Correlation of F0F1-ATPase inhibition and antiproliferative activity of apoptolidin analogues

[structure: see text] Apoptolidin (1) exhibits potent and highly selective apoptosis inducing activity against sensitive cancer cell lines and is hypothesized to act by inhibition of mitochondrial F(0)F(1)-ATP synthase. A series of apoptolidin derivatives, including a new intermolecular Diels-Alder adduct, were analyzed for antiproliferative activity in E1A-transformed rat fibroblasts. Potent F(0)F(1)-ATPase inhibition was not a sufficient determinant of antiproliferative activity for several analogues, suggesting the existence of a secondary biological target or more complex mode of action for apoptolidin.     

Experimental analysis of the reaction layer structure in a gas diffusion electrode

The micro-structure of the reaction layer and the performance of a PTFE-bonded gas diffusion electrode having different PTFE contents have been studied experimentally using electrochemical techniques and a mercury pore sizer. A more practical image of the structure has resulted in comparison with any of the models postulated previously. Maximum performance was obtained at 30% PTFE content for oxygen reduction with ca. 75% utilization of platinum clusters, where an activation process is controlling the performance. The reaction layer consists of two distinctive pore distributions with a boundary of ca. 0.1 μm. The smaller pore (primary pore) was assigned to the space in-between the primary particles in their agglomerate and the larger one (secondary pore) to that in-between the agglomerates. Platinum clusters of ca. 80% were located in the primary pores and most of the PTFE was in the secondary pores. On the basis of the experimental results, a schematic micro-structure for the reaction layer is proposed. It was possible to determine the degree of occupation of each pore by the electrolyte or gas from the experimental results. It was revealed that the primary pore works as a reaction volume while the secondary pore works as main gas channels, e.g. 80% of the former is occupied by electrolyte and 30% of the latter contains gas at the composition of maximum performance. Increased gas channels and high utilization of platinum clusters are essential for a high-performance gas diffusion electrode. They were achieved by dispersing efficiently both the catalysed carbon black and the PTFE.