Inorg. Chem. 1984,23, 3543-3548 Scheme I1
first-row transition-metal hydride complexes can show appreciable acidity,28this degree of acidity is unusual for complexes of the more basic third-row transition metal^.^^^^^ Hydrido transition-metal complexes of R u , ~ ~ and Ir32 have been depronated by strong bases such as alkoxide. The pK, values for hydrido complexes of Os, W, Mo, and Cr are comparable with, or lower than, that of acetic acid.29 The Bransted acidity of cis-[IrH(CO)(dppe)2][BF,], precludes activation of the coordinated CO to nucleophilic attack. Other members in the series of complexes cis- and trans-IrX(CO)(dppe)?+ (X = C1, H) are reactive with nucleophiles such as H 2 0 , OH-, and H- at the C O ligand. The results of these studies will be reported subsequently."
I
0 C
+ f
-k cs/
2+
VI1
Y
3543
+
Alternatively, Ir(dppe)2+,1Zv27 which is in equilibrium with Ir(CO)(dppe)2+, may undergo protonation to afford IrH( d ~ p e ) ~ ~Subsequent +. reaction with CO affords VII. This pathway is used as a synthetic method to produce VII. The complex IrHCl(dppe)*+ could form by the known reaction of HC1 with Ir(dppe)2+.12*16 The acidity of cis-[IrH(CO)(dppe)2][BF,], is remarkable. Reversible deprotonation of this complex by chloride implies that its acidity is on the order of that of HC1. Although
Acknowledgment. This research was supported by the National Science Foundation (Grant CHE-8308076). We thank Johnson-Matthey, Inc., Malvern, PA, for the loan of Ir salts used in this study. Registry No. Ia, 15308-58-4;Ib, 91685-28-8;IIa, 91606-09-6; IIb, 91606-11-0;IIIa, 91606-12-1; IIIb, 91606-14-3;IV, 91685-23-3; Va, 91685-24-4;Vb, 91685-25-5; VI, 91685-27-7; VIIa, 91606-15-4;VIIb, 66350-34-3;[Ir(d~pe)~]Cl, 15390-38-2;[Ir(d~pe)~]BF~, 151 30-28-6; Ir2C12(C8H24)4, 12246-51-4;[Ir(CO)(dppe)2]Br, 15699-66-8. (28) (a) Schunn, R. A. In Transition Metal Hydrides"; Muetterties, E., Ed.; Marcel Dekker: New York, 1971; Vol. 1, pp 203-269. (b) Vidal, J. L.; Walker, W. E. Inorg. Chem. 1981, 20, 249-254. (29) Jordan, R. F.;Norton, J. R. J. Am. Chem.Soc. 1982,104, 1255-1263. (30) But a series of acidic iridium(II1) hydrides has been reported by: Pearson, R. G.; Kresge, C. T. Inorg. Chem. 1981, 20, 1878-1882. (31) Cavit, B. E.; Grundy, K. R.; Roper, W. R. J . Chem. Soc., Chem. Commun. 1972,6C-61. (32) Thorn, D.L. Organometallics 1982, 1 , 197-204.
Contribution from the Department of Radiology, National Biomedical ESR Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, and Department of Chemistry, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53201
Immobile- and Mobile-Phase ESR Spectroscopy of Copper Complexes: Studies on Biologically Interesting Bis( thiosemicarbazonato)copper(II) Chelates WILLIAM E. ANTHOLINE,*+RICCARDO BASOSIJl JAMES S. HYDE? SUZANNE LYMAN,$ and DAVID H. PETERING*n Received April 19, 1984
ESR studies of an analogue of the antitumor agent [3-ethoxy-2-oxobutyraldehydebis(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-oxobutyraldehydebis(p,p-dimethylthiosemicarbazonato)]copper(II), CuKTSM2,clearly establish a low-pH and a high-pH form. Computer simulationsof 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 CuKTSM2was 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, CuKTSM2at 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.
Introduction A number of copper complexes or ligands that bind copper have biological activity. Mono: and bis(thiosemicarbazonato)copper(II) complexes and analogues of the tripeptide H-Gly-His-Lys-OH have cytotoxic and antitumor effect^.^-^ In addition, copper(I1) bleomycin has been extensivelv studied to determine its contribution to the antitumor activit; of bleomycin.s The tripeptide H-Gly-His-Lys-OH
and 2-formylpyridine thiosemicarbazone and derivatives, which respectively have hormonelike properties and antitumor (1) On leave from the Department of Chemistry, University of Siena, Siena, Italy. (2) Recipient, NIH Grant No. CA-22184. (3) Petering, D.H.; Petering, H. G. Handb. Exp. Pharmakol. 1975.38 (2),
-RAI-Rl6 ._
(4) Agrawal, K. C.; Sartorelli, A. C. Handb. Exp. Pharmakol. 1975, 38 (Z), 793-807. (5) Antholine, W. E.; Knight, J. M.; Petering, D. H. J. Med. Chem. 1976,
