Department of Chemistry Dr. J. A.

Gareth Williams Metal complexes of macrocyclic ligands

Applications of macrocyclic metal complexes are numerous. Our own interest lies primarily in:

synthetic strategies for the development of new hexadentate and octadentate ligands based on tetra-azamacrocycles; the preparation of highly luminescent metal complexes for use as sensors for ions and molecules in solution.
1.

New tetra-azamacrocyclic ligands

he macrocycles cyclen and cyclam {[12-ane]N4 and [14-ane]N4} have been known for several decades, and their complexation chemistry with a large variety of metal ions has been studied thoroughly. Such macrocyclic ligands often lead to complexes with enhanced thermodynamic andkinetic stability with respect to metal ion dissociation, compared to their open-chain analogues.

Metal ions with a preference for coordination numbers > 4 will require further ligands to be bound (apart from the four nitrogen atoms of the macrocycle), and

these may be provided by the functionalisation of the macrocycle with additional pendent coordinating groups. This leads to higher-dentate ligands whose properties and selectivity for certain metal ions over others may be quite different from those of the unsubstituted parent macrocycles. During recent work in our group, cyclam-based macrocycles incorporating two additional coordinating groups (eg. pyridyl groups) have been prepared via diN-alkylation. Since cyclam has C2 symmetry, there are three different isomers for a di-N-substituted system, the 1,4-, 1,8- and 1,11-functionalised ligands. We have been investigating the effect of this isomerism on the structures of the complexes formed with various transition metal ions (reference 1). For example, 1,8- and 1,11-bis(pyridylmethyl) cyclam have been synthesised, and it turns out that the stuctures of the complexes they form with copper(II) are completely different!

Below: Molecular structures of the copper(II) complexes formed by the above ligands in the solid state (hydrogen atoms are omitted for clarity). The structures were determined by X-ray crystallography in the laboratory of Professor J.A.K.Howard at Durham.

The nickel(II) complexes are different again. For example, whilst the copper complex of the 1,8-ligand has pyridine groups occupying the axial positions with the four nitrogens of the macrocycle in the orthogonal plane, nickel forms a very different complex, in which the pyridine groups coordinate in mutually cis positions (reference 2). In some closely related work, we have been investigating the chemistry and complexation properties of macrocyclic dioxotetraamines. These macrocycles contain two amino nitrogens and two amides, for example the three macroycles below, which we refer to (non-systematically!) as gem-, cis- and transdioxocyclam.

As with cylam and cyclen, we are able to alkylate the amino nitrogens with additional coordinating groups to obtain new hexadentate ligands. They are able to bind to metals like copper(II) and nickel(II) with simultaneous dissociation of the two amide protons, such that metal binding is highly pHsensitive and reversible (- a very useful property for metal-sensing applications). We have crystallised the copper(II) complex of a functionalisedtrans system at neutral and basic pH, and found very different stuctures according to whether just one or both of the amides are deprotonated. See reference 1 for more details! Selected publications on macrocycle syntheses and complexation with dblock metals: 1. A.E. Goeta, J.A.K. Howard, D. Maffeo, H. Puschmann, J.A.G. Williams and D.S. Yufit, Copper(II) complexes of the isomeric tetraazamacrocyclic ligands 1,11- and 1,8-bis(2-pyridylmethyl)-1,4,8,11-tetraazacyclotetradecane and of the 1,4,8,11-tetraazacyclotetradecane-5,12-dione analogue at neutral and basic pH, J. Chem. Soc., Dalton Trans., 2000, 1880.Available on-line here. 2. A.S. Batsanov, A.E. Goeta, J.A.K. Howard, D. Maffeo, H. Puschmann and J.A.G. Williams, Nickel(II) complexes of the isomeric tetraazamacrocyclic ligands 1,11- and 1,8- bis(2-pyridylmethyl)-cyclam and of a structurally constrained N4,N8-methylene bridged analogue,Polyhedron, 2001, 20, 981986.

