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Introduction Human-cl rhFVIII (Nuwiq®), a new generation recombinant factor VIII (rFVIII), is the first rFVIII produced in a human cell-line approved by the European Medicines Agency. Aims To describe the development, upscaling and process validation for industrial-scale human-cl rhFVIII purification. Methods and results The purification process involves one centrifugation, two filtration, five chromatography columns and two dedicated pathogen clearance steps (solvent/detergent treatment and 20 nm nanofiltration). The key purification step uses an affinity resin (VIIISelect) with high specificity for FVIII, removing essentially all host-cell proteins with >80% product recovery. The production-scale multi-step purification process efficiently removes process- and product-related impurities and results in a high-purity rhFVIII product, with an overall yield of ∼50%. Specific activity of the final product was >9000 IU/mg, and the ratio between active FVIII and total FVIII protein present was >0.9. The entire production process is free of animal-derived products. Leaching of potential harmful compounds from chromatography resins and all pathogens tested were below the limit of quantification in the final product. Conclusions Human-cl rhFVIII can be produced at 500 L bioreactor scale, maintaining high purity and recoveries. The innovative purification process ensures a high-purity and high-quality human-cl rhFVIII product with a high pathogen safety margin. [ABSTRACT FROM AUTHOR]

The phoszone ligand [(PhP)(bis-3,5-CF-Ph)]NN=CH(penta-fluoro-Ph) transformed in liquid CO at room temperature in presence of [Rh(cod)]OTf into [Rh(cod)(η-P,P′-PhPOPPh)]OTf. Replacing the O-atom in PhPOPPh by a PrN-group leads to the ligand PrN(PPh) acting similarly as a bidentate ligand in [Rh(cod)(η-P,P′-PrN(PPh))]OTf. Hydroformylation of 1-octene with in situ catalysts formed by the ligands with [Rh(cod)]OTf showed hydroformylation activities at 50 % conversion of 16,000 h (PrN(PPh)/[Rh(cod)]OTf) and 24,000 h (phoszone/[Rh(cod)]OTf), respectively. Graphical Abstract: [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Mixing CuCl2 ⋅2 H2O with benzylamine in alcoholic solutions led to an extremely colorful chemistry caused by the formation of a large number of different complexes. Many of these different species could be structurally characterized. These include relatively simple compounds such as [Cu(L1)4Cl2] (L1=benzylamine) and (HL1)2[CuCl4]. Most interestingly is the easy formation of two cluster complexes, one based on two cluster units Cu4OCl6(L1)4 connected through one [Cu(L1)2Cl2] complex and one based on a cubane-type cluster ([Cu4O4](C11H14)4Cl4). Both clusters proved to be highly reactive in a series of oxidation reactions of organic substrates by using air or peroxides as oxidants. Furthermore, it was possible to isolate and structurally characterize ([Cu(L1)Cl]3 and [Cu(benz2mpa)2]CuCl2 (benz2mpa=benzyl-(2-benzylimino-1-methyl-propylidene)-amine), two copper(I) complexes that formed in solution, demonstrating the high redox activity of the cluster systems. In addition, it was possible to solve the molecular structures of the compounds Cu4OCl6(MeOH)4, [Cu(MeOH)2Cl2], [Cu(aniline)2Cl2], and an organic side product (HC13H19NOCl). In fact all determined structures are of a known type but the chemical relation between these compounds could be explained for the first time. The paper describes these different compounds and their chemical equilibria. Some of these complexes seem to be relevant in catalytic oxidation reactions and their reactivity is discussed in more detail. [ABSTRACT FROM AUTHOR]

Abstract: The synthesis and X-ray structure determination of an uncommon ionic aluminum bisphenoxide [Al(THF)4(Cl)2]+[Al(mcmip)2]−·1.1 THF (1) and its neutral analogue (mcmip)Al(CH2CH3)(THF) (2) are reported (mcmipH2: 2,2′-methylenebis(4-chloro-3-methyl-6-(isopropyl)phenol). The ligand was reacted in THF with diethyl aluminum chloride, respectively triethyl aluminum, under liberation of ethane to yield crystalline aluminum bisphenoxides. Compound 2 exhibits the usual structural features found in neutral THF-aluminum bisphenoxides adducts whereas the ionic compound 1 consists of a cationic octahedral aluminum dichloride moiety, [Al(THF)4(Cl)2], and an anionic di-bisphenoxide aluminate fragment [Al(mcmip)2] containing two 2,2′-methylenebis(4-chloro-3-methyl-6-(isopropyl)phenol) ligands. Both aluminum bisphenoxides were tested as catalysts in the copolymerization of cyclohexene oxide with CO2 and displayed similar good catalytic activities although the carbonate amounts present in the copolymer remain low. [Copyright &y& Elsevier]

Abstract: Introduction: Host cell lines used for recombinant protein expression differ in their ability to perform post-translational modifications (PTMs). The currently available recombinant human FVIII (rhFVIII) products are produced in mammalian, non-human cell lines. For rhFVIII, glycosylation and sulfation are vital for functionality and von Willebrand factor (VWF)-binding affinity. Here we present the characterisation of the PTMs of a novel, human cell line-derived recombinant human FVIII (human-cl rhFVIII). rhFVIII expression in a human cell line avoids expression of undesirable mammalian glycoforms like Galα1-3Galβ1-GlcNAc-R (α-Gal) and N-glycolylneuraminic acid (Neu5Gc), which constitute epitopes antigenic to humans. Materials and methods: We describe sulfation analysis, glycan profiling and characterisation using liquid chromatography-mass spectrometry and high performance anion exchange chromatography with pulsed amperometric detection. Results and conclusions: Human-cl rhFVIII is confirmed to be sulfated and glycosylated comparable to human plasma-derived FVIII. Most importantly, human-cl rhFVIII is devoid of the antigenic Neu5Gc or α-Gal epitopes observed in Chinese Hamster Ovary- and Baby Hamster Kidney-derived rFVIII products. Both the avoidance of non-human glycan structures and the achievement of complete sulfation are proposed to lower the intrinsic immunogenicity of human-cl rhFVIII compared with current rFVIII products. [Copyright &y& Elsevier]

