Complexation of Lignin Dimers with β‑Cyclodextrin and Binding Stability Analysis by ESI-MS, Isothermal Titration Calorimetry, and Molecular Dynamics Simulations

Lignin derived from lignocellulosic biomass is the largest source of renewable bioaromatics present on earth and requires environmentally sustainable separation strategies to selectively obtain high-value degradation products. Applications of supramolecular interactions have the potential to isolate lignin compounds from biomass degradation fractions by the formation of variable inclusion complexes with cyclodextrins (CDs). CDs are commonly used as selective adsorbents for many applications and can capture guest molecules in their internal hydrophobic cavity. The strength of supramolecular interactions between CDs and lignin model compounds that represent potential lignocellulosic biomass degradation products can be characterized by assessing the thermodynamics of binding stability. Consequently, the inclusion interactions of β-CD and lignin model compounds G-(β-O-4′)-G, G-(β-O-4′)-truncG (guaiacylglycerol-β-guaiacyl ether), and G-(β–β′)-G (pinoresinol) were investigated empirically by electrospray ionization mass spectrometry and isothermal titration calorimetry, complemented by molecular dynamics (MD) simulations. Empirical results indicate that there are substantial differences in binding stability dependent on the linkage type. The lignin model β–β′ dimer showed more potential bound states including 1:1, 2:1, and 1:2 (guest:host) complexation and, based on binding stability determinations, was consistently the most energetically favorable guest. Empirical results are supported by MD simulations that reveal that the capture of G-(β–β′)-G by β-CD is promising with a 66% probability of being bound for G-(β-O-4′)-truncG compared to 88% for G-(β–β′)-G (unbiased distance trajectory and explicit counting of bound states). These outcomes indicate CDs as a promising material to assist in separations of lignin oligomers from heterogeneous mixtures for the development of environmentally sustainable isolations of lignin compounds from biomass fractions.源自木质纤维素生物质的木质素是地球上现存规模最大的可再生生物芳烃来源，亟需采用环境友好的分离策略，以选择性获取高价值降解产物。超分子相互作用的应用潜力在于，可通过与环糊精（cyclodextrins，CDs）形成可变包合复合物，从生物质降解组分中分离木质素类化合物。环糊精常被用作多种场景的选择性吸附剂，能够将客体分子捕获于其内部疏水空腔中。针对作为潜在木质纤维素生物质降解产物的木质素模型化合物，环糊精与它们之间的超分子相互作用强度，可通过评估结合稳定性的热力学性质进行表征。为此，本研究通过电喷雾电离质谱（electrospray ionization mass spectrometry）与等温滴定量热法（isothermal titration calorimetry），并辅以分子动力学（molecular dynamics，MD）模拟，对β-环糊精（β-CD）与三种木质素模型化合物——G-(β-O-4′)-G、G-(β-O-4′)-truncG（愈创木基甘油-β-愈创木基醚）以及G-(β–β′)-G（松脂醇）——的包合相互作用开展了实验研究。实验结果表明，结合稳定性因连接键类型不同存在显著差异。木质素模型β–β′二聚体展现出更多潜在结合态，包括1:1、2:1及1:2（客体:主体）复合形式，且结合稳定性测定结果显示，其始终是热力学上最有利的客体分子。分子动力学模拟验证了上述实验结果：模拟结果显示，β-环糊精捕获G-(β–β′)-G的效果更优，G-(β-O-4′)-truncG的结合概率为66%，而G-(β–β′)-G的结合概率达88%（基于无偏距离轨迹与结合态显式计数分析）。上述结果表明，环糊精是一种极具应用前景的材料，可用于从多组分混合物中分离木质素低聚物，助力开发环境友好的生物质组分中木质素类化合物分离工艺。