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

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 delta of ortho-H8 protons. 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 delta(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.