Self‐Immolative Activation of β‐Galactosidase‐Responsive Probes for In Vivo MR Imaging in Mouse Models

Our lab has developed a new series of self‐immolative MR agents for the rapid detection of enzyme activity in mouse models expressing β‐galactosidase (β‐gal). We investigated two molecular architectures to create agents that detect β‐gal activity by modulating the coordination of water to Gd^III. The first is an intermolecular approach, wherein we designed several structural isomers to maximize coordination of endogenous carbonate ions. The second involves an intramolecular mechanism for q modulation. We incorporated a pendant coordinating carboxylate ligand with a 2, 4, 6, or 8 carbon linker to saturate ligand coordination to the Gd^III ion. This renders the agent ineffective. We show that one agent in particular (6‐C pendant carboxylate) is an extremely effective MR reporter for the detection of enzyme activity in a mouse model expressing β‐gal.     

Photocontrolled Dopamine Polymerization on DNA Origami with Nanometer Resolution

Temporal and spatial control over polydopamine formation on the nanoscale can be achieved by installing an irradiation‐sensitive polymerization system on DNA origami. Precisely distributed G‐quadruplex structures on the DNA template serve as anchors for embedding the photosensitizer protoporphyrin IX, which—upon irradiation with visible light—induces the multistep oxidation of dopamine to polydopamine, producing polymeric structures on designated areas within the origami framework. The photochemical polymerization process allows exclusive control over polydopamine layer formation through the simple on/off switching of the light source. The obtained polymer–DNA hybrid material shows significantly enhanced stability, paving the way for biomedical and chemical applications that are typically not possible owing to the sensitivity of DNA.     

Ion mobility‐mass spectrometry for the separation and analysis of procyanidins

Procyanidins are polymeric flavan‐3‐ones occurring in many plants with antioxidant and other beneficial bioactivities. They are composed of catechin and epicatechin monomeric units connected by single carbon‐carbon B‐type linkages or A‐type linkages containing both carbon‐carbon and carbon‐oxygen‐carbon bonds. Their polymeric structure makes analysis of procyanidin mixtures always difficult. Evaluation of procyanidins according to degree of polymerization (DP) using high‐performance liquid chromatography (HPLC) is time‐consuming and at best has resolved polymeric families up to DP‐17. To expedite studies of procyanidins, the utility of positive ion electrospray ion mobility‐mass spectrometry (IM‐MS) was investigated for the rapid separation and characterization of procyanidins in mixtures. Applying IM‐MS to analyse structurally defined standards containing up to five subunits, procyanidins could be resolved in less than 6 ms not only by degree of polymerization but also by linkage type. A‐type procyanidins could be resolved from B‐type and both could be at least partially resolved from mixed‐type procyanidins of the same DP. IM‐MS separated higher order procyanidins with DP of at least 24 from extracts of cranberry. As DP increased, the abundances of multiply‐charged procyanidins also increased. During IM‐MS of ions of similar m/z, the ion drift times decreased inversely with increasing charge state. Therefore, IM‐MS was shown to separate mixtures of procyanidins containing at least 24 interconnected subunits in less than 16 ms, not only according to DP, but also according to linkage type between subunits and charge state.     

RASS‐Enabled S/P−C and S−N Bond Formation for DEL Synthesis

DNA encoded libraries (DEL) have shown promise as a valuable technology for democratizing the hit discovery process. Although DEL provides relatively inexpensive access to libraries of unprecedented size, their production has been hampered by the idiosyncratic needs of the encoding DNA tag relegating DEL compatible chemistry to dilute aqueous environments. Recently reversible adsorption to solid support (RASS) has been demonstrated as a promising method to expand DEL reactivity using standard organic synthesis protocols. Here we demonstrate a suite of on‐DNA chemistries to incorporate medicinally relevant and C?S, C?P and N?S linkages into DELs, which are underrepresented in the canonical methods.     

