Metallo‐supramolecular block copolymer micelles: Improved preparation and characterization

Micelles prepared from amphiphilic block copolymers in which a poly(styrene) segment is connected to a poly(ethylene oxide) block via a bis‐(2,2′:6′,2″‐terpyridine‐ruthenium) complex have been intensely studied. In most cases, the micelle populations were found to be strongly heterogeneous in size because of massive micelle/micelle aggregation. In the study reported in this article we tried to improve the homogeneity of the micelle population. The variant preparation procedure developed, which is described here, was used to prepare two “protomer”‐type micelles: PS₂₀‐[Ru]‐PEO₇₀ and PS₂₀‐[Ru]‐PEO₃₇₅. The dropwise addition of water to a solution of the compounds in dimethylformamide was replaced by the controlled addition of water by a syringe pump. The resulting micelles were characterized by sedimentation velocity and sedimentation equilibrium analyses in an analytical ultracentrifuge and by transmission electron microscopy of negatively stained samples. Sedimentation analysis showed virtually unimodal size distributions, in contrast to the findings on micelles prepared previously. PS₂₀‐[Ru]‐PEO₇₀ micelles were found to have an average molar mass of 318,000 g/mol (corresponding to 53 protomers per micelle, which is distinctly less than after micelle preparation by the standard method) and an average hydrodynamic diameter (d_h) of 18 nm. For PS₂₀‐[Ru]‐PEO₃₇₅ micelles, the corresponding values were M = 603,000 g/mol (31 protomers per micelle) and d_h = 34 nm. The latter particles were found to be identical to the “equilibrium” micelles prepared in pure water. Both micelle types had a very narrow molar mass distribution but a much broader distribution of s values and thus of hydrodynamic diameters. This indicates a conformational heterogeneity that is stable on the time scale of sedimentation velocity analysis. The findings from electron microscopy were in disagreement with those from the sedimentation analysis both in average micelle diameter and in the width of the distributions, apparently because of imperfections in the staining procedure. The preparation procedure described also may be useful in micelle formation from other types of protomers. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4458–4465, 2004     

Metallo‐supramolecular micelles: Studies by analytical ultracentrifugation and electron microscopy

In aqueous solutions, amphiphilic block copolymers in which a polystyrene (PS) segment is connected to a poly(ethylene oxide) (PEO) block via a bis(2,2′:6′,2″‐ terpyridine ruthenium) complex can form micelles. Such micelles of the protomer type PS₂₀‐[Ru]‐PEO₇₀, according to the preparation procedure representing frozen micelles, were studied by sedimentation velocity and sedimentation equilibrium analysis in an analytical ultracentrifuge and by transmission electron microscopy, with different techniques applied for the sample preparation. The particles obtained were surprisingly multifarious in size. In ultracentrifugation experiments performed at relatively low salt concentrations, the distributions of the sedimentation coefficient s_20,w showed a pronounced peak at 9.6 S and a broad, only partly separated second peak around 14 S. The molar mass of the particles at the peak was around 430,000 g/mol, corresponding to an aggregation number of approximately 85. The average hydrodynamic diameter of the particles in the peak fraction was approximately 13 nm. In electron micrographs of negatively stained samples, spheres of diameters between 10 and 25 nm were the most abundant particles, but larger ones with a wide size range were also visible. The latter particles apparently were composed of smaller ones. The data from both sedimentation analysis and electron microscopy showed that (1) the studied compound formed primary micelles of diameters around 20 nm and (2) the primary micelles had a tendency toward aggregation. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3159–3168, 2003     

“Titration” polymerization of monovinylacetylene

A polymer consisting of a saturated carbon backbone with pendent acetylenic groups was prepared from monovinylacetylene. A titration was performed between the monomer and tertiary butyllithium, its lithiating agent. The charge transfer complex formed between the solvent THF and the tertiary butyllithium was used as an indicator of the unreacted butyllithium. Hence, a stoichiometric quantity of tertiary butyllithium was added dropwise to a solution of monovinylacetylene in THF to form lithiovinylacetylene. The addition of a slight excess of butyllithium led to the polymerization of the lithiated monomer. The obtained polymer was reprotonated and characterized. This polymerization was evaluated as a possible route to synthesize poly(vinylacetylene) with processable molecular weights, for its application as a potential carbon fiber precursor. © 1996 John Wiley & Sons, Inc.     

