Tailor-Made Polydiacetylene Micelles for the Catalysis of 1,3-Dipolar Cycloadditions in Water

Article abstract of DOI:10.1002/adsc.202000795

A colloidal catalyst was developed by complexation of copper chloride in polydiacetylene micelles. The latter were designed to accommodate and stabilize copper salts, by providing a suitable ligand environment. Micelles were valorized as nanoreactors for

Full text of DOI:10.1002/adsc.202000795

Title: Tailor-Made Polydiacetylene Micelles for the Catalysis of 1,3-
Dipolar Cycloadditions in Water
Authors: Ramar Arun Kumar, Dhanaji Jawale, Emmanuel Oheix,
Valerie Geertsen, Edmond Gravel, and Eric Doris
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.202000795
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10.1002/adsc.202000795
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Tailor-Made Polydiacetylene Micelles for the Catalysis of 1,3-
Dipolar Cycloadditions in Water
Ramar Arun Kumar,a,b Dhanaji V. Jawale,a Emmanuel Oheix,a Valérie Geertsen,c
Edmond Gravela* and Eric Dorisa*
a
Université Paris-Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), SCBM,
91191 Gif-sur-Yvette, France. Tel: +33-169 08 80 71, fax: +33-169 08 79 91, edmond.gravel@cea.fr; eric.doris@cea.fr
SRM Research Institute, Department of Chemistry, SRM Institute of Science and Technology, Kattankulathur, 603203
b
Chennai, India.
c
Université Paris-Saclay, CEA, CNRS, NIMBE, 91191 Gif-sur-Yvette, France.
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.
Abstract.
A
colloidal catalyst was developed by
complexation of copper chloride in polydiacetylene micelles.
The latter were designed to accommodate and stabilize
copper salts, by providing a suitable ligand environment.
Micelles were valorized as nanoreactors for the promotion of
the Huisgen cycloaddition reaction in water thanks to their
central hydrophobic core which permitted not only aqueous
dispersion, but also concentration of the reagents at the
vicinity of the catalyst. The system was found to be active on
a variety of substrates and efficiently operated under
sustainable conditions.
Keywords: Micelle; Click; Polydiacetylene; Water solvent;
Sustainable
concentration higher than the critical micelle
concentration (CMC), amphiphiles aggregate into
spherical structures with a hydrophilic outer layer,
interfacing with water, and a central hydrophobic
core. Micelles are valuable tools for organic
transformations, including 1,3-dipolar cycloadditions,
conducted in aqueous medium[10] as the lipophilic
core of the micelles can accommodate hydrophobic
Introduction
The azide-alkyne 1,3-dipolar cycloaddition[1] is a
widely used “click” reaction that has been exploited
in various domains.[2] This [3 + 2] cycloaddition
reaction has originally been disclosed by Huisgen
who reported, in his 1963 paper, a thermally activated
process.[3] More recent developments have led to the
discovery of the copper-catalyzed azide−alkyne 1,3-
dipolar cycloaddition (CuAAC).[4] The CuAAC offers
some key advantages over thermal activation such as
molecules,
concentration.[11]
Our group
allowing
their
dispersion
and
previously developed
stable
polydiacetylene (PDA) micelles made from the self-
assembly of diacetylene (DA) amphiphiles and
milder
operating
conditions,
improved
regioselectivity, and better functional group tolerance. photo-polymerized under UV irradiation.[12] The
In the CuAAC, a Cu(I) catalyst is typically used in a
mixture of aqueous and organic solvents. As copper
salts can be toxic to biological systems and are
difficult to remove from reaction mixtures, copper-
free variants, involving cyclooctynes, have also
emerged.[5] Yet, the strained cyclooctynes lack of
chemoselectivity and are tricky to synthesize.[6]
With the aforementioned features in mind and as
part of our longstanding interest in the development
of catalytic systems,[7] we report here an original
formulation of copper salts that were embedded in
stable polydiacetylene micelles for the promotion of
the [3 + 2] cycloaddition reaction in fully aqueous
medium.[8]
resulting PDA-micelles are robust and fully
insensitive to dilution.[13]
The objective of the present work was accordingly
to i) design amphiphilic diacetylene units capable of
behaving as ligands for copper salts, ii) assemble
stable polydiacetylene micelles containing copper,
and iii) evaluate the hybrid micellar assembly as
nanoreactor[14] for the catalysis of the 1,3-dipolar
cycloaddition reaction in water. In addition, easy
recovery/removal of the catalyst was anticipated.
