Anticancer Activity and Cisplatin Binding Ability of Bis-Quinoline and Bis-Isoquinoline Derived [Pd2L4]4+ Metallosupramolecular Cages
New bis-quinoline (Lq) and bis-isoquinoline-based (Liq) ligands have been synthesized, along with their respective homoleptic [Pd2(Lq or Liq)4]4+ cages (Cq and Ciq). The ligands and cages were characterized by 1H, 13C and diffusion ordered (DOSY) NMR spectroscopies, high resolution electrospray ioni...
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Frontiers Media S.A.
2018-11-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fchem.2018.00563/full |
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| author | Roan A. S. Vasdev Roan A. S. Vasdev Roan A. S. Vasdev Lachlan F. Gaudin Dan Preston Jackmil P. Jogy Gregory I. Giles James D. Crowley James D. Crowley |
| author_facet | Roan A. S. Vasdev Roan A. S. Vasdev Roan A. S. Vasdev Lachlan F. Gaudin Dan Preston Jackmil P. Jogy Gregory I. Giles James D. Crowley James D. Crowley |
| author_sort | Roan A. S. Vasdev |
| collection | DOAJ |
| description | New bis-quinoline (Lq) and bis-isoquinoline-based (Liq) ligands have been synthesized, along with their respective homoleptic [Pd2(Lq or Liq)4]4+ cages (Cq and Ciq). The ligands and cages were characterized by 1H, 13C and diffusion ordered (DOSY) NMR spectroscopies, high resolution electrospray ionization mass spectrometry (HR-ESIMS) and in the case of the bis-quinoline cage, X-ray crystallography. The crystal structure of the Cq architecture showed that the [Pd2(Lq)4]4+ cage formed a twisted meso isomer where the [Pd(quinoline)4]2+ units at either end of the cage architecture adopt the opposite twists (left and right handed). Conversely, Density Functional Theory (DFT) calculations on the Ciq cage architecture indicated that a lantern shaped conformation, similar to what has been observed before for related [Pd2(Ltripy)4]4+ systems (where Ltripy = 2,6-bis(pyridin-3-ylethynyl)pyridine), was generated. The different cage conformations manifest different properties for the isomeric cages. The Ciq cage is able to bind, weakly in acetonitrile, the anticancer drug cisplatin whereas the Cq architecture shows no interaction with the guest under the same conditions. The kinetic robustness of the two cages in the presence of Cl− nucleophiles was also different. The Ciq cage was completely decomposed into free Liq and [Pd(Cl)4]2− within 1 h. However, the Cq cage was more long lived and was only fully decomposed after 7 h. The new ligands (Liq and Lq) and the Pd(II) cage architectures (Ciq and Cq) were assessed for their cytotoxic properties against two cancerous cell lines (A549 lung cancer and MDA-MB-231 breast cancer) and one non-cancerous cell line (HDFa skin cells). It was found that Lq and Cq were both reasonably cytotoxic (IC50S ≈ 0.5 μM) against A549, while Ciq was slightly less active (IC50 = 7.4 μM). Liq was not soluble enough to allow the IC50 to be determined against either of the two cancerous cell lines. However, none of the molecules showed any selectivity for the cancer cells, as they were all found to have similar cytotoxicities against HDFa skin cells (IC50 values ranged from 2.6 to 3.0 μM). |
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| institution | Directory Open Access Journal |
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| last_indexed | 2024-04-12T11:00:15Z |
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| spelling | doaj.art-644e7c7a3137413ca340d352ce4fc7ff2022-12-22T03:35:58ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462018-11-01610.3389/fchem.2018.00563427892Anticancer Activity and Cisplatin Binding Ability of Bis-Quinoline and Bis-Isoquinoline Derived [Pd2L4]4+ Metallosupramolecular CagesRoan A. S. Vasdev0Roan A. S. Vasdev1Roan A. S. Vasdev2Lachlan F. Gaudin3Dan Preston4Jackmil P. Jogy5Gregory I. Giles6James D. Crowley7James D. Crowley8Department of Chemistry, University of Otago, Dunedin, New ZealandMacDiarmid Institute for Advanced Materials and Nanotechnology, Wellington, New ZealandDepartment of Pharmacology and Toxicology, University of Otago, Dunedin, New ZealandDepartment of Chemistry, University of Otago, Dunedin, New