Next Article in Journal
4-Hydroxy-7-methyl-3-phenylcoumarin Suppresses Aflatoxin Biosynthesis via Downregulation of aflK Expressing Versicolorin B Synthase in Aspergillus flavus
Next Article in Special Issue
Eu@C72: Computed Comparable Populations of Two Non-IPR Isomers
Previous Article in Journal
Adamantane-Isothiourea Hybrid Derivatives: Synthesis, Characterization, In Vitro Antimicrobial, and In Vivo Hypoglycemic Activities
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Molecules
Volume 22
Issue 5
10.3390/molecules22050718
molecules-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Non-Chromatographic Purification of Endohedral Metallofullerenes

by
Zhiyong Wang
1,2,
Haruka Omachi
1 and
Hisanori Shinohara
1,*
1
Department of Chemistry and Institute for Advanced Research, Nagoya University, Nagoya 464-8602, Japan
2
Department of Chemistry, Renmin University of China, Beijing 100872, China
*
Author to whom correspondence should be addressed.
Molecules 2017, 22(5), 718; https://doi.org/10.3390/molecules22050718
Submission received: 5 April 2017 / Revised: 25 April 2017 / Accepted: 26 April 2017 / Published: 29 April 2017
(This article belongs to the Special Issue Endohedral Metallofullerenes)
Browse Figures
Versions Notes

Abstract

:
The purification of endohedral metallofullerenes by high performance liquid chromatography is very time-consuming and expensive. A number of rapid and inexpensive non-chromatographic methods have thus been developed for large-scale purification of metallofullerenes. In this review, we summarize recent advances in non-chromatographic purification methods of metallofullerenes. Lewis acid-based complexation is one of the most efficient and powerful methods for separation of metallofullerenes from empty fullerenes. The first oxidation potential of metallofullerenes is a critical factor that affects the separation efficiency of the Lewis acid-based method. Supramolecular methods are effective for separation of fullerenes and metallofullerenes that are different in size and shape. Chemical/electrochemical reduction and exohedral functionalization are also utilized to separate and purify metallofullerenes on a large scale.

1. Introduction

Fullerenes are molecular carbon allotropes with closed cage-like structures. The internal hollow space of fullerenes can adopt atoms, ions, clusters, or molecules to form endohedral fullerenes [1,2]. Fullerenes encapsulating one metal atom, i.e., monometallofullerenes M@C2n, mainly involve rare-earth metals (e.g., Sc, Y, La, Ce, Gd, Lu) and a number of main-group metals such as Li, Ca, etc. [2,3]. Besides the monometallofullerenes, fullerenes can also accommodate two or three metal atoms, forming dimetallofullerenes M2@C2n [4], or trimetallofullerenes M3@C2n [5,6]. Other types of metallofullerenes include metallic nitride, carbide, oxide, or sulfide endohedral clusterfullerenes [7,8,9,10,11]. When metal atoms or metallic clusters are entrapped inside fullerenes, electron transfer occurs from the metal atoms or metallic clusters to the fullerene cages. As a consequence, metallofullerenes usually exhibit different chemical and physical properties from the parent empty fullerenes.
Metallofullerenes are attractive materials for a wide range of potential applications. In 2001, Gd-fullerenol (Gd@C82(OH)n) was found to have a much higher proton relaxivity than that of the commercial magnetic resonance imaging (MRI) contrast agents [12]. Since then, much work has been done for the development of a metallofullerene-based new class of MRI contrast agents [13,14]. Gd-based metallofullerenes also have the potential for cancer therapy. Aggregated Gd@C82(OH)22 nanoparticles were found to exhibit a high anticancer efficiency and a low toxicity at the same time [15]. It has been found that Gd@C82 dissolved in water with the aid of poly(ethylene glycol)-block-poly(2-(N,N-diethylamino)ethyl methacrylate) can be used for neutron capture therapy [16]. Besides the applications in biomedicine, metallofullerenes also hold great promise in other fields such as organic photovoltaics [17].
Large-scale production and purification of metallofullerenes is a crucial step toward their practical applications. Metallofullerenes are usually produced by an arc-discharge method in the laboratory [2,3]. The yields of metallofullerenes are typically in the milligram scale or even much lower. Further studies on their applications are hampered by their low yields. In recent years, new techniques in the mass production of metallofullerenes have been developed [18]. Some specific metallofullerenes, e.g., Gd@C82, can be produced and purified in a gram scale. This progress will pave the way for future research on applications of metallofullerenes.
In most of the previous studies, metallofullerenes were purified by high performance liquid chromatography (HPLC) [2,3]. Solvent-extract of arc-produced soot normally contains a large amount of the so-called empty fullerenes and various types of endohedral fullerenes. Multi-stage HPLC separation on different kinds of chromatographic columns as stationary phases is required to separate/purify the metallofullerenes. In some cases, tedious HPLC recycle performance is necessary to separate metallofullerene fractions with very close retention times [3]. As for large-scale separation/purification of metallofullerenes, the HPLC method is no doubt unfavorable because it is very time-consuming and expensive. Therefore, rapid and inexpensive non-chromatographic methods for separation/purification of metallofullerenes are highly sought after. This review paper summarizes recent advances of non-chromatographic separation/purification of metallofullerenes, which are much more convenient and rapid than the conventional HPLC isolation. In principle, most of the non-chromatographic methods were developed on the basis of the different properties of fullerenes and metallofullerenes toward complexation, oxidation, reduction, or other chemical reactions. The development of non-chromatographic methods makes it much easier to obtain a large quantity of metallofullerenes than it was before.

