Synthesis and in vivo study of metallofullerene based MRI contrast agent

Gd@C₈₂(OH)₄₀ has been developed as a new generation of MRI contrast agent. But recently, it was found that Gd@C₈₂(OH) _x with a larger number of OH (x>36) would lead to cage break and hence, release of highly toxic Gd ions. We synthesized the more stable Gd@C₈₂(OH) _x with less OH-number, Gd@C₈₂(OH)₁₆, and studied its proton relaxivity and MRI images. The results indicate that Gd@C₈₂(OH)₁₆ also gives high proton relaxivity, even higher than that of (NMG)₂-Gd-DTPA. The bio-distribution indicated that Gd@C₈₂(OH)₁₆ tends to be entrapped in the liver and kidney and remained in tissue for about 2 hours. The results suggest that the more stable metallofullerene derivative Gd@C₈₂(OH)₁₆ can be the potential candidate of the new MRI contrast agent.     

Rapid analysis technique for strontium,thorium, and uranium in urine samples

The electronic properties of the metal atoms encaged in a fullerence cage were investigated using synchrotron X-ray photoelectron spectroscopy. Systematic variations in photoemission of valence band of Gd@C₈₂, Gd@C₈₂(OH)₁₂, and Gd@C₈₂(OH)₂₂ were observed in Gd 5p levels. The results suggest that the electronic properties of the inner metal atom can be efficiently modulated by surface chemistry of the fullerene cage.     

Theoretical and Quantitative Structural Relationship Studies of Electrochemical Properties of the Nanostructures of Cis-Unsaturated Thiocrown Ethers and Their Supramolecular Complexes [X-UT-Y][M@C82] (M˭Ce,Gd)

The endohedral lanthanidofullerenes, an important type of organolanthanides, are stabilized by the delocalization of the negative charges on the cages of fullerenes. Since the discovery of these classes of carbon compounds and their unusual structures and properties of these molecules, many potential applications have been suggested. Unsaturated thiocrown ethers with cis-geometry are a group of crown ethers that, in light of the size of their cavities and their conformational restriction compared to a corresponding saturated system (1–9), demonstrate interesting properties for physicochemical studies. Endohedral lanthanidofullerenes M@C_x (x = 82 and M = Ce, Gd) were introduced as a new class of the spherical fullerene group with unique properties. Formation of endohedral metallofullerenes is thought to involve the transfer of electrons from the encapsulated metal atom(s) to the surrounding fullerene cage. Two of these molecules are the Ce@C₈₂ (10) and Gd@C₈₂ (11). The supramolecular complexes of 1–9 with Ce@C₈₂ (10) and Gd@C₈₂ (11) have been shown to possess a host–guest interaction for electron transfer processes, and these behaviors have previously been reported. Topological indices have been successfully used to construct effective and useful mathematical methods for finding good relationships between structural data and the various chemical and physical properties. To establish a good structural relationship between the structures of 1–9 and M@C_x that were introduced here, an index that is represented as μ_cs was utilized. This index is the ratio of summation of the number of carbon atoms (n_c ) and the number of sulfur atoms (n_s ) to the product of these two numbers for 1–9. In this study, the relationship between this index and oxidation potential ( ^oxE₁ ) of 1–9, as well as the free energy of electron transfer (ΔG_et , by the Rehm-Weller equation) between 1–9 and 10 and 11 as [X-UT-Y][Ce@C₈₂] (12) and [X-UT-Y][Gd@C₈₂] (13) complexes, is presented.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Voltammetric Behavior of Water‐Soluble Endohedral Metallofullerene Derivatives

Voltammetric behavior of water‐soluble endohedral metallofullerene derivatives Gd@C₈₂(OH)₅(NHCH₂COOH)₉ (GN) and Gd@C₈₂(OH)₆(NHCH₂CH₂SO₃H)₈ (GS) was characterized in 0.1 M KCl solution by CV and DPV. They showed similar redox behavior, that is, a reversible electroreduction process on HMDE was found; in the mean time, an irreversible oxidation process and an irreversible reduction process on GC electrodes were also observed. The results reveal that these two water‐soluble endohedral metallofullerene derivatives have good electron donating ability and poor electron accepting ability due to hydroxy groups, aminoacetic acid and aminoethyl sulfonic acid connected to the C₈₂ cage in comparison with Gd@C₈₂.     