Abstract: Introduction: Hemophilia A is routinely treated by administration of exogenous coagulation factor VIII (FVIII). As safety and efficacy of FVIII products have improved over the years, development of FVIII-neutralizing antibodies (FVIII inhibitors) has emerged as the most serious complication. The new human cell line-derived recombinant human FVIII (human-cl rhFVIII) is the first recombinant FVIII product produced in a human cell line without additive animal proteins, with a goal of minimizing the risk of inhibitor development. Materials and methods: Biochemical analyzes of purity, molecular and functional attributes of the novel human-cl rhFVIII were undertaken for product characterization. Results and conclusions: Human-cl rhFVIII was shown to be highly pure, with host-cell protein and DNA traces comparable to, or lower than, currently marketed recombinant FVIII (rFVIII) products. Human-cl rhFVIII was shown to have high specific FVIII activity and characteristics similar to full-length rFVIII products. Furthermore, no significant discrepancy between one-stage and chromogenic assay results were observed for human-cl rhFVIII, indicating potency ratios of these assays comparable to the full-length rFVIII products. In functional tests, human-cl rhFVIII exhibited physiological thrombin generation and a normal rate of inactivation by activated protein C. Importantly, human-cl rhFVIII displayed higher binding capacity with von Willebrand factor than comparator products, thus minimizing circulating unbound FVIII and further reducing the potential risk of inhibitor development. [Copyright &y& Elsevier]

Introduction Since the early 1990s, recombinant human clotting factor VIII (rhFVIII) produced in hamster cells has been available for haemophilia A treatment. However, the post-translational modifications of these proteins are not identical to those of native human FVIII, which may lead to immunogenic reactions and the development of inhibitors against rhFVIII. For the first time, rhFVIII produced in a human host cell line is available. Aim We describe here the establishment of the first human production cell line for rhFVIII and the manufacturing process of this novel product. Methods and results A human cell line expressing rhFVIII was derived from human embryonic kidney (HEK) 293 F cells transfected with an FVIII expression plasmid. No virus or virus-like particles could be detected following extensive testing. The stringently controlled production process is completely free from added materials of animal or human origin. Multistep purification employing a combination of filtration and chromatography steps ensures the efficient removal of impurities. Solvent/detergent treatment and a 20 nm pore size nanofiltration step, used for the first time in rhFVIII manufacturing, efficiently eliminate any hypothetically present viruses. In contrast to hamster cell-derived products, this rhFVIII product does not contain hamster-like epitopes, which might be expected to be immunogenic. Conclusions HEK 293 F cells, whose parental cell line HEK 293 has been used by researchers for decades, are a suitable production cell line for rhFVIII and will help avoid immunogenic epitopes. A modern manufacturing process has been developed to ensure the highest level of purity and pathogen safety. [ABSTRACT FROM AUTHOR]

Abstract: A series of iron(II)/(III) and cobalt(II)/(III) complexes with the tetradendate tripodal ligands (2-aminoethyl)bis(2-pyridylmethyl)amine (uns-penp), its methylated derivatives Me2-uns-penp and Me4-uns-penp as well as the amide ligand N-acetyl-N,N-bis[(2-pyridyl)methyl]ethylenediamine (acetyl-uns-penp) were synthesized and structurally characterized. They have been investigated in regard to their reactivity towards dioxygen and/or hydrogen peroxide. Complexes of this type seem to have a high potential to be useful in the activation of dioxygen for selective oxidation reactions of organic substrates. [ABSTRACT FROM AUTHOR]

Abstract: Thermosetting epoxy resins, such as the triglycidyl derivative of 4-aminophenol, can be polymerized using molybdenum, palladium, or rhodium complexes as initiators. The resulting metal-doped materials proved to be efficient catalysts for epoxidation, carbon–carbon coupling, hydrogenation, and hydroformylation reactions. Propylene oxide yields of around 50% were obtained in the epoxidation of propylene with tert-butyl hydroperoxide as the oxidant, and biphenyl yields of ⩾98% were observed in the Suzuki coupling of iodobenzene with phenylboronic acid. Almost quantitative conversions were accomplished in the hydrogenation of ethyl crotonate, ethyl cinnamate, and croton aldehyde, whereas aldehyde yields of around 16% were obtained in the hydroformylation of 1-octene. Organic–inorganic hybrid catalysts can be obtained in a convenient one-step procedure by the addition of inorganic components to the liquid resins and subsequent polymerization. Different metal species can be combined in one thermoset matrix, affording multifunctional catalysts that can be us in various catalytic liquid-phase transformations. Quantification of metal traces in the reaction mixtures by metal enrichment and atomic spectroscopy demonstrated very low metal losses of the catalysts. The catalysts can be simply recovered by filtration and reused without reconditioning while maintaining stability, activity, and selectivity. [Copyright &y& Elsevier]

Abstract: The synthesis, spectroscopic characterisation and X-ray structure determination of the first aluminium para-chloro-bisphenoxides [Al2(mbpcp)2(C2H5)2(THF)2] and [Al3(mbpcp)2(C2H5)5] (mbpcp=2,2′-methylenebis(4-chlorophenol) are reported. 2,2′-Methylenebis(4-chlorophenol) was reacted with triethyl aluminium to yield under liberation of ethane, aluminium para-chloro-2,2′-methylene-bisphenoxides with different molecular complexities: a dinuclear and a trinuclear specie, both displaying two bridging bisphenoxide ligands. The nature of the solvent (coordinating or not) influences the aggregation degree of the final product. The use of a coordinating solvent like THF yields a dimeric structure with a bisphenol:metal ratio of 1 to 1 which displays a trigonal-bipyramidal coordination geometry around the aluminium atoms whereas using an apolar, weak-coordinating solvent like diethyl ether yields a trinuclear species with a bisphenol:metal ratio of 2 to 3, displaying aluminium atoms with both tetrahedral and trigonal-bipyramidal coordination geometries. These compounds were tested in preliminary screening tests as catalysts of the homopolymerisation of cyclohexene oxide (CHO) and copolymerisation of CHO with carbon dioxide. Both aluminium bisphenoxides are highly active in the ring opening polymerisation of CHO (RT, reaction time <5min, M n ranging from 31000 to 40700g/mol, polydispersities from 1.2 to 1.4). Both compound are also active in the copolymerisation of CHO with CO2 although the carbonate amount remains low (75bar, 90°C, reaction time 8h, M n ranging from 6800 to 15200g/mol, polydispersities from 1.9 to 2.5). [Copyright &y& Elsevier]

