Supporting information for "Environmental Tuning of Charge Transfer in Palmatine"

Palmatine is a DNA-binding alkaloid with potential applications in phototherapy due to its environment-dependent photophysics. Using an hybrid quantum mechanics/molecular mechanics (QM/MM) approach with extensive sampling and quantitative wavefunction analysis, we show that the character of the excited states is dramatically different in water and in DNA environment. While the main absorption of palmatine in both environments arises from two broad π → π∗ absorption bands, the lowest excited state is markedly different: In water, S1 exhibits strong charge-transfer (CT) character, whereas intercalated in DNA it is predominantly localized. This quenched intramolecular CT in DNA persist regardless of the sequence of DNA and it is evident only when an extended QM region, including adjacent nucleobases to the chromophore, is employed. These results highlight the crucial role of the biomolecular environment in tuning chromophore photophysics, with implications for the rational design of DNA-targeted photosensitizers.