Excitement in f block : structure, dynamics and function of nine-coordinate chiral lanthanide complexes in aqueous media† David Parker Department of Chemistry, University of Durham, South Road, Durham, UK DH1 3LE. E-mail: david.parker@durham.ac.uk; Fax: +44 (0)191 384 4737; Tel: +44 (0)191 3342033 Received 29th October 2003 First published as an Advance Article on the web 13th February 2004 Lanthanide complexation chemistry has been studied intensively over the past 15 years and progress has been stimulated by the advent of well-defined, kinetically robust systems tailored to applications as bioactive probes for magnetic resonance and luminescence. In this tutorial review, the extent to which an enhanced understanding of the relationship between complex structure and spectral properties is emerging is discussed, together with an examination of the mechanism of ligand exchange processes. Such issues are aiding the development of responsive probes, ranging from simple sensors to more complex studies defining water structure and exchange dynamics. 1 Historical perspective Thirty years ago, undergraduates taking a lecture course in lanthanide chemistry might have had good reason for being rather uninspired by the content of the lectures. Beyond their important spectral and magnetic properties, much of the chemistry discussed would relate to the ubiquity of the tripositive oxidation state, the efficiency of ion exchange chromatography or solvent extraction in devising separations of lanthanide ion mixtures and the origins and validity of the lanthanide contraction, the ‘gadolinium break’ and the Russell-Saunders coupling scheme. How things have changed! Not only is there a rich and important organometallic chemistry of low oxidation states and a worldwide activity in chemo- and stereoselective Lewis-acid catalysed processes, but also a rich and exciting solution coordination chemistry has been defined. An excellent compilation of reviews on lanthanide chemistry has just appeared 1 as well as a book highlighting the role of lanthanide coordination chemistry in biosystems. 2 In this short review, selected recent developments in aqueous lanthanide coordination chemistry are discussed, with an emphasis on the structure, dynamics and function of water-soluble, chiral lanthanide com- plexes. In tracing the development of this work, certain pioneering studies can be readily identified. Shift reagents in NMR were developed for spectral simplification and chiral analysis both in organic and aqueous media 3 but are much less frequently used nowadays because of the advent of high field, pulsed multi- dimensional NMR techniques. This work typically involved studies of formally hexacoordinated Ln(III) species with Lewis bases (Ln, = Eu, Yb, Pr) in which the anisotropic spatial distribution of unpaired f electrons gives rise to a dipolar lanthanide-induced-shift for the bound Lewis base in solution. This is often termed a pseudo- contact shift. In the Gd(III) ion, on the other hand, there is an isotropic distribution of the f 7 electrons so that no NMR dipolar shift is produced. However, when a ligand binds to the para- magnetic Gd(III) centre, both the rates of longitudinal (R 1 ) and transverse (R 2 ) relaxation are enhanced considerably, giving rise to extensive line-broadening in the NMR spectra of bound ligand nuclei. In an early example of the use of the aqua Gd(III) ion as a relaxation agent, the line-broadening induced by a Gd 3+ /lysozyme complex in the proton NMR resonances of the inhibitor, b-methyl- N-acetylglucosamine, was analysed in terms of the distances between the sugar protons and the paramagnetic ion. 4 Such work stimulated a great deal of activity on the application of the aqua lanthanide ions as shift and relaxation probes for NMR, 5 culminat- ing in the development of both gadolinium contrast agents for clinical 6 MRI and the exploration of various shift reagents for magnetic resonance spectroscopy in vivo – for example, in real- time 31 P or 23 Na NMR analyses of perfused cells or intact animals using wide-bore magnets or surface-coil NMR probes. In addition, building on early work in Oxford 7 that established the importance of pseudocontact shift values as constraints in biomolecular structure determination, solution structures of proteins may now be determined with the aid of Ln 3+ NMR probes 8 – often made more precise by the analysis of residual dipolar couplings and the introduction of cross-correlation and relaxation constraints. 5 The lowest energy excited states of several of the lanthanide (III) ions have natural radiative lifetimes of the order of milliseconds, an attractive feature for a luminescent probe as it allows time-resolved detection procedures to be used, affording excellent discrimination between probe emission and background fluorescence or light scattering. Early work centred on the use of Eu and Tb aqua ions as probes for proteins and nucleic acids. 9 For example, binding of the Tb 3+ aqua ion to single-stranded nucleic acids is characterised by an enhanced terbium emission intensity, which is not observed for doubly-stranded systems. Many studies involved the replacement of Ca 2+ in a protein by a Ln 3+ ion of similar size and charge density, for example in the Ca-binding proteins calmodulin, calbindin and parvalbumin. 10 The proximity of the Ln 3+ ion through space to Trp † Based on a 2003/4 Tilden Lectureship of the Royal Society of Chemistry first delivered in Strasbourg, 5 th December 2003. David Parker was educated at the University of Oxford (BA 1978, D.Phil 1980), studying with John Brown, and in Strasbourg as a NATO Fellow with Jean-Marie Lehn. He returned to his native North-East in 1982, as a Lecturer at Durham University, has been a Professor since 1992 and is currently serving his second term as Head of Department. He has gained numerous prizes and awards, most recently being elected a Fellow of the Royal Society (2002). In the same year he received the Tilden Lecture- ship of the Royal Society of Chemistry, upon which this ar- ticle is based. His research inter- ests are diverse and currently embrace many aspects of the chemistry of chiral metal com- plexes in solution. This journal is © The Royal Society of Chemistry 2004 DOI: 10.1039/b311001j 156 Chem. Soc. Rev. , 2004, 33 , 156–165