WO2019200501A1 - 水溶性内嵌钍富勒烯及其制备方法与应用 - Google Patents

水溶性内嵌钍富勒烯及其制备方法与应用 Download PDF

Info

Publication number
WO2019200501A1
WO2019200501A1 PCT/CN2018/083137 CN2018083137W WO2019200501A1 WO 2019200501 A1 WO2019200501 A1 WO 2019200501A1 CN 2018083137 W CN2018083137 W CN 2018083137W WO 2019200501 A1 WO2019200501 A1 WO 2019200501A1
Authority
WO
WIPO (PCT)
Prior art keywords
fullerene
inlaid
water
soluble
graphite
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/CN2018/083137
Other languages
English (en)
French (fr)
Inventor
谌宁
阳威
王姚峰
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Suzhou University
Nantong Textile and Silk Industrial Technology Research Institute
Original Assignee
Suzhou University
Nantong Textile and Silk Industrial Technology Research Institute
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Suzhou University, Nantong Textile and Silk Industrial Technology Research Institute filed Critical Suzhou University
Priority to PCT/CN2018/083137 priority Critical patent/WO2019200501A1/zh
Publication of WO2019200501A1 publication Critical patent/WO2019200501A1/zh
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/04—X-ray contrast preparations
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
    • C01B32/00—Carbon; Compounds thereof
    • C01B32/15—Nano-sized carbon materials
    • C01B32/152—Fullerenes
    • C01B32/154—Preparation

