Quantum chemical investigations of lanthanoid(III) and actinoid(III) texaphyrin complexes as well as of their medical and technical applications

• Applicant: Dr. Xiaoyan Cao
• Subject Area: Theoretical Chemistry: Electronic Structure, Dynamics, Simulation ; Pharmacy ; Theoretical Chemistry: Molecules, Materials, Surfaces
• Term: from 2014 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 259799661

Lanthanide(III) and actinide(III) complexes of the macrocyclic texaphyrin ligand will be studied by quantum chemical methods, i.e., with structure optimizations using density functional and second-order Moeller-Plesset perturbation theory, as well as with single-point calculations using the coupled-cluster ansatz with singles, doubles and perturbative triples in the framework of the incremental scheme in order to calibrate the (relative) energies. The heavy lanthanide and actinide elements will be treated with scalar-relativistic 4f-in-core and 5f-in-core pseudopotentials, respectively, and for calibration purposes also with corresponding 4f- and 5f-in-valence pseudopotentials as well as at the relativistic all-electron level using the second-order Douglas-Kroll-Hess Hamiltonian. Basis sets of at least valence-triple-zeta quality will be applied. The main goal of the study is to gain more insight in mechanistic details of medical applications of lanthanide(III) texaphyrin complexes as well as to clarify if corresponding actinide(III) systems exist and if they might play a role for the separation of lanthanides from actinides, e.g., during the clean-up of nuclear waste.Lanthanide(III) texaphyrin complexes, especially those of Gd and Lu, are investigated as experimental drugs in clinical trials, e.g., as tumor-selective catalysts in X-ray radiation therapy and photosensitizers for photodynamic therapy for oncology. The planned calculations will determine their structures and stabilities, as well as important properties for their medical applications such as their absorption spectra in the wavelength region of the human body's so-called therapeutic window (for the radiation reaching the desired target in the body), singlet-triplet splittings (for direct activation molecular oxygen) and redox potentials (for participating in the generation of reactive oxygen species). The role of the central metal, the side chains as well as the size of the pi-electron system for a favorable tuning of these properties will be investigated. The mechanism of the generation of reactive oxygen species, starting from oxygen and/or water, catalyzed by lanthanide(III) texaphyrin complexes will be calculated. The role of ascorbate and other derivatives of L-ascorbic acid (vitamin C) in these reactions will be studied. For comparison the oxidation of ascorbate without presence of a lanthanide(III) texaphyrin complex as a catalyst will be investigated.Actinide(III) texaphyrin complexes are so far unknown experimentally, most likely due to the difficulties arising form their radioactivity of the actinides. Their structures and stabilities will be investigated and their possible usefulness in lanthanide(III)-actinide(III) separation processes will be addressed. The experimentally known actinyl texaphyrin complexes will also be considered.

• DFG Programme: Research Grants