Highly Sensitive, Easy-to-Use, One-Step Detection of Peroxide-, Nitrate- and Chlorate-Based Explosives with Electron-Rich Ni Porphyrins.

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.

Symmetrical and Mixed Tris(acyl)phosphines: Synthesis, Oxidation and Photochemistry.

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.

Symmetrical and Mixed Tris(acyl)phosphines: Synthesis, Oxidation and Photochemistry.

Invited for the cover of this issue are the groups of M. Haas, G. Gescheidt and H. Grützmacher from the Graz University of Technology and the ETH Zürich. The image depicts a phosphorus mine, where the workers are acid chlorides using their shovels and red phosphorus to provide the chemicals necessary to produce novel reagents. Read the full text of the article at 10.1002/chem.202302535.

Blocked Phosphates as Photolatent Catalysts for Dynamic Photopolymer Networks.

While latent catalysts are a well-established strategy for initiating and controlling the rate of polymerization reactions, their use in dynamic polymer networks is still in its infancy. The ideal latent catalyst should be thermally stable and release a highly active species in response to an external trigger. Here, we have synthesized a temperature resistant (>200 °C) organic phosphate with a photolabile o-nitrobenzyl protecting group that can be cleaved by UV light. Introduced in a visible light curable thiol-click photopolymer, the sequence-dependent λ-orthogonality of the curing and cleavage enables an efficient network formation at 451 nm, without premature release of the catalyst. Once cured, irradiation at 372 nm spatiotemporally activates the phosphate, which catalyzes transesterifications at elevated temperature. The formed catalyst has no effect on the thermal stability of the polymeric network and allows the activation of bond exchange reactions in selected domains of printed 3D objects.

Forced Solid-State Oxidation Studies of Nifedipine-PVP Amorphous Solid Dispersion.

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.

Hydroalkylation of Aryl Alkenes with Organohalides Catalyzed by Molybdenum Oxido Based Lewis Pairs.

Three molybdenum(VI) dioxido complexes [MoO2(L)2] bearing Schiff base ligands were reacted with B(C6F5)3 to afford the corresponding adducts [MoO{OB(C6F5)3}(L)2], which were fully characterized. They exhibit Frustrated Lewis-Pairs reactivity when reacting with silanes. Especially, the [MoO{OB(C6F5)3}(L)2] complex with L=2,4-dimethyl-6-((phenylimino)methyl)phenol proved to be active as catalyst for the hydroalkylation of aryl alkenes with organohalides and for the Atom-Transfer Radical Addition (ATRA) of organohalides to aliphatic alkenes. A series of gem-dichloride and gem-dibromide compounds with potential for further derivatization were synthesized from simple alkenes and organohalides, like chloroform or bromoform, using low catalyst loading.

Activation and Photoinduced Release of Alkynes on a Biomimetic Tungsten Center: The Photochemical Behavior of the W-S-Phoz System.

The synthesis and structural determination of four tungsten alkyne complexes coordinated by the bio-inspired S,N-donor ligand 2-(4',4'-dimethyloxazoline-2'-yl)thiophenolate (S-Phoz) is presented. A previously established protocol that involved the reaction of the respective alkyne with the bis-carbonyl precursor [W(CO)2 (S-Phoz)2 ] was used for the complexes [W(CO)(C2 R2 )(S-Phoz)2 ] (R=H, 1 a; Me, 1 b; Ph, 1 c). Oxidation with pyridine-N-oxide gave the corresponding W-oxo species [WO(C2 R2 )(S-Phoz)2 ] (R=H, 2 a; Me, 2 b; Ph, 2 c). All W-oxo-alkyne complexes (2 a, b, c) were found to be capable of alkyne release upon light irradiation to afford five-coordinate [WO(S-Phoz)2 ] (3). The photoinduced release of the alkyne ligand was studied in detail by in situ 1 H NMR measurements, which revealed correlation of the photodissociation rate constant (2 b>2 a>2 c) with the elongation of the alkyne C≡C bond in the molecular structures. Oxidation of [WO(S-Phoz)2 ] (3) with pyridine-N-oxide yielded [WO2 (S-Phoz)2 ] (4), which shows highly fluxional behavior in solution. Variable-temperature 1 H NMR spectroscopy revealed three isomeric forms with respect to the ligand arrangement versus each other. Furthermore, compound 4 rearranges to tetranuclear oxo compound [W4 O4 (µ-O)6 (S-Phoz)4 ] (5) and dinuclear [{WO(µ-O)(S-Phoz)}2 ] (6) over time. The latter two were identified by single-crystal X-ray diffraction analyses.

Hydrogen Abstraction from the C15 Position of the Cholesterol Skeleton.

