Rheological behavior of self-assembling PEG-beta-cyclodextrin/PEG-cholesterol hydrogels

The rheological properties of a recently developed self-assembling hydrogel system composed of beta-cyclodextrin (betaCD)- and cholesterol-derivatized 8-arm star-shaped poly(ethylene glycol) (PEG8) were investigated. To understand and predict the gel rheological properties, data fitting with the Maxwell model as well as comparing the system's concentration-dependent behavior with Cates' model for reversibly breaking chains were performed. To investigate the influence of the polymer architecture, networks were also prepared by replacing the cholesterol-derivatized 8-arm star-shaped PEG by linear bifunctional PEG-cholesterol or by using 4-arm instead of 8-arm polymers. Rheological analysis showed that the 8-arm polymer-based mixtures yielded tight viscoelastic networks, but their storage and loss moduli significantly deviated from those predicted by the Maxwell model. The scaling of the plateau moduli, relaxation times, and zero-shear viscosities with concentration for gels composed of 8-arm cholesterol- and betaCD-derivatized PEG followed a power law with exponents higher than predicted by Cates' model. On the other hand, hydrogels in which linear bifunctional PEG-cholesterol was used instead of 8-arm star-shaped PEG-cholesterol or which were based on 4-arm polymers showed a substantially better fit with the Maxwell model and reduced differences between empirical and Cates' theoretical scaling exponents. Rheological analysis also showed that the hydrogels were thermoreversible. At low temperatures, the gels showed viscoelastic behavior due to slow overall relaxation of the polymer chains. At higher temperatures, however, a reduced number of betaCD/cholesterol complexes and concomitant faster chain relaxation processes eventually led to liquid-like behavior. The relationship between temperature and the relaxation time was used to determine an activation energy of 46 kJ/mol for breaking and reptation of the polymers.     

Structure elucidation and 1H/13C NMR spectral assignments of four trabectedin related compounds

This article presents the structure elucidation of four new compounds, formed during the hemisynthetic preparation of trabectedin, an anti-tumor natural product from Ecteinascidia turbinata. We report herein on the use of UV, MS and NMR spectroscopic data along with (1)H and (13)C spectral assignments obtained by means of 1D and 2D homo- and heteronuclear NMR techniques.     

Nucleophilic additions to alkylidene bis(sulfoxides): stereoelectronic effects in vinyl sulfoxides

Conjugate additions of nucleophiles (e.g. enolates, amines and malonate anions) to bis(p-tolylsulfinyl)alkenes, alkylidene-1,3-dithiane-1,3-dioxides and alkylidene-1,3-dithiolane-1,3-dioxides have recently been published. Reasons for different selectivities and reaction rates will be discussed by consideration of steric and electronic effects. The preferred mode of attack can be explained by stereoelectronic effects (hyperconjugation) in the primarily carbanion, which is stabilized by n-->S-O-sigma* interaction with an antiperiplanar S=O group. Calculation of the transition states [BP86/aug-TZVP] for the addition of acetone enolate to the dithiane-derived alkylidene bis(sulfoxide) revealed that 6.6-7.3 kJ mol(-1) more energy is needed for an attack leading to a less-stabilized carbanion. Two axial S=O groups in dithiolane-derived alkylidene bis(sulfoxides) lead to a higher reactivity towards nucleophiles.     

Microcapsules ejecting nanosized species into the environment

In this communication we report on microcapsules which eject nanoparticles into the environment. The speed of the nanoparticles ejected in water is approximately 800-fold faster than their Brownian diffusion. Such microcarriers may allow nanosized species to travel long distances, in short times, through highly viscous environments and may find applications in e.g. drug delivery and tissue engineering.     

A liquid chromatography – tandem mass spectrometry method to measure a selected panel of uremic retention solutes derived from endogenous and colonic microbial metabolism

Chronic kidney disease (CKD) is associated with an increased risk of mortality and cardiovascular disease, which is, at least partly, mediated by the accumulation of so-called uremic retention solutes. Although there has been an increasing interest in the behavior of these solutes, derived from both the endogenous and colonic microbial metabolism, methods to simultaneously and accurately measure a broad panel of relevant uremic retention solutes remain scarce.     

Uptake of silver nanoparticles by monocytic THP-1 cells depends on particle size and presence of serum proteins

Human health risks by silver nanoparticle (AgNP) exposure are likely to increase due to the increasing number of NP-containing products and demonstrated adverse effects in various cell lines. Unfortunately, results from (toxicity) studies are often based on exposure dose and are often measured only at a fixed time point. NP uptake kinetics and the time-dependent internal cellular concentration are often not considered. Macrophages are the first line of defense against invading foreign agents including NPs. How macrophages deal with the particles is essential for potential toxicity of the NPs. However, there is a considerable lack of uptake studies of particles in the nanometer range and macrophage-like cells. Therefore, uptake rates were determined over 24 h for three different AgNPs sizes (20, 50 and 75 nm) in medium with and without fetal calf serum. Non-toxic concentrations of 10 ng Ag/mL for monocytic THP-1 cells, representing realistic exposure concentration for short-term exposures, were chosen. The uptake of Ag was higher in medium without fetal calf serum and showed increasing uptake for decreasing NP sizes, both on NP mass and on number basis. Internal cellular concentrations reached roughly 32/10 %, 25/18 % and 21/15 % of the nominal concentration in the absence of fetal calf serum/with fetal calf serum for 20-, 50- and 75-nm NPs, respectively. Our research shows that uptake kinetics in macrophages differ for various NP sizes. To increase the understanding of the mechanism of NP toxicity in cells, the process of uptake (timing) should be considered.     

Suzuki-Miyaura and Stille reactions as key steps in the synthesis of diversely functionalized Amaryllidaceae alkaloid analogs bearing a 5,6,7,8-tetrahydrobenzo[c,e]azocine skeleton

Microwave-assisted Suzuki-Miyaura and Stille cross-coupling reactions for the synthesis of highly electron-rich and diversely functionalized biaryl intermediates are presented. Microwave-irradiation has been demonstrated to be a very powerful tool for performing difficult transition metal-catalyzed cross-coupling reactions with unfavorably substituted coupling partners. The key biaryl intermediates were used for the microwave-enhanced construction of the 5,6,7,8-tetrahydrobenzo[c,e]azocine skeleton of the Apogalanthamine analogs. The success of the strategy is demonstrated by synthesizing a number of hitherto unknown, diversely functionalized, natural product analogs.     

Microwave-assisted transition-metal-catalyzed synthesis of N-shifted and ring-expanded buflavine analogues

Two novel and efficient strategies for the synthesis of hitherto unknown N-shifted and ring-expanded buflavine analogues are presented. Construction of the medium-sized ring system of the title molecules, a difficult task due to the high activation energy needed for the ring-closure with the additional rigidity imposed by the biaryl skeleton, was achieved by using Suzuki-Miyaura biaryl coupling and a ring-closing metathesis reaction as the key steps. The combination of a second-generation Grubbs catalyst and microwave irradiation proved to be highly useful in generating the otherwise difficult to obtain medium-sized ring system of the buflavine analogues.