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Hot-melt extrusion (HME) is a widely used method for creating amorphous solid dispersions (ASDs) of poorly soluble drug substances, where the drug is molecularly dispersed in a solid polymer matrix. This study examines the impact of three different copovidone excipients, their reactive impurity levels, HME barrel temperature, and the distribution of colloidal silicon dioxide (SiO 2 ) on impurity levels, stability, and drug release of ASDs and their tablets. Initial peroxide levels were higher in Kollidon VA 64 (KVA64) and Plasdone S630 (PS630) compared to Plasdone S630 Ultra (PS630U), leading to greater oxidative degradation of the drug in fresh ASD tablets. However, stability testing (50 °C, closed container, 50 °C/30% RH, open conditions) showed lower oxidative degradation impurities in ASD tablets prepared at higher barrel temperatures, likely due to greater peroxide degradation. Plasdone S630 is suitable for ASDs with drugs prone to oxidative degradation, while standard purity grades may benefit drugs susceptible to free radical degradation, as they generate fewer free radicals post-HME. ASD tablets exhibited greater physical stability than milled extrudate samples, likely due to reduced exposure to stability conditions within the tablet matrix. Including SiO 2 in the extrudate composition resulted in greater physical stability of the ASD system in the tablet; however, it negatively affected chemical stability, promoting greater oxidative degradation and hydroxylation of the drug substance. No impact of the distribution of SiO 2 on drug release was observed. The study also confirmed the congruent release of copovidone, the drug substance, and Tween 80 using flow NMR coupled with in-line UV/vis. This research highlights the critical roles of peroxide levels and SiO 2 in influencing the dissolution and physical and chemical stability of ASDs. The findings provide valuable insights for developing stable and effective pharmaceutical formulations, emphasizing the importance of controlling reactive impurities and excipient characteristics in ASD products prepared by using HME.

Homemade explosives, such as peroxides, nitrates, and chlorates, are increasingly abused by terrorists, criminals, and amateur chemists. The starting materials are easily accessible and instructions on how to make the explosives are described on the Internet. Safety considerations raise the need to detect these substances quickly and in low concentrations using simple methods. Conventional methods for the detection of these substances require sophisticated, electrically operated, analytical equipment. The simpler chemical detection methods are multistep and require several chemicals. We have developed a simple, one-step method that works similarly to a pH test strip in terms of handling. The analytical reaction is based on an acid-catalyzed oxidation of an electron-rich porphyrin to an unusually stable radical cation and dication. The detection limit for the peroxide-based explosive triacetone triperoxide (TATP), which is very frequently used by terrorists, is 40 ng and thus low enough to detect the substance without direct contact via the gas phase. It is sufficient to bring the stick close to the substance to observe a color change from red to green. Nitrates and chlorates, such as ammonium nitrate, urea nitrate, or potassium chlorate, are detected by direct contact with a sensitivity of 85-350 ng. A color change from red to dark brown is observed. The test thus detects all homemade explosives and distinguishes between the extremely impact-, shock-, and friction-sensitive peroxides and the less sensitive nitrates and chlorates by color change of a simple test strip.

The symmetric bissilyl-dione 3 reveals two well-separated n → π* absorption bands at λ max = 637 nm ( ε = 140 mol -1 dm 3 cm -1 ) and 317 nm ( ε = 2460 mol -1 dm 3 cm -1 ). Whereas excitation of 3 at λ = 360/365 nm affords an isolable siloxyketene 4 in excellent yields, irradiation at λ = 590/630 nm leads to the stereo-selective and quantitative formation of the siloxyrane 5. These remarkable wavelength-dependent rearrangements are based on the electronic and steric properties provided by the hypersilyl groups. While the siloxyketene 4 is formed via a hitherto unknown 1,3-hypersilyl migration via the population of a second excited singlet state (S 2 , λ max = 317 nm, a rare case of anti-Kasha reactivity), the siloxyrane 5 emerges from the first excited triplet state (T 1 via S 1 λ max = 637 nm). These distinct reaction pathways can be traced back to specific energy differences between the S 2 , S 1 and T 1 , an electronic consequence of the bissilyl substited α-dione (the "pearl"). The hypersilyl groups act as protective ''oyster shell", which are responsible for the clean formation of 4 and 5 basically omitting side products. We describe novel synthetic pathways to achieve hypersilyl substitution (3) and report an in-depth investigation of the photorearrangements of 3 using UV/vis, in situ IR, NMR spectroscopy and theoretical calculations., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Herein, we present a convenient synthesis for symmetrical and mixed substituted tris(acyl)phosphines (TAPs) starting from red phosphorus. All TAPs exhibit a phosphaalkene-acylphosphine equilibrium, which was investigated in detail by variable-temperature (VT) NMR spectroscopy supported by density-functional theory (DFT) calculations. Depending on the substituents, two phosphaalkene derivatives and ten acylphosphine derivatives could be isolated. NMR spectroscopy and single-crystal X-ray crystallography enabled a clear structural assignment of these compounds. Oxidation of selected TAPs led to the formation of the corresponding tris(acyl)phosphine oxides (TAPOs). Furthermore, their spectroscopic properties as well as their photochemistry was investigated. Especially, the TAPO compounds were evaluated for their suitability as photoinitiators by CIDNP spectroscopy, photobleaching measurements and by storage stability tests., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