Cholesterol (Ch) is an integral part of cell membrane, where it is prone to oxidation. In humans, oxidation of Ch is commonly linked to various pathologies like Alzheimer's disease, atherosclerosis, and even cancer, which proceed via mechanisms involving enzymatic and free radical pathways. The latter begin with hydrogen abstraction (HA) from Ch by a reactive free radical. It has been established that the most efficient HA from Ch occurs at C7, although HA from C4 by peroxyl radicals has recently been observed. Conversely, HA from Ch positions other than the thermodynamically preferred C7 or C4 has never been reported. We have designed a Ch derivative where a benzophenone moiety is linked to C7 by a covalent bond. This mirrors a specific orientation of Ch within a confined environment. Product analysis and time-resolved spectroscopic studies reveal an unprecedented HA from C15, which is a thermodynamically unfavorable position. This indicates that a specific topology of reactants is crucial for the reactivity of Ch. The relative orientation of the reactants can also be relevant in biological membranes, where Ch, polyunsaturated fatty acids, and numerous oxidizing species are confined in highly restricted and anisotropic environments.

Proton-Coupled Electron Transfer from Hydrogen-Bonded Phenols to Benzophenone Triplets.

Phenols with intramolecular hydrogen bond between a pendant base and the phenolic OH group react differently in polar and non-polar environments with electron/proton acceptors. This was demonstrated by using time resolved chemically induced dynamic nuclear polarization (TR CIDNP) and theoretical calculations. In benzene, those phenols undergo a concerted electron-proton transfer (EPT) that yields neutral ketyl and phenoxyl radicals. In polar acetonitrile, the reaction mechanism turns into an electron transfer from the phenol to the triplet ketone, accompanied by the shift of a proton from the phenolic OH group to the nitrogen atom of the pendant base to form a distonic radical cation. This behavior is similar to that of tyrosine H-bonded to basic residues in some radical enzymes. This solvent-induced mechanism switch in proton-coupled electron transfers is important in different biological systems, in which the same metabolites and intermediates can react differently depending on the specific local environments.

Tetraacylgermanes: Highly Efficient Photoinitiators for Visible-Light-Induced Free-Radical Polymerization.

In this contribution a convenient synthetic method to obtain tetraacylgermanes Ge[C(O)R]4 (R=mesityl (1 a), phenyl (1 b)), a previously unknown class of highly efficient Ge-based photoinitiators, is described. Tetraacylgermanes are easily accessible via a one-pot synthetic protocol in >85 % yield, as confirmed by NMR spectroscopy, mass spectrometry, and X-ray crystallography. The efficiency of 1 a,b as photoinitiators is demonstrated in photobleaching (UV/Vis), time-resolved EPR (CIDEP), and NMR/CIDNP investigations as well as by photo-DSC studies. Remarkably, the tetraacylgermanes exceed the performance of currently known long-wavelength visible-light photoinitiators for free-radical polymerization.

Star-shaped Polymers through Simple Wavelength-Selective Free-Radical Photopolymerization.

Star-shaped polymers represent highly desired materials in nanotechnology and life sciences, including biomedical applications (e.g., diagnostic imaging, tissue engineering, and targeted drug delivery). Herein, we report a straightforward synthesis of wavelength-selective multifunctional photoinitiators (PIs) that contain a bisacylphosphane oxide (BAPO) group and an α-hydroxy ketone moiety within one molecule. By using three different wavelengths, these photoactive groups can be selectively addressed and activated, thereby allowing the synthesis of ABC-type miktoarm star polymers through a simple, highly selective, and robust free-radical polymerization method. The photochemistry of these new initiators and the feasibility of this concept were investigated in unprecedented detail by using various spectroscopic techniques.

Electronic Structures and Chiroptical Properties of Post-functionalized Helicene Quinones.

The synthesis of redox-active p- and o-quinones 2-phenylamino-4-phenylimino[6]helicene-1-one 1, 2-phenylamino[6]-helicene-1,4-dione 2, and 4-phenyl[6]helicene-1,2-dione 3 in their enantiopure forms by post-functionalization of (P)- and (M)-1,2-dimethoxy[6]helicene is presented. Structural characterization in solution and in the solid state was accomplished by 2D NMR spectroscopy methods and X-ray diffraction analysis, respectively. Interpretation of electrochemical redox data was accompanied by a detailed orbital picture, derived from DFT calculations. The electronic structures of compounds 1-3 were investigated by UV/Vis and electronic circular dichroism (ECD) spectroscopy, complemented by TD-DFT calculations. Quinones 1-3 were chemically reduced to study the EPR signatures of their respective radical anions. DFT methods were used for the atom assignment of the hyperfine coupling constants. The results are discussed within the context of electrochromic chiral switches and molecular recognition.

