Proton and gallium(III) binding properties of a biologically active salicylidene acylhydrazide
| Autor: | Jean-François Boily, Shoghik Hakobyan, Madeleine Ramstedt |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
UV–VIS
Stereochemistry protonation Hydrazone chemistry.chemical_element Protonation Gallium Biochemistry Inorganic Chemistry Hydrolysis complex formation Acetamides Chelation Equilibrium constant Chelating Agents gallium chemistry.chemical_classification Aqueous solution Chemistry Biochemistry and Molecular Biology Hydrazones Biofilm UV-VIS equilibrium constants Complex formation Kemi Combinatorial chemistry Equilibrium constants Hydrazines pH titration Benzaldehydes Chemical Sciences Spectrophotometry Ultraviolet Protons Biokemi och molekylärbiologi |
| Zdroj: | Journal of Inorganic Biochemistry. 138:9-15 |
| ISSN: | 0162-0134 |
| DOI: | 10.1016/j.jinorgbio.2014.04.012 |
| Popis: | Bacterial biofilm formation causes a range of problems in our society, especially in health care. Salicylidene acylhydrazides (hydrazones) are promising antivirulence drugs targeting secretion systems used during bacterial infection of host cells. When mixed with the gallium ion they become especially potent as bacterial and biofilm growth-suppressing agents, although the mechanisms through which this occurs are not fully understood. At the base of this uncertainty lies the nature of hydrazone–metal interactions. This study addresses this issue by resolving the equilibrium speciation of hydrazone–gallium aqueous solutions. The protonation constants of the target 2-oxo-2-[N-(2,4,6-trihydroxy-benzylidene)-hydrazino]-acetamide (ME0163) hydrazone species and of its 2,4,6-trihydroxybenzaldehyde and oxamic acid hydrazide building blocks were determined by UV–visible spectrophotometry to achieve this goal. These studies show that the hydrazone is an excessively strong complexing agent for gallium and that its antivirulence properties are predominantly ascribed to monomeric 1:1Ga–ME0163 complexes of various Ga hydrolysis and ME0163 protonation states. The chelation of Ga(III) to the hydrazone also increased the stability of the compounds against acid-induced hydrolysis, making this group of compounds very interesting for biological applications where the Fe-antagonist action of both Ga(III) and the hydrazone can be combined for enhanced biological effect. |
| Databáze: | OpenAIRE |
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