Metallofullerenol Inhibits Cellular Iron Uptake by Inducing Transferrin Tetramerization

Herein, A549 tumor cell proliferation was confirmed to be positively dependent on the concentration of Fe³⁺ or transferrin (Tf). Gd@C₈₂(OH)₂₂ or C₆₀(OH)₂₂ effectively inhibited the iron uptake and the subsequent proliferation of A549 cells. The conformational changes of Tf mixed with FeCl₃, GdCl₃, C₆₀(OH)₂₂ or Gd@C₈₂(OH)₂₂ were obtained by SAXS. The results demonstrate that Tf homodimers can be decomposed into monomers in the presence of FeCl₃, GdCl₃ or C₆₀(OH)₂₂, but associated into tetramers in the presence of Gd@C₈₂(OH)₂₂. The larger change of SAXS shapes between Tf+C₆₀(OH)₂₂ and Tf+FeCl₃ implies that C₆₀(OH)₂₂ is bound to Tf, blocking the iron‐binding site. The larger deviation of the SAXS shape from a possible crystal structure of Tf tetramer implies that Gd@C₈₂(OH)₂₂ is bound to the Tf tetramer, thus disturbing iron transport. This study well explains the inhibition mechanism of Gd@C₈₂(OH)₂₂ and C₆₀(OH)₂₂ on the iron uptake and the proliferation of A549 tumor cells and highlights the specific interactions of a nanomedicine with the target biomolecules in cancer therapy.     

Study of multihydroxylated processes of Gd@C<Subscript>82</Subscript> by ICP-MASS

The water-solubilization of metallofullerenes is important for their potential applications, but their formation processes are still not clear, and the formation yield is uncontrollable. In this paper, we quantitatively studied the water-solubilizing process of Gd@C₈₂ with hydroxylation reaction using ICP-MASS techniques. For the first time, it was found that the formation yield of the multihydroxylated Gd@C₈₂ is declined quickly with the break up of carbon cage of Gd@C₈₂ in the hydroxylated processes. The observation revealed a way to control the hydroxylation processes and increase the formation yield.     

Synthesis of pyrrolidine ring-fused metallofullerene derivatives

The azomethine ylide generated from the reaction of sarconsine and formaldehyde adds to Gd@C₈₂ to give the mono- through octo-adducts, while the direct interaction of sarcosine with Gd@C₈₂ yields only the mono-adduct, which is characterized by HPLC, MALDI-TOF MS, UV-Vis-NIR and FT-IR. The reaction mechanism for this reaction is proposed to be a 1,3-dipolar addition.     

Quantitative analysis of Gd@C<Subscript>82</Subscript>(OH)<Subscript>22</Subscript> and cisplatin uptake in single cells by inductively coupled plasma mass spectrometry

Cisplatin is a commonly used chemotherapeutic drug in cancer treatment, whereas Gd@C₈₂(OH)₂₂ is a new nanomaterial anti-tumor agent. In this study, we determined intracellular Gd@C₈₂(OH)₂₂ and cisplatin after treatment of Hela and 16HBE cells by single cell inductively coupled plasma-mass spectrometry (SC-ICP-MS), which could provide quantitative information at a single-cell level. The cell digestion method validated the accuracy of the SC-ICP-MS. The concentrations of Gd@C₈₂(OH)₂₂ and cisplatin in cells at different exposure times and doses were studied. The SC-ICP-MS is a promising complement to available methods for single cell analysis and is anticipated to be applied further to biomedical research.

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Graphical Abstract The quantitative results of Gd@C₈₂(OH)₂₂ in single cells determined by SC-ICP-MS and acid digestion method, respectively

     

Clustering of gadolinium endofullerenols in aqueous solutions

Nature of structuring of aqueous solutions of paramagnetic endofullerenols Gd@C _n (OH)_38–40 was determined in relation to the concentration and pH factor from small-angle neutron scattering, viscometric, and conductometric data. Molecular fractal clusters of the type of branched polymers were found, with their correlation radius being about 20 nm and aggregation numbers reaching a value of 104. The clusterized systems obtained are promising as a basis for MRI-contrasting agents and other biomedical preparations for diagnostics and therapy.     

Visible and near-IR spectroscopy of endohedral Gd@C82(C 2v ) and Ho@C82(C 2v ) metallofullerenes and their monoanions

Solutions of endohedral Gd@C₈₂(C _2v ) and Ho@C₈₂(C _2v ) metallofullerenes are studied by means of visible and near-IR spectroscopy upon their conversion from neutral to the anionic form via a redox reaction with the electron donor potassium perchlorotriphenylmethide K(18-crown-6)[C(C₆Cl₅)₃]. The concentrations of the studied solutions of endohedral Gd@C₈₂(C _2v ) and Ho@C₈₂(C _2v ) metallofullerenes in o-dichlorobenzene were determined from the spectroscopic data, and their molar extinction coefficients are calculated.

