An Organoruthenium Anticancer Agent Shows Unexpected Target Selectivity For Plectin

Organometallic metal(arene) anticancer agents require ligand exchange for their anticancer activity and this is generally believed to confer low selectivity for potential cellular targets. However, using an integrated proteomics-based target-response profiling approach as a potent hypothesis-generating procedure, we found an unexpected target selectivity of a ruthenium(arene) pyridinecarbothioamide (plecstatin) for plectin, a scaffold protein and cytolinker, which was validated in a plectin knock-out model in vitro. Plectin targeting shows potential as a strategy to inhibit tumor invasiveness as shown in cultured tumor spheroids while oral administration of plecstatin-1 to mice reduces tumor growth more efficiently in the invasive B16 melanoma than in the CT26 colon tumor model.     

On Fractional Adaptive Control

Introducing fractional operators in the adaptive control loop, and especially in Model Reference Adaptive Control (MRAC), has proven to be a good mean for improving the plant dynamics with respect to response time and disturbance rejection. The idea of introducing fractional operators in adaptation algorithms is very recent and needs to be more established, that is why many research teams are working on the subject. Previously, some authors have introduced a fractional model reference in the adaptation scheme, and then fractional integration has been used to deal directly with the control rule. Our original contribution in this paper is the use of a fractional derivative feedback of the plant output, showing that this scheme is equivalent to the fractional integration, one with a certain benefit action on the system dynamical behaviour and a good robustness effect. Numerical simulations are presented to show the effectiveness of the proposed fractional adaptive schemes.     

A straightforward conversion of aurones to 2-benzoylbenzofurans: transformation of one class of natural products into another

The naturally occurring aurones (2-benzylidene-3(2H)-benzofuran-3-ones) can be easily converted to another class of natural products 2-benzoylbenzo[b]furans, via an effective reduction, acid-mediated rearrangement, and oxidation cascade. This easy conversion was conducted without purification of intermediates. This straightforward conversion may be considered as a possible biosynthesis pathway of 2-benzoylbenzo[b]furans in plants.     

Palladium-catalyzed selective N-(hetero)arylation or N,N′-di(hetero)arylation of 1-aminoindoles

The selective synthesis of N-(hetero)aryl-1-aminoindoles 3 from the corresponding N-aminoindoles and (hetero)aryl halides using a catalyst combination of Pd₂(dba)₃ associated to Josiphos is described. By switching to Xantphos as the ligand, the alternate catalytic system allows the coupling to proceed efficiently for the preparation of symmetrical and unsymmetrical N,N′-diaryl-1-aminoindole derivatives in good yields.     

Photodegradable, Photoadaptable Hydrogels via Radical-Mediated Disulfide Fragmentation Reaction

Various techniques have been adopted to impart a biological responsiveness to synthetic hydrogels for the delivery of therapeutic agents as well as the study and manipulation of biological processes and tissue development. Such techniques and materials include polyelectrolyte gels that swell and deswell with changes in pH, thermosensitive gels that contract at physiological temperatures, and peptide cross-linked hydrogels that degrade upon peptidolysis by cell-secreted enzymes. Herein we report a unique approach to photochemically deform and degrade disulfide cross-linked hydrogels, mitigating the challenges of light attenuation and low quantum yield, permitting the degradation of hydrogels up to 2 mm thick within 120 s at low light intensities (10 mW/cm(2) at 365 nm). Hydrogels were formed by the oxidation of thiol-functionalized 4-armed poly(ethylene glycol) macromolecules. These disulfide cross-linked hydrogels were then swollen in a lithium acylphosphinate photoinitiator solution. Upon exposure to light, photogenerated radicals initiate multiple fragmentation and disulfide exchange reactions, permitting and promoting photodeformation, photowelding, and photodegradation. This novel, but simple, approach to generate photoadaptable hydrogels portends the study of cellular response to mechanically and topographically dynamic substrates as well as novel encapsulations by the welding of solid substrates. The principles and techniques described herein hold implications for more than hydrogel materials but also for photoadaptable polymers more generally.     

