Synthesis and characterization of 4-(5-(diethylamino)-2-formylphenoxy)phthalonitrile, aldehyde-, and Schiff base-substituted peripheral tetra-substituted Co(II), Cu(II), and Zn(II) phthalocyanine compounds. In vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes activity of aldehyde- and Schiff base-substituted cobalt (II), copper (II), and zinc (II) phthalocyanines

In this work, a series of aldehyde-substituted phthalocyanine compounds (1, 3, and 5) were prepared by the cyclotetramerization of the 4-(5-(diethylamino)-2-formylphenoxy) phthalonitrile (a) and the corresponding metal salts. Schiff base-substituted phthalocyanines (2, 4, and 6) were derived from an aldehyde-substituted phthalocyanine (1, 3, and 5) via the reaction of aldehyde-substituted phthalocyanines with an amine reagent. The compounds that were obtained were characterized using FT-IR, ¹H {¹³C} NMR, UV–Vis, and MS spectra (a and 1–6). The inhibitory qualities of synthesized aldehyde and Schiff base-substituted complexes against the enzymes butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) were assessed. The majority of phthalocyanines exhibited strong enzyme-inhibiting properties. Out of the six produced phthalocyanines, 3 and 4 displayed the most intriguing profiles as submicromolar selective AChE inhibitors (IC₅₀ = 0.060 μM), whereas 1 demonstrated the most potent BChE inhibitor (IC₅₀ = 0.024 μM). The aggregation studies of CoPcs, CuPcs, and ZnPcs (1–6) were also carried out in this work.