Journal article
Subtle Chemical Shifts Explain the NMR Fingerprints of Oligomeric Proanthocyanidins with High Dentin Biomodification Potency
Journal of organic chemistry, Vol.80(15), pp.7495-7507
08/07/2015
DOI: 10.1021/acs.joc.5b01082
PMCID: PMC4537297
PMID: 26214362
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,\nent\n-epicatechin-(4β→8)-epicatechin-(2β→\nO\n→7,4β→8)-catechin (\n3\n), 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\n1\nH iterative full spin analysis (QM-HiFSA) of NMR spectra distinguished previously unrecognized details such as higher order\nJ\ncoupling 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\n1\nH and\n13\nC 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.
Details
- Title: Subtitle
- Subtle Chemical Shifts Explain the NMR Fingerprints of Oligomeric Proanthocyanidins with High Dentin Biomodification Potency
- Creators
- Joo-Won Nam - Department of Medicinal Chemistry & Pharmacognosy, University of Illinois at Chicago, Chicago, Illinois 60612, United StatesRasika S Phansalkar - Department of Medicinal Chemistry & Pharmacognosy, University of Illinois at Chicago, Chicago, Illinois 60612, United StatesDavid C Lankin - Department of Medicinal Chemistry & Pharmacognosy, University of Illinois at Chicago, Chicago, Illinois 60612, United StatesJonathan Bisson - Department of Medicinal Chemistry & Pharmacognosy, University of Illinois at Chicago, Chicago, Illinois 60612, United StatesJames B McAlpine - Department of Medicinal Chemistry & Pharmacognosy, University of Illinois at Chicago, Chicago, Illinois 60612, United StatesAriene A Leme - Department of Restorative Dentistry, College of Dentistry, University of Illinois at Chicago, Chicago, Illinois 60612, United StatesCristina M. P Vidal - Department of Restorative Dentistry, College of Dentistry, University of Illinois at Chicago, Chicago, Illinois 60612, United StatesBenjamin Ramirez - UIC Center for Structural Biology, University of Illinois at Chicago, Chicago, Illinois 60612, United StatesMatthias Niemitz - PERCH Solutions Ltd., Puijonkatu 24 B 5, 70110 Kuopio, FinlandAna Bedran-Russo - UIC Center for Structural Biology, University of Illinois at Chicago, Chicago, Illinois 60612, United StatesShao-Nong Chen - Department of Medicinal Chemistry & Pharmacognosy, University of Illinois at Chicago, Chicago, Illinois 60612, United StatesGuido F Pauli - Department of Medicinal Chemistry & Pharmacognosy, University of Illinois at Chicago, Chicago, Illinois 60612, United States
- Resource Type
- Journal article
- Publication Details
- Journal of organic chemistry, Vol.80(15), pp.7495-7507
- DOI
- 10.1021/acs.joc.5b01082
- PMID
- 26214362
- PMCID
- PMC4537297
- NLM abbreviation
- J Org Chem
- ISSN
- 0022-3263
- eISSN
- 1520-6904
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: R01 DE021040
- Language
- English
- Date published
- 08/07/2015
- Academic Unit
- Operative Dentistry
- Record Identifier
- 9984066094202771
Metrics
33 Record Views