Molecular Basis for the Difference in Singlet Oxygen Quantum Yield Between the First Genetically Encoded Photosensitizer, KillerRed, and its Monomeric Counterpart, SuperNova

The application of protein-based photosensitizers in diverse fields has been proposed due to their characteristic to generate reactive oxygen species (ROS) upon light irradiation. However, the first of its kind, KillerRed, has a limitation in its use because of its dimeric nature, so its monomeric counterpart, SuperNova, was developed subsequently to overcome this limitation. What is very intriguing is that, although KillerRed and SuperNova share highly similar structural and optical properties, the singlet oxygen quantum yield of SuperNova is shown to be almost three times larger than that of KillerRed, but the mechanistic details for this difference have not been addressed yet. In the present work, a hybrid quantum mechanics / molecular mechanics (QM/MM) approach with time dependent density functional theory (TDDFT) is employed to examine this issue. Excited state energy surfaces leading to intersystem crossing (ISC) for both KillerRed and SuperNova are explored, and the comparison of those results and additional electrostatic potential (ESP) calculations reveal that the lower singlet oxygen quantum yield of KillerRed is attributed to a high energy (3)n pi* minimum due to a hydrogen bond between the chromophore and neighboring Asn145.