through noncovalent interactions providing size- and shape-
dependent selectivity in addition to an insight into the molecular
recognition phenomena in a confined space that is prevalent in
nature.
Synthesis of Molecular Nanocages by Click
Chemistry
Julia Morales-Sanfrutos, Mariano Ortega-Mun˜oz,
Javier Lopez-Jaramillo, Fernando Hernandez-Mateo, and
Francisco Santoyo-Gonzalez*
The synthesis of three-dimensional shape-persistent molecules
is usually laborious, and different approaches have been
developed.1b These molecular containers can be made as single,
large covalently joined molecules but also as self-assembled
supramolecular constructs using noncovalent interactions. In this
last approach, the use of metal-directed assembling techniques7
provides a great deal of versatility in the construction of complex
geometries, while the formation of capsules via noncovalent
assembling8 of molecules allows a templated assembly in
solution around the guests. Up to the present, most efforts have
been directed toward the construction of self-assembled su-
pramolecular cages having large cavities, and the efficient
covalent synthesis of nanosized cage compounds with high
symmetry still remains a challenge.
Instituto de Biotecnolog´ıa, Departamento de Qu´ımica
Orga´nica, Facultad de Ciencias, Campus FuentenueVa s/n,
UniVersidad de Granada, Granada E-18071, Spain
ReceiVed June 19, 2008
In this context, copper(I)-catalyzed azido-alkyne cycloaddition
(CuAAC),9 nowadays the best reaction under the “click
chemistry” concept,10 appears as an appealing synthetic tool
for the construction of molecular nanocages considering its
efficiency, which has been validated by the numerous applica-
tions that this reaction has found in almost all areas of chemistry
(drug discovery,11 bioconjugation,12 polymer and science ma-
terials,13 and related areas 14) including supramolecular chem-
istry.15 Continuing our efforts in the applications of click
chemistry in the construction of multivalent structures16 and
materials17 with a well-defined architecture, we reported in the
preceeding contribution of this issue the successful implementa-
The covalent synthesis of nanosized cage compounds is
easily performed in high yields using “click chemistry”
methodology through the Cu(I)-catalyzed ligation of adequate
polyalkyne and polyazide derivatives using (EtO)3P · CuI as
catalyst.
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5
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10.1021/jo801324x CCC: $40.75 2008 American Chemical Society
Published on Web 09/04/2008