Definitions

  • the invention belongs to the field of material chemistry, and particularly relates to water-soluble inlaid fullerene (Th@C 82 ) and a preparation method and application thereof.
  • the water-soluble inlaid fullerene is a molecule obtained by first embedding a metal atom into a fullerene carbon cage and then modifying the surface of the fullerene. Due to the embedding of metal atoms in the carbon cage, the structure of the hollow fullerenes and other embedded fullerenes and various physicochemical properties are significantly different, and the fullerene is embedded by surface modification, thereby making it more unique. Excellent properties. According to the current relevant experimental results, it has been expected that such compounds have broad application prospects in the fields of biology, medicine, materials and the like.
  • the main methods for preparing inlaid fullerenes are ion implantation and arc discharge.
  • the ion implantation method for preparing inlaid fullerenes has a low yield, and it is difficult to scale up the preparation scale.
  • the experimental device required for the arc discharge method is relatively simple, and is currently the most mature and widely used method for preparing inlaid fullerenes.
  • the metal source directly affects the yield and selectivity of the target product, as well as stability.
  • the invention provides an effective method for preparing water-soluble embedded fullerenes, which is simple and easy to synthesize water-soluble embedded fullerenes of the target product with high yield and selectivity.
  • a method for preparing water-soluble inlaid fullerene comprises the steps of: using a graphite as a cathode, filling a graphite rod of a ThO 2 /graphite powder mixture as an anode, and performing arc discharge in a He atmosphere to obtain an inlaid ⁇ Fuller The olefin is then mixed with hydrogen peroxide and ammonia water, and stirred under heating to prepare water-soluble inlaid fullerene.
  • the invention also discloses a preparation method of inlaid fullerene, comprising the steps of: using graphite as a cathode, filling a graphite rod of a ThO 2 /graphite powder mixture as an anode, performing arc discharge in a He atmosphere, and obtaining an in-line Fullerene.
  • the invention also discloses a contrast agent based on water-soluble embedded fullerene and a preparation method thereof, comprising the steps of: using a graphite as a cathode, a graphite rod filled with a ThO 2 /graphite powder mixture as an anode, and performing an arc in a He atmosphere Discharging, obtaining inlaid fullerene; then mixing inlaid fullerene with hydrogen peroxide, ammonia water, heating and stirring; then filtering, precipitating, washing, and dialysis the obtained solution to obtain water-based inlaid fullerene Contrast agent.
  • the molar ratio of ThO 2 to graphite powder in the ThO 2 /graphite powder mixture is 1:12 to 30; the anode is pretreated at 1000 ° C for 10 hours in an Ar atmosphere and then used for arc discharge.
  • the pressure of the He atmosphere is 2.5 to 4.0 ⁇ 10 4 Pa; and when the arc is discharged, the current is 90 to 100 A.
  • the yield of inlaid fullerenes is greatly increased, accounting for more than 20% of total fullerenes.
  • the distance between the anode and the cathode is 5 to 10 mm.
  • the hydrogen peroxide mass fraction is 30%
  • the ammonia water mass fraction is 25-28%
  • the heating and stirring is stirred at 50 ° C for 3 hours.
  • the invention also discloses water-soluble inlaid fullerene or inlaid fullerene prepared according to the above preparation method.
  • an anode is prepared by mixing an in-line source with graphite powder, and an in-line fullerene is prepared by arc discharge.
  • the in-line source has a great influence on the yield and product performance, such as a target obtained by using isocyanuric acid as a nitrogen source.
  • the yield of the product is low; the synthesis yield of the fluorenyl fullerene is low, the solubility is poor, the separation is difficult, and there is an unpaired electron on the surface of the carbon cage, which is unstable in the air.
  • the invention adopts a spectral pure graphite rod as a cathode and a hollow graphite rod filled with a ThO 2 /graphite powder mixture as an anode.
  • a high temperature arc is generated between the two electrodes, and the anode graphite and the metal crucible are evaporated under high temperature conditions.
  • surface modification mainly using some nucleophilic groups to add carbon cages, thereby forming water-soluble molecules, which can be engulfed into cells, and irradiated in CT contrast agents.
  • the water-soluble inlaid fluorene fullerene of the invention effectively utilizes the effect of the cross-sectional area of the metal atom on the contrast agent, and utilizes the special embedded in the fullerene.
  • the structural characteristics make the embedded heavy metal ions not released into the human body, avoiding the damage of heavy metals to the human body. Therefore, the present invention also discloses the use of the above water-soluble inlaid fullerene or inlaid fullerene in the preparation of a contrast agent and the use of the above-described inlaid fullerene in the preparation of water-soluble inlaid fullerene .
  • the reaction chamber equipped with the electrode is vacuumed, charged into a He atmosphere, and the electrode is subjected to arc discharge in a He atmosphere to prepare an inlaid fullerene Th@C 82 , and the intrinsic rich is extracted by a Soxhlet extractor.
  • the olefins were then surface modified and dialyzed against a dialysis bag to prepare water-soluble inlaid fullerenes.
  • the invention further comprises the steps of separating and purifying the product after the arc discharge is completed: firstly, the obtained fullerene-rich ash is extracted, and then purified by chromatography.
