Zinc Complexes of Cyclodextrin‐bearing 8‐Hydroxyquinoline Ligands: A Comparative Study

Abstract

The mounting evidence supporting the role of metal ions in several diseases has turned metal-ion chelation therapy into a promising treatment strategy. The design of efficient metal-binding ligands requires in-depth knowledge of molecular structure and stability constants of the complexes formed. This paper presents an extensive overview on the stability of zinc(II) and copper(II) complexes of a series of cyclodextrin-8-hydroxyquinoline conjugates. In order to explain the differences observed in the stability constants between the metal complexes of the 6-functionalized and 3-functionalized cyclodextrin isomers, conformational analysis and DFT simulations were also performed. Molecular simulations allowed us to clarify the binding mode and to explain the differences in the stability constants of the metal complexes of these derivatives.

Structural Isomers of Cyclodextrin‐Bearing IOX1 Compound as Inhibitors of Aβ Aggregation

“…This interaction could be hypothesized in the case of β‐CyD conjugates, along with hydrophobic interactions of amino acid residues of Aβ with IOX moiety as reported for similar CyD derivatives . Furthermore, the structural differences between CyD3IOX and CyD6IOX such as the distortion of the cavity in 3‐functionalized CyDs, could explain the slight difference of the two compounds in inhibiting Aβ aggregation and this aspect should be considered in the design of other similar CyD systems.…”

“…In particular, the 6‐functionalized CyD‐IOX is more efficient than the 3‐funtionalized isomer in inhibiting Aβ aggregation, thus indicating a different behavior of these regioisomers. The slight difference observed for the two isomers could be ascribed to the rim distortion afforded by a chair flip of the modified altrose unit in 3‐functionalized CyD derivatives as observed for similar derivatives …”

“…6‐ and 3‐functionalized derivatives could have significant structural differences resulting from the different synthetic route followed to obtain these systems. In particular, the CyD rim of 3‐functionalized derivatives is quite distorted owing to the presence of the altrose unit, where the HQ moiety is appended, whereas the functionalization at the 6‐position does not markedly influence the CyD cavity . Thus, the design and functionalization strategy used to obtain the CyD conjugates could affect the properties of the resulting conjugates.…”

Synthesis and Study of Multifunctional Cyclodextrin–Deferasirox Hybrids

“…Because of a chair flip of the modified altrose unit in the 3‐functionalized CyD derivatives, the cavity is elliptically distorted, whereas functionalization at the 6‐position does not dramatically influence the CyD cavity, according to the literature . Thus, the kind of functionalization strategy used to obtain the CyD conjugates may confer different properties to the resulting conjugates …”

“…[22,23] Thus, the kind of functionalization strategy used to obtain the CyD conjugates may confer differentp roperties to the resultingc onjugates. [24] The new compounds were furtherc haracterized by 1 Ha nd 13 CNMR spectroscopy.T he 1D spectra of the products were assignedu sing 2D experiments (COSY,T OCSY,H SQC, HMBC,a nd ROESY; FiguresS1-S6 in the Supporting Information). The NMR spectra of 1 and 2 further confirm ligand conjugation,a st hey display signals due to the 3 and CyD moieties, the former resonating in the aromaticr egion.…”