Trends in Organofluorine Chemistry Reveal Gaps in Knowledge on Environmental Persistence

The use of fluorination remains a common functionalization strategy across diverse fields of industrial and medicinal chemistry, but environmental fate studies have largely focused on perfluorinated compounds, leaving critical gaps in our understanding of how partially fluorinated substances degrade in the environment. This perspective discusses trends in modern organofluorine chemistry within the last five years and compares the structures proposed in those publications to those for which environmental fate studies exist. To facilitate comparisons, we define two simple metrics to describe fluorination of diverse chemical backbones: the fluorine atom fraction (FAF), and the presence of specific fluorinated groups, added through appending per- and polyfluorinated functional groups, such as -CF3 or -CF2H, to an existing chemical structure with a known functionality. Newly proposed substances have relatively lower degrees of fluorination than those that have been characterized for environmental degradation yet can achieve similar characteristics associated with "druggability", such as lipophilicity and topological surface area. The extent of defluorination in the environment shows low correlation with FAF, though within subclasses of chemical backbones some trends emerge, highlighting the importance of the local bonding environment when fluorinated moieties are a small part of the overall structure of a chemical. Building a predictive understanding of how the type and degree of fluorination and backbone characteristics intersect to determine the environmental behavior of these compounds will be critical to enabling innovation while safeguarding environmental and human health.