Photoswitchable luminescent lanthanide complexes controlled and interrogated by four orthogonal wavelengths of light.

Optical information storage requires careful control of excitation and emission wavelengths in a reversible and orthogonal manner to enable efficient reading, writing, and erasing of information. Photochromic systems, in which a photoswitch is typcially coupled to an emissive organic fluorophore, have much promise in this regard. However, these suffer from considerable spectral overlap between the switch and fluorophore, such that their emissive and photoswitchable properties are not orthogonal. Here, we overcome this limitation by coupling visible/NIR emissive lanthanide complexes with molecular photoswitches, enabling reversible and orthogonal photoswitching with visible light. Crucially, photoswitching does not lead to sensitised emission from the lanthanide, while excitation of the lanthanide does not induce photoswitching, enabling the state of the system to be probed without perturbation of the switch. This opens up the possibility of developing multi-colour read-write methods for information storage using emissive photoswitches.

Evaluation of Point Group Symmetry in Lanthanide(III) Complexes: A New Implementation of a Continuous Symmetry Operation Measure with Autonomous Assignment of the Principal Axis.

The structure of molecular systems dictates the physical properties, and symmetry is the determining factor for all electronic properties. This makes group theory a powerful tool in quantum mechanics to compute molecular properties. For inorganic compounds, the coordination geometry has been estimated as idealized polyhedra with high symmetry, which, through ligand field theory, provides predictive capabilities. However, real samples rarely have ideal symmetry, and although continuous shape measures (CShM) can be used to evaluate deviation from an ideal reference structure σideal, this often fails for lanthanide(III) complexes with high coordination numbers, no obvious choice of principal axes, and no obvious reference structure. In lanthanide complexes, the unique electronic structures and associated properties are intricately tied to the symmetry around the lanthanide center. Therefore, robust methodologies to evaluate and estimate point group symmetry are instrumental for building structure-property relationships. Here, we have demonstrated an algorithmic approach that orients a molecular structure Q in the best possible way to the symmetry axis of any given point group G and computes a deviation from the ideal symmetry σsym(G,Q). This approach does not compute the deviation from an ideal reference system, but the intrinsic deviation in the structure induced by symmetry operations. If the structure contains the symmetry operation, there is no deviation and σsym(G,Q) = 0. The σsym deviation is generated from all of the symmetry operation ÔS in a point group G using the most correct orientation of the sample structure in each group G. The best orientation is found by an algorithm that minimizes the orientation of the structure with respect to G. To demonstrate the methodology, we have investigated the structure and symmetry of 8- and 9-coordinated lanthanide(III) aqua complexes and correlated the luminescence from 3 europium(III) crystals to their actual symmetry. To document the methodology, the approach has been tested on 26 molecules with different symmetries. It was concluded that the method is robust and fully autonomous.

Optical spectroscopy as a tool for studying the solution chemistry of neodymium(III).

In nature, the elements of the inorganic part of the periodic table are found in three forms: metals, ions in salts & minerals, and ions in solution. The ions may be coordinated to simple or complicated ligands. They may form purely electrostatic or partially covalent bonds. A common trend is that the more covalent bonds an element form, the more we know of its physicochemical properties. The rare earths form purely electrostatic bonds, thus, our understanding of the solution chemistry of these elements is limited-yet important. Most rare earth elements used today pass through hydrometallurgical processes that rely on the solution chemistry of these elements, even through the critical applications are in alloys and functional materials. Through developments in optical spectroscopy, total X-ray scattering, and quantum chemical methods we are posed to remedy this situation: we are ready to create predictive structure-property relationships in the field of lanthanide solution chemistry. The scope of this review is to summarise the state-of-the-art for neodymium(III), to go through the structure-property relationships that are in use. In the form of NdFeB magnets, neodymium plays a crucial role in green energy production and electric propulsion. As a 4f3 ion in solution it is also one of the simpler rare earth ions, and the Nd(III) ion has characteristic optical properties that can be exploited as a handle in physicochemical studies. Here, we start with a critical review of the current concepts used to relate structure and electronic energy levels. We follow with our suggested approach of using the methodology from molecular photophysics to relate optical properties and structure, and conclude with selected literature examples.

