5457-29-4Relevant articles and documents
Synthesis and Biological Studies of Pyrazolyl-Diamine PtII Complexes Containing Polyaromatic DNA-Binding Groups
Gama, Sofia,Mendes, Filipa,Esteves, Teresa,Marques, Fernanda,Matos, Antonio,Rino, Jose,Coimbra, Joana,Ravera, Mauro,Gabano, Elisabetta,Santos, Isabel,Paulo, Antonio
, p. 2352 - 2362 (2012)
New [PtCl(pzNN)]n+ complexes anchored by pyrazolyl-diamine (pzNN) ligands incorporating anthracenyl or acridine orange DNA-binding groups have been synthesized so as to obtain compounds that would display synergistic effects between platination and intercalation of DNA. Study of their interaction with supercoiled DNA indicated that the anthracenyl-containing complex L2Pt displays a covalent type of binding, whereas the acridine orange counterpart L3Pt shows a combination of intercalative and covalent binding modes with a strong contribution from the former. L2Pt showed a very strong cytotoxic effect on ovarian carcinoma cell lines A2780 and A2780cisR, which are, respectively, sensitive to and resistant to cisplatin. In these cell lines, L2Pt is nine to 27 times more cytotoxic than cisplatin. In the sensitive cell line, L3Pt showed a cytotoxic activity similar to that of cisplatin, but like L2Pt was able significantly to overcome cisplatin cross-resistance. Cell-uptake studies showed that L2Pt accumulates preferentially in the cytoplasm, whereas L3Pt reaches the cell nucleus more easily, as clearly visualized by time-lapse confocal imaging of live A2870 cells. Altogether, these findings seem to indicate that interaction with biological targets other than DNA might be involved in the mechanism of action of L2Pt because this compound, despite having a weaker ability to target the cell nucleus than L3Pt, as well as an inferior DNA affinity, is nevertheless more cytotoxic. Furthermore, ultrastructural studies of A2870 cells exposed to L2Pt and L3Pt revealed that these complexes induce different alterations in cell morphology, thus indicating the involvement of different modes of action in cell death.
Isolable Pyridinium Trifluoromethoxide Salt for Nucleophilic Trifluoromethoxylation
Duran-Camacho, Geraldo,Ferguson, Devin M.,Kampf, Jeff W.,Bland, Douglas C.,Sanford, Melanie S.
supporting information, p. 5138 - 5142 (2021/07/19)
An isolable pyridinium trifluoromethoxide salt is prepared from the reaction of 4-dimethylaminopyridine with the commercially available liquid 2,4-dinitro(trifluoromethoxy)benzene. The salt is an effective trifluoromethoxide source for SN2 reactions to form trifluoromethyl ethers.
Copper-Catalyzed Difluoromethylation of Alkyl Iodides Enabled by Aryl Radical Activation of Carbon–Iodine Bonds
Cai, Aijie,Liu, Wei,Wang, Chao,Yan, Wenhao
supporting information, p. 27070 - 27077 (2021/11/18)
The engagement of unactivated alkyl halides in copper-catalyzed cross-coupling reactions has been historically challenging, due to their low reduction potential and the slow oxidative addition of copper(I) catalysts. In this work, we report a novel strategy that leverages the halogen abstraction ability of aryl radicals, thereby engaging a diverse range of alkyl iodides in copper-catalyzed Negishi-type cross-coupling reactions at room temperature. Specifically, aryl radicals generated via copper catalysis efficiently initiate the cleavage of the carbon–iodide bonds of alkyl iodides. The alkyl radicals thus generated enter the copper catalytic cycles to couple with a difluoromethyl zinc reagent, thus furnishing the alkyl difluoromethane products. This unprecedented Negishi-type difluoromethylation approach has been applied to the late-stage modification of densely functionalized pharmaceutical agents and natural products.
