Seed Molecule-Guided Strategy Facilitates the Precise Identification of "Hidden" Polymer Breakdown Products

<title>Abstract</title> Microplastics (MPs) are synthetic polymers that cause severe environmental pollution. However, most studies have primarily focused on the polymers themselves and little information is available regarding their breakdown products during environmental and biological processes. Identifying them is challenging due to structural diversity, especially with variations in both degree of polymerization (DP) and end-group modifications. In this study, we developed a non-targeted platform, named "Oligomer-Finder", which utilizes the liquid chromatography-high resolution mass spectrometry (LC-HRMS) for the screening and annotation of oligomers. Oligomer-Finder is based on the characteristics of oligomers, including repeated neutral losses (rNL), relationship between retention time (RT) and DP, and the mass of end groups (EG). The annotation from mass to structure was aided by custom-built polymer oligomer database (PODB) and oligomer end-group databases (OEGDBs). "Oligomer-Finder" identified dozens of unreported polymer oligomers with various end structures modified by nucleophiles in environmental and biological samples. Additionally, it revealed hundreds of mass spectrometry (MS) features representing unknown polymer breakdown products. Using poly (lactic acid) (PLA) as a model biodegradable plastic, the covalent modification of proteins by oligomers was first discovered, suggesting their biological activity. Our results demonstrate that "Oligomer-Finder" with user-friendly interface can effectively pinpoint oligomers and substantially expand unknown polymer breakdown products, allowing a life-cycle risk assessment.