Catalytically Generated Ferrocene-Containing Guanidines as Efficient Precursors for New Redox-Active Heterometallic Platinum(II) Complexes with Anticancer Activity
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- 作者：Daniel Nieto ; Sonia Bru帽a ; Ana Ma Gonz谩lez-Vadillo ; Josefina Perles ; Fernando Carrillo-Hermosilla ; Antonio Anti帽olo ; Jos茅 M. Padr贸n ; Gabriela B. Plata ; Isabel Cuadrado
- 刊名：Organometallics
- 出版年：2015
- 出版时间：November 23, 2015
- 年：2015
- 卷：34
- 期：22
- 页码：5407-5417
- 全文大小：559K
- ISSN：1520-6041
文摘
The potential of structurally new ferrocene-functionalized guanidines as redox-active precursors for the synthesis of heterometallic platinum(II)鈥揼uanidine complexes with anticancer activity was studied. To this end, an atom-economical catalytic approach was followed by using ZnEt2 to catalyze the addition of aminoferrocene and 4-ferrocenylaniline to N,N鈥?diisopropylcarbodiimide. Furthermore, reaction of a platinum(II) source with the newly obtained guanidines Fc鈥揘鈺怌(NHiPr)2 (3) and Fc(1,4-C6H4)鈥揘鈺怌(NHiPr)2 (4) provided access to the heterometallic complexes [PtCl2{Fc鈥揘鈺怌(NHiPr)2}(DMSO)] (5), [PtCl2{Fc(1,4-C6H4)鈥揘鈺怌(NHiPr)2}(DMSO)] (6), and [PtCl2{Fc(1,4-C6H4)鈥揘鈺怌(NHiPr)2}2] (7). Electrochemical studies evidence the remarkable electronic effect played by the direct attachment of the guanidine group to the ferrocene moiety in 3, making its one-electron oxidation extremely easy. Guanidine-based Fe鈥揚t complexes 5 and 6 are active against all human cancer cell lines tested, with GI50 values in the range 1.4鈥?.6 渭M, and are more cytotoxic than cisplatin in the resistant T-47D and WiDr cell lines.