DIFFERENTIAL HYDRATION THERMODYNAMICS OF STEREOISOMERIC DNA-BENZO[A]PYRENE ADDUCTS DERIVED FROM DIOL EPOXIDE ENANTIOMERS WITH DIFFERENT TUMORIGENIC POTENTIALS

A combination of UV spectroscopy, calorimetry, and density techniques were used to characterize the thermodynamics of complexes with covalen tly bound hydrophobic pyrenyl residues in the minor groove of DNA unde camer duplexes. The control duplex d(CCATCGCTACC)/d(GGTAGCGATGG) and two adduct duplexes in which the chiral (+)-anti-BPDE and (-)-anti-BPD E (the 7R,8S,9S,10R- and 7S,8R,9R,10S-enantiomers of xy-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 (designa ted as the (+)- and (-)-BPDE duplexes, respectively). Both of the BPDE -modified DNA duplexes exhibit lower helix-coil transition temperature s than the control duplex. The complete thermodynamic profiles (Delta V, Delta H, Delta G, Delta S, and Delta n(Na+)) for the formation of e ach duplex were determined at 20 degrees C. Duplex formation is primar ily enthalpy driven, and is accompanied by an uptake of both counterio ns and water molecules (negative Delta V). Relative to the unmodified duplex, the differential thermodynamic profiles of each covalent adduc t duplex reveal an enthalpy-entropy compensation; the Delta Delta V va lue is only marginally smaller for the (-)-BPDE-DNA than for the unmod ified duplex, but the uptake of water is nearly 50% greater for the ()-BPDE duplex. Correlation of the thermodynamic data with the known NM R solution conformations of the BPDE-DNA complexes (de los Santos et a l. Biochemistry 1992, 31, 5245) suggests that these differential therm odynamic parameters, together with the similar values for the uptake o f counterions, correspond to a differential hydration of the BPDE resi dues that are exposed to solvent while in the minor groove of B-DNA. T he formation of the (+)-BPDE duplex results in a greater immobilizatio n of structural water than in the case of the (-)-BPDE duplex; these r esults suggest that the bent conformation at the lesion site apparentl y gives rise to an enhanced exposure of the hydrophobic polycyclic aro matic moiety of the covalently bound BPDE residue to the aqueous solve nt.