Photodynamic Properties of Hypocrellin A, Complexes with Rare Earth Trivalent Ions:  Role of the Excited State Energies of the Metal Ions

Fifteen complexes of hypocrellin A (HA) with rare earth trivalent ions (except Pm³⁺) along with the complex of HA with Sc³⁺ were prepared, and their photodynamic activities, including absorption in the phototherapeutic window (600−900 nm); water-solubility; triplet lifetime; generation of reactive oxygen species (ROS), such as singlet oxygen (¹O₂), superoxide anion radical (O₂^-•), and hydroxyl radical (OH^•); generation of semiquinone anion radical; and affinity to DNA, as well as photosensitized damage on calf thymus DNA (CT DNA), were compared in detail using the UV−visible spectrum, fluorescence spectrum, spin-trapping EPR technique, and laser photolysis technique. All complexes exhibit a red-shifted absorption spectrum, an increased absorbance above 600 nm, improved water solubility, and an enhanced affinity to CT DNA over the parent HA. For ions that possess low-energy excited states, including Ce³⁺, Pr³⁺, Nd³⁺, Sm³⁺, Eu³⁺, Tb³⁺, Dy³⁺, Ho³⁺, Er³⁺, Tm³⁺, and Yb³⁺, the corresponding complexes show undetectable or nearly undetectable fluorescence, a triplet excited-state lifetime, generation of ROS, and photodamage in CT DNA. In contrast, for ions that do not possess low-energy excited states, including Sc³⁺, Y³⁺, La³⁺, Gd³⁺, and Lu³⁺, the corresponding complexes exhibit higher photodamage abilities with CT DNA with respect to HA, benefitting from both their comparable or even higher ¹O₂ quantum yields and an electrostatic affinity that is higher for DNA than HA.