A combination of UV spectroscopy, calorimetry, and density techniques were used to characterize the thermodynamics of complexes with covalently bound hydrophobic pyrenyl residues in the minor groove of DNA undecamer duplexes. The control duplex d(CCATCG*CTACC)/d(GGTAGCGATGG) and two adduct duplexes in which the chiral (+)-anti-BPDE and (-)-anti-BPDE (the 7R,8S,9S,10R- and 7S,8R,9R,10S-enantiomers of 7r,8t-dihydroxy-9t,10t-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene) had been reacted covalently with the exocyclic amino group of the guanine residue G* were studied (designated as the (+)- and (-)-BPDE duplexes, respectively). Both of the BPDE-modified DNA duplexes exhibit lower helix-coil transition temperatures than the control duplex. The complete thermodynamic profiles (Delta V, Delta H, Delta G, Delta S, and Delta n(Na+)) for the formation of each duplex were determined at 20 degrees C. Duplex formation is primarily enthalpy driven, and is accompanied by an uptake of both counterions and water molecules (negative Delta V). Relative to the unmodified duplex, the differential thermodynamic profiles of each covalent adduct duplex reveal an enthalpy-entropy compensation; the Delta Delta V value is only marginally smaller for the (-)-BPDE-DNA than for the unmodified duplex, but the uptake of water is nearly 50% greater for the (+)-BPDE duplex. Correlation of the thermodynamic data with the known NMR solution conformations of the BPDE-DNA complexes (de los Santos et al. Biochemistry 1992, 31, 5245) suggests that these differential thermodynamic parameters, together with the similar values for the uptake of counterions, correspond to a differential hydration of the BPDE residues that are exposed to solvent while in the minor groove of B-DNA. The formation of the (+)-BPDE duplex results in a greater immobilization of structural water than in the case of the (-)-BPDE duplex; these results suggest that the bent conformation at the lesion site apparently gives rise to an enhanced exposure of the hydrophobic polycyclic aromatic moiety of the covalently bound BPDE residue to the aqueous solvent.