The use of a mannitol-derived fused oxacycle as a combinatorial scaffold

An efficient and high-yielding solid-phase synthesis of a small library of compounds containing a cis-fused pyranofuran structural motive is described. With use of the cheap and readily available D-(+)-mannitol, a highly functionalized sugar template was synthesized and immobilized on a solid support via an olefinic linker. Modification of this two-point molecular scaffold and subsequent ring-closing metathesis/cleavage gave access to a series of functionalized conformationally constrained fused oxacycles.     

Well‐Defined Polymer–Paclitaxel Prodrugs by a Grafting‐from‐Drug Approach

We report on the design of a polymeric prodrug of the anticancer agent paclitaxel (PTX) by a grafting‐from‐drug approach. A chain transfer agent for reversible addition fragmentation chain transfer (RAFT) polymerization was efficiently and regioselectively linked to the C2′ position of paclitaxel, which is crucial for its bioactivity. Subsequent RAFT polymerization of a hydrophilic monomer yielded well‐defined paclitaxel–polymer conjugates with high drug loading, water solubility, and stability. The versatility of this approach was further demonstrated by ω‐end post‐functionalization with a fluorescent tracer. In vitro experiments showed that these conjugates are readily taken up into endosomes where native PTX is efficiently cleaved off and then reaches its subcellular target. This was confirmed by the cytotoxicity profile of the conjugate, which matches those of commercial PTX formulations based on mere physical encapsulation.     

Dynamic conic hedging for competitiveness

The paper provides a new hedging methodology permitting systematic hedging choices with wide applications. Dynamic concave bid price, and convex ask price functionals from the recent literature are employed to construct new hedging strategies termed dynamic conic hedging. The primary focus of these strategies is to adopt positions maximizing a nonlinear conditional expectation expressed recursively as a concave current bid price for the one step ahead risk held or minimizing the convex current ask price for the risk promised. Risk management and hedging then have a new market value enhancing perspective different from the classical forms of risk mitigation, local variance minimization, or even expected utility maximization.     

Hamamelitannin Analogues that Modulate Quorum Sensing as Potentiators of Antibiotics against Staphylococcus aureus

The modulation of bacterial communication to potentiate the effect of existing antimicrobial drugs is a promising alternative to the development of novel antibiotics. In the present study, we synthesized 58 analogues of hamamelitannin (HAM), a quorum sensing inhibitor and antimicrobial potentiator. These efforts resulted in the identification of an analogue that increases the susceptibility of Staphylococcus aureus towards antibiotics in vitro, in Caenorhabditis elegans, and in a mouse mammary gland infection model, without showing cytotoxicity.     

Synthesis of fluorescent silica-coated gibbsite platelets

We describe the fluorescent labeling of gibbsite particles. Gibbsite particles are first stabilized with polyvinyl pyrrolidone. Subsequently the particles are covered with a silica layer in which a fluorescent dye is incorporated. Both fluorescein and rhodamine dyes have been used. The fluorescent labeling is applicable to gibbsite particles of various sizes. Particles are transferred to dimethyl formamide by vacuum distillation after dialysis. These particles are used for confocal scanning laser microscopy and confocal fluorescence-recovery after photobleaching.     

Synthesis of alkylated sugar amino acids: conformationally restricted L-Xaa-L-Ser/Thr mimics

Two synthetic strategies for the generation of delta-substituted pyranoid sugar amino acids (SAAs) are evaluated. The first employs chiral nonracemic tert-butane sulfinamides as key reagents. Regardless of the stereochemistry of the applied sulfinamide, the product formed has a stereochemistry resembling that of a d amino acid at C7. Direct Grignard reaction on formyl-tetra-O-benzyl-beta-D-C-glucopyranoside in the second strategy and subsequent Mitsunobu inversion, yields the l,l-dipeptide isosters.     

On the performance of DFT and interatomic potentials in predicting the energetics of (three-membered ring-containing) siliceous materials

We compare the enthalpies of transition for a range of SiO2 phases, including siliceous zeolites and dense polymorphs, calculated using three different interatomic potentials (Sanders-Leslie-Catlow (SLC), Sastre-Gale (SG), van Beest-Kramers-van Santen (BKS)), and from B3LYP periodic DFT calculations, with the experimentally measured values. It is found that the calculated results show a linear correlation with the measured values but that they often either considerably underestimate or overestimate enthalpy differences compared to experiment. Care should thus be taken when comparing experimental and calculated results. A linear rescaling of the calculated enthalpies to put the data on the same energy scale is proposed. Furthermore, it is found that when comparing enthalpies of transitions for materials containing three-membered rings, for which there is no experimental data available, the values, rescaled to the experimental energy scale, are very similar for both DFT and interatomic potentials (except for the BKS potential). The latter result suggests that the energetics of three-membered ring containing materials is well described using both approaches. Finally, we discuss the transition enthalpies of four three-membered ring containing siliceous materials and demonstrate that three-membered ring containing materials are not necessarily energetically disadvantageous but do become so progressively with increasing number of three-membered rings.     

Tunable spectral enhancement of fiber supercontinuum

We demonstrate tunable spectral enhancement of the supercontinuum generated in a microstructured fiber with a fiber long-period grating. The long-period grating leads to phase distortion and loss that, with subsequent high-intensity propagation in uniform fiber, evolves into an enhancement around the grating's resonant wavelengths. Wavelength tunability is achieved by varying the temperature or the ambient refractive index, and the spectral peak can be extinguished by immersing the grating in index-matching oil.