钆基富勒烯磁共振成像分子影像探针的研究进展

含有顺磁性金属钆离子及钆团簇的内嵌金属富勒烯(如Gd@C82,Gd@C60和Gd3 N@C80)及其衍生物是一类高效的MRI分子影像探针,其造影效率远优于传统钆基螯合物造影剂.重要的是,碳笼的高度稳定性保护了内嵌团簇,使之免受体内代谢物质的进攻和防止了外泄,从而大大提高了其生物安全性.同时,碳笼还是其它生物活性物质或分子影像探针的有效载体,易赋予其多功能性,从而提高疾病检测的灵敏度和准确性.本文介绍了多种钆内嵌金属富勒烯分子影像探针的研究进展,讨论了内嵌金属团簇和笼外化学修饰对其弛豫性能的影响,以及不同的功能基团对其生物相容性和动物体内分布的影响,并展望了其兼具多功能分子影像探针载体的应用前景.     

The electronic and vibrational structure of endohedral Tm3N@C80 (I) fullerene--proof of an encaged Tm3+

The electronic and vibrational structure of the nitride clusterfullerene Tm3N@C80 (I) was investigated by cyclic voltammetry, FTIR, Raman, and X-ray photoemission spectroscopy. The electrochemical energy gap of Tm3N@C80 (I) is 1.99 V, which is 0.13 V larger than that of Sc3N@C80 (I). FTIR spectroscopy showed that the C80:7 (I(h)) cages in Tm3N@C80 (I), Er3N@C80 (I), Ho3N@C80 (I), Tb3N@C80 (I), Gd3N@C80 (I), and Y3N@C80 (I) have the same bond order. The analysis of low-energy Raman spectra points to two uniform force constants which can be used to describe the interaction between the encaged nitride cluster and the C80:7 (I(h)) cage in M3N@C80 (I) (M = Tm, Er, Ho, Tb, Gd, and Y). Because the M3N-C80 bond strength is strongly dependent on the charge of the metal ions, this is a direct hint for a 3+ formal valence state of the metal ions in these nitride clusterfullerene series, including Tm3N@C80 (I). Photoemission spectra of the Tm 4d core level and the Tm 4f valence electrons provided a direct proof for a (4f)12 electronic configuration of the encapsulated thulium. In conclusion, thulium in Tm3N@C80 (I) has a formal electronic ground state of +3, in contrast to the +2 state found in Tm@C82. It is demonstrated that the valence state of metal atoms encaged in fullerenes can be controlled by the chemical composition of the endohedral fullerene.     

Pyramidalization of Gd3N inside a C80 cage. The synthesis and structure of Gd3N@C80

The X-ray crystal structure of Gd(3)N@C(80).Ni(II)(OEP).1.5(benzene) shows that the Gd(3)N unit within the I(h) C(80) cage is pyramidal, whereas Sc(3)N@C(80), Sc(3)N@C(78), Sc(3)N@C(68), Lu(3)N@C(80) and Sc(2)ErN@C(80) have planar M(3)N units.     

Expanding the number of stable isomeric structures of the C80 cage: a new fullerene Dy3N@C80

The production, isolation, and spectroscopic characterization of a new Dy3N@C80 cluster fullerene that exhibits three isomers (1-3) is reported for the first time. In addition, the third isomer (3) forms a completely new C80 cage structure that has not been reported in any endohedral fullerenes so far. The isomeric structures of the Dy3N@C80 cluster fullerene were analyzed by studying HPLC retention behavior, laser desorption time-of-flight (LD-TOF) mass spectrometry, and UV-Vis-NIR and FTIR spectroscopy. The three isomers of Dy3N@C80 were all large band-gap (1.51, 1.33, and 1.31 eV for 1-3, respectively) materials, and could be classified as very stable fullerenes. According to results of FTIR spectroscopy, the Dy3N@C80 (I) (1) was assigned to the fullerene cage C80:7 (I(h)), whereas Dy3N@C80 (II) (2) had the cage structure of C80:6 (D(5h)). The most probable cage structure of Dy3N@C80 (III) (3) was proposed to be C80:1 (D(5d)). The significant differences between Dy3N@C80 and other reported M3N@C80 (M = Sc, Y, Gd, Tb, Ho, Er, Tm) cluster fullerenes are discussed in detail, and the strong influence of the metal on the nitride cluster fullerene formation is concluded.     

