Topics in Current Chemistry (2020) 378:15
1 3
2.1.1.4 Cycloaddition Cycloadditions are another important way of functionalizing
the walls of nanotubes to tune their biocompatibility and biodegradability, both crucial characteristics to perform in vivo studies. Delgado and colleagues [71] described
for the first time the [4 + 2] Diels–Alder reaction of o-quinodimethane assisted by
microwaves on SWCNT surface (Scheme 3). More recently, anhydride-functionalized CNTs were produced using a cascade of Diels–Alder cycloaddition reactions
employing 1,3-butadiene generated from 3-sulfolene in the presence of atmospheric
oxygen [72].
A very versatile methodology uses 1,3-dipolar cycloadditions between the nanotube and azomethine ylides generated in situ by condensation of α-amino acids and
aldehydes [73, 74]. This approach yields bi-substituted pyrrolidines and highly functionalized CNTs (Scheme 4) [75, 76]. Using this strategy, Calcio Guadino et al. [77]
obtained multi-decorated SWCNTs in a single step. Single microwave-assisted grafting reaction labels nanotubes’ surface with amino acidic β-cyclodextrin derivative
and the (1,4,7,10-tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid monoamide)
moiety with a 1:1 ratio.
2.1.2 Defect Functionalization
Defect functionalization makes use of the structural weaknesses of CNTs to create
new bonds. Although nanotubes are highly unreactive, all the preparation methods to
obtain them leave some defects in their structure, both in the lateral walls and in the
tips. Among the lateral walls, these defects include dipoles of heptagon–pentagon
pairs in the hexagonal network called Stone–Wales defects, sp
3
-hybridized defects,
and vacancies in the sp
2
network [45]. The nanotube’s ends are usually closed with
fullerene, presenting mixed pentagonal–hexagonal structures more reactive than the
pristine lateral walls [45]. Defect functionalization employs these intrinsic defects
or generates new ones on the nanotube structure, normally by aggressive oxidative
processes either in liquid or gas phase, or by electrochemical oxidation [78]. This
approach has the advantage of generating more functional groups, but also implies
higher structural damage. Using less aggressive oxidative approaches, the structural
damage is minimized preserving CNT’s properties [79]. Defect functionalization
can be classified according to the nature of the chemical transformation occurring at
the defect sites, like oxidation, amidation, thiolation, etc. These attached functional
groups are normally used as the starting point for further derivatization [80].
Oxidation and carboxyl-based coupling constitutes one of the most relevant strategies for CNTs functionalization, including the formation of esters [81, 82], amides
[83], and ammonium carboxylate salts [84]. This modification is achieved in a twostep process. The first one often involves the treatment of commercially available
carbon nanotubes with a mineral acid [85] such as nitric acid [86] or a sulfonitric
mixture [87]. This step shortens CNTs, narrowing length distribution [88], and
reduces the metal concentration left from their synthesis, decreasing toxicity and
improving the preclinical possibilities. Nanotube defects will suffer the effects of
the oxidant creating carboxylic and other oxygen-bearing groups [85]. The second
step occurs via carboxylic acid formation, and can be carried out using two methodologies: (1) employing in situ acid chloride formation with thionyl chloride and
184
Reprinted from the journal
1 3
2.1.1.4 Cycloaddition Cycloadditions are another important way of functionalizing
the walls of nanotubes to tune their biocompatibility and biodegradability, both crucial characteristics to perform in vivo studies. Delgado and colleagues [71] described
for the first time the [4 + 2] Diels–Alder reaction of o-quinodimethane assisted by
microwaves on SWCNT surface (Scheme 3). More recently, anhydride-functionalized CNTs were produced using a cascade of Diels–Alder cycloaddition reactions
employing 1,3-butadiene generated from 3-sulfolene in the presence of atmospheric
oxygen [72].
A very versatile methodology uses 1,3-dipolar cycloadditions between the nanotube and azomethine ylides generated in situ by condensation of α-amino acids and
aldehydes [73, 74]. This approach yields bi-substituted pyrrolidines and highly functionalized CNTs (Scheme 4) [75, 76]. Using this strategy, Calcio Guadino et al. [77]
obtained multi-decorated SWCNTs in a single step. Single microwave-assisted grafting reaction labels nanotubes’ surface with amino acidic β-cyclodextrin derivative
and the (1,4,7,10-tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid monoamide)
moiety with a 1:1 ratio.
2.1.2 Defect Functionalization
Defect functionalization makes use of the structural weaknesses of CNTs to create
new bonds. Although nanotubes are highly unreactive, all the preparation methods to
obtain them leave some defects in their structure, both in the lateral walls and in the
tips. Among the lateral walls, these defects include dipoles of heptagon–pentagon
pairs in the hexagonal network called Stone–Wales defects, sp
3
-hybridized defects,
and vacancies in the sp
2
network [45]. The nanotube’s ends are usually closed with
fullerene, presenting mixed pentagonal–hexagonal structures more reactive than the
pristine lateral walls [45]. Defect functionalization employs these intrinsic defects
or generates new ones on the nanotube structure, normally by aggressive oxidative
processes either in liquid or gas phase, or by electrochemical oxidation [78]. This
approach has the advantage of generating more functional groups, but also implies
higher structural damage. Using less aggressive oxidative approaches, the structural
damage is minimized preserving CNT’s properties [79]. Defect functionalization
can be classified according to the nature of the chemical transformation occurring at
the defect sites, like oxidation, amidation, thiolation, etc. These attached functional
groups are normally used as the starting point for further derivatization [80].
Oxidation and carboxyl-based coupling constitutes one of the most relevant strategies for CNTs functionalization, including the formation of esters [81, 82], amides
[83], and ammonium carboxylate salts [84]. This modification is achieved in a twostep process. The first one often involves the treatment of commercially available
carbon nanotubes with a mineral acid [85] such as nitric acid [86] or a sulfonitric
mixture [87]. This step shortens CNTs, narrowing length distribution [88], and
reduces the metal concentration left from their synthesis, decreasing toxicity and
improving the preclinical possibilities. Nanotube defects will suffer the effects of
the oxidant creating carboxylic and other oxygen-bearing groups [85]. The second
step occurs via carboxylic acid formation, and can be carried out using two methodologies: (1) employing in situ acid chloride formation with thionyl chloride and
184
Reprinted from the journal