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A simple synthetic pathway to obtain glycosilated β-diketo derivatives is proposed. These compounds show a good iron(III) affinity therefore we may suggest the use of their Fe 3+ -complexes as oral iron supplements in the treatment of anaemia. The glycosilated compounds (6-GlcH, 6-GlcOH and 6-GlcOCH 3 ) are characterized by means of spectroscopic (UV, 1 H and 13 C NMR) and potentiometric techniques; they have a good water solubility, are kinetically stable in physiological condition ( t 1/2 > 100 h) and show a low cytotoxicity also in high concentrations (IC 50 > 400 μM). They are able to bind Fe 3+ ion in acid condition (pH ∼ 2) forming complex species thermodynamically more stable than those of other ligands commonly used in the treatment of iron deficiency. The iron complexes show also a good kinetic stability both in acidic and physiological pH and have a good lypophilicity (log P > −0.7) that suggests an efficient gastrointestinal absorption in view of their possible use in oral therapy. In addition they demonstrate a poor affinity for competitive biological metal ion such as Ca 2+ , and in particular 6-GlcOCH 3 is able to inhibit lipid peroxidation.

In the present study, we investigate the structures of glucosylated curcumin derivatives with DFT at B3LYP/6-31G* level. A conformational analysis is performed in order to determine the conformational minimum (GS) and rotational transition state (TS) of curcumin derivatives and then their electronic features are evaluated. HOMO and LUMO frontier orbitals and maps of electron density potential (MEPs) are plotted and compared. In order to correlate their predicted spectroscopic properties with IR, UV–vis and NMR experimental data we extended the theoretical study on electronic properties to different solvents (H2O, MeOH, ACN, DMSO). The main finding is that the curcuminic core maintains the same geometrical and electronic structures in all compounds miming the metal coordination capability showed by curcumin. Therefore, we may confirm that the presence of glucose does not affect the electronic properties of the derivatives. Copyright © 2010 John Wiley & Sons, Ltd.

Turmeric extracts, among which curcumin and bis-demethoxycurcumin, are by far known for their therapeutic activities. In this study we propose easy and low cost synthetic pathways in order to obtain glucosyl-curcuminoids, safe and water soluble potential drugs and dyes, which may be implied in different fields ranging from pharmacology to food chemistry. The complete (1)H and (13)C NMR characterization of naturally occurring curcumin, bis-demethoxycurcumin and new synthetic glucosyl-curcuminoids is reported.

The main target of this study is a high-level computational analysis of Curcumin, employing DFT approach with two different sets of basis functions (B3LYP/6-31G ∗ and B3LYP/6-311G ∗∗ ). Accurate quantum mechanical studies, both in vacuum and in methanol medium, are carried out with the aim to analyze the conformational equilibria, to find the most stable equilibrium structure and to define the nature of the molecular orbitals, fundamental to explain Curcumin binding characteristic. Our theoretical calculations, performed at B3LYP/6-31G ∗ and B3LYP/6-311G ∗∗ levels both in vacuum and in methanol medium, confirm that the keto-enolic forms are more stable than the di-keto one, whose extremely low population suggests that this structure should not influence Curcumin properties. Keto-enolic form C results the most stable, independently on calculation level and solvent (methanol) effect. HOMO and LUMO molecular orbitals are calculated for all the structures with the two sets of basis with very similar results. MEPs show that the negative charge is localized on the oxygen atoms, which, in the keto-enolic forms, point in the same direction enabling metal coordination. NMR, UV–vis and FT-IR experimental data are employed in the comparison with electronic and conformational properties of Curcumin resulting from theoretical calculations. The two different calculation levels (B3LYP/6-31G ∗ and B3LYP/6-311G ∗∗ ) give very similar results. Good linear correlations between the experimental 1 H and 13 C NMR chemical shifts ( δ exp ), in methanol- d 4 (MeOD) and DMSO- d 6 (DMSO), and calculated magnetic isotropic shielding tensors ( σ calc ) are found ( δ exp = a · σ calc + b ). A good prediction of UV–vis experimental maximum absorption ( λ max ) on the basis of conformer populations is obtained. A linear relation with a good correlation coefficient is observed plotting the FT-IR experimental wavenumbers vs . the calculated ones, allowing to predict FT-IR spectra.