金属富勒烯的质谱研究

利用电弧放电法合成笼内金属富勒烯Gd@C₈₂,Gd₂@C₈₀,Gd@C₈₀实验结果表明,两步高温高压法(1,2,4-三甲基苯,吡啶)可有效地提取金属富勒烯Gd@C₈₂.本文分别利用ESI-MS,REC-MS,MALDI-TOF-MS质谱技术研究了Gd@C₈₂,Gd₂@C₈₀,Gd@C₈₀和富勒烯Cn(n=60,70,82,84…)的气相负离子特性.结果表明,包入Gd³⁺后非极性的C₈₂转变为极性的Gd@C₈₂分子;金属离子Gd³⁺处于C₈₂^3-笼中非中心的位置.     

Deviation from the planarity--a large Dy3N cluster encapsulated in an Ih-C80 cage: an X-ray crystallographic and vibrational spectroscopic study

The high-yield synthesis of Dy3N@C80 (I) opens the possibility of characterizing its molecular and vibrational structures. We report on the structure determination of Dy3N@C80 (I) by X-ray crystallographic study of single crystal of Dy3N@C80.Ni(OEP).2C6H6, revealing a nearly planar Dy3N cluster encapsulated in an Ih-C80 cage. The vibrational structure of Dy3N@C80 (I) is studied by Fourier transform infrared (FTIR) and Raman spectroscopy in combination with force-field calculations. A correlation was found between the antisymmetric metal-nitrogen stretching vibration and the structure of the M3N cluster of M3N@C80 (I) (M = Y, Gd, Tb, Dy, Ho, Er, Tm). Moreover, a stronger interaction between the encaged nitride cluster and the C80 carbon cage was found in the class II M3N@C80 (I) (M = Y, Gd, Tb, Dy, Ho, Er, Tm) than in Sc3N@C80 (I). This study demonstrates that the cluster size plays the dominating role in the structure of the M3N cluster in M3N@C80 (I).     

Gd3N@C2n (n = 40, 42, and 44): remarkably low HOMO-LUMO gap and unusual electrochemical reversibility of Gd3N@C88

High-performance liquid chromatography was used to isolate two new trimetallic nitride endohedral fullerenes, Gd3N@C2n (n = 42 and 44), and they were characterized by MALDI-TOF mass spectrometry, UV-vis-NIR, and cyclic voltammetry. It was found that their electronic HOMO-LUMO gaps depend pronouncedly on the size of the cage, from a large band gap for Gd3N@C80 (2.02 V) to a small band gap for Gd3N@C88 (1.49 V). The electrochemical properties also change dramatically with the size of the cage, going from irreversible for the C80 cage to reversible for Gd3N@C88. The latter is the largest trimetallic cluster inside C88 isolated and characterized to date. Gd3N@C88 has one of the lowest electrochemical energy gaps for a nonderivatized metallofullerene.     

Gadolinium-based mixed-metal nitride clusterfullerenes Gd(x)Sc(3-x)N@C80 (x=1, 2).

The first gadolinium-based mixed-metal nitride clusterfullerenes Gd(x)Sc(3-x)N@C(80) (I) (1, x=2; 2, x=1) have been successfully synthesized by the reactive gas atmosphere method and isolated facilely by recycling high-performance liquid chromatography (HPLC). The sum yield of 1 and 2 is 30-40 times higher than that of Gd(3)N@C(80) (I). Moreover, an enhanced relative yield of 2 over the Sc(3)N@C(80) (I) is achieved under the optimized synthesis conditions. According to the UV/Vis/NIR spectroscopic characterization, 1 and 2 are both stable fullerenes with large optical band-gaps while 1 has higher similarity to Gd(3)N@C(80) (I) and 2 resembles Sc(3)N@C(80) (I). The vibrational structures of 1 and 2 are studied by Fourier-transform infrared (FTIR) spectroscopy as well as density functional theory (DFT) computations. In particular, the structures of the encaged Gd(x)Sc(3-x)N clusters within 1 and 2 are analyzed.     

金属氮化物包合物Tb3N@C80的分离和表征

在利用电弧放电法合成铽的富勒烯笼内金属包合物时,首次观察到Tb₃N@C₈₀的存在,并用两步HPLC法将其分离和提纯.进一步的实验结果表明,氮气的加入是导致Tb₃N@C₈₀生成的原因.并用MALDI-TOF-MS和UV-Vis-NIR光谱对其进行了表征.     

