Lanthanoid(III) and Actinoid(III) Motexafins in Photodynamic Therapy – a Computational Study on the Electronic Properties of Motexafin Gadolinium

Lanthanoid(III) motexafins are potential candidates for photosensitizers used in photodynamic therapy. To investigate a possible application of these molecules as catalytically active drugs, a computational study on the electronic properties of lanthanoid and actinoid motexafins with focus on Motexafin Gadolinium has been performed. The molecular structures of trivalent lanthanoid and actinoid motexafins have been optimized on the level of density functional theory including major relativistic effects and taking into account in vivo conditions via the appplication of a solvent model. The results are compared to available crystallographic data and are found to be in good agreement with the experiment. Vertical and adiabatic ionization potentials and electron affinities have been evaluated, as well as reduction potentials in reference to the standard hydrogen electrode. A systematic approach for the evaluation of a suggested mechanism for the production of reactive oxygen species using Motexafin Gadolinium as a catalyst for the singlet electron transfer from reducing metabolites as, e. g., ascorbate species, to oxygen within the scope of radiation therapy is given. These reactive oxygen species, as, e. g., singlet oxygen and hydrogen peroxide are crucial for inducing a programmed cell death (apoptosis) of the cancerous tissue during the therapy. To analyze the absorption properties of Motexafin Gadolinium, UV/Vis spectra in gas phase and aqueous phase have been calculated on the level of time-dependent density functional theory. The electronic structure of the excitations has been analyzed in detail with focus on the performance of the different functionals with regard to possible (long-range) charge transfer transitions and an accurate description of the absorption in the red spectral region, which is especially interesting for an application in radiation therapy. A detailed comparison between the calculated gas phase spectra and calculated spectra in aqueous solution -- represented by continuum models -- is provided. The results are compared to an experimental aqueous phase spectrum of Motexafin Gadolinium.