Electronic Structure of Neodymium(III) and Europium(III) Resolved in Solution Using High-Resolution Optical Spectroscopy and Population Analysis.

Solution chemistry of the lanthanide(III) ions is unexplored and relevant: extraction and recycling processes exclusively operate in solution, MRI is a solution-phase method, and bioassays are done in solution. However, the molecular structure of the lanthanide(III) ions in solution is poorly described, especially for the near-IR (NIR)-emitting lanthanides, as these are difficult to investigate using optical tools, which has limited the availability of experimental data. Here we report a custom-built spectrometer dedicated to investigation of lanthanide(III) luminescence in the NIR region. Absorption, luminescence excitation, and luminescence spectra of five complexes of europium(III) and neodymium(III) were acquired. The obtained spectra display high spectral resolution and high signal-to-noise ratios. Using the high-quality data, a method for determining the electronic structure for the thermal ground states and emitting states is proposed. It combines Boltzmann distributions with population analysis and uses the experimentally determined relative transition probabilities from both excitation and emission data. The method was tested on the five europium(III) complexes and was used to resolve the electronic structures of the ground state and the emitting state of neodymium(III) in five different solution complexes. This is the first step toward correlating optical spectra with chemical structure in solution for NIR-emitting lanthanide complexes.

Dynamics of P-type ATPase transport revealed by single-molecule FRET.

Phosphorylation-type (P-type) ATPases are ubiquitous primary transporters that pump cations across cell membranes through the formation and breakdown of a phosphoenzyme intermediate. Structural investigations suggest that the transport mechanism is defined by conformational changes in the cytoplasmic domains of the protein that are allosterically coupled to transmembrane helices so as to expose ion binding sites to alternate sides of the membrane. Here, we have used single-molecule fluorescence resonance energy transfer to directly observe conformational changes associated with the functional transitions in the Listeria monocytogenes Ca2+-ATPase (LMCA1), an orthologue of eukaryotic Ca2+-ATPases. We identify key intermediates with no known crystal structures and show that Ca2+ efflux by LMCA1 is rate-limited by phosphoenzyme formation. The transport process involves reversible steps and an irreversible step that follows release of ADP and extracellular release of Ca2+.

Electronic Energy Levels and Optical Transitions in Samarium(III) Solvates.

Lanthanide luminescence fascinates with a complicated electronic structure and "forbidden" transitions. By studying the photophysics of lanthanide(III) solvates, a close to ideal average coordination geometry can be used to map both electronic energy levels and transition probabilities. Some lanthanide(III) ions are simpler to study than others, and samarium(III) belongs to the more difficult ones. The 4f5 system has numerous absorption and emission lines in the visible and infrared parts of the spectrum and in this work, the energy levels giving rise to these transitions were mapped, the transition probability between them was calculated, and it was shown that the electronic structures of the samarium(III) solvates in DMSO, MeOH, and water are different.

A Nanobody-on-Quantum Dot Displacement Assay for Rapid and Sensitive Quantification of the Epidermal Growth Factor Receptor (EGFR).

Biosensing approaches that combine small, engineered antibodies (nanobodies) with nanoparticles are often complicated. Here, we show that nanobodies with different C-terminal tags can be efficiently attached to a range of the most widely used biocompatible semiconductor quantum dots (QDs). Direct implementation into simplified assay formats was demonstrated by designing a rapid and wash-free mix-and-measure immunoassay for the epidermal growth factor receptor (EGFR). Terbium complex (Tb)-labeled hexahistidine-tagged nanobodies were specifically displaced from QD surfaces via EGFR-nanobody binding, leading to an EGFR concentration-dependent decrease of the Tb-to-QD Förster resonance energy transfer (FRET) signal. The detection limit of 80±20 pM (16±4 ng mL-1 ) was 3-fold lower than the clinical cut-off concentration for soluble EGFR and up to 10-fold lower compared to conventional sandwich FRET assays that required a pair of different nanobodies.

