The synthesis of a range of novel bidentate and hexadentate ligands containing the chelating moiety 3-hydroxy-2(1H)-pyridinone is described. The pKa values of the ligands and the stability constants of their iron(III) complexes have been determined. The stability constant of the iron(III) complex of one of the hexadentate ligands is comparable to that of desferrioxamine B. The distribution coefficients of the ligands and their iron(III) complexes were also determined. One of the novel hexadentate compounds has been shown to markedly enhance iron(III) excretion from both hepatocytes and iron-overloaded mice.
The 59Fe excretion caused by a range of bidentate N-substituted [R group = methyl (CP20), ethyl (CP21), propyl (CP22), isopropyl (CP23), butyl (CP24) or hexyl (CP25)] 3-hydroxypyrid-4-one chelators in iron-overloaded mice is presented. All the compounds cause significant iron excretion when given intraperito-neally, but that the most hydrophobic compounds, CP24 and CP25, were toxic except at low doses. The excretion caused by CP21, CP22 and CP23 were significantly greater than that caused by CP20 and slightly larger than that caused by an equivalent dose of desferrioxamine. These compounds (CP20 through CP24) also caused significant excretion of 59Fe when administered orally. Compounds CP21, CP22 and CP24 were significantly more active than compounds CP20 and CP23. It is concluded that the N-ethyl or N-propyl 3-hydroxy-pyrid-4-ones are the most promising compounds for clinical application. Preliminary experiments using a hexadentate pyrid-2-one, CP130, show that this causes significant 59Fe excretion both when given intraperitoneally or orally
Naphthalene-l,8-dicarbaldehyde monohydrate has been shown to have a bridged (cyclic) structure in solution, as a cis-trans mixture. The hydrated dialdehyde, as well as the cx,a'-dideuterio isomer, has been shown to undergo a Cannizzaro reaction in 70% (v/v) dioxane-water. The reaction has been found to be intramolecular and of the second order, i.e. first order in the monoanion of the hydrate and in base. The kinetic isotope effect, k,/k,, was found t o be ca. 1.7 and the kinetic solvent isotope effect, kHlo/kDlo, ca. 0.60. The alkaline hydrolysis of the corresponding lactone of 8-(hydroxymethyl) -1 -naphthoic acid (naphthalide) was studied under the same conditions. The lactone can be excluded as an intermediate in the intramolecular Cannizzaro reaction as it cannot be detected directly under conditions where it would be sufficiently long-lived. The evidence for the Cannizzaro reaction indicates a mechanistic pathway involving rate-determining hydride transfer in the chain tautomer of the dianion of the hydrate.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.