Absolute Configuration of Native Oligomeric Proanthocyanidins with Dentin Biomodification Potency

Joo Won Nam, Rasika S. Phansalkar, David C. Lankin, James B. McAlpine, Ariene A. Leme-Kraus, Cristina M.P. Vidal, Li She Gan, Ana Bedran-Russo, Shao Nong Chen, Guido F. Pauli

Research output: Research - peer-reviewArticle

  • 2 Citations

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 how 13C 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.

LanguageEnglish (US)
Pages1316-1329
Number of pages14
JournalJournal of Organic Chemistry
Volume82
Issue number3
DOIs
StatePublished - Feb 3 2017

Fingerprint

Proanthocyanidins
Catechin
Nuclear magnetic resonance
Bioassay
Chemical shift
Biomimetics
Oligomers
Dimers
Gages
Collagen
Elastic moduli
Degradation
Molecules

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Absolute Configuration of Native Oligomeric Proanthocyanidins with Dentin Biomodification Potency. / Nam, Joo Won; Phansalkar, Rasika S.; Lankin, David C.; McAlpine, James B.; Leme-Kraus, Ariene A.; Vidal, Cristina M.P.; Gan, Li She; Bedran-Russo, Ana; Chen, Shao Nong; Pauli, Guido F.

In: Journal of Organic Chemistry, Vol. 82, No. 3, 03.02.2017, p. 1316-1329.

Research output: Research - peer-reviewArticle

Nam JW, Phansalkar RS, Lankin DC, McAlpine JB, Leme-Kraus AA, Vidal CMP et al. Absolute Configuration of Native Oligomeric Proanthocyanidins with Dentin Biomodification Potency. Journal of Organic Chemistry. 2017 Feb 3;82(3):1316-1329. Available from, DOI: 10.1021/acs.joc.6b02161
Nam, Joo Won ; Phansalkar, Rasika S. ; Lankin, David C. ; McAlpine, James B. ; Leme-Kraus, Ariene A. ; Vidal, Cristina M.P. ; Gan, Li She ; Bedran-Russo, Ana ; Chen, Shao Nong ; Pauli, Guido F./ Absolute Configuration of Native Oligomeric Proanthocyanidins with Dentin Biomodification Potency. In: Journal of Organic Chemistry. 2017 ; Vol. 82, No. 3. pp. 1316-1329
@article{a25ad527ddcd4a66b9a31c05fb8613ef,
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 how 13C 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.",
author = "Nam, {Joo Won} and Phansalkar, {Rasika S.} and Lankin, {David C.} and McAlpine, {James B.} and Leme-Kraus, {Ariene A.} and Vidal, {Cristina M.P.} and Gan, {Li She} and Ana Bedran-Russo and Chen, {Shao Nong} and Pauli, {Guido F.}",
year = "2017",
month = "2",
doi = "10.1021/acs.joc.6b02161",
volume = "82",
pages = "1316--1329",
journal = "Journal of Organic Chemistry",
issn = "0022-3263",
publisher = "American Chemical Society",
number = "3",

}

TY - JOUR

T1 - Absolute Configuration of Native Oligomeric Proanthocyanidins with Dentin Biomodification Potency

AU - Nam,Joo Won

AU - Phansalkar,Rasika S.

AU - Lankin,David C.

AU - McAlpine,James B.

AU - Leme-Kraus,Ariene A.

AU - Vidal,Cristina M.P.

AU - Gan,Li She

AU - Bedran-Russo,Ana

AU - Chen,Shao Nong

AU - Pauli,Guido F.

PY - 2017/2/3

Y1 - 2017/2/3

N2 - 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 how 13C 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.

AB - 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 how 13C 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.

UR - http://www.scopus.com/inward/record.url?scp=85011357396&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85011357396&partnerID=8YFLogxK

U2 - 10.1021/acs.joc.6b02161

DO - 10.1021/acs.joc.6b02161

M3 - Article

VL - 82

SP - 1316

EP - 1329

JO - Journal of Organic Chemistry

T2 - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

SN - 0022-3263

IS - 3

ER -