Cryogenic photolysis of activated bleomycin to ferric bleomycin

Activated bleomycin (ABLM) is a drug--Fe(III)-hydroperoxide complex kinetically competent in DNA attack (via H4' abstraction). This intermediate is relatively stable, but its spontaneous conversion to ferric bleomycin (Fe(III).BLM) is poorly characterized because no observable intermediate product accumulates. Light was shown to trigger ABLM attack on DNA in liquid at -30 degrees C, so ABLM was irradiated (at its 350 nm ligand-to-metal charge-transfer transition) at 77 K to stabilize possible intermediates. ABLM photolysis (quantum yield, Phi = 0.005) generates two kinds of product: Fe(III).BLM (with no detectable intermediate) and one or more minor (1-2%) radical O-Fe-BLM byproduct, photostable at 77 K. Adding DNA, even without its target H4', increases the quantum yield of ABLM conversion >10-fold while suppressing the observed radical yield. Since cryogenic solid-phase reactions can entail only constrained local rearrangement, the reaction(s) converting ABLM to Fe(III).BLM must be similarly constrained.     

X-ray mapping in electron-beam instruments.

This review traces the development of X-ray mapping from its beginning 50 years ago through current analysis procedures that can reveal otherwise obscure elemental distributions and associations. X-ray mapping or compositional imaging of elemental distributions is one of the major capabilities of electron beam microanalysis because it frees the operator from the necessity of making decisions about which image features contain elements of interest. Elements in unexpected locations, or in unexpected association with other elements, may be found easily without operator bias as to where to locate the electron probe for data collection. X-ray mapping in the SEM or EPMA may be applied to bulk specimens at a spatial resolution of about 1 microm. X-ray mapping of thin specimens in the TEM or STEM may be accomplished at a spatial resolution ranging from 2 to 100 nm, depending on specimen thickness and the microscope. Although mapping has traditionally been considered a qualitative technique, recent developments demonstrate the quantitative capabilities of X-ray mapping techniques. Moreover, the long-desired ability to collect and store an entire spectrum at every pixel is now a reality, and methods for mining these data are rapidly being developed.     

Solid-phase microextraction of organophosphate pesticides in source waters for drinking water treatment facilities

The rapid detection of contaminants in our nation's drinking water has become a top homeland security priority in this time of increased national vigilance. Real-time monitoring of drinking water for deliberate or accidental contamination is key to national security. One method that can be employed for the rapid screening of pollutants in water is solid-phase microextraction (SPME). SPME is a rapid, sensitive, solvent-free system that can be used to screen for contaminants that have been accidentally or intentionally introduced into a water system. A method using SPME has been developed and optimized for the detection of seven organophosphate pesticides in drinking water treatment facility source waters. The method is tested in source waters for drinking water treatment facilities in Mississippi and Alabama. Water is collected from a deepwater well at Stennis Space Center (SSC), MS, the drinking water source for SSC, and from the Converse Reservoir, the main drinking water supply for Mobile, AL. Also tested are samples of water collected from the Mobile Alabama Water and Sewer System drinking water treatment plant prior to chlorination. The method limits of detection for the seven organophosphates were comparable to those described in several Environmental Protection Agency standard methods. They range from 0.25 to 0.94 microg/L.     

A mild Pummerer-like reaction of carbohydrate-based selenoethers and thioethers involving linear ozonide acetates as putative intermediates

Pummerer-like rearrangements of carbohydrate-based heterocycles containing selenium and sulfur were investigated. To the best of our knowledge, this is the first report on the Pummerer rearrangement in selenoheterocycles. Ozonization of 1,4-anhydro-D-galactitol or 1,5-anhydroxylitol derivatives containing sulfur or selenium as the ring heteroatom gave unstable intermediates that were attributed to ozonides. These intermediates decomposed upon warming to give selenoxides or sulfoxides. Significantly, addition of acetic anhydride at low temperature to the ozonization reaction mixtures gave Pummerer-rearrangement products after warming to ambient temperature. However, when the isolated selenoxides or sulfoxides were treated with acetic anhydride, Pummerer rearrangement occurred but the sulfoxides required much higher reaction temperatures. The latter results are at variance with the former and are interpreted in terms of the rearrangement of the ozonide acetate intermediates in the former cases. To probe whether the rearrangement proceeded heterolytically via extrusion of singlet oxygen or homolytically via the generation of radical species, trapping experiments with rubrene and electron paramagnetic resonance (EPR) studies with the radical trap DMPO were performed. The results of these experiments are consistent with the intermediacy of radical species and suggest a new and milder synthetic method to generate Pummerer-type products.     

Synthesis and structural investigation of internally coordinated alpha-amidoboronic acids

[structure: see text] Six new N-acyl-boroGly derivatives, along with their N-acyl-boroSar analogues, have been synthesized by modification of conventional procedures. Structural characterization of these alpha-amidoboronic acids was accomplished by extensive use of 11B and 1H NMR spectroscopy. These compounds were prepared to determine the extent of intramolecular B-O dative bond formation within the context of a five-membered (:O=C-N-C-B) ring motif. It is shown that the formation of such dative bonds depends on the nature of the substituents at both the acyl carbon and the nitrogen atoms. Computational evidence from second-order M?ller-Plesset perturbation theory is provided in support of these findings.     

