Enveda-180: generation of a large open multimodal MS/MS and ion mobility spectral library for drug-like small molecules

Small-molecule characterization depends heavily on annotated MS/MS spectral libraries for reference matching and, in the case of open-source libraries, for training machine-learning-based structure elucidation. A primary bottleneck is the scarcity of such open data: current libraries such as GNPS, MSnLib, and MassBank, combined, contain spectra for approximately 150,000 unique compounds, representing a small fraction of known chemical space. These libraries are also sparse in complementary measurements such as liquid chromatography retention time (RT) and collisional cross section (CCS) from ion mobility mass spectrometry, the latter of which is seeing growing adoption in the field. To address these gaps, we present Enveda-180, an open spectral library built from high-throughput, pooled characterization of 184,330 structurally diverse small molecules, more than doubling the combined structural coverage of MS/MS open libraries, and more than 5x the combined open CCS values. Compounds were profiled at three collision energies in both positive and negative ion modes. We describe our profiling methods in detail, including the use of ion mobility to resolve multiple species of the same nominal ion structure. Enveda-180 substantially expands the chemical space covered by open MS/MS libraries and enables multimodal learning by integrating retention time, CCS, MS/MS, and metadata within a single resource.