Abstract: Reacting triethyl aluminum and diethyl aluminum chloride with the chelating bisphenol ligands mdtbpH2 and mmcpH2 [mmcpH2: 2,2′-methylenebis(4-methyl-6-(1-methyl-cyclohexyl)phenol); mdtbpH2: 2,2′-methylenebis(4,6-di-tert-butyl-phenol)] afforded monomeric and dimeric aluminum bisphenoxides with reactive Al–Cl and Al–C2H5 moieties. We present here the X-ray structure determination of some of the isolated compounds as well as the preliminary catalytic tests in copolymerization reactions with cyclohexene oxide and carbon dioxide. [Copyright &y& Elsevier]

Abstract: The title compound (1) was prepared by the reaction of 3,5-bis(CF3)C6H3P(i-C3H7)2 (L1) and Co2(CO)8. Its solubility in supercritical carbon dioxide was measured at varying temperatures and pressures using a modified analytical extraction device. Solubility data were determined in the temperature and pressure ranges between 40 and 70°C and between 100 and 300bar, respectively. The solubility of 1 is lower compared to (p-CF3C6H4)3P, but much higher than for transition metal complexes bearing phosphines without fluorinated substituents. [Copyright &y& Elsevier]

Introduction: Simoctocog alfa (Nuwiq®) is a 4th generation recombinant FVIII with proven efficacy for the prevention and treatment of bleeding episodes (BEs) in previously treated patients with severe haemophilia A. The NuProtect study assessed the immunogenicity, efficacy and safety of simoctocog alfa in 108 previously untreated patients (PUPs). The incidence of high-titre inhibitors was 16.2% and no patients with non-null F8 mutations developed inhibitors., Aim: To report the efficacy and safety results from the NuProtect study., Methods: PUPs received simoctocog alfa for prophylaxis, treatment of BEs, or as surgical prophylaxis. The efficacy of prophylaxis (during inhibitor-free periods) was assessed using annualised bleeding rates (ABRs). The efficacy in treating BEs and in surgical prophylaxis was assessed using a 4-point scale. Adverse events were recorded throughout the study., Results: Of 108 PUPs treated with simoctocog alfa, 103 received at least one prophylactic dose and 50 received continuous prophylaxis for at least 24 weeks. In patients on continuous prophylaxis, the median ABR was 0 (mean 0.5) for spontaneous BEs and 2.5 (mean 3.6) for all BEs. In 85 patients who had BEs, efficacy of BE treatment was excellent or good for 92.9% (747/804) of rated BEs; 92.3% of BEs were treated with 1 or 2 infusions. The efficacy of surgical prophylaxis was excellent or good for 94.7% (18/19) of rated procedures. There were no safety concerns and no thromboembolic events., Conclusion: Simoctocog alfa was efficacious and well tolerated as prophylaxis, surgical prophylaxis and for the treatment of BEs in PUPs with severe haemophilia A., (© 2023 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

We report on the crystallite growth of nanometric NpO 2 and UO 2 powders. The AnO 2 nanoparticles (An = U and Np) were synthesized by hydrothermal decomposition of the corresponding actinide(iv) oxalates. NpO 2 powder was isothermally annealed between 950 °C and 1150 °C and UO 2 between 650 °C and 1000 °C. The crystallite growth was then followed by high-temperature X-ray diffraction (HT-XRD). The activation energies for the growth of crystallites of UO 2 and NpO 2 were determined to be 264(26) kJ mol -1 and 442(32) kJ mol -1 , respectively, with a growth exponent n = 4. The value of the exponent n and the low activation energy suggest that the crystalline growth is rate-controlled by the mobility of the pores, which migrate by atomic diffusion along the pore surfaces. We could thus estimate the cation self-diffusion coefficient along the surface in UO 2 , NpO 2 and PuO 2 . While data for surface diffusion coefficients for NpO 2 and PuO 2 are lacking in the literature, the comparison with literature data for UO 2 supports further the hypothesis of a surface diffusion controlled growth mechanism., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Covalency involving the 5f orbitals is regularly invoked to explain the reactivity, structure and spectroscopic properties of the actinides, but the ionic versus covalent nature of metal-ligand bonding in actinide complexes remains controversial. The tetrakis 2,6-di-tert-butylphenoxide complexes of Th, U and Np form an isostructural series of crystal structures containing approximately tetrahedral MO 4 cores. We show that up to 3 GPa the Th and U crystal structures show negative linear compressibility as the OMO angles distort. At 3 GPa the angles snap back to their original values, reverting to a tetrahedral geometry with an abrupt shortening of the M-O distances by up to 0.1 Å. The Np complex shows similar but smaller effects, transforming above 2.4 GPa. Electronic structure calculations associate the M-O bond shortening with a change in covalency resulting from increased contributions to the M-O bonding by the metal 6d and 5f orbitals, the combination promoting MO 4 flexibility at little cost in energy., (© 2022. The Author(s).)

This paper details the first dedicated production of homogeneous nanocrystalline particles of mixed actinide oxide solid solutions containing americium. The target compositions were U 0.75 Pu 0.20 Am 0.05 O 2 , U 0.90 Am 0.10 O 2 and U 0.80 Am 0.20 O 2 . After successful hydrothermal synthesis and chemical characterisation, the nanocrystals were sintered and their structure and behaviour under self-irradiation were studied by powder XRD. Cationic charge distribution of the as-prepared nanocrystalline and sintered U 0.80 Am 0.20 O 2 materials was investigated applying U M 4 and Am M 5 edge high energy resolution XANES (HR-XANES). Typical oxidation states detected for the cations are U(iv)/U(v) and Am(iii)/Am(iv). The measured crystallographic swelling was systematically smaller for the as-synthesised nanoparticles than the sintered products. For sintered pellets, the maximal volumetric swelling was about 0.8% at saturation, in line with literature data for PuO 2 , AmO 2 , (U,Pu)O 2 or (U,Am)O 2 ., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

The ternary neptunium(V) (Np(V)) hydroxides Na 0.5 [NpO 2 (OH) 1.5 ]·0.5H 2 O (I) and Na[NpO 2 (OH) 2 ] (II) were synthesized in aqueous NaOH solutions at T = 80 °C, and their crystal structures were determined to be monoclinic, P 2 1 , Z = 2, a = 5.9859(2), b = 10.1932(3), c = 12.1524(4) Å, β = 98.864(1)°, V = 732.63(4) Å 3 for (I) and orthorhombic, P 2 1 2 1 2 1 , Z = 4, a = 5.856(7), b = 7.621(9), c = 8.174(9) Å, V = 364.8(7) Å 3 for (II) . By combining the detailed structural information with results from systematic solubility investigations, a comprehensive chemical and thermodynamic model of the Np(V) behavior in NaCl-NaOH solutions was evaluated. The results reveal a great stability of the ternary Na-Np(V)-OH solid phases that significantly enhances the predominance field of the entire Np(V) redox state to high alkalinity.

