¹⁹F-labeled molecular probes for fingerprint identification and quantitative analysis of malondialdehyde in urine

Aldehydes are crucial cellular intermediates and early diagnostic biomarkers for numerous diseases and injuries. Despite significant advancements in aldehyde detection, accurately distinguishing and quantifying these biomarkers remains challenging due to their similar chemical reactivities. ¹⁹F nuclear magnetic resonance (¹⁹F NMR) spectroscopy, characterized by a broad spectral range and unique chemical shifts, provides a powerful approach for the simultaneous and quantitative analysis of multiple targets. Here, we rationally designed a class of ¹⁹F-labeled molecular probes featuring a hydrazine moiety as the aldehyde recognition site, enabling specific identification and differentiation of aldehydes via easily interpretable changes in ¹⁹F chemical shifts. The chemical shift of the probe ¹⁹F-AP-1 at δ¹⁹F -120.8 ppm shifted to -112.3 ppm after its reaction with malondialdehyde (MDA). This approach allows for the selective "fingerprint" recognition of malondialdehyde (MDA) within complex aldehyde mixtures under the specified ¹⁹F NMR conditions (256 scans, 376 MHz transmitter frequency) with the acquisition time of 7 min 39 s, overcoming interferences from background matrices. This work provides a robust method that allows for qualitative and quantitative analyses of MDA directly in human urine samples without requiring pretreatment, highlighting its potential applicability for MDA detection across a range of biological fluids.