Stability constants and thermodynamic functions of metal complexes of crown ethers in various solvents published between 1971 and the beginning of 2000 have been critically evaluated. The most studied crown ethers have been selected: 1,4,7,10 tetraoxacyclododecane (12C4), 1,4,7,10,13 pentaoxacyclopentadecane (15C5), and 1,4,7,10,13,16 hexaoxacyclooctadecane (18C6). The metal ions chosen are: alkali and alkaline earth metal ions, Ag⁺, Tl⁺, Cd²⁺, and Pb²⁺. The solvents considered are: water, methanol, ethanol, and their mixtures, as well as acetonitrile, N,N'-dimethylformamide, dimethylsulfoxide, and propylene carbonate. The published data have been examined and grouped into two categories, “accepted” and “rejected”. The “accepted” values were considered as: (i) recommended (R), when the standard deviations (s.d.) on the constant K or on Δ_r H were inferior to 0.05 lg unit or inferior to 1 kJ mol⁻¹, respectively; (ii) provisional (P), when s.d. is superior to 0.05 and inferior to 0.2 for lg K or s.d. is superior to 1 and inferior to 2 kJ mol⁻¹ for Δ_r H; (iii) recommended 1 (R1), if the values were obtained by a single research group, but were considered reliable in comparison with related systems, and considering that the research team usually presents R-level values for other similar systems.

A new series of multifunctional hybrids, based on the structure of the donepezil (DNP) drug, have been developed and evaluated as potential anti Alzheimer’s disease (AD) agents. The rationale of this study was the conjugation of a benzylpiperidine/benzylpiperazine moiety with derivatives of bioactive heterocyclics (benzimidazole or benzofuran), to mimic the main structure of DNP and to endow the hybrids with additional relevant properties such as inhibition of amyloid beta (Aβ) peptide aggregation, antioxidant activity and metal chelation. Overall, they showed good activity for AChE inhibition (IC₅₀=4.0–30.0 μΜ) and moderate ability for inhibition of Aβ_1–42 self-mediated aggregation. The hybrids containing chelating groups showed improvement in the inhibition of Cu-induced Aβ₄₂ aggregation and the antioxidant capacity. Moreover, neuroprotective effects of these compounds were evidenced in neuroblastoma cells after Aβ_1–42 induced toxicity. Structure–activity relationship allowed the identification of some promising compounds and the main determinant structural features for the targeted properties. Graphical Abstract