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An annealing time investigation revealed that the IND-PVP K12 dissolution process was remarkably faster than demixing, which contradicted previously published statements. Thus, the recrystallization method overestimated the solubility of IND in PVP K12 when a 2-h time of annealing was set as the benchmark. Likewise, the MPD and Z-EE methods overestimated the API solubility because of unreliable IND melting endotherm evaluation at lower API loadings and a relatively slow heating rate, respectively. When the experimental results obtained using the S-WD method (in conjunction with the Kwei equation) were applied to the PC-SAFT EOS, which was regarded as the most reliable combination, the predicted IND solubility in PVP K12 at T = 25 °C was approximately 40 wt %. When applicable, the S-WD method offers the advantage of using a limited number of DSC sample pans and API-polymer physical mixture compositions, which is both cost- and time-effective.Using host-guest chemistries in a biphasic system, a novel supramolecular nanoparticle surfactant (s-NPS) with redox-responsiveness is presented to structure liquids. The in situ assembly/jamming and disassembly/unjamming of s-NPSs at the oil-water interface are reversibly controlled by a switchable redox process, imparting a nanoscale redox-responsiveness, affecting the assemblies on all length scales. "Smart" all-liquid constructs including structured emulsions and programmable liquid devices are easily prepared, showing promising applications in responsive delivery, release, and reaction systems.The aim of the study was to investigate the impact of Crohn's disease (CD) on the performance of a lipid-based formulation of ciprofloxacin in a complex gastrointestinal simulator (TIM-1, TNO) and to compare the luminal environment in terms of bile salt and lipid composition in CD and healthy conditions. CD conditions were simulated in the TIM-1 system with a reduced concentration of porcine pancreatin and porcine bile. The bioaccessibility of ciprofloxacin was similar in simulated CD and healthy conditions considering its extent as well as its time course in the jejunum and ileum filtrate. Differences were observed in terms of the luminal concentration of triglycerides, monoglycerides, and fatty acids in the different TIM-1 compartments, indicating a reduction and delay in the lipolysis of formulation excipients in CD. The quantitative analysis of bile salts revealed higher concentrations for healthy conditions (standard TIM-1 fasted-state protocol) in the duodenum and jejunum TIM-1 compartments compared to published data in human intestinal fluids of healthy subjects. The reduced concentrations of bile salts in simulated CD conditions correspond to the levels observed in human intestinal fluids of healthy subjects in the fasted state.A lipidomics approach with ultra performance liquid chromatography (UPLC)/mass spectrometry (MS) has proven to be a time-efficient method to semiquantitatively analyze differences in fatty acid and bile salt levels between healthy and CD conditions. The dynamic luminal environment in CD and healthy conditions after administration of a lipid-based formulation can be simulated using the TIM-1 system. selleck compound For ciprofloxacin, an altered luminal lipid composition had no impact on its performance indicating a low risk of altered performance in CD patients.In this Letter we report on the colossal spin splitting (on the order of several electronvolts) in the collinear antiferromagnetic (AFM) MnF2 (110) monolayer, which we obtained from first-principles calculations and explain in terms of group-theoretical analysis. This Pekar-Rashba AFM-induced spin splitting with a magnetic mechanism does not require the presence of spin-orbit coupling such as with a traditional Rashba-Dresselhaus electric mechanism. Furthermore, it was observed for all wave vectors, including high-symmetry points of the two-dimensional (2D) Brillouin zone. This is in contrast to recently reported AFM-induced spin splitting in the bulk structure of MnF2, which was both smaller by at least an order of magnitude and required to vanish by symmetry at several high-symmetry points and directions of the three-dimensional Brillouin zone. The crucial part of our group-theoretical analysis is the determination of the magnetic layer group for the monolayer structure for which we propose a simple and generic procedure.Here, we report a solid-phase approach to synthesize azobenzene and spiropyran derivatives. The divergent synthesis process requires no purification steps to obtain the desired product with a 28-55% yield, depending on the specific compound. For the spiropyran compounds, solid-phase resin cleavage is performed under mild conditions to minimize spiropyran ring opening. The solid-phase method enables the synthesis of a library of azobenzene and spiropyran derivatives without the need to develop purification strategies for each derivative.CYP17A1 is an essential human steroidogenic enzyme, which catalyzes two sequential reactions leading to the formation of androstenedione from progesterone and dehydroepiandrosterone from pregnenolone. The second reaction is the C17-C20 bond scission, which is strongly dependent on the presence of cytochrome b5 and displays a heretofore unexplained more pronounced acceleration when 17OH-progesteone (17OH-PROG) is a substrate. The origin of the stimulating effect of cytochrome b5 on C-C bond scission catalyzed by CYP17A1 is still debated as mostly due to either the acceleration of the electron transfer to the P450 oxy complex or allosteric effects of cytochrome b5 favoring active site conformations that promote lyase activity. Using resonance Raman spectroscopy, we compared the effect of Mn-substituted cytochrome b5 (Mn-Cytb5) on the oxy complex of CYP17A1 with both proteins co-incorporated in lipid nanodiscs. For CYP17A1 with 17OH-PROG, a characteristic shift of the Fe-O mode is observed in the presence of Mn-b5, indicating reorientation of a hydrogen bond between the 17OH group of the substrate from the terminal to the proximal oxygen atom of the Fe-O-O moiety, a configuration favorable for the lyase catalysis. For 17OH-pregnenolone, no such shift is observed, the favorable H-bonding orientation being present even without Mn-Cytb5. These new data provide a precise allosteric interpretation for the more pronounced acceleration seen for the 17OH-PROG substrate.

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