Spiers memorial lecture dynamics of surface reactions

The dynamics of electrode processes is discussed in the framework of the general hierarchy of dynamic processes underlying interface reactions. On the quantum level, the energy transfer between the various degrees of freedom of a reacting system may now be studied by ultrafast (femtosecond) laser techniques. On the atomic level the mechanism of surface reactions may be investigated by STM and spectroscopic methods. Frequently a surface reaction will affect the structure of the substrate on the mesoscopic scale. The kinetics of such phase transformations proceeds either by a nucleation and growth mechanism or by spinodal decomposition. The latter can be studied in electrodissolution by combining STM with very short potential pulses. In this context, a novel technique for electrochemical micromachining is presented. Finally, some aspects of nonlinear kinetics on the macroscopic level associated with spatio-temporal pattern formation are briefly discussed.     

Adrenaline recognition in water

Host molecule 1 displays a high affinity in water towards catecholamines and especially related structures such as beta-blockers with extended aromatic pi-faces (up to 7x10(3) M(-1) for each single complexation step or 5x10(7) M(-2) for both steps). The amphiphilic structural design leads to an extensive self-association of host molecules through their aromatic flanks. Above a cmc (critical micelle concentration) of 3x10(-4) M, host 1 forms micelles that produce a favorable microenvironment for hydrophobic interactions with the included guest molecules. Electrostatic attraction of the ammonium alcohol by the phosphonate anions is thus combined with hydrophobic contributions between the aromatic moieties. Ionic hydrogen bonds with polar OH or NH groups of the guest enforce the non-covalent interactions, and finally lead to increased specificity. Both its affinity and its selectivity towards adrenergic receptor substrates are greatly enhanced if the receptor molecule 1 is transferred from water into a lipid monolayer. Catecholamines and beta-blockers lead to drastically different effects at concentrations approaching the micromolar regime. Especially beta-blockers with minute structural changes can be easily distinguished from each other. In both cases, extensive hydrophobic interactions with a self-associated and/or self-organized microenvironment are largely responsible for the observed high efficiency and specificity.     

Saludimerines A and B, novel-type dimeric alkaloids with stereogenic centers and configurationally semistable biaryl axes

The first biarylic bis-morphinanedienone alkaloids, saludimerines A (3a) and B (3b), isolated from a tree of Croton flavens (Euphorbiaceae) are described. These naturally occurring dimers of the known alkaloid salutaridine are joined together via a rotationally hindered biaryl axis, giving rise to atropo-diastereomers that are configurationally stable at room temperature but slowly interconvert in methanolic solution within several days. Their structures were established by spectroscopic methods and by partial synthesis, which was achieved by a highly atropo-diastereoselective biomimetic oxidative coupling of the monomeric precursor, salutaridine. Their axial configurations were elucidated by circular dichroism (CD) investigations, which succeeded despite the fact that the two atropo-diastereomers exhibit near-identical CD spectra. This remarkable phenomenon was rationalized by quantum chemical CD calculations. The configurational assignment of saludimerines A (3a) as P-axial and B (3b) as M was corroborated by atropisomer-specific NOE interactions between protons of the one molecular half with nuclei in the other.     

Approaches to the description and prediction of the binding affinity of small-molecule ligands to macromolecular receptors

The influence of a xenobiotic compound on an organism is usually summarized by the expression biological activity. If a controlled, therapeutically relevant, and regulatory action is observed the compound has potential as a drug, otherwise its toxicity on the biological system is of interest. However, what do we understand by the biological activity? In principle, the overall effect on an organism has to be considered. However, because of the complexity of the interrelated processes involved, as a simplification primarily the "main action" on the organism is taken into consideration. On the molecular level, biological activity corresponds to the binding of a (low-molecular weight) compound to a macromolecular receptor, usually a protein. Enzymatic reactions or signal-transduction cascades are thereby influenced with respect to their function for the organism. We regard this binding as a process under equilibrium conditions; thus, binding can be described as an association or dissociation process. Accordingly, biological activity is expressed as the affinity of both partners for each other, as a thermodynamic equilibrium quantity. How well do we understand these terms and how well are they theoretically predictable today? The holy grail of rational drug design is the prediction of the biological activity of a compound. The processes involving ligand binding are extremely complicated, both ligand and protein are flexible molecules, and the energy inventory between the bound and unbound states must be considered in aqueous solution. How sophisticated and reliable are our experimental approaches to obtaining the necessary insight? The present review summarizes our current understanding of the binding affinity of a small-molecule ligand to a protein. Both theoretical and empirical approaches for predicting binding affinity, starting from the three-dimensional structure of a protein-ligand complex, will be described and compared. Experimental methods, primarily microcalorimetry, will be discussed. As a perspective, our own knowledge-based approach towards affinity prediction and experimental data on factorizing binding contributions to protein-ligand binding will be presented.     