The isomers of gadolinium scandium nitride clusterfullerenes GdxSc3-xN@C(80) (x=1, 2) and their influence on cluster structure

The isomers of gadolinium scandium mixed-metal nitride clusterfullerenes GdxSc3-xN@C(80) [x=2 (1, 4); x=1 (2, 5)] have been synthesized by the "reactive gas atmosphere" method and isolated facilely by recycling HPLC. The yield of GdxSc3-xN@C80 (I, II) (x=1, 2) relative to the homogenous clusterfullerenes Sc3N@C80 [I (3), II (6)] was determined. According to the UV/Vis/NIR spectroscopic data, 1, 2, 4, and 5 are all stable fullerenes with large optical gaps. Fullerene 1 has greater similarity to Gd3N@C80 (I) and 2 seems to resemble Sc3N@C80 (I). The quite similar overall absorption features of 4 and 5 suggest pronounced similarity in electronic structure. Vibrational spectroscopic studies led to the assignment of the cage symmetries of GdxSc3-xN@C80 (I, II), that is, Ih for 1, 2 and D5h for 4, 5. The cluster-cage interactions in GdxSc3-xN@C80 (I, II) were analyzed by means of the low-energy Raman lines. The splitting of the metal-nitrogen stretching vibrational mode in GdxSc3-xN@C80 (I, II) was studied in detail. Scalar-relativistic DFT calculations were performed to reveal the geometry parameters and the magnetic state of the GdxSc3-xN@C80 (I, II) molecules.     

Synthesis, isolation, and spectroscopic characterization of holmium-based mixed-metal nitride clusterfullerenes: HoxSc3-xN@C80 (x=1, 2)

The synthesis, isolation and spectroscopic characterization of holmium-based mixed metal nitride clusterfullerenes Ho(x) Sc(3-x) N@C(80) (x=1, 2) are reported. Two isomers of Ho(x) Sc(3-x) N@C(80) (x=1, 2) were synthesized by the reactive gas atmosphere method and isolated by multistep recycling HPLC. The isomeric structures of Ho(x) Sc(3-x) N@C(80) (x=1, 2) were characterized by laser-desorption time-of-flight (LD-TOF) mass spectrometry and UV/Vis/NIR, FTIR and Raman spectroscopy. A comparative study of M(x) Sc(3-x) N@C(80) (M=Gd, Dy, Lu, Ho) demonstrates the dependence of their electronic and vibrational properties on the encaged metal. Despite the distinct perturbation induced by 4f(10) electrons, we report the first paramagnetic (13) C?NMR study on Ho(x) Sc(3-x) N@C(80) (I; x=1, 2) and confirm I(h) -symmetric cage structure. A (45) Sc NMR study on HoSc(2) N@C(80) (I, II) revealed a temperature-dependent chemical shift in the temperature range of 268-308?K.     

Synthesis and purification of a metallic nitride fullerene bisadduct: exploring the reactivity of Gd3N@C80

This research represents initial functionalization of a Gd3N@C80 metallic nitride fullerene (MNF). Results demonstrate that a bisadduct can be prepared in an isolable yield for this MRI precursor MNF. This Gd3N@C80 bisadduct is synthesized and purified, and preliminary characterization is reported. This is a significant finding as, to date, only MNF monoadducts have been purified.     

Gd2@C79N: isolation, characterization, and monoadduct formation of a very stable heterofullerene with a magnetic spin state of S = 15/2

The dimetallic endohedral heterofullerene (EHF), Gd(2)@C(79)N, was prepared and isolated in a relatively high yield when compared with the earlier reported heterofullerene, Y(2)@C(79)N. Computational (DFT), chemical reactivity, Raman, and electrochemical studies all suggest that the purified Gd(2)@C(79)N, with the heterofullerene cage, (C(79)N)(5-) has comparable stability with other better known isoelectronic metallofullerene (C(80))(6-) cage species (e.g., Gd(3)N@C(80)). These results describe an exceptionally stable paramagnetic molecule with low chemical reactivity with the unpaired electron spin density localized on the internal diatomic gadolinium cluster and not on the heterofullerene cage. EPR studies confirm that the spin state of Gd(2)@C(79)N is characterized by a half-integer spin quantum number of S = 15/2. The spin (S = ?) on the N atom of the fullerene cage and two octet spins (S = 7/2) of two encapsulated gadoliniums are coupled with each other in a ferromagnetic manner with a small zero-field splitting parameter D. Because the central line of Gd(2)@C(79)N is due to the Kramer's doublet with a half-integer spin quantum number of S = 15/2, this relatively sharp line is prominent and the anisotropic nature of the line is weak. Interestingly, in contrast with most Gd(3+) ion environments, the central EPR line (g = 1.978) is observable even at room temperature in a toluene solution. Finally, we report the first EHF derivative, a diethyl bromomalonate monoadduct of Gd(2)@C(79)N, which was prepared and isolated via a modified Bingel-Hirsch reaction.     