2. Separation/Purification of Metallofullerenes with Lewis Acids

Fullerenes and endohedral fullerenes have π-electron-rich surfaces, so generally they are reactive toward strong Lewis acids. When fullerenes/endohedral fullerenes are mixed with Lewis acids in a solution, complexation and/or redox reaction may take place, leading to precipitation of fullerenes/endohedral fullerenes. The reactivity of fullerenes/endohedral fullerenes toward Lewis acids is correlated to their intrinsic electronic structures. In 1994, Olah and coworkers reported that C70 forms a complex with AlCl3 in carbon disulfide much faster than C60 does [19]. This difference in the reaction rate allows the purification of C60 on a large scale. Most of C70 can be removed after a reaction period of several days. AlCl3 was also used as a strong oxidant to oxidize insoluble metallofullerenes such as Gd@C72 and Gd@C74 into soluble cations [20,21]. In 2009, Stevenson and coworkers reported that metallic nitride and oxometallic endohedral fullerenes exhibit different reactivity toward Lewis acids such as AlCl3 or FeCl3 [22]. They found that the reactivity order was Sc4O2@Ih-C80 > Sc3N@C78 > Sc3N@C68 > Sc3N@D5h-C80 > Sc3N@Ih-C80. The empty-cage fullerenes, such as C60 and C70, are largely unreactive toward the Lewis acids. A separation scheme was designed for the separation of the metallofullerenes on the basis of selective complexation and precipitation.
Recently, our group and coworkers reported a TiCl4-based non-chromatographic purification method [23,24], as schematically described in Figure 1, which is much more effective and easy-to-handle than any other Lewis acids. We found that metallofullerenes and empty fullerenes behave very differently toward TiCl4 complexation. When a certain amount of TiCl4 is added to an organic solution of fullerene/metallofullerene mixture, the metallofullerenes form a complex with TiCl4 immediately and then precipitate from the solution. The empty fullerenes, on the contrary, are almost unreactive toward TiCl4 and remain in the solution. The metallofullerenes and empty fullerenes can be separated from each other very easily by filtration. Then, the metallofullerenes are recovered completely by hydrolysis of the metallofullerene-TiCl4 complex. One of the advantages of this TiCl4-based method is that the purification process is very fast. Typically, only several minutes is needed to precipitate the metallofullerenes completely.
The TiCl4-based method is applicable to the separation/purification of all of the metallofullerenes that we have examined so far. Monometallofullerenes M@C2n based on both trivalent metal ions (e.g., Y3+, La3+, Ce3+, Er3+, Gd3+, Lu3+) and divalent metal ions (e.g., Sm2+, Eu2+, Tm2+, Yb2+) can be separated from empty fullerenes with up to >99% purity in a single step through complexation with TiCl4. Additionally, dimetallofullerenes M2@C2n, and clusterfullerenes, e.g., M2C2@C2n and M3N@C2n, can also be purified with TiCl4 treatment. Some typical results of separation/purification with TiCl4 are described in Figure 2.
We have examined the effects of solvent and reaction time on the separation efficiency of the La@C82 metallofullerene (Figure 3). When the reaction time is within 10 min, a separation efficiency of >99% is achieved for solvents of carbon disulfide, toluene, o-xylene, or 1,2,4-trichlorobenzene (TCB). However, the separation efficiency decreases gradually if the reaction time is longer than 100 min, which is presumably caused by an irreversible evolution of the La@C82-TiCl4 complex under ambient conditions.
Importantly, in addition to pristine metallofullerenes, TiCl4 is equally effective at separating/purifying metallofullerene derivatives. Recently, we reported the solvent-extraction and isolation of missing small-bandgap metallofullerenes through exterior functionalization with CF3 groups [25,26]. The trifluoromethylated derivatives of small-bandgap metallofullerenes, Y@C2n(CF3)m (2n = 60, 70, 72, or 74, m = 1 or 3), exhibit high reactivity toward TiCl4 (Figure 4) [25], which are similar to the case of pristine metallofullerenes. The removal of the empty fullerenes (e.g., C60, C70) with TiCl4 is a critical step for final purification of M@C2n(CF3)m. Because the derivatives have very similar retention times with C60 and C70 on chromatographic columns, it would be very difficult to isolate the derivatives by HPLC if the sample contains large amounts of C60 and C70.
To gain a better understanding on the complexation of metallofullerenes with TiCl4, we investigated the origin and mechanism of the separation/purification process. We found that the first oxidation potential is a crucial physical parameter that determines the reactivity of fullerenes and metallofullerenes toward TiCl4 complexation [24]. The reactivity of fullerenes and metallofullerenes with first oxidation potentials ranging from −0.07 to 1.26 V versus Fc/Fc+ (Fc = ferrocene) has been examined. Interestingly, metallofullerenes with first oxidation potentials of −0.07–0.62 V are reactive toward TiCl4; on the other hand, the empty fullerenes with first oxidation potentials of 0.72–1.26 V are almost nonreactive. Thus, the threshold value in the first oxidation potential for reaction with TiCl4 is determined to be 0.62–0.72 V (Figure 5). To the best of our knowledge, all of the reported metallofullerenes have first oxidation potentials below or close to this threshold value. Thus, the TiCl4-based purification method can be applied to virtually all of the reported metallofullerenes. For example, a nitride clusterfullerene Dy3N@Ih-C80, which has a first oxidation potential of 0.70 V, can be purified efficiently with TiCl4 in our laboratory.
The reaction mechanism between metallofullerenes and TiCl4 was investigated by monitoring the absorption spectrum. It was found that the absorption features of metallofullerene disappear and a new band from metallofullerene cation arises immediately after the addition of TiCl4 [24]. This dramatic change indicates that electron transfer occurs from metallofullerene to TiCl4. Element analysis reveals that the molar ratio of metallofullerene to TiCl4 is about 1:18-19 in the metallofullerene-TiCl4 complex [23]. The metallofullerene might be surrounded by the TiCl4 molecules. Further work is needed to determine the precise structure of the complex. There are several reports on the interaction between TiCl4 and empty cage fullerenes [27,28,29]. For example, TiCl4 has been used to chlorinate C70 fullerene [27]. The structures of TiCl4-solvated empty fullerenes, such as C60•3TiCl4 and C70•2TiCl4, have been crystallographically characterized [28,29]. It is possible to disclose the structure of the metallofullerene-TiCl4 complex by crystallographic study in the future.
Besides TiCl4, there are some other metal halides (e.g., AlCl3, FeCl3, and CuCl2) that can be used to separate and purify metallofullerenes through selective complexation [22,30,31,32]. The metal halides differ from each other with respect to their complexation abilities toward metallofullerenes. As compared with TiCl4, CuCl2 is a much weaker Lewis acid. It has been found that the precipitation threshold in the first oxidation potential for CuCl2 is about 0.19 V (vs. Fc/Fc+) [30], which is much lower than that for TiCl4 (0.62–0.72 V). Therefore, CuCl2 can be used to selectively precipitate the most reactive metallofullerenes. For example, metallofullerenes Sc3C2@Ih-C80 and Sc4O2@Ih-C80, with a first oxidation potential of −0.03 and 0.00 V, respectively, can be separated rapidly from a more inert metallofullerene Sc3N@Ih-C80 by using CuCl2; Sc3N@Ih-C80 can be subsequently purified through a second step of complexation with a stronger Lewis acid (e.g., FeCl3) [30]. For a mixture of metallofullerenes, the purification process can be greatly simplified if a number of Lewis acids are used consecutively to separate the metallofullerenes into distinct classes in terms of their reactivity. Stevenson and coworkers investigated the reactivity of a series of Lewis acids and reported the order of increasing reactivity as follows: CaCl2 < ZnCl2 < NiCl2 < MgCl2 < MnCl2 < CuCl2 < WCl4 ≪ WCl6 < ZrCl4 < AlCl3 < FeCl3 [31]. They have isolated Gd3N@D2(35)-C88 and CeLu2N@Ih-C80 by using the Lewis acid method [32,33]. The precipitation thresholds in the first oxidation potential of metallofullerenes for different Lewis acids are summarized in Table 1.
Because the metallofullerene isomers usually have different oxidation potentials, it is possible to separate them on the basis of selective chemical oxidation. In 2005, Echegoyen and coworkers reported that Ih and D5h isomers of Sc3N@C80 can be separated by selective oxidation with tris(p-bromophenyl)aminium hexachloroantimonate (TPBAH) [34]. Because of its lower first oxidation potential, the D5h isomer of Sc3N@C80 is oxidized preferentially by TPBAH. The resulted cation of Sc3N@D5h-C80 and neutral Sc3N@Ih-C80 are then separated with a silica column. This method was recently modified by using acetylferrocenium tetrakis(pentafluorophenyl)borate ([Fe(COCH3C5H4)Cp][TFAB]) instead of TPBAH as the oxidant [35]. The oxidation ability of [Fe(COCH3C5H4)Cp][TFAB] is weaker than that of TPBAH. In addition to Sc3N@D5h-C80 and Sc3N@Ih-C80, Sc3N@C68 and Sc3N@C78 are also purified or fractionated by using [Fe(COCH3C5H4)Cp][TFAB].

