Petrosamine Revisited. Experimental and Computational Investigation of Solvatochromism, Tautomerism and Free Energy Landscapes of a Pyridoacridinium Quaternary Salt

Petrosamine (1)—a colored pyridoacridine alkaloid from the Belizean sponge, Petrosia sp., that is also a potent inhibitor of acetylcholine esterase (AChE)—was investigated by spectroscopic and computational methods. Analysis petrosamine-free energy landscapes, pKa tautomerism, revealed an accurate electronic depiction molecular structure 1 as di-keto form, with net charge q = +1, rather than dication (q +2) under ambient conditions isolation-purification. The pronounced solvatochromism (UV-vis) reported for 1, related analogs were in detail best explained delocalization stabilization ground state (HOMO) equilibrium competing tautomers. Refinement QM methods complements published docking studies to define contact points enzyme active site may improve design new AChE inhibitors based on skeleton.