Automated Structural Activity Screening of β‐Diketonate Assemblies with High‐Throughput Ion Mobility‐Mass Spectrometry

Abstract

Embracing complexity in design, metallo‐supramolecular self‐assembly presents an opportunity for fabricating materials of economic significance. The array of accessible supramolecules is alluring, along with favourable energy requirements. Implementation is hampered by an inability to efficiently characterise complex mixtures. The stoichiometry, size, shape, guest binding properties and reactivity of individual components and combinations thereof are inherently challenging to resolve. A large combinatorial library of four transition metals (Fe, Cu, Ni and Zn), and six β‐diketonate ligands at different molar ratios and pH was robotically prepared and directly analysed over multiple timepoints with electrospray ionisation travelling wave ion mobility‐mass spectrometry. The dataset was parsed for self‐assembling activity without first attempting to structurally assign individual species. Self‐assembling systems were readily categorised without manual data‐handling, allowing efficient screening of self‐assembly activity. This workflow clarifies solution phase supramolecular assembly processes without manual, bottom‐up processing. The complex behaviour of the self‐assembling systems was reduced to simpler qualities, which could be automatically processed.

Ion Mobility Mass Spectrometry for Large Synthetic Molecules: Expanding the Analytical Toolbox

“…Due to the high accuracy and resolving power of modern mass analysers, overlapping signals rarely occur, except for isomeric species with the exact same chemical composition, and the possibility of high-throughput (as applied in "omics" workflows) makes mass spectrometry an applicable tool to study synthetic products in industry. 7 Over the past two decades, the commercialization of certain techniques has further improved the standing of mass spectrometry among its analytical competitors: (1) implementation of better ion optics for soft ionization techniques such as (nano)-electrospray ionization (ESI and nESI), cryosprayionization (CSI) and matrix-assisted-laser desorption ionization (MALDI), facilitating the transfer of low concentration labile analytes and intermediates to the gas phase; 8 (2) hyphenation with gas and liquid chromatography for additional separation; (3) developments in tandem mass spectrometry (MS 2 ), which better enable the characterization of products from activated ions; 9 and (4) the addition of ion mobility (IM) to mass spectrometers, enabling the separation of ions not only based on their m/z, but also on their charge, shape and size (Table 1). 10,11 The focus of this perspective will be on the use of ion mobility coupled to mass spectrometry (IM-MS).…”

“…Modern mass spectrometry (MS) is well suited to overcome the experimental challenges in analyzing large synthetic complexes, and can provide large, robust and reproducible data sets with high throughput capabilities, which will in turn inform predictive computational design. , As ions are separated by their mass to charge ratio, which is determined by their chemical composition, the mass of a given analyte can be predicted and compared to measurement. Due to the high accuracy and resolving power of modern mass analysers, overlapping signals rarely occur, except for isomeric species with the exact same chemical composition, and the possibility of high-throughput (as applied in “omics” workflows) makes mass spectrometry an applicable tool to study synthetic products in industry …”