3. Size-Selective Separation/Purification of Metallofullerenes with Cycloparaphenelenes

Supramolecular host-guest chemistry is a powerful tool for non-chromatographic fullerene separation [36,37], and there are many examples of the complexation with metallofullerenes [38,39,40,41,42,43]. Akasaka and coworkers reported the selective extraction of lanthanum endohedral metallofullerenes from the as-synthesized mixture by the complexation with azacrown ether, 1,4,7,10,13,16-hexaazacyclooctadecane [38]. However, the selective extraction of a single metallofullerene has not been demonstrated yet due to the difficulty of the size-selective separation.
For the achievement of size-selective extraction, we have used cycloparapheneylenes (CPPs), which are cyclic compounds composed of solely para-substituted benzenes (Figure 6a) [44,45,46]. Some groups including the present laboratory have already reported that the pi-conjugated system is effective for the metallofullerene-selective complexation [40,41,42,43]. In order to realize size-selectivity, cyclic paraphenylene cavities are suitable candidates for the encapsulation of fullerenes [47,48,49]. Notably, [11]CPP has an ideal inner space with a diameter of 1.51 nm [50] for the inclusion of M@C82 families (0.85 nm in diameter) considering the interlayer distance of convex–concave pi-pi interactions such as fullerene nano-peapods (ca. 0.33 nm) [51]. A theoretical calculation also suggested that C82 could be fit almost completely into the cavity of [11]CPP (Figure 6b) [52].
After the establishment of the first selective synthesis of [11]CPP [53], we determined the binding abilities of [11]CPP to a series of C82-based metallofullerenes by fluorescence quenching experiments [52]. The fluorescence intensity of [11]CPP gradually decreased with the addition of metallofullerenes (Figure 6c). The binding constant (Ka) of [11]CPP with Gd@C82 is 1.8 × 106 M−1, which is one of the highest values for the complexes of higher metallofullerenes [40,41,42]. With other metallofullerenes such as Tm@C82, Lu2@C82, and Sc3N@C80, subequal binding constants were recorded. In contrast, the strong fluorescence quenching of larger [12]CPP [54] (1.66 nm in diameter) was not observed with the addition of C82-based metallofullerenes.
The separation protocol of Gd@C82 is described below. To a toluene solution of the fullerene mixture from raw soot that included Gd@C82, [11]CPP was added. After the solution was concentrated under reduced pressure, a brown solid precipitated out. Low solubility of the complex between Gd@C82 and [11]CPP realizes this non-chromatographic extraction separation technology. A positive-ion laser desorption mass spectra (LD-MS) of the crude extract, the filtrate solution, and the separated precipitate are shown in Figure 7. The depression of the Gd@C82 peak in the filtrate and a strong peak of Gd@C82 with the fragmentation of [11]CPP from the precipitate were observed. These results indicate that most of Gd@C82 are collected as the precipitate. It should be emphasized that higher metallofullerenes such as Gd@C94 are not extracted by the complexation with [11]CPP due to size mismatch between the fullerene molecule and the cavity of [11]CPP.
Table 2 summarizes a comparison of the extraction efficiency of Gd@C82 (yield, amount of solvent used, and time required) using the complexation method and the multistage HPLC method. The HPLC extraction of Gd@C82 was carried out for the same amount (10 mg) of crude fullerene mixture. The amounts of each Gd@C82 obtained were determined from the reported absorption coefficient. Although the HPLC method is somewhat superior in yield (72 μg vs. 56 μg), the present complexation method is much superior to the multistage HPLC method in terms of the amount of solvent used (50 mL vs. 5 L) and the time required for extraction (30 min vs. 5 h).
After our report of the size-selective extraction of metallofullerenes with CPPs, the group of Yamago revealed the partial electron transfer from [11]CPP to La@C82 [55]. This polar complex formation might support the selective recognition of metallofullerene and trigger a change to poor solubility in non-polar solvents like toluene.

4. Separation/Purification of Metallofullerenes through Chemical/Electrochemical Reduction

The electrochemical properties of empty fullerenes and metallofullerenes have been extensively studied during the past two decades [3,56]. The reported redox potentials provide useful information for separation/purification of metallofullerenes based on selective reduction/oxidation. Due to their higher first reduction potentials, the metallofullerenes are much easier to reduce as compared with the empty fullerenes. For example, La@C82 and La2@C80 in TCB extract of La soot can be selectively reduced into anions electrochemically [57]. The anions can easily be separated from neutral fullerenes as they have different solubilities in organic solvents. Subsequent oxidation of the anions with dichloroacetic acid leads to the recovery of the neutral metallofullerenes. In addition to the classical metallofullerene M@C82, there are a large number of the so-called missing small-bandgap metallofullerenes such as M@C60 and M@C70 [2]. The small-bandgap metallofullerenes are insoluble in organic solvents because they tend to form polymers or oligomers in raw soot. Alford and coworkers reported that the small-bandgap metallofullerenes become soluble and stable in organic solvents after electrochemical reduction [58], thus enabling further separation/purification of these unconventional metallofullerenes.
When an organic solvent such as carbon disulfide or o-xylene is used to extract metallofullerenes from raw soot, a large number of empty fullerenes are also dissolved in the solvent. To selectively extract metallofullerenes, some chemical reduction-based routes have been developed. Gu and coworkers reported the simultaneous reduction and extraction of metallofullerenes using Al-Ni alloy in a mixed solvent of toluene and tetrahydrofuran (THF) [59,60]. They found that the composition of the extracted metallofullerenes is dependent on the composition of the solvents used. Specifically, a mixture of Gd@C82/Gd2@C80 or pure Gd2@C80 can be extracted by tuning the ratio of toluene to THF. Their work provides a simple method for selective extraction of M2@C80 metallofullerene. Kodama and coworkers reported that Ce-metallofullerenes (Ce@C82, Ce2@C78, Ce2@C80) can be extracted selectively using a mixed solvent of triethylamine and acetone [61]. They proposed that the reduction of Ce-metallofullerenes by triethylamine or the formation of metallofullerene-triethylamine donor-accepter complexes is responsible for the selective extraction of metallofullerenes.
Unlike non-polar solvents such as carbon disulfide and o-xylene, N,N-dimethylformamide (DMF) was found to be a special solvent that can dissolve metallofullerenes preferentially, excepting empty fullerenes [62,63,64,65,66]. Akasaka and coworkers proposed that the metallofullerenes dissolved in DMF are actually in the form of anions, not neutral metallofullerenes; these might be formed during the high-temperature extraction process [66]. As such, metallofullerenes with high first reduction potentials dominate the DMF extract.

