Anisotropy enhanced X-ray scattering from solvated transition metal complexes

Time-resolved X-ray scattering patterns from photoexcited molecules in solution are in many cases anisotropic at the ultrafast time scales accessible at X-ray Free Electron Lasers (XFELs). This anisotropy arises from the interaction of a linearly polarized UV-vis pump laser pulse with the sample, which induces anisotropic structural changes that can be captured by femtosecond X-ray pulses. In this work we describe a method for quantitative analysis of the anisotropic scattering signal arising from an ensemble of molecules and we demonstrate how its use can enhance the structural sensitivity of the time-resolved X-ray scattering experiment. We apply this method on time-resolved X-ray scattering patterns measured upon photoexcitation of a solvated di-platinum complex at an XFEL and explore the key parameters involved. We show that a combined analysis of the anisotropic and isotropic difference scattering signals in this experiment allows a more precise determination of the main photoinduced structural change in the solute, i.e. the change in Pt-Pt bond length, and yields more information on the excitation channels than the analysis of the isotropic scattering only. Finally, we discuss how the anisotropic transient response of the solvent can enable the determination of key experimental parameters such as the Instrument Response Function.Comment: Accepted for publication in Journal of Synchrotron Radiatio

Oral and Intravenous Amoxicillin Dosing Recommendations in Neonates:A Pooled Population Pharmacokinetic Study

BACKGROUND: There is a lack of evidence on oral amoxicillin pharmacokinetics and exposure in neonates with possible serious bacterial infection (pSBI). We aimed to describe amoxicillin disposition following oral and intravenous administration and to provide dosing recommendations for preterm and term neonates treated for pSBI.METHODS: In this pooled-population pharmacokinetic study, 3 datasets were combined for nonlinear mixed-effects modeling. In order to evaluate amoxicillin exposure following oral and intravenous administration, pharmacokinetic profiles for different dosing regimens were simulated with the developed population pharmacokinetic model. A target of 50% time of the free fraction above the minimal inhibitory concentration (MIC) with an MICECOFF of 8 mg/L (to cover gram-negative bacteria such as Escherichia coli) was used.RESULTS: The cohort consisted of 261 (79 oral, 182 intravenous) neonates with a median (range) gestational age of 35.8 weeks (range, 24.9-42.4) and bodyweight of 2.6 kg (range, 0.5-5). A 1-compartment model with first-order absorption best described amoxicillin pharmacokinetics. Clearance (L/h/kg) in neonates born after 30 weeks' gestation increased with increasing postnatal age (PNA day 10, 1.25-fold; PNA day 20, 1.43-fold vs PNA day 3). Oral bioavailability was 87%. We found that a twice-daily regimen of 50 mg/kg/day is superior to a 3- or 4-times daily schedule in the first week of life for both oral and intravenous administration.CONCLUSIONS: This pooledpopulation pharmacokinetic description of intravenous and oral amoxicillin in neonates provides age-specific dosing recommendations. We conclude that neonates treated with oral amoxicillin in the first weeks of life reach adequate amoxicillin levels following a twice-daily dosing regimen. Oral amoxicillin therapy could therefore be an adequate, cost-effective, and more patient-friendly alternative for neonates worldwide.</p

Atomistic characterization of the active-site solvation dynamics of a model photocatalyst

The interactions between the reactive excited state of molecular photocatalysts and surrounding solvent dictate reaction mechanisms and pathways, but are not readily accessible to conventional optical spectroscopic techniques. Here we report an investigation of the structural and solvation dynamics following excitation of a model photocatalytic molecular system [Ir 2 (dimen) 4 ] 2+, where dimen is para-diisocyanomenthane. The time-dependent structural changes in this model photocatalyst, as well as the changes in the solvation shell structure, have been measured with ultrafast diffuse X-ray scattering and simulated with Born-Oppenheimer Molecular Dynamics. Both methods provide direct access to the solute-solvent pair distribution function, enabling the solvation dynamics around the catalytically active iridium sites to be robustly characterized. Our results provide evidence for the coordination of the iridium atoms by the acetonitrile solvent and demonstrate the viability of using diffuse X-ray scattering at free-electron laser sources for studying the dynamics of photocatalysis