  • the extraction uses a Soxhlet extractor using a solvent such as chlorobenzene or o-dichlorobenzene.
  • the chromatographic method is high performance liquid chromatography, and the column used is Buckyprep.
  • the M column has a mobile phase of toluene at a flow rate of 10 mL/min and a detection wavelength of 330 nm.
  • the dialysis bag used has a molecular weight cutoff of 3,500 and a dialysis time of 3 to 7 days.
  • the ratio of hydrogen peroxide, ammonia water, and inlaid fullerene used is 7 ml: 3 ml: 5 mg; the water-soluble fullerene thus formed can be compatible with the organism to avoid rejection.
  • the preparation method of the water-soluble inlaid fluorene fuller provided by the present invention has the following advantages compared with the prior art:
  • the present invention embeds a metal element lanthanum into a hollow fullerene, and performs surface modification with hydrogen peroxide and ammonia water to form a water-soluble fullerene, which can be attached to various targeting groups through an amino group on the surface.
  • the unique intermediate product has simple production process, high yield and strong operability.
  • the water-soluble substance is stable in nature, the carbon cage is not easily damaged, it will not leak cockroaches, avoiding harm to the human body, and is conducive to the development of subsequent research and development, with great research and development and market. Investment value.
  • FIG. 1 is a graph showing the elution of a toluene solution containing a mixture of inlaid fullerene (Th@C 82 ) on a Buckyprep M column;
  • Example 2 is a mass spectrum of a mixture containing inlaid fullerene (Th@C 82 ) prepared in Example 1;
  • Figure 3 is a partially enlarged view showing the mass spectrum of the mixture containing the inlaid fullerene (Th@C 82 ) in the first embodiment;
  • Figure 4 is an XPS diagram of the water-soluble inlaid fullerene (Th@C 82 ) of Example 1;
  • Figure 5 is a topographical fit of the water-soluble inlaid fullerene (Th@C 82 ) of Example 1;
  • FIG. 6 is an ultraviolet diagram of the first embodiment of the inlaid fullerene (Th@C 82 ) for surface modification;
  • Example 7 is an ultraviolet diagram of the surface modification of the fullerene (Th@C 82 ) embedded in Example 1;
  • Figure 8 is a CT image of a second embodiment of a water-soluble inlaid fullerene-based contrast agent and an existing contrast agent.
  • Chlorobenzene (analytical grade, Shanghai Sinopharm);
  • High temperature tube furnace Hefei Kejing GSL-1500X
  • Vacuum electric arc furnace (Beijing Ticono VDK-250);
  • Ammonia (analytical grade, 25-28%, Aladdin);
  • Hydrogen peroxide (analytical grade, 30%, Aladdin).
  • the pretreated graphite rod is installed in the anode of the vacuum arc furnace and fixed, the furnace cavity is sealed, the vacuum pump is turned on, and the vacuum pump is turned off when the gas pressure is lower than 10 Pa, and the vacuum chamber is turned into a high-purity He gas.
  • the gas pressure in the furnace chamber is about 2.95 ⁇ 10 4 Pa.
  • the inner circle of the arc is green, the outer ring is red, and the temperature is as high as 4000 K or more.
  • Graphite, metal particles, and He gas atomize or form a high-temperature plasma in a high-temperature discharge region, and react with each other in the process of leaving the arc region to recombine fullerene.
  • the power supply is cut off to stop the discharge.
  • the Ar is filled to normal pressure, and the generated ash is collected by the electric arc furnace.
  • the present invention provides synthesis of other inlaid metal sources (Sc, Y (Y), Ti (Ti), Vanadium (V) and lanthanide metals) for comparison. Synthesis of inlaid fullerenes consumes a carbon rod. The time is about one hour, and the yield is 2% to 4%; and the time required for the inlaid fluorene fullerene of the present invention to consume one carbon rod is about 10 Min, the yield is as high as 20%.
  • FIG. 2 and 3 are mass spectra of the above mixture containing indoleful fullerene (Th@C 82 ).
  • Fig. 4 is an XPS diagram of the above water-soluble inlaid fullerene (Th@C 82 );
  • Fig. 5 is a result of peak-matching of the C1s, O1s, and N1s binding energies of the target product, respectively.
  • Figure 6 is a UV diagram after modification of the carbon cage
  • Figure 7 is an ultraviolet absorption peak of Th@C82. It was found that the characteristic absorption peak of Th@C82 disappeared, indicating that the conjugated structure on the surface of the carbon cage was destroyed, and the hydroxyl group and the amine group were attached to the carbon cage.
  • Example 1 The solution obtained in the first step (4) of Example 1 was filtered through a 0.45 um filter, distilled to 1 mL under reduced pressure, and a poor solvent ethanol embedded in water-soluble fullerene was added to precipitate a yellow precipitate, which was collected by centrifugation and washed three times with ethanol.
  • the solid was dissolved in deionized water and dialyzed against a dialysis bag having a molecular weight cutoff of 3,500 to obtain a contrast agent based on water-soluble inlaid fullerene.
  • the obtained contrast agent based on water-soluble inlaid fullerene is CT imaged, and its performance is better than that of iodofluoroalcohol. See Figure 8, the first line of iodofluoroalcohol CT imaging, the second line is based on water solubility. CT imaging of contrast agent embedded in fullerene.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nanotechnology (AREA)
  • Inorganic Chemistry (AREA)
  • Materials Engineering (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Carbon And Carbon Compounds (AREA)