5. Separation/Purification of Metallofullerenes through Exohedral Organic Reactions

Organic chemistry of fullerenes/metallofullerenes has been an active research area since their discovery. Exohedral functionalization of fullerenes and metallofullerenes provides new routes to realize efficient separation of fullerenes and metallofullerenes. Dorn and coworkers reported that metal nitride clusterfullerenes can be separated from empty fullerenes and classical metallofullerenes by using a column packed with cyclopentadienyl-functionalized resin (Figure 8a) [67]. Empty fullerenes and metallofullerenes are bound to the resin by the Diels-Alder reaction, whereas, metal nitride clusterfullerenes remain intact and pass through the column due to their inertness. The bound empty fullerenes and metallofullerenes can be recovered upon heating in the presence of maleic anhydride. Stevenson and coworkers reported an alternative way to separate metal nitride clusterfullerenes through selective reaction with cyclopentadienyl- or amino-functionalized silica, which they call the “Stir and Filter Approach” (SAFA) (Figure 8b) [68,69,70,71,72]. This approach can be used to remove Sc3N@D5h-C80 rapidly from its structural isomer, Sc3N@Ih-C80 [70]. Further studies demonstrate that the content of water and the substituents on the aromatic solvent molecules have significant effects on the separation efficiency of metal nitride clusterfullerenes when using amino-functionalized silica [72].
In addition to the support-based separation strategies, some support-free chemical methods have also been reported for purification of metal nitride clusterfullerenes. For example, molten 9-methylanthracene was employed to react with a solid mixture of empty fullerenes and metal nitride clusterfullerenes [73]. The empty fullerenes were converted to 9-methylanthracene adducts that have different solubilities in organic solvents as compared with intact metal nitride clusterfullerenes. After washing away the fullerene derivatives with ether, metal nitride clusterfullerenes was enriched to about 60% purity within one day. Another example of a non-chromatographic method is based on selective extraction with 2-aminoethanol [74]. Empty cage fullerenes are much more reactive than the endohedral metallofullerenes Sc3N@C2n (n = 34, 39, 40) toward nucleophilic 2-aminoethanol. The empty cage fullerenes were selectively transferred to the 2-aminoethanol layer after reaction, and the endohedral metallofullerenes Sc3N@C2n were enriched in the original solution. Wang and coworkers reported a purification method based on Prato-type 1,3-dipolar cycloaddition [75]. Both empty fullerenes and metal nitride clusterfullerenes undergo cycloaddition with N-ethylglycine and paraformaldehyde [76]; subsequent retro-cycloaddition using 3-chloroperoxybenzoic acid, however, only takes place for the derivatives of metal nitride clusterfullerenes. This difference realizes a facile separation of metal nitride clusterfullerenes from empty fullerenes.

6. Summary

In order to realize convenient and rapid separation/purification of metallofullerenes, a number of non-chromatographic methods have been developed. Lewis acid-based complexation is one of the most efficient and powerful methods for separation of metallofullerenes from empty fullerenes. For this Lewis acid-based method, the separation efficiency is basically determined by the first oxidation potentials of the metallofullerenes. Supramolecular methods are effective for separation of fullerenes and metallofullerenes that are different in size and shape. The metallofullerene M@C82 can be isolated through selective complexation with [11]CPP. Chemical/electrochemical reduction and exohedral functionalization are also utilized to separate metallofullerenes in a large scale. It is much easier to obtain a large quantity of metallofullerenes than it was before by using the non-chromatographic methods. The development of non-chromatographic methods is a crucial step toward future industrial production of metallofullerenes.

Acknowledgments

The authors thank MEXT/JSPS KAKENHI Grant Number JP16H06350 for the partial support of the present work. Zhiyong Wang is very grateful for the support from the National Natural Science Foundation of China (Grant Number 21601203).

