331943-39-6Relevant articles and documents
Electrocatalytic H2 Evolution of Bis(3,5-di-methylpyrazol-1-yl)acetate Anchored Hexa-coordinated Co(II) Derivative
Das, Kuheli,Beyene, Belete B.,Datta, Amitabha,Garribba, Eugenio,Hung, Chen-Hsiung
, p. 2703 - 2708 (2018)
A mononuclear Co(II) derivative, (1) is afforded by employing a ‘scorpionate’ type precursor, bdtbpza [bdtbpza = bis(3,5-di-t-butylpyrazol-1-yl)acetate]. Single crystal X-ray structure reveals that the CoII ion exhibits an octahedral geometry possessing on a O6 coordination environment. Detailed EPR interpretation and electrocatalytic hydrogen evolution study are reported. Electrochemical and catalytic study of 1 in DMSO with the presence of acetic acid as weak proton source shows an observed rate constant of 3.7 × 103?s?1 and hydrogen evolution Faradaic efficiency of 74.7%. The catalytic process requires two-electron reduction of the catalyst and formation of a cobalt(II)-hydride species as reactive intermediate.
Copper binding agents acting as copper ionophores lead to caspase inhibition and paraptotic cell death in human cancer cells
Tardito, Saverio,Bassanetti, Irene,Bignardi, Chiara,Elviri, Lisa,Tegoni, Matteo,Mucchino, Claudio,Bussolati, Ovidio,Franchi-Gazzola, Renata,Marchio, Luciano
supporting information; experimental part, p. 6235 - 6242 (2011/05/30)
We report a quantitative structure-activity relationship study of a new class of pyrazole-pyridine copper complexes that establishes a clear correlation between the ability to promote copper accumulation and cytotoxicity. Intracellular metal accumulation is maximized when ligand lipophilicity allows the complex to rapidly cross the membrane. Copper and ligand follow different uptake kinetics and reach different intracellular equilibrium concentrations. These results support a model in which the ligand acts as an ionophore for the metal ion, cycling between intra- and extracellular compartments as dissociated or complexed entities. When treating cancer cells with structurally unrelated disulfiram and pyrazole-pyridine copper complexes, as well as with inorganic copper, the same morphological and molecular changes were reproduced, indicating that copper overload is responsible for the cytotoxic effects. Copper-based treatments drive sensitive cancer cells toward paraptotic cell death, a process hallmarked by endoplasmic reticulum stress and massive vacuolization in the absence of apoptotic features. A lack of caspase activation, as observed in copper-treated dying cells, is a consequence of metal-mediated inhibition of caspase-3. Thus, copper acts simultaneously as an endoplasmic reticulum (ER) stress inducer and a caspase-3 inhibitor, forcing the cell into caspase-independent paraptotic death. The establishment of a mechanism of action common to different copper binding agents provides a rationale for the exploitation of copper toxicity as an anticancer tool.
Alkylzinc complexes with achiral and chiral monoanionic N,N,O heteroscorpionate ligands
Hegelmann, Ina,Beck, Alexander,Eichhorn, Christian,Weibert, Bernhard,Burzlaff, Nicolai
, p. 339 - 347 (2007/10/03)
The synthesis of the new chiral ligand (3,5-di-tertbutylpyrazol-1-yl) (3′,5′-dimethylpyrazol-1-yl) acetic acid (bpaHtBu2,Me2) (4) has been achieved. Two different synthetic routes to its precursor 3,5-di-tert-butyl-1-[(3,5-dimethyl-1H-pyrazol-1-yl)methyl]-1H-pyrazole (bpmtBu2,Me2) (3) are reported. Deprotonation at the methylene group, followed by reaction with carbon dioxide, yielded a racemic mixture of 4. The chemical behaviour of bis(3,5-di-tert-butylpyrazol-1-yl)acetic acid (bdtbpzaH) (2) and the new chiral N,N,O scorpionate ligand 4 involving their coordination to zinc ions was studied. [Zn(bpatBu2,Me2)Cl] (5) was formed from a mixture of ZnCl2, 4 and base. Reaction of bis(3,5-di-tert-butylpyrazol-1-yl)acetic acid (bdtbpzaH) (2) with Zn(CH3)2 or Zn(CH2CH3)2 gave the alkylzinc complexes Zn(bdtbpza)(CH3)] (6) and [Zn(bdtbpza)(CH2CH3)] (7). [Zn(bpatBu2,Me2)(CH3)] (8) was obtained from a synthesis analogous to that of 6 with 4. The further reactions of 6 and 8 with acetic acid resulted in the acetato complexes [Zn(OAc)(bdtbpza)] (9) and [Zn(OAc)(bpatBu2,Me2)] (10). The chiral methyl complex 8 may serve as a precursor for structural model complexes of the active sites of zinc enzymes, such as thermolysin or carboxypeptidase A. [Zn(bpatBu2,Me2)2] (11) was formed from a side reaction. Crystal structures of 4, 5, 8 and 11 were obtained; 5 crystallised as the dimer [Zn(bpatBu2,Me2) Cl]2; 11 presents an unusual zinc binding geometry. Wiley-VCH Verlag GmbH & Co KGaA, 69451 Weinheim, Germany, 2003.
