Evaluation of Iron(III)-N(amine)₂N(py)₂ complexes as potential bioreductively activated carriers for naphthoquinone-based drugs

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• 作者：Aline Farias Moreira da Silva^a ; Carlos Basí ; lio Pinheiro^b ; Jackson Antô ; nio Lamounier Camargos Resende^a ; ¹ ; Mauricio Lanznaster^a ; ^ml@id.uff.br ; ^{mlanznaster@gmail.com}
• 关键词：Bioreductively activated prodrugs ; Prodrugs activated by hypoxia ; Bioreducible carrier ; PDAH ; Iron(III)
• 刊名：Polyhedron
• 出版年：2017
• 出版时间：17 February 2017
• 年：2017
• 卷：123
• 期：Complete
• 页码：132-137
• 全文大小：977 K
• 卷排序：123

文摘

Two new iron(III) complexes, [Fe(bhnq)(L1)]NO3·CH3OH·2H2O (1) and [Fe(bhnq)(L2)]ClO4·CH3OH (2) (L1 = N,N′-bis(pyridin-2-ylmethyl)ethylenediamine and L2 = N,N′-dimethyl-N,N′-bis(pyridin-2-ylmethyl)ethylenediamine), were investigated as potential candidates for bioreductively activated prodrugs. These complexes present a distorted octahedral structure with 2,2′-bis(3-hydroxy-1,4-naphthoquinone), (bhnq)2−, coordinated in a bidentate fashion to the iron(III) ion. A reversible wave associated with the Fe3+/Fe2+couple was observed in MeCN for 1 and 2 respectively at −0.05 V and 0.01 V versus SHE. Unlike previously studied cobalt(III)-based analogs and one iron(III) platform that showed efficient bioreductive activation, complexes 1 and 2 undergo fast dissociation in aqueous buffered solutions with immediate release of the bhnq2− ligand. Therefore, we conclude that the labile 3d5 iron(III) ion is a limited bioreducible carrier for naphthoquinone-based prodrugs when coordinated to this [N2NPy2] platform. Considerable modification of the current ligands or the meticulous selection of other alternative ligand platforms may be necessary to attain this goal.