The role of fluorine in drug design and development is expanding rapidly as we learn more about the unique properties associated with this unusual element and how to deploy it with greater ...sophistication. The judicious introduction of fluorine into a molecule can productively influence conformation, pK a, intrinsic potency, membrane permeability, metabolic pathways, and pharmacokinetic properties. In addition, 18F has been established as a useful positron emitting isotope for use with in vivo imaging technology that potentially has extensive application in drug discovery and development, often limited only by convenient synthetic accessibility to labeled compounds. The wide ranging applications of fluorine in drug design are providing a strong stimulus for the development of new synthetic methodologies that allow more facile access to a wide range of fluorinated compounds. In this review, we provide an update on the effects of the strategic incorporation of fluorine in drug molecules and applications in positron emission tomography.
Since its first use in the steroid field in the late 1950s, the use of fluorine in medicinal chemistry has become commonplace, with the small electronegative fluorine atom being a key part of the ...medicinal chemist's repertoire of substitutions used to modulate all aspects of molecular properties including potency, physical chemistry and pharmacokinetics. This review will highlight the special nature of fluorine, drawing from a survey of marketed fluorinated pharmaceuticals and the medicinal chemistry literature, to illustrate key concepts exploited by medicinal chemists in their attempts to optimize drug molecules. Some of the potential pitfalls in the use of fluorine will also be highlighted.
The factors limiting the conductivity of fluorine‐doped tin dioxide (FTO) produced via atmospheric pressure chemical vapor deposition are investigated. Modeling of the transport properties indicates ...that the measured Hall effect mobilities are far below the theoretical ionized impurity scattering limit. Significant compensation of donors by acceptors is present with a compensation ratio of 0.5, indicating that for every two donors there is approximately one acceptor. Hybrid density functional theory calculations of defect and impurity formation energies indicate the most probable acceptor‐type defects. The fluorine interstitial defect has the lowest formation energy in the degenerate regime of FTO. Fluorine interstitials act as singly charged acceptors at the high Fermi levels corresponding to degenerately n‐type films. X‐ray photoemission spectroscopy of the fluorine impurities is consistent with the presence of substitutional FO donors and interstitial Fi in a roughly 2:1 ratio in agreement with the compensation ratio indicated by the transport modeling. Quantitative analysis through Hall effect, X‐ray photoemission spectroscopy, and calibrated secondary ion mass spectrometry further supports the presence of compensating fluorine‐related defects.
Compensating acceptor defects dramatically reduce electronic performance of F:SnO2 transparent conductor grown by chemical vapor deposition. Electron carrier mobilities are seen to be greatly diminished from the theoretically predicted optimum. Using hybrid density functional theory calculations and experimental methods, and analysis, the defect responsible for self‐compensation in F:SnO2 is determined to be the fluorine interstitial.
The emission of per- and polyfluoroalkyl substances (PFAS) from functional textiles was investigated via an outdoor weathering experiment in Sydney, Australia. Polyamide (PA) textile fabrics treated ...with different water-repellent, side-chain fluorinated polymers (SFPs) were exposed on a rooftop to multiple natural stressors, including direct sunlight, precipitation, wind, and heat for 6-months. After weathering, additional stress was applied to the fabrics through abrasion and washing. Textile characterization using a multiplatform analytical approach revealed loss of both PFAS-containing textile fragments (e.g., microfibers) as well as formation and loss of low molecular weight PFAS, both of which occurred throughout weathering. These changes were accompanied by a loss of color and water repellency of the textile. The potential formation of perfluoroalkyl acids (PFAAs) from mobile residuals was quantified by oxidative conversion of extracts from unweathered textiles. Each SFP-textile finish emitted a distinct PFAA pattern following weathering, and in some cases the concentrations exceeded regulatory limits for textiles. In addition to transformation of residual low molecular weight PFAA-precursors, release of polymeric PFAS from degradation and loss of textile fibers/particles contributed to overall PFAS emissions during weathering.
A robust and green electrochemical dearomatization of indoles was developed by merging a fluorine-containing group to an indole nucleus under oxidant-free conditions, delivering a diverse array of ...tri- and difluoromethylated 3,3-spiroindolines with good functional group tolerance.
The special properties of fluorine atoms and fluorine-containing groups have led to an increasing number of applications for fluorine-containing organic compounds, which are also extremely widely ...used in the field of new drug development. Unfortunately, naturally fluorinated organics are rare in nature, so the selective introduction of fluorine atoms or fluorine-containing groups into organic molecules is very important for pharmaceutical/synthetic chemists. N-2,2,2-trifluoroethylisatin ketimines have received the attention of many chemists since they were first developed as fluorine-containing synthons in 2015. This paper reviews the organic synthesis reactions in which trifluoroethyl isatin ketimine has been involved in recent years, focusing on the types of reactions and the stereoselectivity of products, and also provides a prospect of its application in this field.
Over the last 100–120 years, due to the ever-increasing importance of fluorine-containing compounds in modern technology and daily life, the explosive development of the fluorochemical industry led ...to an enormous increase of emission of fluoride ions into the biosphere. This made it more and more important to understand the biological activities, metabolism, degradation, and possible environmental hazards of such substances. This comprehensive and critical review focuses on the effects of fluoride ions and organofluorine compounds (mainly pharmaceuticals and agrochemicals) on human health and the environment. To give a better overview, various connected topics are also discussed: reasons and trends of the advance of fluorine-containing pharmaceuticals and agrochemicals, metabolism of fluorinated drugs, withdrawn fluorinated drugs, natural sources of organic and inorganic fluorine compounds in the environment (including the biosphere), sources of fluoride intake, and finally biomarkers of fluoride exposure.
Fluorine ion migration in normally-off AlN/GaN HEMTs fabricated by fluorine ion plasma implantation technology is evidenced. Devices under test are co-integrated into the OMMIC commercial ...D006GH/D01GH MMIC process, providing fluorine-free normally-on HEMTs. Gate reverse bias step-stress experiment at a drain fixed voltage of 0 V, carried out as well on normally-on ones as on normally-off ones, shows a permanent negative shift in the threshold voltage Vth of normally-off devices only. Vth degradation is starting at a VGS,stress of −8 V, with a negative shift from 0 V to −0.4 V at VGS,stress = −30 V, while the transconductance gm and gm,max remains unchanged prior to breakdown that occurred at VGS,stress ranging between −26 and −32 V. Since the positive threshold voltage of these devices is induced by F-ions dose and position, the above result suggests a possible drift of F-ions away from the 2DEG channel. A field-assisted migration mechanism of fluorine ions is proposed and supported by the absence of Vth degradation in fluorine-free normally-on devices.
The development of diversity-oriented synthesis based on fluorine-containing building blocks has been one of the hot research fields in fluorine chemistry. β-CFsub.3-1,3-enynes, as one type of ...fluorine-containing building blocks, have attracted more attention in the last few years due to their distinct reactivity. Numerous value-added trifluoromethylated or non-fluorinated compounds which have biologically relevant structural motifs, such as O-, N-, and S-heterocycles, carboncycles, fused polycycles, and multifunctionalized allenes were synthesized from these fluorine-containing building blocks. This review summarizes the most significant developments in the area of synthesis of organofluorine compounds based on β-CFsub.3-1,3-enynes, providing a detailed overview of the current state of the art.
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