Bis(azol-1-yl)carboxylic acids are convenient starting materials for the synthesis of neutral heteroscorpionate systems based on bis(azol-1-yl)methane linked by acetate, acetamide or thioacetamide moieties. Recently, we have focused the research work on the development of two bis(pyrazol-1-yl)acetates, [HC(COOH)(pz)2] (LH) and [HC(COOH)(pzMe2)2] (L2H) and the related analogues esterified with several alcohols such as methanol, ethanol, isopropanol and hexanol. All ligands have been used to obtain the copper(II) complexes starting from Cu(II) acceptors and to synthesize the related Cu(I) complexes by reaction of Cu(CH3CN)4PF6 and 1,3,5-triaza-7-phosphaadamantane (PTA), tris(hydroxymethyl)phosphine (thp) and triphenylphosphine (PPh3) with LH and L2H ligands in acetonitrile solution. In addition, based on the observation that copper nitroimidazole conjugates have recently shown additive or synergistic selectivity for tumor hypoxia compared to their individual components,1 Cu(I) and Cu(II) complexes of 5-nitroimidazole conjugated heteroscorpionate ligands have been prepared. The new ligands LMN and L2MN have been synthesized by direct coupling of preformed side chain acids LH and L2H with 5-nitroimidazole and their coordination chemistry has been investigated towards Cu(I/II) acceptors.2 Finally, LH and L2H have been bioconjugated with the NMDA receptor antagonist (±)-(6,6-diphenyl-1,4-dioxan-2-yl)methanamine and the resulting ligands have been used to synthesize the related copper derivatives, potentially acting through synergistic mechanisms of action due to the presence of the NMDA ligand and copper in the same chemical entity.3 Several new copper complexes as well as the corresponding uncoordinated ligands were evaluated for their cytotoxic activity against 2D monolayer cultures of multiple human cancer cell lines and the most promising derivatives also against 3D-cultured HCT-15 colon cancer spheroids. The investigation of their catalytic activity in the radical allylic oxidation of olefins, using the Kharasch-Sosnovsky reaction, is also in progress.

Design, synthesis, reactivity, biological and catalytic applications of functionalized bis(pyrazolyl)acetate copper complexes

L. Bagnarelli;LUCIANI, LORENZO;F. Del Bello;W. Quaglia;C. Cimarelli;S. Gabrielli;C. Santini;M. Pellei
2018

Abstract

Bis(azol-1-yl)carboxylic acids are convenient starting materials for the synthesis of neutral heteroscorpionate systems based on bis(azol-1-yl)methane linked by acetate, acetamide or thioacetamide moieties. Recently, we have focused the research work on the development of two bis(pyrazol-1-yl)acetates, [HC(COOH)(pz)2] (LH) and [HC(COOH)(pzMe2)2] (L2H) and the related analogues esterified with several alcohols such as methanol, ethanol, isopropanol and hexanol. All ligands have been used to obtain the copper(II) complexes starting from Cu(II) acceptors and to synthesize the related Cu(I) complexes by reaction of Cu(CH3CN)4PF6 and 1,3,5-triaza-7-phosphaadamantane (PTA), tris(hydroxymethyl)phosphine (thp) and triphenylphosphine (PPh3) with LH and L2H ligands in acetonitrile solution. In addition, based on the observation that copper nitroimidazole conjugates have recently shown additive or synergistic selectivity for tumor hypoxia compared to their individual components,1 Cu(I) and Cu(II) complexes of 5-nitroimidazole conjugated heteroscorpionate ligands have been prepared. The new ligands LMN and L2MN have been synthesized by direct coupling of preformed side chain acids LH and L2H with 5-nitroimidazole and their coordination chemistry has been investigated towards Cu(I/II) acceptors.2 Finally, LH and L2H have been bioconjugated with the NMDA receptor antagonist (±)-(6,6-diphenyl-1,4-dioxan-2-yl)methanamine and the resulting ligands have been used to synthesize the related copper derivatives, potentially acting through synergistic mechanisms of action due to the presence of the NMDA ligand and copper in the same chemical entity.3 Several new copper complexes as well as the corresponding uncoordinated ligands were evaluated for their cytotoxic activity against 2D monolayer cultures of multiple human cancer cell lines and the most promising derivatives also against 3D-cultured HCT-15 colon cancer spheroids. The investigation of their catalytic activity in the radical allylic oxidation of olefins, using the Kharasch-Sosnovsky reaction, is also in progress.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11581/424129
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