Proanthocyanidin Dimers and Trimers from Vitis vinifera Provide Diverse Structural Motifs for the Evaluation of Dentin Biomodification

Abstract

Aimed at exploring the dentin biomodification potential of proanthocyanidins (PACs) for the development of dental biomaterials, this study reports the phytochemical and dental evaluation of nine B-type PACs from grape seed extract (GSE). Out of seven isolated dimers (1−7), four new compounds (2, 3, 5, and 6) involved relatively rare entcatechin or ent-epicatechin monomeric flavan-3-ol units. Lowtemperature NMR analyses conducted along with phloroglucinolysis and electronic circular dichroism enabled unequivocal structural characterization and stereochemical assignment. Additionally, one known (8) and one new (9) B-type trimer were characterized. Differential 13 C NMR chemical shifts (Δδ) were used to determine the absolute configuration of 9, relative to the dimers 1 and 2 as the possible constituent subunits. Compared to the dimers, the trimers showed superior dentin biomodification properties. The dimers, 1−7, exhibited pronounced differences in their collagenase inhibitory activity, while enhancing dentin stiffness comparably. This suggests that PAC structural features such as the degree of polymerization, relative and absolute configuration have a differential influence on enhancement of dentin biomechanical and biostability. As mechanical enhancement to dentin and resistance to proteolytic biodegradation are both essential properties functional and stable dentin substrate, the structurally closely related PACs suggest a new metric, the dentin biomodification potential (DBMP) that may rationalize both properties.

Tri- and Tetrameric Proanthocyanidins with Dentin Bioactivities from Pinus massoniana

“…Access to the full 3D structure of PAC trimers, tetramers, and even higher oligomers in their native, underivatized form is critical to establish structure activity relationships from the subsequent biological evaluation, such as for the dentin biomodification potential of the compounds presented here, which were isolated from fractions with known bioactivity. The presented structural data expands both our prior reports [9][10][11] as well as other PAC literature by providing accurately and precisely assigned 13 C NMR resonances. This forms the knowledge base for making absolute stereochemical assignments of PAC monomers via inclusion of the -gauche effect observed in the 13 C NMR resonances of PACs, as well as the determination of differential (s.c.s) 13 C chemical shift values (C) relative to those in the terminal monomers and analogous dimers (here: 2 and 46).…”

“…ABSTRACT: Guided by dentin biomechanical bioactivity, this phytochemical study led to the elucidation of an extended set of structurally demanding proanthocyanidins (PACs). Unambiguous structure determination involved detailed spectroscopic and chemical characterization of four A-type dimers (2,(4)(5)(6), seven trimers (10)(11)(12)(13)(14)(15)(16), and six tetramers (17)(18)(19)(20)(21)(22). New outcomes confirm the feasibility of determining the absolute configuration of the catechol monomers in oligomeric PACs by 1D and 2D NMR.…”

“…In addition to the four known A-type dimers, epicatechin-(2→O→7,4→8)-catechin (2), 9 epicatechin-(2→O→7,4→8)-epicatechin (4), 9 epicatechin-(2→O→7,4→8)-ent-catechin (5), 10 and epicatechin-(2→O→7,4→8)-ent-epicatechin (6) 10 reported previously from this plant, seven trimers (10−16) and six tetramers (17−22) were isolated and characterized (Figure 1). Among these 13 PACs, eight are new structures, and one (11) 9 was revised based on new NMR evidence. In order to achieve rigorous structural evidence for these PACs, the following strategies were applied: (i) all NMR data sets were acquired at low temperatures (278 and/or 255 K) to achieve assignable spectra with high resolution.…”

Tri- and Tetrameric Proanthocyanidins with Dentin Bioactivities from Pinus massoniana

“…ABSTRACT: Guided by dentin biomechanical bioactivity, this phytochemical study led to the elucidation of an extended set of structurally demanding proanthocyanidins (PACs). Unambiguous structure determination involved detailed spectroscopic and chemical characterization of four A-type dimers (2, 4-6), seven trimers (10)(11)(12)(13)(14)(15)(16), and six tetramers (17)(18)(19)(20)(21)(22). New outcomes confirm the feasibility of determining the absolute configuration of the catechol monomers in oligomeric PACs by 1D and 2D NMR.…”

“…In the context of previously reported dentin-bioactive PACs, accurately and precisely assigned 13 C NMR resonances enabled absolute stereochemical assignments of PAC monomers via (i) inclusion of the 13 C NMR -gauche effect, and (ii) determination of differential 13 C chemical shift values (C) in comparison with those of the terminal monomer (unit II) in the dimers 2 and 46. Among the 13 fully elucidated PACs, eight were identified as new, and one structure (11) was revised based on new knowledge gained regarding the subtle, stereospecific spectroscopic properties of PACs.…”