Results and Discussion
Micelles are classically made from the self-
The starting amphiphile 1 was designed in order to
incorporate an amino-triazole unit in between the
assembly of amphiphilic molecules in water.[9] At a
1
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10.1002/adsc.202000795
Advanced Synthesis & Catalysis
lipophilic diacetylene chain and the hydrophilic
polyethyleneglycol (PEG) polar head. It has been
previously demonstrated by others that amino-triazole
motifs are capable of binding copper salts to provide
stable complexes which were used for the catalysis of
“click” reactions, in the presence of sodium ascorbate
and in a binary mixture of solvents (H2O/EtOH).[15]
The amino-triazole unit, incorporated in the structure
of the amphiphile, should thus provide a suitable
ligand environment to accommodate and stabilize
copper salts within the micelle.[16]
an ene-yne conjugated network in the core of each
individual micelle and providing better cohesion to
the assembly. The polymerized micellar solution was
then dialyzed against water to remove unbound
amphiphiles and free copper salts.
The resulting supramolecular assembly (p1-Cu
micelle) is made of a central polymerized lipophilic
core, an intermediate copper-complexed amino-
triazole domain, and an outer hydrophilic layer made
of PEG chains that provide full aqueous dispersion to
the hybrid micelle (Figure 1b). Dynamic light
scattering (DLS) analysis of the polymerized micelles
incorporating copper chloride indicated a mean
hydrodynamic diameter of ca. 9 nm (Figure 1c).
Copper concentration of the aqueous micelle
suspension was measured by inductively coupled
Amphiphile 1 was readily synthesized in five steps,
starting
from
commercially
available
pentacosadiynoic acid 2 which was first activated as a
succinimidyl ester by reaction with N-
hydroxysuccinimide (NHS) and 1-ethyl-3-(3-
dimethylaminopropyl)carbodiimide (EDC, Scheme 1). plasma mass spectrometry (ICP-MS, [Cu] = 1 mM).
The activated ester was then reacted with propargyl
amine, leading to an amide intermediate which was
reduced with lithium aluminium hydride (LAH). The
resulting secondary amine 3 was obtained in 45%
yield, over three steps. The cycloaddition reaction of
The micelle-encapsulated copper salts were then
evaluated with regard to their catalytic properties, and
more specifically their ability to promote the Huisgen
1,3-dipolar cycloaddition in aqueous medium, at
room temperature.
3
with azido-terminated polyethylene glycol
monomethyl ether (PEG550, MW = 550 Da), in the
presence of CuI, led to the formation of the target
amphiphile 1, incorporating the copper-complexing
amino-triazole unit, in 63% yield. The choice of
small PEG550 units as outer layer components of the
micelle was governed by the fact that the moderate
steric hindrance of short PEG chains should allow
reagents to enter the central nanoreactor compartment.
Figure 1. a) Structure of the 1-Cu complex; b) Assembly
and polymerization of amphiphilic 1-Cu into p1-Cu
micelles; c) Hydrodynamic diameter distribution obtained
by DLS for p1-Cu micelles.
Scheme 1. Synthesis of copper-complexing amphiphile 1.
With amphiphile 1 in hands, we next induced the
complexation of copper salts with the amino-triazole
ligand by incubation of 1 with stoichiometric
amounts of CuCl2 in methanol. The mixture was
stirred overnight at room temperature and the solvent
was evaporated under vacuum to afford the 1-Cu
amphiphile complex, whose formation was confirmed
by mass spectrometry (see Figure S1). It is to be
noted that we also observed a green coloration of the
amphiphile which was used as such in the next step.
The above amphiphile (1-Cu, Figure 1a) was then
assembled into the corresponding micelle by
dispersion in deionized water (10 mg of 1-Cu per mL
of H2O) using an ultrasonic probe. The micellar
suspension was subjected to UV light irradiation at
254 nm for 3 h, under an inert argon atmosphere. UV
irradiation triggered the topochemical polymerization
of the diacetylene units, leading to the formation of
As opposed to previously reported procedures, in
which a reductant such as sodium ascorbate was
added to trigger Cu(II) to Cu(I) reduction,[17] we
initially selected more straightforward conditions by
exploiting the intrinsic one-electron transition from
Cu(II) to Cu(I) observed in the course of the homo-
coupling of terminal alkynes. This process, known as
the Glaser-Eglinton-Hay coupling,[18] affords dimeric
alkynes together with reduced copper(I).[19]
Cycloaddition reactions were thus run with an excess
of the alkyne partner in order to promote in situ
generation of the active Cu(I) species.