Photoinduced Reactivity of the Soft Hydrotris(6-tert-butyl-3-thiopyridazinyl)borate Scorpionate Ligand in Sodium, Potassium, and Thallium Salts.

The soft scorpionate ligand hydrotris(6-tert-butyl-3-thiopyridazinyl)borate (Tn) was found to exhibit pronounced photoreactivity. Full elucidation of this process revealed the formation of 6-tert-butylpyridazine-3-thione (PnH) and 4,5-dihydro-6-tert-butylpyridazine-3-thione (H2PnH). Under exclusion of light, no solvolytic reactions occur, allowing the development of high-yield preparation protocols for the sodium, potassium, and thallium salts and improving the yield for their derived copper boratrane complex. The photoreactivity is relevant for all future studies with electron-deficient scorpionate ligands.

Short-lived phenoxyl radicals formed from green-tea polyphenols and highly reactive oxygen species: an investigation by time-resolved EPR spectroscopy.

Polyphenols are effective antioxidants and their behavior has been studied in depth. However, a structural characterization of the species formed immediately upon hydrogen-atom transfer (HAT), a key reaction of oxidative stress, has not been achieved. The reaction of catechin and green-tea polyphenols with highly reactive O-centered H-abstracting species was studied at the molecular level and in real time by using time-resolved electron paramagnetic resonance (EPR) spectroscopy. This mirrors the reaction of highly reactive oxygen species with polyphenols. The results show that all phenolic OH groups display essentially identical reactivity. Accordingly, there is no site specificity for HAT and initial antioxidative events are demonstrated to be largely ruled by statistical (entropic) factors.

Acylgermanes: photoinitiators and sources for Ge-centered radicals. insights into their reactivity.

Acylgermanes have been shown to act as efficient photoinitiators. In this investigation we show how dibenzoyldiethylgermane 1 reacts upon photoexcitation. Our real-time investigation utilizes femto- and nanosecond transient absorption, time-resolved EPR (50 ns), photo-chemically induced dynamic nuclear polarization, DFT calculations, and GC-MS analysis. The benzoyldiethylgermyl radical G• is formed via the triplet state of parent 1. On the nanosecond time scale this radical can recombine or undergo hydrogen-transfer reactions. Radical G• reacts with butyl acrylate at a rate of 1.2 ± 0.1 × 10(8) and 3.2 ± 0.2 × 10(8) M(-1) s(-1), in toluene and acetonitrile, respectively. This is ~1 order of magnitude faster than related phosphorus-based radicals. The initial germyl and benzoyl radicals undergo follow-up reactions leading to oligomers comprising Ge-O bonds. LC-NMR analysis of photocured mixtures containing 1 and the sterically hindered acrylate 3,3-dimethyl-2-methylenebutanoate reveals that the products formed in the course of a polymerization are consistent with the intermediates established at short time scales.

Phosphinoindenyl and phosphazidoindenyl complexes of lanthanum and samarium: synthesis, characterisation, and hydroamination catalysis.

The phosphinoindenyl rare-earth metal complexes [1-(Ph2P)-η5-C9H6]2LnIIIN(SiMe3)2, Ln = La (1-La), Sm (1-Sm), were prepared by heating two equivalents of 1-(Ph2P)C9H7 with LnIII[N(SiMe3)2]3 in toluene at 100 °C. The treatment of 1-La with one equivalent of benzonitrile gave (PhCN)[1-(Ph2P)-η5-C9H6]2LaIIIN(SiMe3)2, 2, while no adduct was formed in case of the samarium derivative 1-Sm. The reaction of 1-La and 1-Sm with two equivalents of benzyl azide yielded the (phosphazido)indenyl complexes {1-[BnN3-κN(Ph2)P]-η5-C9H6}{1-[BnN3-κ2N,N'(Ph2)P]C9H6}LnIIIN(SiMe3)2, Ln = La (3-La), Sm (3-Sm), respectively. The five complexes catalyse the intramolecular hydroamination/cyclisation of 2,2-diphenylpent-4-ene-1-amine using 2% catalyst loading. All compounds were characterised by NMR and UV-Vis spectroscopy, single-crystal X-ray diffraction, and elemental analysis and DFT calculations were performed for 3-La.

Probing lipid peroxidation by using linoleic acid and benzophenone.

