Subtle Chemical Shifts Explain the NMR Fingerprints of Oligomeric Proanthocyanidins with High Dentin Biomodification Potency.
Subtle Chemical Shifts Explain the NMR Fingerprints of Oligomeric Proanthocyanidins with High Dentin Biomodification Potency.
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DOI：
10.1021/acs.joc.5b01082
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发表时间：
2015-08-07
期刊：
影响因子：
--
通讯作者：
Pauli GF
中科院分区：
文献类型：
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作者：
Nam JW;Phansalkar RS;Lankin DC;Bisson J;McAlpine JB;Leme AA;Vidal CM;Ramirez B;Niemitz M;Bedran-Russo A;Chen SN;Pauli GF
某些低聚原花青素(OPAC)增强牙本质生物力学性能的能力涉及通过蛋白质-多酚相互作用使1.3-4.5 nm宽空间的胶原交联。对松树皮生物活性原理的系统跨学科研究已经产生了三聚体PAC，ent-epicatechin-(4β→8)-epicatechin-(2β→O→7，4β→8)-catechin(3)，它代表了迄今为止能够增强牙本质硬度的最有效的单一化学实体。从两个同类的PAC二聚体构建的案例中，详细的结构分析破译了三个牙本质生物调节剂的立体化学、空间排列和化学性质。核磁共振谱的量子力学驱动的1H迭代全旋分析(QM-HIFSA)区分了以前未被识别的细节，如高阶J耦合，并提供了关于3D结构的有价值的信息。通过QM-Hifsa对H/D交换效应的检测和定量，确定C-8和C-6是(Re)活性部位，解释了生物合成中的偏好，并暗示它们参与了牙本质的交联活性。这些分子性质的图谱强调了在1H和13C核磁共振波谱中高δ精度的重要性。发生在低到亚ppb水平上，这些新表征的ppb中的化学位移差异是OPAC药效团固有的动态过程的微小但诊断性测量，并有助于增强我们对生物修饰牙本质大分子中纳米级分子间相互作用的理解。
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 1H 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 1H and 13C 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.