Driving high quantum yield NIR emission through proquinoidal linkage motifs in conjugated supermolecular arrays

High quantum yield NIR fluorophores are rare. Factors that drive low emission quantum yields at long wavelength include the facts that radiative rate constants increase proportional to the cube of the emission energy, while nonradiative rate constants increase in an approximately exponentially with decreasing S₀–S₁ energy gaps (in accordance with the energy gap law). This work demonstrates how the proquinoidal BTD building blocks can be utilized to minimize the extent of excited-state structural relaxation relative to the ground-state conformation in highly conjugated porphyrin oligomers, and shows that 4-ethynylbenzo[c][1,2,5]thiadiazole (E-BTD) units that terminate meso-to-meso ethyne-bridged (porphinato)zinc (PZn_n) arrays, and 4,7-diethynylbenzo[c][1,2,5]thiadiazole (E-BTD-E) spacers that are integrated into the backbone of these compositions, elucidate new classes of impressive NIR fluorophores. We report the syntheses, electronic structural properties, and emissive characteristics of neoteric PZn-(BTD-PZn)_n, PZn₂-(BTD-PZn₂)_n, and BTD-PZn_n-BTD fluorophores. Absolute fluorescence quantum yield (ϕ_f) measurements, acquired using a calibrated integrating-sphere-based measurement system, demonstrate that these supermolecules display extraordinary ϕ_f values that range from 10–25% in THF solvent, and between 28–36% in toluene solvent over the 700–900 nm window of the NIR. These studies underscore how the regulation of proquinoidal conjugation motifs can be exploited to drive excited-state dynamical properties important for high quantum yield long-wavelength fluorescence emission.

Incorporation of proquinoidal BTD building blocks into conjugated porphyrin oligomers minimizes the extent of excited-state structural relaxation relative to the ground-state conformation, elucidating new classes of impressive NIR fluorophores.     

Critical factors for high-performance physically adsorbed (dynamic) polymeric wall coatings for capillary electrophoresis of DNA

Physically adsorbed (dynamic) polymeric wall coatings for microchannel electrophoresis have distinct advantages over covalently linked coatings. In order to determine the critical factors that control the formation of dynamic wall coatings, we have created a set of model polymers and copolymers based on N,N-dimethylacrylamide (DMA) and N,N-diethylacrylamide (DEA), and studied their adsorption behavior from aqueous solution as well as their performance for microchannel electrophoresis of DNA. This study is revealing in terms of the polymer properties that help create an "ideal" wall coating. Our measurements indicate that the chemical nature of the coating polymer strongly impacts its electroosmotic flow (EOF) suppression capabilities. Additionally, we find that a critical polymer chain length is required for polymers of this type to perform effectively as microchannel wall coatings. The effective mobilities of double-stranded (dsDNA) fragments within dynamically coated capillaries were determined in order to correlate polymer hydrophobicity with separation performance. Even for dsDNA, which is not expected to be a strongly adsorbing analyte, wall coating hydrophobicity has a deleterious influence on separation performance.     

Towards two-dimensional electrophoresis mapping of the cerebrospinal fluid proteome from a single individual

We test the ability of state-of-the-art two-dimensional electrophoresis (2-DE) technology to enable the proteome mapping of ante mortem cerebrospinal fluid (CSF) from a single individual. Using the sensitive technologies of a fluorescent protein stain and fluorescence laser scanning of 2-DE gels, combined with matrix-assisted laser desorption/ionization-time of flight/time of flight-mass spectrometry (MALDI-TOF/TOF-MS) for protein identification, a highly detailed 2-DE map of the CSF proteome was created. The 2-DE map contains 600 identified spots representing 82 different proteins. Of the 82 proteins identified, 25 have not appeared in any previously published 2-DE map of CSF, and 11 have not been previously reported to exist in CSF. Most of the identifications originate from an ante mortem CSF sample collected from a single hydrocephalus patient. A supplemental map created from neurologically normal patients is also presented. A webpage with protein identification and scoring information from both maps is available at http://www.leelab.org/csfmap.     

