Novel copolymers of styrene. 13. Methyl and methoxy ring-trisubstituted butyl 2-cyano-3-phenyl-2-propenoates

Novel electrophilic trisubstituted ethylenes, methyl and methoxy ring-trisubstituted butyl 2-cyano-3-phenyl-2-propenoates, RPhCH=C(CN)CO₂C₄H₉ where R is 2,4,5-trimethyl, 2,4,6-trimethyl, 2,3-dimethyl-4-methoxy, 2,5-dimethyl-4-methoxy, 2,4-dimethoxy-3-methyl, 2,3,4-trimethoxy, 2,4,5-trimethoxy, 2,4,6-trimethoxy, 3,4,5-trimethoxy were prepared and copolymerized with styrene. The monomers were synthesized by the piperidine catalyzed Knoevenagel condensation of ring-trisubstituted benzaldehydes and butyl cyanoacetate, and characterized by CHN analysis, IR, ¹H and ¹³C-NMR. All the ethylenes were copolymerized with styrene (M₁) in solution with radical initiation (ABCN) at 70°C. The compositions of the copolymers were calculated from nitrogen analysis and the structures were analyzed by IR, ¹H and ¹³C-NMR. Decomposition of the copolymers in nitrogen occurred in two steps, first in the 200–500°C range with residue (2–5% wt), which then decomposed in the 500–800°C range.     

Synthesen und Kristallstrukturen neuer sulfidoverbrückter Rutheniumclusterverbindungen

Syntheses and Crystal Structures of New Sulfido‐bridged Ruthenium Clusters The reaction of S(SiMe₃)₂ or NaSH with [RuCl₂(PPh₃)₃] or [Ru₃Cl₈(PEt₃)₄] leads to the formation of sulfidobridged ruthenium clusters. In this publication the compounds [Ru₆S₈(PPh₃)₆][PF₆] ( 1 ), [Ru₆S₈(PPh₃)₆][RuCl₄(PPh₃)₂] ( 2 ), [Ru₆S₈(PEt₃)₆] ( 3 ) and [Ru₃S₄Cl₂(PPh₃)₃]₂ ( 4 ) are described. The structures of these compounds were elucidated by single crystal X‐ray structural analyses.     

Mechanistic insights into intramolecular phosphate group transfer during collision induced dissociation of phosphopeptides

We report on the rearrangement chemistry of model phosphorylated peptides during collision‐induced dissociation (CID), where intramolecular phosphate group transfers are observed from donor to acceptor residues. Such “scrambling” could result in inaccurate modification localization, potentially leading to misidentifications. Systematic studies presented herein provide mechanistic insights for the unusually high phosphate group rearrangements presented some time ago by Reid and coworkers (Proteomics 2013, 13 [6], 964‐973). It is postulated here that a basic residue like histidine can play a key role in mediating the phosphate group transfer by deprotonating the serine acceptor site. The proposed mechanism is consistent with the observation that fast collisional activation by collision‐cell CID and higher‐energy collisional dissociation (HCD) can shut down rearrangement chemistry. Additionally, the rearrangement chemistry is highly dependent on the charge state of the peptide, mirroring previous studies that less rearrangement is observed under mobile proton conditions.     

Simple and Sensitive Determination of Sibutramine in Slimming Tea Beverages Using a Carbon Screen‐printed Electrode with Adsorptive Stripping Voltammetry

The stimulant sibutramine is an anorexic agent found as an adulterant in natural products and multivitamins supplements used for weight‐loss. In this work, a carbon graphite screen‐printed electrode (SPE‐Gr) with adsorptive stripping pulse differential voltammetry (AdSDPV) is presented for the sensitive and simple detection of sibutramine in slimming tea beverages. The proposed electrochemical method shows a linear working range from 2.0 to 120 μM with a low LOD (0.3 μM) for sibutramine determination in slimming tea samples. The analytical performance of the SPE‐Gr with AdSDPV for sibutramine detection suggests its possible application as an easy, fast and low‐cost method to analyse adulterated tea samples with this stimulant at low levels (<0.1 %).     

MALDI Mass Spectrometry Imaging for Evaluation of Therapeutics in Colorectal Tumor Organoids

Patient-derived colorectal tumor organoids (CTOs) closely recapitulate the complex morphological, phenotypic, and genetic features observed in in vivo tumors. Therefore, evaluation of drug distribution and metabolism in this model system can provide valuable information to predict the clinical outcome of a therapeutic response in individual patients. In this report, we applied matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to examine the spatial distribution of the drug irinotecan and its metabolites in CTOs from two patients. Irinotecan is a prodrug and is often prescribed as part of therapeutic regimes for patients with advanced colorectal cancer. Irinotecan shows a time-dependent and concentration-dependent permeability and metabolism in the CTOs. More interestingly, the active metabolite SN-38 does not co-localize well with the parent drug irinotecan and the inactive metabolite SN-38G. The phenotypic effect of irinotecan metabolism was also confirmed by a viability study showing significantly reduced proliferation in the drug treated CTOs. MALDI-MSI can be used to investigate various pharmaceutical compounds in CTOs derived from different patients. By analyzing multiple CTOs from a patient, this method could be used to predict patient-specific drug responses and help to improve personalized dosing regimens.

