The π N → e +e−N reaction close to the vector-meson production threshold

The π^? p→e ⁺ e ^? n and π⁺ n→e ⁺ e ^? p reaction cross sections are calculated below and in the vicinity of the vector-meson (?⁰,ω) production threshold. These processes are largely responsible for the emission of e ⁺e^? pairs in pion-nucleus reactions and contribute to the dilepton spectra observed in relativistic heavy ion collisions. They are dominated by the decay of low-lying baryon resonances into vector-meson-nucleon channels. The vector mesons materialize subsequently into e ⁺ e^? pairs. Using πN→?⁰ N and πN→ωN, amplitudes calculated in the center of mass energy interval 1.4 < √s<1.8 GeV, we compute the π^? p→e ⁺ e ^? n and π⁺ n→e ⁺ e ^? p reaction cross sections in these kinematics. Below the vector-meson production threshold, the π⁰?ω interference in the e ⁺ e^? channel appears largely destructive for the π^? p→e ⁺ e ^? n cross section and constructive for the π⁺ n→e ⁺ e ^? p cross section. The pion beam and the HADES detector at GSI offer a unique possibility to measure these effects. Such data would provide strong constraints on the coupling of vector-meson-nucleon channels to low-lying baryon resonances.     

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.