Breakdown of Exciton Splitting through Electron Donor–Acceptor Interaction: A Caveat for the Application of Exciton Chirality Method in Macromolecules

Circular dichroism spectra for a series of structurally analogous hairpin oligonucleotides, tethered at the 5′-end with an axially chiral naphthalenimide-perylenimide dyad (NP), is dependent on the nature (AT vs GC) and the orientation (5′-C vs 5′-G) of the adjacent base pair that stacks with the dyad. Charge transfer (CT) interaction between the naphthalenimide unit of the dyad NP and the adjacent guanine–cytosine (5′-C) base pair has been characterized by UV–vis absorption and fluorescence measurements. Molecular dynamics simulations of the dyad end-capped hairpin DNA ODN6i and TD-DFT calculations of the naphthalenimide and perylenimide units confirm that the CT transition dipole orients perpendicular to the perylenimide transition dipole. The orthogonality of the cross product of the CT and the perylenimide transition dipoles with the displacement vector connecting the two dipoles in space results in the zeroing out of the rotational strength of the perylenimide transition dipole, subsequently leading to the DNA-induced nonexciton coupled circular dichroism corresponding to perylenimide, in concurrence with experimental CD spectrum. Singular value decomposition of thermal denaturation of the hairpin DNA having CT interaction (ODN6i) revealed the denaturation proceeded through an additional intermediary stage compared to the hairpin DNA without the CT interaction (ODN6). Dissimilar CD (induced CD for ODN6i vs exciton-coupled CD for ODN6) spectra corresponding to perylenimide unit obtained for similar NP end-capped hairpin DNA sequences cautions against the indiscriminate use of the exciton chirality method, particularly in systems like DNA and proteins containing polarizable chromophores that can interact with reporter transition dipoles.