Background  Immune tolerance induction (ITI) with repeated factor VIII (FVIII) administration is the only strategy proven to eradicate inhibitors. The observational ITI study is evaluating ITI with a range of FVIII products. Methods  This subgroup analysis reports prospective interim data for patients treated with a plasma-derived, von Willebrand factor-stabilized FVIII concentrate (pdFVIII/VWF, octanate). Complete success (CS) of ITI required achievement of three criteria: inhibitor titer < 0.6 BU/mL; FVIII recovery ≥ 66%; FVIII half-life ≥6 hours. Partial success (PS) required achievement of two criteria and partial response (PR) one. ITI success was defined as CS or PS. Data were analyzed for patients who achieved CS, had 36 months' observation, or failed ITI. Results  One-hundred prospectively enrolled patients were included in the analysis; 91 had poor prognosis factors for ITI success. The mean (standard deviation) daily ITI dose was 116.4 (61.1) IU FVIII/kg in 14 low responders (< 5 BU/mL) and 173.7 (112.0) IU FVIII/kg in 86 high responders (≥ 5 BU/mL). Inhibitor titers < 0.6 BU/mL were achieved in 71% of patients in a median of 4.01 months, accompanied by a 93% reduction in bleeding rate. ITI success was achieved by 70% of patients and 56 of 72 (78%) primary (first-line) ITI patients. PR was achieved by 5 patients; ITI failed in 25 patients. PS and CS were achieved in a median of 5.55 and 11.25 months, respectively. Conclusions  ITI with pdFVIII/VWF led to rapid eradication of FVIII inhibitors, normalization of FVIII pharmacokinetics in the majority of patients, and a significant reduction in bleeding rates., Competing Interests: Conflict of Interest C. Escuriola Ettingshausen has acted as a consultant and received speaker's fees and/or research funding from the following companies: Bayer, Biomarin, Biotest, Chugai, CSL Behring, Grifols, Kedrion, Novo Nordisk Octapharma, Roche, Swedish Orphan Biovitrum and Takeda. V. Vdovin has participated in studies sponsored by Bayer, Generium, Novo Nordisk, Octapharma and Roche. N. Zozulya has acted as a consultant and received speaker's fees and/or research funding from the following companies: CSL Behring, Generium, Novo Nordisk, Octapharma, Roche, SOBI and Takeda. T. Andreeva has received speaker's fees and/or research funding from Bayer, Baxalta, Biomarin, Catalis, CSL Behring, Generium, Grifols, Novo Nordisk, Octapharma and Roche, and has consulted for CSL Behring, Generium, Novo Nordisk, Octapharma, Roche, Shire and Swedish Orphan Biovitrum. V Jiménez-Yuste has acted as a consultant and/or received speaker's fees and/or research funding from the following companies: Bayer, Grifols, Novo Nordisk, Octapharma, Pfizer, Swedish Orphan Biovitrum and Takeda. L. Kitanovski has acted as a consultant and received speaker's fees from the following companies: Bayer, Novo Nordisk, Octapharma, Roche, Takeda and Swedish Orphan Biovitrum. S. Zupančić Šalek has acted as a consultant and/or received speaker's fees and/or research funding from following companies: Bayer, Novo Nordisk, Octapharma, Roche, Swedish Orphan Biovitrum and Takeda. A. Pavlova has participated in studies sponsored by Octapharma AG. A. Bátorová has acted as a consultant and/or received speaker's fees and/or research funding from the following companies: Grifols, Novo Nordisk, Octapharma, Pfizer, Swedish Orphan Biovitrum and Takeda. C. Montaño Mejía has received speaker's fees from Octapharma and Roche; travel support from CSL Behring, Grifols, Novo Nordisk, Octapharma, Pfizer, Roche and Takeda. J. Oldenburg has acted as a consultant and/or received speaker's fees, honoraria and research funding from the following companies: Bayer, Biogen Idec, Biotest, CSL Behring, Grifols, Novo Nordisk, Octapharma, Pfizer, Swedish Orphan Biovitrum and Takeda. S. Knaub, S. Lowndes, L. Belyanskaya and O. Walter are employees of Octapharma AG. M. Jansen is an employee of Octapharma Pharmazeutika Produktionsges.mbH. P. Svirin, M. Benedik-Dolničar and G. Abdilova stated that they had no conflicts of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Neptunium was the first actinide element to be artificially synthesized, yet, compared with its more famous neighbours uranium and plutonium, is less conspicuously studied. Most neptunium chemistry involves the neptunyl di(oxo)-motif, and transuranic compounds with one metal-ligand multiple bond are rare, being found only in extended-structure oxide, fluoride or oxyhalide materials. These combinations stabilize the required high oxidation states, which are otherwise challenging to realize for transuranic ions. Here we report the synthesis, isolation and characterization of a stable molecular neptunium(V)-mono(oxo) triamidoamine complex. We describe a strong Np≡O triple bond with dominant 5f-orbital contributions and σ u  > π u energy ordering, akin to terminal uranium-nitrides and di(oxo)-actinyls, but not the uranium-mono(oxo) triple bonds or other actinide multiple bonds reported so far. This work demonstrates that molecular high-oxidation-state transuranic complexes with a single metal-ligand bond can be stabilized and studied in isolation., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

