Some New Heterocyclic Sulphonates with potential antimicrobial activity

4-(Phenylhydrazono-4′-benzenesulphonato)-3-methyl-2-pyrazolin-5-one ( 2 ) was prepared by treating 4-(4′-hydroxyphenylhydrazono)-3-methyl-2-pyrazolin-5-one ( 1 ) with benzenesulphonyl chloride. Heating 2 with acetic anhydride, chloroacetyl chloride and benzenesulphonyl chloride afforded the N-acetyl ( 3 ), N-chloroacetyl ( 4 ) and O-benzenesulphonyl ( 5 ) derivatives, respectively. 2 reacted with benzenesulphonyl chloride under cooling conditions to give the N-benzenesulphonyl derivative ( 6 ). 2 undergoes Mannich reaction to give the N-Mannich base ( 7 ). Reaction of 2 with formaldehyde in methanol afforded the N-hydroxymethyl derivative ( 8 ) which undergoes condensation with ethyl acetoacetate, ethyl cyanoacetate and malononitrile to give compounds 9 , 10 and 11 respectively. The antimicrobial activity of these products against gram-positive (+ve), gram-negative (−ve) bacteria and fungi was screened. They showed potential bactericidal activity and some of them exhibited high fungicidal activity.     

A Hybrid Magneto-Optic Capacitive Memory with Picosecond Writing Time

The long-term future of information storage requires the use of sustainable nanomaterials in architectures operating at high frequencies. Interfaces can play a key role in this pursuit via emergent functionalities that break out from conventional operation methods. Here, spin-filtering effects and photocurrents are combined at metal-molecular-oxide junctions in a hybrid magneto-capacitive memory. Light exposure of metal-fullerene-metal oxide devices results in spin-polarized charge trapping and the formation of a magnetic interface. Because the magnetism is generated by a photocurrent, the writing time is determined by exciton formation and splitting, electron hopping, and spin-dependent trapping. Transient absorption spectroscopy measurements show changes in the electronic states as a function of the magnetic history of the device within picoseconds of the optical pumping. The stored information is read using time-resolved scanning magneto optic Kerr effect measurements during microwave irradiation. The emergence of a magnetic interface in the picosecond timescale opens new paths of research to design hybrid magneto-optic structures operating at high frequencies for sensing, computing, and information storage.     

Characterization of reinforcing effect of alumina nanoparticles on the novolac phenolic resin

Very fine alumina nanoparticles were loaded in novolac type phenolic resin (PF) using solution mixing method. The concentration of nanoalumina in PF was varied between 2.5 to 20 wt%. All the compounds were compression molded and then subjected to scanning electron microscopy (SEM), tensile, flexural, and dynamic mechanical analysis (DMA) tests. SEM analysis showed that the nanoalumina were dispersed uniformly at low concentrations, however, at high concentrations, dispersion was suppressed leading to agglomerates in the composites. Mechanical testing revealed that the nanoalumina had a great influence on the strength and stiffness of PF resin particularly at concentrations below 5 wt%. However, at concentration above 5 wt%, the stress concentrations were developed because of the formation of big aggregates that results in strength reduction. Theoretical analyses based on Pukanszky and micromechanical models of tensile modulus revealed that strong interfacial interaction and thick interphase region around the alumina nanoparticles is formed. DMA results suggested that the nanoalumina increased the crosslinking density of the PF resin, possibly around the interface region. It was also postulated that an apparent percolation state is established above 5 wt% loading of nanoalumina in which interphase region comes to contact before direct contact of particle leading to continuous interphase region. POLYM. COMPOS., 35:1285–1293, 2014. © 2013 Society of Plastics Engineers     

A Degron Blocking Strategy Towards Improved CRL4CRBN Recruiting PROTAC Selectivity**

Small molecules inducing protein degradation are important pharmacological tools to interrogate complex biology and are rapidly translating into clinical agents. However, to fully realise the potential of these molecules, selectivity remains a limiting challenge. Herein, we addressed the issue of selectivity in the design of CRL4^CRBN recruiting PROteolysis TArgeting Chimeras (PROTACs). Thalidomide derivatives used to generate CRL4^CRBN recruiting PROTACs have well described intrinsic monovalent degradation profiles by inducing the recruitment of neo-substrates, such as GSPT1, Ikaros and Aiolos. We leveraged structural insights from known CRL4^CRBN neo-substrates to attenuate and indeed remove this monovalent degradation function in well-known CRL4^CRBN molecular glues degraders, namely CC-885 and Pomalidomide. We then applied these design principles on a previously published BRD9 PROTAC (dBRD9-A) and generated an analogue with improved selectivity profile. Finally, we implemented a computational modelling pipeline to show that our degron blocking design does not impact PROTAC-induced ternary complex formation. We believe that the tools and principles presented in this work will be valuable to support the development of targeted protein degradation.