Understanding the Localization of Berylliosis: Interaction of Be2+ with Carbohydrates and Related Biomimetic Ligands
Understanding the Localization of Berylliosis: Interaction of Be2+ with Carbohydrates and Related Biomimetic Ligands
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DOI：
10.1002/chem.201903439
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发表时间：
2019-11
期刊：
影响因子：
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通讯作者：
Matthias Müller;M. R. Buchner
中科院分区：
文献类型：
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作者：
Matthias Müller;M. R. Buchner
摘要金属离子与多糖的相互作用对肺部免疫识别具有重要意义。由于铍相关疾病局限于肺，铍碳水化合物复合物可能在铍中毒的发展中起着至关重要的作用。在此，我们详细研究了Be 2+离子与果糖和葡萄糖以及更简单的仿生配体（模拟糖的结合动机）的相互作用。通过NMR和IR光谱以及单晶X射线衍射，辅以竞争反应，我们能够确定这些配体结合亲和力的独特趋势。这表明，在生理条件下，铍离子仅在相应生物分子提供准理想四面体环境和κ4-配位的情况下才不可逆地结合在糖蛋白或多糖中。此外，刘易斯酸诱导的配体转化和存在的OH-基团的Brønstedt酸度的极大增加意味着在封闭Be 2+时，糖蛋白或多糖中的金属离子可能诱导改变。此外，Be‐O‐杂环的频繁形成表明多核铍化合物可能是铍中毒的实际触发因素。铍配位化学的研究是通过对所选仿生配体与Al ~（3+）、Zn ~（2+）、Mg ~（2+）和Li ~（2+）的结合研究来补充的，结果表明，在给定的条件下，这些铍相关离子都没有四面体配位。因此，铍化合物的代谢研究不能用其他硬阳离子作为有害的Be 2+的替代品。
Abstract The interplay of metal ions with polysaccharides is important for the immune recognition in the lung. Due to the localization of beryllium associated diseases to the lung, it is likely that beryllium carbohydrate complexes play a vital role for the development of berylliosis. Herein, we present a detailed study on the interaction of Be2+ ions with fructose and glucose as well as simpler biomimetic ligands, which emulate binding motives of saccharides. Through NMR and IR spectroscopy as well as single‐crystal X‐ray diffraction, complemented by competition reactions we were able to determine a distinctive trend in the binding affinity of these ligands. This suggests that under physiological conditions beryllium ions are only bound irreversibly in glycoproteins or polysaccharides if a quasi ideal tetrahedral environment and κ4‐coordination is provided by the respective biomolecule. Furthermore, Lewis acid induced conversions of the ligands and an extreme increase in the Brønstedt acidity of the present OH‐groups imply that upon enclosure of Be2+, alterations may be induced by the metal ion in glycoproteins or polysaccharides. In addition the frequent formation of Be‐O‐heterocycles indicates that multinuclear beryllium compounds might be the actual trigger of berylliosis. This investigation on beryllium coordination chemistry was supplemented by binding studies of selected biomimetic ligands with Al3+, Zn2+, Mg2+, and Li+, which revealed that none of these beryllium related ions was tetrahedrally coordinated under the give conditions. Therefore, studies on the metabolization of beryllium compounds cannot be performed with other hard cations as a substitute for the hazardous Be2+.