We performed a systematic study of the complexes of trivalent lanthanide cations with the hydridotris(1-pyrazolyl)borato (Tp) ligand (LnTp 3 ; Ln = La, Ce, Pr, Nd, Sm, Eu, Tb, Dy, Ho, Er, Tm, Yb, and Lu) using both high-energy-resolution fluorescence-detected X-ray absorption near-edge structure (HERFD-XANES) and resonant inelastic X-ray scattering (RIXS) at the lanthanide L 3 absorption edge. Here, we report the results obtained and we discuss them against calculations performed using density functional theory (DFT) and atomic multiplet theory. The spectral shape and the elemental trends observed in the experimental HERFD-XANES spectra are well reproduced by DFT calculations, while the pre-edge energy interval is better described by atomic multiplet theory. The RIXS data show a generally rather complex pattern that originates from the intra-atomic electron-electron interactions in the intermediate and final states, as demonstrated by the good agreement obtained with calculations using an atomic-only model of the absorber. Guided by theoretical predictions, we discuss the possible origins of the observed spectral features and the trends in energy splitting across the series. The insight into the electronic structure of trivalent lanthanide compounds demonstrated here and obtained with advanced X-ray spectroscopies coupled with theoretical calculations can be applied to any lanthanide-bearing compound and be of great interest for all research fields involving lanthanides.

When in contact with oxidizing media, UO 2 pellets used as nuclear fuel may transform into U 4 O 9 , U 3 O 7 , and U 3 O 8 . The latter starts forming by stress-induced phase transformation only upon cracking of the pristine U 3 O 7 and is associated with a 36% volumetric expansion with respect to the initial UO 2 . This may pose a safety issue for spent nuclear fuel (SNF) management as it could imply a confinement failure and hence dispersion of radionuclides within the environment. In this work, UO 2 with different grain sizes (representative of the grain size in different radial positions in the SNF) was oxidized in air at 300 °C, and the oxidation mechanisms were investigated using in situ synchrotron X-ray diffraction. The formation of U 3 O 8 was detected only in UO 2 pellets with larger grains (3.08 ± 0.06 μm and 478 ± 17 nm), while U 3 O 8 did not develop in sintered UO 2 with a grain size of 163 ± 9 nm. This result shows that, in dense materials, a sufficiently fine microstructure inhibits both the cracking of U 3 O 7 and the subsequent formation of U 3 O 8 . Hence, the nanostructure prevents the material from undergoing significant volumetric expansion. Considering that the peripheral region of SNF is constituted by the high burnup structure, characterized by 100-300 nm-sized grains and micrometric porosity, these findings are relevant for a better understanding of the spent nuclear fuel behavior and hence for the safety of the nuclear waste storage.

In view of safe management of the nuclear wastes, a sound knowledge of the atomic-scale properties of U 1- x M x O 2+ y nanoparticles is essential. In particular, their cation valences and oxygen stoichiometries are of great interest as these properties drive their diffusion and migration behaviors into the environment. Here, we present an in-depth study of U 1- x Ce x O 2+ y , over the full compositional domain, by combining X-ray diffraction and high-energy resolution fluorescence detection X-ray absorption near-edge structure. We show, on one hand, the coexistence of U IV , U V , and U VI and, on the other hand, that the fluorite structure is maintained despite this charge distribution.

A series of tetradentate N2O2-type Schiff base complexes with tetravalent 4f- and 5f-block metals, [M(salpn)2] (H2salpn = N,N'-disalicylidene-1,3-diaminopropane; M = Ce, Th, U, Np, and Pu), were prepared to systematically investigate their solid state structure, and their complexation behaviour in solution with the goal to investigate the subtle differences between 4f- and 5f-elements. X-ray diffraction revealed that all investigated metal cations form [M(salpn)2] complexes. All the complexes show the same ligand arrangement with meridional conformation, amongst which only Ce(iv) exhibits unique behaviour upon crystallisation. [Ce(salpn)2] crystallises in two less symmetric systems (P1[combining macron] or P21/n), whilst all the other [M(salpn)2] crystallise in a more symmetric orthorhombic system (Pban). Quantum chemical calculations suggest that the observed structural peculiarity of Ce(iv) stems from the geometrical flexibility due to the more "ionic" nature of bonds to the 4f element. 1H NMR measurements revealed that [M(salpn)2] forms two different species in solution with and without an additional solvent molecule, where the relative distribution of the two species depends mainly on the ionic radius of the metal centre. Again, Ce(iv) behaves differently from the tetravalent actinides with a higher ratio of the solvent-molecule-coordinated species than the ratio expected from its ionic radius. Hence, this study is successful in observing subtle differences between 4f- (i.e. Ce) and 5f-elements (actinides; Th, U, Np, and Pu) both in the solid state and in solution on an analytically distinguishable level, and in relating the observed subtle differences to their electronic structure.

A systematic investigation is presented which examines the structural chemistry of anhydrous and hydrous ternary hexavalent uranium and neptunium dinitrato, trinitrato, and tetranitrato complexes. Using slow evaporation methods under acidic conditions the uranium and neptunium nitrate complexes γ-K[UO 2 (NO 3 ) 3 ], K 2 [UO 2 - cis -(NO 3 ) 4 ], [NpO 2 (NO 3 ) 2 (H 2 O) 2 ]·4H 2 O, and Cs[NpO 2 (NO 3 ) 3 ] have been synthesized and their structures refined using single-crystal X-ray diffraction data. γ-K[UO 2 (NO 3 ) 3 ] adopts an orthorhombic structure in space group Pbca consisting of antiparallel aligned [UO 2 (NO 3 ) 3 ] - moieties. K 2 [UO 2 - cis -(NO 3 ) 4 ] adopts a monoclinic structure in space group P 2 1 / c consisting of [UO 2 (NO 3 ) 4 ] 2- moieties with two monodentate and two bidentate nitrate ligands that are arranged in a cis configuration about the uranyl, UO 2 2+ , center. Previous investigations have only identified trans variants of this monoclinic structure, and this is the first report of the cis form and also the occurrence of geometric isomerism in uranyl nitrates. [NpO 2 (NO 3 ) 2 (H 2 O) 2 ]·4H 2 O adopts an orthorhombic structure in space group Cmc 2 1 consisting of parallel aligned [NpO 2 (NO 3 ) 2 (H 2 O) 2 ] moieties that are in a trans configuration with respect to the bidentate nitrate ligands. Cs[NpO 2 (NO 3 ) 3 ] adopts a hexagonal structure in space group R 3 c consisting of parallel aligned [NpO 2 (NO 3 ) 3 ] - moieties. It was found that despite using a Np(V) nitrate solution as the starting reagent, Np(VI) nitrate structures were consistently recovered under acidic conditions. These observations are discussed and rationalized with respect to standard reduction potentials, particularly how redox conditions and acidity affect the oxidation state of Np and subsequent structure formation. The structures uncovered in this investigation are discussed comparatively and systematically in detail with other reported anhydrous and hydrous ternary hexavalent uranium and neptunium dinitrato, trinitrato, and tetranitrato complexes, particularly with respect to how synthesis conditions, including pH and geometric isomerism, affect the structural chemistry.

