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Optical Circular Dichroism Spectroscopy of Ions in the Mass Spectrometer: from Handedness to Helices

Objective

Chirality is not only a fascinating feature of the molecules of Life; it influences biological activity, optical behavior, and the performance of pharmaceuticals and functional materials. Mass spectrometry (MS) excels at resolving molecular stoichiometries and complex mixtures, yet it remains blind to chirality. In contrast, circular dichroism (CD), especially in the UV-visible range (optical CD or OCD), is a key technique for probing molecular folding and chirality in solution. CHIRAMASS will integrate both approaches and directly probe the chirality of ions in the mass spectrometer using chiral light. Although we previously managed to record electronic CD spectra of DNA structures in the gas phase by monitoring electron detachment upon irradiation with circularly polarized laser light (Science, 2020), electron photodetachment remains limited to multiply charged anions. CHIRAMASS aims to develop a much more broadly applicable concept of OCD ion spectroscopy: by implementing cold ion tagging and monitoring photodissociation, we will be able to study singly charged and positively charged ions—greatly expanding the scope of gas-phase chiral analysis. Beyond inert gas tagging, we will also explore creative tagging strategies, such as ion–molecule complexes with aromatic or chiral compounds, to probe chirality transfer and diastereoisomer formation. CHIRAMASS will address fundamental questions (e.g. What determines the balance between tag loss, photodissociation, and electron photodetachment? How does the chromophore identity influence this competition?), and the coupling of MS with OCD and ion mobility spectrometry will enable us to explore hot topics, such as the secondary structures of soluble oligomers of amyloid-forming proteins, the ligand binding modes of DNA complexes, solvent and aggregation effects on amino acid CD signals, and practical applications such as assigning absolute configurations of drugs and natural products directly in MS.

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(opens in new window) ERC-2025-ADG

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Host institution

UNIVERSITE DE GENEVE
Net EU contribution

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€ 3 287 555,00
Address
RUE DU GENERAL DUFOUR 24
1211 Geneve
Switzerland

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Region
Schweiz/Suisse/Svizzera Région lémanique Genève
Activity type
Higher or Secondary Education Establishments
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Total cost

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Beneficiaries (1)