Abstract

本发明公开了水溶性内嵌钍富勒烯及其制备方法与应用。具体而言，该方法首先将配备电极的反应室抽成真空后，充入压力为2.5~3.5×10 4 Pa的He气氛，以光谱纯石墨棒作为阴极，内填ThO 2/石墨粉混合物的空心石墨棒作为阳极，阴阳两极在上述混合气氛中于90~100 A电流强度下进行电弧放电，以制备内嵌钍富勒烯Th@C 82。色谱提纯后，加入双氧水和氨水的混合溶剂（比例为7:3），加热50℃搅拌3h，可制备水溶性的内嵌钍富勒烯。本发明可以将Th@C 82的表面修饰上亲水基团，同时表面的氨基还便于进一步和其它生物活性分子偶联以增加靶向性，达到靶向诊疗的效果，为后续开发提供了广阔的选择空间。

Description

水溶性内嵌钍富勒烯及其制备方法与应用 技术领域
本发明属于材料化学领域，具体涉及水溶性的内嵌钍富勒烯（Th@C 82）及其制备方法与应用。
背景技术
水溶性的内嵌富勒烯是先嵌入金属原子到富勒烯碳笼内部，后对富勒烯表面进行修饰而制成的分子。由于碳笼内金属原子的嵌入，与空心富勒烯和其他内嵌富勒烯的结构以及各种物理化学性质有明显的不同，再通过表面修饰内嵌富勒烯，从而使其具有更加独特优异的性质。根据目前的相关实验结果，已经可以预期这类化合物在生物、医药、材料等领域均具有较广泛的应用前景。
制备内嵌富勒烯的主要方法有：离子注入法和电弧放电法。其中离子注入法制备内嵌富勒烯产量很低，很难放大制备规模。电弧放电法所需的实验装置比较简单，是目前制备内嵌富勒烯最为成熟和广泛应用的方法。在内嵌金属原子簇富勒烯的制备过程中，金属源直接影响目标产物的产率和选择性，以及稳定性。
 技术问题
本发明提供了一种制备水溶性内嵌富勒烯的有效方法，该方法简便易行，能够以较高的收率和选择性来合成目标产物水溶性内嵌富勒烯。
 技术解决方案
具体而言，本发明通过下列技术方案来实现：
一种水溶性内嵌钍富勒烯的制备方法，包括如下步骤，以石墨为阴极、填充ThO 2/石墨粉混合物的石墨棒为阳极，在He气氛中进行电弧放电，得到内嵌钍富勒烯；然后将内嵌钍富勒烯与双氧水、氨水混合，加热搅拌，制备水溶性内嵌钍富勒烯。
本发明还公开了一种内嵌钍富勒烯的制备方法，包括如下步骤，以石墨为阴极、填充ThO 2/石墨粉混合物的石墨棒为阳极，在He气氛中进行电弧放电，得到内嵌钍富勒烯。
本发明还公开了基于水溶性内嵌钍富勒烯的造影剂及其制备方法，包括如下步骤，以石墨为阴极、填充ThO 2/石墨粉混合物的石墨棒为阳极，在He气氛中进行电弧放电，得到内嵌钍富勒烯；然后将内嵌钍富勒烯与双氧水、氨水混合，加热搅拌；然后将得到的溶液过滤、沉淀、洗涤、透析，得到基于水溶性内嵌钍富勒烯的造影剂。
上述技术方案中，所述ThO 2/石墨粉混合物中ThO 2与石墨粉的摩尔比为1:12～30；所述阳极在Ar气氛下于1000 ℃ 预处理10小时再用于电弧放电。
上述技术方案中，所述He气氛的压力为2.5～4.0×10 4 Pa；所述电弧放电时，电流为90～100 A。将内嵌富勒烯的产量大大提高，占总富勒烯的20%以上。
    上述技术方案中，所述电弧放电时，阳极与阴极的间距为5～10 mm。
上述技术方案中，所述电弧放电完成后进行分离纯化，得到内嵌钍富勒烯，具体为首先对灰炱进行萃取，然后采用色谱法进行纯化，得到内嵌钍富勒烯。
上述技术方案中，所述双氧水质量分数为30%，氨水质量分数为25~28%；所述加热搅拌为50℃下搅拌3h。
本发明还公开了根据上述制备方法制备的水溶性内嵌钍富勒烯或者内嵌钍富勒烯。
现有技术用内嵌物源与石墨粉混合制备阳极，电弧放电制备内嵌富勒烯，内嵌物源对产率以及产品性能影响很大，比如以异氰酸胍为氮源得到的目标产物的产率较低；钆基富勒烯的合成产率低、溶解性差、分离困难，并且其碳笼表面还有一个未成对电子，在空气中不稳定。
