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Steffen Zahn

Publications and source records attributed to Steffen Zahn.

8 recordsLinked to original sources
PubMed2006

Redox-induced ligand reorganization and helicity inversion in copper complexes of N,N-dialkylmethionine derivatives.

N,N'-Dipicolyl, bis(stilbylvinylpyridylmethyl), and diquinaldyl methionine derivatives form stable Cu(II) complexes with metal ligation by three nitrogen atoms and the carboxylate. One-electron reduction results in the exchange of carboxylate for sulfide in the complexes. This ligand reorganization is accompanied by inversion of the helical orientation of the two arms containing nitrogen heterocycles, resulting in nearly mirror image circular dichroism spectra. This paper provides details for the synthesis of these complexes and the evidence for the remarkable stereochemical interconversion that accompanies the reduction reaction. Detailed analysis of the electronic spectra of the ligands and metal complexes is provided along with X-ray crystallographic structures of Cu(II) and Zn(II) complexes of the N,N'-dipicolylmethionine complexes.

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PubMed2004

Reduction of ICAM-1 and LFA-1-positive leukocytes in the perivascular space of arteries under mycophenolate mofetil therapy reduces rat heart transplant vasculopathy.

BACKGROUND: The interaction of lymphocyte function-associated antigen-1 (LFA-1)-positive host leukocytes with intercellular adhesion molecule-1 (ICAM-1) on graft endothelium may play a key role in allograft recognition, triggering the development of transplant vasculopathy (TVP). We investigated the correlation between TVP and ICAM-1 expression and accumulation of LFA-1-positive leukocytes in the perivascular space (PVS) of arteries under different immunosuppressive drugs. METHODS: After cardiac transplantation (Lewis to Fisher) animals were randomized 4 groups: cyclosporine (CsA), 3 mg/kg/day (n=74); mycophenolate mofetil (MMF), 40 mg/kg/day (n=96); FK 506, 0.3 mg/kg/day (n=96); and control, no therapy (n=74). Three or 4 animals from each group were harvested at intervals of 1 to 4 days within the study period of 60 days. Using immunohistochemistry, LFA-1-positive leukocytes were analyzed in intra- and epicardial arteries. ICAM-1 expression was scored histologically. TVP was assessed by digitizing morphometry and expressed as mean vascular occlusion. RESULTS: Accumulation of LFA-1-positive leukocytes in the PVS of arteries and the myocardium correlated with expression of ICAM-1 on graft endothelium. The severity of TVP in arteries correlated with the accumulation of LFA-1-positive leukocytes in PVS. All immunosuppressive drugs significantly reduced ICAM-1 expression, LFA-1 accumulation and extent of TVP, compared with controls. In MMF-treated animals, we also found a significant reduction of ICAM-1 expression, LFA-1 accumulation and extent of TVP compared with the groups treated with CsA and FK 506 (p <0.005). CONCLUSION: These data support an essential role of LFA-1/ICAM-1 interaction in the genesis of TVP that may be abrogated, especially by the use of MMF.

Animals↗
PubMed2003

Mycophenolate mofetil significantly reduces leukocyte graft infiltration after heterotopic cardiac transplantation in a rat model: comparative study with cyclosporine and FK 506.

