Literatur

Ohne Zusammenfassung     

Dipyrrinato-Iridium(III) Complexes for Application in Photodynamic Therapy and Antimicrobial Photodynamic Inactivation

The generation of bio-targetable photosensitizers is of utmost importance to the emerging field of photodynamic therapy and antimicrobial (photo-)therapy. A synthetic strategy is presented in which chelating dipyrrin moieties are used to enhance the known photoactivity of iridium(III) metal complexes. Formed complexes can thus be functionalized in a facile manner with a range of targeting groups at their chemically active reaction sites. Dipyrrins with N- and O-substituents afforded (dipy)iridium(III) complexes via complexation with the respective Cp*-iridium(III) and ppy-iridium(III) precursors (dipy=dipyrrinato, Cp*=pentamethyl-η⁵-cyclopentadienyl, ppy=2-phenylpyridyl). Similarly, electron-deficient [Ir^III(dipy)(ppy)₂] complexes could be used for post-functionalization, forming alkenyl, alkynyl and glyco-appended iridium(III) complexes. The phototoxic activity of these complexes has been assessed in cellular and bacterial assays with and without light; the [Ir^III(Cl)(Cp*)(dipy)] complexes and the glyco-substituted iridium(III) complexes showing particular promise as photomedicine candidates. Representative crystal structures of the complexes are also presented.     

Artificial Ribozyme Switches Containing Natural Riboswitch Aptamer Domains

RNA Lego : The use of natural riboswitch aptamers in synthetic RNA switches (see picture) should broaden the scope of artificial RNA regulators dramatically. It is shown that thiamine pyrophosphate (TPP) aptamers can be used in engineered devices as very sensitive switches of gene expression in unmodified organisms. The approach demonstrates that intrinsic metabolites can be utilized as external effectors of cellular functions.

     

Ag-catalyzed diastereo- and enantioselective vinylogous Mannich reactions of alpha-ketoimine esters. Development of a method and investigation of its mechanism

An efficient diastereo- and enantioselective Ag-catalyzed method for additions of a commercially available siloxyfuran to alpha-ketoimine esters is disclosed. Catalytic transformations require an inexpensive metal salt (AgOAc) and an air stable chiral ligand that is prepared in three steps from commercially available materials in 42% overall yield. Aryl- as well as heterocyclic substituted ketoimines can be used effectively in the Ag-catalyzed process. Additionally, two examples regarding reactions of alkyl-substituted ketoimines are presented. An electronically modified N-aryl group is introduced that is responsible for high reaction efficiency (>98% conversion, 72-95% yields after purification) as well as diastereo- (up to >98:2 dr) and enantioselectivity (up to 97:3 er or 94% ee). The new N-aryl unit is crucial for conversion of the asymmetric vinylogous Mannich (AVM) products to the unprotected amines in high yields. Spectroscopic and X-ray data are among the physical evidence provided that shed light on the identity of the Ag-based chiral catalysts and some of the mechanistic subtleties of this class of enantioselective C-C bond forming processes.     

Characterization of hemoglobin Würzburg (alpha2beta2 4(A1)Thr-->Asn), a new electrophoretically silent variant, by mass spectrometry and molecular modeling studies

The first hemoglobin (Hb) variant carrying a mutation at beta4 was identified as beta4(A1)Thr-->Asn or Hb Würzburg and constituted 38% of the total hemoglobin. It showed a slightly elevated oxygen affinity and a slightly decreased cooperativity index (n50 = 2.3 versus n50 = 2.8). The analysis of the electrostatic potential showed an increased negative charge at the site of the mutation with a displacement of beta6(A3)Glu by 1.3A. The replacement of threonine by asparagine seems to stabilize the R conformation. This may explain partially both the high affinity and the reduction in cooperativity.     

EXAFS study of U(VI) uptake by calcium silicate hydrates

Among the different cement minerals, calcium silicate hydrates (C-S-H) are the prime candidates for heavy metal binding because of their abundance and appropriate structure. Immobilization processes of heavy metals by cementitious materials, and in particular C-S-H phases, thus play an important role in multibarrier concepts developed worldwide for the safe disposal of hazardous and radioactive wastes. In this study, the uptake of U(VI) by C-S-H has been investigated using X-ray absorption fine structure (XAFS) spectroscopy. C-S-H phases were synthesized using two different procedures: One is based on the mixing of CaO and SiO2 solids ("direct reaction" method); for the other one starting solutions of Ca and Si are used ("solution reaction" method). XAFS investigations were carried out on samples doped with U(VI). U(VI) was either sorbed onto previously precipitated C-S-H phases (sorption samples) or added during C-S-H synthesis (coprecipitation samples). The coordination environment of U(VI) in the sorption samples was found to be independent of the procedure used for C-S-H synthesis. A split equatorial oxygen shell (Oeq1: R=2.23-2.27 A; Oeq2: R=2.36-2.45 A), neighboring silicon atoms at short (R=3.07-3.11 A) and long (R=3.71-3.77 A) distances, and neighboring Ca atoms (R=3.77-3.81 and 4.15-4.29 A) were observed for all the samples. The structural parameters resemble those reported for uranophane. The coordination environment of U(VI) in the coprecipitation samples depends on the method used for C-S-H synthesis, and further, the spectra differ from those determined for the sorption samples. UU backscattering contributions were observed in the samples prepared using the direct reaction method, whereas no split equatorial shell appeared in the samples prepared using the solution reaction method.     

Macro- and micro-scale studies on U(VI) immobilization in hardened cement paste

Wet chemistry and synchrotron-based (micro-)spectroscopic investigations have been carried out to determine the uptake and speciation of U(VI) in hardened cement paste (HCP). The wet chemistry experiments included kinetic studies and the determination of the sorption isotherm. The latter measurements allowed conditions for linear sorption to be distinguished from those where precipitation occurred. Micro-X-ray fluorescence and X-ray absorption spectroscopy (μ-XRF/XAS) were used to determine the elemental distribution and the coordination environment of U(VI) in an intact HCP sample at the atomic level. The sample was prepared by in-diffusion of U(VI) into HCP over 9 months. Micro-XRF maps revealed a heterogeneous distribution of U(VI) in a ten micron thick layer on the surface of the HCP disk. Micro-XAS measurements on a U(VI) hot spot showed that the coordination environment of U(VI) is similar to that in U(VI) doped HCP and in C-S-H sorption samples. To the best of our knowledge this is the first synchrotron-based micro-spectroscopic study on the speciation of diffusing uranyl ions with micro-scale spatial resolution.