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Chai, Y.; Guo, T.; Jin, C.M.; Haufler, R.E.; Chibante, L.P.F.; Fure, J.; Wang, L.H.; Alford, J.M.; Smalley, R.E. Fullerenes with Metals Inside. J. Phys. Chem. 1991, 95, 7564–7568. [Google Scholar] [CrossRef]
  2. Shinohara, H. Endohedral Metallofullerenes. Rep. Prog. Phys. 2000, 63, 843–892. [Google Scholar] [CrossRef]
  3. Popov, A.A.; Yang, S.F.; Dunsch, L. Endohedral Fullerenes. Chem. Rev. 2013, 113, 5989–6113. [Google Scholar] [CrossRef] [PubMed]
  4. Alvarez, M.M.; Gillan, E.G.; Holczer, K.; Kaner, R.B.; Min, K.S.; Whetten, R.L. La2C80—A Soluble Dimetallofullerene. J. Phys. Chem. 1991, 95, 10561–10563. [Google Scholar] [CrossRef]
  5. Popov, A.A.; Zhang, L.; Dunsch, L. A Pseudoatom in a Cage: Trimetallofullerene Y3@C80 Mimics Y3N@C80 with Nitrogen Substituted by a Pseudoatom. ACS Nano 2010, 4, 795–802. [Google Scholar] [CrossRef] [PubMed]
  6. Xu, W.; Feng, L.; Calvaresi, M.; Liu, J.; Liu, Y.; Niu, B.; Shi, Z.J.; Lian, Y.F.; Zerbetto, F. An Experimentally Observed Trimetallofullerene Sm3@Ih-C80: Encapsulation of Three Metal Atoms in a Cage without a Nonmetallic Mediator. J. Am. Chem. Soc. 2013, 135, 4187–4190. [Google Scholar] [CrossRef] [PubMed]
  7. Stevenson, S.; Rice, G.; Glass, T.; Harich, K.; Cromer, F.; Jordan, M.R.; Craft, J.; Hadju, E.; Bible, R.; Olmstead, M.M.; et al. Small-Bandgap Endohedral Metallofullerenes in High Yield and Purity. Nature 1999, 401, 55–57. [Google Scholar]
  8. Zhang, J.Y.; Stevenson, S.; Dorn, H.C. Trimetallic Nitride Template Endohedral Metallofullerenes: Discovery, Structural Characterization, Reactivity, and Applications. Acc. Chem. Res. 2013, 46, 1548–1557. [Google Scholar] [CrossRef] [PubMed]
  9. Wang, C.-R.; Kai, T.; Tomiyama, T.; Yoshida, T.; Kobayashi, Y.; Nishibori, E.; Takata, M.; Sakata, M.; Shinohara, H. A Scandium Carbide Endohedral Metallofullerene: (Sc2C2)@C84. Angew. Chem. Int. Ed. 2001, 40, 397–399. [Google Scholar] [CrossRef]
  10. Stevenson, S.; Mackey, M.A.; Stuart, M.A.; Phillips, J.P.; Easterling, M.L.; Chancellor, C.J.; Olmstead, M.M.; Balch, A.L. A Distorted Tetrahedral Metal Oxide Cluster inside an Icosahedral Carbon Cage. Synthesis, Isolation, and Structural Characterization of Sc4(μ3-O)2@Ih-C80. J. Am. Chem. Soc. 2008, 130, 11844–11845. [Google Scholar] [CrossRef] [PubMed]
  11. Dunsch, L.; Yang, S.; Zhang, L.; Svitova, A.; Oswald, S.; Popov, A.A. Metal Sulfide in a C82 Fullerene Cage: A New Form of Endohedral Clusterfullerenes. J. Am. Chem. Soc. 2010, 132, 5413–5421. [Google Scholar] [CrossRef] [PubMed]
  12. Mikawa, M.; Kato, H.; Okumura, M.; Narazaki, M.; Kanazawa, Y.; Miwa, N.; Shinohara, H. Paramagnetic water-soluble metallofullerenes having the highest relaxivity for MRI contrast agents. Bioconj. Chem. 2001, 12, 510–514. [Google Scholar] [CrossRef]
  13. Bolskar, R.D. Gadofullerene MRI contrast agents. Nanomedicine 2008, 3, 201–213. [Google Scholar] [CrossRef] [PubMed]
  14. Fatouros, P.P.; Shultz, M.D. Metallofullerenes: a new class of MRI agents and more? Nanomedicine 2013, 8, 1853–1864. [Google Scholar] [CrossRef] [PubMed]
  15. Chen, C.; Xing, G.; Wang, J.; Zhao, Y.; Li, B.; Tang, J.; Jia, G.; Wang, T.; Sun, J.; Xing, L.; et al. Multihydroxylated [Gd@C82(OH)22]n nanoparticles: Antineoplastic activity of high efficiency and low toxicity. Nano Lett. 2005, 5, 2050–2057. [Google Scholar] [CrossRef] [PubMed]
  16. Horiguchi, Y.; Kudo, S.; Nagasaki, Y. Gd@C82 metallofullerenes for neutron capture therapy—fullerene solubilization by poly(ethylene glycol)-block-poly(2-(N, N-diethylamino)ethyl methacrylate) and resultant efficacy in vitro. Sci. Technol. Adv. Mater. 2011, 12, 044607. [Google Scholar] [CrossRef] [PubMed]
  17. Ross, R.B.; Cardona, C.M.; Guldi, D.M.; Sankaranarayanan, S.G.; Reese, M.O.; Kopidakis, N.; Peet, J.; Walker, B.; Bazan, G.C.; Van Keuren, E.; et al. Endohedral fullerenes for organic photovoltaic devices. Nat. Mater. 2009, 8, 208–212. [Google Scholar] [CrossRef] [PubMed]
  18. Sun, B.Y.; Cui, R.L. The Macroscopic Preparation of Endohedral Metallofullerene. In Proceedings of the 225th ECS Meeting, Orlando, FL, USA, 11–15 May 2014. [Google Scholar]
  19. Bucsi, I.; Aniszfeld, R.; Shamma, T.; Prakash, G.K.S.; Olah, G.A. Convenient Separation of High-Purity C60 from Crude Fullerene Extract by Selective Complexation with AlCl3. Proc. Natl. Acad. Sci. USA 1994, 91, 9019–9021. [Google Scholar] [CrossRef] [PubMed]
  20. Bolskar, R.D.; Alford, J.M. Chemical oxidation of endohedral metallofullerenes: identification and separation of distinct classes. Chem. Commun. 2003, 1292–1293. [Google Scholar] [CrossRef]
  21. Raebiger, J.W.; Bolskar, R.D. Improved production and separation processes for gadolinium metallofullerenes. J. Phys. Chem. C 2008, 112, 6605–6612. [Google Scholar] [CrossRef]
  22. Stevenson, S.; Mackey, M.A.; Pickens, J.E.; Stuart, M.A.; Confait, B.S.; Phillips, J.P. Selective Complexation and Reactivity of Metallic Nitride and Oxometallic Fullerenes with Lewis Acids and Use as an Effective Purification Method. Inorg. Chem. 2009, 48, 11685–11690. [Google Scholar] [CrossRef] [PubMed]
  23. Akiyama, K.; Hamano, T.; Nakanishi, Y.; Takeuchi, E.; Noda, S.; Wang, Z.Y.; Kubuki, S.; Shinohara, H. Non-HPLC Rapid Separation of Metallofullerenes and Empty Cages with TiCl4 Lewis Acid. J. Am. Chem. Soc. 2012, 134, 9762–9767. [Google Scholar] [CrossRef] [PubMed]
  24. Wang, Z.Y.; Nakanishi, Y.; Noda, S.; Akiyama, K.; Shinohara, H. The Origin and Mechanism of Non-HPLC Purification of Metallofullerenes with TiCl4. J. Phys. Chem. C 2012, 116, 25563–25567. [Google Scholar] [CrossRef]
  25. Wang, Z.Y.; Nakanishi, Y.; Noda, S.; Niwa, H.; Zhang, J.Y.; Kitaura, R.; Shinohara, H. Missing Small-Bandgap Metallofullerenes: Their Isolation and Electronic Properties. Angew. Chem. Int. Ed. 2013, 52, 11770–11774. [Google Scholar] [CrossRef] [PubMed]
  26. Wang, Z.; Aoyagi, S.; Omachi, H.; Kitaura, R.; Shinohara, H. Isolation and Structure Determination of a Missing Endohedral Fullerene La@C70 through In Situ Trifluoromethylation. Angew. Chem. Int. Ed. 2016, 55, 199–202. [Google Scholar] [CrossRef] [PubMed]
  27. Troyanov, S.I.; Popov, A.A. A [70]Fullerene Chloride, C70Cl16, Obtained by the Attempted Bromination of C70 in TiCl4. Angew. Chem. Int. Ed. 2005, 44, 4215–4218. [Google Scholar] [CrossRef] [PubMed]