Purification and characterization of a new Bacillus thuringiensis bacteriocin active against Listeria monocytogenes, Bacillus cereus and Agrobacterium tumefaciens

This study reports on the identification, characterization and purification of a new bacteriocin, named Bacthuricin F103, from a Bacillus thuringiensis strain BUPM103. Bacthuricin F103 production began in the early exponential phase and reached a maximum in the middle of the same phase. Two chromatographic methods based on high performance liquid chromatography and fast protein liquid chromatography systems were used to purify Bacthuricin F103. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis revealed that this bacteriocin had a molecular weight of approximately 11 kDa. It also showed a wide range of thermostability of up to 80 °C for 60 min and a broad spectrum of antimicrobial activity over a pH range of 3.0–10.0. This bacteriocin was noted, and for the first time, to exhibit potent antimicrobial activity against Agrobacterium subsp. strains, the major causal agents of crown gall disease in tomato and vineyard crops, and against several challenging organisms in food, such as Listeria monocytogenes and Bacillus cereus. Complete killing with immediate impact on cells was observed within a short period of time. The sequence obtained for Bacthuricin F103 by direct N-terminal sequencing shared considerable homology with hemolysin. Bacthuricin F103 was noted to act through the depletion of intracellular ions, which suggest that the cell membrane was a possible target to Bacthuricin F103.     

High-throughput analysis using gated multi-inlet mass spectrometry

Gated multi-inlet mass spectrometry is introduced for high-throughput chemical analysis. In this design, multiple high-pressure liquid chromatography (HPLC) columns or capillary electrophoresis (CE) capillaries are attached to multiple electrosprayers (one for each column or capillary) that spray toward a gated multi-inlet time-of-flight mass spectrometer (TOF-MS). Although all of the sprayers are spraying continuously, only one inlet is exposed at any given time for a specific duration set by the MS data system. The gated multi-sprayer, multi-inlet design significantly enhances the performance of the multi-ESI, multi-inlet TOF-MS with minimal cost and reduces analysis time. The gated multi-sprayer, multi-inlet design was applied to the investigation of column-to-column reproducibility of multiple HPLCs using a peptide mixture and to the simultaneous analysis of four protein digests. In addition, it was applied to the analysis of peptide mixtures using eight CE capillaries. The gated multi-inlet MS has several advantages compared to our previous non-gated multi-inlet MS. For example, because only one inlet is open at one time, the original manufacturer's inlet inner diameter and pumping system can be used, which enhances the sensitivity of detection for each inlet and minimizes the manufacturing cost. In addition, the number of inlets can be increased as desired. The maximum number of liquid streams that can be concurrently analyzed is limited by: (1) the number of inlets, (2) the chromatographic (electrophoretic) peak width, and (3) how fast the gate can move from one position to the next.     

A flexible, unified radical-based approach to polycyclic structures

Cis- and trans-decalins, trans-perhydroazulenes, and [5.3.1]-bicyclo-undecanone scaffolds can be readily constructed starting from unsaturated ketones and using the degenerative xanthate transfer technology to accomplish unusual and otherwise difficult radical cyclisations.     

Chemical and nanomechanical analysis of rice husk modified by ATRP-grafted oligomer

Rice husk (RH), an abundant agricultural residue, was reacted with 2-bromoisobutyryl bromide, to convert it to a heterogeneous polyfunctional macroinitiator for Atom Transfer Radical Polymerization (ATRP). The number of active sites placed on the RH surface was small, but they were ATRP active. Non-polar methyl methacrylate (MMA) and polar acrylonitrile (AN) were polymerized from the RH, and a sequential monomer addition was used to prepare an amphiphilic PMMA-b-PAN copolymer on RH surface. FTIR qualitatively confirmed the grafting. Gravimetric and XPS analysis of the different RH surface compositions indicated thin layers of oligomeric PMMA, PAN, and PMMA-b-PAN. The modified surfaces were mapped by nanomechanical AFM to measure surface roughness, and adhesion and moduli using the Derjaguin-Muller-Toropov model. RH grafted with MMA possessed a roughness value of 7.92, and a hard and weakly adhering surface (13.1 GPa and 16.7 nN respectively) while RH grafted with AN yielded a roughness value of 29 with hardness and adhesion values of 4.0 GPa and 23.5 nN. The PMMA-b-PAN modification afforded a surface with a roughness value of 51.5 nm, with hardness and adhesion values of 3.0 GPa and 75.3 nN.