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空间位阻、配体逐出及相关顺铂(II)多吡啶配合物的光细胞毒性性质。

Steric hindrance, ligand ejection and associated photocytotoxic properties of ruthenium(II) polypyridyl complexes.

机构信息

Departament de Química Inorgànica i Orgànica, Facultat de Química, Secció de Química Inorgànica, Universitat de Barcelona, Martí i Franquès, 1-11, 08028, Barcelona, Spain.

Institute of Nanoscience and Nanotechnology (IN2UB), Universitat de Barcelona, Barcelona, Spain.

出版信息

J Biol Inorg Chem. 2023 Jun;28(4):403-420. doi: 10.1007/s00775-023-01998-z. Epub 2023 Apr 15.

DOI:10.1007/s00775-023-01998-z
PMID:37059909
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10149480/
Abstract

Two ruthenium(II) polypyridyl complexes were prepared with the {Ru(phen)} moiety and a third sterically non-hindering bidentate ligand, namely 2,2'-dipyridylamine (dpa) and N-benzyl-2,2'-dipyridylamine (Bndpa). Hence, complexes Ru(phen)(dpa) (1) and Ru(phen)(Bndpa) (2) were characterized and their photochemical behaviour in solution (acetonitrile and water) was subsequently investigated. Compounds 1 and 2, which do not exhibit notably distorted octahedral coordination environments, contrarily to the homoleptic "parent" compound Ru(phen), experience two-step photoejection of the dpa and Bndpa ligand upon irradiation (1050-430 nm) for several hours. DNA-binding studies revealed that compounds 1 and 2 affect the biomolecule differently upon irradiation; while 2 solely modifies its electrophoretic mobility, complex 1 is also capable of cleaving it. In vitro cytotoxicity studies with two cancer-cell lines, namely A549 (lung adenocarcinoma) and A375 (melanoma), showed that both 1 and 2 are not toxic in the dark, while only 1 is significantly cytotoxic if irradiated, 2 remaining non-toxic under these conditions. Light irradiation of the complex cation [Ru(phen)(dpa)] leads to the generation of transient Ru species that is present in the solution medium for several hours, and that is significantly cytotoxic, ultimately producing non-toxic free dpa and [Ru(phen)(OH)].

摘要

两种钌（II）多吡啶配合物是用{Ru（phen）}部分和第三个空间位阻非阻碍性双齿配体，即 2,2'-联吡啶胺（dpa）和 N-苄基-2,2'-联吡啶胺（Bndpa）制备的。因此，合成了[Ru（phen）（dpa）]（PF）（1）和[Ru（phen）（Bndpa）]（PF）（2），并对其在溶液（乙腈和水）中的光化学行为进行了研究。化合物 1 和 2 不具有明显扭曲的八面体配位环境，与同系物“母体”化合物[Ru（phen）]（PF）相反，在光照（1050-430nm）数小时后经历了 dpa 和 Bndpa 配体的两步光解出。DNA 结合研究表明，化合物 1 和 2 在光照下对生物分子的影响不同；虽然 2 仅改变其电泳迁移率，但复合物 1 也能够切割它。在两个癌细胞系 A549（肺腺癌细胞）和 A375（黑色素瘤）的体外细胞毒性研究中表明，1 和 2 在黑暗中均无毒性，而只有 1 在光照下具有明显的细胞毒性，而 2 在这些条件下仍无毒性。[Ru（phen）（dpa）]配合物阳离子的光照射导致瞬态 Ru 物种的生成，该物种在溶液介质中存在数小时，并且具有显著的细胞毒性，最终产生无毒的游离 dpa 和[Ru（phen）（OH）]。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/310d/10149480/9406d563f556/775_2023_1998_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/310d/10149480/3283f254542a/775_2023_1998_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/310d/10149480/856a79c374a0/775_2023_1998_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/310d/10149480/a7620c1ed533/775_2023_1998_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/310d/10149480/3752f92c831e/775_2023_1998_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/310d/10149480/ca618581851e/775_2023_1998_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/310d/10149480/9406d563f556/775_2023_1998_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/310d/10149480/558b7cc1d6c7/775_2023_1998_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/310d/10149480/9224eea0bae9/775_2023_1998_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/310d/10149480/a4d60c5fe667/775_2023_1998_Sch1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/310d/10149480/3283f254542a/775_2023_1998_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/310d/10149480/856a79c374a0/775_2023_1998_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/310d/10149480/a7620c1ed533/775_2023_1998_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/310d/10149480/3752f92c831e/775_2023_1998_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/310d/10149480/ca618581851e/775_2023_1998_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/310d/10149480/9406d563f556/775_2023_1998_Fig8_HTML.jpg

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