Aromatization within the putative bio-medical action mechanism of berberine and related cationic alkaloids with double iso-quinolinoid skeleton. A theoretical study

• Published in: Journal of molecular structure. Theochem Vol. 546; no. 1; pp. 243 - 260
• Main Authors: Freile, M.L., Masman, M.F., Suvire, F.D., Zacchino, S.A., Balzaretti, V., Enriz, R.D.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 16.07.2001
• Subjects: Ab initio MO; Aromatization by dehydrogenation; DFT study; HOMO/LUMO study; Hydride transfer and deprotonation; Nucleophilic addition to heteroaromatic cations; Nucleophilic addition to heteroaromatic cations; HOMO/LUMO study; Aromatization by dehydrogenation; DFT study; Ab initio MO; Hydride transfer and deprotonation
• ISSN: 0166-1280; 1872-7999
• DOI: 10.1016/S0166-1280(01)00508-5

In the putative mechanism of action for berberin, to prevent DNA replication the first step is aromatization. The aromatization process, via dehydrogenation has been studied for a series of compounds related to berberine. In contrast to the covalent dehydrogenation, which is endothermic, the aromatization under ionic conditions was found to be exothermic. The availability of the hydride for ionic aromatization was indicated by the effective HOMO of berberine and related compounds. The results indicate that in the aromatization process the ease of hydride ion removal parallels the stabilizations energy of the aromatic compounds to be formed. Comparing the nucleophilic additions to the π-system, the LUMO energy values suggested a greater accessibility of the N (+) heterocycles in comparison to the polycycle aromatic hydrocarbons.