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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.
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“PFASs also play an important role in medical imaging and diagnostics, serving as contrast agents for MRI, ultrasound, PET, and multimodal imaging [52].”
From Industrial Applications, Environmental Fate, Human Exposure, and Health Effects of PFAS (2025) · cites this paper as [52]
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Sorted by citations
Historical and current usage of per- and polyfluoroalkyl substances (PFAS): A literature review
Gaines, L. G. T. (2023) · American Journal of Industrial Medicine · doi:10.1002/ajim.23362 · Cited by 665
Ultra-stable all-solid-state sodium metal batteries enabled by perfluoropolyether-based electrolytes
Wang, X., Zhang, C., Sawczyk, M., Sun, J. T., Yuan, Q., Chen, F., Mendes, T. C., Howlett, P. C., Fu, C., Wang, Y., et al. (2022) · Nature Materials · doi:10.1038/s41563-022-01296-0 · Cited by 355
Self-citationLiang, R., Xu, S., Han, Z., Yang, Y., Wang, K., Huang, Z., Rushlow, J., Cai, P., Samorı́, P., & Zhou, H.-C. “. (2024) · Journal of the American Chemical Society · doi:10.1021/jacs.3c14487 · Cited by 189
Fluorination Promotes the Cytosolic Delivery of Genes, Proteins, and Peptides
Lv, J., Wang, H., Rong, G., & Cheng, Y. (2022) · Accounts of Chemical Research · doi:10.1021/acs.accounts.1c00766 · Cited by 157
Gao, S., Rao, Y., Wang, X., Zhang, Q., Zhang, Z., Wang, Y., Guo, J., & Yan, F. (2024) · Advanced Materials · doi:10.1002/adma.202307585 · Cited by 144
Metadata
- Authors
- Zhang, C., Yan, K., Fu, C., Peng, H., Hawker, C. J., & Whittaker, A. K.
- Affiliations
- University of California, Santa Barbara (US)
- Shaanxi University of Science and Technology (CN)
- The University of Queensland (AU)
- Corresponding author
- Zhang, Cheng
- Yan, Kai
- Hawker, Craig J.
- Whittaker, Andrew K.
- Venue
- Chemical Reviews
- Publisher
- American Chemical Society (ACS)
- Published
- 2021-10-05
- Volume
- 122
- Issue
- 1
- Pages
- 167-208
- ISSN
- 0009-2665 (ISSN-L)
- 1520-6890
- OpenAlex
- W3203050184
- Cited by
- 493
- References
- 307
- Citations by year
- 2026: 92 · 2025: 126 · 2024: 117 · 2023: 87 · 2022: 69 · 2021: 1
- FWCI
- 6.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Chemical Reviews (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Army Research Office (W911NF-19-2-0026)
- National Health and Medical Research Council (APP1157440)
- China Postdoctoral Science Foundation (2018M633503)
- Australian Research Council (CE140100036)
- National Natural Science Foundation of China (51803112)
- Topics
- Physical Sciences › Chemistry › Organic Chemistry › Fluorine in Organic Chemistry
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Physical Sciences › Materials Science › Polymers and Plastics › Synthesis and properties of polymers
- Keywords
- fluorinated compounds, C-F bonds, fluorine-fluorine interactions, 19F MRI, molecular imaging, drug delivery, membrane permeability, pharmacokinetics, per- and polyfluoroalkyl substances, PFAS, environmental remediation, health risks, bioengineering, nanotechnology
- MeSH terms
- Pharmaceutical Preparations, Fluorine, Humans, Positron-Emission Tomography, Environmental Restoration and Remediation, Molecular Imaging
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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