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How to obtain Pt(IV) complexes suitable for the conjugation to nanovectors from the oxidation of [PtCl(terpyridine)]+

Gabano, Elisabetta, Perin, Elena, Fielden, Catherine, Platts, James Alexis, Gallina, Andrea, Rangone, Beatrice and Ravera, Mauro 2017. How to obtain Pt(IV) complexes suitable for the conjugation to nanovectors from the oxidation of [PtCl(terpyridine)]+. Dalton Transactions 46 (31) , pp. 10246-10254. 10.1039/C7DT01706E

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Abstract

Oxidation of [Pt(II)Cl(terpy)]+ (terpy = 2,2’:6’,2”-terpyridine) has been attempted with several oxidizing agents and in different experimental conditions in order to obtain a Pt(IV) complex suitable for the conjugation to nanovectors to be used in drug delivery targeting for anticancer therapy. The best compromise in terms of yield and purity of the final complex was obtained by microwave-assisted reaction at 70 °C in 50% aqueous H2O2 for 2 h. Under these conditions the quantitative formation of [Pt(IV)Cl(OH)2(terpy)]+ was observed. Subsequent synthetic steps were i) functionalization of [Pt(IV)Cl(OH)2(terpy)]+ in the axial position with succinic anhydride to obtain [Pt(IV)Cl(OH)(succinato)(terpy)]+, and ii) reaction of the latter with nonporous silica nanoparticles (SNPs) with an external shell containing primary amino groups to obtain a nanovector able to transport the Pt(IV) antitumor prodrug in form of conjugate Pt-SNP. Finally, the antiproliferative activity and cell accumulation of [Pt(II)Cl(terpy)]+, [Pt(IV)Cl(OH)2(terpy)]+, and Pt-SNP conjugate were measured on three cancer cell lines. Despite highly effective accumulation of Pt-SNP into cells, a modest increase in activity was observed with respect to the molecular species. Further experiments showed that the Pt-SNP conjugate can release [Pt(II)Cl(terpy)]+ upon reduction, but this metabolite may undergo hydrolysis, and the resulting aquo complex could coordinate once again the free amino groups of the SNPs. In the resulting tetraamine form, the Pt(II) complex conjugated to the SNPs cannot completely exert its antiproliferative activity.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Advanced Research Computing @ Cardiff (ARCCA)
Chemistry
Subjects: Q Science > QD Chemistry
Publisher: Royal Society of Chemistry
ISSN: 1477-9226
Date of First Compliant Deposit: 18 July 2017
Date of Acceptance: 11 July 2017
Last Modified: 12 Jul 2018 17:11
URI: http://orca-mwe.cf.ac.uk/id/eprint/102552

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