On the origin of selective nitrous oxide N-N bond cleavage by three-coordinate molybdenum(III) complexes

Reaction of Mo(N[R]Ar)(3) (R = Bu-t or (CD3)(2)CH3) with N2O gives rise exclusively to a 1: 1 mixture of nitride NMo(N[R]Ar)(3) and nitrosyl ONMo(N[R]Ar)(3), rather than the known oxo complex OMo(N[R]Ar)(3) and dinitro-en. Solution calorimetry measurements were used to determine the heat of reaction of Mo(N[R]Ar)3 with N2O and, independently, the heat of reaction of Mo(N[R]Ar)3 with NO. Derived from the latter measurements is an estimate (155.3 +/- 3.3 kcal . mol(-1)) of the molybdenum-nitrogen bond dissociation enthalpy for the terminal nitrido complex, NMo(N[R]Ar)(3). Comparison of the new calorimetry data with those obtained previously for oxo transfer to Mo(N[R]Ar)(3) shows that the nitrous oxide N-N bond cleavage reaction is under kinetic control. Stopped-flow kinetic measurements revealed the reaction to be first order in both Mo(N[R]Ar)(3) and N2O, consistent with a mechanism featuring post-rate-determining dinuclear N-N bond scission, but also consistent with cleavage of the N-N bond at a single metal center in a mechanism requiring the intermediacy of nitric oxide. The new 2-adamantyl-substituted molybdenum complex Mo(N[2-Ad]Ar)(3) was synthesized and found also to split N2O, resulting in a 1:1 mixture of nitrosyl and nitride products;,the reaction exhibited first-order kinetics and was found to be ca. 6 times slower than that for the tert-butyl-substituted derivative. Discussed in conjunction with studies of the 2-adamantyl derivative Mo(N[2-Ad]Ar)(3) is the role of ligand-imposed steric constraints on small-molecule, e.g. N-2 and N2O, activation reactivity. Bradley's chromium complex Cr((NPr2)-Pr-i)(3) was found to be competitive with Mo(N[R]Ar)(3) for NO binding, while on its own exhibiting no reaction with N2O. Competition experiments permitted determination of ratios of second-order rate constants for NO binding by the two molybdenum complexes and the chromium complex. Analysis of the product mixtures resulting from carrying out the N2O cleavage reactions with Cr((NPr2)-Pr-i)(3) present as an in situ NO scavenger rules out as dominant any mechanism involving the intermediacy of NO. Simplest and consistent with all the available data is a post-rate-determining bimetallic N-N scission process. Kinetic funneling of the reaction as indicated is taken to be governed by the properties of nitrous oxide as a ligand, coupled with the azophilic nature of three-coordinate molybdenum(III) complexes

Ouabain-induced perturbations in intracellular ionic homeostasis regulate death receptor-mediated apoptosis

Apoptosis is defined by specific morphological and biochemical characteristics including cell shrinkage (termed apoptotic volume decrease), a process that results from the regulation of ion channels and plasma membrane transporter activity. The Na(+)-K(+)-ATPase is the predominant pump that controls cell volume and plasma membrane potential in cells and alterations in its function have been suggested to be associated with apoptosis. We report here that the Na(+)-K(+)-ATPase inhibitor ouabain, potentiates apoptosis in the human lymphoma Jurkat cells exposed to Fas ligand (FasL) or Tumor necrosis factor--related apoptosis-inducing ligand (TRAIL) but not other apoptotic agents such as H(2)O(2), thapsigargin or UV-C implicating a role for the Na(+)-K(+)-ATPase in death receptor-induced apoptosis. Interestingly, ouabain also potentiated perturbations in cell Ca(2+) homeostasis only in conjunction with the apoptotic inducer FasL but not TRAIL. Ouabain did not affect alterations in the intracellular Ca(2+) levels in response to H(2)O(2), thapsigargin or UV-C. FasL-induced alterations in Ca(2+) were not abolished in Ca(2+)-free medium but incubation of cells with BAPTA-AM inhibited both Ca(2+) perturbations and the ouabain-induced potentiation of FasL-induced apoptosis. Our data suggest that the impairment of the Na(+)-K(+)-ATPase activity during apoptosis is linked to perturbations in cell Ca(2+) homeostasis that modulate apoptosis induced by the activation of Fas by FasL