  28. Troyanov, S.I.; Kemnitz, E. Structure of fullerene C60 in the crystalline adduct C60•3TiCl4. Russ. J. Inorg. Chem. 2001, 46, 1547–1552. [Google Scholar]
  29. Troyanov, S.I. Structure of C70 fullerene in the crystalline adduct C70•2TiCl4. Russ. J. Inorg. Chem. 2001, 46, 1612–1616. [Google Scholar]
  30. Stevenson, S.; Rottinger, K.A. CuCl2 for the Isolation of a Broad Array of Endohedral Fullerenes Containing Metallic, Metallic Carbide, Metallic Nitride, and Metallic Oxide Clusters, and Separation of Their Structural Isomers. Inorg. Chem. 2013, 52, 9606–9612. [Google Scholar] [CrossRef] [PubMed]
  31. Stevenson, S.; Rottinger, K.A.; Fahim, M.; Field, J.S.; Martin, B.R.; Arvola, K.D. Tuning the Selectivity of Gd3N Cluster Endohedral Metallofullerene Reactions with Lewis Acids. Inorg. Chem. 2014, 53, 12939–12946. [Google Scholar] [CrossRef] [PubMed]
  32. Stevenson, S.; Arvola, K.D.; Fahim, M.; Martin, B.R.; Ghiassi, K.B.; Olmstead, M. M.; Balch, A. L. Isolation and Crystallographic Characterization of Gd3N@D2(35)-C88 through Non-Chromatographic Methods. Inorg. Chem. 2016, 55, 62–67. [Google Scholar] [CrossRef] [PubMed]
  33. Stevenson, S.; Thompson, H.R.; Arvola, K.D.; Ghiassi, K.B.; Olmstead, M.M.; Balch, A.L. Isolation of CeLu2N@Ih-C80 through a Non-Chromatographic, Two-Step Chemical Process and Crystallographic Characterization of the Pyramidalized CeLu2N within the Icosahedral Cage. Chem. Eur. J. 2015, 21, 10362–10368. [Google Scholar] [CrossRef] [PubMed]
  34. Elliott, B.; Yu, L.; Echegoyen, L. A simple isomeric separation of D5h and Ih Sc3N@C80 by selective chemical oxidation. J. Am. Chem. Soc. 2005, 127, 10885–10888. [Google Scholar] [CrossRef] [PubMed]
  35. Ceron, M.R.; Li, F.F.; Echegoyen, L. An Efficient Method to Separate Sc3N@C80 Ih and D5h Isomers and Sc3N@C78 by Selective Oxidation with Acetylferrocenium [Fe(COCH3C5H4)Cp]+. Chem. Eur. J. 2013, 19, 7410–7415. [Google Scholar] [CrossRef] [PubMed]
  36. Atwood, J.L.; Koutsantonis, G.A.; Raston, C.L. Purification of C60 and C70 by selective complexation with calixarenes. Nature 1994, 368, 229–231. [Google Scholar] [CrossRef]
  37. Suzuki, T.; Nakashima, K.; Shinkai, S. Very convenient and efficient purification method for fullerene C60 with 5,11,17,23,29,35,41,47-octa-tert-butylcalix[8]arene-49,50,51,52,53,54,55,56-octol. Chem. Lett. 1994, 23, 699–702. [Google Scholar] [CrossRef]
  38. Tsuchiya, T.; Sato, K.; Kurihara, H.; Wakahara, T.; Nakahodo, T.; Maeda, Y.; Akasaka, T.; Ohkubo, K.; Fukuzumi, S.; Kato, T.; et al. Host-guest complexation of endohedral metallofullerene with azacrown ether and its application. J. Am. Chem. Soc. 2006, 128, 6699–6703. [Google Scholar] [CrossRef] [PubMed]
  39. Tsuchiya, T.; Sato, K.; Kurihara, H.; Wakahara, T.; Maeda, Y.; Akasaka, T.; Ohkubo, K.; Fukuzumi, S.; Kato, T.; Nagase, S. Spin-site exchange system constructed from endohedral metallofullerenes and organic donors. J. Am. Chem. Soc. 2006, 128, 14418–14419. [Google Scholar] [CrossRef] [PubMed]
  40. Yang, S.F.; Yang, S.H. Preparation and Film Formation Behavior of the Supramolecular Complex of the Endohedral Metallofullerene Dy@C82 with Calix[8]arene. Langmuir 2002, 18, 8488–8495. [Google Scholar] [CrossRef]
  41. Tsuchiya, T.; Kurihara, H.; Sato, K.; Wakahara, T.; Akasaka, T.; Shimizu, T.; Kamigata, N.; Mizorogi, N.; Nagase, S. Supramolecular complexes of La@C82 with unsaturated thiacrown ethers. Chem. Commun. 2006, 3585–3587. [Google Scholar] [CrossRef] [PubMed]
  42. Pagona, G.; Economopoulos, S.P.; Aono, T.; Miyata, Y.; Shinohara, H.; Tagmatarchis, N. Molecular recognition of La@C82 endohedral metallofullerene by an isophthaloyl-bridged porphyrin dimer. Tetrahedron Lett. 2010, 51, 5896–5899. [Google Scholar] [CrossRef]
  43. Kamimura, T.; Ohkubo, K.; Kawashima, Y.; Nobukuni, H.; Naruta, Y.; Tani, F.; Fukuzumi, S. Submillisecond-lived photoinduced charge separation in inclusion complexes composed of Li+@C60 and cyclic porphyrin dimers. Chem. Sci. 2013, 4, 1451–1461. [Google Scholar] [CrossRef]
  44. Omachi, H.; Segawa, Y.; Itami, K. Synthesis of Cycloparaphenylenes and Related Carbon Nanorings: A Step toward the Controlled Synthesis of Carbon Nanotubes. Acc. Chem. Res. 2012, 45, 1378–1389. [Google Scholar] [CrossRef] [PubMed]
  45. Hirst, E.; Jasti, R. Bending benzene: Syntheses of [n]cycloparaphenylenes. J. Org. Chem. 2012, 77, 10473–10478. [Google Scholar] [CrossRef] [PubMed]
  46. Yamago, S.; Kayahara, E.; Iwamoto, T. Organoplatinum-Mediated Synthesis of Cyclic π-Conjugated Molecules: Towards a New Era of Three-Dimensional Aromatic Compounds. Chem. Rec. 2014, 14, 84–100. [Google Scholar] [CrossRef] [PubMed]
  47. Iwamoto, T.; Watanabe, Y.; Sadahiro, T.; Haino, T.; Yamago, S. Size-Selective Encapsulation of C60 by [10]Cycloparaphenylene: Formation of the Shortest Fullerene-Peapod. Angew. Chem. Int. Ed. 2011, 50, 8342–8344. [Google Scholar] [CrossRef] [PubMed]
  48. Xia, J.; Bacon, J.W.; Jasti, R. Gram-scale synthesis and crystal structures of [8]- and [10]CPP, and the solid-state structure of C60@[10]CPP. Chem. Sci. 2012, 3, 3018–3021. [Google Scholar] [CrossRef]
  49. Iwamoto, T.; Watanabe, Y.; Takaya, H.; Haino, T.; Yasuda, N.; Yamago, S. Size- and Orientation-Selective Encapsulation of C70 by Cycloparaphenylenes. Chem. Eur. J. 2013, 19, 14061–14068. [Google Scholar] [CrossRef] [PubMed]
  50. Segawa, Y.; Omachi, H.; Itami, K. Theoretical Studies on the Structures and Strain Energies of Cycloparaphenylenes. Org. Lett. 2010, 12, 2262–2265. [Google Scholar] [CrossRef] [PubMed]
  51. Smith, B.W.; Monthioux, M.; Luzzi, D.E. Encapsulated C60 in carbon nanotubes. Nature 1998, 396, 323–324. [Google Scholar] [CrossRef]
  52. Nakanishi, Y.; Omachi, H.; Matsuura, S.; Miyata, Y.; Kitaura, R.; Segawa, Y.; Itami, K.; Shinohara, H. Size-selective complexation and extraction of endohedral metallofullerenes with cycloparaphenylene. Angew. Chem. Int. Ed. 2014, 53, 3102–3106. [Google Scholar] [CrossRef] [PubMed]
  53. Ishii, Y.; Nakanishi, Y.; Omachi, H.; Matsuura, S.; Matsui, K.; Shinohara, H.; Segawa, Y.; Itami, K. Size-selective synthesis of [9]–[11] and [13]cycloparaphenylenes. Chem. Sci. 2012, 3, 2340–2345. [Google Scholar] [CrossRef]
