Covalent Functionalization of Multilayer Fullerenes (CarbonNano-Onions) using a Fluorescein-modified PolyethyleneGlycol Chain
ABSTRACTTwo contrasting methods for covalently functionalizingmultilayer fullerenes (carbon nano-onions) using a fluo-rescein-terminated polyethylene glycol (PEG) chain weredesigned and carried out. The first involved independentsynthesis of the fluorescein-PEG molecule with subsequentattachment to the carbon nano-onion, while the second in-volved its stepwise construction on the carbon nano-onionsurface. Subsequent characterization was used to compareand contrast both the effectiveness and efficiency of theabove methods. The resulting species display significantlyenhanced solubility and, with further functionalization,may have potentially attractive biomedical applications.
The extensive research and interest revolving around syntheticcarbon allotropes in the past two decades owes much to the dis-covery of the buckminsterfullerene in 1985
and carbon nanotubes(CNTs) in 1991
. The period described as the
has also seen the discovery of other, less fa-miliar carbon nanostructures such as the multilayer fullerene
,more commonly referred to as the carbon nano-onion (CNO) dueto its shell-like structure. It is reasonable to conclude that CNOshave not been subjected to similar research efforts as their fulle-rene or CNT relatives based upon the limited publications dealingwith these curious allotropes. However, despite this, possessionof several singular properties such as a graphene-like network of carbon atoms, a large surface area to volume ratio (934 m
/kg), lowdensity and a multilayer morphology
mean CNOs are indepen-dently beginning to generate increasing interest regarding potentialapplications.A further advantage of CNOs is the diversity of their chemistry.Depending upon their method of formation, different trends inreactivity are apparent when dealing with CNOs. Small CNOs (6
8 shells, produced through annealing of nanodiamonds
) behavechemically in a manner similar to fullerenes, being predominantlyreactive towards nucleophiles. Their reactivity tends to decreasewith increasing shell number, however, as less strain is incurred onthe outermost surface and so larger CNOs (20
30 shells, pro-duced through arc discharge of graphite
) display a graphite-likereactivity.
Unlike CNTs, no helicity arises within the structure of a nano-onion and so the reactivity of a given sample is generallyuniform.This diversity in chemical reactivity is important when exploringpotential applications for CNOs. Applications in catalysis
, elec-tromagnetic shielding
, gas storage
and optical limiting
havebeen investigated previously. However, biomedical applicationsfor CNOs are essentially non-existent due to the ambiguity sur-rounding their cytotoxicity. Equally, like CNTs, CNOs displaypoor solubility and dispersibility in aqueous and organic solventsand so, in their pristine form, are not ideal biomedical agents.However, given the contrasts in reactivity between CNOs of dif-ferent sizes, a wide variety of methods are viable to chemicallyfunctionalize the surface of a CNO with simple hydrophilic moie-ties and subsequently increase its solubility. Methods previouslysuccessful in this regard include the 1,3-dipolar cycloaddition,
[2 + 1] cycloaddition of nitrenes
or therecently developed
Overcoming solubility issues gives rise to numerous biomedicalpossibilities involving CNOs. In our work, we explored the no-tion of CNOs as a novel cellular imaging unit or an agent of drugdelivery through design and synthesis of CNOs chemically func-tionalized with a fluorescein-terminated polyethylene glycol(PEG) chain. Initial functionalization involved the introduction of benzoic acid moieties onto the external surface of the CNOs
diazonium generation by Flavin
(Scheme 1). Whilst increasing the relative solubility of the sample,the modified CNOs also retained the potential for further functio-nalization. Exploiting this, two methods were investigated forintroduction of the fluorescein-PEG (Figure 1) onto the CNOsurface:1.
independent construction of the fluorescein-PEG andsubsequent attachment (through the formation of anamide bond) to the benzoic acid-functionalized CNOs.2.
stepwise construction of the fluorescein-PEG on thesurface of the benzoic acid-functionalized CNOs.In characterizing the resulting species, we considered not only theeffectiveness, but equally the efficiency, of each method in cova-lently functionalizing the CNOs.