2. Luminescent macrocylic metal complexes for use as sensors

We are studying metal ions which have emissive metal-centred excited states (d-d or f-f), especially those where the natural lifetime of luminescence is long. These include the first row transition metal ion chromium(III), and several of the lanthanide(III) ions, especially europium(III) and terbium(III), which emit in the visible region of the spectrum. Although the natural (i.e. theoretical!) lifetimes of these ions are long (of the order of milliseconds), the aqua ions are quenched efficiently under ambient conditions by non-radiative processes. Incorporation into a macrocycle can provide the rigidity and protection necessary to inhibit these competitive processes: macrocyclic complexes of these metal ions may emit sufficiently strongly to render them attrcative for use in sensors amenable to time-resolved detection procedures. What is a luminescent sensor ? Why bother with metal complexes ? Owing to the very low extinction coefficient of the lanthanides, direct metal excitation is inefficient and it is preferable to sensitise the excited state via a suitable chromophore covalently linked to the ligand. This chromophore needs to act as an "antenna", absorbing light very strongly in a suitable region of the spectrum, and transferring the energy of the absorbed light to the excited state of the lanthanide ion.

Ultimately, the efficiency of light-emission (as measured by the quantum yield of luminescence lum) depends on the triplet yield of the chromophore (T), the efficiency of energy transfer ET and the efficiency of metal centred luminescence Ln: lum = TETLn Currently, we are looking at ways to optimise the overall efficiency of the process. Ln can be maximised by complexing the metal ion to an octadentate ligand which protects it efficiently from the deactivating effect of solvent water molecules. The quantities T and ET depend on the choice of chromophore. We have found that aryl ketones are attractive from this point of view. For the complex shown below which incorporates benzophenone as sensitiser, T is unity, which leads to particularly impressive lum values of 0.1 (0.01) and 0.27 (0.03) for the europium and terbium complexes respectively (air-equilibrated aqueous solution, 293K). All four macrocycle nitrogens bind to the metal ion, as do the three carboxylates and the amide oxygen, leading to outstanding thermodynamic and kinetic stability with respect to metal ion dissociation and excellent protection from solvent water molecules.

A brief introduction to luminescent sensors What is a luminescent sensor ?

A "sensor" is a device used for the selective detection of a substance in a sample. The substance may be a simple ion (eg. H+) or it may be a large molecule (eg. insulin). The sample could be of biological origin (eg. serum) or from the environment (eg. river water) but the principles are the same in each case... the sensor has to incorporate a binding site (represented by < in the diagram below) for the substance to be detected (the analyte) and a group to report back to us in some way, to inform us whether binding of the analyte has taken place (the shaded circle). A luminescent sensor is such a system where the "reporter" is a light-emitting group and where the binding of the analyte leads to some change in the light emission (eg. a change in the wavelength, intensity of lifetime of emission).

What about the lifetime of emission ?

There are a very large number of purely organic sensor molecules commercially available, for a wide range of analytes. However, these are almost invariablyfluorescent sensors. In other words, the emission is due to transitions between electronic states of the same spin (usually singlet states) and is shortlived: the light decays within a few nanoseconds of excitation (1 nanosecond = 10-9 s). Our interest lies in developing sensors with longer lifetimes of emission (on the microsecond to millisecond timescale, 10-6 - 10-3 s). The reason is that long-lived emission can be discriminated readily from short-lived background fluorescence that is often a problem in biological and enviornmental samples. The emission can be monitored after a pre-set time interval, during which such background emission decays to negligible levels, as illustrated in the figure below.

So why bother with metal complexes ?

Very few organic molecules emit light on a long timescale under ambient conditions (room temperature in the presence of oxygen). To see long-lived phosphorescence from a molecule like naphthalene, for example, you usually have to cool the sample down to 77K and eliminate oxygen, otherwise the excited state is quenched by other processes. Metal complexes have a greater range of excited states available to them. They may have metal-centred states (eg. d-d states of the transition metals, f-f states of lanthanides), ligand-centred states (eg. and n- states of conjugated ligands) and charge-transfer states (ligand-to-metal, metal-to-ligand, metal-to-metal, referred to as LMCT, MLCT, MMCT). In some cases, the emissive state is long-lived even under ambient conditions, making such complexes potentially interesting for sensing.