BACKGROUND: The purpose of the study was to evaluate the effects of cyclosporine (CsA), FK 506 and mycophenolate mofetil (MMF) on graft-infiltrating leukocytes (CD4, CD8, CD11a, CD18) after cardiac transplantation in rats. METHODS: Three hundred forty animals were transplanted and randomly divided into 4 groups: CsA, 3 mg/kg/d (n = 74); MMF, 40 mg/kg/d (n = 96); FK 506, 0.3 mg/kg/d (n = 96); and a control group receiving no immunosuppressive therapy (n = 74). Three or 4 animals from each group were killed at intervals of 1 to 4 days up to Day 60. Immunohistochemistry was performed using monoclonal antibodies (MAb) against CD4, CD8, CD11a and CD18. Positively stained cells were analyzed in the perivascular space (PVS) of intra- and epicardial arteries. Statistical analysis was performed using area-under-the-curve assessment with an extended t-test. RESULTS: CsA and FK 506 reduced the presence graft-infiltrating leukocytes (CD4, CD8, CD11a, CD18) in the PVS of intra- and epicardial arteries when compared with control animals. MMF therapy resulted in a further significant reduction in infiltrating leukocytes when compared with the 2 calcineurin inhibitors. MMF had a faster onset of action than the calcineurin inhibitors. CsA and FK 506 required 12 to 20 additional days to achieve the reducing effect of graft infiltration seen in MMF-treated animals. CONCLUSION: MMF possesses potent infiltration-blocking properties and its application leads to a greater reduction of cellular infiltration in the course of transplant rejection when compared with calcineurin inhibitors.

Animals↗
PubMed2002

Crystal-driven distortion of ligands in copper coordination complexes: conformational pseudo-enantiomers.

The ligand in [Cu(6)CH3CN]-(ClO4)2 adopts two conformations that may be described as "pseudo-enantiomers" in that they possess approximately mirror-image molecular helicity, although they differ in the orientation of a single methyl substituent. The two conformations differ in energy as judged by analogy to other compounds studied previously, computation of the relative free energies of formation of the isomers, and measurement of solution circular dichroism spectra. The solid-state structures of both single enantiomer and racemic forms of the complex were determined by X-ray crystallography. In the chiral complex, a quasi-racemate was observed with both pseudo-enantiomeric conformers present in the asymmetric unit. Packing forces induce a higher energy conformation in order to achieve higher apparent symmetry in the solid state. In contrast, the racemic complex only displayed a single conformation corresponding to the lower energy one of the two observed in the single enantiomer structure.

Journal Article↗
PubMed2002

Cu(I/II) redox control of molecular conformation and shape in chiral tripodal ligands: binary exciton-coupled circular dichroic states.

This manuscript describes the design, synthesis, and characterization of a coordination complex that demonstrates reversible interconversion between two redox states that show very different chiroptical properties. Reported here are three chiral N(4)-tetradentate ligands, prepared in enantiopure form by asymmetric synthesis, and their circular dichroic and other properties, as well as those of numerous Cu(I) and Cu(II) complexes. While the chiroptical spectra of the free ligands are unremarkable, the CD spectra of the complexes are very intense, and spectral features indicate that they derive from exciton coupling. Comparison of complexes with one, two, or three chromophores provides strong supportive evidence for this assignment, and semiquantitative correlation with intensity as rationalized by additivity. A Cu(I)(L)/Cu(II)(L) redox couple was identified that showed dramatically different circular dichroic properties that was further shown to be easily oxidized and reduced chemically between two states with remarkable retention of signal. A structural hypothesis for the interconversion is given and supported by a variety of spectroscopic evidence.

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PubMed2002

Synthesis and circular dichroism studies of N,N-bis(2-quinolylmethyl)amino acid Cu(II) complexes: determination of absolute configuration and enantiomeric excess by the exciton coupling method.

We report a method to determine the absolute configuration of alpha-amino acids by exciton coupled circular dichroism (ECCD). Naturally occurring amino acids were successfully derivatized with 2-bromomethylquinoline. Complexation of these conformationally flexible ligands with Cu(II) salts yielded defined propeller-like structures. The direction of the twist (i.e., the relative orientation of the chromophores to each other) is governed by the asymmetric amino acid carbon center. The transition moments of the chromophores couple and yield a bisignate circular dichroism spectrum, the sign of which corresponds to the absolute configuration of the chiral center of the amino acid. Enantiomeric excess (e.e.) of amino acid derivatives is linearly related to the differential extinction coefficient Delta(epsilon) and can be assessed easily utilizing a standard curve. This efficient, sensitive technique requires low analyte concentrations, offers several advantages over established methods, and could be applied in medicinal, pharmaceutical, or chemical retail and manufacturing industry.

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