Saintmont Fabrice, Hoyas Sébastien, Rosu Frédéric, Gabélica Valérie, Brocorens Patrick, Gerbaux Pascal
Organic Synthesis & Mass Spectrometry Laboratory, Interdisciplinary Center for Mass Spectrometry (CISMa), Center of Innovation and Research in Materials and Polymers (CIRMAP), University of Mons - UMONS, 23 Place du Parc, 7000 Mons, Belgium.
Laboratory for Chemistry of Novel Materials, Center of Innovation and Research in Materials and Polymers, Research Institute for Science and Engineering of Materials, University of Mons - UMONS, 23 Place du Parc, 7000 Mons, Belgium.
J Am Soc Mass Spectrom. 2022 Aug 3;33(8):1555-1568. doi: 10.1021/jasms.2c00122. Epub 2022 Jul 24.
The combination between ion mobility mass spectrometry and molecular dynamics simulations is demonstrated for the first time to afford valuable information on structural changes undergone by dendriplexes containing ds-DNA and low-generation dendrimers when transferred from the solution to the gas phase. Dendriplex ions presenting 1:1 and 2:1 stoichiometries are identified using mass spectrometry experiments, and the collision cross sections (CCS) of the 1:1 ions are measured using drift time ion mobility experiments. Structural predictions using Molecular Dynamics (MD) simulations showed that gas-phase relevant structures, i.e., with a good match between the experimental and theoretical CCS, are generated when the global electrospray process is simulated, including the solvent molecule evaporation, rather than abruptly transferring the ions from the solution to the gas phase. The progressive migration of ammonium groups (either NH from the buffer or protonated amines of the dendrimer) into the minor and major grooves of DNA all along the evaporation processes is shown to compact the DNA structure by electrostatic and hydrogen-bond interactions. The subsequent proton transfer from the ammonium (NH or protonated amino groups) to the DNA phosphate groups allows creation of protonated phosphate/phosphate hydrogen bonds within the compact structures. MD simulations showed major structural differences between the dendriplexes in solution and in the gas phase, not only due to the loss of the solvent but also due to the proton transfers and the huge difference between the solution and gas-phase charge states.
首次证明了离子淌度质谱与分子动力学模拟相结合，能够提供有关含双链DNA和低代树枝状大分子的树枝状复合物从溶液转移到气相时所经历结构变化的有价值信息。通过质谱实验鉴定出化学计量比为1:1和2:1的树枝状复合物离子，并使用漂移时间离子淌度实验测量1:1离子的碰撞截面（CCS）。使用分子动力学（MD）模拟进行的结构预测表明，当模拟包括溶剂分子蒸发在内的整体电喷雾过程时，会生成与气相相关的结构，即实验和理论CCS之间具有良好匹配，而不是将离子从溶液突然转移到气相。在整个蒸发过程中，铵基团（来自缓冲液的NH或树枝状大分子的质子化胺）逐渐迁移到DNA的小沟和大沟中，通过静电和氢键相互作用使DNA结构紧凑。随后铵（NH或质子化氨基）向DNA磷酸基团的质子转移允许在紧凑结构内形成质子化磷酸/磷酸氢键。MD模拟显示了树枝状复合物在溶液和气相中的主要结构差异，这不仅是由于溶剂的损失，还由于质子转移以及溶液和气相电荷状态之间的巨大差异。
