Chemistry Research Laboratory, University of Oxford, Mansfield Road, OX1 3TA, UK.
Department of Earth Sciences, University of Oxford, OX1 3AN, UK.
Dalton Trans. 2021 Jun 29;50(25):8761-8767. doi: 10.1039/d1dt01688a.
Platinum compounds are a vital part of our anti-cancer arsenal, and determining the location and speciation of platinum compounds is crucial. We have synthesised a lanthanide complex bearing a salicylic group (Ln = Gd, Eu) which demonstrates excellent cellular accumulation and minimal cytotoxicity. Derivatisation enabled access to bimetallic lanthanide-platinum(ii) and lanthanide-platinum(iv) complexes. Luminescence from the europium-platinum(iv) system was quenched, and reduction to platinum(ii) with ascorbic acid resulted in a "switch-on" luminescence enhancement. We used diffusion-based 1H NMR spectroscopic methods to quantify cellular accumulation. The gadolinium-platinum(ii) and gadolinium-platinum(iv) complexes demonstrated appreciable cytotoxicity. A longer delay following incubation before cytotoxicity was observed for the gadolinium-platinum(iv) compared to the gadolinium-platinum(ii) complex. Functionalisation with octanoate ligands resulted in enhanced cellular accumulation and an even greater latency in cytotoxicity.
铂化合物是我们抗癌武器库中的重要组成部分，确定铂化合物的位置和形态至关重要。我们合成了一种含有水杨酸基团的镧系元素配合物（Ln = Gd，Eu），该配合物具有出色的细胞积累能力和最小的细胞毒性。衍生化使我们能够获得双金属镧系元素-铂（ii）和镧系元素-铂（iv）配合物。铕-铂（iv）体系的发光被猝灭，用抗坏血酸还原为铂（ii）导致“开启”发光增强。我们使用基于扩散的 1H NMR 光谱方法来定量细胞积累。镓-铂（ii）和镓-铂（iv）配合物表现出相当大的细胞毒性。与镓-铂（ii）配合物相比，观察到镓-铂（iv）配合物在孵育后出现更长的延迟才表现出细胞毒性。用辛酸酯配体进行功能化可提高细胞积累，并使细胞毒性的潜伏期更长。
