Electrospray Ionization Mass Spectrometry in Catalytic Mechanisms

Electrospray ionization mass spectrometry (ESI-MS) has emerged as a pivotal analytical tool for elucidating catalytic pathways at the molecular level. By gently transferring ionic species from solution into the gas phase, ESI-MS enables direct observation of charged intermediates, catalyst–substrate adducts and transient complexes that are often inaccessible by conventional spectroscopic or crystallographic methods. Advances in source design, ion‐mobility separation and tandem mass spectrometry have significantly improved sensitivity and structural resolution, allowing real‐time reaction monitoring and quantitative kinetic measurements. These innovations have fostered a deeper mechanistic understanding of homogeneous and heterogeneous catalysis, revealing key steps such as ligand exchange, oxidative addition, reductive elimination and substrate activation. Moreover, ambient ionization techniques and microfluidic coupling now permit in situ studies under near-operando conditions, bridging the gap between simplified model systems and practical catalytic environments. Collectively, these developments have transformed ESI-MS from a mere detection technique into a comprehensive platform for mapping entire catalytic cycles, quantifying rate constants and dissecting structure–reactivity relationships with unprecedented clarity.

Research from Nature Portfolio

Recent studies have demonstrated the power of real-time ESI-MS to capture fleeting catalytic intermediates in complex reaction networks. One report employed rapid‐sampling loops coupled to high‐resolution ESI-MS to observe and quantify sequential oxidative addition and migratory insertion steps in palladium-catalysed cross-coupling, enabling direct determination of rate‐limiting barriers. Another advance integrated ion-mobility separation with trapped ion mobility spectrometry to resolve isomeric rhodium hydride and σ-alkene complexes during asymmetric hydrogenation, revealing the influence of ligand geometry on enantioselectivity. A third study applied microfluidic electrospray interfaces to follow enzyme-catalysed oxidation in real time, detecting covalent flavin intermediates and protonation states that dictate catalytic turnover. These contributions highlight the maturation of ESI-MS into a quantitative and structural probe for both organometallic and biocatalytic systems.

Electrospray Ionization Mass Spectrometry in Catalytic Mechanisms publication trend

The graph below shows the total number of articles in electrospray ionization mass spectrometry in catalytic mechanisms across all publications each year (not limited to Nature Index journals).

Technical terms

Electrospray ionization (ESI): A soft ionization method that generates gas-phase ions from solution by applying a high voltage to a liquid stream, preserving non-covalent interactions and labile intermediates.

Ion mobility spectrometry (IMS): A gas-phase separation technique that differentiates ions based on their collision cross-section, enabling resolution of isomeric or conformational species.

Collision-induced dissociation (CID): A tandem MS approach in which ions are energetically activated by collisions with an inert gas, causing fragmentation for structural elucidation.

Oxidative addition / reductive elimination: Fundamental elementary steps in organometallic catalysis where a metal centre increases or decreases its oxidation state by forming or breaking bonds with ligands or substrates.

References

1. Kinetics of ligand exchange in solution: a quantitative mass spectrometry approach. Chemical Science (2023).
2. Identifying reactive intermediates by mass spectrometry. Chemical Science (2020).
3. The Expanding Role of Electrospray Ionization Mass Spectrometry for Probing Reactive Intermediates in Solution. Molecules (2012).
4. Autocatalysis in Eschenmoser Coupling Reactions. Chemistry - A European Journal (2023).