Thermodynamic and kinetic data for adduct formation, cis-trans isomerization and redox reactions of ML4 complexes: a case study with rhodium- and iridium-tropp complexes in d8, d9 and d10 valence electron configurations (tropp=dibenzotropylidene phosphanes)

The formation of adducts of the square-planar 16-electron complexes trans-[M(tropp(ph))(2)](+) and cis-[M(tropp(ph))(2)](+) (M=Rh, Ir; tropp(Ph)=5-diphenylphosphanyldibenzo[a,d]cycloheptene) with acetonitrile (acn) and Cl(-), and the redox chemistry of these complexes was investigated by various physical methods (NMR and UV-visible spectroscopy, square-wave voltammetry), in order to obtain some fundamental thermodynamic and kinetic data for these systems. A trans/cis isomerization cannot be detected for [M(tropp(ph))(2)](+) in non-coordinating solvents. However, both isomers are connected through equilibria of the type trans-[M(tropp(ph))(2)](+)+L<==>[ML(tropp(ph))(2)](n)<==>cis-[M(tropp(ph))(2)](+)+L, involving five-coordinate intermediates [ML(tropp(ph))(2)](n) (L=acn, n=+1; L=Cl(-), n=0). Values for K(d) (K(f)), that is, the dissociation (formation) equilibrium constant, and k(d) (k(f)), that is, the dissociation (formation) rate constant, were obtained. The formation reactions are fast, especially with the trans isomers (k(f)>1x10(5) m(-1) s(-1)). The reaction with the sterically more hindered cis isomers is at least one order of magnitude slower. The stability of the five-coordinate complexes [ML(tropp(ph))(2)](n) increases with Ir>Rh and Cl(-)>acn. The dissociation reaction has a pronounced influence on the square-wave (SW) voltammograms of trans/cis-[Ir(tropp(ph))(2)](+). With the help of the thermodynamic and kinetic data independently determined by other physical means, these reactions could be simulated and allowed the setting up of a reaction sequence. Examination of the data obtained showed that the trans/cis isomerization is a process with a low activation barrier for the four-coordinate 17-electron complexes [M(tropp(ph))(2)](0) and especially that a disproportionation reaction 2 trans/cis-[M(tropp(ph))(2)](0)-->[M(tropp(ph))(2)](+)+[M(tropp(ph))(2)](-) may be sufficiently fast to mask the true reactivity of the paramagnetic species, which are probably less reactive than their diamagnetic equilibrium partners.     

Zur reaktionsweise von triafulvenen mit azomethinyliden

The reaction of the azomethine ylides 2a–c with cyclopropenones 3 and of 2a with methylene cyclopropenes 7 leads via (3+3)-cycloaddition to pyridones-4 5 and 1,4 - dihydro - N - methyl - 4 - methylene - pyridines 8, respectively. The merocyanine systems 8 exhibit marked solvatochromic and thermochromic properties.     

Enediynes in 11-membered rings. Synthesis, structure, and reactivity of highly strained but unusually stable macrocycles.

The synthesis of two new aromatic cyclic enediynes 1a and 1b using a double Wittig condensation, followed by bromination and di-dehydrobromination, is reported. The structures were determined using X-ray crystallography. The observed C(1)-C(6) distances of the enediyne moiety in the oxygen- and sulfur-containing eleven-membered rings are quite short with 3.44 and 3.50 A, respectively, indicating the highly strained nature of these compounds. Isodesmic calculations at the B3LYP/6-31G level of theory indicate a strain energy of 8.2 and 5.8 kcal/mol, respectively. Despite the highly strained ring system, the compounds were found to be stable under thermal, photochemical, and electron-transfer conditions. Using BLYP/6-311+G/BLYP/6-31G calculations, the origin of this unusual stability was traced to the high energy of the 1,4 benzyne diradicals formed via Bergman cyclization. For the radical cation, both the C(1)-C(6) and the C(1)-C(5) cyclization mode previously reported for acyclic analogues of 1 were found to be energetically prohibitive.     

Analytical procedures for quantification of peptides in pharmaceutical research by liquid chromatography–mass spectrometry

Peptide quantification by liquid chromatography–mass spectrometry (LC–MS) combines the high resolving power of reversed-phase (RP) chromatography with the excellent selectivity and sensitivity of mass spectrometric detection. On the basis of comprehensive practical experience in the analysis of small molecules, pharmaceutical research is developing technologies for analysis of a growing number of peptidic drug candidates. This article is a detailed review of procedures based on LC–MS techniques for quantitative determination of peptides. With the focus on pharmaceutical applications several technologies for sample preparation, various aspects of peptide chromatography, important characteristics of ESI–MS, selectivity of MS-detection modes, the large variability of internal standards, and modern instrumentation are discussed. The demand for reliable, robust, sensitive, and accurate methods is discussed using numerous examples from the literature, complemented by experiments and results from our laboratory.     

Structure of New 2-Oxo-2,8-dihydro-[l,2,4]oxadiazolo-[2,3-a]pyrimidinecarbamates

The structure of new 2-oxo-2,8-dihydro-[l,2,4]oxadiazolo-[2,3-a]pyrimidine-carbamates 1 was established by correlating the IR. and NMR. data with these of analogous compounds. A X-ray crystallographic analysis of 1c gave an unequivocal proof of structural assignment.     