Benzyl azide (4a) and phenylacetylene (5a) were
chosen as model substrates. Reaction conditions were
2
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10.1002/adsc.202000795
Advanced Synthesis & Catalysis
set by working in pure water, at room temperature,
and under air atmosphere.
(entry 2) and 5c (entry 3), and with aliphatic
propargyl alcohol 5d (entry 4). These substrates
underwent smooth cycloaddition in nearly
quantitative yields (95-96%) with the exception of 5d,
which afforded the desired cycloadduct 6ad in a more
moderate 65% yield.
Table 1. Different conditions investigated for the
Huisgen cycloaddition reaction.a
In parallel, the compatibility of our system with an
array of different azides was investigated, using
phenylacetylene 5a as the dipolarophile partner. The
scrutinized 1,3-dipoles included electron-rich 2,4-
dimethoxybenzyl azide 4b (entry 5, 88%), electron-
deficient para-cyanobenzyl azide 4c (entry 6, 96%)
and 4-(methoxycarbonyl)benzyl azide 4d (entry 7,
70%).
entry
Cu (mol%)
additive
yield (%)b
1
2
3
4
5
6
-
-
< 5c
25
p1-Cu micelle (0.1)
p1-Cu micelle (0.2)
CuSO4 (0.2)
CuCl2 (0.2)
-
Table 2. Scope of the p1-Cu micelle-catalyzed
aqueous Huisgen reaction.a
-
98
Na ascorbate
48
-
17
-
Cu-free p1 micelled
< 5c
a) 4a (0.1 mmol), 5a (0.2 mmol), H2O (0.5 mL), Cu source,
room temperature, 24 h. b) Yield of isolated product. c)
1H-NMR yield. d) 1 mg mL−1.
entry
azide
4
alkyne
5
Product 6
(yield %)b
5a
6aa (98)
6ab (96)
1
4a
4a
When compounds 4a and 5a were reacted together in
water in the absence of the Cu-loaded micelles, only
trace amounts (< 5%) of 6aa were detected after 24 h
(Table 1, Entry 1). More gratifyingly, 0.1 mol% of
the micelle-complexed copper (p1-Cu micelles)
promoted partial cycloaddition to afford 6aa in 25%
yield (Entry 2). Yet, the best results were obtained by
increasing the Cu loading to 0.2 mol% (Entry 3), as
in this case we observed a nearly quantitative
conversion after 24 h (98% yield), upon reaction with
p1-Cu micelles (the participation of a Cu(I) species
was demonstrated by spectrophotometric titration of
the active copper, see ESI for details). These results
have to be compared to those obtained under classical
“click” reaction conditions, e.g. 0.2 mol% of
copper(II) sulfate in combination with sodium
ascorbate in excess, which only lead to half-
conversion after 24 h (Entry 4). Additional control
experiments included the use of CuCl2 which poorly
catalyzed the reaction (17%, Entry 5), and that of
copper-free p1 micelles which failed to activate any
cycloaddition (Entry 6).
These results emphasize the key role played by the
micellar system which not only acted as a colloidal
stabilizer of copper salts but also as a nanoreactor
which allowed aqueous dispersion of the reagents and
their concentration at the vicinity of the active sites of
the catalyst. Noteworthy, running the cycloaddition
reaction on a larger scale (e.g., 1.5 mmol) also
provided a nearly quantitative yield of 6aa (96%).
The scope of the p1-Cu micelle-catalyzed dipolar
cycloaddition reaction was then studied on a variety
of alkynes and azides under the optimized reaction
conditions in water (Table 2). In addition to phenyl
acetylene (5a, entry 1), benzyl azide also reacted with
trifluoromethyl-substituted phenyl acetylenes 5b
5b
5c
2
3
4a
4a
6ac (95)
5d
5a
6ad (65)
6ba (88)
4
5
4b
4c
4d
5a
5a
6ca (96)
6da (70)
6
7
4e
4f
5a
5a
5a
5a
5a
6ea (86)
6fa (92)
6ga (75)
6ha (93)
6ia (97)
8
9
10
11
12
4g
4h
4i
3
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10.1002/adsc.202000795
Advanced Synthesis & Catalysis
a) 4 (0.1 mmol), 5 (0.2 mmol), H2O (0.5 mL), p1-Cu
micelles (0.2 mol%), room temperature, 24 h. b) Yield of
isolated product.
from oxidation by performing the different runs under
an inert argon atmosphere were ineffective as
reactions proceeded more sluggishly. As the
performances of the catalyst were not fully
satisfactory in terms of recycling, it was decided to
investigate the potential benefit of adding sodium
ascorbate to the reaction mixture.
