Computational Studies of Enzymes for C−F Bond Degradation and Functionalization

Organofluorine compounds have revolutionized chemical and pharmaceutical industries, serving as essential components in numerous applications and aspects of modern life. However, their bioaccumulation and resistance to degradation have resulted in environmental pollution, posing significant risks to human and animal health. The exceptionally strong C-F bond in these compounds makes their degradation challenging, with current methods often requiring extreme experimental conditions. Therefore, the development of eco-friendly approaches that operate under milder conditions is crucial, with enzyme-mediated C-F bond cleavage strategies emerging as a particularly promising solution. In this review, we present an overview of how computational approaches, including molecular docking, molecular dynamics simulations, quantum mechanics/molecular mechanics calculations, and bioinformatics, have been utilized to investigate the mechanisms underlying enzymatic C-F bond degradation and functionalization. This review highlights how these computational approaches provide critical insights into the atomic-level interactions and energetics underlying enzymatic processes, offering a foundation for the rational design and engineering of enzymes capable of addressing the challenges posed by fluorinated compounds. This review covers several types of enzymes including: fluoroacetate dehalogenases, cysteine dioxygenase, L-2-haloacid dehalogenase, cytochrome P450, fluorinase and tyrosine hydroxylase.