Mechanism of the glutathione transferase-catalyzed conversion of antitumor 2-crotonyloxymethyl-2-cycloalkenones to GSH adducts

Human glutathione (GSH) transferase (hGSTP1-1) processes with similar kinetic efficiencies the antitumor agents 2-crotonyloxymethyl-2-cyclohexenone (COMC-6), 2-crotonyloxymethyl-2-cycloheptenone (COMC-7), and 2-crotonyloxymethyl-2-cyclopentenone (COMC-5) to 2-glutathionylmethyl-2-cyclohexenone, 2-glutathionylmethyl-3-glutathionyl-2-cycloheptenone, and 2-glutathionylmethyl-2-cyclopentenone, respectively. This process likely involves initial enzyme-catalyzed Michael addition of GSH to the COMC derivative to give a glutathionylated enol(ate), which undergoes nonstereospecific ketonization, either while bound to the active site or free in solution, to a glutathionylated exocyclic enone. Free in solution, GSH reacts at the exomethylene carbon of the exocyclic enone, displacing the first GSH to give the final product. This mechanism is supported by the observation of multiphasic kinetics in the presence of high concentrations of hGSTP1-1 and the ability to trap kinetically competent exocyclic enones in aqueous acid using COMC-6 and COMC-7 as substrates. That the exocyclic enone is formed by nonstereospecific ketonization of an enol(ate) species is indicated by the observation that COMC-6 (chirally labeled with deuterium at the exomethylene carbon) gives stereorandomly labeled exocyclic enone. The isozymes hGSTP1-1, hGSTA1-1, hGSTA4-4, and hGSTM2-2 catalyze the conversion of COMC-6 to final product with similar efficiencies (K(m) = 0.08-0.34 mM, k(cat) = 1.5-6.1 s(-)(1)); no activity was detected with the rat rGSTT2-2 isozyme. Molecular docking studies indicate that in hGSTP1-1, the hydroxyl group of Tyr108 might serve as a general acid catalyst during substrate turnover. The possible significance of these observations with respect to the metabolism of COMC derivatives in multidrug resistant tumors is discussed.     

Extraction voltammetric determination of phosphorus

The proposed method for the determination of phosphorus is based on the extraction of molybdophosphoric acid. A mixture of methyl-iso-butyl-ketone and cyclohexane is used as extractant. The addition of cyclohexane allows the separation from silicon. Sodium chlorate is used as oxidant and gives rise to a catalytic current. The voltammetric behaviour of molybdophosphoric acid is described, comparing the dropping mercury electrode and the glassy carbon electrode. The 3-detection limit is 2.3 · 10^–8 mol P/l. The method was applied to water samples from the river Spree.Dedicated to Professor Dr. W. Fresenius on the occasion of his 80th birthday     

Correlations of13C chemical shifts and geometry modifications

The effect of geometry modifications of¹³C chemical shifts has been investigated in a small subset of molecules using both LO-INDO and Gaussian 70 (4–31) calculations. The Gaussian calculations, while known to give poor absolute shifts, compare well to the reparameterized semi-empirical INDO determinations in calculated shift changes. In virtually all cases the signs of the shift changes were found to be opposite to that of the changes in the calculated electronic energy.     

The hyperfine structure and nuclear moments of some neutron-deficient as isotopes

The hyperfine structure of the¹³⁹La II line 5d ^{2 3} F→5d4f ³ F ₄ ⁰ atλ=579.8 nm has been investigated by means of collinear laser spectroscopy on a fast La⁺ beam. AmongΔF=0, ±1 hyperfine transitions,gDF=±2 transitions have been observed. An interpretation of theseΔF=±2 transitions as well as their relative line strengths is given by means of a three-quantum process.     

Protein dynamics tightly connected to the dynamics of surrounding and internal water molecules.

Proteins are key components of biological cells. For example, enzymes catalyze biochemical reactions, membrane transporters are responsible for uptake and release of critical and superfluous components from the cell environment, and structural proteins are responsible for the stability of the cell wall and cytoskeleton. Many of the diverse protein functions involve dynamic transitions ranging from small local atomic displacements up to large allosteric conformational changes. In any conformation, proteins are in contact with the universal solvent medium of cells, water. Water not only surrounds proteins but is often an integral part of proteins and also is involved in key mechanistic steps. This Minireview discusses recent experimental and theoretical results on the role of water for protein dynamics and function.     

The `cyclophene' [2.2.2](1,2,4)cyclophan‐9‐ene

In the title compound, C₁₈H₁₆, the [2.2]paracyclophane geometry is restrained to a considerable extent despite the introduction of the extra C=C bridge; typical paracyclophane features, such as the elongated C—C bridges, are still observed. However, the bridgehead atoms of the C=C bridge are forced into unusually close proximity [2.657 (3) Å], which in turn causes the rings to be rotated to an interplanar angle of 13.7 (2)°. The packing involves hexagonally close‐packed layers of molecules parallel to the xy plane, corresponding to the known `7,11' pattern of paracyclophanes, but without significant short intermolecular contacts.