The system was also equally efficient on two azido
arene derivatives, i.e. plain azido benzene 4e (entry 8,
86%) and 2-methoxyphenyl azide 4f (entry 9, 92%),
and on aliphatic 1,3-dipoles such as 3-azido propanol
4g (entry 10, 75%), azido cyclohexane 4h (entry 11,
93%), and sulfur-containing azide 4i (entry 12, 97%).
It is to be noted that, for all the above examples, the
micelle-catalyzed [3 + 2] cycloaddition reaction
proceeded in a regioselective fashion affording solely
the 1,4-substituted triazole.
To further look into the applicability of our
colloidal catalyst, the p1-Cu micelle was evaluated in
the 1,3-cycloaddition reaction of a terminal alkyne
with an in situ generated organic azide.[20] A tandem
substitution-cycloaddition was planned, starting from
benzyl bromide, sodium azide and phenyl acetylene
in the presence of p1-Cu micelles (Scheme 2). We
anticipated that benzyl azide could be produced in
situ by nucleophilic displacement of the bromide
atom and react with phenylacetylene. The one-pot
sequence (R-X → R-N3 → “click”) offers the
advantage of a straightforward process without the
need to pre-synthesize the azido partner. The three-
component reaction was carried out at room
temperature, under air, using 0.2 mol% of the p1-Cu
micelle catalyst in water. We were pleased to observe
that the expected cycloadduct 6aa was produced in
excellent 90% yield after 24 h.
Before being applied to the recycling of the
catalyst, the ascorbate/p1-Cu micelle process was
validated on selected substrates (Figure 2).
Gratifyingly, the addition of sodium ascorbate (2
equiv.) to micellar copper proved beneficial to the
click reaction as the cycloaddition of benzyl azide 4a
with phenylacetylene 5a proceeded in 96% yield
within 2 h and required only one equivalent of the
alkyne partner. This result has to be compared to that
of the initial procedure (ascorbate-free) which
previously afforded triazole 6aa in comparable yields,
but in 24 h and using two equivalents of the alkyne.
The same comment holds true for more complex
substrates such as the coumarin-derived 6ja (obtained
by
reaction
of
azido-coumarin
4j
with
phenylacetylene 5a) and biotin-based 6ae (benzyl
azide 4a + biotin-alkyne 5e) which were obtained in
nearly quantitative yield by the ascorbate/p1-Cu
micelle procedure after 2 h of reaction. As a
comparison, 36 h are needed to produce coumarin 6ja
and biotin 6ae in satisfactory yields by the initial
ascorbate-free process. These results highlight the
effectiveness of ascorbate-mediated click reactions
but also the mildness of the operating conditions (w/
and w/o ascorbate) which permitted efficient access
to rather sophisticated molecular structures in pure
water.
Scheme 2. One-pot reaction of benzyl bromide, sodium
azide, and phenyl acetylene.
In order to establish the sustainability of the process,
we assessed the recyclability of the p1-Cu micelle
catalyst. To this end, four consecutive cycloaddition
reactions of 4a with 5a were carried out using the
same batch of p1-Cu catalyst which was recovered
after each run and reused in subsequent reactions.
After the reaction was completed, the aqueous phase
was simply extracted with an organic solvent and the
colloidal catalyst reused as such in water. It is to be
noted that, although the system remained active, we
observed a decrease in the catalytic performances, as
the reactions gradually needed more time (from 24 to
48 h) to afford satisfactory yields of product 6aa
(Entries 1-4, Table S1). These results were surprising,
as ICP-MS analysis of the organic extract after
reaction did not reveal any copper that could have
leached from the aqueous phase. Slow deactivation
by aerobic oxidation of copper is thus likely
responsible for the degradation of the catalyst
performances. Yet, attempts to protect the catalyst
Figure 2. Examples of p1-Cu micelle-catalyzed reactions
in the presence or absence of sodium ascorbate. Reaction
conditions: 1) w/ ascorbate: azide (0.1 mmol), alkyne (0.1
mmol), sodium ascorbate (0.2 mmol), H2O (0.5 mL), Cu-
micelle (0.2 mol% of Cu), room temp.; 2) w/o ascorbate:
azide (0.1 mmol), alkyne (0.2 mmol), H2O (0.5 mL), Cu-
micelle (0.2 mol% of Cu), room temp.