     

Quantum-chemical modeling of endohedral derivatives of buckminsterfullerenes Gd@C<Subscript>60</Subscript>(CHR)<Subscript>2</Subscript> and Gd@C<Subscript>80</Subscript>(CHR)<Subscript>2</Subscript>

The structural energies of the endohedral derivatives of buckminsterfullerenes Gd@C₆₀(CHR)₂ and Gd@C₈₀(CHR)₂ were calculated by quantum-chemical methods – semiempirical PM3 and nonempirical RHF SCF MO LCAO with the S. Huzinaga MINI minimum basis set and GAMESS software.     

Size‐Selective Complexation and Extraction of Endohedral Metallofullerenes with Cycloparaphenylene

A new strategy for the non‐chromatographic extraction of metallofullerenes from solutions of arc‐processed raw soot is based on the size‐selective complexation with cycloparaphenylene (CPP). [11]CPP has a high affinity for M_x@C₈₂ (x=1, 2); for example, Gd@C₈₂ can be selectively extracted from a fullerene mixture by the addition of [11]CPP. This approach should open new opportunities in metallofullerene chemistry, including for the bulk extraction of metallofullerenes.     

Endohedral gadolinium-containing metallofullerenes in the trifluoromethylation reaction

An efficient method for the synthesis of trifluoromethyl derivatives of endohedral gadolinium-containing metallofullerenes was proposed. High-purity (98–99%) trifluoromethyl derivatives Gd@C₈₂(CF₃)₅ (two isomers) and Gd₂@C₈₀(CF₃) have been synthesized for the first time. They were isolated and characterized by HPLC, MALDI-TOF mass spectrometry, and UV-Vis spectroscopy. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1457–1462, July, 2008.     

New insights into the selective and systematic preparation of arylgermanium hydrides

A series of novel arylgermanium hydrides Ar_nGeH_4–n (n = 1–3) and diaryl(chloro)germanium hydrides Ar₂Ge(Cl)H were synthesized and characterized. Systematic preparation and purification were achieved via the lithium chloride–triflic acid and the optimized Grignard route. Arylgermanium hydrides ArnGeH_4–n (Ar = 2,5-Me₂C₆H₃, n = 1–3) were characterized by ¹H and ⁷³Ge NMR spectroscopy and single crystal X-ray diffractometry.     

Theoretical study of H⋯P and X⋯P interactions of methylphosphines with HSX molecules

Ab initio calculations were used to analyze the interactions between thiohypohalous acids (HSX; X = F, Cl, Br, I) and methylphosphine derivatives (PH _n Me_3?n , n = 0–3) at the MP2/aug-cc-pVDZ level of theory. Interaction of HSX with PH _n Me_3?n leads to both hydrogen bond (HSX–PH _n Me_3?n –HB) as well as halogen bond (HSX–PH _n Me_3?n –XB) complexes. Stabilities of both HB and XB complexes increase with basicity of the phosphines. However, HB complexes of a phosphine molecule with different HSX have the same order of stabilities, but XB complexes of heavier thiohypohalous acids are more stable. Electron densities of complexes were characterized with the atoms in molecules methodology. The charge transfer within dimers was analyzed by means of natural bond orbitals.     

Gas phase ion chemistry of molybdenum hexacarbonyl

In an ion cyclotron resonance (ICR) cell, Mo(CO)_n⁺ ions (n = 0–6), generated by electron ionization (EI) with 70 eV electrons, on collisions with Mo(CO)₆ undergo charge exchange (confirmed by isotopic experiments), collision-induced dissociation (CID), and association reactions to produce Mo_m(CO)_n⁺ ions (m = 1–6). Reactions are essentially complete within 9 s at a pressure of 3 × 10⁻⁹ Torr, as recorded by the manifold ion gauge (uncalibrated); Mo(CO)_n⁺ ions with n = 0–5 have been consumed within this time whereas Mo(CO)₆⁺ ions have achieved a steady concentration. All Mo₂(CO)_n⁺ ions (n = 0–11) were observed: the abundances of dimolybdenum-containing ions with n < 7 decrease at extended reaction times, whereas those with n ≥ 7 remain steady or increase slowly, implying that reactivity decreases with increasing CO content. The major dimers have n = 7, 9, and 10. When subjected to CID the Mo₂(CO)₇⁺ ion yields Mo₂(CO)_n⁺ ions (n = 0–6). Most Mo₃(CO)_n⁺ ions (n = 0–13) were observed, those with n = 9 being formed most readily. Similar observations apply to larger clusters, the most abundant ions being those with CO:Mo ratios of 2–3:1. Mo(CO)_n⁺ ions (n = 0, 3–6) formed by EI with 15 eV electrons are unreactive for reaction times of at least 5 s at the same pressure. General reaction sequences are proposed. Negative ions generated with 70 eV electrons (∼ 90% Mo(CO)₅⁻) are much less reactive but also lead to cluster ion formation on reaction with Mo(CO)₆.     