Life expectancy of HIV-infected patients followed at the largest hospital in Guinea-Bissau is one-fourth of life expectancy of the background population.

PURPOSE: To estimate the life expectancy (LE) of HIV-infected patients in the West African country Guinea-Bissau and compare it with the background population. METHODS: Using data from the largest HIV outpatient clinic at the Hospital Nacional Simão Mendes in the capital Bissau, a retrospective observational cohort study was performed. The study included patients attending the clinic between June 2005 and January 2018. A total of 8958 HIV-infected patients were included. In the analysis of the background population, a total of 109,191 people were included. LE incorporating loss to follow-up (LTFU) was estimated via Kaplan-Meier estimators using observational data on adult HIV-infected patients and background population. RESULTS: The LE of 20-year-old HIV-infected patients was 9.8 years (95% CI 8.3-11.5), corresponding to 22.3% (95% CI 18.5-26.7%) of the LE of the background population. (LE for 20-year-olds in the background population was 44.0 years [95% CI 43.0-44.9].) Patients diagnosed with CD4 cell counts below 200 cells/µL had a LE of 5.7 years (95% CI 3.6-8.2). No increase in LE with later calendar period of diagnosis was observed. CONCLUSIONS: LE was shown to be markedly lower among HIV-infected patients compared with the background population. While other settings have shown marked improvements in prognosis of HIV-infected patients in recent years, no improvement in Bissau was observed over time (9.8 years (95% CI 7.6-12.2) and 9.9 years (95% CI 7.6-12.1) for the periods 2005-2010 and 2014-2016, respectively).

Electronic Structure of Ytterbium(III) Solvates-a Combined Spectroscopic and Theoretical Study.

The wide range of optical and magnetic properties of lanthanide(III) ions is associated with their intricate electronic structures which, in contrast to lighter elements, is characterized by strong relativistic effects and spin-orbit coupling. Nevertheless, computational methods are now capable of describing the ladder of electronic energy levels of the simpler trivalent lanthanide ions, as well as the lowest energy term of most of the series. The electronic energy levels result from electron configurations that are first split by spin-orbit coupling into groups of energy levels denoted by the corresponding Russell-Saunders terms. Each of these groups are then split by the ligand field into the actual electronic energy levels known as microstates or sometimes mJ levels. The ligand-field splitting directly informs on the coordination geometry and is a valuable tool for determining the structure and thus correlating the structure and properties of metal complexes in solution. The issue with lanthanide complexes is that the determination of complex structures from ligand-field splitting remains a very challenging task. In this paper, the optical spectra-absorption, luminescence excitation, and luminescence emission-of ytterbium(III) solvates were recorded in water, methanol, dimethyl sulfoxide (DMSO), and N,N-dimethylformamide (DMF). The electronic energy levels, that is, the microstates, were resolved experimentally. Subsequently, density functional theory calculations were used to model the structures of the solvates, and ab initio relativistic complete active space self-consistent field calculations (CASSCF) were employed to obtain the microstates of the possible structures of each solvate. By comparing the experimental and theoretical data, it was possible to determine both the coordination number and solution structure of each solvate. In water, methanol, and N,N-dimethylformamide, the solvates were found to be eight-coordinated and have a square antiprismatic coordination geometry. In DMSO, the speciation was found to be more complicated. The robust methodology developed for comparing experimental spectra and computational results allows the solution structures of homoleptic lanthanide complexes to be determined.

Temperature Dependence of Fundamental Photophysical Properties of [Eu(MeOH-d4)9]3+ Solvates and [Eu·DOTA(MeOH-d4)]- Complexes.

