Terpsichorean movements of pentaammineruthenium on pyrimidine and isocytosine ligands

Pentaammineruthenium moves on ambidentate nitrogen heterocycles by both rot ation and linkage isomerization, which may affect the biological activity o f potential ruthenium metallopharmaceuticals. The rapid rotation rates of [ (NH3)(5)sRu(III)] coordinated to the exocyclic nitrogens of isocytosine (IC yt) and 6-methylisocytosine (6MeICyt) have been determined by LH NMR. Since these rotamers can be stabilized by hydrogen bonding between the coordinat ed ammines acid the N1 and N3 endocyclic nitrogens,rotamerization is under pH control. Spectrophotometrically (UV-vis) measured pK(a) values for the t wo endocyclic sites for the ICyt complex are 2.78 and 9.98, and for 6MeICyt are 3.06 and 10.21, which are probably weighted averages for ionization fr om N3 and N1, respectively. Activation parameters for the rotamerizations w ere determined by variable-temperature NMR at pK(al) < pH < pK(a2) for the complexes with (ICyt(kappa)(-)(N2))-, (6MeICyt kappa (N2))-, and 2AmPyrm ka ppac(N2): For [(6MeICyt kappa (N2))-(NH3)(5)RUIII](2+), DeltaH* = 1.6 kcal/ mol, DeltaS* = -37 cal/mol K, and E-a = 2.2 kcal/mol. Due to strong Ru-III- N pi -bonding, the activation enthalpies are approximately 10 kcal lower th an the expected values for the free ligands. Rotameric structure is correla ted with pK(a) values, pH-dependent reduction potentials, and H-1 NMR param eters. Linkage isomers of [(2AmPym)(NH3)(5)Ru](n+) are reported in which Ru -II is coordinated to the endocyclic nitrogen (NZ) and Ru-III to the exocyc lic nitrogen (N2). The rate constant for the kappa (N2) --> kappa (N1) isom erization as part of an ECE mechanism is 3.9 s(-1) at pH 3. The pH dependen ce of the acid-catalyzed hydrolysis of [(2AmPym kappa (N1))(NH3)(5)RU](2+) is determined.