Drug Pharmacokinetics Determined by Real‐Time Analysis of Mouse Breath

Noninvasive, real‐time pharmacokinetic (PK) monitoring of ketamine, propofol, and valproic acid, and their metabolites was achieved in mice, using secondary electrospray ionization and high‐resolution mass spectrometry. The PK profile of a drug influences its efficacy and toxicity because it determines exposure time and levels. The antidepressant and anaesthetic ketamine (Ket) and four Ket metabolites were studied in detail and their PK was simultaneously determined following application of different sub‐anaesthetic doses of Ket. Bioavailability after oral administration vs. intraperitoneal injection was also investigated. In contrast to conventional studies that require many animals to be sacrificed even for low‐resolution PK curves, this novel approach yields real‐time PK curves with a hitherto unmatched time resolution (10 s), and none of the animals has to be sacrificed. This thus represents a major step forward not only in animal welfare, but also major cost and time savings.     

Arabinoxylan structure affects the reinforcement of films by microfibrillated cellulose

The chemical structure of rye arabinoxylan (rAX) was systematically modified, exploiting selective enzymes to mimic different naturally occurring xylans, i.e., its degree of substitution (DS) was decreased using α-l-arabinofuranosidase, and a controlled decrease in the degree of polymerization (DP) was performed using endo-1,4-β-d-xylanase. The arabinose to xylose ratio was decreased from 0.45 to 0.27 and the weight-average molar mass was decreased from 184,000 to 49,000 g/mol. The resulting samples were used to prepare films, as such, and with 15% (wt. − %) softwood-derived microfibrillated cellulose (MFC) to obtain novel plant-derived biocomposite materials. The enzymatic tailoring of rAX increased the crystallinity of films, evidenced by X-ray diffraction studies, and the addition of MFC to the debranched, low DS rAX induced the formation of ordered structures visible with polarizing optical microscopy. MFC decreased the moisture uptake of films and increased the relative humidity of softening of the films, detected with moisture scanning dynamic mechanical analysis. For the first time, the chemical structure of xylan was proven to significantly affect the reinforcement potential of nano-sized cellulose, as the tensile strength of films from high DP rAXs, but not that of low DP rAXs, clearly increased with the addition of MFC. At the same time, MFC only increased the Young’s modulus of films from rAX with high arabinose content, regardless of DP.     

Computational study of the adsorption and dissociation of phenol on Pt and Rh surfaces

The adsorption of phenol on flat and stepped Pt and Rh surfaces and the dissociation of hydrogen from the hydroxyl group of phenol on Pt(111) and Rh(111) were studied by density functional calculations. On both Pt(111) and Rh(111), phenol adsorbs with the aromatic ring parallel to the surface and the hydroxyl group tilted away from the surface. Furthermore, adsorption on stepped surfaces was concluded to be unfavourable compared to the (111) surfaces due to the repulsion of the hydroxyl group from the step edges. Transition state calculations revealed that the reaction barriers, associated with the dissociation of phenol into phenoxy, are almost identical on Pt and Rh. Furthermore, the oxygen in the dissociated phenol is strongly attracted by Rh(111), while it is repelled by Pt(111).     

Oligoamide Foldamers as Helical Chloride Receptors—the Influence of Electron‐Withdrawing Substituents on Anion‐Binding Interactions

The anion‐binding properties of three closely related oligoamide foldamers were studied using NMR spectroscopy, isothermal titration calorimetry and mass spectrometry, as well as DFT calculations. The ¹H NMR spectra of the foldamers in [D₆]acetone solution revealed partial preorganization by intramolecular hydrogen bonding, which creates a suitable cavity for anion binding. The limited size of the cavity, however, enabled efficient binding by the inner amide protons only for the chloride anion resulting in the formation of a thermodynamically stable 1:1 complex. All 1:1 chloride complexes displayed a significant favourable contribution of the entropy term. Most likely, this is due to the release of ordered solvent molecules solvating the free foldamer and the anion to the bulk solution upon complex formation. The introduction of electron‐withdrawing substituents in foldamers 2 and 3 had only a slight effect on the thermodynamic constants for chloride binding compared to the parent receptor. Remarkably, the binding of chloride to foldamer 3 not only produced the expected 1:1 complex but also open aggregates with 1:2 (host:anion) stoichiometry.     

Analysis of nitromethane from samples exposed in vitro to chloropicrin by stable isotope dilution headspace gas chromatography with mass spectrometry

Chloropicrin (trichloronitromethane) is a widely used soil fumigant and an old chemical warfare agent. The metabolism of chloropicrin is not well known in mammals but nitromethane has been shown to be one of its main metabolites. Here, a fast and simple headspace gas chromatography with mass spectrometry method was applied for the measurement of nitromethane from aqueous samples. The analytical method was validated using stable isotope labeled internal standard and a small sample volume of 260 μL. No conventional sample preparation steps were needed. The method was accurate (relative standard deviations ≤1.5%) and linear (R² = 0.9996) within the concentration range of 0.1?6.0 μg/mL. This method was used to measure nitromethane in in vitro incubations with human and pig liver cell fractions containing enzymes for xenobiotic metabolism, exposed to chloropicrin. The results indicate that the presence of glutathione is necessary for the formation of nitromethane from chloropicrin. Also, nitromethane was formed mostly in liver cytosol fractions, but not in microsomal fractions after the incubation with chloropicrin. Our results suggest that although nitromethane is not the unequivocal biomarker of chloropicrin exposure, this method could be applied for screening the elevated levels in humans after chloropicrin exposure.     

