Extreme Ultraviolet Photodissociation Decodes the Chain Modifications of Lipids

Chain modifications play critical roles in the modulation of biological functions. However, current mass spectrometry (MS) methods fall short in providing the diagnostic fragments of lipid chain modifications due to the limitations of vibrational excited fragmentations. Herein, we introduce a novel extreme ultraviolet photodissociation (EUPD), which integrates a tunable-wavelength extreme ultraviolet-free electron laser (EUV-FEL) into the MS dissociation chamber, enabling ultrafast photoexcitation and -dissociation of lipids via the dissociation pathways in electronic excited states. EUPD offers unprecedented photochemical manipulations over fragmentation patterns by tuning the EUV photon energy, enabling the highly selective cleavage of specific chemical bonds according to their different dissociation thresholds. This wavelength tunability generates rich types of diagnostic fragments for diverse lipid chain modifications, including methyl branching (95-100 nm), cyclopropane rings (100-150 nm), polyunsaturation (90-100 nm), and oxidation (140-150 nm). EUPD exhibits great potential to revolutionize MS-based lipid analysis and significantly promotes the elucidation of lipid structure-function relationships.