Microfluidic liquid sheets as large-area targets for high repetition XFELs

The high intensity of X-ray free electron lasers (XFELs) can damage solution-phase samples on every scale, ranging from the molecular or electronic structure of a sample to the macroscopic structure of a liquid microjet. By using a large surface area liquid sheet microjet as a sample target instead of a standard cylindrical microjet, the incident X-ray spot size can be increased such that the incident intensity falls below the damage threshold. This capability is becoming particularly important for high repetition rate XFELs, where destroying a target with each pulse would require prohibitively large volumes of sample. We present here a study of microfluidic liquid sheet dimensions as a function of liquid flow rate. Sheet lengths, widths and thickness gradients are shown for three styles of nozzles fabricated from isotropically etched glass. In-vacuum operation and sample recirculation using these nozzles is demonstrated. The effects of intense XFEL pulses on the structure of a liquid sheet are also briefly examined

Ligand manipulation of charge transfer excited state relaxation and spin crossover in [Fe(2,2'-bipyridine)_2(CN)_2]

We have used femtosecond resolution UV-visible and Kβ x-ray emission spectroscopy to characterize the electronic excited state dynamics of [Fe(bpy)_2(CN)_2], where bpy=2,2'-bipyridine, initiated by metal-to-ligand charge transfer (MLCT) excitation. The excited-state absorption in the transient UV-visible spectra, associated with the 2,2'-bipyridine radical anion, provides a robust marker for the MLCT excited state, while the transient Kβ x-ray emission spectra provide a clear measure of intermediate and high spin metal-centered excited states. From these measurements, we conclude that the MLCT state of [Fe(bpy)_2(CN)_2] undergoes ultrafast spin crossover to a metal-centered quintet excited state through a short lived metal-centered triplet transient species. These measurements of [Fe(bpy)_2(CN)_2] complement prior measurement performed on [Fe(bpy)_3]^(2+) and [Fe(bpy)_4(CN)]^(2-) in dimethylsulfoxide solution and help complete the chemical series [Fe(bpy)_N(CN)_(6-2N)]^(2N-4), where N = 1-3. The measurements confirm that simple ligand modifications can significantly change the relaxation pathways and excited state lifetimes and support the further investigation of light harvesting and photocatalytic applications of 3 transition metal complexes

Finding intersections between electronic excited state potential energy surfaces with simultaneous ultrafast X-ray scattering and spectroscopy

Light-driven molecular reactions are dictated by the excited state potential energy landscape, depending critically on the location of conical intersections and intersystem crossing points between potential surfaces where non-adiabatic effects govern transition probabilities between distinct electronic states. While ultrafast studies have provided significant insight into electronic excited state reaction dynamics, experimental approaches for identifying and characterizing intersections and seams between electronic states remain highly system dependent. Here we show that for 3d transition metal systems simultaneously recorded X-ray diffuse scattering and X-ray emission spectroscopy at sub-70 femtosecond time-resolution provide a solid experimental foundation for determining the mechanistic details of excited state reactions. In modeling the mechanistic information retrieved from such experiments, it becomes possible to identify the dominant trajectory followed during the excited state cascade and to determine the relevant loci of intersections between states. We illustrate our approach by explicitly mapping parts of the potential energy landscape dictating the light driven low-to-high spin-state transition (spin crossover) of [Fe(2,2′-bipyridine)3]2+, where the strongly coupled nuclear and electronic dynamics have been a source of interest and controversy. We anticipate that simultaneous X-ray diffuse scattering and X-ray emission spectroscopy will provide a valuable approach for mapping the reactive trajectories of light-triggered molecular systems involving 3d transition metals