DOI: 10.1002/chem.201402289
Communication
&
Magnetic Antioxidants
Linking an a-Tocopherol Derivative to Cobalt(0) Nanomagnets:
Magnetically Responsive Antioxidants with Superior Radical
Trapping Activity and Reduced Cytotoxicity
[
a]
[a]
[a]
[b]
Caterina Viglianisi, Veronica Di Pilla, Stefano Menichetti,* Vincent M. Rotello,
[c]
[c]
[d]
Gabriele Candiani, Chiara Malloggi, and Riccardo Amorati*
medical applications of NPs, such as targeted drug delivery or
contrast agents, that require to avoid the use of intrinsically cy-
Abstract: Covalent attachment of a phenolic antioxidant
analogue of a-tocopherol to graphite-coated magnetic
cobalt nanoparticles (CoNPs) provided a novel magnetical-
ly responsive antioxidant capable of preventing the autox-
idation of organic materials and showing a reduced toxici-
ty toward human cells.
[7a–b]
totoxic materials.
Linking antioxidants to NPs may there-
fore represent a new strategy to reduce the toxicity of NPs.
Herein, we report the synthesis, the study of the chain-
breaking antioxidant activity and the evaluation of the toxicity
in human cells of graphite-coated cobalt magnetic NPs
[8]
(
CoNPs) covalently linked to a phenolic vitamin E analogue
antioxidant. These CoNPs have been recently proposed for
[9]
[10]
many applications including catalysis, water purification,
[11]
Antioxidants are actively investigated not only for technologi-
cal purposes (i.e., for the stabilization of plastic, oils, and
and in vivo blood detoxification, and represent a promising
scaffold to obtain novel “magnetic antioxidants”. Our results
enlighten an unexpected role of NPs in increasing the radical
scavenging, and suggest a possible role of the pendant vita-
min E analogue in the reduction of the cytotoxicity of CoNPs.
Magnetic CoNPs functionalized with azido moieties (CoNPsÀ
[
1a–c]
food)
but also because they can modulate the redox bal-
ance inside the cells, and can thus influence some important
biological processes, such as oxidative damage and cell death
[
2a,b]
in a wide range of pathologies.
Engineered nanoparticles
(NPs) have recently emerged as an innovative and little ex-
N ), were purchased from TurboBeadsꢀ, Switzerland. The nano-
3
plored method to obtain novel antioxidants with enhanced
characteristics. For instance, bio-degradable NPs have been
used to improve the bioavailability of natural antioxidants
particles have a metallic cobalt core, with a diameter of about
30 nm, coated by approximately three layers of graphitic
[8]
carbon that render them air stable. In CoNPsÀN , the concen-
3
[
3a–c]
À1 [9]
(
such as curcumin),
and a covalent link between SiO ÀNPs
tration of azido functional groups is about 0.1 mmolg .
2
[8]
and gallic acid was proposed for reducing its leaching and vol-
From the density of the CoNPs and their mean radius, we
[
4]
atility. Cerium oxide NPs (nanoceria) have been shown to be
powerful antioxidants in biological systems acting as superox-
could calculate that about 6000 -N groups are attached to
3
each CoNP. Preliminary experiments showed that these CoNPs
(either with or without the azido functionalization) were inert
toward the reaction with tert-butylhydroperoxide, a model for
the hydroperoxides often present in organic materials (see the
Supporting Information). The graphite layers efficiently isolate
the metallic core, avoiding the pro-oxidant activity arising from
homolytic decomposition of hydroperoxides, commonly ob-
[
5]
ide dismutase mimics. Additionally, the generation of free
radicals and the induction of oxidative stress have been in-
voked to rationalize the toxicity of many types of NPs in bio-
[
6a–f]
logical systems.
This is a particularly serious limitation to
[
a] Dr. C. Viglianisi, V. D. Pilla, Prof. S. Menichetti
Department of Chemistry “U. Schiff’’, Universitꢀ di Firenze
Via della Lastruccia, 3-13, 50019, Sesto Fiorentino (Italy)
Fax: (+39)055-4573531
[12]
served for magnetic NPs. For use in our studies the CoNPsÀ
N were covalently linked to selected alkynes using an azide–
3
E-mail: stefano.menichetti@unifi.it
alkyne cycloaddition catalyzed by CuI (CuAAC) under reaction
conditions previously reported for similar multi functionalized
[
b] Prof. V. M. Rotello
[9]
Department of Chemistry, University of Massachusetts
systems (Scheme 1).
7
10 North Pleasant St., Amherst, MA, 01003 (USA)
Two particles were generated for our study. A control parti-
[
c] Dr. G. Candiani, C. Malloggi
Department of Chemistry
Materials and Chemical Engineering “Giulio Natta”
Politecnico di Milano, Via Mancinelli 7, 20131 Milano (Italy)
cle (CoNPsÀOct) was obtained through reaction of CoNPsÀN
3
with 1-octyne (Oct). The terminal acetylenic antioxidant por-
tion (TOH) was obtained by condensing undec-10-yn-1-ol with
Trolox, a phenolic antioxidant analogue of a-tocopherol (the
[
d] Dr. R. Amorati
[1]
Department of Chemistry “Ciamician”, University of Bologna
Via San Giacomo 11, 40126 Bologna (Italy)
Fax: (+39)051-209-5688
main and more active component of vitamin E). The resulting
alkyne TOH was then reacted with CoNPsÀN in toluene under
3
ultrasound irradiation (that was a safe operation for TOH pend-
ants, see the Supporting Information for details) as depicted in
Scheme 1. The conjugated CoNPsÀOct and CoNPsÀTOH were
E-mail: riccardo.amorati@unibo.it
Supporting information for this article is available on the WWW under
Chem. Eur. J. 2014, 20, 6857 – 6860
6857
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim