Tunable Arene Ruthenium Metallaprisms to Transport, Shield, and Release Porphin in Cancer Cells

Three neutral dinuclear p-cymene ruthenium complexes
(1a–1c) of the general formula (p-cymene)2Ru2(μ4-L)­Cl2, bridged by substituted hydroxybenzoquinonato spacers (La = 2,5-dihydroxy-3-phenyl-1,4-benzoquinonato; Lb = 2,5-dihydroxy-3,6-diphenyl-1,4-benzoquinonato; Lc =
2,5-dihydroxy-3,6-(3,5-dimethylphenyl)-1,4-benzoquinonato) have been
synthesized and characterized. The corresponding p-cymene ruthenium metallaprisms, [{(p-cymene)2Ru2(μ4-L)}3(tpt)2]­[CF3SO3]6 (2a–2c), were obtained by mixing in methanol the
neutral dinuclear complexes 1a–1c, AgCF3SO3, and 2,4,6-tri­(pyridin-4-yl)-1,3,5-triazine
(tpt). In a similar fashion, addition of porphin during the formation
of the metallaprisms afforded the host–guest systems [porphin⊂{(p-cymene)2­Ru2(μ4-L)}3(tpt)2]­[CF3SO3]6 ([porphin⊂2]­[CF3SO3]6). The biological activity of all complexes was
estimated on the colon cancer cell line HT-29, showing low cytotoxicity
in the dark (IC50 > 5 μM). On the other hand,
the
phototoxicity of the porphin-in-the-cage systems under standard irradiation
conditions (20 J/cm2) is quite spectacular, being in the
lower nanomolar range for [porphin⊂2c]­[CF3SO3]6.

本研究合成并表征了三类通式为(p-伞花烃)₂Ru₂(μ₄-L)Cl₂的中性双核对伞花烃（p-cymene）钌配合物（1a~1c），其桥联间隔基为取代羟基苯醌合配体：Lₐ=2,5-二羟基-3-苯基-1,4-苯醌合配体；Lᵦ=2,5-二羟基-3,6-二苯基-1,4-苯醌合配体；L_c=2,5-二羟基-3,6-(3,5-二甲基苯基)-1,4-苯醌合配体。通过将中性双核配合物1a~1c、三氟甲磺酸银（AgCF₃SO₃）与2,4,6-三(吡啶-4-基)-1,3,5-三嗪（2,4,6-tri(pyridin-4-yl)-1,3,5-triazine, TPT）在甲醇中混合，得到了对应的对伞花烃钌金属棱柱配合物[{(p-cymene)₂Ru₂(μ₄-L)}₃(tpt)₂][CF₃SO₃]₆（2a~2c）。类似地，在金属棱柱的合成过程中加入卟吩（porphin），即可得到主客体体系[porphin⊂{(p-cymene)₂Ru₂(μ₄-L)}₃(tpt)₂][CF₃SO₃]₆（简写为[porphin⊂2][CF₃SO₃]₆）。所有配合物的生物活性均通过结肠癌细胞株HT-29进行评估，结果显示其在黑暗条件下细胞毒性较低（半抑制浓度IC₅₀ > 5 μM）。与之相对，包合卟吩的笼状体系在标准辐照条件（20 J/cm²）下展现出极为优异的光毒性，其中[porphin⊂2c][CF₃SO₃]₆的活性低至纳摩尔级别。