Diserinol Isophthalamide: A Novel Reagent for Complexation with Biomolecular Anions in Electrospray Ionization Mass Spectrometry
Diserinol Isophthalamide: A Novel Reagent for Complexation with Biomolecular Anions in Electrospray Ionization Mass Spectrometry
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DOI：
10.1021/jasms.3c00010
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发表时间：
2023-03-28
影响因子：
3.2
通讯作者：
Thomas，Daniel A.
中科院分区：
文献类型：
--
作者：
Schultz，Madeline;Parker，Sarah L.;Thomas，Daniel A.
将生物分子从溶液转移到真空，通过将感兴趣的分子从复杂的环境中分离出来，促进了对分子结构和动力学的详细分析。然而，离子去溶过程中固有的是失去溶剂氢键伙伴，这对凝聚相结构的稳定性至关重要。因此，离子转移到真空有利于结构重排，特别是在溶剂可接近的电荷位附近，在没有溶剂的情况下，这些电荷位倾向于采用分子内氢键基元。单烷基铵部分(如赖氨酸侧链)与冠醚(如18-冠-6)的络合作用不利于质子化中心的结构重排，但还没有研究过去质子化基团的等价配体。在此，我们描述了一种用于生物分子中阴离子部分的气相络合的新试剂--二色酚间苯二甲酰胺(DIP)。在电喷雾电离质谱仪(ESI-MS)研究中，观察到模型小肽GD、Ge、GG、DF-OME、Vyv、YGGFL和EYMPME的C末端或侧链发生络合作用。此外，还观察到与磷酸丝氨酸和磷酸酪氨酸的磷酸盐和羧酸基的络合作用。与现有的阴离子识别试剂1，1‘-(1，2-亚苯基)双(3-苯基脲)相比，DIP表现出更好的性能，后者在有机溶剂中表现出中等的羧酸盐结合。在ESI-MS实验中，这种改进的性能归因于减少了与较大分子的羧酸基络合的空间约束。总体而言，异苯二甲酸二色胺是一种有效的络合剂，可用于未来研究溶液相结构的保留、研究内在分子性质和考察溶剂化效应。
Transferring biomolecules from solution to vacuum facilitates a detailed analysis of molecular structure and dynamics by isolating molecules of interest from a complex environment. However, inherent in the ion desolvation process is the loss of solvent hydrogen bonding partners, which are critical for the stability of a condensed-phase structure. Thus, transfer of ions to vacuum can favor structural rearrangement, especially near solvent-accessible charge sites, which tend to adopt intramolecular hydrogen bonding motifs in the absence of solvent. Complexation of monoalkylammonium moieties (e.g., lysine side chains) with crown ethers such as 18-crown-6 can disfavor structural rearrangement of protonated sites, but no equivalent ligand has been investigated for deprotonated groups. Herein we describe diserinol isophthalamide (DIP), a novel reagent for the gas-phase complexation of anionic moieties within biomolecules. Complexation is observed to the C-terminus or side chains of the small model peptides GD, GE, GG, DF-OMe, VYV, YGGFL, and EYMPME in electrospray ionization mass spectrometry (ESI–MS) studies. In addition, complexation is observed with the phosphate and carboxylate moieities of phosphoserine and phosphotyrosine. DIP performs favorably in comparison to an existing anion recognition reagent, 1,1′-(1,2-phenylene)bis(3-phenylurea), that exhibits moderate carboxylate binding in organic solvent. This improved performance in ESI–MS experiments is attributed to reduced steric constraints to complexation with carboxylate groups of larger molecules. Overall, diserinol isophthalamide is an effective complexation reagent that can be applied in future work to study retention of solution-phase structure, investigate intrinsic molecular properties, and examine solvation effects.