The trivalent lanthanide ions show optical transitions between energy levels within the 4f shell. All these transitions are formally forbidden according to the quantum mechanical selection rules used in molecular photophysics. Nevertheless, highly luminescent complexes can be achieved, and terbium(III) and europium(III) ions are particularly efficient emitters. This report started when an apparent lack of data in the literature led us to revisit the fundamental photophysics of europium(III). The photophysical properties of two complexes-[Eu·DOTA(MeOH-d4)]- and [Eu(MeOH-d4)9]3+-were investigated in deuterated methanol at five different temperatures. Absorption spectra showed decreased absorbance as the temperature was increased. Luminescence spectra and time-resolved emission decay profiles showed a decrease in intensity and lifetime as the temperature was increased. Having corrected the emission spectra for the actual number of absorbed photons and differences in the non-radiative pathways, the relative emission probability was revealed. These were found to increase with increasing temperature. The transition probability for luminescence was shown to increase with temperature, while the transition probability for light absorption decreased. The changes in transition probabilities were correlated with a change in the symmetry of the absorber or emitter, with an average increase in symmetry lowering absorbance and access to more asymmetric structures increasing the emission rate constant. Determining luminescence quantum yields and the Einstein coefficient for spontaneous emission allowed us to conclude that lowering symmetry increases both. Furthermore, it was found that collisional self-quenching is an issue for lanthanide luminescence, when high concentrations are used. Finally, detailed analysis revealed results that show the so-called "Werts' method" for calculating radiative lifetimes and intrinsic quantum yields is based on assumptions that do not hold for the two systems investigated here. We conclude that we are lacking a good theoretical description of the intraconfigurational f-f transitions, and that there are still aspects of fundamental lanthanide photophysics to be explored.

Volition in prospective Memory: Evidence against differences between free and fixed target events.

Volition is the extent to which actions are generated as a result of internal states in contrast to responses to external conditions or dictated by external events. Delayed intentions about future action are stored in prospective memory until the intended action has to be formed at a later point in time. It is unknown how voluntary choice affects prospective memory. We compared the difference between freely chosen and fixed targets on the reaction times and task performance in the ongoing task and for the target stimuli in a prospective memory task. The task performance and the reaction time was modelled using a Bayesian hierarchical drift-diffusion model. The analysis showed no differences between self-chosen and fixed prospective memory cues on task responses. The result suggests that volition in choosing the cue to act upon or given a fixed cue does not make a difference for prospective memory task performance.

Including and Declaring Structural Fluctuations in the Study of Lanthanide(III) Coordination Chemistry in Solution.

The physicochemical properties of lanthanide(III) ions are directly linked to the structure of the surrounding ligands. Rapid ligand exchange prohibits direct structure-property relationships from being formed for simple complexes in solution because the property measured will be an average over several structures. For kinetically inert lanthanide(III) complexes, the simpler speciation may alleviate the problem, yet the archetypical complexes formed by ligands derived from cyclen are known to have at least four different forms in solution-each with a variation in the crystal field that gives rise to significantly different properties. Slow interchange between forms has been engineered, so that a single complex geometry can be studied, but fast or intermediate interchange between forms is much more commonly observed. The rapid structural fluctuation can report on the changing chemical environment and can be disregarded if a specific property of a lanthanide(III) complex is exploited in an application. However, if we are to understand the chemistry of the lanthanide(III) ions in solution, we must include the structural fluctuation that takes place even in kinetically inert lanthanide(III) complexes in our studies. Here, we have scrutinized the processes that determine the speciation of lanthanide(III) complexes of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (DOTA)-like ligands, in particular the processes that enable exchange between forms that have different physicochemical properties, exemplified by the exchange between the diastereomeric capped square-antiprismatic (cSAP) and capped twisted-square-antiprismatic (cTSAP) forms of DOTA-like lanthanide(III) complexes. In the characterization of a kinetically inert f-element complex, understanding the structural fluctuation in the system is critical because a single observed property can arise from a weighted average, from all forms present, or from a single form with a dominating contribution. Further, the experimental condition will influence both the distribution of lanthanide(III) species in solution and the rates of the processes that change the coordination sphere of the lanthanide(III) ions. This is highlighted using data from a series of cyclen-derived ligands with different pendant arms and different denticity. The data were obtained in experiments that take place on different time scales to show that the rate of the process that results in a structural change must be considered against the time of the experiment. We conclude that the structural fluctuations must be taken into account and that they cannot be predicted from the ligand structure. Thus, an estimate of the exchange rates between forms, the relative concentrations of the specific forms, and the effect of the specific structure of each form of the complex must be included in the description of the solution properties of f-element chelates.

