Synthesis, characterisation and in-vitro cytotoxicity of mixed ligand Pt(II) oxadiazoline complexes with hexamethylenetetramine and 7-nitro-1,3,5-triazaadamantane.

Hdl Handle:
http://hdl.handle.net/10034/620651
Title:
Synthesis, characterisation and in-vitro cytotoxicity of mixed ligand Pt(II) oxadiazoline complexes with hexamethylenetetramine and 7-nitro-1,3,5-triazaadamantane.
Authors:
Sieste, Stefanie; Lifincev, Irina; Stein, Nina; Wagner, Gabriele
Abstract:
Trans-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.
Affiliation:
University of Ulm (Germany); University of Chester (UK)
Citation:
Sieste, 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/C7DT02406A
Publisher:
Royal Society of Chemistry
Journal:
Dalton Transactions
Publication Date:
21-Aug-2017
URI:
http://hdl.handle.net/10034/620651
DOI:
10.1039/C7DT02406A
Additional Links:
http://pubs.rsc.org/en/content/articlepdf/2014/DT/C7DT02406A?page=search
Type:
Article
Language:
en
EISSN:
1477-9234
Appears in Collections:
Natural Sciences

Full metadata record

DC FieldValue Language
dc.contributor.authorSieste, Stefanieen
dc.contributor.authorLifincev, Irinaen
dc.contributor.authorStein, Ninaen
dc.contributor.authorWagner, Gabrieleen
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.en
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 Transactionsen
dc.date.accepted2017-08-19-
or.grant.openaccessYesen
rioxxterms.funderUniversity of Ulmen
rioxxterms.identifier.projectUnfundeden
rioxxterms.versionAMen
rioxxterms.licenseref.startdate2018-08-21-
This item is licensed under a Creative Commons License
Creative Commons
All Items in ChesterRep are protected by copyright, with all rights reserved, unless otherwise indicated.