Donor-Acceptor Complexes of Alkylcarbazole and Dicarbazolylalkane Donors with the Acceptors Tetracyanoethylene and Tetranitromethane

Electron donor−acceptor complexes of conformationally flexible 1,n-dicarbazolylalkanes (C12H8N−(CH2)n−NC12H8), where n = 1−5, were examined. Carbazole, methylcarbazole, ethylcarbazole, and cyanoethylcarbazole also were studied as monochromophoric analogues for comparison. In dichloromethane solution, the dicarbazolylalkanes form 1:1 complexes with the terminal carbazolyl chromophores acting as independent donors when n ≥ 2. With the acceptor tetranitromethane (TNM), the carbazoles form contact complexes displaying small positive enthalpies of formation. In contrast, stable complexes form with the acceptor tetracyanoethylene (TCNE). Crystalline TCNE complexes were isolated for the bichromophoric donors with n = 2−4. The solid complexes and their uncomplexed donor components were analyzed by single-crystal X-ray diffraction. The solid-state stoichiometries of (carbazolyl donor):(TCNE acceptor) were found to depend on the donor conformation. Dicarbazolylalkane donors separated by two or four methylene units exhibit a 1:1 donor:acceptor ratio and form stacked arrays of alternating donor and acceptor groups. A three-carbon bridging alkyl chain leads to local sandwich-type complexes in the solid state with a resulting donor:acceptor ratio of 4:1

Fracture phenomena in micro- and nano-layered polycarbonate/poly(vinylidene fluoride- co -hexafluoropropylene) films under electric field for high energy density capacitors

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TLR5 agonist entolimod reduces the adverse toxicity of TNF while preserving its antitumor effects.

Tumor necrosis factor alpha (TNF) is capable of inducing regression of solid tumors. However, TNF released in response to Toll-like receptor 4 (TLR4) activation by bacterial lipopolysaccharide (LPS) is the key mediator of cytokine storm and septic shock that can cause severe tissue damage limiting anticancer applications of this cytokine. In our previous studies, we demonstrated that activation of another Toll-like receptor, TLR5, could protect from tissue damage caused by a variety of stresses including radiation, chemotherapy, Fas-activating antibody and ischemia-reperfusion. In this study, we tested whether entolimod could counteract TNF-induced toxicity in mouse models. We found that entolimod pretreatment effectively protects livers and lungs from LPS- and TNF-induced toxicity and prevents mortality caused by combining either of these agents with the sensitizer, D-galactosamine. While LPS and TNF induced significant activation of apoptotic caspase 3/7, lipid tissue peroxidation and serum ALT accumulation in mice without entolimod treatment, these indicators of toxicity were reduced by entolimod pretreatment to the levels of untreated control mice. Entolimod was effective when injected 0.5-48 hours prior to, but not when injected simultaneously or after LPS or TNF. Using chimeric mice with hematopoiesis differing in its TLR5 status from the rest of tissues, we showed that this protective activity was dependent on TLR5 expression by non-hematopoietic cells. Gene expression analysis identified multiple genes upregulated by entolimod in the liver and cultured hepatocytes as possible mediators of its protective activity. Entolimod did not interfere with the antitumor activity of TNF in mouse hepatocellular and colorectal tumor models. These results support further development of TLR5 agonists to increase tissue resistance to cytotoxic cytokines, reduce the risk of septic shock and enable safe systemic application of TNF as an anticancer therapy