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Full-Text Articles in Other Chemistry

Cu(Ii) Phenanthroline-Phenazine Complexes Dysregulate Mitochondrial Function And Stimulate Apoptosis, Garret Rochford, Zara Molphy, Kevin Kavanagh, Malachy Mccann, Michael Devereux, Andrew Kellett, Orla L. Howe Jan 2020

Cu(Ii) Phenanthroline-Phenazine Complexes Dysregulate Mitochondrial Function And Stimulate Apoptosis, Garret Rochford, Zara Molphy, Kevin Kavanagh, Malachy Mccann, Michael Devereux, Andrew Kellett, Orla L. Howe

Articles

Herein we report an in-depth study on the cytotoxic mechanism of action of four developmental cytotoxic copper(II) complexes: [Cu(phen)2]2+ (Cu-Phen); [Cu(DPQ)(Phen)]2+ (Cu-DPQ-Phen); [Cu(DPPZ)(Phen)]2+; and [Cu(DPPN)(Phen)]2+ (where Phen = 1,10-phenanthroline, DPQ = dipyrido[3,2-f:20,30-h]quinoxaline, DPPZ = dipyrido[3,2-a:20,30-c]phenazine, and DPPN = benzo[i]dipyrido[3,2-a:20,30-c]phenazine). This complex class is known for its DNA intercalative properties and recent evidence—derived from an in vivo proteomic study—supports the potential targeting of mitochondrial function. Therefore, we focused on mitochondrial-mediated apoptosis related to cytotoxic activity and the potential impact these agents have on mitochondrial function. The Cu(II) complexes demonstrated superior activity regardless of aromatic extension within the phenazine ligand to the …


Highly Selective Fluorimetric Turn-Off Detection Of Copper (Ii) By Two Different Mechanisms In Calix[4]Arene-Based Chemosensors And Chemodosimeters, Justine O'Sullivan, John Colleran, Brendan Twamley, Frances Heaney Jan 2019

Highly Selective Fluorimetric Turn-Off Detection Of Copper (Ii) By Two Different Mechanisms In Calix[4]Arene-Based Chemosensors And Chemodosimeters, Justine O'Sullivan, John Colleran, Brendan Twamley, Frances Heaney

Articles

Isoxazolo‐pyrene tethered calix[4]arenes selectively detect copper(II) ions without interference from related perchlorate ions. The fluorescence emission of the probes, synthesised by nitrile oxide alkyne cycloaddition, and characterised by spectroscopic and crystallographic data, is rapidly reduced by Cu(II) ions. Detection limits are in the micromolar or sub‐micromolar range (0.3–3.6 μM) based on a 1 : 1 sensor:analyte interaction. Voltammetric behaviour and 1H NMR data provide new insights into the sensing mechanism which is dependent on the calixarene substitution pattern. When the calixarene lower rim is fully substituted, Cu(II) detection occurs through a traditional chelation mechanism. In contrast, for calixarenes 1,3‐disubstituted on …


3-Hydroxykynurenine And 3-Hydroxyanthranilic Acid Generate Hydrogen Peroxide And Promote Α-Crystallin Cross Linking By Metal Ion Reduction, Lee E. Goldstein, Michael C. Leopold, Xudong Huang, Craig S. Atwood, Aleister J. Saunders, Mariana Hartshorn, James T. Lim, Et Al. Jan 2000

3-Hydroxykynurenine And 3-Hydroxyanthranilic Acid Generate Hydrogen Peroxide And Promote Α-Crystallin Cross Linking By Metal Ion Reduction, Lee E. Goldstein, Michael C. Leopold, Xudong Huang, Craig S. Atwood, Aleister J. Saunders, Mariana Hartshorn, James T. Lim, Et Al.

Chemistry Faculty Publications

The kynurenine pathway catabolite 3-hydroxykynurenine (3HK) and redox-active metals such as copper and iron are implicated in cataractogenesis. Here we investigate the reaction of kynurenine pathway catabolites with copper and iron, as well as interactions with the major lenticular structural proteins, the R-crystallins. The o-aminophenol kynurenine catabolites 3HK and 3-hydroxyanthranilic acid (3HAA) reduced Cu(II)>Fe(III) to Cu(I) and Fe(II), respectively, whereas quinolinic acid and the nonphenolic kynurenine catabolites kynurenine and anthranilic acid did not reduce either metal. Both 3HK and 3HAA generated superoxide and hydrogen peroxide in a copper-dependent manner. In addition, 3HK and 3HAA fostered copper-dependent R-crystallin cross-linking. 3HK- …


Cu(Ii) Potentiation Of Alzheimer A Neurotoxicity, Xudong Huang, Math P. Cuajungco, Craig S. Atwood, Mariana A. Hartshorn, Joel D. A. Tyndall, Graeme R. Hanson, Karen C. Stokes, Michael C. Leopold, Et Al. Dec 1999

Cu(Ii) Potentiation Of Alzheimer A Neurotoxicity, Xudong Huang, Math P. Cuajungco, Craig S. Atwood, Mariana A. Hartshorn, Joel D. A. Tyndall, Graeme R. Hanson, Karen C. Stokes, Michael C. Leopold, Et Al.

Chemistry Faculty Publications

Oxidative stress markers as well as high concentrations of copper are found in the vicinity of Aβ amyloid deposits in Alzheimer's disease. The neurotoxicity of Aβ in cell culture has been linked to H2O2generation by an unknown mechanism. We now report that Cu(II) markedly potentiates the neurotoxicity exhibited by Aβ in cell culture. The potentiation of toxicity is greatest for Aβ1–42 > Aβ1–40 ≫ mouse/rat Aβ1–40, corresponding to their relative capacities to reduce Cu(II) to Cu(I), form H2O2 in cell-free assays and to exhibit amyloid pathology. The copper complex of Aβ1–42 has a highly positive formal reduction potential (≈+500–550 mV versus …