Significant parameters in the optimization of MALDI-TOF-MS for synthetic polymers

One of the most significant issues in any analytical practice is optimization. Optimization and calibration are key factors in quantitation. In matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), instrument optimization is a limitation restricting quantitation. An understanding of the parameters that are most influential and the effects of these parameters on the mass spectrum is required for optimization. This understanding is especially important when characterizing synthetic polymers by MALDI-TOF-MS, due to the breadth of the polymer molecular mass distribution (MMD). Two considerations are important in quantitation, additivity of signal and signal-to-noise (S/N). In this study, the effects of several instrument parameters were studied using an orthogonal experimental design to understand effects on the signal-to-noise (S/N) of a polystyrene distribution. The instrument parameters examined included detector voltage, laser energy, delay time, extraction voltage, and lens voltage. Other parameters considered were polymer concentration and matrix. The results showed detector voltage and delay time were the most influential of the instrument parameters for polystyrene using all trans-retinoic acid (RA) as the matrix. These parameters, as well as laser energy, were most influential for the polystyrene with dithranol as the matrix.     

Solvent-extraction and Langmuir-adsorption-based transport in chemically functionalized nanopore membranes

We have investigated the transport properties of nanopore alumina membranes that were rendered hydrophobic by functionalization with octadecyltrimethoxysilane (ODS). The pores in these ODS-modified membranes are so hydrophobic that they are not wetted by water. Nevertheless, nonionic molecules can be transported from an aqueous feed solution on one side of the membrane, through the dry nanopores, and into an aqueous receiver solution on the other side. The transport mechanism involves Langmuir-type adsorption of the permeating molecule onto the ODS layers lining the pore walls, followed by solid-state diffusion along these ODS layers; we have measured the diffusion coefficients associated with this transport process. We have also investigated the transport properties of membranes prepared by filling the ODS-modified pores with the water-immiscible (hydrophobic) liquid mineral oil. In this case the transport mechanism involves solvent extraction of the permeating molecule into the mineral oil subphase confined with the pores, followed by solution-based diffusion through this liquid subphase. Because of this different transport mechanism, the supported-liquid membranes show substantially better transport selectivity than the ODS-modified membranes that contain no liquid subphase.     

Amphiphilic Polymethacrylate‐ and Polystyrene‐Based Chemical Delivery Systems for Damascones

Amphiphilic polystyrene‐ and polymethacrylate‐based β‐acyloxy ketones were investigated as potential delivery systems for the controlled release of damascones by retro‐1,4‐addition in applications of functional perfumery. A series of random copolymers being composed of the hydrophobic damascone‐release unit and a second hydrophilic monomer were obtained by radical polymerization in organic solution by using 2,2′‐azobis[2‐methylpropanenitrile] (AIBN) as the radical source (Schemes 2 and 3). A first evaluation of the polymer conjugates in acidic or alkaline buffered aqueous solution, and in the presence of a surfactant, showed that polymethacrylates and polystyrenes having a carboxylic acid function as hydrophilic group are particularly interesting for the targeted applications (Table 2). The release of δ‐damascone ( 1 ) from polymers with poly(methacrylic acid) and poly(vinylbenzoic acid) comonomers in different stoichiometric ratios was thus followed over several days at pH 4, 7, and 9 by comparison of fluorescence probing, solvent extraction, and particle‐size measurements (Tables 3 and 4). In acidic media, the polymers were found to be stable, and almost no δ‐damascone ( 1 ) was released. In neutral or alkaline solution, where the carboxylic acid functions are deprotonated, the concentration of 1 increased over time. In the case of the polymethacrylates, the fluorescence probing experiments showed an increasing hydrophilicity of the polymer backbone with increasing fragrance release, whereas in the case of the polystyrene support, the hydrophilicity of the environment remained constant. These results suggest that the nature of the polymer backbone may have a stronger influence on the fragrance release than the ratio of hydrophilic and hydrophobic monomers in the polymer chain.     

Coupling of the Polymer Threading a Membrane Transition to the Membrane Adsorption Transition

A polymer molecule threading through a pore in a plane membrane is allowed to adsorb on either or both sides of the membrane. Further, it is confined to the vicinity of the membrane by two plane barriers lying on either side of the membrane. A lattice model of this problem is exactly solvable by matrix techniques. The equilibrium translocation behavior is described as a function of the polymer MW, the membrane adsorption energies, the solution properties, the barrier separations, applied force, and the temperature. The transition is first-order, meaning that small changes in any of these 9 quantities can in the limit of infinite MW, completely translocate the polymer. The work of Park and Sung who used Smoluchowski-like equations to calculate translocation transit times can be generalized by use of the sea-snake model which is relevant to isolated polymer chains in solution. The physics behind the sea-snake model is that if one monomer is pulled into the membrane, the distance the center of mass of the untranslocated portion of the chain moves is MW^−1/2 of the distance between monomer units. This reduces the effective friction coefficient by MW^1/2. It is found for the sea-snake model that the MW dependence of transit times varies as MW^3/2 or MW depending on whether we use a free draining or a non-free draining picture for the polymer.