Ferric Complexes of 3-Hydroxy-4-pyridinones Characterized by Density Functional Theory and Raman and UV–vis Spectroscopies

摘要

ABSTRACT: Deferiprone and other 3-hydroxy-4-pyridinonesnare used in metal chelation therapy of iron overload. Toninvestigate the structure and stability of these compounds innthe natural aqueous environment, ferric complexes ofndeferiprone and amino acid maltol conjugates were synthesizednand studied by computational and optical spectroscopicnmethods. The complexation caused characteristic intensitynchanges, a 300× overall enhancement of the Raman spectrum,nand minor changes in UV−vis absorption. The spectra wereninterpreted on the basis of density functional theory (DFT)ncalculations. The CAM-B3LYP and ωB97XD functionals with CPCM solvent model were found to be the most suitable fornsimulations of the UV−vis spectra, whereas B3LYP, B3LYPD, B3PW91, M05-2X, M06, LC-BLYP, ωB97XD, and CAM-B3LYPnfunctionals were all useful for simulation of the Raman scattering. Characteristic Raman band frequencies for 3-hydroxy-4-npyridinones were assigned to molecular vibrations. The computed conformer energies consistently suggest the presence ofnanother isomer of the deferiprone-ferric complex in solution, in addition to that found previously by X-ray crystallography.nHowever, the UV−vis and Raman spectra of the two species are similar and could not be resolved. In comparison to UV−vis, thenRaman spectra and their combination with calculations appear more promising for future studies of iron sequestrating drugs andnartificial metalloproteins as they are more sensitive to structural details.