexpressed IL-13Rα2 receptors. The functionalized metallofullerene was characterized by X-ray photoelectron spectroscopy. Upon lipopolysaccharide (LPS) stimulation, macrophage Raw 264.7 cells showed elevated IL-13Rα2 expression via immunofluorescence staining and increased MRI probe binding via built-in TAMRA fluorescence imaging. Trauma was induced in both tibia of mice and bacteria soaked suture was inserted into the right tibia to initiate infection. During the acute phase (1.5 weeks), luminol-bioluminescence imaging revealed much higher myeloperoxidase activity in the infected tibia compared to the sham. In the chronic phase (4 weeks), X-ray radiography illustrated bone deformation in the infected tibia compared to the sham. With T1 weighted sequences, the probe clearly exhibited hyperintensity in the infection foci at both acute and chronic phases, which was not observed in the sham tibia. Histological analysis revealed severe bone structural destruction and massive inflammatory cell infiltration in the infected tibia. Immunohistochemistry confirmed abundant expression of IL-13Rα2 in the infection site. In summary, we developed a noninvasive imaging approach to detect and differentiate CPO from aseptic inflammation using a new IL-13Rα2 targeted metallofullerene MRI probe. In addition, for the first time, IL-13Rα2 was investigated as a unique biomarker in the context of osteomyelitis. Our data established a foundation for the translational application of this MRI probe in the clinical differentiation of CPO.

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. Additionally, peptides and other agents are readily covalently attached to this nanoprobe for targeting applications. The recent progress in developing metallofullerenes for next-generation biomedical applications is described. Of special interest are magnetic resonance imaging (MRI) contrast agents. Several recent studies reported cumulative gadolinium deposition in the brain and bones of individuals using commercial clinical MRI contrast agents. Gadolinium-based metallofullerenes provide 2-3 orders of magnitude improvement in MRI relaxivity and potentially lower clinical levels of toxic Gd3+ ions deposited. Other potential biomedical applications are also reviewed herein.

Negatively Charged Carbon Nanohorn Supported Cationic Liposome Nanoparticles: A Novel Delivery Vehicle for Anti-Nicotine Vaccine.

Tobacco addiction is the second-leading cause of death in the world. Due to the nature of nicotine (a small molecule), finding ways to combat nicotine's deleterious effects has been a constant challenge to the society and the medical field. In the present work, a novel anti-nicotine vaccine based on nanohorn supported liposome nanoparticles (NsL NPs) was developed. The nano-vaccine was constructed by using negatively charged carbon nanohorns as a scaffold for the assembly of cationic liposomes, which allow the conjugation of hapten conjugated carrier proteins. The assembled bio-nanoparticles are stable. Mice were immunized subcutaneously with the nano-vaccine, which induced high titer and high affinity of nicotine specific antibodies in mice. Furthermore, no evidence of clinical signs or systemic toxicity followed multiple administrations of NsL-based anti-nicotine vaccine. These results suggest that NsL-based anti-nicotine vaccine is a promising candidate in treating nicotine dependence and could have potential to significantly contribute to smoking cessation.

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. In this paper, we report the preparation of a new functionalized trimetallic nitride template endohedral metallofullerene (TNT EMF), Gd3N@C80(OH)x(NH2)y, with a cage surface bearing positively charged amino groups (-NH3(+)) and directly compare it with a similar carboxyl and hydroxyl functionalized derivative. This new nanoparticle was characterized by X-ray photoelectron spectroscopy (XPS), dynamic light scattering (DLS), and infrared spectroscopy. It exhibits excellent (1)H MR relaxivity. Previous studies have clearly demonstrated that the cytokine interleukin-13 (IL-13) effectively targets glioblastoma multiforme (GBM) cells, which are known to overexpress IL-13Rα2. We also report that this amino-coated Gd-nanoplatform, when subsequently conjugated with interleukin-13 peptide IL-13-Gd3N@C80(OH)x(NH2)y, exhibits enhanced targeting of U-251 GBM cell lines and can be effectively delivered intravenously in an orthotopic GBM mouse model.

