The anticancer activity of cisplatin arises from its ability to bind covalently to DNA, forming primarily intrastrand cross-links to adjacent guanine residues. This work is an effort to understand the hydration effects and energetics associated with the incorporation of cisplatin into duplex DNA. A combination of spectroscopy, calorimetry, density, and ultrasonic techniques was employed to investigate the unfolding (and folding) thermodynamics of a 10-mer DNA duplex with a d(GpG) platinated cross-link and its control unplatinated duplex. The platinated duplex unfolds with a lower T-M value (and lower DeltaG degrees (DSC) term by 3.4 kcal/mol), which results from the compensation of an unfavorable enthalpy term with a favorable entropy term. The hydration parameters at 20 degreesC indicated an uptake of structural water by the platinated duplex and a release of electrostricted water by the control duplex. Relative to the control duplex, the folding of the platinated duplex at 20 degreesC yielded a positive differential DeltaG degrees term (and positive differential enthalpy - entropy compensation) and a negative differential volume change. The opposite signs of the Delta DeltaG degrees and Delta DeltaV terms also indicated an uptake of structural water molecules by the platinated duplex. This effect is consistent with the DNA bending and unwinding induced by the cross-link and creating a hydrophobic notch at the lesion site.