本发明以光谱纯石墨棒作为阴极、填充ThO 2/石墨粉混合物的空心石墨棒为阳极，在通电以及He气氛的条件下两电极间产生高温电弧，阳极石墨和金属钍在高温条件下蒸发，从而生成内嵌富勒烯；然后再进行表面修饰，主要是应用一些亲核基团对碳笼进行加成，从而形成水溶性的分子，可以通过包吞进入细胞，在CT造影剂方面等放射医学方面有重要的潜在应用价值。相比于目前已有应用于造影剂方面的药物，本发明水溶性的内嵌钍富勒烯既有效利用了金属原子截面积大在造影剂方面的功效，利用了内嵌富勒烯特殊的结构特性，使得内嵌的重金属离子不会释放到人体内，避免了重金属对人体的伤害。因此本发明还公开了上述水溶性内嵌钍富勒烯或者内嵌钍富勒烯在制备造影剂中的应用以及上述内嵌钍富勒烯在制备水溶性内嵌钍富勒烯中的应用。
本发明将配备电极的反应室抽成真空后，充入He气氛，电极在He气氛中进行电弧放电，以制备内嵌钍富勒烯Th@C 82，利用索氏提取器提取出内嵌富勒烯，然后进行表面修饰，通过透析袋透析制备出水溶性的内嵌富勒烯。
本发明在所述电弧放电完成后，还包括对产物进行分离纯化的步骤：首先对所得的富含富勒烯的灰炱进行萃取，然后采用色谱法进行纯化。所述萃取使用索氏提取器，所用的溶剂为氯苯或邻二氯苯。所述色谱法为高效液相色谱法，所用的色谱柱为Buckyprep M柱，流动相为甲苯，流速为10 mL/min，检测波长为330 nm；所用的透析袋为截留分子量为3500，透析时间为3~7天。所用的双氧水、氨水、内嵌钍富勒烯的比例为7ml∶3ml∶5mg；这样形成的水溶性富勒烯可以与生物体相溶，避免出现排斥反应。
 有益效果
由于上述技术方案的运用，本发明提供的水溶性的内嵌钍富勒烯的制备方法与现有技术相比具有如下优点：
（1）本发明将金属元素钍嵌入空心富勒烯中，利用双氧水和氨水进行表面修饰制成可溶于水的富勒烯，可以通过表面的氨基接各种靶向基团，是一种性质独特的中间产物，生产过程比较简单，产率高，可操作性强。
（2）与传统的钍医疗药物相比，该水溶物性质稳定，碳笼不易被破坏，不会泄露钍，避免造成对人体的伤害，有利于后续研发工作的开展，极具科研开发和市场投资价值。
 附图说明
图1为实施例一制备含内嵌钍富勒烯（Th@C 82）的混合物甲苯溶液在Buckyprep M色谱柱上的流出曲线图；
图2为实施例一制备含内嵌钍富勒烯（Th@C 82）的混合物的质谱谱图；
图3为实施例一制备含内嵌钍富勒烯（Th@C 82）的混合物的质谱谱部分放大图；
图4为实施例一水溶性的内嵌钍富勒烯（Th@C 82）的XPS图；
图5为实施例一水溶性的内嵌钍富勒烯（Th@C 82）的XPS分峰拟合图；
图6为实施例一内嵌钍富勒烯（Th@C 82）进行表面修饰前的紫外图；
图7为实施例一内嵌钍富勒烯（Th@C 82）进行表面修饰后的紫外图；
图8为实施例二基于水溶性内嵌钍富勒烯的造影剂与现有造影剂的CT成像图。
 本发明的实施方式
下面结合具体实施例，进一步阐述本发明。应理解，这些实施例仅用于说明本发明而不用于限制本发明的范围。此外应理解，在阅读了本发明讲授的内容之后，本领域技术人员可以对本发明作各种改动或修改，这些等价形式同样落于本申请所附权利要求书所限定的范围。此外，如无特殊说明，下述实施例中所用材料，试剂等均可从商业途径获得。
所需的试剂和仪器如下所述：
光谱纯石墨棒（上海锋溢碳素有限公司）；
石墨粉（含碳量99.95%，青岛金日来石墨有限公司）；
ThO 2（苏州大学放射医学与防护学院）；
氯苯（分析纯，上海国药）；
邻二氯苯（分析纯，上海国药）；
甲苯（分析纯，上海国药）；
高纯气体（苏州成兴工业气体有限公司）；
高温管式炉（合肥科晶GSL-1500X）；
真空电弧炉（北京泰科诺VDK-250）；
高效液相色谱仪（日本分析工业LC-9210NEXT）；
