The equilibrium transition from B-DNA to Z-DNA is driven by salt cations and by neutral osmolytes. Transition metal complex cations, such as cobalthexammine and cobalttrisethylenediamine, stabilize the Z-DNA form of poly[d(G-C)] through electrostatic interactions with the DNA backbone and site-specific hydrogen bonds. These complexes can be used to measure the position of the B-Z equilibrium in the presence of osmolytes. Previous studies in our lab and Donald Rau's lab (1) have shown that applying an osmotic stress in osmolyte solutions decreases the concentrations of complex required to form the more sparsely hydrated Z-DNA. We have found that the cobalttrisethylenediamine complex is less effective than the cobalthexammine complex in driving the transition, possibly because the three bidentate ligands in the former result in a lower conformational entropy than the six monodentate ligands in the latter. On the other hand, the binding of cobalttrisethylenediamine to Z-DNA appears to be more strongly subject to competition by hydrating water molecules, as indicated by greater sensitivity to osmotic stress (2). For example, a sucrose concentration of 4.07 osmolal decreased the transition midpoint concentration of the trisethylenediamine complex by 2.5-fold, while the midpoint concentration of the hexammine complex was decreased by only about one-third. Similar trends were also observed with monohydroxylic osmolytes such as methanol and dihydroxylic compounds such as propylene glycol. Future studies will compare the (+) and (-) enantiomers of cobalttrisethylenediamine, in an attempt to explore stereospecific aspects of their binding to DNA. Supported by Towson University Undergraduate Research Grants (to M. Cisse, A. Diedrich and D. Rey-Ardila) and by the Towson University Department of Chemistry.1. Preisler et al (1995) Biochemistry 34, 14400-144072. Ashman et al (2011) Biophysical Society meeting poster presentation