Intrinsic properties of a compound (e.g., electronic structure, crystallographic structure, optical and magnetic properties) define notably its chemical and physical behavior. In the case of nanomaterials, these fundamental properties depend on the occurrence of quantum mechanical size effects and on the considerable increase of the surface to bulk ratio. Here, we explore the size dependence of both crystal and electronic properties of CeO 2 nanoparticles (NPs) with different sizes by state-of-the art spectroscopic techniques. X-ray diffraction, X-ray photoelectron spectroscopy, and high-energy resolution fluorescence-detection hard X-ray absorption near-edge structure (HERFD-XANES) spectroscopy demonstrate that the as-synthesized NPs crystallize in the fluorite structure and they are predominantly composed of Ce IV ions. The strong dependence of the lattice parameter with the NPs size was attributed to the presence of adsorbed species at the NPs surface thanks to Fourier transform infrared spectroscopy and thermogravimetric analysis measurements. In addition, the size dependence of the t 2g states in the Ce L III XANES spectra was experimentally observed by HERFD-XANES and confirmed by theoretical calculations.

Here we provide evidence that the formation of PuO 2 nanoparticles from oxidized Pu VI under alkaline conditions proceeds through the formation of an intermediate Pu V solid phase, similar to NH 4 PuO 2 CO 3 , which is stable over a period of several months. For the first time, state-of-the-art experiments at Pu M 4 and at L 3 absorption edges combined with theoretical calculations unambiguously allow to determine the oxidation state and the local structure of this intermediate phase., (© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Background: Accurate determination of coagulation factor VIII activity (FVIII:C) is essential for effective and safe FVIII replacement therapy., Fviii: C can be measured by one-stage and chromogenic substrate assays (OSAs and CSAs, respectively); however, there is significant interlaboratory and interassay variability., Aims: This international comparative field study characterized the behaviour of OSAs and CSAs used in routine laboratory practice to measure the activity of Nuwiq ® (human-cl rhFVIII, simoctocog alfa), a fourth-generation recombinant human FVIII produced in a human cell line., Methods: FVIII-deficient plasma was spiked with Nuwiq ® or Advate ® at 1, 5, 30 and 100 international units (IU)/dL. Participating laboratories analysed the samples using their routine procedures and equipment. Accuracy, inter- and intralaboratory variation, CSA:OSA ratio and the impact of different OSA and CSA reagents were assessed., Results: Forty-nine laboratories from 9 countries provided results. Mean absolute FVIII:C was comparable for both products at all concentrations with both OSA and CSA, with interproduct ratios (Nuwiq ® :Advate ® ) of 1.02-1.13. Mean recoveries ranged from 97% to 191% for Nuwiq ® , and from 93% to 172% for Advate ® , with higher recoveries at lower concentrations. Subgroup analyses by OSA and CSA reagents showed minor variations depending on reagents, but no marked differences between the two products. CSA:OSA ratios based on overall means ranged from 0.99 to 1.17 for Nuwiq ® and from 1.01 to 1.17 for Advate ® ., Conclusions: Both OSAs and CSAs are suitable for the measurement of FVIII:C of Nuwiq ® in routine laboratory practice, without the need for a product-specific reference standard., (© 2019 The Authors. Haemophilia Published by John Wiley & Sons Ltd.)

Recent developments and results from the organometallic chemistry of the actinides are reviewed. In the last one and a half years the structural data of about 15 organometallic complexes of transuranium actinides (Np or Pu) have been published, all involving π-ligands in the coordination sphere of the metal ion. On the basis of these data, a comparison of these molecules is presented. Depending on the steric demands of the ligands, effects like the actinide contraction seem to be stronger or weaker in the structural features. This indicates that the interplay between the actinide ion and the π-ligand is rather flexible, enabling the formation of stable bonds over a broad range of actinide ion oxidation states., (© 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Kinetic measurements on the grain growth of PuO 2 nano-crystals are presented. On the basis of isothermal XRD measurements at temperatures of 820 °C, 900 °C, 1000 °C, and 1100 °C the activation energy for the crystallite growth of PuO 2 nanopowder is determined as 351(5) kJ mol -1 in the temperature range from 820 to 1000 °C. Modelling shows that in this T range growth happens likely through surface diffusion., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

A study of neptunium (Np) chemistry in the complex oxo-selenium system has been performed. Hereby, two sets of precipitation experiments were conducted, investigating the influence of the initial oxidation state of selenium using Se IV O 2 and H 2 Se VI O 4 with Np V in alkali nitrate solution, keeping the ratio of Np/Se constant. Surprising results were observed. Five novel neptunium and selenium bearing compounds have been obtained by slow evaporation from aqueous solution. The novel Np IV phase K 4-x [Np(SeO 3 ) 4-x (HSeO 3 ) x ]·(H 2 O) 1.5 (1) crystallizes in green-colored, plate-shaped crystals and was obtained by adding SeO 2 and ANO 3 to a Np V stock solution. Single-crystal X-ray diffraction reveals one-dimensional chain structures composed of square antiprismatic NpO 8 polyhedra linked via four trigonal pyramidal SeO 3 and HSeO 3 units. Raman spectral analysis supports the presence of both selenite and hydroselenite due to the presence of corresponding modes within the spectra. The addition of selenic acid to a Np V stock solution resulted in the precipitation of elongated rose prisms of K 2 [(NpO 2 ) 2 (SeO 4 ) 3 (H 2 O) 2 ]·(H 2 O) 1.5 (2), Rb 2 [(NpO 2 ) 2 (SeO 4 ) 3 (H 2 O) 2 ]·(H 2 O) 2 (3) and K 9 [(NpO 2 ) 9 (SeO 4 ) 13.5 (H 2 O) 6 ]·(H 2 O) 12 (4) as well as light red plates of Cs 2 [(NpO 2 ) 2 (SeO 4 ) 3 ] (5). To our knowledge, this is the first report of Np VI selenates. All four structures show two-dimensional layered structures with alkali cations acting as charge balancing counter cations. Hereby the layers of compounds 2 and 3 are found to be orientational geometric isomers. Distinctly different phenomena are made responsible for the phase formation within these systems. The kinetically driven process of Np V disproportionation led to the formation of the Np IV selenites in the Se IV -based system, whereas the oxidation of Np V by reduction of nitrate in acidic conditions is responsible for the formation of the Np VI selenates in the Se VI system. The influence of air oxygen is also discussed for the latter reaction.