ZealandDepartment of Chemistry, University of Otago, Dunedin, New ZealandDepartment of Pharmacology and Toxicology, University of Otago, Dunedin, New ZealandDepartment of Pharmacology and Toxicology, University of Otago, Dunedin, New ZealandDepartment of Chemistry, University of Otago, Dunedin, New ZealandMacDiarmid Institute for Advanced Materials and Nanotechnology, Wellington, New ZealandNew bis-quinoline (Lq) and bis-isoquinoline-based (Liq) ligands have been synthesized, along with their respective homoleptic [Pd2(Lq or Liq)4]4+ cages (Cq and Ciq). The ligands and cages were characterized by 1H, 13C and diffusion ordered (DOSY) NMR spectroscopies, high resolution electrospray ionization mass spectrometry (HR-ESIMS) and in the case of the bis-quinoline cage, X-ray crystallography. The crystal structure of the Cq architecture showed that the [Pd2(Lq)4]4+ cage formed a twisted meso isomer where the [Pd(quinoline)4]2+ units at either end of the cage architecture adopt the opposite twists (left and right handed). Conversely, Density Functional Theory (DFT) calculations on the Ciq cage architecture indicated that a lantern shaped conformation, similar to what has been observed before for related [Pd2(Ltripy)4]4+ systems (where Ltripy = 2,6-bis(pyridin-3-ylethynyl)pyridine), was generated. The different cage conformations manifest different properties for the isomeric cages. The Ciq cage is able to bind, weakly in acetonitrile, the anticancer drug cisplatin whereas the Cq architecture shows no interaction with the guest under the same conditions. The kinetic robustness of the two cages in the presence of Cl− nucleophiles was also different. The Ciq cage was completely decomposed into free Liq and [Pd(Cl)4]2− within 1 h. However, the Cq cage was more long lived and was only fully decomposed after 7 h. The new ligands (Liq and Lq) and the Pd(II) cage architectures (Ciq and Cq) were assessed for their cytotoxic properties against two cancerous cell lines (A549 lung cancer and MDA-MB-231 breast cancer) and one non-cancerous cell line (HDFa skin cells). It was found that Lq and Cq were both reasonably cytotoxic (IC50S ≈ 0.5 μM) against A549, while Ciq was slightly less active (IC50 = 7.4 μM). Liq was not soluble enough to allow the IC50 to be determined against either of the two cancerous cell lines. However, none of the molecules showed any selectivity for the cancer cells, as they were all found to have similar cytotoxicities against HDFa skin cells (IC50 values ranged from 2.6 to 3.0 μM).https://www.frontiersin.org/article/10.3389/fchem.2018.00563/fullpalladium(II)anticancerself-assemblymetallosupramolecularquinoline |
| spellingShingle | Roan A. S. Vasdev Roan A. S. Vasdev Roan A. S. Vasdev Lachlan F. Gaudin Dan Preston Jackmil P. Jogy Gregory I. Giles James D. Crowley James D. Crowley Anticancer Activity and Cisplatin Binding Ability of Bis-Quinoline and Bis-Isoquinoline Derived [Pd2L4]4+ Metallosupramolecular Cages Frontiers in Chemistry palladium(II) anticancer self-assembly metallosupramolecular quinoline |
| title | Anticancer Activity and Cisplatin Binding Ability of Bis-Quinoline and Bis-Isoquinoline Derived [Pd2L4]4+ Metallosupramolecular Cages |
| title_full | Anticancer Activity and Cisplatin Binding Ability of Bis-Quinoline and Bis-Isoquinoline Derived [Pd2L4]4+ Metallosupramolecular Cages |
| title_fullStr | Anticancer Activity and Cisplatin Binding Ability of Bis-Quinoline and Bis-Isoquinoline Derived [Pd2L4]4+ Metallosupramolecular Cages |
| title_full_unstemmed | Anticancer Activity and Cisplatin Binding Ability of Bis-Quinoline and Bis-Isoquinoline Derived [Pd2L4]4+ Metallosupramolecular Cages |
| title_short | Anticancer Activity and Cisplatin Binding Ability of Bis-Quinoline and Bis-Isoquinoline Derived [Pd2L4]4+ Metallosupramolecular Cages |
| title_sort | anticancer activity and cisplatin binding ability of bis quinoline and bis isoquinoline derived pd2l4 4 metallosupramolecular cages |
| topic | palladium(II) anticancer self-assembly metallosupramolecular quinoline |
| url | https://www.frontiersin.org/article/10.3389/fchem.2018.00563/full |
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