  54. Takaba, H.; Omachi, H.; Yamamoto, Y.; Bouffard, J.; Itami, K. Selective Synthesis of [12]Cycloparaphenylene. Angew. Chem. Int. Ed. 2009, 48, 6112–6116. [Google Scholar] [CrossRef] [PubMed]
  55. Iwamoto, T.; Slanina, Z.; Mizorogi, N.; Guo, J.; Akasaka, T.; Nagase, S.; Takaya, H.; Yasuda, N.; Kato, T.; Yamago, S. Partial Charge Transfer in the Shortest Possible Metallofullerene Peapod, La@C82⊂[11]Cycloparaphenylene. Chem. Eur. J. 2014, 20, 14403–14409. [Google Scholar] [CrossRef] [PubMed]
  56. Chaur, M.N.; Melin, F.; Ortiz, A.L.; Echegoyen, L. Chemical, Electrochemical, and Structural Properties of Endohedral Metallofullerenes. Angew. Chem. Int. Ed. 2009, 48, 7514–7538. [Google Scholar] [CrossRef] [PubMed]
  57. Tsuchiya, T.; Wakahara, T.; Shirakura, S.; Maeda, Y.; Akasaka, T.; Kobayashi, K.; Nagase, S.; Kato, T.; Kadish, K.M. Reduction of endohedral metallofullerenes: A convenient method for isolation. Chem. Mater. 2004, 16, 4343–4346. [Google Scholar] [CrossRef]
  58. Diener, M.D.; Alford, J.M. Isolation and Properties of Small-Bandgap Fullerenes. Nature 1998, 393, 668–671. [Google Scholar]
  59. Sun, B.Y.; Gu, Z.N. Solvent-dependent anion studies on enrichment of metallofullerene. Chem. Lett. 2002, 1164–1165. [Google Scholar] [CrossRef]
  60. Lu, X.; Li, H.J.; Sun, B.Y.; Shi, Z.J.; Gu, Z.N. Selective reduction and extraction of Gd@C82 and Gd2@C80 from soot and the chemical reaction of their anions. Carbon 2005, 43, 1546–1549. [Google Scholar] [CrossRef]
  61. Kodama, T.; Higashi, K.; Ichikawa, T.; Suzuki, S.; Nishikawa, H.; Ikemoto, I.; Kikuchi, K.; Achiba, Y. Selective Extraction of Endohedral Metallofullerenes Using a Mixed Solvent of Triethylamine and Acetone. Chem. Lett. 2005, 34, 464–465. [Google Scholar] [CrossRef]
  62. Ding, J.Q.; Yang, S.H. Efficient N,N-dimethylformamide extraction of endohedral metallofullerenes for HPLC purification. Chem. Mater. 1996, 8, 2824–2827. [Google Scholar] [CrossRef]
  63. Sun, D.Y.; Huang, H.J.; Yang, S.H.; Liu, Z.Y.; Liu, S.Y. A simple method for the selective enrichment of endohedral metallofullerenes. Chem. Mater. 1999, 11, 374–377. [Google Scholar] [CrossRef]
  64. Sun, B.Y.; Feng, L.; Shi, Z.J.; Gu, Z.N. Improved extraction of metallofullerenes with DMF at high temperature. Carbon 2002, 40, 1591–1595. [Google Scholar] [CrossRef]
  65. Lian, Y.F.; Shi, Z.J.; Zhou, X.H.; Gu, Z.N. Different extraction Behaviors between divalent and trivalent endohedral metallofullerenes. Chem. Mater. 2004, 16, 1704–1714. [Google Scholar] [CrossRef]
  66. Tsuchiya, T.; Wakahara, T.; Lian, Y.F.; Maeda, Y.; Akasaka, T.; Kato, T.; Mizorogi, N.; Nagase, S. Selective Extraction and Purification of Endohedral Metallofullerene from Carbon Soot. J. Phys. Chem. B 2006, 110, 22517–22520. [Google Scholar] [CrossRef] [PubMed]
  67. Ge, Z.X.; Duchamp, J.C.; Cai, T.; Gibson, H.W.; Dorn, H.C. Purification of endohedral trimetallic nitride fullerenes in a single, facile step. J. Am. Chem. Soc. 2005, 127, 16292–16298. [Google Scholar] [CrossRef] [PubMed]
  68. Stevenson, S.; Harich, K.; Yu, H.; Stephen, R.R.; Heaps, D.; Coumbe, C.; Phillips, J.P. Nonchromatographic "stir and filter approach" (SAFA) for isolating Sc3N@C80 metallofullerenes. J. Am. Chem. Soc. 2006, 128, 8829–8835. [Google Scholar] [CrossRef] [PubMed]
  69. Stevenson, S.; Rottinger, K.A.; Field, J.S. Fractionation of rare-earth metallofullerenes via reversible uptake and release from reactive silica. Dalton Trans. 2014, 43, 7435–7441. [Google Scholar] [CrossRef] [PubMed]
  70. Stevenson, S.; Mackey, M.A.; Coumbe, C.E.; Phillips, J.P.; Elliott, B.; Echegoyen, L. Rapid removal of D5h isomer using the “stir and filter approach” and isolation of large quantities of isomerically pure Sc3N@C80 metallic nitride fullerenes. J. Am. Chem. Soc. 2007, 129, 6072–6073. [Google Scholar] [CrossRef] [PubMed]
  71. Stevenson, S.; Rose, C.B.; Maslenikova, J.S.; Villarreal, J.R.; Mackey, M.A.; Mercado, B.Q.; Chen, K.; Olmstead, M.M.; Balch, A.L. Selective Synthesis, Isolation, and Crystallographic Characterization of LaSc2N@Ih-C80. Inorg. Chem. 2012, 51, 13096–13102. [Google Scholar] [CrossRef] [PubMed]
  72. Stevenson, S.; Rose, C.B.; Robson, A.A.; Heaps, D.T.; Buchanan, J.P. Effect of Water and Solvent Selection on the SAFA Purification Times for Metallic Nitride Fullerenes. Fullerenes Nanotubes Carbon Nanostruct. 2014, 22, 182–189. [Google Scholar] [CrossRef]
  73. Angeli, C.D.; Cai, T.; Duchamp, J.C.; Reid, J.E.; Singer, E.S.; Gibson, H.W.; Dorn, H.C. Purification of trimetallic nitride templated endohedral metallofullerenes by a chemical reaction of congeners with eutectic 9-methylanthracene. Chem. Mater. 2008, 20, 4993–4997. [Google Scholar] [CrossRef]
  74. Sarina, E.A.; Mercado, B.Q.; Franco, J.U.; Thompson, C.J.; Easterling, M.L.; Olmstead, M.M.; Balch, A.L. 2-Aminoethanol Extraction as a Method for Purifying Sc3N@C80 and for Differentiating Classes of Endohedral Fullerenes on the Basis of Reactivity. Chem. Eur. J. 2015, 21, 17035–17043. [Google Scholar] [CrossRef] [PubMed]
  75. Wu, B.; Wang, T.S.; Zhang, Z.X.; Feng, Y.Q.; Gan, L.H.; Jiang, L.; Wang, C.R. An effective retro-cycloaddition of M3N@C80 (M = Sc, Lu, Ho) metallofulleropyrrolidines. Chem. Commun. 2013, 49, 10489–10491. [Google Scholar] [CrossRef] [PubMed]
  76. Maggini, M.; Scorrano, G.; Prato, M. Addition of azomethine ylides to C60: synthesis, characterization, and functionalization of fullerene pyrrolidines. J. Am. Chem. Soc. 1993, 115, 9798–9799. [Google Scholar] [CrossRef]
Molecules 22 00718 g001 550
Figure 1. Separation and purification scheme of metallofullerenes on the basis of selective complexation with TiCl4.
Figure 1. Separation and purification scheme of metallofullerenes on the basis of selective complexation with TiCl4.
Molecules 22 00718 g001
Molecules 22 00718 g002 550
Figure 2. (a) HPLC profiles of crude extract containing Gd@C82 and empty fullerenes (top line) and Gd@C82 purified by complexation with TiCl4 (bottom line); (b–d) Positive-ion laser desorption mass spectra (LD-MS) of crude extracts, filtered solutions, and precipitates for Gd-, Tm-, and Lu-metallofullerenes, respectively. Empty fullerenes are removed completely after a single step treatment with TiCl4. Reproduced with permission from [23]. Copyright 2012 American Chemical Society.