Buckyprep M色谱柱（20×250 mm，日本Nacalai公司）；
质谱仪（Bruker BIFLEX-III，德国布鲁克公司）；X射线光电子能谱仪（美国赛默飞世尔科技公司）；
氨水（分析纯，25-28%，阿拉丁）；
双氧水（分析纯，30%，阿拉丁）。
实施例一
（1）富勒烯的制备：把直径为8 mm，长度为100 mm的实心光谱纯石墨棒钻成内径为6 mm，深度为80 mm左右的空心石墨棒。将ThO 2和石墨粉的混合物（摩尔比为1:24）填充至上述空心石墨棒中并压实。将填充好的石墨棒置于高温管式炉中在高纯Ar气氛下加热至1000℃，保持10个小时，作为阳极。实心光谱纯石墨棒作为阴极。
将预处理过的石墨棒安装在真空电弧炉的阳极并固定，密封炉腔，打开真空泵，将炉腔内抽至气压低于10 Pa时，关闭真空泵，向炉腔内充入高纯He气体，炉腔内气压约为2.95×10 4 Pa。打开循环冷却水，开启电焊机，调节电流至90 A，移动阴极使其与阳极接近，以便产生电弧。由于阳极在电弧中不断蒸发消耗，需移动阴极，使两电极间距离保持在5~10 mm，在这一条件下电弧放电较稳定。在He气氛中，电弧内圈为绿色，外圈为红色，温度高达4000 K以上。石墨、金属颗粒以及He气体在高温放电区域原子化或形成高温等离子体，并在离开电弧区域的过程中相互反应进而重组成富勒烯。阳极石墨棒消耗完全后（大约10分钟），切断电源停止放电，待电弧炉冷却后，充入Ar至常压，打开电弧炉收集产生的灰炱。
（2）富勒烯的提取：使用索式萃取器，用氯苯萃取灰炱中的富勒烯，过滤，除溶剂后得到富含富勒烯的萃取物。
（3）富勒烯的纯化及鉴定：将富含富勒烯的萃取物用甲苯溶解，过滤后用高效液相色谱法（HPLC）进行纯化，得到内嵌钍富勒烯(Th@C 82)，所用的色谱柱为Buckyprep M柱，流动相为甲苯，流速为10 mL/min，检测波长330 nm，C 60、C 70的保留时间最短，约为8-15分钟左右，内嵌钍富勒烯和其他大富勒烯的保留时间较长，大多数在18分钟以上，相应色谱结果如图1所示，收率为20%。
本发明给出其他内嵌金属源（钪（Sc），钇（Y），钛（Ti），钒（V）和镧系金属）合成作为对比，合成内嵌富勒烯消耗一根碳棒的时间约为一个小时，产率为2%～4%；而本发明内嵌钍富勒烯消耗一根碳棒需要的时间大约是10 min，产率高达20%。
（4）富勒烯的表面修饰：称取5mg的内嵌钍富勒烯(Th@C 82)于单口烧瓶中，加入比例为7:3的双氧水和氨水的混合溶液10ml，加热至50℃，搅拌3h，即可生成水溶性的内嵌钍富勒烯，为溶液状态。
图2、图3为上述含内嵌钍富勒烯（Th@C 82）的混合物的质谱谱图。图4为上述水溶性的内嵌钍富勒烯（Th@C 82）的XPS图；图5是对目标产物的 C1s，O1s，N1s 结合能分别进行分峰拟合的结果。图中可以看到三种形式的碳，其中结合能 284.8 eV 处对应的是 C-C 和 C=C 等无氧碳，286.4 eV 处对应的是 C-O、C-N 等与羟基和氨基相连的碳，而 288.2 eV 处则对应于 C=O 等与羰基相连的碳。
图6是碳笼修饰后的紫外图，图7是Th@C82的紫外吸收峰。对比发现Th@C82其特征吸收峰消失，表明碳笼表面的共轭结构被破坏，有羟基和胺基接在碳笼上。
实施例二
将实施例一步骤（4）得到的溶液用0.45um的滤膜过滤，减压蒸馏至1mL，加入水溶性的内嵌钍富勒烯的不良溶剂乙醇，析出黄色沉淀，离心收集并用乙醇洗涤三次，再将固体溶于去离子水，用截留分子量为3500的透析袋进行透析，得到基于水溶性内嵌钍富勒烯的造影剂。后将得到的基于水溶性内嵌钍富勒烯的造影剂进行CT成像，其性能优于碘氟醇，见图8，第一行碘氟醇CT成像图，第二行是基于水溶性内嵌钍富勒烯的造影剂CT成像图。