Die Abstimmung chromatographischer Flie?mittel auf Aluminiumoxide eingestellter Aktivit?t

Zusammenfassung Aluminiumoxid, das mit Wasser vorbelegt ist, gibt an organische Lösungsmittel einen Teil davon ab und ändert dadurch seine Aktivität. In einer chromatographischen Trennsäule können sich hieraus ernste Störungen ergeben. Man vermeidet sie durch die Anwendung von Fließ-mitteln mit passendem Wasserzusatz. Auf die Trocknung von Pyridin an aktivem Aluminiumoxid wird kurz eingegangen.

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Summary Aluminium oxide containing a certain amount of water transfers it in part to organic solvents, thus changing its activity. Serious interferences in chromatographic column separations can arise from that fact. They can be prevented by use of solvents with adjusted water content. The use of active aluminium oxide for desiccation of pyridine is described shortly.

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Ein Teil der Ergebnisse wurde bereits in verschiedenen Vorträgen mitgeteilt.

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Roscher, G.: Diss. Univ. Erlangen 1960.     

Characterization of Autocatalytic Reactions in Modified Cellulose/NMMO Solutions by Thermal Analysis and UV/VIS Spectroscopy

The thermal stability of cellulose/N-methylmorpholine-N-oxide (NMMO) solutions were investigated using UV/VIS spectrometry with a temperature programming cuvette and caloric measurements by means of the Systag calorimeter RADEX (mini-autoclave). Both analytical methods allow to characterize the influences of stabilizers and additives. With the temporal course of the optical density, temperature and pressure thermal runaway reactions with gas evolution and accumulation of chromophoric degradation products were recognized. Kinetic model calculations compared with UV/VIS measurements demonstrate the existence of autocatalytic reactions in cellulose/NMMO solutions. Varying the heating rate autocatalysis can be proved by dynamic caloric measurements as well.     

Slow water diffusion in micellar solutions

Slowly diffusing water molecules were found by quasi-elastic neutron scattering (QENS) in a sodium dodecyl sulfate (SDS) micellar solution, and both their diffusion coefficient (4.33 x 10(-6) cm2 x s(-1)) and mole fraction (0.057) were determined. After successfully checking the mean slowing down of solvent molecules by the gradient compensated stimulated spin-echo (GCSTE) pulse sequence NMR method, a similar effect was observed with this technique in the solvent phase of dodecyl trimethylammonium bromide (DTAB) and differing chain length (X = 12, 20, 30, and 40) ethoxylated nonyl phenol (9NX) micellar systems. Following the literature, the experimental results are qualitatively explained by assuming that, apart from ionic hydration, H-bonds may form between the solvent molecules and the O or N atoms present in the hydrophilic (head)groups of the micelle-forming monomers.     

Voltammetrische Bestimmung von Coffein in Kaffee,Tee und coffeinhaltigen Getränken

Zusammenfassung Zur Bestimmung von Coffein in Erfrischungsgetränken (Cola), Kaffee und Tee wird die Differential-Pulsvoltammetrie verwendet. Bei dieser Methode wird Coffein bei pH 1,2 an einer glasartigen Kohlenstoffelektrode oxydiert und quantitativ bestimmt. Die voltammetrisch ermittelten Analysenergebnisse werden mit den Resultaten der Flüssigkeistchromatographie verglichen. Um einen weiteren Einblick in den Reaktionsverlauf zu erhalten, wurde Coffein anodisch bei pH 1,2, 2,3 und pH 6 oxydiert. Die Reaktionsprodukte wurden kathodisch durch Differential-Pulspolarographie identifiziert.

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Voltammetric determination of caffeine in coffee, tea, and soft drinks

Summary Differential pulse voltammetry is used for the determination of caffeine in soft drinks, coffee, and tea. In this method caffeine is oxidised at a glassy carbon electrode at pH 1.2 and determined quantitatively. The voltammetric results are compared with those found by HPLC. To elucidate the mechanism of the electrode processes the reaction products were produced by anodic oxidation of caffeine at pH 1.2, 2.3 und pH 6 and then identified by cathodic differential pulse polarography.