Action of 1,10-phenanthroline transition metal chelates on P388 mouse lymphocytic leukaemic cells

Abstract

1. (1)Fully coordinated 1,10-phenanthroline and 2,2′-bipyridine chelates of Ru(II) are lethal in vitro to cultured and ascites P388 mouse lymphocytic leukaemic cells; 1,10-phenanthroline chelates are generally more potent than corresponding 2,2′-bipyridine compounds, and mixed-ligand (acetylacetonato) monovalent chelates of both series are more active than the corresponding identical-ligand divalent chelates. Lethal potency is greatest for Ru(II) chelates containing highly alkylated ligands. 2. (2)Within two series of tetramethyl-1,10-phenanthroline chelates, the inert Ru(II) and Ni(II) members are less active against P388 cultured and ascites cells than the corresponding more labile chelates of Cu(II), Cd(II), Zn(II), Fe(II) and Co(II); for the ascites cells, the rank order of lethal potency of the chelates correlates reasonably well with their anticipated rank order of kinetic reactivity. 3. (3)Repeated subculture of P388 cells in the presence of a mixed-ligand Ru(II) chelate has produced a cell line that shows a stable 10-fold resistance to the chelate; the resistant cell line is selectively cross-resistant to certain Ru(II) identical and mixed-ligand chelates. 4. (4)The presence of a fluorescent Ru(II) chelate has been demonstrated at the surface and within the cytoplasm and nucleus of P388 ascites cells exposed to it either in vitro or in the mouse. 5. (5)Ru(II) and Cu(II) chelates of tetramethyl-1,10-phenanthroline do not appear to be chemotherapeutically active against P388 ascites cells in the mouse.