Claims (10)

  1. 一种水溶性内嵌钍富勒烯的制备方法，其特征在于，包括如下步骤，以石墨为阴极、填充ThO 2/石墨粉混合物的石墨棒为阳极，在He气氛中进行电弧放电，得到内嵌钍富勒烯；然后将内嵌钍富勒烯与双氧水、氨水混合，加热搅拌，制备水溶性内嵌钍富勒烯。
  2. 一种内嵌钍富勒烯的制备方法，其特征在于，包括如下步骤，以石墨为阴极、填充ThO 2/石墨粉混合物的石墨棒为阳极，在He气氛中进行电弧放电，得到内嵌钍富勒烯。
  3. 基于水溶性内嵌钍富勒烯的造影剂的制备方法，其特征在于，包括如下步骤，以石墨为阴极、填充ThO 2/石墨粉混合物的石墨棒为阳极，在He气氛中进行电弧放电，得到内嵌钍富勒烯；然后将内嵌钍富勒烯与双氧水、氨水混合，加热搅拌得到溶液；然后将得到的溶液过滤、沉淀、洗涤、透析，得到基于水溶性内嵌钍富勒烯的造影剂。
  4. 根据权利要求1、2或者3所述的制备方法，其特征在于，所述He气氛的压力为2.5～4.0×10 4 Pa；所述电弧放电时，电流为90～100 A。
  5. 根据权利要求1、2或者3所述的制备方法，其特征在于，所述电弧放电时，阳极与阴极的间距为5～10 mm。
  6. 根据权利要求1、2或者3所述的制备方法，其特征在于，所述电弧放电完成后进行分离纯化，得到内嵌钍富勒烯，具体为首先对灰炱进行萃取，然后采用色谱法进行纯化，得到内嵌钍富勒烯。
  7. 根据权利要求1、2或者3所述的制备方法，其特征在于，所述ThO 2/石墨粉混合物中ThO 2与石墨粉的摩尔比为1∶12～30；所述阳极在Ar气氛下于1000℃预处理10小时再用于电弧放电。
  8. 根据权利要求1所述水溶性内嵌钍富勒烯的制备方法，其特征在于，所述双氧水质量分数为30%，氨水质量分数为25～28%；所述加热搅拌为50℃下搅拌3h。
  9. 根据权利要求1、2或者3所述的制备方法制备的水溶性内嵌钍富勒烯、内嵌钍富勒烯或者基于水溶性内嵌钍富勒烯的造影剂。
  10. 权利要求9所述水溶性内嵌钍富勒烯或者内嵌钍富勒烯在制备造影剂中的应用；权利要求9所述内嵌钍富勒烯在制备水溶性内嵌钍富勒烯中的应用。
PCT/CN2018/083137 2018-04-15 2018-04-15 水溶性内嵌钍富勒烯及其制备方法与应用 Ceased WO2019200501A1 (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/CN2018/083137 WO2019200501A1 (zh) 2018-04-15 2018-04-15 水溶性内嵌钍富勒烯及其制备方法与应用

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2018/083137 WO2019200501A1 (zh) 2018-04-15 2018-04-15 水溶性内嵌钍富勒烯及其制备方法与应用

Publications (1)

Publication Number Publication Date
WO2019200501A1 true WO2019200501A1 (zh) 2019-10-24

Family

ID=68239294

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2018/083137 Ceased WO2019200501A1 (zh) 2018-04-15 2018-04-15 水溶性内嵌钍富勒烯及其制备方法与应用

Country Status (1)

Country Link
WO (1) WO2019200501A1 (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111063604A (zh) * 2020-01-13 2020-04-24 华南师范大学 加热毛细管液体阴极辉光放电电离装置