Recognition of alkali metal halide contact ion pairs by uranyl-salophen receptors bearing aromatic sidearms. The role of cation-pi interactions

Hard anions have long been known to bind strongly to the uranium of uranyl-salophen complexes. Upon functionalization of the salophen framework with one or two benzyloxy substituents, efficient ditopic receptors for alkali metal ions are obtained. The solid-state structures of complexes formed by the two-armed receptor 1 with CsF and with the chlorides of K+, Rb+, and Cs+ reported here reveal the existence of dimeric supramolecular assemblies in which two receptor units assemble into capsules fully enclosing (MX)2 ion quartets. In addition to the strong coordinative binding of the anion to the uranyl center and to electrostatic cation-anion interactions, stabilizing interactions arise from coordination of each cation to six oxygens, three from each receptor, and most importantly, to two aromatic sidearms belonging to different receptors. There are marked differences in organization at the supramolecular level in the CsCl complex of the one-armed receptor 3, in that four uranyl-salophen units instead of two are assembled in a capsule-like arrangement housing a (CsCl)2 ion quartet. However, both receptors achieve the common goal of having each metal cation in close contact with carbon atoms of two aromatic rings. 1H NMR data provide strong evidence that cation-pi(arene) interactions with the sidearms participate in binding also in solution.     

Synthesis, characterization, and complexation of tetraarylborates with aromatic cations and their use in chemical sensors

Five aromatic borate anions, namely tetrakis(4-phenoxyphenyl)borate (1), tetrakis(biphenyl)borate (2), tetrakis(2-naphthyl)borate (3), tetrakis(4-phenylphenol)borate (4), and tetrakis(4-phenoxy)borate (5), have been prepared and tested as ion-recognition sites in chemical sensors for certain aromatic cations and metal ions. To gain further insight into the complexation of the cations, some complexes have been prepared and structurally characterized. The complexation behavior of 1 and 2 towards N-methylpyridinium (6), 1-ethyl-4-(methoxycarbonyl)pyridinium (7), tropylium (8), imidazolium (9), and 1-methylimidazolium (10) cations has been studied, and the stability constants of the complexes of 1 with cations 6 and 8 have been measured to compare them with the values for the previously studied complexes of tetraphenylborate. The structures of the borate anions and their complexes have been characterized by NMR and mass spectrometric methods. X-ray crystal structures have been determined for potassium tetrakis(4-phenoxyphenyl)borate (K(+)1), N-methylpyridinium tetrakis(4-phenoxyphenyl)borate (61), 1-ethyl-4-(methoxycarbonyl)pyridinium tetrakis(4-phenoxyphenyl)borate (71), tropylium tetrakis(4-phenoxyphenyl)borate (81), and imidazolium tetrakis(biphenyl)borate (92). The results show that borate derivatives are potential candidates for a completely new family of charged carriers for use in cation-selective electrodes.     

Crown Ether Complexes of Six-Membered N-heteroaromatic Cations

Crown ether complexes of six-membered N-heteroaromatic cations and the closely related bicyclic purinium cation (6) have been studied by ¹H NMR, mass spectrometric and crystallographic methods. The stability constants for the complexes were determined by ¹H NMR titration in acetonitrile solution and the complexation stoichiometry by ¹H NMR and ESI mass spectrometric methods. Altogether six crystal structures of complexes were determined to study the complexation in the solid state. Hydrogen bonding was observed to be the most important interaction for the complexation both in solution and in the solid state but – interactions also contribute to it. All crystal structures of the DB18C6 complexes with six-membered N-heteroaromatic cations, except for 4-hydroxypyridinium, are isomorphous to previously studied five-membered N-heteroaromatic cations and pyridinium complexes. Such a close resemblance is not observed in B18C6 and 18C6 complexes or DB18C6purinium (6).     

Addition of chlorine,bromine and bromine chloride to some α,β-unsaturated methyl esters

The additions of chlorine, bromine and bromine chloride to trans methyl 2-butenoate 1, trans methyl 2-methyl-2-butenoate 2 and methyl 3-methyl-2-butenoate 3 under ionic conditions were studied. Bromine chloride addition always gave as a major regioisomer the 2-bromo-3--chloro compound,almost quantitatively in the case of 3. The mechanism of bromonium ion ring-opening (S_N1 or S_N2) is discussed with respect to the double bond substitution and regioisomer proportions. The dihalo products were identified by MS, ¹H and ¹³C NMR.