Rapid and convenient semi-automated microwave-assisted solid-phase synthesis of arylopeptoids

A facile and expedient route to the synthesis of arylopeptoid oligomers (N-alkylated aminomethyl benz-amides) using semi-automated microwave-assisted solid-phase synthesis is presented. The synthesis was optimized for the incorporation of side chains derived from sterically hindered or unreactive amines and both ortho- and para-substituted arylo-backbones. By utilizing this optimized protocol a complex nonameric arylopeptoid was synthesized in less than 11 h, featuring a novel alternating ortho-, meta-, and para-substituted backbone pattern and a variety of chemically diverse and challenging side chains.     

Electromembrane extraction of basic drugs from untreated human plasma and whole blood under physiological pH conditions

The present work describes the first systematic study of electromembrane extraction (EME) from biological matrices under physiological conditions. Six basic drugs with protein binding in the range of 20–97% were extracted from untreated human plasma and whole blood through a supported liquid membrane (SLM) consisting of 1-ethyl-2-nitrobenzene impregnated in the walls of a hollow fiber, and into an acidified aqueous solution inside the lumen of the fiber. The electrical potential difference over the membrane reduced the protein binding of the drugs and transported the free drug fraction over the membrane. Recoveries in the range 25–65% were obtained with 10-min extraction time and an applied voltage of only 10 V over the SLM. Interday precision better than 20% RSD and linearity in the range 0.5–10 μg/mL were obtained for nortriptyline and methadone. Extraction from untreated whole blood was also demonstrated with recoveries in the range 19–51%.     

Electrokinetic migration across artificial liquid membranes Tuning the membrane chemistry to different types of drug substances

Twenty different basic drugs were electrokinetically extracted across a thin artificial organic liquid membrane with a 300 V d.c. electrical potential difference as the driving force. From a 300 microl aqueous sample (acidified corresponding to 10mM HCl), the drugs were extracted for 5 min through a 200 microm artificial liquid membrane of a water immiscible organic solvent immobilized in the pores of a polypropylene hollow fiber, and into a 30 microl aqueous acceptor solution of 10mM HCl inside the lumen of the hollow fiber. Hydrophobic basic drugs (logP>1.7) were effectively isolated utilizing 2-nitrophenyl octyl ether (NPOE) as the artificial liquid membrane, with recoveries up to 83%. For more hydrophilic basic drugs (logP<1.0), a mixture of NPOE and 25% (w/w) di-(2-ethylhexyl) phosphate (DEHP) was required to ensure efficient extraction, resulting in recoveries up to 75%. DEHP was expected to act as an ion-pair reagent ion-pairing the protonated hydrophilic drugs at the interface between the sample and the membrane, resulting in permeation of the interface.     

Source levels and harmonic content of whistles in white-beaked dolphins (Lagenorhynchus albirostris)

Recordings of white-beaked dolphin whistles were made in Faxafl6i Bay (Iceland) using a three-hydrophone towed linear array. Signals from the hydrophones were routed through an amplifier to a lunch box computer on board the boat and digitized using a sample rate of 125 kHz per channel. Using this method more than 5000 whistles were recorded. All recordings were made in sea states 0-1 (Beaufort scale). Dolphins were located in a 2D horizontal plane by using the difference of arrival time to the three hydrophones, and source levels were estimated from these positions using two different methods (I and II). Forty-three whistles gave a reliable location for the vocalizing dolphin when using method II and of these 12 when using method I. Source level estimates on the center hydrophone were higher using method I [average source level 148 (rms) +/- 12 dB, n = 36] than for method II [average source level 139 (rms) +/- 12 dB, n = 36]. Using these rms values the maximum possible communication range for whistling dolphins given the local ambient noise conditions was then estimated. The maximum range was 10.5 km for a dolphin whistle with the highest source level (167 dB) and about 140 m for a whistle with the lowest source level (118 dB). Only two of the 43 whistles contained an unequal number of harmonics recorded at the three hydrophones judging from the spectrograms. Such signals could be used to calculate the directionality of whistles, but more recordings are necessary to describe the directionality of white-beaked dolphin whistles.     

High-resolution magnetic resonance flow imaging in a model of porous bone-implant interface

PURPOSE: To evaluate the application of high-resolution MRI methodology for characterizing the fluid velocity field and evaluate fluid shear field within a simplified in vitro model of a bone-implant interface. MATERIALS AND METHODS: The study used a specific micromotion canine bone implant that has been used for over a decade in the experimental evaluation of anatomical, biomaterial, mechanical and surgical factors influencing the quality of the implant interface. To allow its implementation in an MR coil, a nonmagnetic model of the micromotion implant was fabricated. The model consisted of a cylinder of polymethylmethacrylate (PMMA) representing the implant, located within an annular controlled gap into a block of coralline-derived bulk porous hydroxyapatite (HA; Interpore Cross International, Irvine, CA, USA). The assembly was potted in a polycarbonate shell and connected to a gravity-feed flow system consisting of a water fluid reservoir and peristaltic pump. Cross-sectional fluid velocity images through the principal axis of the implant were generated using a phase-encoding MR imaging technique; axial fluid flow was derived, and fluid shear was evaluated using a Newtonian fluid model. RESULTS: Due to the nonuniform gap of the actual experimental construct, a highly nonuniform flow through the annular gap and a secondary flow through the porous HA block were observed. Axial velocity magnitudes in the range 0.04 to 14 mm/s were measured, and the flow velocities within the annular gap and the surrounding bone differed by nearly two orders of magnitude. Image analysis showed that 95% of total flow passed through the annular gap and 5% was transported through the porous HA block. Fluid shear was computed within the porous structure and the annular gap, and they differed by one order of magnitude. CONCLUSION: We demonstrated that high-resolution MR flow imaging has the resolution to measure fluid transport processes noninvasively through a nonmagnetic model bone implant. Gap fluid flow and fluid flow into the permeable skeleton (HA block) were quantified, and these data allowed the noninvasive determination of fluid shear. These promising results are encouraging for applications in biological tissue, artificial bone substitutes, tissue engineering and clinically relevant studies concerning implant fixation.     

Tandem facial amphiphiles for membrane protein stabilization

We describe a new type of synthetic amphiphile that is intended to support biochemical characterization of intrinsic membrane proteins. Members of this new family displayed favorable behavior with four of five membrane proteins tested, and these amphiphiles formed relatively small micelles.     

A simple and efficient route to N-functionalized dithieno[3,2-b:2',3'-d]pyrroles: fused-ring building blocks for new conjugated polymeric systems

A general synthetic route has been developed for the simple and efficient preparation of N-functionalized dithieno[3,2-b:2',3'-d]pyrroles. These synthetic methods utilize N-functionalized N-(3'-thienyl)-3-aminothiophenes produced from the Pd-catalyzed amination of 3-bromothiophene with primary amines, followed by a one-pot bromination/cyclization process. This combination allows the convenient preparation of a variety of N-functionalized dithieno[3,2-b:2',3'-d]pyrroles (where substituent = hexyl, octyl, decyl, tert-butyl, and p-hexylphenyl) in good yield (65-82%). Characterization of the structure and reactivity of this class of compounds is also described, including electrochemical and photophysical data for all compounds and X-ray structural data for the octyl-, tert-butyl-, and p-hexylphenyl-functionalized compounds.