Download binding properties of aroylhydrazones derived from

25th Croatian meeting of chemists and chemical engineers, Poreč, 2017.
Gallium(III) binding properties of aroylhydrazones derived from
nicotinohydrazide
Kompleksacija galija(III) aromatskim hidrazonima izvedenim iz
nikotinohidrazida
Ana
Budimir,1
…
Darko Kontrec,2 Nives Galić3
1
Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovačića 1, Zagreb, Croatia
2
Department of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička 54, Zagreb,
Croatia
3
Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, Zagreb, Croatia
E-mail: [email protected]
…
One strategy that has been explored to evade the bacterial resistance to drugs is to target
the iron metabolism of bacteria, since iron is critical for all bacteria growth. Three major
concepts have been evaluated to exploit limitations in the bacterial iron metabolism:
reducing the availability of free iron with iron-chelating agents; inhibiting iron metabolism in
the infected host, and the “Trojan Horse strategy” which takes advantages of natural ironuptake systems to deliver antimicrobial compounds inside the cells that then kill them [1].
Biological systems have difficulties to differentiate between Fe 3+ and Ga3+ ions due to
their nearly identical ionic radii, same charge, preferred coordination number and chemical
behavior. However, Ga3+ lacks the redox activity of iron (3+/2+ redox chemistry) and the
substitution of Ga3+ into metalloenzymes can result in a loss of enzymatic function, with
cellular toxicity as a result, which has marked Ga3+ the “Trojan Horse” in biological systems.
Recent studies have shown that biologically active salicylidene acylhydrazide is an
excessively strong complexing agent for gallium and that chelation of Ga(III) to the
hydrazone increase the stability of the compounds against acid-induced hydrolysis [2]. In this
study we prepared structurally similar aromatic hydrazones (Scheme) and investigated their
binding properties toward gallium(III) ions. Complexation was monitored in methanol/water
1/1 mixture by spectrophotometric batch titrations at pH = 2.52 due to ligands’ hydrolysis.
References
[1] M. Ballouche, P. Cprnelis, C. Baysse, Recent Patents on Anti-Infective Drug Discovery, Iron
Metabolism: A Promising Target for Antibacterial Strategies 4 (2009) 190–205.
[2] S. Hakobyan, J-F. Boily, M. Ramstedt, Journal of Inorganic Biochemistry, Proton and gallium(III)
binding properties of a biologically active salicylidene acylhydrazide, 138 (2014) 9–15.
The research was supported by the Croatian Science Foundation (project IP-2014-09-4841)