A variable temperature 1H NMR and DFT study of procyanidin B2 conformational interchange

Two procyanidin B2 conformers were identified in a relative abundance ratio of approximately 3:1 at 298 K by ¹H NMR experiments in acetonitrile. The conformational interchange reactions between these two conformers are 1st order in both reactions, with ?G^? for forward and reverse of 57.12?±?5.62 and 54.56?±?5.48 kJ mol^?1, respectively. The experimentally obtained standard thermodynamic energies for this reaction are ΔH⁰_rxn (3.67?±?0.22 kJ mol^?1), ΔS⁰_rxn (4.05?±?1.57 kJ mol^?1 K^?1), and ΔH⁰_rxn (2.96?±?0.33 kJ.mol^?1). Conformational search results at the DFT (PBE, PBE-D2, and B3LYP with 6-311++g**) level of theory yielded four novel conformations, named fully compact (FC), partially compact (PC), partially extended (PE), and fully extended (FE). Although the FC conformer is electronically the most stable of the four as a result of extensive intramolecular non-covalent interactions, the PC and FE conformers are thermodynamically favored in a 5:1 ratio (B3LYP), with the FC and PE conformers present in negligible amounts at equilibrium. The DFT computed standard reaction energies using the B3LYP functional for the PC_major to FE_minor conformational interchange reaction compare exceptionally well with experimental data at 298 K: ?G⁰_rxn (3.86 kJ mol^?1), ΔH⁰_rxn (5.34 kJ mol^?1), and ?S⁰_rxn (4.97 kJ mol^?1 K^?1). It was found that inclusion of solvation energies is crucial to obtain accurate thermodynamic energies. The secondary equilibria found in chromatographic separations are predicted to be highly dependent on solvent polarity and temperature. Similar conformational diversity and hierarchies should exist for all non-rigid procyanidin oligomers and the unique chromatographic behavior of these compounds may be a result of conformational interchange.