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

本文将用量子化学方法研究大环文门罗素配体的稀土(III)和吖系(III)络合物，即用密度泛函和二阶Moeller-Plesset微扰理论进行结构优化，以及在增量方案的框架下用耦合簇单、双和微扰三元组进行单点计算，以标定(相对)能量。用标量相对论4f-In-core和5f-in-core赝势分别处理重稀土元素和Ac元素，并使用二阶Douglas-Kroll-Hess哈密顿量在相对论全电子水平上处理相应的4f和5f-In-价赝势。将应用至少具有价态三重Zeta质量的基组。这项研究的主要目的是为了更深入地了解稀土(III)纹理蛋白络合物在医学上应用的机理细节，并澄清是否存在相应的鳗系元素(III)体系，以及它们是否可能在核废料的清除过程中起到分离稀土元素和吖系元素的作用。稀土元素(III)纹理蛋白络合物，特别是Gd和Lu的络合物，在临床试验中被作为实验药物进行研究，例如作为X射线放射治疗中的肿瘤选择性催化剂和用于肿瘤光动力学治疗的光敏剂。计划中的计算将确定它们的结构和稳定性，以及它们在医学应用中的重要性质，如它们在人体所谓治疗窗口波长区域的吸收光谱(用于辐射到达体内所需的目标)、单重态-三重态分裂(用于直接激活分子氧)和氧化还原电位(用于参与产生活性氧物种)。我们将研究中心金属、侧链以及电子体系的大小对这些性质的有利调节作用。计算了稀土(III)我们将研究抗坏血酸和L的其他衍生物--抗坏血酸(维生素C)在这些反应中的作用。为了进行比较，我们将研究在没有稀土(III)文孔蛋白络合物作为催化剂的情况下抗坏血酸的氧化。目前为止还没有实验上的未知结果，很可能是因为它们的辐系元素的放射性引起的困难。将研究它们的结构和稳定性，并讨论它们在镧系元素(III)-榄系元素(III)分离过程中的可能用途。实验上已知的光化叶面蛋白络合物也将被考虑。

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.