134
4 Applications of Nitrile Imine Derivatives
[128]. When the NI is present in excess, it was shown that each [60]fullerene molecule
was able to undergo multiple cycloaddition reactions.
Other carbon allotropes have also been shown to act as NI dipolarophiles, such as
carbon nanotubes (CNTs) [129]. This was first accomplished by Garcia and Langa
in 2004, with the synthesis of two analogues using an electron-rich and an electronpoor NI, following on from an initial theoretical study by Lu one year earlier [129,
130]. Relatively forcing conditions were required to ensure competent cycloaddition,
employing hydrazonyl chlorides as an NI precursor. Recent computational efforts
from Zhao have elucidated that cycloaddition may be accelerated by Stone-Wales
defects [131] within the nanotube, however this has yet to be experimentally confirmed [132]. This chemistry was applied in the development of a gold nanoparticlefunctionalised CNT in 2014, by Hamme II [133]. Cycloaddition between the NI,
again generated via the hydrazonyl halide, and the CNT furnished intermediates that
were then further functionalised by the nanoparticles (Scheme 4.41). The resulting
hybrids were successfully shown to exhibit anti-bacterial properties through detection
of E. Coli and adhesion to the surface of the bacteria.
Additionally, graphene may behave as a compatible substrate within NI chemistry [134]. Treatment of exfoliated graphene flakes with an appropriate hydrazonyl
chloride was shown to furnish the desired adducts under microwave irradiation at
170 °C for one hour (Scheme 4.42). Interestingly, conventional heating under otherwise identical reaction conditions required 6 days to reach completion, highlighting
the importance of the microwave to the methodology. Computational data reported
in the same article indicated that the NI dipole would react preferentially with the
edge of the graphene sheet, as opposed to the more heavily substituted internal sites.
4.3.4 Surface Chemistry
Surface chemistry, at the interface of small molecule and macromolecular research, is
a diverse field with broad applications throughout materials science. Within the past
ten years, the NI dipole has become a popular ligation agent in this area [135]. This
approach to surface modification is attractive to researchers owing to the orthogonality and high reactivity of the procedure, with the additional benefit that the NI may be
generated using only UV light if using a tetrazole as a precursor. The most straightforward example of this application is the immobilisation of a polymer onto the surface
of an organic or inorganic network. This was first exemplified in two independent
publications from Barner-Kowollik and Nallani and Liedberg in 2011 [136, 137]. The
former modified a silicon wafer and a sample of cellulose with a 2,5-tetrazole moiety, which were then exposed to UV light in the presence of a poly(methyl)acrylate
derivative capped with a maleimide dipolarophile (Scheme 4.43). The liberated NI
rapidly formed the desired cycloadduct, attaching the polymer to the surface. Nallani and Liedberg demonstrated similar reactivity in the ligation of the horseradish
peroxidase enzyme to the surface of a polymersome, a synthetic replica of liposomes
[138].
4 Applications of Nitrile Imine Derivatives
[128]. When the NI is present in excess, it was shown that each [60]fullerene molecule
was able to undergo multiple cycloaddition reactions.
Other carbon allotropes have also been shown to act as NI dipolarophiles, such as
carbon nanotubes (CNTs) [129]. This was first accomplished by Garcia and Langa
in 2004, with the synthesis of two analogues using an electron-rich and an electronpoor NI, following on from an initial theoretical study by Lu one year earlier [129,
130]. Relatively forcing conditions were required to ensure competent cycloaddition,
employing hydrazonyl chlorides as an NI precursor. Recent computational efforts
from Zhao have elucidated that cycloaddition may be accelerated by Stone-Wales
defects [131] within the nanotube, however this has yet to be experimentally confirmed [132]. This chemistry was applied in the development of a gold nanoparticlefunctionalised CNT in 2014, by Hamme II [133]. Cycloaddition between the NI,
again generated via the hydrazonyl halide, and the CNT furnished intermediates that
were then further functionalised by the nanoparticles (Scheme 4.41). The resulting
hybrids were successfully shown to exhibit anti-bacterial properties through detection
of E. Coli and adhesion to the surface of the bacteria.
Additionally, graphene may behave as a compatible substrate within NI chemistry [134]. Treatment of exfoliated graphene flakes with an appropriate hydrazonyl
chloride was shown to furnish the desired adducts under microwave irradiation at
170 °C for one hour (Scheme 4.42). Interestingly, conventional heating under otherwise identical reaction conditions required 6 days to reach completion, highlighting
the importance of the microwave to the methodology. Computational data reported
in the same article indicated that the NI dipole would react preferentially with the
edge of the graphene sheet, as opposed to the more heavily substituted internal sites.
4.3.4 Surface Chemistry
Surface chemistry, at the interface of small molecule and macromolecular research, is
a diverse field with broad applications throughout materials science. Within the past
ten years, the NI dipole has become a popular ligation agent in this area [135]. This
approach to surface modification is attractive to researchers owing to the orthogonality and high reactivity of the procedure, with the additional benefit that the NI may be
generated using only UV light if using a tetrazole as a precursor. The most straightforward example of this application is the immobilisation of a polymer onto the surface
of an organic or inorganic network. This was first exemplified in two independent
publications from Barner-Kowollik and Nallani and Liedberg in 2011 [136, 137]. The
former modified a silicon wafer and a sample of cellulose with a 2,5-tetrazole moiety, which were then exposed to UV light in the presence of a poly(methyl)acrylate
derivative capped with a maleimide dipolarophile (Scheme 4.43). The liberated NI
rapidly formed the desired cycloadduct, attaching the polymer to the surface. Nallani and Liedberg demonstrated similar reactivity in the ligation of the horseradish
peroxidase enzyme to the surface of a polymersome, a synthetic replica of liposomes
[138].