In vivo determination of the time and location of mucoadhesive drug delivery systems disintegration in the gastrointestinal tract

OBJECTIVE: The objective of this study was to use magnetic resonance imaging (MRI) to detect the time when and the location at which orally delivered mucoadhesive drugs are released. MATERIALS AND METHODS: Drug delivery systems comprising tablets or capsules containing a mucoadhesive polymer were designed to deliver the polymer to the intestine in dry powder form. Dry Gd-DTPA [diethylenetriaminepentaacetic acid gadolinium(III) dihydrogen salt hydrate] powder was added to the mucoadhesive polymer, resulting in a susceptibility artifact that allows tracking of the application forms before their disintegration and that gives a strong positive signal on disintegration. Experiments were performed with rats using T(1)-weighted spin-echo imaging on a standard 1.5-T MRI system. RESULTS: The susceptibility artifact produced by the dry Gd-DTPA powder in tablets or capsules was clearly visible within the stomach of the rats and could be followed during movement towards the intestine. Upon disintegration, a strong positive signal was unambiguously observed. The time between ingestion and observation of a positive signal was significantly different for different application forms. Quantification of the remaining mucoadhesive polymer in the intestine 3 h after observed release showed significant differences in mucoadhesive effectiveness. CONCLUSION: MRI allows detection of the exact time of release of the mucoadhesive polymer in vivo, which is a prerequisite for a reliable quantitative comparison between different application forms.     

Raman spectroscopy of laser‐induced oxidation of titanomagnetites

Titanomagnetites are important carriers of magnetic remanence in nature and can track redox conditions in magma. The titanium concentration in magnetite bears heavily on its magnetic properties, such as saturation moment and Curie temperature. On land and in the deep ocean, however, these minerals are prone to alteration which can mask the primary magnetic signals they once recorded. Thus, it is essential to characterize the cation composition and oxidation state of titanomagnetites that record the paleomagnetic field. Raman spectroscopy provides a unique tool for both purposes. Nonetheless, the heat generated by the excitation laser can itself induce oxidation. We show that the laser power threshold to produce oxidation decreases with increasing titanium content. With confocal Raman spectroscopy and magnetic force microscopy (MFM) on natural and synthetic titanomagnetites, a non‐destructive Raman imaging protocol was established. We applied this protocol to map out the composition and magnetization state within a single ex‐solved titanomagnetite grain in a deep‐sea basalt. Copyright © 2011 John Wiley & Sons, Ltd.     

Aryl Triflates in On-Surface Chemistry

The reactivity of aryl triflates in on-surface C−C coupling is reported. It is shown that the triflate group in aryl triflates enables regioselective homo coupling with preceding or concomitant hydrodetriflation on Cu(111). Three different symmetrical π-systems with two and three triflate functionalities were used as monomers leading to oligomeric conjugated π-systems. The cascade, comprising different intermediates at different reaction temperatures as observed for one of the molecules, proceeds via initial removal of the trifluoromethyl sulfonyl group to give an aryloxy radical which in turn is deoxygenated to the corresponding aryl radical. Thermodynamically driven regioselective 1,2-hydrogen atom transfer leads to a translocated aryl radical which in turn undergoes coupling. For a sterically more hindered bistriflate, where one ortho position was blocked, dehydrogenative coupling occurred at remote position with good regioselectivity. Starting materials, intermediates as well as products were analyzed by scanning tunneling microscopy. Structures and suggested mechanism were further supported by DFT calculations.     

