Conformational and Cs+ complexation properties of norbadione-A: a molecular modeling study

Abstract

We report a quantum mechanical (QM) and classical molecular dynamics (MD) study of the conformational and complexation properties of norbadione-A (NBA), a key pigment involved in the Cs⁺ complexation by mushrooms. The Z versus E isomers of its pulvinic moieties are compared in their neutral (Pulv⁰), mono- (Pulv^–1) and di-deprotonated (Pulv^–2) states, and the ¹H chemical shifts are calculated ab initio. Pulv^–1 is found to be stabilized in the E form by an internal COOH⋯^–O(enolate) hydrogen-bond. No energy minimum is found for the corresponding COO^–⋯HO(enol) state, indicating that the conjugated enol function of Pulv⁰ is more acidic than the COOH function. Further deprotonation leads to the Z and E forms of Pulv^–2 that are close in energy and both account for a marked downfield shift δ of ortho-H₈protons. A similar shift is found upon deprotonation of the enol function of an ester analogue of Pulv⁰. Therefore, contrary to previous assumptions (ref. 7: P. Kuad, et al., J. Am. Chem. Soc., 2005, 127, 1323), the large shift of δ(H₈) around pH 9.5 upon deprotonation of NBA or of pulvinic acid cannot be taken as an indicator of an E-to-Z conformational switch, but merely reflects the pH-induced conformational change of the carboxylate group adjacent to the (H₈)-ring. The QM and MD studies on NBA^2– and NBA^4– support the view that both species prefer the E/E form with two intramolecular COOH⋯^–O(enolate) hydrogen-bonds in the gas phase and in solution. Finally, we simulated mono- and di-nuclear complexes of Cs⁺ with NBA^2– and NBA^4– by MD, showing that only the NBA^4– state populated at high pH values can bind two Cs⁺ cations, with both E and Z conformations of the pulvinic arms.