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Issue 43, 2007
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Modifications of boronic ester pro-chelators triggered by hydrogen peroxide tune reactivity to inhibit metal-promoted oxidative stress

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Abstract

Several new analogs of salicylaldehyde isonicotinoyl hydrazone (SIH) and salicylaldehyde benzoyl hydrazone (SBH) that contain an aryl boronic ester (BSIH, BSBH) or acid (BASIH) in place of an aryl hydroxide have been synthesized and characterized as masked metal ion chelators. These pro-chelators show negligible interaction with iron(III), although the boronic acid versions exhibit some interaction with copper(II), zinc(II) and nickel(II). Hydrogen peroxide oxidizes the aryl boronate to phenol, thus converting the pro-chelators to tridentate ligands with high affinity metal binding properties. An X-ray crystal structure of a bis-ligated iron(III) complex, [Fe(SBH(m-OMe)3)2]NO3, confirms the meridonal binding mode of these ligands. Modifications of the aroyl ring of the chelators tune their iron affinity, whereas modifications on the boron-containing ring of the pro-chelators attenuate their reaction rates with hydrogen peroxide. Thus, the methoxy derivative pro-chelator (p-OMe)BASIH reacts with hydrogen peroxide nearly 5 times faster than the chloro derivative (m-Cl)BASIH. Both the rate of pro-chelator to chelator conversion as well as the metal binding affinity of the chelator influence the overall ability of these molecules to inhibit hydroxyl radical formation catalyzed by iron or copper in the presence of hydrogen peroxide and ascorbic acid. This pro-chelator strategy has the potential to improve the efficacy of medicinal chelators for inhibiting metal-promoted oxidative stress.

Graphical abstract: Modifications of boronic ester pro-chelators triggered by hydrogen peroxide tune reactivity to inhibit metal-promoted oxidative stress

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Publication details

The article was received on 05 Apr 2007, accepted on 19 Jun 2007 and first published on 19 Sep 2007


Article type: Paper
DOI: 10.1039/B705199A
Citation: Dalton Trans., 2007,0, 5031-5042

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    Modifications of boronic ester pro-chelators triggered by hydrogen peroxide tune reactivity to inhibit metal-promoted oxidative stress

    L. K. Charkoudian, D. M. Pham, A. M. Kwon, A. D. Vangeloff and K. J. Franz, Dalton Trans., 2007, 0, 5031
    DOI: 10.1039/B705199A

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