title: Subtle Chemical Shifts Explain the NMR Fingerprints of Oligomeric Proanthocyanidins with High Dentin Biomodification Potency.
abstract: The ability of certain oligomeric proanthocyanidins (OPACs) to enhance the biomechanical properties of dentin involves collagen cross-linking of the 1.3-4.5 nm wide space via protein-polyphenol interactions. A systematic interdisciplinary search for the bioactive principles of pine bark has yielded the trimeric PAC, ent-epicatechin-(4β→8)-epicatechin-(2β→O→7,4β→8)-catechin (3), representing the hitherto most potent single chemical entity capable of enhancing dentin stiffness. Building the case from two congeneric PAC dimers, a detailed structural analysis decoded the stereochemistry, spatial arrangement, and chemical properties of three dentin biomodifiers. Quantum-mechanics-driven (1)H iterative full spin analysis (QM-HiFSA) of NMR spectra distinguished previously unrecognized details such as higher order J coupling and provided valuable information about 3D structure. Detection and quantification of H/D-exchange effects by QM-HiFSA identified C-8 and C-6 as (re)active sites, explain preferences in biosynthetic linkage, and suggest their involvement in dentin cross-linking activity. Mapping of these molecular properties underscored the significance of high δ precision in both (1)H and (13)C NMR spectroscopy. Occurring at low- to subppb levels, these newly characterized chemical shift differences in ppb are small but diagnostic measures of dynamic processes inherent to the OPAC pharmacophores and can help augment our understanding of nanometer-scale intermolecular interactions in biomodified dentin macromolecules.
authors.forename: Joo-Won
authors.initials: JW
authors.lastname: Nam
authors.forename: Rasika S
authors.initials: RS
authors.lastname: Phansalkar
authors.forename: David C
authors.initials: DC
authors.lastname: Lankin
authors.forename: Jonathan
authors.initials: J
authors.lastname: Bisson
authors.forename: James B
authors.initials: JB
authors.lastname: McAlpine
authors.forename: Ariene A
authors.initials: AA
authors.lastname: Leme
authors.forename: Cristina M P
authors.initials: CM
authors.lastname: Vidal
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ramirez
authors.affiliation: ⊥PERCH Solutions Ltd., Puijonkatu 24 B 5, 70110 Kuopio, Finland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Niemitz
authors.forename: Ana
authors.initials: A
authors.lastname: Bedran-Russo
authors.forename: Shao-Nong
authors.initials: SN
authors.lastname: Chen
authors.forename: Guido F
authors.initials: GF
authors.lastname: Pauli
mesh_terms: D001669:Biochemical Phenomena; D002392:Catechin / Q000737:chemistry*; D003804:Dentin / Q000737:chemistry*; D046911:Macromolecular Substances / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D059808:Polyphenols / Q000737:chemistry*; D044945:Proanthocyanidins / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D046911:Macromolecular Substances; D059808:Polyphenols; D044945:Proanthocyanidins; D002392:Catechin