Common Shortcomings in Study on Radiopharmaceutical Design Research: A Case Study of 99mTc-Labelled Methotrexate

The aim of the work carried out was to draw attention to shortcomings that often appear at the stage of designing new radiopharmaceuticals. Based on a case study of ^99mTc-labelled methotrexate, this article describes frequent mistakes or misconceptions present not only in the referenced studies, but also in numerous radiopharmaceutical studies. The recommendations provided in this article highlight fundamental aspects of the credibility of radiopharmaceutical scientific research leading to the reliable results.     

Pyridine Adducts of Tricyano- and Dicyanoboranes

Cyanoborane adducts of the Lewis acids B(CN)₃, BF(CN)₂, and BH(CN)₂ with pyridine and 4-cyanopyridine have been obtained in high yields. The syntheses were accomplished by oxidation of the readily available potassium salts of the cyano(hydrido)borate anions [BH(CN)₃]⁻ ( MHB ), [BFH(CN)₂]⁻ ( FHB ), and [BH₂(CN)₂]⁻ ( DHB ) with bromine in the presence of the respective pyridine derivative C₅H₅N or 4-CN-C₅H₄N as starting material. All six cyanoborane adducts have been characterized by NMR and vibrational spectroscopy, elemental analysis, and single-crystal X-ray diffraction. The reduction of the cyanoborane adducts has been investigated by cyclic voltammetry and the Lewis acidity of the different cyanoboranes has been assessed using the Gutmann-Beckett method. Selected experimental data and trends are compared to theoretical ones, for example fluoride ion affinities (FIAs).     

Catalytic activity of glucose oxidase after dielectrophoretic immobilization on nanoelectrodes

Dielectrophoresis (DEP) is an AC electrokinetic effect that is proven to be effective for the immobilization of not only cells, but also of macromolecules, for example, antibodies and enzyme molecules. In our previous work, we have already demonstrated the high catalytic activity of immobilized horseradish peroxidase after DEP. To evaluate the suitability of the immobilization method for sensing or research in general, we want to test it for other enzymes, too. In this study, glucose oxidase (GOX) from Aspergillus niger was immobilized on TiN nanoelectrode arrays by DEP. Fluorescence microscopy showed the intrinsic fluorescence of the immobilized enzymes flavin cofactor on the electrodes. The catalytic activity of immobilized GOX was detectable, but a fraction of less than 1.3% of the maximum activity that was expected for a full monolayer of immobilized enzymes on all electrodes was stable for multiple measurement cycles. Therefore, the effect of DEP immobilization on the catalytic activity strongly depends on the used enzyme.     

Catalytic Alkyne Semihydrogenation with Polyhydride Ni/Ga Clusters

The bimetallic, decanuclear Ni₃Ga₇-cluster of the formula [Ni₃(GaTMP)₃(μ²-GaTMP)₃(μ³-GaTMP)] ( 1 , TMP=2,2,6,6-tetramethylpiperidinyl) reacts reversibly with dihydrogen under the formation of a series of (poly-)hydride clusters 2 . Low-temperature 2D NMR experiments at −80 °C show that 2 consist of a mixture of a di- ( 2_Di ), tetra- ( 2_Tetra ) and hexahydride species ( 2_Hexa ). The structures of 2_Di and 2_Tetra are assessed by a combination of 2D NMR spectroscopy and DFT calculations. The cooperation of both metals is essential for the high hydrogen uptake of the cluster. Polyhydrides 2 are catalytically active in the semihydrogenation of 4-octyne to 4-octene with good selectivity. The example is the first of its kind and conceptually relates properties of molecular, atom-precise transition metal/main group metal clusters to the respective solid-state phase in catalysis.     

Hydrogen Peroxide Production of Individual Nanosecond Pulsed Discharges Submerged in Water of Elevated Conductivity

The production of hydrogen peroxide (H₂O₂) is a key parameter for the performance of pulsed discharges submerged in water utilized as advanced oxidation process. So far, any related assessment of the underlying mechanism was conducted for the application of several hundred discharges, which did not allow for a correlation with physical processes. Moreover, the production was rarely investigated depending on water conductivity as one of the most important parameters for the development of submerged discharges. Accordingly, hydrogen peroxide generation was investigated here for individual single discharge events instigated with 100 ns high-voltage pulses in water with three different conductivities and was associated with the discharge development, i. e. spatial expansion and dissipated electrical energy. The approach necessitated the improvement of an electrochemical flow injection analysis based on the reaction of Prussian blue with H₂O₂. Hydrogen peroxide concentrations were quadratically increasing with propagation time and stable for different water conductivities. H₂O₂ production per unit volume of a discharge was constant over time with an estimated rate constant of 3.2 mol ⋅ m⁻¹ s⁻¹, averaged over the crosssectional area of all discharge filaments. However, the individually dissipated energy increased with conductivity, hence, the production efficiency decreased from 6.1 g ⋅ kWh⁻¹ to 1.4 g ⋅ kWh⁻¹, which was explained by increased resistive losses within the bulk liquid.     