Recyclability of the p1-Cu catalyst was thereafter
investigated under the new reaction conditions,
involving sodium ascorbate (Table 3). Four
consecutive cycloaddition reactions of benzyl azide
4a with phenylacetylene 5a were carried out using
the same batch of the micellar p1-Cu catalyst which
4
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10.1002/adsc.202000795
Advanced Synthesis & Catalysis
was recovered after each run and reused in
subsequent reactions. After completion of the
reaction (2 h), the aqueous phase was extracted with
an organic solvent and the colloidal catalyst reused in
the presence of fresh reagents. Pleasingly, the catalyst
remained active over the different cycles, giving
access to triazole 6aa in yields ≥ 95% (Entries 1-4).
Interestingly, no decrease of the performances of the
catalyst was observed in the case of the ascorbate-
mediated reaction which supports the hypothesis that
the observed deactivation under ascorbate-free
conditions (Table S1) was likely due to in situ
oxidation of the active copper species.
With the non-polymerized copper-loaded micelles in
hands, we next examined their ability to promote the
Huisgen cycloaddition reaction on our model reaction
between benzyl azide 4a and phenylacetylene 5a.
Although the non-polymerized copper-loaded
micelles catalyzed the click reaction under both
conditions (w/ and w/o ascorbate), we observed a
dramatic increase in the reaction times as 6 h were
needed to produce triazole 6aa in 91% yield in the
presence of ascorbate (vs 2 h for the polymerized
micelles) and 40 h were required to yield 87% of 6aa
without ascorbate (vs 24 h for the polymerized
micelles). The lower catalytic activity of non-
polymerized micelles could be ascribed to the
intrinsic dynamic nature of the micelles in which an
exchange of copper-containing amphiphiles between
micellar arrays is taking place. This phenomenon
reduces the time spent by the reagents in close
contact with the metal centers in the environment of
the nanoreactor, thus increasing reaction times. In
addition, recycling of the catalyst could not be
achieved in the case of the non-polymerized micelles,
since work-up of the reaction using an organic
solvent led to the extraction of most of the copper-
bonded amphiphile, removing Cu from the aqueous
phase which could no longer catalyze the click
reaction. As a reminder, this phenomenon was not
observed with the copper-loaded polymerized
micelles that were retained in the aqueous phase,
recycled, and reused.
Table 3. Recycling experiment.a
entry
catalyst
Fresh
yield (%)b
98
1
2
3
4
1st reuse
2nd reuse
3rd reuse
98
95
96
a) 4a (0.1 mmol), 5a (0.1 mmol), sodium ascorbate (0.2
mmol), H2O (0.5 mL), Cu-micelle (0.2 mol% of Cu), room
temp., 2 h. b) Yield of isolated product.
Taken together our findings indicate that the Cu-
complexing polymerized micelles behaved superiorly
compared to their non-polymerized counterparts and
that the addition of ascorbate enhances the
performances of the system in terms of kinetics and
recycling. In that sense, the p1-Cu micelles compare
favorably to related micellar “click” catalysts which
classically require either heating,[21] higher catalytic
loadings,[22] or controlled atmosphere.[23]
We next investigated the influence of the
polymerization of the micelles on the overall
performances of the copper-based catalyst. For this
purpose, non-polymerized micelles were assembled
starting from the simple amphiphile
1
(yet
incorporating the copper-complexing amino-triazole
domain), and loaded with CuCl2 (Scheme 3). Final
copper concentration in the micellar stock solution
was adjusted to 1 mM by addition of water.
Interestingly, the non-polymerizable amphiphile 1’
was synthesized by a p1-Cu-catalyzed click reaction
(in the presence of sodium ascorbate) between alkyne
3’ and azido-PEG550, in 94% yield (Scheme 3).
Conclusion
We have designed a new type of tailor-made copper-
complexing micelles that were produced from the
self-assembly, polymerization, and Cu-loading of
amino-triazole-based amphiphiles. The stabilized
hybrid micelles were valorized in the catalysis of the
Huisgen cycloaddition, by taking advantage of the
nanoreactor effect offered by the micellar
environment, which allowed dispersion of the
reagents and their concentration close to the active
copper sites. The aqueous process efficiently operates
on an array of substrates with low catalytic loadings,
in the presence or absence of ascorbate and under
sustainable conditions, as it neither requires heating
nor controlled atmosphere. A one-pot sequence was
Scheme 3. Assembly of non-polymerized micelles
containing copper.
