ConspectusLigand-sensitized, luminescent lanthanide(III) complexes are of considerable importance because their unique photophysical properties (microsecond to millisecond lifetimes, characteristic and narrow emission bands, and large Stokes shifts) make them well suited as labels in fluorescencebased bioassays. The long-lived emission of lanthanide(III) cations can be temporally resolved from scattered light and background fluorescence to vastly enhance measurement sensitivity. One challenge in this field is the design of sensitizing ligands that provide highly emissive complexes with sufficient stability and aqueous solubility for practical applications.In this Account, we give an overview of some of the general properties of the trivalent lanthanides and follow with a summary of advances made in our laboratory in the development of highly luminescent Tb(III) and Eu(III) complexes for applications in biotechnology. A focus of our research has been the optimization of these compounds as potential commercial agents for use in Homogeneous Time-Resolved Fluorescence (HTRF) technology. Our approach involves developing high-stability octadentate Tb(III) and Eu(III) complexes that rely on all-oxygen donor atoms and using multi-chromophore chelates to increase molar absorptivity; earlier examples utilized a single pendant chromophore (that is, a single "antenna").Ligands based on 2-hydroxyisophthalamide (IAM) provide exceptionally emissive Tb(III) complexes with quantum yield values up to ∼60% that are stable at the nanomolar concentrations required for commercial assays. Through synthetic modification of the IAM chromophore and timedependent density functional theory (TD-DFT) calculations, we have developed a method to predict absorption and emission properties of these chromophores as a tool to guide ligand design. Additionally, we have investigated chiral IAM ligands that yield Tb(III) complexes possessing both high quantum yield values and strong circularly polarized luminescence (CPL) activity.To efficiently sensitize Eu(III) emission, we have used the 1-hydroxypyridin-2-one (1,2-HOPO) chelate to create remarkable ligands that combine excellent photophysical properties and exceptional aqueous stabilities. A more complete understanding of this chromophore has been achieved by combining low-temperature phosphorescence measurements with the same TD-DFT approach used with the IAM system. Eu(III) complexes with strong CPL activity have also been obtained with chiral 1,2-HOPO ligands. We have also undertaken the kinetic analysis of radiative and non-radiative decay pathways for a series of Eu(III) complexes; the importance of the metal ion symmetry on the ensuing photophysical properties is clear. Lastly, we describe a Tb(III)-IAM compound-now carried through to commercial availability-that offers improved performance in the common HTRF platform and has the potential to vastly improve sensitivity. IntroductionThe 'rare earths' consist of elements Z=21 (Sc), Z=39 (Y), and Z=57-71 (La-Lu). 1 Despite this classification,...

We discuss recent progress towards the establishment of important structure-propertyfunction relationships in eumelanins -key functional bio-macromolecular systems responsible for photo-protection and immune response in humans, and implicated in the development of melanoma skin cancer. We focus on the link between eumelanin's secondary structure and optical properties such as broad band UV-visible absorption and strong non-radiative relaxation; both key features of the photo-protective function. We emphasise the insights gained through a holistic approach combining optical spectroscopy with first principles quantum chemical calculations, and advance the hypothesis that the robust functionality characteristic of eumelanin is related to extreme chemical and structural disorder at the secondary level. This inherent disorder is a low cost natural resource, and it is interesting to speculate as to whether it may play a role in other functional bio-macromolecular systems.

SummaryThe synthesis of poly(1actic acids) from the cyclic lactides and properties of the polymem prepared have been described. Degradation rates in vitro under homogeneous and heterogeneous conditions have been meaqured. The kinetics of deesterification under homogeneous conditions is second order and an activation energy of 11 Kcal/mol has been calculated. This is comparable to the value found for the hydrolysis of alkyl acetates. A biological in vilro method for determining the degradation of poly(1actic acids) has been described. The method indicates, in accordance with expectations, that poly (dl-lactic acid) degrades at a faster rate than L(+) lactic acid. Initial results of medical evaluation of the polymers in suture, rod, and film form are presented.

The synthesis, characterization, and luminescent behavior of trivalent Sm, Eu, Dy, and Tb complexes of two enantiomeric, octadentate, chiral, 2-hydroxyisophthalamide ligands are reported. These complexes are highly luminescent in solution. Functionalization of the achiral parent ligand with a chiral 1-phenylethylamine substituent on the open face of the complex in close proximity to the metal center yields complexes with strong circularly polarized luminescence (CPL) activity. This appears to be the first example of a system utilizing the same ligand architecture to sensitize four different lanthanide cations and display CPL activity. The luminescence dissymmetry factor, g lum , recorded for the Eu(III) complex is one of the highest values reported, and this is the first time the CPL effect has been demonstrated for a Sm(III) complex with a chiral ligand. The combination of high luminescence intensity with CPL activity should enable new bioanalytical applications of macromolecules in chiral environments.