Background and line interference corrections in quantitative GD-OES – New approaches to an old problem

The origin of radiative background in GD-OES is discussed, in connection with the problem of multi-matrix measurements in depth profile analysis. Backed by some experimental evidence in the form of line scans, it is argued that line emission from sample material and the plasma gas (Ar) make up the dominating contributions to the radiative background. The contribution from Ar, in this work termed Matrix-independent Background (MIB), is investigated in more detail. It is shown that, at constant voltage and current, the Ar emission intensity is nearly constant and independent of the pressure, but somewhat matrix-dependent. It is suggested that the MIB can be expressed as a linear function of the intensity of an Ar reference line. This idea is tested experimentally by making intensity measurements on a large set of calibration standards of varying composition. The results are fitted to a calibration function which allows optional definitions of the MIB. It is shown that with a MIB defined as a linear function of the Ar intensity, the different contributions to the spectral background can be more accurately determined than with the MIB defined as a constant.     

Quantitative depth profiling in glow discharge spectroscopies – A new deconvolution technique to separate effects of an uneven erosion crater shape

An algorithm is presented as a concept for the quantification in direct current and radiofrequency glow discharge (GD) modes for GD optical emission spectroscopy. The algorithm is divided into excitation and sputtering part and thus it is possible to distinguish between the different excitation processes and to consider equivalent sputtering crater formations in both modes. Intensity-time profiles are affected corresponding to the method by several effects. One important effect is that sputtering occurs at a single time in different depths because of curved crater bottoms, this is usually called crater effect. The main purpose is to introduce an iterative deconvolution technique which for the quantification numerically takes into account the curved sputtering crater bottom. Input data for the deconvolution technique are the calibrated mass-time profile, the partial densities of the sample constituents and the measured final shape of the sputtering crater. Using a relatively simple model for ion sputtering the deconvolution technique improves iteratively the calculated layer structure by means of information on crater formation. The mathematical handling is illustrated for the quantification of a depth profile of a multilayer sample of ten 100 nm layers. The resulting concentration-depth profile reflects excellently the real elemental distribution of the multilayer system.     

Photocontrolled Release of Chemicals from Nano‐ and Microparticle Containers

A benzoin‐derived diol linker was synthesized and used to generate biocompatible polyesters that can be fully decomposed on demand upon UV irradiation. Extensive structural optimization of the linker unit was performed to enable the defined encapsulation of diverse organic compounds in the polymeric structures and allow for a well‐controllable polymer cleavage process. Selective tracking of the release kinetics of encapsulated model compounds from the polymeric nano‐ and microparticle containers was performed by confocal laser scanning microscopy in a proof‐of‐principle study. The physicochemical properties of the incorporated and released model compounds ranged from fully hydrophilic to fully hydrophobic. The demonstrated biocompatibility of the utilized polyesters and degradation products enables their use in advanced applications, for example, for the smart packaging of UV‐sensitive pharmaceuticals, nutritional components, or even in the area of spatially selective self‐healing processes.     

Synthesis of Renewable meta‐Xylylenediamine from Biomass‐Derived Furfural

We report the synthesis of biomass‐derived functionalized aromatic chemicals from furfural, a building block nowadays available in large scale from low‐cost biomass. The scientific strategy relies on a Diels–Alder/aromatization sequence. By controlling the rate of each step, it was possible to produce exclusively the meta aromatic isomer. In particular, through this route, we describe the synthesis of renewably sourced meta‐xylylenediamine (MXD). Transposition of this work to other furfural‐derived chemicals is also discussed and reveals that functionalized biomass‐derived aromatics (benzaldehyde, benzylamine, etc.) can be potentially produced, according to this route.     

Catenation and Aggregation of Multi‐Cavity Coordination Cages

A series of metal‐mediated cages, having multiple cavities, was synthesized from Pd^II cations and tris‐ or tetrakis‐monodentate bridging ligands and characterized by NMR spectroscopy, mass spectrometry, and X‐ray methods. The peanut‐shaped [Pd₃L¹₄] cage deriving from the tris‐monodentate ligand L¹ could be quantitatively converted into its interpenetrated [5Cl@Pd₆L¹₈] dimer featuring a linear {[Pd‐Cl‐]₅Pd} stack as an unprecedented structural motif upon addition of chloride anions. Small‐angle neutron scattering (SANS) experiments showed that the cigar‐shaped assembly with a length of 3.7 nm aggregates into mono‐layered discs of 14 nm diameter via solvophobic interactions between the hexyl sidechains. The hepta‐cationic [5Cl@Pd₆L¹₈] cage was found to interact with polyanionic oligonucleotide double‐strands under dissolution of the aggregates in water, rendering the compound class interesting for applications based on non‐covalent DNA binding.