Synthesis of polyfunctional hydroxamic acids for potential use in iron chelation therapy |
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| Affiliation: | 1. Department of Organic Chemistry, University of Szeged, Dóm tér 8, Szeged, H-6720 Hungary;2. Materials and Solution Structure Research Group, Institute of Chemistry, University of Szeged, Aradi Vértanúk tere 1, Szeged, H-6720 Hungary;3. Department of Applied and Environmental Chemistry, University of Szeged, Rerrich Béla tér 1, Szeged, H-6720 Hungary;4. MTA-SZTE Reaction Kinetics and Surface Chemistry Research Group, Rerrich Béla tér 1, Szeged, H-6720 Hungary;5. MTA-SZTE “Lendület” Porous Nanocomposites Research Group, Rerrich Béla tér 1, Szeged, H-6720 Hungary;6. Max-IV Laboratory, Lund University, Lund, Sweden;7. Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, Szeged, H-6720 Hungary;1. South China Institute of Environmental Sciences, Ministry of Environmental Protection (MEP), Guangzhou 510655, PR China;2. South China Subcenter of State Environmental Dioxin Monitoring Center, Guangzhou 510655, PR China;3. Innovative Laboratory for Environmental Functional Materials and Environmental Applications of Microwave Irradiation, Guangzhou 510655, PR China;4. Environmental Engineering and Science Program, Department of Biomedical, Chemical and Environmental Engineering (DBCEE), University of Cincinnati, Cincinnati, OH 45221-0012, USA |
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| Abstract: | Two new multidentate N-methylhydroxamic acids were prepared and characterized. β-Cyclodextrin was esterified by treatment with succinic anhydride. The resulting carboxyl groups (14 per cyclodextrin) were converted to the N-hydroxysuccinimide esters and then on to the hydroxamic acids by treatment with N-methylhydroxylamine. Tetracyanoethylation of cyclohexanone followed by hydrolysis of the nitrile and conversion of the carboxylic acid to hydroxamic acid produced a tetrahydroxamic acid derivative of cyclohexanone. Infrared, 1H NMR, and 13C NMR were consistent with the proposed structures. The hydroxamic acids were water soluble and formed the typical red-brown iron complexes. Stability constants (log K) of 29–30 for the iron complexes indicated a strong chelate effect. Animal tests indicated that the two compounds were only weakly effective in removing iron in vivo from iron-overloaded mice. The potency was only 0.1 that of the standard drug desferrioxamine-B. |
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