Network toxicology, AlphaFold 3 and molecular docking for analysing the toxicity of heavy metal ions and their organic complexes in environmental pollutants: A case of Cobalt(II) ion & Bis-(2,4-pentanedionato)cobalt(II)

The aim of this study is to advance the application of network toxicology, AlphaFold 3 and molecular docking techniques in the toxicity analysis of heavy metal ions (HMIs) and heavy metal ions organic complexes (HMIOCs) in environmental pollutants. In this study, the potential toxicity and molecular mechanisms of HMIs and HMIOCs in environmental pollutants were effectively investigated using Cobalt(II) ion & Bis-(2,4-pentanedionato)cobalt(II) (Co(II) & BPCo(II)) as examples. It was found that Co(II) & BPCo(II) regulates multiple signaling pathways by modulating hub targets such as APP, NR3C1, ESR1, CASP3, MMP9, and PTGS2. These pathways include Serotonergic synapse, Cocaine addiction, Pathways of neurodegeneration-multiple diseases, Calcium signaling pathway, Neuroactive ligand-receptor interactions, Alzheimer disease and other pathways, which in turn affects the Blood-Brain Barrier (BBB) in order to destroy neuronal cells, ultimately leading to a variety of mental illnesses (MIs) and nervous system diseases (NSDs), such as Schizophrenia, Depressive disorder, nervous system disorder and Alzheimer Disease, Late Onset. In this study, the toxic effects and molecular mechanisms of Co(II) and BPCo(II) were elucidated, while the limitations of conventional toxicological methods—such as safety issues, time constraints, high expenses, ethical concerns regarding animal use, and limited predictive power—were effectively addressed. These results contribute to the foundation for studying disease diagnosis associated with environmental exposure to HMIs and HMIOCs.