title: Absolute Configuration of Native Oligomeric Proanthocyanidins with Dentin Biomodification Potency.
abstract: The structurally complex oligomeric proanthocyanidins (OPACs) are promising biomimetic agents, capable of strengthening the macromolecular backbone of teeth via intermolecular and intermicrofibrillar cross-linking. This study establishes analytical methods capable of determining the absolute configuration of the catechin-type monomeric units of underivatized OPACs. This preserves the capacity of their biological evaluation, aimed at understanding the inevitably stereospecific interactions between the OPACs and dentin collagen. Guided by dental bioassays (modulus of elasticity, long-term stability), two new trimeric and tetrameric A-type OPACs were discovered as dentin biomodifiers from pine (Pinus massoniana) bark: epicatechin-(2β→O→7,4β→8)-epicatechin-(2β→O→7,4β→8)-catechin (5) and epicatechin-(2β→O→7,4β→8)-epicatechin-(2β→O→7,4β→6)-epicatechin-(2β→O→7,4β→8)-catechin (6), respectively. Combining 1D/2D NMR, HRESIMS, ECD,1H iterative full spin analysis (HiFSA), and gauge-invariant atomic orbital (GIAO) δ calculations, we demonstrate how13C NMR chemical shifts (diastereomeric building blocks (A-type dimers)) empower the determination of the absolute configuration of monomeric units in the higher oligomers 5 and 6. Collectively, NMR with ECD reference data elevates the level of structural information achievable for these structurally demanding molecules when degradation analysis is to be avoided. Considering their numerous and deceptively subtle, but 3D impactful, structural variations, this advances the probing of OPAC chemical spaces for species that bind selectively to collagenous and potentially other biologically important biomacromolecules.
authors.affiliation: College of Pharmacy, Yeungnam University , Gyeongsan, Gyeongbuk 712-749, Korea.
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: James B
authors.initials: JB
authors.lastname: McAlpine
authors.affiliation: Department of Restorative Dentistry, College of Dentistry, University of Illinois at Chicago , Chicago, Illinois 60612, United States.
authors.forename: Ariene A
authors.initials: AA
authors.lastname: Leme-Kraus
authors.affiliation: Department of Restorative Dentistry, College of Dentistry, University of Illinois at Chicago , Chicago, Illinois 60612, United States.
authors.forename: Cristina M P
authors.initials: CM
authors.lastname: Vidal
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University , Hangzhou 310058, People's Republic of China.
authors.forename: Li-She
authors.initials: LS
authors.lastname: Gan
authors.affiliation: Department of Restorative Dentistry, College of Dentistry, University of Illinois at Chicago , Chicago, Illinois 60612, United States.
authors.forename: Ana
authors.initials: A
authors.lastname: Bedran-Russo
authors.forename: Shao-Nong
authors.identifier: 0000-0003-0748-0863
authors.initials: SN
authors.lastname: Chen
authors.forename: Guido F
authors.identifier: 0000-0003-1022-4326
authors.initials: GF
authors.lastname: Pauli
mesh_terms: D003804:Dentin / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008968:Molecular Conformation; D028223:Pinus / Q000737:chemistry*; D044945:Proanthocyanidins / Q000737:chemistry*
chemical_list: D044945:Proanthocyanidins; C013221:proanthocyanidin