Porous chromatographic materials as substrates for preparing synthetic nuclear explosion debris particles

Several porous chromatographic materials were investigated as synthetic substrates for preparing surrogate nuclear explosion debris particles. Eighteen metals, including some of forensic interest, were loaded onto materials by immersing them in metal solutions (556 mg/L of each metal) to fill the pores, applying gentle heat (110 °C) to drive off water, and then treating them at high temperatures (up to 800 °C) in air to form less soluble metal species. High-boiling-point metals were uniformly loaded on spherical controlled-pore glass to emulate early fallout, whereas low-boiling-point metals were loaded on core–shell silica to represent coated particles formed later in the nuclear fallout-formation process. Analytical studies characterized material balance and the formation of recalcitrant species. Metal loading was 1.5–3 times higher than expected from the pore volume alone, a result attributed to surface coating. Most metals were passively loaded; that is, solutions filled the pores without active metal discrimination. However, niobium and tin concentrations were lower in solutions after pore filling, and were found in elevated concentrations in the final products, indicating selective loading. High-temperature treatments caused reduced solubility of several metals, and the loss of some volatile species (rhenium and tellurium). Sample preparation reproducibility was high (the inter- and intra-batch relative standard deviations were 7.8 and 0.84 %, respectively) indicating suitability for use as a working standard for analytical methods development. We anticipate future standardized radionuclide-loaded materials will find use in radioanalytical methods development and/or serve as a starting material for the synthesis of more complex nuclear explosion debris forms (e.g., Trinitite).     

With a focus on ‘Grundvorstellungen’ Part 2: ‘Grundvorstellungen’ as a theoretical and empirical criterion

The first part of this serial pointed out the integration of the German concept Grundvorstellungen into current concepts, especially its central position as a mediator between reality and mathematics. The next stage is therefore to explain the use of the proportion and percentage calculations within this concept and how it can be used as a criterion to detect the demands of mathematical problems. Firstly, we will take a look at a classification of mathematical items. This classification shows the complexity of the mathematical item in respect of Grundvorstellungen. The consequences of this consideration have hierarchical levels of demand on these items. Furthermore to show how to describe and interpret these results on the basis of these levels, we refer to selected results of the PISA 2000 comparative study.     

Accelerated degradation of syntactic polysulfide in the presence of Viton A

Headspace SPME GC/MS was used to monitor the volatile degradation products generated by syntactic polysulfide alone and in the presence of Viton A at elevated temperature. This approach allowed the identification of products from two distinct degradation mechanisms. In one degradation mechanism, which is associated with lead oxide-cured polysulfide, a single cyclic disulfide compound dominated the outgassing signature. The second mechanism was evident only when the polysulfide was in the presence of Viton A at 70 °C. In as little as 24 h, the Viton-exposed polysulfide generated multiple outgassing species indicative of an acid-catalyzed degradation process. Within one week of exposure to Viton A, the syntactic polysulfide softened significantly and lost over 6% of its initial mass, and after four weeks, the polysulfide was no longer a solid material.     

Morse Novikov theory and cohomology with forward supports

We present a new approach to Morse and Novikov theories, based on the deRham Federer theory of currents, using the finite volume flow technique of Harvey and Lawson [HL]. In the Morse case, we construct a noncompact analogue of the Morse complex, relating a Morse function to the cohomology with compact forward supports of the manifold. This complex is then used in Novikov theory, to obtain a geometric realization of the Novikov Complex as a complex of currents and a new characterization of Novikov Homology as cohomology with compact forward supports. Two natural ``backward-forward' dualities are also established: a Lambda duality over the Novikov Ring and a Topological Vector Space duality over the reals.     

How Many Are Too Many? Managing OnLine Growing Pains

The Physical Chemistry OnLine Consortium (PCOL) is dedicated to enhancing undergraduate physical chemistry by encouraging faculty and challenging students to conduct short-term (~4 weeks) Webbased, mathematically sophisticated activities. PCOL projects involve students and faculty at geographically dispersed institutions. In the fall of 2000, PCOL sponsored three very different projects involving faculty and 175 students from 16 different institutions. This paper discusses strategies for dealing with the growing pains that our successful Web-based educational endeavor has encountered.Presented at the ACS Division of Chemical Education sponsored symposium on web-assisted learning in chemistry at its 221st national meeting in San Diego, CA April 1–5, 2001.