Formation of Carbohydrate–Metal Adducts from Solvent Mixtures during Electrospray: A Molecular Dynamics and ESI-MS Study

Abstract

Electrospray ionization (ESI) is frequently used to produce gas-phase ions for mass spectrometry (MS)-based techniques. The composition of solvents used in ESI-MS is often manipulated to enhance analyte ionization, including for carbohydrates. Moreover, to characterize analyte structures, ESI has been coupled to hydrogen/deuterium exchange, ion mobility, and tandem MS. Therefore, it is important to understand how solvent composition affects the structure of carbohydrates during and after ESI. In this work, we use molecular dynamics to simulate the desolvation of ESI droplets containing a model carbohydrate and observe the formation of carbohydrate adducts with metal ions. Molecular-level details on the effects of formulating mixtures of water, methanol, and acetonitrile to achieve enhanced ionization are presented. We complement our simulations with ESI-MS experiments. We report that when sprayed from aqueous mixtures containing volatile solvents, carbohydrates ionize to form metal−ion adducts rapidly due to rapid solvent evaporation rather than changes in the ionization mechanism. We find that when sprayed from solvent mixtures, carbohydrates are primarily solvated by water due to the migration of more volatile solvents to the surface of the droplet. Ultimately, the structure of the carbohydrate varies depending on its solvent environment, as inter-and intramolecular interactions are affected. We propose that solvents with 25% or more water may be used to enhance the ionization of carbohydrates with minimal effect on the structure during and after ESI.

Supercritical Fluid Nanospray Mass Spectrometry

“…The longer acyl chains showed higher signal intensity across all parameters investigated. This may be due to different interactions between analytes and the ionizing modifiers affecting the ionization mechanism and the corresponding MS detection sensitivity. , …”

“…This may be due to different interactions between analytes and the ionizing modifiers affecting the ionization mechanism and the corresponding MS detection sensitivity. 46,47 nSF Optimization. The robustness of the system was evaluated by comparing analyte signal intensity and the nESI current to changes in linear flow rate, spray voltage, and solvent composition.…”

ESI-MS reveals preferential complex formation of carbohydrates with Z-sinapinic acid compared with the E-isomer

“…(Frc, Glc > M7, βCD), (ii) the fructan is more efficiently ionized than the maltose (Frc > Glc; F5 > M5), whereas (iii) a cyclic maltose is more efficiently ionized than its linear equivalent (βCD > M7). Recently, Gallagher and collaborators 34 have provided further insight into the molecular interactions that govern the formation of [Carb + Na] + adduct ions from solvent mixtures during ESI using computational methods and ESI-MS experiments. Interestingly, they concluded that solvent mixtures with 25% or larger proportions of water in methanol are best for ESI-MS experiments.…”

Supercritical Fluid Nanospray Mass Spectrometry: II. Effects on Ionization

“…63 The nSF system showed fewer adducts, which may be due to the low methanol percentage in the droplet, less organic interferent counterions, and other alkali metal adducts. 14,64 The system provides enhanced sensitivity, especially in complex matrices. 65 The efficient nSF desolvation using 90:10 sCO 2 :CH 3 OH with 0.01% formic acid may have provided better ionization, desolvation, and ionic transmission and a small number of adduct peaks.…”