The synthesis, structure, and photophysical properties of several Tb(III) complexes with octadentate, macrotricyclic ligands that feature a bicapped topology and 2-hydroxyisopthalamide (IAM) chelating units are reported. These Tb(III) complexes exhibit highly efficient emission (Φtotal ≥ 50%), large extinction coefficients (εmax ≥ 20,000 M−1cm−1), and long luminescence lifetimes (τH2O ≥ 2.45 ms) at dilute concentrations in standard biological buffers. The structure of the methyl-protected ligand was determined by single-crystal X-ray diffraction, and confirms the macrotricyclic structure of the parent ligand; the amide groups of the methyl-protected cage compound generate an anion binding cavity that complexes a chloride anion. Once the ligand is deprotected a conformational change generates a similar cavity, formed by the phenolate and ortho amide oxygen groups that strongly bind lanthanide ions. The Tb(III) complexes thus formed display long term stability, with little if any change in their spectral properties (including lifetime, quantum yield, and emission spectrum) over time or in different chemical environments. Procedures to prepare functionalized derivatives with a terminal amine, carboxylate and N-hydroxysuccinimide groups suitable for derivatization and protein bioconjugation have also been developed. These bifunctional ligands have been covalently attached to a number of different proteins and the terbium complexes' exceptional photophysical properties are retained. These compounds establish a new aqueous stability and quantum yield standard for long-lifetime lanthanide reporters.

The synthesis, structure, and characterization of a new class of luminescent agents based on the 1,2-hydroxypyridinone chelator are reported. The prototype complex, [Eu(5LIO-1,2-HOPO)2]-, demonstrates superb aqueous stability [pEu = 18.64(10)] and is highly emissive [Phit = 0.21(3)], emitting almost pure "red" light (lambdaem = 612 nm). The crystal structure reveals a coordination geometry reminiscent of a "butterfly", hence the soubriquet of "Cymothoe sangaris" to identify with the unique species of red butterfly found only in Central Africa.

The synthesis, X-ray structure, stability, and photophysical properties of several trivalent lanthanide complexes formed from two differing bis-bidentate ligands incorporating either alkyl or alkyl ether linkages and featuring the 1-hydroxy-2-pyridinone (1,2-HOPO) chelate group in complex with Eu(III), Sm(III) and Gd(III) are reported. The Eu(III) complexes are among some of the best examples, pairing highly efficient emission ( Eu tot Φ ~ 21.5 %,) with high stability (pEu ~ 18.6) in aqueous solution, and are excellent candidates for use in biological assays. A comparison of the observed behavior of the complexes with differing backbone linkages shows remarkable similarities, both in stability and photophysical properties. Low temperature photophysical measurements for a Gd(III) complex were also used to gain insight into the electronic structure, and were found to agree with corresponding TD-DFT calculations for a model complex. A comparison of the high resolution Eu(III) emission spectra in solution and from single crystals also revealed a more symmetric coordination geometry about the metal ion in solution due to dynamic rotation of the observed solid state structure.

Circularly polarized luminescence (CPL) is the emission analogue of circular dichroism (CD). While CD spectroscopy has been widely used to investigate the configurational as well as conformational changes in biological systems, CPL also has great, albeit currently under-developed, potential due to the general sensitivity of luminescence measurements combined with the high specificity of the signal for the chiral environment. 1 Lanthanide luminescence (especially Eu(III) and Tb(III)) with its advantageous characteristics (large Stokes shift, long lifetimes, narrow emission bands) is an ideal candidate for the development of chiral CPL probes. 2 We have earlier reported the 2-hydroxyisophthalamide (IAM) motif as a highly efficient sensitizer for the luminescence of four different Ln(III) cations (Sm, Eu, Tb, Dy). 3 In an extension of this work, enantiopure versions were recently successfully developed for use as CPL probes. 4 While these species retain the excellent brightness of their nonchiral analogues, the insolubility in physiologically relevant media remains a limitation for analytical applications. In order to address this problem, enantiopure, octadentate ligands with decreased hydrophobicity have now been developed. As an additional feature of this new approach, the stereogenic centers are introduced in the ligand backbone instead of incorporating them into the sensitizer units, thus separating the chiral information from the chromophore and allowing for a much more generally applicable, modular synthesis of chiral ligands for CPL applications. 1-Hydroxy-2-pyridinone (1,2-HOPO), which has recently proven to be a good sensitizer for Eu(III) luminescence, 5 and IAM (for Tb(III)) were chosen as model chromophores ( Figure 1).The chiral information in H 4 1 (the first chiral ligand with the 1,2-HOPO motif) and H 4 2 is easily accessible from either enantiopure amino acids or by resolution of chiral diamines. In the case of H 4 1, the four stereogenic centers are located in the tetrapodal arms, whereas H 4 2 displays vicinal stereocenters in the central portion of the oligoamine backbone. The synthesis of the ligands is outlined in Scheme 1. 6 The hexamine backbone of H 4 1 was prepared by selective ring opening of enantiopure (R)-2-ethyl-Ntosylaziridine 7 with ethylene diamine, followed by deprotection of the tosyl groups, and ion exchange chromatography in analogy to previous reports. 8 Similarly, the backbone of H 4 2 was prepared from enantiopure (R,R)-1,2-diaminocyclohexane 9 and N-tosylaziridine. 10 The optical purity of both hexamines was confirmed by 1 H NMR spectroscopy after in situ transformation to the corresponding tetrakis(urea) derivatives with commercially available, enantiopure (R)-1-phenylethylisocyanate (Sigma-Aldrich, >98% ee). In each case, only one set of signals was observed with all four arms being equivalent on the NMR time scale, consistent with complete regioand diastereoselectivity of the aziridine ring-opening reaction.Coupling of the two backbones to protected, activated carboxy...