Predicted binding rate of new cephalosporin antibiotics by a 3D-QSAR method: a new approach

Abstract  

Antibiotics are chemotherapeutic agents with activity against microorganisms, for example bacteria, fungi, or protozoa, used for the treatment of many types of diseases. Binding of antibiotics to serum proteins in human plasma is a major determinant of their pharmacodynamic and pharmacokinetic behavior and, consequently, can affect their systemic distribution in the body. Here, the predicted binding rates of ceftazidime and 13 other pharmacological agents classified as antibiotics to plasma proteins (percentage fraction bound; PFB) were evaluated by use of 3D-QSAR models. We attempted to establish the contribution of hydrogen bond donor/acceptor and hydrophobic properties supplied by electrostatic fields to the PFB. Significant cross-validated correlation q ² (0.5–0.7) and the fitted correlation r ² (0.7–0.97) coefficients revealed that these models have reasonable power to predict the design 19 new antibiotics using ceftazidime as template, these compounds being our suggestion for further studies.     

Asynchronous sampling for ultrafast experiments with low momentum compaction at the ANKA ring

A high‐repetition‐rate pump–probe experiment is presented, based on the asynchronous sampling approach. The low‐α mode at the synchrotron ANKA can be used for a time resolution down to the picosecond limit for the time‐domain sampling of the coherent THz emission as well as for hard X‐ray pump–probe experiments, which probe structural dynamics in the condensed phase. It is shown that a synchronization of better than 1 ps is achieved, and examples of phonon dynamics of semiconductors are presented.     

Controlled Synthesis of Large Single Crystals of Metal-Organic Framework CPO-27-Ni Prepared by a Modulation Approach: In situ Single-Crystal X-ray Diffraction Studies

The size of single crystals of the metal-organic framework CPO-27-Ni was incrementally increased through a series of modulated syntheses. A novel linker modulated synthesis using 2,5-dihydroxyterephthalic acid and the isomeric ligand 4,6-dihydroxyisophthalic acid yielded large single crystals of CPO-27-Ni (∼70 μm). All materials were shown to have high crystallinity and phase purity through powder X-ray diffraction, electron microscopy methods, thermogravimetry, and compositional analysis. For the first time single-crystal structure analyses were carried out on CPO-27-Ni. High BET surface areas and nitric oxide (NO) release efficiencies were recorded for all materials. Large single crystals of CPO-27-Ni showed a prolonged NO release and proved suitable for in situ single-crystal diffraction experiments to follow the NO adsorption. An efficient activation protocol was developed, leading to a dehydrated structure after just 4 h, which subsequently was NO-loaded, leading to a first NO loaded single-crystal structural model of CPO-27-Ni.     

Polyurea microcapsules from isocyanatoethyl methacrylate copolymers

The synthesis of two types of isocyanate side chain containing copolymers, poly(methyl methacrylate‐co‐isocyanatoethyl methacrylate) (P(MMA‐co‐IEM)) and poly(benzyl methacrylate‐co‐isocyanatoethyl methacrylate) (P(BnMA‐co‐IEM)), which were synthesized by Cu(0)‐mediated radical polymerization, is reported. Polymerization proceeded to high conversion giving polymers of relatively narrow molar mass distributions. The incorporation of the bulky aromatic groups in the latter copolymer rendered it sufficiently stable toward hydrolysis and enabled the isolation of the product and its characterization by ¹H and ¹³C NMR, and FTIR spectroscopy and SEC. Both P(MMA‐co‐IEM) and P(BnMA‐co‐IEM) were functionalized with dibutylamine, octylamine, and (R)‐(+)‐α‐methylbenzyl‐amine, which further proved the successful incorporation of the isocyanate groups. Furthermore, P(BnMA‐co‐IEM) was used for the fabrication of liquid core microcapsules via oil‐in‐water interfacial polymerization with diethylenetriamine as crosslinker. The particles obtained were in the size range of 10–90 µm in diameter independent of the composition of copolymer. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 2698–2705     

Angle‐dependent light scattering by highly uniform colloidal rod‐shaped microparticles: Experiment and simulation

While extensive theoretical work has been devoted to analyzing scattering behavior for nonspherical particles, few experimental studies of the light‐scattering properties of such particles are available, largely because of the difficulty of synthesizing such particles with uniform geometries. Here we report the synthesis of highly uniform, volume‐equivalent rod‐shaped colloidal particles prepared from their commercial spherical counterparts, on which we performed light scattering experiments as a function of scattering angle for micro rods with varying aspect ratio and volume. These results were compared to values calculated using the T‐Matrix method. Good agreement with theoretical predictions was found for the experimentally measured scattering cross sections and the angular dependence of the scattering intensity. An increase in the forward scattering intensity is observed and predicted for particles with larger aspect ratios relative to their volume equivalent spheres, with only minor differences observed at both mid‐range and backscattering angles. Furthermore, the light scattering results for the rod‐shaped particles did not show the scattering fringes seen in scattering by the spheres, indicating that as three‐dimensional symmetry is broken, the associated Lorenz–Mie resonances are strongly attenuated. This observation also was predicted by theory. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016 , 54, 1889–1895