ISMSC 2007 - Università degli Studi di Pavia

PSA 53
Electronic spectroscopy of emissive cryptophane-based molecules and
their Xe containing complexes
Heather A. Fogarty, Thierry Brotin, and Jean-Pierre Dutasta
Ecole Normale Supérieure de Lyon, Stéréochimie et Interactions Moléculaires UMR 5532
CNRS/ENS Lyon, 46 Allée d’Italie, 69364 Lyon France
Many aspects of cryptophanes, such as their ability to encapsulate atoms and small
molecules,[1] their complexation dynamics,[2] the nature of the interior cavity, and their
energetically accessible conformations,[3] have been studied extensively using NMR, IR,
crystallographic and computational methods. Cryptophane-A, 1, and a water soluble derivative
are known to complex Xe with very high binding constants (3900 M -1 in Cl4C2H2;[4] 6900 M -1 in
H2O)[5] prompting work toward their application as probes for MRI.[6] The resolution of chiral
cryptophanes allowed both their CD and VCD spectra to be analyzed.[7] Although their UV-Vis
electronic excitation energies are known, their behavior upon excitation has yet to be
elucidated. We have used electronic circular dichroism, UV-Vis and photoluminescence
spectroscopy to investigate the intrinsic photophysical behavior of the prototypic and most
intensively studied cryptophane, 1, a 9-ethoxy anthracene substituted derivative, 2, and a new
cryptophane, as well as the effect of Xe complexation on their emissive behaviour, at room
temperature and at 77 K.
H 3CO
O
O
OCH3 H3CO O OCH
O
3
OCH3 O
O
O
R
1 R = CH 3
2 R = CH 2
The presence of a Xe atom inside the cryptophane cavity quenches statically the initially
excited S1 state reducing the fluorescence yield. At low temperature phosphorescence can be
observed for certain Xe@cryptophane complexes. An understanding of the photophyscial
processes occurring among the cryptophane cage, guest and photoluminescent label will be
used to design a second generation of emissive cryptophanes. It is desired that the nature of
the environment surrounding the cryptophane cage can be studied by taking advantage of both
the inherent sensitivity of luminescence techniques and the great sensitivity of the 129 Xe
chemical shift.
[1] G. Huber, L. Dubois, H. Desvaux, J.-P. Dutasta, T. Brotin, P. Berthault, J. Phys. Chem. A
2004, 108, 9608-9615.
[2] T. Brotin, T. Devic, A. Lesage, L. Emsley, A. Collet, Chem. Eur. J. 2001, 7, 1561-1573.
[3] P. D. Kirchhoff, J.-P. Dutasta, A. Collet, J. A. McCammon, J. Am. Chem.Soc. 1999, 121,
381-390.
[4] K. Bartik, M. Luhmer, J.-P. Dutasta, A. Collet, J. Reisse, J. Am. Chem.Soc. 1998, 120, 784-
791.
[5] G. Huber, T. Brotin, L. Dubois, H. Desvaux, J.-P. Dutasta, P. Berthault, J. Am. Chem.Soc.
2006, 128, 6239-6246.
[6] L. Schroder, T. J. Lowery, C. Hilty, D. E. Wemmer, A. Pines, Science 2006, 446-449.
[7] T. Brotin, D. Cavagnat, J.-P. Dutasta, T. Buffeteau, J. Am. Chem.Soc. 2006, 128, 5533-
5540.
O
PSA 54
Insights on the binding recognition of novel Dioxatetraaza macrocycle by
G-Quadruplex telomeric DNA: a molecular dynamics investigation.
N. Fonseca a , P. J. A. Ribeiro-Claro and V. Félix
Departamento Química, CICECO, Universidade de Aveiro, 3810-193 Aveiro, Portugal.
a e-mail: nfonseca@dq.ua.pt
Human telomerase is a ribonucleoprotein composed of a catalytic subunit, human telomerase
reverse transcriptase and a 451-nucleotide-long RNA (hTR), which acts as a template for the
addition of the repetitive hexameric motif (5'-GGTTAG-3') at the end of the telomeres. Several
recent studies show that telomerase expression is associated with cell immortalization and
tumorigenesis [1, 2]. Telomerase is over expressed in a large number of tumors, whereas it is
not expressed in most somatic cells, which usually have longer telomeres. Such differential
expression was used as starting point for the evaluation of telomerase inhibitors as potential
anticancer drugs. G-Quadruplex DNA has been widely used as a target model for drug design
of human telomerase inhibitors, since it conserves the
major properties of telomeric units[3].
protonated macrocyclic polyamines, incorporating
extended aromatic rings, are capable of binding strongly
the G-quartets of the G-quadruplex DNA, mainly due to
the multiple cooperative strong electrostatic interactions
between the positively charged ammonium groups of the
macrocyclic ligand and the negatively charged phosphate
groups of the DNA receptor. In addition, the pi - pi
stacking interaction between the aromatic groups, of both
species, contributes to the overall binding stability of these
supramolecular associations.
In this work the theoretical binding studies between the
dioxatetraaza macrocycle (Hi[26]phen2N4O2) i + (left)
incorporating two phenantroline units (H2L 2+ and H3L 3+
forms) and G4, are reported. Molecular dynamics
simulations in explicit water were carried with AMBER8
and the binding free energies involved in the recognition
process were estimated by post-processing the MD trajectory files using the MM-PBSA [4]
methodology. The results obtained demonstrate that (Hi[26]phen2N4O2) i+ Figure 1: Cartoon representation of the G4-
DNA complexed with the dioxatetraaza
macrocycle.
ligand has a highest
binding affinity to the G-Quadruplex DNA target.
Acknowledgements:
Nelson Fonseca thanks FCT – Fundação para a Ciência e Tecnologia – for the financial support
under the PhD scholarship SFRH/BD/25115/2005.
[1] Holt S. E., Shay J. W., J. Cell. Physiol. (1999), 180, 10-18.
[2] McEachern M. J., Krauskopf A., Blackburn E. H., Annu. Rev. Genet. (2000), 34, 331-358.
[3] Kerwin S.M., Cur. Pharm. Design (2000), 6, 441-471.
[4] P. A. Kollman et al, Accts. Chem. Res., (2000), 33, 889-897.