Chemical nano shifts explain the NMR fingerprints of dentin-enhancing oligomeric proanthocyanidins

1D NMR spectra contain a wealth of vital structural information that can enhance the description of bioactive molecules. The present study demonstrates how quantum-mechanics driven ¹H iterative Full Spin Analysis (QM-HiFSA) is capable of distinguishing spectral detail that cannot be interpreted manually or visually, but provides important information of the 3D structure and bonding (re-)activity of the molecules. This approach is established by analyzing 1D NMR spectra of oligomeric proanthocyanidins (OPACs), which exhibit high dentin bioactivity, and were isolated from the inner bark of pine. The higher order coupling and proton-deuterium exchange effects observed in these complex molecules were fully explained and quantified by QM-HiFSA. Dimeric and trimer OPACs provide evidence that high δ precision is applicable to ¹³C, in addition to ¹H 1D NMR spectra, requiring reporting to the ppb level and below. Both the nano chemical shifts (ppb) and the associated nano substituent chemical shifts (s.c.s.) are significant properties of the ¹H and ¹³C NMR spectra and enable recognition of structural properties that are relevant to better understanding of the intermolecular interactions between the OPAC pharmacophores and dentin micromolecules triggering enhanced tissue mechanics.