Existing single-walled carbon nanotube synthesis methods are not easily scalable, operate under severe conditions, and involve high capital and operating costs. The current cost of SWNT is exceedingly high. A catalytic method of synthesis has been developed that has shown potential advantages over the existing methods. This method is based on a catalyst formulation that inhibits the formation of undesired forms of carbon; it can be scaled-up and may result in lower production costs. 相似文献
Protein kinases control virtually every aspect of normal and pathological cell physiology and are considered ideal targets for drug discovery. Most kinase inhibitors target the ATP binding site and interact with residue of a hinge loop connecting the small and large lobes of the kinase scaffold. Resistance to kinase inhibitors emerges during clinical treatment or as a result of in vitro selection approaches. Mutations conferring resistance to ATP site inhibitors often affect residues that line the ATP binding site and therefore contribute to selective inhibitor binding. Here, we show that mutations at two specific positions in the hinge loop, distinct from the previously characterized "gatekeeper," have general adverse effects on inhibitor sensitivity in six distantly related kinases, usually without consequences on kinase activity. Our results uncover a unifying mechanism of inhibitor resistance of protein kinases that might have widespread significance for drug target validation and clinical practice. 相似文献
Bimodal polyethylenes comprising varying proportions of high‐ and low‐molecular‐weight fractions are synthesized in a single polymerization stage, via the co‐immobilization of a chromium and an iron catalyst on an MgCl2/AlEtn(OEt)3?n support. Changes observed in the viscoelastic response of the polymer melt with increasing content of the high‐molecular‐weight fraction indicate effective mixing in the bimodal blend. In flow, chains in the high‐molecular weight fraction tend to orient and stretch under shear. Due to the longer relaxation time of the high‐molecular‐weight component, X‐ray diffraction and scattering reveal that shear‐induced crystallization takes place at temperatures close to the equilibrium melting point of linear polyethylene. The so‐crystallized high‐molecular‐weight component suppresses the nucleation barrier for further crystallization, leading to the formation of a “shish‐kebab” polymer morphology.
Unusually structure-selective growth of single-walled carbon nanotubes (SWNTs) has been attained using a CVD method with a solid supported catalyst. In this method, CO feedstock disproportionates on silica-supported catalytic nanoclusters of Co that are formed in situ from mixed salts of Co and Mo. The nanotube products are analyzed by spectrofluorimetry to reveal distributions resolved at the level of individual (n,m) structures. Two structures, (6,5) and (7,5), together dominate the semiconducting nanotube distribution and comprise more than one-half of that population. The average diameter of produced SWNTs is only 0.81 nm, and a strong propensity is found favoring chiral angles near the armchair limit. 相似文献
The four steps preparation of 2-[(E)-hex-1′-enyl]tetrahydropyran starting from 3-nitro-4,5-dihydro-6H-pyran has been carried out in 40% overall yield. 相似文献
The understanding of the interaction between non-steroidal anti-inflammatory drugs and human serum albumin plays a fundamental role in the development of new drugs and new therapeutic strategies. Several studies have been performed, nevertheless, the interaction phenomena are still not fully understood. In this work, high-field solution Nuclear Magnetic Resonance (NMR) spectroscopy was applied to compare the strength of the interaction of diclofenac sodium salt, ketorolac tris salt and flurbiprofen sodium salt toward albumin. To this aim, mono- and bi-selective relaxation rate measurements were performed by applying selective π-pulses at the selected frequencies and by following magnetization recovery. On the basis of the dependence of relaxation parameters on albumin concentration, normalized affinity indexes were calculated for several protons of the drugs. Affinity indexes for diclofenac were about five-fold higher in comparison with ketorolac and flurbiprofen. Aromatic moieties of the three drugs and methine protons at the chiral centers of ketorolac and flurbiprofen were more involved in the interaction with albumin. In conclusion, NMR spectroscopy allows not only for the comparison of drug-to-protein affinities but also points out the nature of the drug sites that are more extensively involved in the interaction. 相似文献
Cisplatin is widely employed as a first-line chemotherapeutic agent for many solid tumors, including malignant pleural mesothelioma (MPM). However, its clinical use is limited by heavy side effects and acquired resistance, the latter being mainly related to enhanced DNA repair. Many clinical trials using combinations of platinum drugs and PARP-1 inhibitors (PARPis) have been carried out, with the hope that such combinations might lead to improved therapeutic efficacy against tumors. Here, the synthesis and efficacy in reducing MPM cell viability of four cisplatin-based Pt(IV) prodrugs containing the PARPi 3-aminobenzamide (3-ABA) fragment are described. The most promising conjugate is more effective than cisplatin or cisplatin/3-ABA combination, administered in equimolar doses, in inhibiting PARP-1 activity and inducing apoptosis in BRCA1/2 wild type MPM cells, grown as monolayer or as multicellular spheroids. 相似文献