Solution Structure, Electronic Energy Levels, and Photophysical Properties of [Eu(MeOH)n-2m(NO3)m]3-m+ Complexes.

The structure of lanthanide(III) ions in solutions high in nitrate has been debated since the early days of lanthanide coordination chemistry. The structure and properties of lanthanides in these solutions are essential in industrial rare-earth separation, as well as in the fundamental solution chemistry of these elements. Pending decades of debate, it was established that nitrate is bidentate and coordinates in the inner sphere, and complexes have been observed with as many as four nitrates coordinated to a single lanthanide(III) center in nonaqueous solutions. We revisit the interactions between nitrate and europium(III) in methanol using optical spectroscopy, X-ray total scattering, and the current understanding of europium(III) photophysics. By a combination of direct and indirect methods to probe the structure, it was found that four distinct species from Eu(MeOH)93+ to [Eu(MeOH)3(NO3)3] are present in solutions containing from 0 to 2 M NO3- ions. It was shown that the changes in transition probabilities together with high-resolution spectra can provide information on speciation and how the minute changes in ligand field affect the microstates. By a comparison to total X-ray scattering, it was concluded that the optical spectra alone allow the constitution and symmetry of the europium(III) species to be determined. Most notably, the minute changes in the all oxygen atom coordination imply significant changes in the optical properties of the europium(III) center.

The effect of weighted averages when determining the speciation and structure-property relationships of europium(iii) dipicolinate complexes.

Lanthanide(iii) coordination chemistry in solution is inherently complicated by the lack of directional interactions and rapid ligand exchange. The latter can be eliminated in kinetically inert complexes, but remains a challenge in complexes between lanthanide(iii) ions and smaller ligands. As multiple conformations and partial decomplexation is an issue even with multidentate ligands, it will influence the observed solution properties of complexes of smaller ligands common in the field of f-elements coordination chemistry such as acetylacetonates and dipicolinates. Here, europium(iii) complexes with one, two and three dipicolinates were investigated in a series of 13 samples, where the composition was varied from 0 to 3 equivalents of dipicolinate. While the results did show the formation of three distinct europium(iii) dipicolinate complexes confirming the literature data on the system, clear discrepancies in speciation related properties were evident when comparing the results from absorption and luminescence spectroscopy. It was concluded that the difference is due to the difference in time constant of the two experiments. Furthermore, it is shown that the information obtained from luminescence arises from a weigthed average, and with discepancies between the observed and actual concentration exceeding 25%, it is advised that the weighted averages are taken into consideration when reporting on solution properties of lanthanide(iii) complexes. From the resolved optical spectra of [Eu(H2O)9]3+, [Eu(DPA)(H2O)6]+, [Eu(DPA)2(H2O)3]-, and [Eu(DPA)3]3-, the excited energy levels and transition probabilities are determined, and it was concluded that both transition probabilities and ligand field effects on the microstates are different in all four species.

The genome of the recently domesticated crop plant sugar beet (Beta vulgaris).

Sugar beet (Beta vulgaris ssp. vulgaris) is an important crop of temperate climates which provides nearly 30% of the world's annual sugar production and is a source for bioethanol and animal feed. The species belongs to the order of Caryophylalles, is diploid with 2n = 18 chromosomes, has an estimated genome size of 714-758 megabases and shares an ancient genome triplication with other eudicot plants. Leafy beets have been cultivated since Roman times, but sugar beet is one of the most recently domesticated crops. It arose in the late eighteenth century when lines accumulating sugar in the storage root were selected from crosses made with chard and fodder beet. Here we present a reference genome sequence for sugar beet as the first non-rosid, non-asterid eudicot genome, advancing comparative genomics and phylogenetic reconstructions. The genome sequence comprises 567 megabases, of which 85% could be assigned to chromosomes. The assembly covers a large proportion of the repetitive sequence content that was estimated to be 63%. We predicted 27,421 protein-coding genes supported by transcript data and annotated them on the basis of sequence homology. Phylogenetic analyses provided evidence for the separation of Caryophyllales before the split of asterids and rosids, and revealed lineage-specific gene family expansions and losses. We sequenced spinach (Spinacia oleracea), another Caryophyllales species, and validated features that separate this clade from rosids and asterids. Intraspecific genomic variation was analysed based on the genome sequences of sea beet (Beta vulgaris ssp. maritima; progenitor of all beet crops) and four additional sugar beet accessions. We identified seven million variant positions in the reference genome, and also large regions of low variability, indicating artificial selection. The sugar beet genome sequence enables the identification of genes affecting agronomically relevant traits, supports molecular breeding and maximizes the plant's potential in energy biotechnology.