Obstrucción intestinal debida al anudamiento como presentación atípica de la apendicitis aguda: presentación de un caso y comparación clínica con 13 casos internacionales / Bowel obstruction due to knotting as an atypical presentation of acute appendicitis: case presentation and clinical comparison with 13 international cases

Acute appendicitis is one of the main indications for an emergent abdominal surgical intervention. The classic presentation includes abdominal pain, nausea and vomiting. However, it has a variety of atypical presentations, especially in late adulthood. Subject and methods We report a case of an elderly patient with a positive past abdominal surgical history whose initial symptoms and imaging suggested bowel obstruction with signifcant clinical deterioration. The surgical management consisted of an exploratory laparotomy, fnding an intestinal obstruction at the ileocecal valve due to a necrotic appendix wrapped around it; named Appendiceal Tie Syndrome. We reviewed the literature to look for similar cases in MEDLINE database. Of the eligible papers, we selected only case reports. We performed a clinical comparison of our case with the previous reports. Results In the reviewed articles, 13 reported cases were similar to ours. Including our patient, seven cases were older than 60 years of age and 10 were male. The most common duration of symptoms was 3 to 4 days prior surgery. Among the 14 cases of acute appendicitis with knotting, fve reported bowel resection. In the majority of cases that involved elderly patients, a bowel resection was necessary due to small bowel necrosis. In contrast, in our case, there was no evidence of necrosis, nor need of bowel resection, despite the age of the patient and the prolonged evolution of 63 hours from the onset of symptoms and surgical resolution. The possible explanation for the preservation of the intestine is that the strength of the ileocecal valve helped to safeguard its vascularity preventing necrosis. Conclusion This case let us emphasize the importance of early detection and surgical resolution of an atypical acute appendicitis particularly in patients with signs and symptoms of bowel obstruction. Furthermore, it is critical not to underestimate the possible complications of this apparently simple diagnosis because it can cause high morbidity and mortality. In addition, we considered that our fndings, supported by other published case reports, suggest an association between appendix knotting and a history of past abdominal surgeries

La apendicitis aguda es una de las principales indicaciones para una intervención quirúrgica abdominal de emergencia. La presentación clásica incluye dolor abdominal, náusea y vómito. Sin embargo, existe una gran variedad de presentaciones atípicas, especialmente en los pacientes adultos mayores. Sujeto y métodos Se presenta el caso de una paciente adulta mayor con antecedentes de cirugías abdominales previas, cuyos síntomas y exámenes de imagen iniciales sugirieron un proceso de obstrucción intestinal con deterioro clínico signifcativo. El manejo quirúrgico consistió en una laparotomía exploratoria. Entre los hallazgos se encontró una obstrucción intestinal en la válvula íleo-cecal debido a que el apéndice en estado necrótico lo estaba envolviendo, lo que se denomina Síndrome por Anudamiento Apendicular. Se efectuó una búsqueda en MEDLINE y se realizó una comparación clínica con los reportes de casos internacionales. Resultados Se identifcaron otros 13 casos similares reportados internacionalmente. Incluyendo nuestro paciente, siete casos fueron mayores de 60 años de edad y 10 eran hombres. La duración más común de los síntomas fue de 3 a 4 días antes de la cirugía. Entre los 14 casos de anudamiento apendicular, cinco reportaron una resección intestinal. En la mayoría de los casos correspondientes a pacientes adultos mayores, la resección intestinal fue necesaria debido a necrosis del intestino delgado. En contraste, en nuestro caso no hubo evidencia de necrosis, ni necesidad de resección intestinal, a pesar de la edad del paciente y la evolución prolongada de 63 horas desde el inicio de los síntomas y la resolución quirúrgica. La posible explicación para la preservación del intestino es que la fuerza de la válvula ileocecal ayudó a salvaguardar la vascularidad y prevenir la necrosis. Conclusión Este caso permite enfatizar la importancia de una detección y resolución quirúrgica temprana en una apendicitis aguda con presentación atípica, particularmente en pacientes con signos y síntomas de obstrucción intestinal. Es muy importante no subestimar las posibles complicaciones que este diagnóstico aparentemente simple, ya que puede causar alta morbilidad y mortalidad. Además, nuestros hallazgos y los casos publicados, sugieren una posible asociación entre el anudamiento apendicular y los antecedentes de cirugías abdominales previas

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. The Gd3N@C84 derivative exhibits a higher (1)H MR relaxivity compared to that of the Gd3N@C80 derivative synthesized the same way, at low (0.47 T), medium (1.4 T), and high (9.4 T) magnetic fields. The Gd3N@C(s)-C84 derivative exhibits a higher hydroxyl content and aggregate size, as confirmed by X-ray photoelectron spectroscopy (XPS) and dynamic light scattering (DLS) experiments, which could be the main reasons for the higher relaxivity.