ROLE OF HYDROPHOBIC EFFECTS IN THE REACTION OF A POLYNUCLEAR AROMATICDIOL EPOXIDE WITH OLIGODEOXYNUCLEOTIDES IN AQUEOUS-SOLUTIONS

The need for large-scale direct synthesis of stereochemically defined and site-specific benzo[a]pyrenediol epoxide-oligodeoxyribonucleotide adducts for detailed NMR and other biochemical and physicochemical stu dies has necessitated a better understanding of variables that lead to an enhancement of the reaction yields. It is shown that, in aqueous s olution, the formation of noncovalent hydrophobic complexes between 7r ,8t-dihydroxy-9t, 10t-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) a nd the single-stranded oligonucleotide 5'-d(CCATCGCTACC) precedes the covalent binding reaction of BPDE with the single deoxyguanosine resid ue. The yield of covalent reaction products (involving reaction of BPD E at the C10 position with the exocyclic amino group of the dG residue ) increases with increasing DNA concentration and tends toward saturat ion at oligonucleotide single-strand concentrations above similar to 3 mM. The addition of NaCl (0.3 M) also tends to enhance the adduct rea ction yields. However, organic solvents such as tetrahydrofuran in the reaction mixtures (10-40%) decrease the stabilities of the noncovalen t complexes, which in turn leads to reductions in the yields of covale nt BPDE-dG oligonucleotide adducts, The efficiencies of formation of h ydrophobic complexes were probed by fluorescence and UV absorption tec hniques using the BPDE tetrol hydrolysis product 7,8,9,-10-tetrahydrox ytetrahydrobenzo[a]pyrene as a model system.