Figure 2. (a) HPLC profiles of crude extract containing Gd@C82 and empty fullerenes (top line) and Gd@C82 purified by complexation with TiCl4 (bottom line); (b–d) Positive-ion laser desorption mass spectra (LD-MS) of crude extracts, filtered solutions, and precipitates for Gd-, Tm-, and Lu-metallofullerenes, respectively. Empty fullerenes are removed completely after a single step treatment with TiCl4. Reproduced with permission from [23]. Copyright 2012 American Chemical Society.
Molecules 22 00718 g002
Molecules 22 00718 g003 550
Figure 3. Separation efficiency of La@C82 with TiCl4 in solvents of carbon disulfide, toluene, o-xylene, and 1,2,4-trichlorobenzene (TCB) for various reaction periods. Reproduced with permission from [23]. Copyright 2012 American Chemical Society.
Figure 3. Separation efficiency of La@C82 with TiCl4 in solvents of carbon disulfide, toluene, o-xylene, and 1,2,4-trichlorobenzene (TCB) for various reaction periods. Reproduced with permission from [23]. Copyright 2012 American Chemical Society.
Molecules 22 00718 g003
Molecules 22 00718 g004 550
Figure 4. Positive-ion LD-MS of (a) crude extract of yttrium soot and (b) Y-metallofullerene derivatives separated with TiCl4. The derivatives Y@C2n(CF3)m are decomposed by laser irradiation, so the fragment signals from Y@C2n+ are observed in the spectra. Reprinted from [25] with permission from Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Figure 4. Positive-ion LD-MS of (a) crude extract of yttrium soot and (b) Y-metallofullerene derivatives separated with TiCl4. The derivatives Y@C2n(CF3)m are decomposed by laser irradiation, so the fragment signals from Y@C2n+ are observed in the spectra. Reprinted from [25] with permission from Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Molecules 22 00718 g004
Molecules 22 00718 g005 550
Figure 5. Plot of first oxidation potential (vs. ferrocene (Fc/Fc+)) of fullerenes and metallofullerenes and the threshold (dashed line) in the first oxidation potential for reaction with TiCl4. Blue and red colors denote the reactive and nonreactive fullerenes/metallofullerenes, respectively. Reproduced with permission from [24]. Copyright 2012 American Chemical Society.
Figure 5. Plot of first oxidation potential (vs. ferrocene (Fc/Fc+)) of fullerenes and metallofullerenes and the threshold (dashed line) in the first oxidation potential for reaction with TiCl4. Blue and red colors denote the reactive and nonreactive fullerenes/metallofullerenes, respectively. Reproduced with permission from [24]. Copyright 2012 American Chemical Society.
Molecules 22 00718 g005
Molecules 22 00718 g006 550
Figure 6. (a) Chemical Structure of [n]Cycloparaphenylene ([n]CPP). (b) A space-filling model of C82@[11]CPP. (c) Fluorescence spectra and plot for determination of the binding constant of Gd@C82/[11]CPP titration. Reprinted from [52] with permission from Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Figure 6. (a) Chemical Structure of [n]Cycloparaphenylene ([n]CPP). (b) A space-filling model of C82@[11]CPP. (c) Fluorescence spectra and plot for determination of the binding constant of Gd@C82/[11]CPP titration. Reprinted from [52] with permission from Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Molecules 22 00718 g006
Molecules 22 00718 g007 550
Figure 7. Positive-ion LD-MS spectra of the crude mixture with low contents of metallofullerenes, the filtrate, and the precipitate after the addition of [11]CPP. Reprinted from [52] with permission from Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Figure 7. Positive-ion LD-MS spectra of the crude mixture with low contents of metallofullerenes, the filtrate, and the precipitate after the addition of [11]CPP. Reprinted from [52] with permission from Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Molecules 22 00718 g007
Molecules 22 00718 g008 550
Figure 8. Schematic illustration of purification processes for metal nitride clusterfullerenes. (a) The cyclopentadienyl-functionalized resin method. Reproduced with permission from [67]. Copyright 2005 American Chemical Society. (b) The “Stir and Filter Approach” using reactive silica (MNF = metallic nitride fullerenes). Reproduced with permission from [68]. Copyright 2006 American Chemical Society.
Figure 8. Schematic illustration of purification processes for metal nitride clusterfullerenes. (a) The cyclopentadienyl-functionalized resin method. Reproduced with permission from [67]. Copyright 2005 American Chemical Society. (b) The “Stir and Filter Approach” using reactive silica (MNF = metallic nitride fullerenes). Reproduced with permission from [68]. Copyright 2006 American Chemical Society.
Molecules 22 00718 g008
Table
Table 1. The precipitation threshold in the first oxidation potential of metallofullerenes for different Lewis acids.
Table 1. The precipitation threshold in the first oxidation potential of metallofullerenes for different Lewis acids.
Lewis AcidsPrecipitation Threshold (vs. Fc/Fc+)
TiCl40.62–0.72 V
WCl6, ZrCl4, AlCl3, FeCl30.6 V
MgCl2, MnCl2, WCl40.1–0.5 V
CuCl20.19 V
CaCl2, ZnCl2, NiCl20.1 V
Table
Table 2. A comparison of the extraction efficiency between a multistage HPLC method and the cycloparapheneylene (CPP) method from 10 mg of crude extract.
Table 2. A comparison of the extraction efficiency between a multistage HPLC method and the cycloparapheneylene (CPP) method from 10 mg of crude extract.
HPLC MethodCPP Method
Collected Gd@C8272 µg56 µg
Amount of solvent used~5 L~50 mL
Time required~5 h~30 min

Share and Cite

MDPI and ACS Style

Wang, Z.; Omachi, H.; Shinohara, H. Non-Chromatographic Purification of Endohedral Metallofullerenes. Molecules 2017, 22, 718. https://doi.org/10.3390/molecules22050718

AMA Style

Wang Z, Omachi H, Shinohara H. Non-Chromatographic Purification of Endohedral Metallofullerenes. Molecules. 2017; 22(5):718. https://doi.org/10.3390/molecules22050718

Chicago/Turabian Style

Wang, Zhiyong, Haruka Omachi, and Hisanori Shinohara. 2017. "Non-Chromatographic Purification of Endohedral Metallofullerenes" Molecules 22, no. 5: 718. https://doi.org/10.3390/molecules22050718

Article Metrics

Back to TopTop