In-silico green toxicology approach toward discovering safer ligands for development of safe-by-design metal–organic frameworks

A vast variety of chemical compounds have been fabricated and commercialized, they not only result in industrial exposure during manufacturing and usage, but also have environmental impacts throughout their whole life cycle. Consequently, attempts to assess the risk of chemicals in terms of toxicology have never ceased. In-silico toxicology, also known as predictive toxicology, has advanced significantly over the last decade as a result of the drawbacks of experimental investigations. In this study, ProTox-III was applied to predict the toxicity of the ligands used for metal-organic framework (MOF) design and synthesis. Initially, 35 ligands, that have been frequently utilized for MOF synthesis and fabrication, were selected. Subsequently, canonical simplified molecular-input line-entry system (SMILES) of ligands were extracted from the PUBCHEM database and inserted into the ProTox-III online server. Ultimately, webserver outputs including LD₅₀ and the probability of toxicological endpoints (cytotoxicity, carcinogenicity, mutagenicity, immunotoxicity, and ecotoxicity) were obtained and organized. According to retrieved LD₅₀ data, the safest ligand was 5-hydroxyisophthalic. In contrast, the most hazardous ligand was 5-chlorobenzimidazole, with an LD₅₀ of 8 mg/kg. Among evaluated endpoints, ecotoxicity was the most active and was detected in several imidazolate ligands. This data can open new horizons in design and development of green MOFs.