Synthesis of a digermane-containing tricylic nonadecadienedione incorporating an equivalent of ring-opened THF

The combination of 2 equiv of bis[bis(trimethylsilyl)amide]germylene (5) with 2 equiv of 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) in tetrahydrofuran (THF) results in the ring-opening of 1 equiv of THF to form 2,2,8,8-tetrakis(1,1,1,3,3,3-hexamethyl-disilazan-2-yl)-5,16-diphenyl-7,9,14-trioxa-1,3,5,16,18,19-hexaaza-2,8-digerma-tricyclo[13.2.1.13,6]nonadeca-6(19),15(18)-diene-4,17-dione (6). This fast and nearly quantitative reaction builds a 15-membered ring from five different molecules. The new ring, structurally assigned by X-ray crystallography, contains a flexible methylene chain that moves rapidly on the NMR time scale.     

Liquid crystal effects on bacterial viability

The primary objective of this research was to test the hypothesis that lyotropic chromonic liquid crystals (neutral grey, red 14, blue 27, cromolyn) are not toxic to bacteria as compared with surfactant-based lyotropic (CPCl and CsPFO) or thermotropic (5CB and E7) liquid crystals. Biocompatibility of most liquid crystals is currently unknown and is required for the development of systems interfacing liquid crystals and biological systems. Potential liquid crystal toxicity was evaluated by two methods. The first examined bacterial survival measured by bacterial growth over 24 hours, after exposure to various liquid crystals. The second toxicity method evaluated liquid crystal effects on bacterial membrane permeability using two fluorescent dyes. Three different types of bacteria were evaluated to assess bacterial structure differences with respect to liquid crystal toxicity. The results of this study indicate that lyotropic chromonic liquid crystals are not toxic to bacteria, whereas thermotropic and surfactant-based lyotropic liquid crystals are toxic to one or more forms of bacteria. We conclude that lyotropic chromonic liquid crystals may be the preferred material in designing liquid crystal-based systems that interact with biological systems, especially in the use of liquid crystal-based biosensors.     

Synthesis of racemic cis-5-hydroxy-3-phthalimidoglutarimide. A metabolite of thalidomide isolated from human plasma

[reaction: see text] A synthesis of the glutarimide-derived metabolite of thalidomide, 5'-hydroxythalidomide (2), is described. The synthesis employed the lactone derivative of N-benzyloxycarbonyl (CBZ)-protected 4-hydroxyglutamic acid 12, which is prepared by a de novo route from diethyl acetamidomalonate. The reaction of 12 with 4-methoxybenzylamine gave the corresponding isoglutamine, which then provided the key CBZ-protected N-PMB-glutarimide 14 after dehydration. Deprotection of both the CBZ and PMB groups followed by phthalimidation and deacetylation of the 3-amino-5-acetoxyglutarimide 16 afforded 2.     

DNA sequencing and genotyping in miniaturized electrophoresis systems

Advances in microchannel electrophoretic separation systems for DNA analyses have had important impacts on biological and biomedical sciences, as exemplified by the successes of the Human Genome Project (HGP). As we enter a new era in genomic science, further technological innovations promise to provide other far-reaching benefits, many of which will require continual increases in sequencing and genotyping efficiency and throughput, as well as major decreases in the cost per analysis. Since the high-resolution size- and/or conformation-based electrophoretic separation of DNA is the most critical step in many genetic analyses, continual advances in the development of materials and methods for microchannel electrophoretic separations will be needed to meet the massive demand for high-quality, low-cost genomic data. In particular, the development (and commercialization) of miniaturized genotyping platforms is needed to support and enable the future breakthroughs of biomedical science. In this review, we briefly discuss the major sequencing and genotyping techniques in which high-throughput and high-resolution electrophoretic separations of DNA play a significant role. We review recent advances in the development of technology for capillary electrophoresis (CE), including capillary array electrophoresis (CAE) systems. Most of these CE/CAE innovations are equally applicable to implementation on microfabricated electrophoresis chips. Major effort is devoted to discussing various key elements needed for the development of integrated and practical microfluidic sequencing and genotyping platforms, including chip substrate selection, microchannel design and fabrication, microchannel surface modification, sample preparation, analyte detection, DNA sieving matrices, and device integration. Finally, we identify some of the remaining challenges, and some of the possible routes to further advances in high-throughput DNA sequencing and genotyping technologies.     

