Hydroxyquinoline based binders: Promising ligands for chelatotherapy?

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

“…The larger stability of the Cu 2 + over the Zn 2 + complex is expected in keeping with values reported for other HQ-basedl igands. [25,26] Thist rend is consistentw ith the Irving-Williams series. Upon deprotonation of the phenolic groups, 1 mayf orm also aM L 2 species in such aw ay that the resulting complexi sn eutral;t he structure of this complex may be supposed to be similart ot hat reported for HQ and clioquinol in which Zn 2 + is coordinated to the two HQ units.…”

“…The log b value for the ML speciesi sl arger than the values reported for Zn 2 + complexes of 1 and HQ. [26] This feature was previously observed in the case of the corresponding Cu 2 + complex and may be attributed to the presence of the aminog roup in the backbone of the ligand which provides an additional nitrogen donor atom for the metal ion and allows for the formation of two five-membered chelate rings. [24,31] The central ion binds the pyridine N-atom, the phenolate O-atom and the exocyclic amino group which imparts additional stabilizationt ot he ML complex.…”

Cyclodextrins 3‐Functionalized with 8‐Hydroxyquinolines: Copper‐Binding Ability and Inhibition of Synuclein Aggregation

“…The conditional stability constant of the ML speciesf ormed by Cu 2 + with 2 (determined by competition titrations, Figures S6 and S7) is larger than those found for the analogous complexes with 1,H Q, and clioquinol. [28] This finding may be ascribed to the presence of an aminog roup (FigureS5) in the backboneo ft he ligand,w hich provides an additional amino donora tom for the metal ion and can form two five-membered chelate rings, as reported for similar systems of CyD. [22,29] The Cu 2 + ion is hence bound to the Na tom of the pyridine ring, the phenolate ion, and the exocyclic amino group (Figure S5), whichf urther stabilizes the ML complex regardlesso f the positiono ft he HQ substituent in the CyD scaffold.…”

8-Hydroxyquinolines: a review of their metal chelating properties and medicinal applications

“…Moreover, halogen groups are known to increase its lipophilicity to allow its absorption to target sites in the brain 9. CQ selectively chelates Cu and Zn ions,9,23 which play a vital role in misfolded protein production, aggregation, and accumulation that ultimately leads to neurotoxicity in AD 9,24. However, the selectivity of the compound can minimize the chance of developing a depletion in systemic metal ions 9…”