J. Am. Chem. Soc. 1981, 103, 5747-5752 5741 Structural Correlation and Metal Ion Movement in Stable Pentaammineruthenium( 111)-H ypoxant hine Complexes M. E. Kastner, K. F. Coffey, M. J. Clarke,* S. E. Edmonds, and K. Eriks Contribution from the Departments of Chemistry, Boston College, Chestnut Hill, Massachusetts 02167, and Boston University, Boston, Massachusetts 0221 5. Received January 26, 1981. Revised Manuscript Received April 30, 1981 Abstract The crystal and molecular structures of 7-[(Hyp)(NH3)SR~]C13.3Hz0 and 9-[(7-MeHyp)(NH3)5R~]C13 are reported. Crystals of both compounds belong to the orthorhombic space group Pnma with unit cell dimensions: a = 11.465 (3) A, b = 6.820 (2) A, and c = 22.520 (9) A for the former; a = 11.146 (4) A, b = 6.835 (2) A, and c = 21.490 (9) A for the latter. The hypoxanthine complex was prepared under neutral to mildly acidic conditions with deoxyinosine as the initial ligand. Chromatographic analysis of the final product showed the 7-coordinated complex to be the only monomeric species present, which verifies N(7) as the preferred coordination site for (NH3)SR~11*’1’ ions with inosine and guanosine ligands. When hypoxanthine or 7-methylhypoxanthine were employed as ligand, the 3- and 9-coordinated isomers formed. Under acidic conditions the (NH&RulI1 was observed to undergo linkage isomerization from the N(3) to the N(9) positions with a rate of 1.25 X lo4 s-I at 37 OC, whereas in neutral media this rate was depressed to 2.2 X lod s-l, due to proton ionization from the N(1) site. Activation parameters in acidic media are AH‘ = 90 kJ/mol and AS* = -31 J/(mol K). An empirical correlation is found between ApK, values of various ruthenium(II1)-purine, -pyrimidine, and -imidazole complexes and 1 /12, where r is the distance between the metal ion and the deprotonationsite. A similar correlation is observed between 1/12 and the decrease in the Ru(II1) reduction potential, AE, on deprotonation of the complexes. A free energy correlation is also noted between the ApK, and AE values for these complexes. The coordination of transition-metal ions to nucleotides, nucleic acids, and their constituent bases has assumed an increasing importance in recent years due to the mutagenicity’ and anticancer activity of a number of transition-metal complexes.24 In par- ticular, recent studies have shown that a range of ruthenium complexes are mutagenics7 and several also show promise in the development of anticancer pharmaceutical^.^^^ The pentaammineruthenium(II1)-hypoxanthine compounds treated here were initially prepared in an effort to establish the differing physical and chemical effects of a metal ion firmly coordinated at various sites on a purine ring. The effects of varying the coordination site between the N(3), N(7), and N(9) positions on (1) the ligand to metal charge-transfer bands, (2) the acidity of the ligand, and (3) the reduction potential of the metal ion have since been reported.1° In order to assign the various linkage isomers unequivocally, it was also necessary to firmly establish the molecular structures of at least two of the three possible isomers. Moreover, since deoxyinosine, which was employed in the synthesis of the N(7)-coordinated hypoxanthine complex, provides an excellent model for guanosine ligands, the structure determination of this complex coupled with a correspondence in spectroscopic and chemical properties makes it possible to verify the coordination site of pentaammineruthenium(II1) on various guanosine ligands and on these ligands in nucleic acids. In previous investigations it had been shown that the N(3)- bound isomer undergoes linkage isomerization to the N(9)-co- ordinated form in acidic media.IO The work reported here quantitates the rate of this isomerization and further shows that the same process occurs (with a significantly dimiminished rate) even at neutral pH. Finally, the structural parameters made available from this and other studies of pentaammineruthenium(II1) complexes with purine, pyrimidine, and imidazole ligands provide the basis for several empirical linear free energy correlations. These rela- tionships allow the prediction of the acidic properties of the ligand and the reduction potential of the metal or can be used to estimate the distance between the metal coordination and proton ionization sites in new complexes. Experimental Section Chemicals and Reagents. The hypoxanthinecomplexes were prepared by previously reported methods.I0 All kinetic runs were done at an ionic strength adjusted to 1.0 with a standard LiCl solution and with buffer *Address correspondence to this author at Boston College. concentrations in the range of 0.17-0.2 M. Buffers employed in the appropriate pH ranges were HCI, pH 0-1.85, glycine/HCl, pH 2-3.7, sodium acetate/acetic acid, pH 4-5, and phosphate, pH 5-7. Kinetic Studies. Kinetic studies were performed spectrophotometric- ally or by using an HPLC technique to follow the concentrations of the reactants or products. Spectrophotometric results were obtained on a Perkin-Elmer Model 575 spectrophotometer with temperature control of the cuvette compartment held within fO.l OC. The change in absorbance was followed at 325 nm over at least 6 half-lives, and the data over the first 2-3 half-lives were treated by the method of Guggenheim13 as a first-order reaction and then fitted by a standard nonweighted linear least-squares method to determine the observed rate. Above pH 5.2 isosbestic points were no longer observed over the entire course of the reaction and HPLC was used to monitor reactant and product concen- trations. Product analysis by HPLC was performed by injecting samples onto a Varian Model 5000 HPLC fitted with a Varian CH-10 or a Waters Micro-Bondapak-C- 18 column and a Varichrome UV-visible detector. A 0.2 M solution of ammonium propionate at pH 5.5 was used as the eluant. Capacity factors for the N(3) and N(9) isomers under these conditions were 1.9 and 1.7, respectively. Concentrations were followed by peak-height analysis. Rate constants were obtained from a weighted least-squares fit of eq 1 to a plot of k~ vs. [H+].I3 Values of A€.f and ALP were obtained from a linear regression analysis of a plot of In (kl/7‘) vs. 1/T. Crystallography. Single crystals of 7-[(Hyp)(NH3),Ru]C13.3Hz0 and 9-[(7-MeHyp)(NH3)5Ru]C13 were grown by ethanol diffusion into 0.1 M HCI solutions of the respective complexes. An orange single crystal ~ ~ ~ (1) Flessel, C. P. In “Trace Metals in Health and Disease”; Kharasch, N., Ed.; Raven Press: New York, 1980; pp 109-122 and other articles in this volume. (2) Barton, J. K.; Lippard, S. J. Met. Ions Biol. 1980, I, 31-114. (3) Marzilli, L. G.; Kistenmacher, T. J.; Eichhorn, G. L. Mer. Ions Biol. (4) See various articles in Mer. Ions Biol. sysr. 1980, 10 and 11. (5) Yasbin, R. E.; Matthews, C. R.; Clarke, M. J. Chem.-Eiol. Znrerocr. (6) Clarke, M. J. Znorg. Chem. 1980, 19, 1103-1 104. (7) Durig, J. R.; Danneman, J.; Behnke, W. D.; Mercer, E. E. Chem.-Biol. Znrerocr. 1976, 13, 287. (8) Clarke, M. J. In “Inorganic Chemistry in Biology and Medicine”; Martell, A. E., Ed.; American Chemical Society: Washington, DC, 1980; in press. (9) Clarke, M. J. Mer. Zons Biol. Sysr. 1980, 11, 231-283. (10) Clarke, M. J. Znorg. Chem. 1977, 16, 738. (11) Clarke, M. J.; Taube, H. J. Am. Chem. Soc. 1975, 97, 1397. (12) Clarke, M. J. J. Am. Chem. Soc. 1978, 100, 5068-5075. (1 3) Wilkins, R. G. “The Study of Kinetics and Mechanism of Reactions of Transition Metal Complexes”; Allyn and Bacon: Boston, 1974; pp 13-45. 1980, I, 179-250. 1980, 31, 355-365. 0002-7863/8l/lS03-5747$01.25/0 0 1981 American Chemical Society