ISMSC 2007 - Università degli Studi di Pavia

Constrained cyclam derivatives as ligands for copper(II).
Jan Plutnar, Jana Havlíková, Petr Hermann, Jan Kotek, Vojtch Kubíek
PSA 71
Department of Inorganic Chemistry, Universita Karlova (Charles University), Hlavova 2030, 128
43 Prague 2, Czech Republic
Copper radiopharmaceuticals utilizing 64 Cu or 67 Cu isotopes are increasingly investigated and
used in experimental cancer treatment due to convenient properties of the isotopes [1]. The
copper isotopes have been attached to several biological vectors including e.g. antibodies or
small peptides. Most of ligands suitable for stable copper(II) complexation are based on cyclen
or cyclam skeleton. Among them, DOTA and TETA derivatives are widely employed. However,
properties of the ligands and the complexes are far from ideal ones.
Some years ago, cross-bridged cyclam ("CB", at positions 1,8-) derivatives were
suggested to improve chemical and pharmacological properties of their copper(II) complexes
and Cu-based radiopharmaceuticals [2]. It was shown that in vivo stability was increased due
higher stability of the complexes induced by the additional constrain added to the cyclam ring.
There is another possibility to rigidity cyclam ring by addition of a carbon chain between "cis"
nitrogen atoms, e.g. at 1,4-positions (side-bridged, "SB"). Despite ongoing activity in this field
[3], thermodynamic stability of any such derivatives has not been investigated.
In our contribution, we synthesized several CB- and SB-cyclam derivatives containing
nitrobenzyl and/or coordinating groups (carboxylic or phosphonic/phosphinic acid groups). The
ligands were prepared from cyclam-glyoxal aminal through selective alkylation and reduction
followed by Mannich reaction (for phosphorus containing ligands). The ring amine dissociation
constants are generally higher (the first protonation) and lower (the second protonation) than
those of cyclam itself. Stability constants with divalent copper are lower than those of cyclam
mainly due a less favourable arrangement of nitrogen atoms. Thermodynamic equilibrium was
reached only after days at room temperatures (SB-cyclams) or at 80 C (CB-cyclams).
Several crystal structures of the ligands and complexes was determined. Among them,
unusual quarternary salt of SB-cyclam derivative has acetate group attached on piperazine
nitrogen atoms. Copper(II) complex of nitrobenzyl derivative of SB-cyclam is five-coordinated
(square pyramid) with benzene ring located close to the "sixth octahedral" position.
Bis(methylphosphonate) derivative of CB-cyclam forms octahedral copper(II) complex where
both phosphonate groups are monoprotonated.
[1] Handbook of Radiopharmaceuticals. Radiochemistry and Applications, Ed. M. J. Welch and
C. S. Redvanly, Wiley, Chichester, UK, 2003.
[2] C. A. Boswell, X. K. Sun, W. J. Niu, G. R.Weisman, E. H.Wong, A. L., Rheingold and C. J.
Anderson, J. Med. Chem., 2004, 47, 1465–1474.
[3] J. D. Silversides, .C. C. Allan and S. J. Archibald, Dalton Trans., 2007, 971–978
PSA 72
Molecular Tectonics: STM Study of 2D Nanostructures and Design of Chiral
Networks.
Fatima Helzy, Adam Duong, James D. Wuest.
Département de chimie, Université de Montréal, C.P. 6128, succursale. Centre-ville Montréal,
Québec Canada H3C 3J7
Molecular tectonics is a strategy for the design and construction of new ordered materials from
special molecules called tectons. These subunits are able to associate strongly with the help of
non-covalent bonds to generate robust, adjustable architectures by the process of spontaneous
self-assembly. This strategy has proven to be an efficient way to direct arrangement of
molecules in the solid state and to form predictable 3D frameworks. 1
Recently, we have been interested in applying this approach to program the construction of 2D
molecular networks on surface. Scanning tunnelling microscopy (STM) is an effective tool for
characterizing the structures of the resulting nanopatterned surfaces.
We will describe the self-assembly of 2D network formed by 2,2’-bipyridine-4,4’-dicarboxylic
acid when deposited from solution on highly oriented pyrolytic graphite (HOPG). STM images
suggest that each molecule is bound flat on the surface and forms hydrogen bonds with four
neighbours. The 2D organization is different from the one found in 3D crystals of the compound,
although both structures feature similar pyridine-carboxylic acid interactions. 2
We are also interested in the introducting chirality into networks bproduced by the strategy of
molecular tectonics. In particular, we have targeted tectons bearing a sulfoxide group as a
stereogenic center.
A series of enantiomerically pure tectons of this type have been prepared in good yield by
efficient methods.
We are optimistic that 3D networks resulting from the assocaition of thes compounds will
provide a source of new chiral porous materials with interesting properties, such the
enantioselective inclusion of guests.
[1] J.D Wuest, Chem. Commun., 2005, 5830-5837 and references cited therein.
[2] E. Tynan, P. Jensen, P. E. Kruger, A. C. Lees and M. Nieuwnhuyzen, Dalton Trans., 2003,
1223-1228