The blood-red plutonocene complex Pu(1,3-COT'')(1,4-COT'') (4; COT''=η 8 -bis(trimethylsilyl)cyclooctatetraenyl) has been synthesized by oxidation of the anionic sandwich complex Li[Pu(1,4-COT'') 2 ] (3) with anhydrous cobalt(II) chloride. The first crystal structure determination of an organoplutonium(IV) complex revealed an asymmetric sandwich structure for 4 where one COT'' ring is 1,3-substituted while the other retains the original 1,4-substitution pattern. The electronic structure of 4 has been elucidated by a computational study, revealing a probable cause for the unexpected silyl group migration., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Neptunium complexes in the formal oxidation states II, III, and IV supported by cyclopentadienyl ligands are explored, and significant differences between Np and U highlighted as a result. A series of neptunium(iii) cyclopentadienyl (Cp) complexes [Np(Cp) 3 ], its bis-acetonitrile adduct [Np(Cp) 3 (NCMe) 2 ], and its KCp adduct K[Np(Cp) 4 ] and [Np(Cp') 3 ] (Cp' = C 5 H 4 SiMe 3 ) have been made and characterised providing the first single crystal X-ray analyses of Np III Cp complexes. In all NpCp 3 derivatives there are three Cp rings in η 5 -coordination around the Np III centre; additionally in [Np(Cp) 3 ] and K[Np(Cp) 4 ] one Cp ring establishes a μ-η 1 -interaction to one C atom of a neighbouring Np(Cp) 3 unit. The solid state structure of K[Np(Cp) 4 ] is unique in containing two different types of metal-Cp coordination geometries in the same crystal. Np III (Cp) 4 units are found exhibiting four units of η 5 -coordinated Cp rings like in the known complex [Np IV (Cp) 4 ], the structure of which is now reported. A detailed comparison of the structures gives evidence for the change of ionic radii of ca. -8 pm associated with change in oxidation state between Np III and Np IV . The rich redox chemistry associated with the syntheses is augmented by the reduction of [Np(Cp') 3 ] by KC 8 in the presence of 2.2.2-cryptand to afford a neptunium(ii) complex that is thermally unstable above -10 °C like the U II and Th II complexes K(2.2.2-cryptand)[Th/U(Cp') 3 ]. Together, these spontaneous and controlled redox reactions of organo-neptunium complexes, along with information from structural characterisation, show the relevance of organometallic Np chemistry to understanding fundamental structure and bonding in the minor actinides.

A dramatic difference in the ability of the reducing An(III) center in AnCp3 (An=U, Np, Pu; Cp=C5 H5 ) to oxo-bind and reduce the uranyl(VI) dication in the complex [(UO2 )(THF)(H2 L)] (L="Pacman" Schiff-base polypyrrolic macrocycle), is found and explained. These are the first selective functionalizations of the uranyl oxo by another actinide cation. At-first contradictory electronic structural data are explained by combining theory and experiment. Complete one-electron transfer from Cp3 U forms the U(IV) -uranyl(V) compound that behaves as a U(V) -localized single molecule magnet below 4 K. The extent of reduction by the Cp3 Np group upon oxo-coordination is much less, with a Np(III) -uranyl(VI) dative bond assigned. Solution NMR and NIR spectroscopy suggest Np(IV) U(V) but single-crystal X-ray diffraction and SQUID magnetometry suggest a Np(III) -U(VI) assignment. DFT-calculated Hirshfeld charge and spin density analyses suggest half an electron has transferred, and these explain the strongly shifted NMR spectra by spin density contributions at the hydrogen nuclei. The Pu(III) -U(VI) interaction is too weak to be observed in THF solvent, in agreement with calculated predictions., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Studies of transuranic organometallic complexes provide a particularly valuable insight into covalent contributions to the metal-ligand bonding, in which the subtle differences between the transuranium actinide ions and their lighter lanthanide counterparts are of fundamental importance for the effective remediation of nuclear waste. Unlike the organometallic chemistry of uranium, which has focused strongly on U(III) and has seen some spectacular advances, that of the transuranics is significantly technically more challenging and has remained dormant. In the case of neptunium, it is limited mainly to Np(IV). Here we report the synthesis of three new Np(III) organometallic compounds and the characterization of their molecular and electronic structures. These studies suggest that Np(III) complexes could act as single-molecule magnets, and that the lower oxidation state of Np(II) is chemically accessible. In comparison with lanthanide analogues, significant d- and f-electron contributions to key Np(III) orbitals are observed, which shows that fundamental neptunium organometallic chemistry can provide new insights into the behaviour of f-elements.

