Comparison of binding sites and affinity of flavonol–Cu(II) complexes with the same parent nucleus: Synthesis, DFT prediction, and coordination pattern

•Coordination chemistry of three structurally analogous flavonols was studied.•A novel synthesis method for flavonol–Cu(II) coordination compounds is introduced.•Consistent binding patterns of Cu ions with flavonols mainly at 4,5 sites observed.•Binding affinity of the flavonols for Cu ions is: myricetin > quercetin > kaempferol. This study explores the coordination dynamics between dietary polyphenols, specifically kaempferol, quercetin, and myricetin, and Cu ions in aqueous environments. A novel synthesis method for flavonol–Cu(II) coordination compounds is introduced, effectively reducing interference from free metal ions. Our results reveal consistent binding patterns of Cu ions with flavonols (2:1 ratio of flavonol to Cu(II)), predominantly at the 4,5 sites. Various analytical techniques are used to validate these coordination ratios and sites. The binding affinity of the flavonols for Cu ions follows a descending sequence: myricetin > quercetin > kaempferol. Notably, coordination with Cu ions enhances the free-radical scavenging activities of these flavonols. These findings hold substantial importance for food chemistry, biology, and medicine, providing crucial insights into the way dietary flavonols form stable structures in environments similar to human body fluids and their interactions with metal ions, opening new possibilities for their application and understanding in diverse scientific domains.