The solubility of fullerene C70 in monocarboxylic acids C n − 1H2n − 1COOH (n = 1–9) over the temperature range 20–80°C

The isothermal (20°C) solubility of fullerene C₇₀ in solvents of the homologous series of monocarboxylic acids C _{n ? 1}H_{2n ? 1}COOH (n = 1–9) and polythermal solubility over the temperature range 20–80°C of fullerene C₇₀ in solvents of the homologous series of monocarboxylic acids C _{n ? 1}H_{2n ? 1}COOH (n = 4–9) were studied. The corresponding solubility diagrams were obtained and characterized.     

Ion—molecule reactions in GeH4/SiH4 systems studied by ion trap mass spectrometry

Gas phase ion—molecule reactions occurring in GeH₄/SiH₄ systems under different partial pressures and their mechanisms have been investigated by ion trap mass spectrometry (ITMS). SiH⁺_n (n=0–3) and GeH⁺_n (n = 0–3) are the main ionic species at zero reaction time when the GeH₄: SiH₄ ratio is in the range 1:1 to 1:12. Self-condensation sequences are observed at increasing reaction times. Moreover, formation of ions containing GeSi bonds, such as GeSiH⁺_n (in = 2–5) and GeSi₂H⁺_n (n = 4, 5), occurs by reactions of Si₂H⁺_n (n = 2–5) and Si₃H⁺_n (n = 4, 5) with GeH₄. At longer reaction times, further substitution of silicon with germanium in GeSiH⁺_n (n = 2–5) ions has been observed, to give Ge₂H⁺_n (n = 2–5).     

Determination of molar extinction coefficients for endohedral metallofullerene Dy@C<Subscript>82</Subscript>(C<Subscript>2v</Subscript>)

Isomerically pure endohedral metallofullerene Dy@C₈₂(C _2v) was synthesized by the electric arc method, extracted from the soot with o-dichlorobenzene, isolated from the extract by HPLC, and characterized by mass spectrometry and spectrophotometry. The spectrophotometric titration of a solution of endohedral metallofullerene Dy@C₈₂(C _2v) was conducted with potassium perchlorotriphenylmethide. The concentration of Dy@C82(C _2v) in o-dichlorobenzene was determined, and the molar absorption coefficients for its neutral and anionic forms were calculated (3.0?10³ (at 927 nm) and 4.0?10³ mol^–1 L cm^–1 (at 884 nm), respectively.     

Electrochemical deposition of praseodymium (III) and copper (II) and extraction of praseodymium on copper electrode in LiCl-KCl melts

Cyclic voltammogram and square wave voltammograms indicated that Cu (II) ion being reduced to Cu(0) was a two-electron process: Cu(II)?+?e^??→?Cu(I) and Cu(I)?+?e^??→?Cu(0). The diffusion activation energy for Cu (I) ions was calculated as 42.85 kJ mol^?1. The equilibrium potential and apparent standard potential for Cu (I)/Cu(0) redox couple was measured by open circuit chronopotentiometry at a temperature of 773–923 K. Three reduction peaks, corresponding to the formation of Pr_xCu_y intermetallic compounds, were detected from cyclic voltammogram and square wave voltammogram obtained by co-reduction of Pr (III) and Cu (II) or electrodeposition of Pr (III) on Cu electrode. Furthermore, potentiostatic electrolysis was performed to extract the element Pr on Cu electrode, and the electrolytic products were analyzed by scanning electron microscopy equipped with energy dispersive spectrometry. Meanwhile, the highest extraction efficiency of Pr (III) ions could reach about 99.81% at ??2.20 V for 22 h at 823 K.