ISMSC 2007 - Università degli Studi di Pavia

PSA 31
Anion-promoted deprotonation processes in urea-metallocyclam conjugates
Guido Colucci, Luigi Fabbrizzi, Mauro Garolfi, Maurizio Licchelli
Dipartimento di Chimica Generale, viale T. Taramelli 12, I-27100 Pavia, Italy
The metal complexes of the azacyclam derivative 1 were prepared by a one-pot synthesis
involving the condensation of the open-chain tetraamine 1,9-diamino-3,7-diazanonane with
formaldehyde and 4-nitrophenylurea, in the presence of Cu II or Ni II . Similar template reactions
have been extensively investigated along the last two decades and allow one to introduce a
variety of functionalities onto the cyclam framework [1].
450 nm
Complexes [Cu(1)] 2+ and [Ni(1)] 2+ display the expected solution properties of macrocyclic
complexes, in particular, a high stability toward demetallation, even in strongly acidic media.
The absorption spectrum of [Cu(1)] 2+ shows a strong band centred at 335 nm (14700 M 1 cm 1 )
ascribed to the nitrophenylurea moiety and a much weaker band at 520 nm due to a d-d
transition. On addition of fluoride, the band at 335 nm decreases, while a new band appears at
452 nm, whose intensity reaches a limiting value at 2 equiv. of F . This spectral change has to
be ascribed to the deprotonation of the NH fragment, with formation of HF2 and has been
previously observed in urea derivatives containing strongly electron-withdrawing substituents
[2]. Similar results were observed on titration with acetate.
On titration of the model urea derivative 2, the new band begins to develop only on addition of
large excess of fluoride (or acetate) and its intensity is in any case much lower than that
observed in the case of [Cu(1)] 2+ . These results show that the proximate metallocyclam subunit
strongly enhances the acidity of the urea NH fragment, probably due to the coordination of the
deprotonated amide group to the metal centre, according to a scorpionate mode. Further
studies are in progress in order to define the role of the metal in the anion interaction at the
amide functionality in azacyclam complexes.
[1] A. De Blas, G. De Santis, L. Fabbrizzi, M. Licchelli, A. M. Manotti Lanfredi, P. Morosini, P.
Pallavicini, F. Ugozzoli, J. Chem. Soc., Dalton Trans. 1993, 1411-1416 and references therein.
[2] (a) M. Boiocchi, L. Del Boca, D Gomez, L. Fabbrizzi, M. Licchelli, E. Monzani, J. Am. Chem.
Soc. 2004, 126, 16507-16514; (b) V. Amendola, D. Esteban-Gomez, L. Fabbrizzi, M Licchelli,
Acc. Chem. Res. 2006, 39, 343-353.
Novel jellyfish-shaped amphiphilic cyclic oligosaccharide analogues:
synthesis and self-aggregation properties
Cinzia Coppola, Lorenzo De Napoli, Giovanni Di Fabio and Daniela Montesarchio
Dipartimento di Chimica Organica e Biochimica, Università degli Studi di Napoli “Federico II”,
Complesso Universitario di Monte S. Angelo, via Cintia, 4, I-80126 Napoli, Italy
Carbohydrates are attractive scaffolds for the construction of macrocycles since they are
rigidified building blocks, displaying multiple, selectively manipulable hydroxyl functional groups
with a well defined stereochemistry. Among the plethora of natural or artificial macrocycles
known from the literature, a great deal of attention is currently devoted to amphiphilic
cyclodextrins 1 , obtained by grafting lipophilic appendages on the cyclic oligosaccharide core.
Sugar-containing amphiphilic molecules are cell membrane mimics and are expected to be
biocompatible. They may be inserted into lipid systems as natural or artificial membranes
through their hydrophobic moiety and act as transmembrane ion channels 2 . Fine tuning of the
properties and complexation abilities of cyclic oligosaccharides can be achieved by selectively
modifying their oligosaccharide backbone, for example by replacing the O-glycosidic bonds with
more chemically and enzymatically stable interglycosidic linkages.
In this frame we focused our attention on a new family of cyclic oligosaccharide analogues
having the glucoside units connected through phosphodiester linkages. In particular, we have
synthesized, by exploiting both solid phase and classical solution approaches, cyclic phosphatelinked
oligosaccharides (CyPLOS) composed of phenyl-β-D-glucopyranosyl monomers 4,6linked
through phosphodiester bonds (1-3, Figure). Key intermediate in our synthetic strategy
was a suitable phosphoramidite derivative of phenyl-β-D-glucopyranoside (4). 3
PhO
HO
O
O
P
O
-O OH
O O
P
O
O
-
O
HO
1 (n=1)
2 (n=2)
3 (n=3)
O
OH
OPh
n
NC
N
P
O
O
BzO
4
ODMT
O
OPh
OBz
PSA 32
Starting from differently derivatised carbohydrate scaffolds, our synthetic efforts are currently
devoted to cyclic phosphate-linked oligosaccharides with a broader chemical diversity. We here
present a set of novel jellyfish-shaped amphiphilic CyPLOS, functionalised with long aliphatic,
flexible chains on the secondary hydroxyls. The self-aggregation properties of these cyclic
oligosaccharides have been investigated by means of 1 H and 31 P NMR, CD and UV
spectroscopy. We envisage that these novel artificial carbohydrate analogues can display
interesting properties, by virtue of their characteristic amphiphilic nature, as well-defined selfassembling
materials able to selectively transport cations through membranes.
[1] a) A.R. Hedges, Chem. Rev., 1998, 98, 2035-2044; b) B. Perly, S. Moutard, F. Djedaïni-
Pilard, PharmaChem, 2005, 4, 4-9.
[2] L. Jullien, T. Lazrak, J. Canceill, L. Lacombe, J. M. Lehn, J. Chem. Soc., Perkin Trans. 2
1993, 1011.
[3] a) G. Di Fabio, A. Randazzo, J. D’Onofrio, C. Ausin, A. Grandas, E. Pedroso, L. De Napoli
and D. Montesarchio, J. Org. Chem., 2006, 9, 3395-3408. b) J. D’Onofrio, C. Coppola, G. Di
Fabio, L. De Napoli, and D. Montesarchio, Eur. J. Org. Chem., 2007, in press.