Systematically lower structural brain connectivity in individuals with elevated food addiction symptoms.

Symptoms of food addiction have been observed in both obesity and eating disorders. The food addiction model may therefore posit a continuum of dysfunctional personality traits, including increased impulsivity and poor decision-making. The current study explored the neuroanatomy of addictive-like eating behavior from a novel triadic model of addiction. Specifically, we focused on three interacting neural systems; a sensitized impulsive, reward system associated with striatal structures, a desensitized reflective control system governed by prefrontal cortex, and a disrupted insula-mediated interoceptive system responsible for integrating and translating interoceptive, somatic signals into feelings of anticipation, desires, or cravings. Sixty-four healthy-weight Chinese university students were scanned for high-resolution structural and diffusion imaging. Data from the Yale Food Addiction Scale (YFAS), Binge Eating Scale, Eating Attitude Test-26, UPPS-P Impulsive Behavior Scale, and Delay Discounting Task were collected. Based on YFAS-score, participants were divided into a High Food Addiction group (HFA) and a Low Food Addiction group (LFA). Diffusion tensor imaging results revealed that compared to LFA, HFA had lower structural connectivity between insula and anterior cingulate cortex, insula and caudate, and ventromedial Prefrontal Cortex (vmPFC) and putamen. The Voxel-Based Morphometry analysis suggested marginally lower gray matter volume in the left vmPFC in HFA. Finally, behavioral results, indicated that higher food addiction symptoms were associated with personality traits exhibited in eating disorders including impulsive decision-making. These findings suggest that even in a healthy population, some individuals may be more susceptible to develop unhealthy relationships to food, which at least partially is manifested in lower structural connectivity between brain regions associated with interoceptive awareness, decision-making, and reward.

Early Mobilization After Volar Locking Plate Osteosynthesis of Distal Radial Fractures in Older Patients-A Randomized Controlled Trial.

PURPOSE: To investigate if early mobilization after open reduction internal fixation of distal radius fractures improved the functional outcome. We hypothesized that early mobilization would lead to improved patient-reported outcome. Second, we aimed to assess whether early mobilization increased the risk of postoperative implant loosening or breakage. METHODS: All included patients were treated with a volar locking plate. After surgery, patients were randomized to either early mobilization (E-MOB) with a removable orthosis (wrist lacer) and daily wrist exercises or to late mobilization (L-MOB) with a standard dorsal plaster cast for 2 weeks and, after that, a removable orthosis and exercises. We measured all patients at 4 weeks and at 3, 6, and 12 months after surgery. At each postoperative visit, we measured range of motion and grip strength and patients filled out the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire. Radiographic implant loosening or breakage was assessed 14 days after surgery. RESULTS: A total of 47 patients were allocated to E-MOB and 48 to L-MOB. The DASH score improved substantially throughout the follow-up period with no significant differences between the 2 groups at any time point. Implant loosening and fracture redisplacement was observed in 1 patient in the E-MOB group. Range of motion and grip strength were similar between the 2 groups at all time points. CONCLUSIONS: Early mobilization after surgical treatment of distal radius fractures does not lead to improved patient-reported outcome. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I.

HOCl Responsive Lanthanide Complexes Using Hydroquinone Caging Units.

