Chemical Aspects of Human and Environmental Overload with Fluorine

Abstract

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and trends of the advance of fluorine-containing pharmaceuticals and agrochemicals, metabolism of fluorinated drugs, withdrawn fluorinated drugs, natural sources of organic and inorganic fluorine compounds in the environment (including the biosphere), sources of fluoride intake, and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.

Flurbiprofen: A Study of the Behavior of the Scalemate by Chromatography, Sublimation, and NMR

“…Of wider and greater significance, this first comprehensive study of the SDE properties of a marketed fluorinated drug opens up a new line of enquiry that should be pursued by industrial and academic research laboratories [77]. Thus, when considering the ever growing number of fluorine-containing drugs on the pharmaceutical market [78][79][80][81][82][83], the importance of including the SDE for a complete description of the physicochemical and biological [84] properties of a modern pharmaceutical can hardly be ignored.…”

Recommended Tests for the Self-Disproportionation of Enantiomers (SDE) to Ensure Accurate Reporting of the Stereochemical Outcome of Enantioselective Reactions

“…Indeed, substances containing fluorine [ 86 , 87 ] are known to often express exceptionally high SDE magnitudes by chromatography [ 34 ], sublimation [ 88 , 89 ], and even distillation [ 59 , 60 , 61 , 62 , 63 , 64 ]. This aspect is particularly important considering the rapid growth in the number of chiral, fluorine-containing pharmaceuticals [ 90 , 91 , 92 , 93 , 94 , 95 , 96 ] and agrochemicals [ 97 , 98 , 99 , 100 ]. Sulfoxides 3 , due to the highly polarized S–O bond, are another example of an SDE-phoric group [ 26 , 71 , 85 , 101 , 102 ].…”

“…In general, the introduction of fluorine into an organic compound, in particular, a trifluoromethyl or perfluoroalkyl group, noticeably increases the volatility of the resulting derivative. Considering the ever-increasing research into the design and synthesis of biologically active fluorinated compounds [ 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 132 , 133 ], this property of fluorine-containing molecules should be taken very seriously. Thus, since many small organic compounds, especially fluorine-containing ones, possess sufficiently high volatilities, they are prone to the SDE during processes involving gas-phase transformations.…”

Expanding organofluorine chemical space: the design of chiral fluorinated isosteres enabled by I(i)/I(iii) catalysis

“…21 A conspicuous feature of these bioactive molecules is the presence of both short alkyl fragments and vicinal oxidation patterns. Indeed, this latter feature commonly occurs in the low molecular weight APIs such as the bronchodilator Salbutamol (Ventolin®) (12). 22 It was envisaged that integrating these two common structural features in the development of a short, chiral uorinated group would also provide a much-needed solution to generating a bioisostere of the vicinal diol motif.…”