Dirhodium(II,II) complexes: Molecular characteristics that affect in vitro activity

In the series Rh-2(O2CR)(4) (R) CH3, 1; R) CF3, 2), [Rh-2(O2CR)(2)(phen)(2)](2+) (R) CH3, 3; R) CF3, 4), and [Rh-2(O2CR)(2)( dppz)(2)](2+) (R) CH3, 5; R) CF3, 6), 2, 4, and 6 are twice as cytotoxic as 1, 3, and 5, respectively. The substitution reactions of 2 with 9-ethylguanine at various temperatures take place at faster rates than those of 1, and the activation energy E-a(1) = 69 +/- 4 kJ/mol is twice E-a(2) = 35 +/- 2 kJ/mol. The higher cytotoxicities of [Rh-2(mu-O2CCH3) 2(eta(1)-O2CCH3) L(MeOH)](+) (L = dppz, 7; L = dppn, 8) relative to [Rh-2(mu-O2CCH3)(2)(bpy) L](2+) (L) dppz, 10; L = dppn, 11) are attributed to the labile equatorial groups in 7 and 8 not present in 10 and 11. The toxicities of complexes 1-8 are not related to their charge or the ease by which they transverse the cellular membrane but to the lability of the ligands on the dirhodium core.