In situ IR detection of photoreactions induced by the light of LEDs at appropriate wavelengths provides a simple, cost-effective, and versatile method to get insight into mechanistic details. In particular, conversions of functional groups can be selectively followed. Overlapping UV-Vis bands or fluorescence from the reactants and products and the incident light do not obstruct IR detection. Compared with in situ photo-NMR, our setup does not require tedious sample preparation (optical fibers) and offers a selective detection of reactions, even at positions where 1 H-NMR lines overlap or 1 H resonances are not clear-cut. We illustrate the applicability of our setup following the photo-Brook rearrangement of (adamant-1-yl-carbonyl)-tris(trimethylsilyl)silane, address photo-induced α-bond cleavage (1-hydroxycyclohexyl phenyl ketone), study photoreduction using tris(bipyridine)ruthenium(II), investigate photo-oxygenation of double bonds with molecular oxygen and the fluorescent 2,4,6-triphenylpyrylium photocatalyst, and address photo-polymerization. With the LED/FT-IR combination, reactions can be qualitatively followed in fluid solution, (highly) viscous environments, and in the solid state. Viscosity changes during the reaction (e.g., during a polymerization) do not obstruct the method., (© 2023. The Author(s).)

Azo compounds are efficient electron acceptors. Upon one-electron reduction they generally isomerize forming the thermodynamically most stable radical anion. Herein we show that the size of the central ring in 1,2-diazocines and diazonines has a ruling influence on the configuration of the one-electron reduced species. Markedly, diazonines, which bear a central nine membered heterocycle, show light-induced E/Z isomerization, but retain the configuration of the diazene N=N moiety upon one-electron reduction. Accordingly, E/Z isomerization is not induced by reduction., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

In the present study, the oxidative degradation behavior of nifedipine (NIF) in amorphous solid dispersions (ASDs) prepared with poly(vinyl pyrrolidone) (PVP) with a short (K30) and a long (K90) chain length was investigated. The ASDs were prepared via dry ball-milling and analyzed using Fourier transform infrared (IR) spectroscopy, X-ray scattering, and differential scanning calorimetry. The ASDs were exposed to accelerated thermal-oxidative conditions using a pressurized oxygen headspace (120 °C for 1 day) and high temperatures at atmospheric pressure (60-120 °C for a period of 42 days). Additionally, solution-state oxidative degradation studies showed that pure NIF degrades to a greater extent than in the presence of PVP. Electronic structure calculations were performed to understand the impact of drug-polymer intermolecular interactions on the autoxidation of drugs. While no drug degradation was observed in freshly prepared ASD samples, alkyl free radicals were detected via electron paramagnetic resonance (EPR) spectroscopy. The free radicals were found to be consumed to a greater extent by PVP K30- than PVP K90-based ASDs upon exposure to high oxygen pressures. This was consistent with the greater solid-state oxidative degradation of NIF observed in ASDs with PVP K30 than with PVP K90. As no drug recrystallization occurred during this study period, the lower glass-transition temperature and presumed greater molecular mobility of PVP K30 and its ASD as compared to the PVP K90 system appear to contribute to the greater drug degradation in PVP-K30-based ASDs. The extent and the rate of oxidative degradation were higher in the case of PVP-K30-based ASD as compared to that in PVP-K90-based ASD, and the overall degradation increased with an increase in temperature. IR spectral analysis of drug-polymer interactions supports the electronic calculations of the oxidation process. We infer that, apart from the initial free radical content, the difference in the extent of drug-polymer intermolecular interactions in ASDs and amorphous stabilization during the forced oxidation experiments contribute to the observed differences in the autoxidative reactivity of the drug in ASDs with different PVP chain lengths. Overall, the chemical degradation of NIF in ASDs with two PVP chain lengths obtained from accelerated solid-state oxidation studies was in qualitative agreement with that obtained from long-term (3 years) storage under ambient conditions. The study highlights the ability of accelerated processes to determine the oxidative degradation behavior of polymeric ASDs and suggests that the polymer chain length could factor into chemical as well as physical stability considerations.

