Two-Parameter Power Formalism for Structural Screening of Ion Mobility Trends: Applied Study on Artificial Molecular Switches

Recent literature provides increasing samples of structural studies relying on ion mobility coupled to mass spectrometry in view of characterizing gas-phase conformation and energetics properties of biomolecular ions. A typical framework consists in experimentally monitoring the collisional cross sections for various experimental conditions and using them as references to select appropriate candidate structures issued from theoretical modeling. Although it has proved successful for structural assignment, this process is resource costly and lengthy, namely due to intricacies in the selection of appropriate input geometries. In the present work, we propose simplified methodologies dedicated to the systematic screening of ion mobility data acquired on systems built from repetitive subunits and detail their application to challenging artificial molecular switch systems. Capitalizing on coarse-grained design, we first demonstrate how the assimilation of subunits into adequately assembled building-blocks can be used for fast assignments of a system topology. Further focusing on topology-specific differential ion mobility trends, we show that the building-block assemblies can be fused into single fully convex solid figure models, i.e., sphere and cylinder, whose projected areas follow a two-parameter power formalism A × nB. We show that the fitting parameters A and B were assigned as structural descriptors respectively associated with the dimensions of each constitutive subunit, i.e., size parameter, and with their assembled tridimensional arrangement, i.e., shape parameter. The present work provides a ready-to-use method for the screening of IM-MS data sets that is expected to facilitate the eventual design of input structures whenever advanced modeling calculations are required

Dynamics of Rayleigh Fission Processes in ∼100 nm Charged Aqueous Nanodrops

Fission of micron-size charged droplets has been observed using optical methods, but little is known about fission dynamics and breakup of smaller nanosize droplets that are important in a variety of natural and industrial processes. Here, spontaneous fission of individual aqueous nanodrops formed by electrospray is investigated using charge detection mass spectrometry. Fission processes ranging from formation of just two progeny droplets in 2 ms to production of dozens of progeny droplets over 100+ ms are observed for nanodrops that are charged above the Rayleigh limit. These results indicate that Rayleigh fission is a continuum of processes that produce progeny droplets that vary widely in charge, mass, and number

Dynamics of Rayleigh Fission Processes in ∼100 nm Charged Aqueous Nanodrops

Fission of micron-size charged droplets has been observed using optical methods, but little is known about fission dynamics and breakup of smaller nanosize droplets that are important in a variety of natural and industrial processes. Here, spontaneous fission of individual aqueous nanodrops formed by electrospray is investigated using charge detection mass spectrometry. Fission processes ranging from formation of just two progeny droplets in 2 ms to production of dozens of progeny droplets over 100+ ms are observed for nanodrops that are charged above the Rayleigh limit. These results indicate that Rayleigh fission is a continuum of processes that produce progeny droplets that vary widely in charge, mass, and number

Determination of Sialic Acid Isomers from Released <i>N</i>‑Glycans Using Ion Mobility Spectrometry

Complex carbohydrates are ubiquitous in nature and represent one of the major classes of biopolymers. They can exhibit highly diverse structures with multiple branched sites as well as a complex regio- and stereochemistry. A common way to analytically address this complexity is liquid chromatography (LC) in combination with mass spectrometry (MS). However, MS-based detection often does not provide sufficient information to distinguish glycan isomers. Ion mobility-mass spectrometry (IM-MS)a technique that separates ions based on their size, charge, and shapehas recently shown great potential to solve this problem by identifying characteristic isomeric glycan features such as the sialylation and fucosylation pattern. However, while both LC-MS and IM-MS have clearly proven their individual capabilities for glycan analysis, attempts to combine both methods into a consistent workflow are lacking. Here, we close this gap and combine hydrophilic interaction liquid chromatography (HILIC) with IM-MS to analyze the glycan structures released from human alpha-1-acid glycoprotein (hAGP). HILIC separates the crude mixture of highly sialylated multi-antennary glycans, MS provides information on glycan composition, and IMS is used to distinguish and quantify α2,6- and α2,3-linked sialic acid isomers based on characteristic fragments. Further, the technique can support the assignment of antenna fucosylation. This feature mapping can confidently assign glycan isomers with multiple sialic acids within one LC-IM-MS run and is fully compatible with existing workflows for N-glycan analysis