Biological Utility of Fluorinated Compounds: from Materials Design to Molecular Imaging, Therapeutics and Environmental Remediation

Abstract

The applications of fluorinated molecules in bioengineering and nanotechnology are expanding rapidly with the controlled introduction of fluorine being broadly studied due to the unique properties of C−F bonds. This review will focus on the design and utility of C−F containing materials in imaging, therapeutics, and environmental applications with a central theme being the importance of controlling fluorine−fluorine interactions and understanding how such interactions impact biological behavior. Low natural abundance of fluorine is shown to provide sensitivity and background advantages for imaging and detection of a variety of diseases with 19 F magnetic resonance imaging, 18 F positron emission tomography and ultrasound discussed as illustrative examples. The presence of C−F bonds can also be used to tailor membrane permeability and pharmacokinetic properties of drugs and delivery agents for enhanced cell uptake and therapeutics. A key message of this review is that while the promise of C−F containing materials is significant, a subset of highly fluorinated compounds such as per-and polyfluoroalkyl substances (PFAS), have been identified as posing a potential risk to human health. The unique properties of the C−F bond and the significant potential for fluorine−fluorine interactions in PFAS structures necessitate the development of new strategies for facile and efficient environmental removal and remediation. Recent progress in the development of fluorine-containing compounds as molecular imaging and therapeutic agents will be reviewed and their design features contrasted with environmental and health risks for PFAS systems. Finally, present challenges and future directions in the exploitation of the biological aspects of fluorinated systems will be described.

Study of Carbamoyl Fluoride: Synthesis, Properties and Applications

“…This is mainly due to the specific properties brought by fluorinated groups to molecules [1] . Thus, fluorinated substrates are present in a wide range of applications such as materials, [2] agrochemicals, [3] medicinal chemistry [4] or medical imaging [4f,5] …”

Photochemical Activation of Sulfur Hexafluoride: A Tool for Fluorination and Pentafluorosulfanylation Reactions

“…The incorporation of fluorinated substituents into organic molecules significantly affects their physical, chemical, biological and pharmaceutical properties. Fluorinated compounds play not only an important role in pharmaceutical chemistry, 27,28 but also in agrochemistry, 29 dye chemistry, 30 and material chemistry including optoelectronics. 28,31 Fluorination of a lead structure often increases metabolic stability and bioavailability and reduces the pKa of acidic groups in the surroundings.…”

“…Fluorinated compounds play not only an important role in pharmaceutical chemistry, 27,28 but also in agrochemistry, 29 dye chemistry, 30 and material chemistry including optoelectronics. 28,31 Fluorination of a lead structure often increases metabolic stability and bioavailability and reduces the pKa of acidic groups in the surroundings. 32 The most routinely used fluorinated motif is the trifluoromethyl (CF3) group.…”

“…Fluorinated compounds not only play an important role in pharmaceutical chemistry, 27,28 but also in agrochemistry, 29 dye chemistry, 30 and materials chemistry including optoelectronics. 28,31 Fluorination of a lead structure often increases met- This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.…”

An Activatable 19F MRI Molecular Probe for Sensing and Imaging of Norepinephrine

“…[23][24] 19 F, which is of 100 % natural abundance, a wide range of chemical shifts, a gyromagnetic ratio close to 1 H (94 % relative to 1 H), [25] is regarded as an ideal type of nuclei complementary to 1 H for MRI. Most importantly, [26][27] the 19 F content in the human body is extremely low (< 10 À 6 m), [28][29] which allows 19 F MRI to detect low concentration species with negligible background and render their distributions as "hot-spot" images. [30][31][32][33][34][35][36] Therefore, 19 F MRI is gaining momentum in the field of sensing and imaging low concentration bioactive species.…”