Sub-10 nm Radiolabeled Barium Sulfate Nanoparticles as Carriers for Theranostic Applications and Targeted Alpha Therapy

The treatment of cancer patients with α-particle-emitting therapeutics continues to gain in importance and relevance. The range of radiopharmaceutically relevant α-emitters is limited to a few radionuclides, as stable chelators or carrier systems for safe transport of the radioactive cargo are often lacking. Encapsulation of α-emitters into solid inorganic systems can help to diversify the portfolio of candidate radionuclides, provided, that these nanomaterials effectively retain both the parent and the recoil daughters. We therefore focus on designing stable and defined nanocarrier-based systems for various clinically relevant radionuclides, including the promising α-emitting radionuclide ²²⁴Ra. Hence, sub-10 nm barium sulfate nanocontainers were prepared and different radiometals like ⁸⁹Zr, ¹¹¹In, ¹³¹Ba, ¹⁷⁷Lu or ²²⁴Ra were incorporated. Our system shows stabilities of >90 % regarding the radiometal release from the BaSO₄ matrix. Furthermore, we confirm the presence of surface-exposed amine functionalities as well as the formation of a biomolecular corona.     

Influence of viscoelasticity on drop deformation and orientation in shear flow: Part 1. Stationary states

The influence of matrix and droplet viscoelasticity on the steady deformation and orientation of a single droplet subjected to simple shear is investigated microscopically. Experimental data are obtained in the velocity–vorticity and velocity–velocity gradient plane. A constant viscosity Boger fluid is used, as well as a shear-thinning viscoelastic fluid. These materials are described by means of an Oldroyd-B, Giesekus, Ellis, or multi-mode Giesekus constitutive equation. The drop-to-matrix viscosity ratio is 1.5. The numerical simulations in 3D are performed with a volume-of-fluid algorithm and focus on capillary numbers 0.15 and 0.35. In the case of a viscoelastic matrix, viscoelastic stress fields, computed at varying Deborah numbers, show maxima slightly above the drop tip at the back and below the tip at the front. At both capillary numbers, the simulations with the Oldroyd-B constitutive equation predict the experimentally observed phenomena that matrix viscoelasticity significantly suppresses droplet deformation and promotes droplet orientation. These two effects saturate experimentally at high Deborah numbers. Experimentally, the high Deborah numbers are achieved by decreasing the droplet radius with other parameters unchanged. At the higher capillary and Deborah numbers, the use of the Giesekus model with a small amount of shear-thinning dampens the stationary state deformation slightly and increases the angle of orientation. Droplet viscoelasticity on the other hand hardly affects the steady droplet deformation and orientation, both experimentally and numerically, even at moderate to high capillary and Deborah numbers.     

Analytical evaluation of a rapid on-site oral fluid drug test

There is a need for a reliable rapid on-site oral fluid test that can be used in police controls to detect impaired drivers. We evaluated the Varian Oralab®6 and collected two oral fluid samples from 250 subjects, one with the Varian Oralab®6 and one with the StatSure? Saliva?Sampler?. The Oralab®6 can detect six drug types: amphetamines, methamphetamine, cocaine, opiates, delta9-tetrahydrocannabinol (THC), and phencyclidine (PCP). On-site results were obtained within 10 to 15 min. The sample collected with StatSure? was analyzed using liquid chromatography–tandem mass spectrometry after liquid–liquid extraction and these results were used as a reference to determine prevalence, sensitivity, and specificity. Two cut-off values were used in the evaluation. The Varian cut-off values were: amphetamine 50 ng/mL, cocaine 20 ng/mL, opiates 40 ng/mL, and THC 50 ng/mL. The DRUID cut-offs were: amphetamine 25 ng/mL, cocaine 20 ng/mL, opiates 20 ng/mL, and THC 1 ng/mL. Applying the first cut-offs, prevalence, sensitivity, and specificity were: amphetamine 10%, 76%, 100%; cocaine 23%, 34%, 100%; opiates 38%, 83%, 94%; and THC 18%, 41%, 99%. The DRUID cut-off values gave the following results: amphetamine 14%, 56%, 100%; cocaine 28%, 34%, 100%; opiates 49%, 68%, 98%, and THC 45%, 16%, 99%. The specificity of the Oralab®6 is generally good. For both cut-offs, sensitivity was low for cocaine and THC. Therefore, the Varian Oralab®6 test is not sensitive enough to be applied during roadside police controls.     

The role of innovations in secondary school performance – Evidence from a conditional efficiency model

This paper studies the influence of educational innovations on school performance. We apply a tailored, fully nonparametric conditional efficiency model to study secondary school efficiency in the Netherlands. The application uses official school data and a self-collected questionnaire on recent innovations in schools. In the nonparametric model, it is assumed that schools aim to maximize educational attainments of students under a budget constraint. The results suggest that innovations are positively related to efficiency. We find that profiling, pedagogic, process and education chain innovations are significantly related to school efficiency, whereas innovations in the professionalization of teachers are insignificantly related to school efficiency. Furthermore, the number of locations per school and the number of schools per governing body are negatively and significantly related to school efficiency. School type and region significantly influence school efficiency, whereas share of disadvantaged students, degree of urbanization and student/teacher ratio do not have significant influence.     