Redox biology is still looking for tools to monitor redox potential in cellular biology and, despite a large and sustained effort, reliable molecular probes have yet to emerge. In contrast, molecular probes for reactive oxygen and nitrogen have been widely explored. In this manuscript, three kinetically inert lanthanide complexes that selectively react with hypochlorous acid are prepared and characterized. The design is based on 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A) and 1,4,7,10-tetraazacyclododecane-1,7-diacetic acid (DO2A) ligands appended with one or two redox active hydroquinone derived arms, thereby forming octadentate ligands ideally suited to complex trivalent lanthanide ions. The three complexes are found to react selectively with hypochlorous acid to form highly symmetric lanthanide(III) 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacedic acid (DOTA) complexes. The conversion of the probe to [Ln.DOTA]- is followed by luminescence, absorption, and NMR spectroscopy in a model system comprised of a Triton-X modified HEPES buffer. It was concluded that the design principle works, and that simple caging units like hydroquinones can work well in conjugation with lanthanide(III) complexes.

VMXi: a fully automated, fully remote, high-flux in situ macromolecular crystallography beamline.

VMXi is a new high-flux microfocus macromolecular crystallography beamline at Diamond Light Source. The beamline, dedicated to fully automated and fully remote data collection of macromolecular crystals in situ, allows rapid screening of hundreds of crystallization plates from multiple user groups. Its main purpose is to give fast feedback at the complex stages of crystallization and crystal optimization, but it also enables data collection of small and delicate samples that are particularly difficult to harvest using conventional cryo-methods, crystals grown in the lipidic cubic phase, and allows for multi-crystal data collections in drug discovery programs. The beamline is equipped with two monochromators: one with a narrow band-pass and fine energy resolution (optimal for regular oscillation experiments), and one with a wide band-pass and a high photon flux (optimal for fast screening). The beamline has a state-of-the-art detector and custom goniometry that allows fast data collection. This paper describes the beamline design, current status and future plans.

Multimetallic Lanthanide Complexes: Using Kinetic Control To Define Complex Multimetallic Arrays.

Kinetically inert lanthanide complexes are proving to be highly effective building blocks for the preparation of complex heterometallic architectures, allowing complete control of metal ion domains, which cannot be achieved under thermodynamic control. Kinetic stability may render perceivable labile coordination bonds more durable than several types of covalent interactions. For complexes in clinical use, the significance of kinetic stability cannot be overstated, and this Account treats the topic accordingly. Kinetically inert complexes can be used as building blocks for elaborate synthesis. For instance, it is now possible to prepare heterometallic lanthanide complexes containing two or more different lanthanide ions by linking kinetically robust complexes together. This approach can yield bimetallic (f-f' or d-f) and trimetallic (f-f'-f″) lanthanide complexes. In this Account, we describe our studies exploiting the slow dissociation of lanthanide complexes derived from 1,4,7,10-tetraazadodecane-1,4,7,10-tetraacetic acid (DOTA) related ligands to link complexes together through synthetic manipulation of pendent groups on the ligand skeleton or through coordination of bridging donor groups to a d-block metal center. In the course of this work, we have developed a variety of such methods, ranging from peptide coupling and diazotization to Ugi and click chemistry and have also explored the use of alternative strategies that combine orthogonal protecting group chemistry with sequential complexation of different lanthanide ions or that use self-assembly to deliver well-defined multimetallic systems. These well-defined bimetallic systems also have considerable scope for exploitation. Since the earliest studies, it has been clear that there is potential for application in the burgeoning field of molecular imaging. Heterometallic lanthanide complexes can be used as single-molecule bimodal imaging agents through incorporation of MRI active and luminescent components. Alternatively, conventional luminescence methods can be exploited in conjunction with lanthanide luminescence. In the simplest cases, a single lanthanide can be used to achieve a switchable response in combination with a transition metal complex. Bimetallic f-f' complexes allow the full potential of the approach to be realized in systems in which one lanthanide responds to changes in the concentration of an analyte, while a second lanthanide center can be used to define the concentration of the probe itself. This offers a new solution to the old dichotomy of ratiometric imaging that can potentially be applied widely.