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dc.contributor.authorSieste, Stefanie*
dc.contributor.authorLifincev, Irina*
dc.contributor.authorStein, Nina*
dc.contributor.authorWagner, Gabriele*
dc.date.accessioned2017-10-12T16:02:00Z
dc.date.available2017-10-12T16:02:00Z
dc.date.issued2017-08-21
dc.identifier.citationSieste, S., Lifincev, I., Stein, N., & Wagner, G. (2017). Synthesis, characterisation and in-vitro cytotoxicity of mixed ligand Pt(II) oxadiazoline complexes with hexamethylenetetramine and 7-nitro-1,3,5-triazaadamantane. Dalton Transactions, 46, 12226-12238. DOI: 10.1039/C7DT02406Aen
dc.identifier.doi10.1039/C7DT02406A
dc.identifier.urihttp://hdl.handle.net/10034/620651
dc.description.abstractTrans-platinum(II) oxadiazoline complexes with 7-nitro-1,3,5-triazaadamantane (NO2-TAA) or hexamethylenetetramine (hmta) ligands have been synthesised from trans-[PtCl2(PhCN)2] via cycloaddition of nitrones to one of the coordinated nitriles, followed by exchange of the other nitrile by NO2-TAA or hmta. Stoichiometric control allows for the selective synthesis of mono- and dinuclear complexes where 7-NO2TAA and hmta act as mono- and bidentate ligands, respectively. Precursors and the target complexes trans-[PtCl2(hmta)(oxadiazoline)], trans-[PtCl2(NO2-TAA)(oxadiazoline)] and trans-[{PtCl2(oxadiazoline)}2(hmta)] were characterised by elemental analysis, IR and multinuclear (1H, 13C, 195Pt) NMR spectroscopy. DFT (B3LYP/6-31G*/LANL08) and AIM calculations suggest a stronger bonding of hmta with the [PtCl2(oxadiazoline)] fragment, in agreement with the experimentally observed reactivity in the ligand exchange (hmta > 7-NO2TAA). Replacement of the nitrile by hmta is predicted more exothermic than that with 7-NO2-TAA, although the activation barriers are similar. Protonation of the non-coordinated N atoms is anticipated to weaken the Pt-N bond and lower the activation barrier for ligand exchange. This effect might help activate these compounds in a slightly acidic environment such as some tumour tissues. Ten of the new compounds were tested for their in vitro cytotoxicity in the human cancer cell lines HeLa and A549. Some of the mononuclear complexes are more potent than cisplatin, and their activity is still high in A549 where cisplatin shows little effect. The dinuclear complexes are inactive, presumably due to their lipophilicity and reduced solubility in water.
dc.language.isoenen
dc.publisherRoyal Society of Chemistryen
dc.relation.urlhttp://pubs.rsc.org/en/content/articlepdf/2014/DT/C7DT02406A?page=searchen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectPlatinum complexesen
dc.subjectCancer therapyen
dc.subjectOxadiazolineen
dc.subjectHexamethylenetetramineen
dc.subjectAzaadamantaneen
dc.titleSynthesis, characterisation and in-vitro cytotoxicity of mixed ligand Pt(II) oxadiazoline complexes with hexamethylenetetramine and 7-nitro-1,3,5-triazaadamantane.en
dc.typeArticleen
dc.identifier.eissn1477-9234
dc.contributor.departmentUniversity of Ulm (Germany); University of Chester (UK)en
dc.identifier.journalDalton Transactions
dc.internal.reviewer-noteVersion oken
dc.date.accepted2017-08-19
or.grant.openaccessYesen
rioxxterms.funderUniversity of Ulmen
rioxxterms.identifier.projectUnfundeden
rioxxterms.versionAMen
rioxxterms.licenseref.startdate2018-08-21
refterms.dateFCD2019-07-15T09:55:35Z
refterms.versionFCDAM
html.description.abstractTrans-platinum(II) oxadiazoline complexes with 7-nitro-1,3,5-triazaadamantane (NO2-TAA) or hexamethylenetetramine (hmta) ligands have been synthesised from trans-[PtCl2(PhCN)2] via cycloaddition of nitrones to one of the coordinated nitriles, followed by exchange of the other nitrile by NO2-TAA or hmta. Stoichiometric control allows for the selective synthesis of mono- and dinuclear complexes where 7-NO2TAA and hmta act as mono- and bidentate ligands, respectively. Precursors and the target complexes trans-[PtCl2(hmta)(oxadiazoline)], trans-[PtCl2(NO2-TAA)(oxadiazoline)] and trans-[{PtCl2(oxadiazoline)}2(hmta)] were characterised by elemental analysis, IR and multinuclear (1H, 13C, 195Pt) NMR spectroscopy. DFT (B3LYP/6-31G*/LANL08) and AIM calculations suggest a stronger bonding of hmta with the [PtCl2(oxadiazoline)] fragment, in agreement with the experimentally observed reactivity in the ligand exchange (hmta > 7-NO2TAA). Replacement of the nitrile by hmta is predicted more exothermic than that with 7-NO2-TAA, although the activation barriers are similar. Protonation of the non-coordinated N atoms is anticipated to weaken the Pt-N bond and lower the activation barrier for ligand exchange. This effect might help activate these compounds in a slightly acidic environment such as some tumour tissues. Ten of the new compounds were tested for their in vitro cytotoxicity in the human cancer cell lines HeLa and A549. Some of the mononuclear complexes are more potent than cisplatin, and their activity is still high in A549 where cisplatin shows little effect. The dinuclear complexes are inactive, presumably due to their lipophilicity and reduced solubility in water.


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