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.