5
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10.1002/adsc.202000795
Advanced Synthesis & Catalysis
C. R. Bertozzi, Proc. Natl. Acad. Sci. USA 2007, 104,
16793; b) J. C. Jewetta, C. R. Bertozzi, Chem. Soc. Rev.
2010, 39, 1272.
also developed for the 1,3-dipolar cycloaddition
reaction by in situ generation of the organic azide
from the corresponding halide. This further
demonstrates the potential of the micellar system in
terms of efficacy and the overall green aspect of the
process.
[6] J. Dommerholt, F. P. J. T. Rutjes, F. L. van Delft, Top.
Curr. Chem. 2016, 374, 16.
[7] a) J. John, E. Gravel, A. Hagège, H. Li, T. Gacoin, E.
Doris, Angew. Chem. Int. Ed. 2011, 50, 7533; b) D.V.
Jawale, E. Gravel, E. Villemin, N. Shah, V. Geertsen, I.
N. N. Namboothiri, E. Doris, Chem. Commun. 2014, 50,
15251; c) D. V. Jawale, E. Gravel, C. Boudet, N. Shah,
V. Geertsen, H. Li, I. N. N. Namboothiri, E. Doris,
Chem. Commun. 2015, 51, 1739; d) D. Clarisse, P.
Prakash, V. Geertsen, F. Miserque, E. Gravel, E. Doris,
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Experimental Section
General Procedure for click reactions w/o ascorbate: p1-
Cu micelles (200 µL of a 1 mM aqueous suspension, 0.2
mol%) were added to a suspension of aliphatic/aromatic
azide (0.1 mmol) and terminal alkyne (0.2 mmol) in H2O
(300 µL). The reaction mixture was stirred at room
temperature for 24 h, extracted with Et2O or AcOEt (3 × 3
mL). The combined organic phases were dried over
anhydrous Na2SO4, filtered, and concentrated under
vacuum. The crude product was purified by preparative
thin layer chromatography.
[8] A. Adenot, E. B. Landstrom, F. Gallou, B. H. Lipshutz,
General Procedure for click reactions w/ ascorbate: p1-
Cu micelles (200 µL of a 1 mM aqueous suspension, 0.2
mol%) were added to a suspension of aliphatic/aromatic
azide (0.1 mmol), terminal alkyne (0.1 mmol), and sodium
ascorbate (0.2 mmol) in H2O (300 µL). The reaction
mixture was stirred at room temperature for 2 h, extracted
with Et2O or AcOEt (3 × 3 mL). The combined organic
phases were dried over anhydrous Na2SO4, filtered, and
concentrated under vacuum. The crude product was
purified by preparative thin layer chromatography.
Green Chem. 2017, 19, 2506.
[9] a) D. Lombardo, M. A. Kiselev, S. Magazù, P.
Calandra, Adv. Cond. Matter Phys. 2015, 151683; b) J.
Alliot, I. Theodorou, D. V. Nguyen, C. Forier, F.
Ducongé, E. Gravel, E. Doris, Nanoscale 2019, 11,
9756; c) J. Alliot, I. Theodorou, F. Ducongé, E. Gravel,
E. Doris, Chem Commun. 2019, 55, 14968.
[10] a) G. La Sorella, G. Strukul, A. Scarso, Green Chem.
2015, 17, 644; b) B. H. Lipshutz, S. Ghorai, M. Cortes-
Clerget, Chem. Eur. J. 2018, 24, 6672 ; c) D. K.
Romney, F. H. Arnold, B. H. Lipshutz, C. J. Li, J. Org.
Chem. 2018, 83, 7319.
Acknowledgements
R. A. K. thanks the Enhanced Eurotalents program for support.
Dr. Annelaure Damont (CEA/DRF/DMTS/SPI) is gratefully
acknowledged for helpful discussions. The “Service de Chimie
Bioorganique et de Marquage” (SCBM) belongs to the
Laboratory of Excellence in Research on Medication and
Innovative Therapeutics (ANR-10-LABX-0033-LERMIT) and is a
partner of NOMATEN, a Centre of Excellence in Multifunctional
Materials for Industrial and Medical Applications.
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FULL PAPER
Tailor-Made Polydiacetylene Micelles for the
Catalysis of 1,3-Dipolar Cycloadditions in Water
Adv. Synth. Catal. Year, Volume, Page – Page
Ramar Arun Kumar, Dhanaji V. Jawale, Emmanuel
Oheix, Valérie Geertsen, Edmond Gravel*, Eric
Doris*
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