Syntheses and biological evaluation of vinblastine congeners

Sixty-two congeners of vinblastine (VLB), primarily with modifications of the piperidine ring in the carbomethoxycleavamine moiety of the binary alkaloid, were synthesized and evaluated for cytotoxicity against murine L1210 leukemia and RCC-2 rat colon cancer cells, and for their ability to inhibit polymerization of microtubular protein at < 10(-6) M, and for induction of spiralization of microtubular protein, and for microtubular disassembly at 10(-4) M concentrations. An ID50 range of >10(7) M concentrations was found for L1210 inhibition by these compounds, with the most active 1000x as potent as vinblastine.     

Diffusion-induced instability in chemically reacting systems: Steady-state multiplicity,oscillation, and chaos

The dynamical behavior of two coupled cells or reactors is described. The cells are coupled by diffusion, e.g., through a semipermeable membrane, and the chemical reactions and initial or feed concentrations of all species are the same in the two cells. Each cell has only a single stable steady state in the absence of coupling, and the coupled system may exhibit multiple steady states, periodic oscillation, or chaos. The attractors of the coupled system may be either homogeneous (the two cells have equal concentrations) or inhomogeneous. Three two-variable kinetic models are examined: the Brusselator, a model of the chlorine dioxide-iodine-malonic acid reaction, and the Degn-Harrison model. The dynamical behavior of the coupled system is determined by the nonlinearities in the uncoupled subsystems and by two ratios, that of the diffusion constants of the two species and that of the area of the membrane to the product of the membrane thickness and the volume of a cell.     

The potential of autofluorescence for the detection of single living cells for label-free cell sorting in microfluidic systems

A novel method for studying unlabeled living mammalian cells based on their autofluorescence (AF) signal in a prototype microfluidic device is presented. When combined, cellular AF detection and microfluidic devices have the potential to facilitate high-throughput analysis of different cell populations. To demonstrate this, unlabeled cultured cells in microfluidic devices were excited with a 488 nm excitation light and the AF emission (> 505 nm) was detected using a confocal fluorescence microscope (CFM). For example, a simple microfluidic three-port glass microstructure was used together with conventional electroosmotic flow (EOF) to switch the direction of the fluid flow. As a means to test the potential of AF-based cell sorting in this microfluidic device, granulocytes were successfully differentiated from human red blood cells (RBCs) based on differences in AF. This study demonstrated the use of a simple microfabricated device to perform high-throughput live cell detection and differentiation without the need for cell-specific fluorescent labeling dyes and thereby reducing the sample preparation time. Hence, the combined use of microfluidic devices and cell AF may have many applications in single-cell analysis.     

Superspreading driven by Marangoni flow

The spontaneous spreading (called superspreading) of aqueous trisiloxane ethoxylate surfactant solutions on hydrophobic solid surfaces is a fascinating phenomenon with several practical applications. For example, the ability of trisiloxane ethoxylate surfactants to enhance the spreading of spray solutions on waxy weed leaf surfaces, such as velvetleaf (Abutilion theophrasti), makes them excellent wetting agents for herbicide applications. The superspreading ability of silicone surfactants has been known for decades, but its mechanism is still not well understood. In this paper, we suggest that the spreading of trisiloxane ethoxylates is controlled by a surface tension gradient, which forms when a drop of surfactant solution is placed on a solid surface. The proposed model suggests that, as the spreading front stretches, the surface tension increases (the surfactant concentration becomes lower) at the front relative to the top of the droplet, thereby establishing a dynamic surface tension gradient. The driving force for spreading is due to the Marangoni effect, and our experiments showed that the higher the gradient, the faster the spreading. A simple model describing the phenomenon of superspreading is presented. We also suggest that the superspreading behavior of trisiloxane ethoxylates is a consequence of the molecular configuration at the air/water surface (i.e. small and compact hydrophobic part), as shown by molecular dynamics modeling. We also found that the aggregates and vesicles formed in trisiloxane solutions do not initiate the spreading process and therefore these structures are not a requirement for the superspreading process.     

From an electron micrograph to a postage stamp

Soon following Dan Shechtman’s discovery of quasicrystals, Ágnes Csanády and her associates started producing beautiful quasicrystals of flowerlike morphology. The image of one of their specimen appeared on the Israeli postage stamp honoring Shechtman’s discovery, his Nobel Prize, and the International Year of Crystallography.     

James D. Watson 88—the discovery of the double helix was an iconic event in structural chemistry

The ingenuity of James D. Watson and Francis Crick, the convergence of the advances in X-ray crystallography, the accumulated knowledge of structural chemistry, and the breakthroughs in chemical methods of analysis led to the discovery of the double helix structure of DNA. The discovery catapulted Watson to a career that helped DNA and the applications of the knowledge about its structure triumph in biomedical sciences. Watson’s eighty-eighth birthday is an occasion to have a look at his path to success, his personality, and assess his legacy.     

Direct electrophilic monofluoromethylation

Monofluoromethyl derivatives of various nucleophiles have been synthesized using a new electrophilic monofluoromethylating reagent developed. The S-(monofluoromethyl)diarylsulfonium tetrafluoroborate has been shown to be effective for the introduction of an electrophilic monofluoromethyl group into C, S, O, N, and P nucleophiles. This methodology has been expanded for the synthesis of various biologically important compounds.     

Nanoparticles prepared by self-assembly of Chitosan and poly-γ-glutamic acid

The present paper describes the preparation and characterization of novel biodegradable nanoparticles based on self-assembly of poly-gamma-glutamic acid (γ-PGA) and chitosan (CH). The nanosystems were stable in aqueous media at low pH conditions. Solubility of the systems was determined by turbidity measurements. Surface charge and mobility were measured electrophoretically. The particle size and the size distribution of the polyelectrolyte complexes were identified by dynamic light scattering and transmission electron microscopy (TEM). It was found that the size and size distribution of the nanosystems depends on the concentrations of γ-PGA and CH solutions and their ratio as well as on the pH of the mixture and the order of addition. The diameter of individual particles was in the range of 20–285 nm measured by TEM, and the average hydrodynamic diameters were between 150 and 330 nm. These biodegradable, self-assembling stable nanocomplexes might be useful for several biomedical applications.     

Effect of digitonin on the rhodopsin meta I-meta II equilibrium

Absorbance difference spectra were recorded from 10 micros to 540 ms after photoexcitation of sonicated suspensions of hypotonically washed bovine rod outer segments with varying amounts of the detergent digitonin added (0 to 2%) at 20 degrees C. Metarhodopsin I480 and metarhodopsin II displayed the expected anomalous pH dependence at pH 6 and 8 (i.e. opposite to that expected from direct protonation of the chromophore Schiff base). However, increasing levels of digitonin eliminated the pH dependence of the equilibrium, and at 2% digitonin the pH 6 and pH 8 data were both similar to the data collected at pH 8 without digitonin. Addition of 0.5% azolectin restored approximately 50% of the anomalous pH dependence at pH 6 in the 2% digitonin sample. The possibility that digitonin induced large-scale aggregation of rhodopsin in the disk membrane that could be reversed by azolectin was tested using time-resolved linear dichroism. Those results showed that even 0.3% digitonin disrupted the membrane, and no large aggregates were detectable under any conditions. Thus, digitonin reduces the activity of a component of the disk membrane required for metarhodopsin II formation, and that deficiency can be compensated for by azolectin.     

Honoring Vladimir Ya. Shevchenko

This Editorial introduces a selection of papers honoring Professor Vladimir Ya. Shevchenko on the occasion of his 75th birthday.