Biopolymers and cell. 2007; 23 (1): 28 - 34

Non-empirical quantum-chemical study of various structural forms of berberin alkaloid

V. I. Danilov, V.V. Dailidonis, D. M. Hovorun, L. A. Zayika, N. Kurita, A. I. Potopalsky, V. M. Kharchenko

    The results of the extensive theoretical study on the energy and structural properties of all possible alkaloid berberine forms (berberine cation and three tautomeric forms of berberine), displaying a great variety of biological and pharmacological activities, are presented. The DFT method with exchange-correlation (combined) functionals (PW91, BLYP, PBEPW91) and hybrid functionals (B3LYP, B3PW91) as well as MP2 method were used for the berberine cation.

    Molecular orbitals were represented by the atomic basis sets 6-31G(d,p) and 6-311G(d,p). The ammonium, carbinol (pseudobase) and amino-aldehyde forms were calculated by the DFT method with B3LYP/6-31G(d,p) functional. Full geometry optimization regardless of the theory level was shown to result in the intrinsically non-planar propeller-twisted and buckled spatial structure of all berberine forms. The calculated lengths and angles of bonds were shown to have good correlation with the experimental data obtained by X-ray analysis.

    From the comparison of relative stabilities of the tautomeric forms, it was elucidated that carbinol form is the most preferable tautomer in gas phase, while amino-aldehyde form is less stable (by 12.65 kcal/mol). The least stable tautomer was the ammonium one, being 10.65 kcal/mol less stable than amino aldehyde tautomer.

Keywords: berberine, tautomerism, pseudobase, quantum chemical calculations, DFT, MP2, spatial structure.