We have synthesized the first isolable geminal bisenolates L 2 K 2 Ge[(CO)R] 2 ( R =2,4,6-trimethylphenyl ( 2 a , b ), L=THF for ( 2 a ) or [18]-crown-6 for ( 2 b )), a new synthon for the synthesis of organometallic reagents. The formation of these derivatives was confirmed by NMR spectroscopy and X-ray crystallographic analysis. The UV/Vis spectra of these anions show three distinct bands, which were assigned by DFT calculations. The efficiency of 2 a , b to serve as new building block in macromolecular chemistry is demonstrated by the reactions with two different types of electrophiles (acid chlorides and alkyl halides). In all cases the salt metathesis reaction gave rise to novel Ge-based photoinitiators in good yields., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Angewandte Chemie published by Wiley-VCH GmbH.)

Acylgermanes are known as highly efficient photoinitiators. In this contribution, we present the synthesis of new diacylgermanes 4a-evia a multiple silyl abstraction methodology. The method outperforms the state-of-the-art approach (Corey-Seebach reaction) towards diacylgermanes in terms of group tolerance and toxicity of reagents. Moreover, these compounds are decorated with bulky mesityl groups in order to improve their storage stability. The isolated diacylgermanes were characterized by multinuclear NMR-, UV-Vis spectroscopy and X-ray crystallography, as well as photolysis experiments (photobleaching) and photo-DSC measurements (photopolymerization behavior). Upon irradiation with an LED emitting at 385 nm, all compounds except for 4a and 4c bleach efficiently with quantum yields above 0.6. Due to their broad absorption bands, the compounds can be also bleached with blue light (470 nm), where especially 4e bleaches more efficiently than Ivocerin®.

We present a systematic investigation of the photophysical properties of diazocines in aqueous media. The Z - E photoconversion yields of CH 2 CH 2 - and CH 2 S-bridged diazocines decrease with increasing water content in acetonitrile. However, there is one exception. A CH 2 -NAc-bridged diazocine mostly retains its photostationary state in water (85 to 72%) because of the high quantum yields for the Z → E conversion. Moreover, it is water-soluble without further substitution and is therefore ideally suited as a photoswitch in biological (aqueous) environments.

Tetraacylgermanes are known as highly efficient photoinitiators. Herein, the synthesis of mixed tetraacylgermanes 4 a-c and 6 a-e with a nonsymmetric substitution pattern is presented. Germenolates are crucial intermediates of these new synthetic protocols. The synthesized compounds show increased solubility compared with symmetrically substituted tetraacylgermanes 1 a-d. Moreover, these mixed derivatives reveal broadened n-π* absorption bands, which enhance their photoactivity. Higher absorption of these new compounds at wavelengths above 450 nm causes efficient photobleaching when using an LED emitting at 470 nm. The quantum yields are in the range of 0.15-0.57, depending on the nature of the aroyl substituents. On the basis of these properties, mixed-functionalized tetraacylgermanes serve as ideal photoinitiators in various applications, especially in those requiring high penetration depth. The synthesized compounds were characterized by elemental analysis, IR spectroscopy, NMR and CIDNP spectroscopy, UV/Vis spectroscopy, photolysis experiments, and X-ray crystallography. The CIDNP data suggest that the germyl radicals generated from the new tetraacylgermanes preferentially add to the tail of the monomer butyl acrylate. In the case of 6 a-e only the mesitoyl groups are cleaved off, whereas for 4 a-c both the mesitoyl and the aroyl group are subject to α-cleavage., (© 2020 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)