Immobile and mobile phase EPR spectroscopy of copper complexes: studies on biological interesting bis (thiosemicarbazonato) Cu(II) chelates

ESR studies of an analogue of the antitumor agent [3-ethoxy-2-oxobutyraldehyde bis(thiosemicarbazonato)]copper(II), CuKTS, were undertaken to provide model data before studying the interaction of the analogues with Ehrlich cells. ESR data were taken at room temperature in anticipation of monitoring the fluidity of the environment about the copper complex. Room-temperature data vs. pH for [3-ethoxy-2-oxobutyraldehyde bis(N4,N4-dimethylthiosemicarbazonato)]copper(II), CuKTSM2, clearly establish a low-pH and a high-pH form. Computer simulations of these spectra and spectra from published data are interpreted with use of a superposition of only these two distinct pH forms. The room-temperature ESR signal rapidly disappeared for CuKTS after incubation in Ehrlich ascites tumor cells and is consistent with previous reports of thiol reduction of CuKTS in Ehrlich cells. In contrast, the ESR signal for CuKTSM2 was stable after incubation in Ehrlich cells and is consistent with the notion that CuKTS localizes in the cytoplasm and CuKTSM2 localizes in the membrane. Surprisingly, CuKTSM2 at low concentrations is essentially immobilized in its association with Ehrlich cells. This observation has not been previously made because only spectra for CuKTS in frozen samples of Ehrlich cells have been previously investigated. © 1984, American Chemical Society. All rights reserved.