Robust Equilibria in Indefinite Linear-Quadratic Differential Games

Equilibria in dynamic games are formulated often under the assumption that the players have full knowledge of the dynamics to which they are subject. Here, we formulate equilibria in which players are looking for robustness and take model uncertainty explicitly into account in their decisions. Specifically, we consider feedback Nash equilibria in indefinite linear-quadratic differential games on an infinite time horizon. Model uncertainty is represented by a malevolent input which is subject to a cost penalty or to a direct bound. We derive conditions for the existence of robust equilibria in terms of solutions of sets of algebraic Riccati equations.     

On the determination of factor systems of PUA-representations

A method is developed to obtain a complete set of inequivalent factor systems of PUA-representations of a group with a subgroup of index two from the factor systems of this subgroup.     

Model-based electron microscopy: From images toward precise numbers for unknown structure parameters

Statistical parameter estimation theory is proposed as a method to quantify electron microscopy images. It aims at obtaining precise and accurate values for the unknown structure parameters including, for example, atomic column positions and types. In this theory, observations are purely considered as data planes, from which structure parameters have to be determined using a parametric model describing the images. The method enables us to measure positions of atomic columns with a precision of the order of a few picometers even though the resolution of the electron microscope is one or two orders of magnitude larger. Moreover, small differences in averaged atomic number, which cannot be distinguished visually, can be quantified using high-angle annular dark field scanning transmission electron microscopy images. Finally, it is shown how to optimize the experimental design so as to attain the highest precision. As an example, the optimization of the probe size for nanoparticle radius measurements is considered. It is also shown how to quantitatively balance signal-to-noise ratio and resolution by adjusting the probe size.     

Bioorthogonal Click of Colloidal Gold Nanoparticles to Antibodies In vivo

Combining nanotechnology and bioorthogonal chemistry for theranostic strategies offers the possibility to develop next generation nanomedicines. These materials are thought to increase therapeutic outcome and improve current cancer management. Due to their size, nanomedicines target tumors passively. Thus, they can be used for drug delivery purposes. Bioorthogonal chemistry allows for a pretargeting approach. Higher target-to-background drug accumulation ratios can be achieved. Pretargeting can also be used to induce internalization processes or trigger controlled drug release. Colloidal gold nanoparticles (AuNPs) have attracted widespread interest as drug delivery vectors within the last decades. Here, we demonstrate for the first time the possibility to successfully ligate AuNPs in vivo to pretargeted monoclonal antibodies. We believe that this possibility will facilitate the development of AuNPs for clinical use and ultimately, improve state-of-the-art patient care.     

Computer-aided library search of combined LC-Retention and diode-array-UV-spectral data

An automated library search system for computer-aided identification of organic compounds using combined UV-spectral and LC-retention data, as acquired by HPLC with linear diodearray-UV-detection, is presented.The keystone of the system is a set of similarity indices which have been developed on the basis of mathematical-statistical models of the reproducibility of the spectral and retention data. The similarity indices have the form of a significance probability, a quantity originating from the general theory of hypothesis testing. The output of the LC-UV retrieval system is a compound identity or a list of identities (if any) for which the relevant similarity index has a value above a preset threshold. The data base used in this investigation contained 186 sets of UV-spectral and LC-retention data of 74 organophosphorus pesticides measured from standard solutions under various experimental conditions. A test set consisted of 186 alternative data sets of the same compounds as contained in the data base, however measured under different experimental conditions. The performance of the LC-UV reproducibility-based retrieval (LUVRR) system was evaluated using recall/reliability plots. The results appeared to be quite promising: for 95% of the unknowns, the target reference (correct positive) was on top of the hit list with a similarity index value being significantly higher than values found for false positives.The software is written in Pascal. The present (experimental) version of the system runs on a Data General Eclipse MV/4000 minicomputer.     

Crystal and molecular structure of 3,6-dihydro-4,5-dimethyl-2-[2-(methoxymethyl)pyrrolydinesulfonyl]-2-phenyl-2H-thiapyran-1-oxide,C19H27NO4S2

The crystal structure of a dihydrothiapyranS-oxide was determined from single-crystal diffractometer data, C₁₉H₂₇NO₄S₂, MoK radiation: orthorhombic, space groupP2₁2₁2₁, usinga=8.9604(10),b=13.5928(15),c=16.5621(19) Å,z=4. The molecule has theE-geometry, and the absolute configuration isR at C₁ andS at S₁.