Negatively charged hyperbranched polyether-based polyelectrolytes

The preparation of carboxylated hyperbranched polyglycerols of narrow polydispersity was achieved by modification (78–90%) of the hydroxyl end groups via Michael addition of acrylonitrile, followed by hydrolysis. High conversion could only be achieved for low molecular weight starting materials (520 and 1,030 g mol⁻¹). The solution properties of the resulting materials were investigated by dynamic light scattering (DLS), showing the formation of large aggregates with size depending on the pH value. After deposition on a negatively charged mica surface, the structures observed by atomic force microscope (AFM) show the coexistence of aggregates and single macromolecules. Most interesting, in the case of the lower molecular weight sample (PG 520 g mol⁻¹), extended and ordered terrace structures were formed, which are unprecedented for hyperbranched polymers and are of interest for surface modification in general.     

Vesicle adsorption and lipid bilayer formation on glass studied by atomic force microscopy

The adsorption of phosphatidylcholine (PC) vesicles (30, 50, and 100 nm nominal diameters) and of dye-labeled PC vesicles (labeled with 6% Texas Red fluorophore (TR) and encapsulated carboxy fluorescein (CF)) to glass surfaces was studied by contact mode atomic force microscopy in aqueous buffer. These studies were performed in part to unravel details of the previously observed isolated rupture of dye-labeled PC vesicles on glass (Johnson, J. M.; Ha, T.; Chu, S.; Boxer, S. G. Biophys. J. 2002, 83, 3371-3379), specifically to differentiate partial rupture, that is, pore formation and leakage of entrapped dye, from full rupture to form bilayer disks. In addition, the adhesion potential of PC vesicles on glass was calculated based upon the adhesion-driven flattening of adsorbed vesicles and a newly developed theoretical model. The vesicles were found to flatten considerably upon adsorption to glass (width-to-height ratio of approximately 5), which leads to an estimate for the adhesion potential and for the critical rupture radius of 1.5 x 10(-4) J/m2 and 250 nm, respectively. Independent of vesicle size and loading with dye molecules, the adsorption of intact vesicles was observed at all concentrations below a threshold concentration, above which the formation of smooth lipid bilayers occurred. In conjunction with previous work (Johnson, J. M.; Ha, T.; Chu, S.; Boxer, S. G. Biophys. J. 2002, 83, 3371-3379), these data show that 6% TR 20 mM CF vesicles adsorb to the surface intact but undergo partial rupture in which they exchange content with the external buffer.     

Adaptive approach for nonlinear sensitivity analysis of reaction kinetics

We present a unified approach for linear and nonlinear sensitivity analysis for models of reaction kinetics that are stated in terms of systems of ordinary differential equations (ODEs). The approach is based on the reformulation of the ODE problem as a density transport problem described by a Fokker-Planck equation. The resulting multidimensional partial differential equation is herein solved by extending the TRAIL algorithm originally introduced by Horenko and Weiser in the context of molecular dynamics (J. Comp. Chem. 2003, 24, 1921) and discussed it in comparison with Monte Carlo techniques. The extended TRAIL approach is fully adaptive and easily allows to study the influence of nonlinear dynamical effects. We illustrate the scheme in application to an enzyme-substrate model problem for sensitivity analysis w.r.t. to initial concentrations and parameter values.     

Measurement of biological parameters during fermentation processes

Efficient fermentation control requires the measurement of biological parameters. Three techniques were tested for monitoring. In the first, the NADH-fluorescence of micro-organisms was measured in batch and in continuous cultures under aerobic and anaerobic conditions, providing information on the metabolic status of the cells. The effects of cell concentration and of different substrates (glucose, ethanol and oxygen) were studied. The second technique is the calorimetric determination of various substrates, such as penicillin or enzymes, by an enzyme/thermistor device. With immobilized penicillin acylase (E.C. 3.5.1.11) or penicillinase (E.C. 3.5.2.6), penicillin was determined selectively in a fermentation broth. The thermistor was also used to measure penicillin acylase activity. The third technique is laser flow cytometry. A commercial double-beam flow cytometry system was used to determine cell size, light scattering and the protein, DNA and RNA contents of single cells. Flow cytometry allows rapid and sensitive control of fermentation processes with genetically modified E. coli 5K (pHM12) cells. The results of monitoring the cell size, light scattering, and protein and DNA contents of different micro-organisms during fermentation are outlined.     

The effect of electronegative atoms on the structures of hydrocarbons. ab initio calculations on molecules containing fluorine or (carbonyl) oxygen

A series of ab initio calculations have been carried out, using the 4-21G basis set. Ethane and propane were first studied to obtain reference points. The effect of adding an electronegative atom (fluorine, or carbonyl oxygen) onto the framework was then studied as a function of the torsional angle about the single bond. Some pronounced trends in structural changes were observed, and these can in part be correlated with hyperconjugative effects. For example, fluoroethane has bond lengths which are shorter than those in ethane itself, by 0.024 Åin the C C bond, and 0.003 Åin the α C H bonds. These changes are essentially torsionally independent. On the other hand, in propionaldehyde, the C C bond length of the methyl group and the C H bond lengths of the hydrogens attached to the alpha carbon vary as a function of the torsion angle. If the methyl C C bond in the carbonyl plane is taken as a reference, the bond stretches .016 Åwhen the torsion angle is increased to 90°, an α C H bond similarly stretches up to .007 Å. Many of these geometric changes are large, well beyond the experimental errors in modern measurements.