Table 1.

Relative flipping free energy barriers are correlated with lesion-base stacking energies and relative NER susceptibilities in investigated intercalated adducts. Standard deviations are given in parentheses.

PAH-DNA adduct	Structural characteristics	Ensemble average vdW stacking energy of partner (kcal/mol)a	Relative flipping barrier ΔΔGFlipping (kcal/mol)b,c	NERd
R-DB[a,l]P-dA	Fjord region, 5′-intercalation from major groove, 5 aromatic rings	−16.6 (1.6)	−3.2 (0.7)	Resistant
R-B[a]P-dA	Bay region, 5′-intercalation from major groove, 4 aromatic rings	−15.2 (1.4)	−4.1 (0.6)	Modest
R-DB[a,l]P-dG	Fjord region, 3′-intercalation from minor groove, 5 aromatic rings	−12.0 (0.7)	−7.7 (1.0)	High

^aTable S1, Supporting Information, provides breakdowns of van der Waals stacking interaction energies between the flipping base and all nearby bases and the PAH aromatic ring system (See Methods).

^bFlipping data for the 14R-DB[a,l]P-dG adduct and its corresponding unmodified duplex was published previously.⁴¹

^cThe maximal base flipping barrier energy ΔG is 11.8 ± 0.6 kcal/mol for the 14R-DB[a,l]P-dA adduct, 10.9 ± 0.2 kcal/mol for the 10R-B[a]P-dA adduct, and 15.0 ± 0.3 kcal/mol for the corresponding dA unmodified, 10.4 ± 0.6 kcal/mol for the 14R-DB[a,l]P-dG adduct and 18.1± 0.8 kcal/mol for the corresponding dG unmodified. See Figure 4. ΔΔG is the difference between the ΔG for the unmodified and the corresponding modified duplex.

^dNER data for the 14R-DB[a,l]P-dA adduct is from Ref³⁸, for the 10R-B[a]P-dA adduct it is from Refs ^33,39,40 (for sequence 5′-CTCTCA*CTTCC-3′ with the identical central 5-mer as the current work), and for the 14R-DB[a,l]P-dG adduct it is from Ref ³⁸. See Figure 6 for the relative NER data.