Facilitated column selection in pharmaceutical analyses using a simple column classification system

In this paper, the performance of a previously developed classification system applied to pharmaceutical chromatographic analyses, is investigated. The separation of seven different drug substances from their respective impurities was studied. The chromatographic procedure for acetylsalicylic acid, clindamycin hydrochloride, buflomedil hydrochloride, chloramphenicol sodium succinate, nimesulide and phenoxymethylpenicillin was performed according to the corresponding European Pharmacopoeia (Ph. Eur.) monograph. The separation of dihydrostreptomycin sulphate was performed according to the literature. It is shown that the column ranking system is a helpful tool in the selection of a suitable column in these analyses.     

Unexpected four-membered over six-membered ring formation during the synthesis of azaheterocyclic phosphonates: experimental and theoretical evaluation

The cyclization of functionalized aminophosphonates is studied on both experimental and theoretical grounds. In a recently described route to phosphono-beta-lactams [Stevens C. V.; Vekemans, W.; Moonen, K.; Rammeloo, T. Tetrahedron Lett. 2003, 44, 1619], it was found that starting from an ambident allylic anion only four-membered rings were formed without any trace of six-membered lactams. New anion trapping experiments revealed that the gamma-anion is highly reactive in intermolecular reactions. Ab initio calculations predict higher reaction barriers for the gamma-anion due to restricted rotation about the C-N bond and due to highly strained transition states during ring closure. The sodium or lithium counterion, explicit dimethyl ether solvent molecules, and bulk solvent effects were properly taken into account at various levels of theory.     

Structural diversity of transition-metal coordination polymers derived from isophthalic acid and bent bis(imidazole) ligands

Four coordination polymers associated with bent bis(imidazole) 1,3-bis(imidazol-l-yl-methyl)benzene (mbix) and isophthalic acid (H₂ip) or 5-methylisophthalic acid (H₂mip) ligands, formulated as {[Cd(mbix)(mip)]·H₂O} _n (1), {[Co(mbix)(mip)]·0.4H₂O} _n (2) [Ni(mbix)(mip)H₂O] _n (3) and [Ni(mbix)(ip)] _n (4), were synthesized under hydrothermal conditions and characterized by physico-chemical and spectroscopic methods. Complexes 1 and 2 are isomorphous and exhibit a 1D loop-like chain. Complex 3 features a 2D (4,4) layer, which further extends into an unusual 2D (3,5)-connected 3,5L2 double-layered supramolecular network via classical O–H···O hydrogen bonding interactions. Complex 4 is a 3D network, which shows a rare binodal (3,5)-connected 3,5T1 framework. Moreover, the luminescence and catalytic properties of the complexes for the degradation of methyl orange by sodium persulfate in a Fenton-like process are reported.     

Enantioselective Assembly of a Ruthenium(II) Polypyridyl Complex into a Double Helix

Evolution can increase the complexity of matter by self‐organization into helical architectures, the best example being the DNA double helix. One common aspect, apparently shared by most of these architectures, is the presence of covalent bonds within the helix backbone. Here, we report the unprecedented crystal structures of a metal complex that self‐organizes into a continuous double helical structure, assembled by non‐covalent building blocks. Built up solely by weak stacking interactions, this alternating tread stairs‐like double helical assembly mimics the DNA double helix structure. Starting from a racemic mixture in aqueous solution, the ruthenium(II) polypyridyl complex forms two polymorphic structures of a left‐handed double helical assembly of only the Λ‐enantiomer. The stacking of the helices is different in both polymorphs: a crossed woodpile structure versus a parallel columnar stacking.     

Suspect screening and target quantification of multi-class pharmaceuticals in surface water based on large-volume injection liquid chromatography and time-of-flight mass spectrometry

The ever-growing number of emerging micropollutants such as pharmaceuticals requests rapid and sensitive full-spectrum analytical techniques. Time-of-flight high-resolution mass spectrometry (TOF-HRMS) is a promising alternative for the state-of-the-art tandem mass spectrometry instruments because of its ability to simultaneously screen for a virtually unlimited number of suspect analytes and to perform target quantification. The challenge for such suspect screening is to develop a strategy, which minimizes the false-negative rate without restraining numerous false-positives. At the same time, omitting laborious sample enrichment through large-volume injection ultra-performance liquid chromatography (LVI-UPLC) avoids selective preconcentration. A suspect screening strategy was developed using LVI-UPLC-TOF-MS aiming the detection of 69 multi-class pharmaceuticals in surface water without the a priori availability of analytical standards. As a novel approach, the screening takes into account the signal-intensity-dependent accurate mass error of TOF-MS, hereby restraining 95 % of the measured suspect pharmaceuticals present in surface water. Application on five Belgian river water samples showed the potential of the suspect screening approach, as exemplified by a false-positive rate not higher than 15 % and given that 30 out of 37 restrained suspect compounds were confirmed by the retention time of analytical standards. Subsequently, this paper discusses the validation and applicability of the LVI-UPLC full-spectrum HRMS method for target quantification of the 69 pharmaceuticals in surface water. Analysis of five Belgian river water samples revealed the occurrence of 17 pharmaceuticals in a concentration range of 17 ng L^?1 up to 3.1 μg L^?1.