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Excited-state acid-base chemistry: evidence for a dissociative excited state

Excitation (410 nm) of the bimetallic [(bpy)(2)Ru(CN)(mu-CN)Rh(NH(3))(4)Br](2+) produces the MLCT state localized on the (bpy)(2)Ru(CN)(2) ligand. Photoinduced cleavage of the bimetallic occurs in the presence of [H(+)], and the dependence yields a K(a) equivalent to that for ground-state cis-(bpy)(2)Ru(CN)(2) implying separation of the bimetallic prior to relaxation. The pH dependence and the emissivity of a bimetallic composed of components that individually quench at a diffusion controlled rate suggest that rupture of the RuCN-Rh bond is due to the reduction in electron density at the cyano ligand that occurs on population of the MLCT state. Unlike known photoinduced metal ligand dissociations, where the excitation energy is consumed in the dissociation, the dissociated "(bpy)(2)Ru(CN)(2) ligand" remains excited.     

Stimulus-responsiveness and drug release from porous silicon films ATRP-grafted with poly(N-isopropylacrylamide)

In this report, we employ surface-initiated atom transfer radical polymerization (SI-ATRP) to graft a thermoresponsive polymer, poly(N-isopropylacrylamide) (PNIPAM), of controlled thickness from porous silicon (pSi) films to produce a stimulus-responsive inorganic-organic composite material. The optical properties of this material are studied using interferometric reflectance spectroscopy (IRS) above and below the lower critical solution temperature (LCST) of the PNIPAM graft polymer with regard to variation of pore sizes and thickness of the pSi layer (using discrete samples and pSi gradients) and also the thickness of the PNIPAM coatings. Our investigations of the composite's thermal switching properties show that pore size, pSi layer thickness, and PNIPAM coating thickness critically influence the material's thermoresponsiveness. This composite material has considerable potential for a range of applications including temperature sensors and feedback controlled drug release. Indeed, we demonstrate that modulation of the temperature around the LCST significantly alters the rate of release of the fluorescent anticancer drug camptothecin from the pSi-PNIPAM composite films.     

Insights into the development of strategy from a complexity perspective

This paper provides an account of an ongoing project with an independent school in the UK. The project focuses on a strategy development intervention which, from the start, was systemic in orientation. The intention was to integrate simple systems concepts and approaches into the strategy development process to: address power relations in actively engaging a wide range of stakeholders with the school’s strategy-making process; generate a range of good ideas; and make the strategy-making process transparent in order to inspire stakeholder confidence in, and commitment to, it and its outcomes. This paper describes how seeking to meet these aims entailed a series of workshops during the course of which an awareness of the relevance, in our interpretation, of Complex Adaptive Systems concepts grew.     

Toxicological Screening of Four Bioactive Citroflavonoids: In Vitro,In Vivo,and In Silico Approaches

Many studies describe different pharmacological effects of flavonoids on experimental animals and humans. Nevertheless, few ones are confirming the safety of these compounds for therapeutic purposes. This study aimed to investigate the preclinical safety of naringenin, naringin, hesperidin, and quercetin by in vivo, in vitro, and in silico approaches. For this, an MTT-based cytotoxicity assay in VERO and MDCK cell lines was performed. In addition, acute toxicity was evaluated on Wistar rats by OECD Guidelines for the Testing of Chemicals (Test No. 423: Acute Oral Toxicity-Class Method). Furthermore, we used the ACD/Tox Suite to predict toxicological parameters such as hERG channel blockade, CYP450 inhibition, and acute toxicity in animals. The results showed that quercetin was slightly more cytotoxic on cell lines (IC₅₀ of 219.44 ± 7.22 mM and 465.41 ± 7.44 mM, respectively) than the other citroflavonoids. All flavonoids exhibited an LD₅₀ value > 2000 mg/kg, which classifies them as low-risk substances as OECD guidelines established. Similarly, predicted LD⁵⁰ was LD₅₀ > 300 to 2000 mg/kg for all flavonoids as acute toxicity assay estimated. Data suggests that all these flavonoids did not show significant toxicological effects, and they were classified as low-risk, useful substances for drug development.