内掺三金属氮化物富勒烯Er3N@C80的几何结构与电子性质理论研究

采用密度泛函理论中的广义梯度近似对Ih-Er3N@C80的几何结构和电子性质进行理论研究. 结构优化发现当Er3N的三个Er原子偏离Ih-C80中五边形和六边形公共边中点时形成的结构最稳定. Er—C和Er—N键是离子键. 能级分析可知: 掺入Er3N后, 碳笼的稳定性提高. 局部态密度图和自旋聚居数分析表明: Er3N的掺入使Ih-C80磁性变大, 而Er3N仍然具有一定的磁性. 垂直电离能和垂直亲和能分析表明: 掺入Er3N后, 碳笼的得失电子能力都有所降低.     

Titanium/yttrium mixed metal nitride clusterfullerene TiY2N@C80: synthesis, isolation, and effect of the group-III metal

Titanium/yttrium mixed metal nitride clusterfullerene (MMNCF) TiY(2)N@C(80) has been successfully synthesized, representing the first Ti-containing non-scandium MMNCF. TiY(2)N@C(80) has been isolated by multistep HPLC and characterized by various spectroscopies in combination with DFT computations. The electronic absorption property of TiY(2)N@C(80) was characterized by UV-vis-NIR spectroscopy, indicating the resemblance to that of TiSc(2)N@C(80) with broad shoulder absorptions. The optical band gap of TiY(2)N@C(80) (1.39 eV) is very close to that of TiSc(2)N@C(80) (1.43 eV) but much smaller than that of Y(3)N@C(80)(I(h), 1.58 eV). Such a resemblance of the overall absorption feature of TiY(2)N@C(80) to TiSc(2)N@C(80) suggests that TiY(2)N@C(80) has a similar electronic configuration to that of TiSc(2)N@C(80), that is, (TiY(2)N)(6+)@C(80)(6-). FTIR spectroscopic study and DFT calculations accomplish the assignment of the C(80):I(h) isomer to the cage structure of TiY(2)N@C(80), with the C(1) conformer being the lowest energy structure, which is different from the C(s) conformer assigned to TiSc(2)N@C(80). The electrochemical properties of TiY(2)N@C(80) were investigated by cyclic voltammetry, revealing the reversible first oxidation and first reduction step with E(1/2) at 0.00 and -1.13 V, respectively, both of which are more negative than those of TiSc(2)N@C(80), while the electrochemical energy gap of TiY(2)N@C(80) (1.11 V) is almost the same as that of TiSc(2)N@C(80) (1.10 V). Contrary to the reversible first reduction step, the second and third reduction steps of TiY(2)N@C(80) are irreversible, and this redox behavior is dramatically different from that of TiSc(2)N@C(80), which shows three reversible reduction steps, indicating the strong influence of the encaged group-III metal (Y or Sc) on the electronic properties of TiM(2)N@C(80) (M = Y, Sc).     

Tuning electronic properties of metallic atom in bondage to a nanospace

The possibility of modulating the electronic configurations of the innermost atoms inside a nanospace, nano sheath with chemical modification was investigated using synchrotron X-ray photoelectron spectroscopy. Systems of definite nanostructures were chosen for this study. Systematic variations in energy, intensity, and width of pi and sigma O 1s core level spectra, in absorption characteristics of C 1s-->pi transition, in photoabsorption of pre-edge and resonance regions of the Gd 4d-->4f transition, were observed for Gd@C(82) (an isolated nanospace for Gd), Gd@C(82)(OH)(12) (a modified nanospace for Gd), and Gd@C(82)(OH)(22) (a differently modified nanospace for Gd), and the reference materials Gd-DTPA (a semi-closed space for Gd) and Gd(2)O(3). A sandwich-type electronic interaction along [outer modification group]-[nano sheaths]-[inner metallic atom] was observed in the molecules of modifications. This makes it possible to control electron-donation directions, either from the innermost metallic atom toward the outer nano sheaths or the reverse. The results suggest that one may effectively tune the fine structures of electronic configurations of such a metallic atom being astricted into nanostructures through changing the number or category of outer groups of chemical modifications. This may open a door to realizing the desired designs for electronic and magnetic properties of functionalized nanomaterials.     

