We use high-precision acoustic and densimetric techniques to determine, at 25 degrees C, the changes in volume, delta V, and adiabatic compressibility, delta Ks, that accompany the binding of
netropsin to the poly(dAdT).poly(dAdT) and
poly(dA).poly(dT) duplexes, as well as to the
poly(dT).
poly(dA).poly(dT) triplex. We find that
netropsin binding to the heteropolymeric poly(dAdT).poly(dAdT) duplex is accompanied by negative changes in volume, delta V, and small positive changes in compressibility, delta Ks. By contrast,
netropsin binding to the homopolymeric
poly(dA).poly(dT) duplex is accompanied by large positive changes in both volume, delta V, and compressibility, delta Ks. Furthermore,
netropsin binding to the
poly(dT).
poly(dA).poly(dT) triplex causes changes in both volume and compressibility that are nearly twice as large as those observed when
netropsin binds to the
poly(dA).poly(dT) duplex. We interpret these macroscopic data in terms of binding-induced microscopic changes in the hydration of the
DNA structures and the
drug. Specifically, we find that
netropsin binding induces the release of approximately 22 waters from the hydration shell of the poly(dAdT).poly(dAdT) heteropolymeric duplex, approximately 40 waters from the hydration shell of the
poly(dA).poly(dT) homopolymeric duplex, and about 53 waters from the hydration shell of the
poly(dA).poly(dT), induces the release of 18 more water molecules than
netropsin binding to the heteropolymeric duplex, poly(dAdT).poly(dAdT). On the basis of apparent molar volume, phi V, and apparent molar adiabatic compressibility, phi Ks, values for the initial
drug-free and final
drug-bound states of the two all-AT duplexes, we propose that the larger
dehydration of the
poly(dA).poly(dT) duplex reflects, in part, the formation of a less hydrated
poly(dA).poly(dT)-
netropsin complex compared with the corresponding poly(dAdT).poly(dAdT)-
netropsin complex. In conjunction with our previously published entropy data [Marky, L. A., & Breslauer, K. J. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 4359-4363], we calculate that each water of hydration released to the bulk
solvent by
ligand binding contributes 1.6 cal K-1 mol-1 to the entropy of binding. This value corresponds to the average difference between the partial molar entropy of water in the bulk state and water in the hydration shells of the two all-AT duplexes. When
netropsin binds to the
poly(dT).
poly(dA).poly(dT) triplex, the changes in both volume and compressibility suggest that the binding event induces more
dehydration of the triplex than of the duplex state. Specifically, we calculate that
netropsin binding to the
poly(dT).
poly(dA).poly(dT) triplex causes the release of 13 more waters than
netropsin binding to the
poly(dA).poly(dT) duplex.(ABSTRACT TRUNCATED AT 400 WORDS)