ISMSC 2007 - Università degli Studi di Pavia

PL 7
Calixarenes in Action: From Anion Recognition to DNA Condensation and
RNA Cleavage
Rocco Ungaro
Dipartimento di Chimica Organica e Industriale, Università degli Studi di Parma and INSTM,
Sezione di Parma, Viale G.P. Usberti 17/A, I-43100-Parma (Italy)
Anion Recognition is an important topic in Supramolecular Chemistry and has been tackled
using various strategies depending on the particular application which one aims to. For many
years we have been particularly interested in the synthesis of selective receptors for carboxylate
anions, which are substrates of biological interest, using calixarenes as scaffolds and hydrogen
bonding as the main supramolecular interaction. [1]
More recently, we have adorned the upper rim of calix[n]arenes, having different sizes and
Figure
Cl Cl
Cl
+
H2N H N
+
+
2 NH2 H N
Cl
2 NH
+
2
NH
HN
NH2 HN
H N
HN
2
NH2 O O O O
R
R R R
R = C 3 H 7 : 4G4Pr-cone
R = C 6 H 13 : 4G4Hex-cone
R = C 8 H 17 : 4G4Oct-cone
Cl
H2N +
H
N
NH 2
+ NH2 Cl
H N NH
2
OMe MeO
OMe
HN
Cl
+ NH2 shapes, with guanidinium groups and used the resulting water soluble multivalent ligands
(Figure) in DNA binding and cell transfection. By Atomic Force Microscopy (AFM) it has been
possible to correlate the topology of the ligands with their DNA condensation and transfection
ability. [2]
In collaboration with Mandolini’s and Reinhoudt’s groups we have synthesized a series of
calix[4]arenes bearing at the upper rim a variable number of metal ion chelating units such as
aza macrocycles ([12]aneN3) or 2,6-bis[(dimethylamino)methyl]pyridine (DMAP). The Zn(II) or
Cu(II) complexes of these multivalent ligands are able to catalyze the methanolysis of aryl
esters and the cleavage of phosphodiester bonds in oligoribonucleotides, showing substrate
selectivity and cooperativity between the metal centers. [3]
An overview of the most recent results obtained using anion receptors, multivalent ligands, and
supramolecular catalysts based on calixarenes will be given in the lecture.
[1] A. Casnati, F. Sansone, R. Ungaro, Acc. Chem. Res. 2003, 36, 246-254. A.V.
Yakovenko,.I. Boyko, V. Kalchenko, L. Baldini, A. Casnati, F. Sansone, R. Ungaro, J. Org.
Chem. 2007, 72(9), 3223-3231.
[2] F. Sansone, M. Dudi, G. Donofrio, C. Rivetti, L. Baldini, A. Casnati, S. Cellai, R.Ungaro, J.
Am. Chem. Soc. 2006, 128, 14528 – 14536. L. Baldini, A. Casnati, F. Sansone, R. Ungaro,
Chem. Soc. Rev. 2007, 34, 254-266.
[3] R. Cacciapaglia, A. Casnati, L. Mandolini, D.N. Reinhoudt, R. Salvio, A. Sartori, R. Ungaro,
J. Am. Chem. Soc. 2006, 128, 12322-12330 and references therein.
OMe
NH 2
N
H 2
n-3
N
H
n = 4: 4G4Me-mobile
n = 6: 6G6Me-mobile
n = 8: 8G8Me-mobile
Cl
+
NH2 +
+
Cl
H
Cl
2N NH2 N
H 2
NH
O
O O
HN
O
NH 2
NH
HN
Cl
H2N +
NH2 H2N 4G4Pr-alt
Cl
NH2 +
PL 8
From Supramolecular Chemistry to Constitutional Dynamic Chemistry
Jean-Marie Lehn
ISIS, Université Louis Pasteur, Strasbourg and Collège de France, Paris
Supramolecular chemistry is actively exploring the design of systems undergoing selforganization,
i.e. systems capable of spontaneously generating well-defined functional
supramolecular architectures by self-assembly from their components, on the basis of the
molecular information stored in the covalent framework of the components and read out at the
supramolecular level through specific interactional algorithms, thus behaving as programmed
chemical systems.
The implementation of such molecular information-controlled self-organizing processes for
the generation of functional nanostructures provides a powerful approach to nanoscience and
nanotechnology .
Supramolecular chemistry is intrinsically a dynamic chemistry in view of the lability of the
interactions connecting the molecular components of a supramolecular entity and the resulting
ability of supramolecular species to exchange their constituents. The same holds for molecular
chemistry when the molecular entity contains covalent bonds that may form and break
reversibility, so as to allow a continuous change in constitution by reorganization and exchange
of building blocks. These features define a Constitutional Dynamic Chemistry (CDC) on both the
molecular and supramolecular levels.
CDC introduces a paradigm shift with respect to constitutionally static chemistry. The latter
relies on design for the generation of a target entity, while CDC takes advantage of dynamic
diversity to allow variation and selection. The implementation of selection in chemistry
introduces a fundamental change in outlook. Thus, self-organization by design strives to
achieve full control over the output molecular or supramolecular entity by explicit programming,
whereas self-organization with selection operates on dynamic constitutional diversity in
response to either internal or external factors to achieve adaptation.
Applications of this approach in biological systems as well as in materials science will be
described.
The merging of the features: - information and programmability, - dynamics and reversibility,
-constitution and structural diversity, points towards the emergence of adaptive chemistry.
Lehn, J.-M., Supramolecular Chemistry: Concepts and Perspectives, VCH Weinheim, 1995.
Lehn, J.-M., Dynamic combinatorial chemistry and virtual combinatorial libraries, Chem. Eur.
J., 1999, 5, 2455.
Lehn, J.-M., Programmed chemical systems : Multiple subprograms and multiple
processing/expression of molecular information, Chem. Eur. J., 2000, 6, 2097.
Lehn, J.-M., Toward complex matter: Supramolecular chemistry and self-organization, Proc.
Natl. Acad. Sci. USA, 2002, 99, 4763.
Lehn, J.-M., Toward self-organization and complex matter, Science, 2002, 295, 2400.
Lehn, J.-M., Dynamers : Dynamic molecular and supramolecular polymers,
Prog. Polym. Sci., 2005, 30, 814.
Lehn, J.-M., From supramolecular chemistry towards constitutional dynamic chemistry and
adaptive chemistry, Chem. Soc. Rev., 2007, 36, 151.