Chemical reactivity of sc3n @ c80 and la2 @ c80

Sc3N@C80 has a lower thermal reactivity than La2@C80, although Sc3N@C80 has the same carbon cage (Ih) and oxidation state (C806-) as La2@C80. This result is attributed to the difference in the energy level and distribution of LUMO between Sc3N@C80 and La2@C80.     

Charge-induced reversible rearrangement of endohedral fullerenes: electrochemistry of tridysprosium nitride clusterfullerenes Dy3N@C2n (2n=78, 80)

The electrochemistry of three new clusterfullerenes Dy3N@C2n (2n=78, 80), namely two isomers of Dy3N@C80 (I and II) as well as Dy3N@C78 (II), have been studied systematically including their redox-reaction mechanism. The cyclic voltammogram of Dy3N@C80 (I) (Ih) exhibits two electrochemically irreversible but chemically reversible reduction steps and one reversible oxidation step. Such a redox pattern is quite different from that of Sc3N@C80 (I), and this can be understood by considering the difference in the charge transfer from the encaged cluster to the cage. A double-square reaction scheme is proposed to explain the observed redox-reaction behavior, which involves the charge-induced reversible rearrangement of the Dy3N@C80 (I) monoanion. The first oxidation potential of Dy3N@C80 (II) (D5h) has a negative shift of 290 mV relative to that of Dy3N@C80 (I) (Ih), indicating that lowering the molecular symmetry of the clusterfullerene cage results in a prominent increase in the electron-donating property. The first and second reduction potentials of Dy3N@C78 (II) are negatively shifted relative to those of Dy3N@C80 (I, II), pointing to the former's lowered electron-accepting ability. The significant difference in the electrochemical energy gaps of Dy3N@C80 (I), Dy3N@C80 (II), and Dy3N@C78 (II) is consistent with the difference in their optical energy gaps.     

Does Gd@C82 have an anomalous endohedral structure? Synthesis and single crystal X-ray structure of the carbene adduct

We report here the results on single crystal X-ray crystallographic analysis of the Gd@C82 carbene adduct (Gd@C82(Ad), Ad = adamantylidene). The Gd atom in Gd@C82(Ad) is located at an off-centered position near a hexagonal ring in the C2v-C82 cage, as found for M@C82 (M = Sc and La) and La@C82(Ad). Theoretical calculation also confirms the position of the Gd atom in the X-ray crystal structure.     

Structure and enhanced reactivity rates of the D5h Sc3N@C80 and Lu3N@C80 metallofullerene isomers: the importance of the pyracylene motif

In this paper we report enhanced reactivity of the D(5h) isomers in comparison with the more common I(h) isomers of Sc(3)N@C(80) and Lu(3)N@C(80) toward Diels-Alder and 1,3-dipolar tritylazomethine ylide cycloaddition reactions. Also, the structure of the D(5h) isomer of Sc(3)N@C(80) has been determined through single-crystal X-ray diffraction on D(5h)-Sc(3)N@C(80).Ni(OEP).2benzene (OEP = octaethylporphyrin). The Sc(3)N portion of D(5h)-Sc(3)N@C(80) is strictly planar, but the plane of these four atoms is tipped out of the noncrystallographic, horizontal mirror plane of the fullerene by 30 degrees . The combination of short bond length and high degree of pyramidization for the central carbon atoms of the pyracylene sites situated along a belt that is perpendicular to the C(5) axis suggests that these are the sites of greatest reactivity in the D(5h) isomer of Sc(3)N@C(80). Consistent with the observation of higher reactivity observed for the D(5h) isomers, cyclic voltammetry and molecular orbital (MO) calculations demonstrate that the D(5h) isomers have slightly smaller energy gaps than those of the I(h) isomers. The first mono- and bis-adducts of D(5h) Sc(3)N@C(80) have been synthesized via 1,3-dipolar cycloaddition of tritylazomethine ylide. The NMR spectrum for the monoadduct 2b is consistent with reaction at the 6,6-ring juncture in the pyracylene unit of the D(5h) Sc(3)N@C(80) cage and is the thermodynamically stable isomer. On the other hand, monoadduct 2a undergoes thermal conversion to other isomeric monoadducts, and three possible structures are proposed.