Thermoresponsive N,N-dialkylacrylamide copolymer blends as DNA sieving matrices with a thermally tunable mesh size

In an earlier study we showed that a blend of thermoresponsive and nonthermoresponsive hydroxyalkylcelluloses could be used to create a thermally tunable polymer network for double-stranded (ds) DNA separation. Here, we show the generality of this approach using a family of polymers suited to a wider range of DNA separations: a blended mixture of N,N-dialkylacrylamide copolymers with different thermoresponsive behaviors. A mixture of 47% w/w N,N-diethylacrylamide (DEA)/53% w/w N,N-dimethylacrylamide (DMA) (DEA47; thermoresponsive, transition temperature = 55 degrees C in water) and 30% w/w DEA/70% w/w DMA (DEA30; nonthermoresponsive, transition temperature > 85 degrees C in water) copolymers in the ratio of 1:5 w/w DEA47:DEA30 was used to separate a dsDNA restriction digest (PhiX174-HaeIII). We investigated the effects of changing mesh size on dsDNA separation, as controlled by temperature. We observed good DNA separation performance with the copolymer blend at temperatures ranging from 25 degrees C to 48 degrees C. The separation selectivity was evaluated quantitatively for certain DNA fragment pairs as a function of temperature. The results were compared with those obtained with a control matrix consisting only of the nonthermoresponsive DEA30. Different DNA fragment pairs of various sizes show distinct temperature-dependent selectivities. Over the same temperature range, no significant temperature dependence of selectivity is observed for these DNA fragment pairs in the nonthermoresponsive control matrix. Overall, the results show similar trends in the temperature dependency of separation selectivity to what was previously observed in hydroxyalkylcellulose blends, for the same DNA fragment pairs. Finally, we showed that a ramped temperature scheme enables improved separation in the blended copolymer matrix for both small and large DNA fragments, simultaneously in a single capillary electrophoresis (CE) run.     

Synthesis and anti-cancer activity of dinuclear platinum(II) complexes containing bis(thioalkyl)dicarba-closo-dodecaborane(12) ligands

A series of novel, dinuclear (2,2':6',2'-terpyridine)platinum(ii) complexes containing bis(thioalkyl)-dicarba-closo-dodecaborane(12)(carborane) ligands were prepared and characterised, and their preliminary anti-cancer characteristics have been determined in vitro; the complexes are the first examples of bis-intercalator complexes containing a boron-rich carborane cage.     

The equilibrium shapes of crystals and of cavities in crystals

Surface free energies are assumed to be the sum of the excess free energies of bonding of molecules in or near the surface, and the stable form of a crystal or cavity is assumed to be the form that makes the sum of these excess free energies a minimum. When only plane surfaces are allowed, this model predicts the same shapes for crystals as an equation of Wulff (2. Kristallogr. 34, 449 (1901)), which is based on the macroscopic thermodynamic relation of Gibbs (“The Collected Works, Vol. 1.: Thermodynamics,” Longmans, Green, New York (1931)). The model predicts rounding of edges and corners of kinds which are not allowed by the Wulff relation and predicts that spherical forms of particles and cavities can be stable despite anisotropic surface free energies. The model provides a useful framework for analysis of whether unstable crystal or cavity shapes will evolve into stable or metastable forms. Some crystals and cavities that have been assumed to have equilibrium shapes instead have metastable shapes.