The slightly yellow-coloured title complex, [Zn(C18H16N4O4)(H2O)] n , crystallizes with one mol-ecule in the asymmetric unit. The structure clearly shows the mer-η(4) O,O,N,N-binding mode of the N,N'-bis-(2-cyano-ethyl-propeno-yl)-1,2-di-amido-benzene ligand stabilizing the Zn centre of a distorted octa-hedral environment. The fifth coordination site in one apical position is held by a coordinating solvent water mol-ecule whereas the complete octa-hedral coordination sphere is completed by coordination of one N atom from a CN group of a neighbouring mol-ecule, leading to the final polymeric structure consisting of zigzag staggered chains in parallel orientation along the c-axis direction. Between the coord-in-ated water solvent molecule and the N atoms of uncoord-in-ated cyano-groups of neighboured units, two H-bridge bonds are formed. One of these H-bridge bonds is of inter- whereas the other of intra-strand nature, leading to a two-dimensional network parallel to (110) stabilizing the supramolecular structure. Six Zn-O or Zn-N bonds are found with lengths ranging from 2.061 (1) to 2.185 (1) Å and bond angles about the Zn atom are clustered in the ranges 79.83 (4)-104.21 (4) and 167.05 (4)-170.28 (4)°.

The title compound, C12H20N2O4, represents one example of a zwitterionic imidazolium salt with a carboxyl-ate group at the 2-position of the imidazolium ring. The dihedral angle between the heterocyclic ring and the carboxyl-ate group is 31.3 (1)°. The side chain linking the N atom of the ring and the methine C atom has a gauche-anti-anti conformation [torsion angles = -60.3 (2), -175.7 (2) and 178.7 (2)°, respectively]. In the crystal, mol-ecules are linked by short C-H⋯O hydrogen bonds involving the C-H groups in the aromatic ring to generate (001) sheets.

The colourless title complex, [Zn2(C10H11O5)4(C2H6OS)2], crystallizes with one half-mol-ecule in the asymmetric unit, the other half of the mol-ecule being generated by a crystallographic inversion center. The structure shows a μ2-O:O'-bridging mode of the four 3,4,5-tri-meth-oxy-benzoate ligands finally stabilizing the two Zn(II) atoms in the dinuclear complex in a distorted square-pyramidal environment. The fifth coord-in-ation site in the apical position of the pyramid is occupied by a coordinating dimethyl sulfoxide solvent mol-ecule equally disordered over two positions.

In the colourless title compound, [Pr(CF3O3S)3(CH3CN)3] n , the three trifluoro-methane-sulfonate anions form three bridges via O:O'-coordination between two Pr(III) atoms. The structure contains [Pr(NCMe)3-μ2(OTf)3-Pr(NCMe)3-μ2(OTf)3] n (NCMe is acetonitrile; OTf is trifluoromethanesulfonate) chains parallel to the a axis. The Pr(III) atom is nine-coordinate in a distorted tricapped trigonal-prismatic environment.

The structure of the title complex, [ReBr(C(13)H(19)OP)(CO)(3)], displays a facial coordination of the three CO ligands and a κ(2)O,P coordination mode of the 2-diisopropyl-phosphino-benzaldehyde ligands. The Re-C bond distance for the CO ligand trans to the P atom is, due to its trans influence, elongated to 1.943 (3) Å, showing that this CO ligand is more weakly bound to the Re centre than the other two.

The copper(II) complexes [Cu(4)(1,3-tpbd)(2)(H(2)O)(4)(NO(3))(4)](n)(NO(3))(4n)·13nH(2)O (1), [Cu(4)(1,3-tpbd)(2)(AsO(4))(ClO(4))(3)(H(2)O)](ClO(4))(2)·2H(2)O·0.5CH(3)OH (2), [Cu(4)(1,3-tpbd)(2)(PO(4))(ClO(4))(3)(H(2)O)](ClO(4))(2)·2H(2)O·0.5CH(3)OH (3), [Cu(2)(1,3-tpbd){(PhO)(2)PO(2)}(2)](2)(ClO(4))(4) (4), and [Cu(2)(1,3-tpbd){(PhO)PO(3)}(2)(H(2)O)(0.69)(CH(3)CN)(0.31)](2)(BPh(4))(4)·Et(2)O·CH(3)CN (5) [1,3-tpbd = N,N,N',N'-tetrakis(2-pyridylmethyl)-1,3-benzenediamine, BPh(4)(-) = tetraphenylborate] were prepared and structurally characterized. Analyses of the magnetic data of 2, 3, 4, and [Cu(2)(2,6-tpcd)(H(2)O)Cl](ClO(4))(2) (6) [2,6-tpcd = 2,6-bis[bis(2-pyridylmethyl)amino]-p-cresolate] show the occurrence of weak antiferromagnetic interactions between the copper(II) ions, the bis-terdentate 1,3-tpbd/2,6-tpcd, μ(4)-XO(4) (X = As and P) μ(1,2)-OPO and μ-O(phenolate) appearing as poor mediators of exchange interactions in this series of compounds. Simple orbital symmetry considerations based on the structural knowledge account for the small magnitude of the magnetic couplings found in these copper(II) compounds.

Ruthenium complexes, mer-[RuX(3)(MeCN)(3)] and cis/trans-[RuX(2)(MeCN)(4)] with X=Br, Cl, were investigated as precatalysts in homogeneously catalyzed hydrosilylation of CO(2). The oxidation state of ruthenium and nature of the halide in the precatalysts were found to influence the catalytic activity in the conversion of Me(2)PhSiH to the formoxysilane Me(2)PhSiOCHO, with Ru(III) having chloride ligands being most active. Monitoring the reactions by in-situ IR spectroscopy in MeCN as the solvent indicates an interaction of the precatalyst with the silane prior to activation of CO(2). In the absence of CO(2), hydrosilylation of the MeCN solvent occurs. Catalytic activity in CO(2) hydrosilylation is enhanced by Me(2)PhSiCl, generated during reduction of Ru(III) in mer-[RuX(3)(MeCN)(3)] to Ru(II) or, when added as promoter to Ru(II) precatalysts. The reaction mechanism for the catalytic cycle has been calculated by DFT methods for the reaction of Me(3)SiH. The key steps are: Transfer of the Me(3)Si moiety to a coordinated halide ligand, resulting in an L(n)RuH(XSiMe(3)) intermediate --> CO(2) coordination --> Me(3)Si transfer to CO(2) --> reductive elimination of formoxysilane product. This reaction sequence is more favorable energetically for chloride complexes than for the analogous bromide complexes, which accounts for their differences in catalytic activity. Calculations also explain the rate increase observed experimentally in the presence of Me(2)PhSiCl. A parallel reaction pathway leads to (Me(3)Si)(2)O as a minor byproduct which arises from the condensation of two initially formed Me(3)SiOH molecules.