Water-soluble functionalized fullerenes

Once functionalized, the toxic effects of CNTs are lowered. The increased compatibility with cells may arise from increased hydrophilicity. A study compared fullerenes(C6o) functionalized with a varying degree of oxygen-containing functional groups. The report shows that as the water-solubility of fullerene increases, the cytotoxicity in cells significantly decreases. Although this study was conducted with it is a representative model and an important parallel to work with CNTs. 

Fullerene Cgo also functions efficiently as an antioxidant, actually being better than other lipid-soluble antioxidants at scavenging reactive oxygen species (ROS) (Wang et al., 1999). Water-soluble derivatives of C o, such as a poly-hydroxyl form, are able to function in the same respect in aqueous environments. 

In addition, the use of appropriate hydrophilic constituents on the aldehyde or glycine reactants can result in excellent water solubility of the (To derivative. Two such modification arms can be added simultaneously to the pyrrolidine ring, thus providing a functional group for further conjugation and a hydrophilic arm for increased water solubility. PEG derivatives have been formed in this manner, which create highly soluble fullerene derivatives. 

Various commercial suppliers now offer fullerene derivatives with functionalities available for bioconjugation, including carboxylic and poly-hydroxylic derivatives, which are very hydrophilic and water-soluble (BuckyUSA, NanoLab, NanoNB, Nano-C, and Aldrich). 

In principle, there are four basic strategies to compensate for the repulsive effects between the hydrophobic fullerene surface and water (a) encapsulation in the internal hydrophobic moiety of water-soluble hosts like cyclodextrins (Andersson et al., 1992 Murthy and Geckeler, 2001), calixarenes (Kunsagi-Mate et al., 2004) or cyclotriveratrylenes (Rio and Nierengarten, 2002) (b) supramolecular or covalent incorporation of fullerenes or derivatives into water-soluble polymers (Giacalone and Martin, 2006) or biomolecules like proteins (Pellarini et al., 2001 Yang et al., 2007) (c) suspension with the aid of appropriate surfactants and (d) direct exohe-dral functionalization in order to introduce hydrophilic moieties. 

In recent years, a great diversity of structurally well-defined functionalized fullerenes has been designed and synthesized for that purpose. Some of them exhibit pronounced solubility in water (vide infra). But even for compounds being virtually insoluble in water, stable aqueous phases can be obtained in plenty of cases by diluting stock solutions of the compounds in polar organic solvents with various amounts of water. Notably, dimethyl sulfoxide (DMSO) and tetrahydro-furan (THF) have turned out to be excellent surfactants for preparing stable aqueous fullerene solutions (Angelini et al., 2005 Cassell et al., 1999 Da Ros et al., 1996 Gun kin et al., 2006 Illescas et al., 2003). Also cosolvents such as dimethylforma-mide (DMF) and methanol can be used to promote water solubility. After subsequent dilution of a saturated solution of C60 in benzene with THF, acetone and finally water, actually stable aqueous suspensions of pristine fullerene can be obtained (Scrivens et al., 1994). 

The two most commonly used derivatization methods for exohedral functionalization are the nucleophilic cyclopropanation with malonates (Bingel, 1993) and the formation of fulleropyrrolidines (Maggini et al., 1993). Both of these protocols have been used extensively to produce water-soluble fullerenes for biomedical applications. Other stable water-soluble fullerene adducts have also been reported (Hirsch and Brettreich, 2005). Sections 3.2.2-3.2.5 will give a short overview on the state-of-the-art of water-soluble fullerene derivatives and outline some general trends for designing such molecular structures. 

In conclusion, by varying the number and kind of the attached substructures for exohedrally functionalized fullerenes the solubility in water can be fine-tuned. From a pharmacological point of view, a well-balanced arrangement of both hydrophilic and lipophilic behaviour is required in order to achieve favourable biodistribution. Amphiphilic monoadducts containing long lipophilic alkyl chains like 8 are promising candidates for potential medical applications. 

The second way to prepare water soluble fullerenes is by adding functional groups to the molecules exterior (Brettreich and Hirsch, 1998 Foley et al., 2002b Guldi et al., 1999 Nakajima et al., 1996 Rajagopalan et al., 1996 Sayes et al., 2004 Wang et al., 1999). Numerous efforts have pushed for fullerene functionalization to be the most useful way to make water soluble fullerenes. Fullerene functionalization... 

As with fullerenes, carbon nanotubes are also hydrophobic and must be made soluble for suspension in aqueous media. Nanotubes are commonly functionalized to make them water soluble although they can also be non-covalently wrapped with polymers, polysaccharides, surfactants, and DNA to aid in solubilization (Casey et al., 2005 Kam et al., 2005 Sinani et al., 2005 Torti et al., 2007). Functionalization usually begins by formation of carboxylic acid groups on the exterior of the nanotubes by oxidative treatments such as sonication in acids, followed by secondary chemical reactions to attach functional molecules to the carboxyl groups. For example, polyethylene glycol has been attached to SWNT to aid in solubility (Zhao et al., 2005). DNA has also been added onto SWNT for efficient delivery into cells (Kam et al., 2005). 

Contrary to the electron transfer in organic solvents, the reduction process of functionalized fullerenes in aqueous solutions is very complex. Although some adducts are sufficiently water-soluble (Fig. 22) no reduction could be observed [181,183,187], This is attributed to the irreversible formation of fullerene clusters in aqueous media, which seem to prevent electron transfer. Consequently, efficient triplet-triplet annihilation within the clusters is observed resulting in short triplet lifetimes (< 0.1 (xs compared to microseconds for their monomeric analogue) [182,187],... 

Fullerenes are widely investigated with the respect to their interesting physical properties for the one hand and their biological activity for the other hand. It is clear that for medical and biological applications the fullerenes must be solved in water in any way. It is well known that fullerenes are not soluble in water per se [1], That is why most attention is presently paid to investigation of water-soluble C6o derivatives, which, in turn, can be able to form colloidal solutions. Mono-functional fullerene Ceo derivatives have the... 

Fullerenes and their water soluble derivatives are of great deal interest for scientific research due to their biological activity [1]. Therefor, the problems of modification and functionalization of nanomaterials to obtain their water soluble derivatives are very challenging task. In present work we have investigated low-temperature y -induced copolymerization of vinyl monomers such as acrylamide and acrylic acid with fullerene C6o to obtain their water soluble polymers containing fullerene. 

Viable means of overcoming the insolubility of pristine fullerenes in polar solvents involve (i) incorporation of pristine fullerenes into the hydrophobic cavity of water-soluble host structures (e.g. cyclodextrin [77, 78], surfactants [79-82], and vesicles [81, 83, 84], or (ii) functionalization of the fullerene core with hydrophilic addends (e.g. C6oC(COO-)2, C60 [C(0CH2CH2)3CH3]2, C6o(C4HioN+), etc.) [2]... 

Because monofunctionalization of fullerenes shows that a single hydrophilic addend is insufficient to prevent the strong hydrophobic interactions among the compounds [89, 90, 93, 94], multiple functionalized derivatives were examined as water-soluble probes. In particular, introduction of a second hydrophilic ligand (e.g., pyrrolidinium salts or carboxylates) to the fullerene core enhances the surface coverage of the hydrophobic fullerene surface. In turn, it was expected that fullerene aggregation might be suppressed. It should be stated that these water-soluble derivatives are important alternatives to the y-CD-incorporated and surfactant-embedded fullerenes. 

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