A thorough mechanistic study has been performed on the reaction between benzophenone (BZP) and a series of 1,4-dienes, including 1,4-cyclohexadiene (CHD), 1,4-dihydro-2-methylbenzoic acid (MBA), 1,4-dihydro-1,2-dimethylbenzoic acid (DMBA) and linoleic acid (LA). A combination of steady-state photolysis, laser flash photolysis (LFP), and photochemically induced dynamic nuclear polarization (photo-CIDNP) have been used. Irradiation of BZP and CHD led to a cross-coupled sensitizer-diene product, together with 6, 7, and 8. With MBA and DMBA as hydrogen donors, photoproducts arising from cross-coupling of sensitizer and diene radicals were found; compound 7 was also obtained, but 6 and o-toluic acid were only isolated in the irradiation of BZP with MBA. Triplet lifetimes were determined in the absence and in the presence of several diene concentrations. All three model compounds showed similar reactivity (k(q) ≈10(8) M(-1) s(-1)) towards triplet excited BZP. Partly reversible hydrogen abstraction of the allylic hydrogen atoms of CHD, MBA, and DMBA was also detected by photo-CIDNP on different timescales. Polarizations of the diamagnetic products were in full agreement with the results derived from LFP. Finally, LA also underwent partly reversible hydrogen abstraction during photoreaction with BZP. Subsequent hydrogen transfer between primary radicals led to conjugated derivatives of LA. The unpaired electron spin population in linoleyl radical (LA(.)) was predominantly found on H(1-5) protons. To date, LA-related radicals were only reported upon hydrogen transfer from highly substituted model compounds by steady-state EPR spectroscopy. Herein, we have experimentally established the formation of LA(.) and shown that it converts into two dominating conjugated isomers on the millisecond timescale. Such processes are at the basis of alterations of membrane structures caused by oxidative stress.

Probing the antioxidant activity of polyphenols by CIDNP: from model compounds to green tea and red wine.

Polyphenols occur naturally in a vast variety of plants. One of their predominant properties is their antioxidant activity. To provide a deeper understanding of the antioxidant mechanism, (1)H CIDNP spectroscopy (CIDNP=chemically induced dynamic nuclear polarization) is used to study model hydrogen abstraction reactions with four catechin-based polyphenols: catechin (CA), gallocatechin (GC), epigallocatechin (EGC), and epigallocatechin gallate (EGCG). The experiments involve photoinduced hydrogen-atom transfer to a hydrogen abstractor (e.g., excited isopropylthioxanthone) followed under steady-state conditions and in a time-resolved fashion (resolution 500 ns-1 ms). It is found that hydrogen abstraction is an essentially stochastic process with a slight preference for the B rings in the catechin-based polyphenols. Remarkably, analogous reactivity patterns could be followed in the "real systems", green tea and red wine. We also show that CIDNP can be used as a semiquantitative tool to assess chemical reactivity.

Feasibility of rapidly assessing reactive impurities mediated excipient incompatibility using a new method: A case study of famotidine-PEG system.

The present work demonstrates the utility of temperature controlled set up with pressurized headspace oxygen as an approach to effectively reduce the time required for solid-state drug-excipient compatibility study. To illustrate the utility, the incompatibility of polyethylene glycol (PEG) and polyethylene oxide (PEO) with Famotidine (Fam) was shown. Owing to thermal and oxidative stress, polyethylene ether moieties of PEG generated reactive impurities, resulting in the degradation of Fam. The chemical degradation was evaluated via liquid chromatography. Around 20% of degradation was observed in the pressurized oxygen set up, whereas, no degradation was found in the absence of oxidative stress. On increasing the excipient fraction, the Fam degradation increased proportionally. Formation of aldehydes and free radicals from excipients were proposed as the precursors for Fam degradation. The generation of aldehydes and free radicals was confirmed by infrared and Electron Spin Resonance (ESR) spectroscopic analysis, respectively. Overall, the present study demonstrated the utility of pressurized oxygen set up as a rapid and routine tool for studying drug-excipient incompatibility at temperatures relevant drug-product manufacture.

Paramagnetic Molecular Grippers: The Elements of Six-State Redox Switches.

The development of semiquinone-based resorcin[4]arene cavitands expands the toolbox of switchable molecular grippers by introducing the first paramagnetic representatives. The semiquinone (SQ) states were generated electrochemically, chemically, and photochemically. We analyzed their electronic, conformational, and binding properties by cyclic voltammetry, ultraviolet/visible (UV/vis) spectroelectrochemistry, electron paramagnetic resonance (EPR) and transient absorption spectroscopy, in conjunction with density functional theory (DFT) calculations. The utility of UV/vis spectroelectrochemistry and EPR spectroscopy in evaluating the conformational features of resorcin[4]arene cavitands is demonstrated. Guest binding properties were found to be enhanced in the SQ state as compared to the quinone (Q) or the hydroquinone (HQ) states of the cavitands. Thus, these paramagnetic SQ intermediates open the way to six-state redox switches provided by two conformations (open and closed) in three redox states (Q, SQ, and HQ) possessing distinct binding ability. The switchable magnetic properties of these molecular grippers and their responsiveness to electrical stimuli has the potential for development of efficient molecular devices.