Optimization of Pathogen Capture in Flowing Fluids with Magnetic Nanoparticles

Magnetic nanoparticles have been employed to capture pathogens for many biological applications; however, optimal particle sizes have been determined empirically in specific capturing protocols. Here, a theoretical model that simulates capture of bacteria is described and used to calculate bacterial collision frequencies and magnetophoretic properties for a range of particle sizes. The model predicts that particles with a diameter of 460 nm should produce optimal separation of bacteria in buffer flowing at 1 L h⁻¹. Validating the predictive power of the model, Staphylococcus aureus is separated from buffer and blood flowing through magnetic capture devices using six different sizes of magnetic particles. Experimental magnetic separation in buffer conditions confirms that particles with a diameter closest to the predicted optimal particle size provide the most effective capture. Modeling the capturing process in plasma and blood by introducing empirical constants (c_e), which integrate the interfering effects of biological components on the binding kinetics of magnetic beads to bacteria, smaller beads with 50 nm diameters are predicted that exhibit maximum magnetic separation of bacteria from blood and experimentally validated this trend. The predictive power of the model suggests its utility for the future design of magnetic separation for diagnostic and therapeutic applications.     

Annular‐ring slot antenna designs with circular polarization radiation

The design of a microstrip‐fed annular‐ring slot antenna (ARSA) with circular polarization (CP) radiation is initially studied. To obtain CP radiation with broad 3‐dB axial ratio (AR) bandwidth that can cover the WiMAX 2.3 GHz (2305–2320 MHz, 2345–2360 MHz) and WLAN 2.4 GHz (2400–2480 MHz) bands, a novel technique of extending an inverted L‐shaped slot from the bottom section of the annular‐ring is proposed. To suppress the harmonic modes induced by the CP ARSA, the technique of integrating a defected ground structure into the annular‐ring slot is further introduced. From the measured results, 10‐dB impedance bandwidth and 3‐dB AR bandwidth of 44.86 and 9.68% were achieved by the proposed harmonic suppressed CP ARSA. Furthermore, average gain and radiation efficiency of ～4.7 dBic and 71%, respectively, were also exhibited across the bands of interest. © 2014 Wiley Periodicals, Inc. Int J RF and Microwave CAE 25:337–345, 2015.     

Tetrahydroindoles as Multipurpose Screening Compounds and Novel Sirtuin Inhibitors

Indoles are privileged structures in medicinal and bioorganic chemistry that are particularly well suited to serve as platforms for diversity. Among many other therapeutic areas, the indole scaffold has been used to design aromatic compounds useful to interfere with enzymes engaged in the regulation of substrate acylation status, such as sirtuins. However, the planarity of the indole ring is not necessarily optimal for all target enzymes, especially when functionalization with aromatic side chains is required. Replacement of flat scaffolds by nonplanar molecular cores dominated by sp³ hybridization is a common strategy to avoid the disadvantages associated with poor solubility and high promiscuity, while covering less-well-explored areas of chemical space. Thus, we synthesized fragment-like tetrahydroindoles suitable for fragment-based drug discovery as well as a well-characterized small library intended as multipurpose screening compounds. For proof of principle, these compounds were screened against sirtuins 1–3, enzymes known to be addressable by indoles. We found that 2,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxamides are potent and selective SIRT2 inhibitors. Compound 16 t displayed an IC₅₀ value of 0.98 μm and could serve as exquisite starting point for hit-to-lead profiling.     

Preparation and physicochemical study of jute and glass composites of epoxy resin of (2E, 6E)-bis(4-hydroxybenzylidene)cyclohexanone

Polymer Bulletin - Jute and glass composites of epoxy resin of (2E, 6E)-bis(4-hydroxybenzylidene)cyclohexanone (EBHBC) were prepared by compressing molding technique using three different hardeners...     

The Critical Role of Passive Permeability in Designing Successful Drugs

Passive permeability is a key property in drug disposition and delivery. It is critical for gastrointestinal absorption, brain penetration, renal reabsorption, defining clearance mechanisms and drug-drug interactions. Passive diffusion rate is translatable across tissues and animal species, while the extent of absorption is dependent on drug properties, as well as in vivo physiology/pathophysiology. Design principles have been developed to guide medicinal chemistry to enhance absorption, which combine the balance of aqueous solubility, permeability and the sometimes unfavorable compound characteristic demanded by the target. Permeability assays have been implemented that enable rapid development of structure-permeability relationships for absorption improvement. Future advances in assay development to reduce nonspecific binding and improve mass balance will enable more accurately measurement of passive permeability. Design principles that integrate potency, selectivity, passive permeability and other ADMET properties facilitate rapid advancement of successful drug candidates to patients.