An Isolable Gallium-Substituted Nitrilimine and its Reactivity with B−H,Si−H and B−B Bonds

Reaction of the Ga(I) compound NacNacGa ( 9 ) with the diazo compound N₂CHSiMe₃ affords the nitrilimine compound NacNacGa(N-NCSiMe₃)(CH₂SiMe₃) ( 10 ). Carrying out this reaction in the presence of pyridine does not lead to C−H activation on the transient alkylidene NacNacGa=CHSiMe₃ but generates a metallated diazo species NacNacGa(NHN=CHSiMe₃)(CN₂SiMe₃) ( 13 ) that further rearranges into the isonitrile compound NacNacGa(NHN=CHSiMe₃)(N(NC)SiMe₃) ( 15 ). Reactions of 10 with the silane H₃SiPh and the borane HBcat furnished products of 1,3 addition to the nitrilimine moiety NacNacGa{N(ER_n)NCSiMe₃}(CH₂SiMe₃), whereas reaction with the diborane B₂cat₂ gave the product of formal nitrene insertion into the B−B bond. DFT calculations suggest that the interaction of 9 with N₂CHSiMe₃ proceeds through intermediate formation of an alkylidene compound that undergoes CH activation with a second molecule of N₂CHSiMe₃. Insertion into the B−B bond likely proceeds through an initial 1,3-addition of the diborane, followed by boryl migration to the former nitrene center.     

Photochemical Reactions in the Synthesis of Protein–Drug Conjugates

The ability to modify biologically active molecules such as antibodies with drug molecules, fluorophores or radionuclides is crucial in drug discovery and target identification. Classic chemistry used for protein functionalisation relies almost exclusively on thermochemically mediated reactions. Our recent experiments have begun to explore the use of photochemistry to effect rapid and efficient protein functionalisation. This article introduces some of the principles and objectives of using photochemically activated reagents for protein ligation. The concept of simultaneous photoradiosynthesis of radiolabelled antibodies for use in molecular imaging is introduced as a working example. Notably, the goal of producing functionalised proteins in the absence of pre-association (non-covalent ligand-protein binding) introduces requirements that are distinct from the more regular use of photoactive groups in photoaffinity labelling. With this in mind, the chemistry of thirteen different classes of photoactivatable reagents that react through the formation of intermediate carbenes, electrophiles, dienes, or radicals, is assessed.     

Enzyme‐Compatible Dynamic Nanoreactors from Electrostatically Bridged Like‐Charged Surfactants and Polyelectrolytes

Reported is an unanticipated mechanism of attractive electrostatic interactions of fully neutralized polyacrylic acid (PAA) with like‐charged surfactants. Amphiphilic polymer‐surfactant complexes with high interfacial activity and a solubilization capacity exceeding that of conventional micelles are formed by bridging with Ca²⁺ ions. Incorporation of a protease into such dynamic nanoreactors results in a synergistically enhanced cleaning performance because of the improved solubilization of poorly water‐soluble immobilized proteins. Competitive interfacial and intermolecular interactions on different time‐ and length‐scales have been resolved using colorimetric analysis, dynamic tensiometry, light scattering, and molecular dynamic simulations. The discovered bridging association mechanism suggests reengineering of surfactant/polymer/enzyme formulations of modern detergents and opens new opportunities in advancing labile delivery systems.     

Circumventing Dedicated Electrolytes in Light‐Emitting Electrochemical Cells

Light‐emitting electrochemical cells (LECs) are devices that utilize efficient ion redistribution to produce high‐efficiency electroluminescence in a simple device architecture. Prototypical polymer LECs utilize three components in the active layer: a luminescent conducting polymer, a salt, and an electrolyte. Similarly, many small‐molecule LECs also utilize an electrolyte to disperse salts. In these systems, the electrolyte is incorporated to efficiently conduct ions and to maintain phase compatibility between all components. However, certain LEC approaches and materials systems enable device operation without a dedicated electrolyte. This review describes the general methods and materials used to circumvent the use of a dedicated electrolyte in LECs. The techniques of synthetically coupling electrolytes, incorporating ionic liquids, and introducing inorganic salts are presented in view of research efforts to date. The use of these techniques in emerging classes of light‐emitting electrochemical cells is also discussed. These approaches have yielded some of the most efficient, long‐lasting, and commercially applicable LECs to date.     

Multiple weak supramolecular interactions stabilize a surprisingly twisted As2L3 assembly

A combined crystallographic, DFT and NMR spectroscopic study of a flexible As(2)(3) assembly reveals temperature dependent conformational behavior in solution and a highly asymmetric structure stabilized by As-pi and edge-to-face aromatic interactions.