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104129775A (zh) * 2014-07-16 2014-11-05 苏州大学 一种内嵌钪氧化物团簇富勒烯的制备方法
CN108275672A (zh) * 2018-02-06 2018-07-13 苏州大学 内嵌富勒烯与空心富勒烯的分离方法
CN108298520A (zh) * 2018-04-08 2018-07-20 苏州大学张家港工业技术研究院 水溶性内嵌钍富勒烯及其制备方法与应用

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104129775A (zh) * 2014-07-16 2014-11-05 苏州大学 一种内嵌钪氧化物团簇富勒烯的制备方法
CN108275672A (zh) * 2018-02-06 2018-07-13 苏州大学 内嵌富勒烯与空心富勒烯的分离方法
CN108298520A (zh) * 2018-04-08 2018-07-20 苏州大学张家港工业技术研究院 水溶性内嵌钍富勒烯及其制备方法与应用

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
LI, QU ET AL.: "Study of Rare Earth Encapsulated Carbon Nanomolecules for Biomedical Uses", JOURNAL OF ALLOYS AND COMPOUNDS, vol. 408 -412, 27 June 2005 (2005-06-27), pages 400 - 404, XP027999550 *
MIKAWA, M. ET AL.: "Paramagnetic Water-Soluble Metallofullerenes Having the Highest Relaxivity for MRI Contrast Agents", BIOCONJUGATE CHEMISTRY, vol. 12, no. 4, 27 June 2001 (2001-06-27), pages 510 - 514, XP055136074, DOI: 10.1021/bc000136m *
WANG, YAOFENG ET AL.: "Unique Four-Electron Metal-to-Cage Charge Transfer of Th to a C82 Fullerene Cage: Complete Structural Characterization of Th@C3v(8)-C82", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 139, no. 4, 17 March 2017 (2017-03-17), pages 5110 - 5116, XP055644416 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111063604A (zh) * 2020-01-13 2020-04-24 华南师范大学 加热毛细管液体阴极辉光放电电离装置

Similar Documents

Publication Publication Date Title
CN104129775B (zh) 一种内嵌钪氧化物团簇富勒烯的制备方法
CN108298520B (zh) 水溶性内嵌钍富勒烯及其制备方法与应用
CN106381143B (zh) 批量绿色合成氮、磷掺杂荧光碳点的方法
Hu et al. Recent advances in the synthesis and applications of carbon dots
US20030065206A1 (en) Derivatization and solubilization of insoluble classes of fullerenes
CN107522190B (zh) 一种碳量子点的合成方法
JP3926331B2 (ja) 金属内包フラーレン類及びその他のフラーレン類の化学的精製方法
CN109399607B (zh) 一种通过微波法快速合成两亲性碳量子点的制备方法
Sun et al. Improved extraction of metallofullerenes with DMF at high temperature
Wei et al. Microplasma electrochemistry (MIPEC) strategy for accelerating the synthesis of metal organic frameworks at room temperature
CN106268887B (zh) 一种复合光催化剂CdS/LaPO4及其制备方法和应用
WO2019200501A1 (zh) 水溶性内嵌钍富勒烯及其制备方法与应用
CN102205958B (zh) 内嵌氮化物原子簇富勒烯的制备方法
EP3792273A1 (en) Refining method for vasopressin
CN111286322A (zh) 能够即时可视化检测次氯酸的碳点及其制备方法和应用
CN114213345A (zh) 一种从碳量子点中分离出黄色荧光物质的方法
CN109456269B (zh) 内嵌钍富勒烯衍生物及其制备方法和应用
Kaiming et al. Green preparation and application of carbon quantum dots
WO2015156385A1 (ja) ホウ素化合物を内包および外壁に担持するカーボンナノホーン及びその製造方法
CN104910904B (zh) 一种以磺化煤为碳源通过臭氧氧化光还原技术简单快速制备荧光碳量子点的方法
CN109734074B (zh) 一种内包金属氮化物簇富勒烯及其制备方法
CN113023690B (zh) 金属氮化物内嵌富勒烯及其制备方法
CN112569997B (zh) 纳米氮碳材料及其制备方法和环烷烃的催化氧化方法
JP2005289755A (ja) 原子または分子を内包する内包フラーレンの製造方法およびそれにより得られる内包フラーレン
Huo et al. High-Efficiency Synthesis of Giant Fullerenes from Single-Carbon Molecules

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 18915672

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 18915672

Country of ref document: EP

Kind code of ref document: A1