Research Activities
Supramolecular Assemblies Using Macrocyclic Compounds as Hosts
Macrocycles of large cavity size are able to bind more than one metal ion and/or anions or neutral molecules. Hydrogen bonds, electrostatic interactions and other weaker interactions are mainly responsible for the behaviour of supramolecular compounds. The present project intends to synthesize new macrocycles with structures which complement that of often used pesticides and other comparatively small molecules. Pesticides are important industrial chemicals and already widespread in our environment. There exists a need for their analytical determination and for techniques for their removal from water and soil. The highly selective recognition of a given pesticide, compared with other molecules, by the macrocycle or its complexes with metals or anions leads to the formation of stable supramolecular assemblies. Potential applications are sensors for pesticides and devices for their removal from water. The first target will be the herbicide "Roundup".
Self-assembled infinite metal complexes with specific network topologies are also envisaged in this project due to their fascinating molecular structures and their potential properties as solid materials. A deliberate choice of the components (macrocyclic host and guest molecules/ions) as building blocks leads to predefined structures of the crystals which can contain channels or cavities of specific shapes and sizes ("crystal engineering"). We are also interested in the development of molecular magnetic materials by the appropriate assembly of building blocks containing many paramagnetic metal centres.
Redox-Sensitive Building Blocks in Macrocyclic Chemistry: Sensor Applications
The complexation of a metal ion or a neutral molecule often changes the conformation and the electronic properties of a macrocycle considerably. Introducing a building block which can communicate such a change to the outside leads to sensors which indicate complexation of a metal ion or a neutral guest by the macrocycle. The communication can be optical or electrical. The present project uses the second approach by introducing ferrocene in the macrocycle. The complexation of a metal ion can be detected by a change in the redox potential of the Fe(II)/Fe(III) couple. We have already introduced ferrocenyl methyl groups in the pendant arms of a pyridine-containing macrocycle which shows high stability constants with some transition metals, especially copper(II). The change in the redox potential is considerable although the ferrocene moieties are already relatively far away from the site of complexation. Our new synthetic approach uses ferrocene as a bridge spanning the cavity of the macrocycle which brings the redox-active centre in close vicinity to the coordination site. This should allow for even higher sensitivity in the detection of transition metal ions.
Taylor-Made Macrocycles for Lanthanide and Group 3a Ions: Potencial Pharmaceuticals (in collaboration with I. Santos, ITN)
The introduction of substituents with functional groups like acetate and phosphonate acids at the donor atoms of macrocycles ("pendant arms") leads to compounds which show high stability constants for the complexation of lanthanide and other ions and increase the kinetic inertness of the complexes towards dissociation. For some lanthanides like samarium and holmium, and group 3a elements like gallium and indium, radioactive isotopes (153Sm, 166Ho, 67Ga, 111In) with comparatively rapid decay are accessible from nuclear reactors, such as the Portuguese Research Reactor. Complexes of the lanthanide isotopes are already used in the treatment of cancer, despite several disadvantages like large excess of toxic ligands and insufficient enrichment in the bone. The synthesis of new macrocycles with deliberately placed carboxylate and phosphonate groups in the pendant arms showing enhanced complexation properties for samarium and improved bone-seeking properties will allow to reduce the dosage of the radiopharmaceuticals and increase the lifetime of the patients. In addition, these functional groups are natural links for the attachment of biological molecules (e.g. small proteins) leading to bioconjugates with selectivity for receptor sites, allowing for the development of improved therapeutic radiopharmaceuticals.
