Fluorine biological roles

Fluorine is an essential element involved in several enzymatic reactions in various organs, it is present as a trace element in bone mineral, dentine and tooth enamel and is considered as one of the most efficient elements for the prophylaxis and treatment of dental caries. In addition to their direct effect on cell biology, fluoride ions can also modify the physico-chemical properties of materials (solubility, structure and microstructure, surface properties), resulting in indirect biological effects. The biological and physico-chemical roles of fluoride ions are the main reasons for their incorporation in biomaterials, with a pre-eminence for the biological role and often both in conjunction. This chapter focuses on fluoridated bioceramics and related materials, including cements. The specific role of fluorinated polymers and molecules will not be reviewed here. 

Electrostatic interactions resulting from the polarity of the carbon-fluorine bond play an important role in the binding of fluorinated biologically active compounds to their effectors [22] (discussed in detail in Sections 4.5 and 4.6) and for the me-sophase behavior of fluorinated liquid crystals [23] (Section 4.4). The consequences of the low polarizability of perfluorinated molecular substructures have been put into commercial use for chlorofluorocarbon (CFG) refrigerants, fire fighting chemicals, lubricants, polymers with anti-stick and low-friction properties, and fluorosur-factants. 

The periodic table shown highlights the essential elements in the human body. Of special interest are the trace elements, such as iron (Fe), copper (Cu), zinc (Zn), iodine (I), cobalt (Co), selenium (Se), and fluorine (F), which together make up about 0.1 percent of the body s mass. Although the trace elements are present in very small amounts, they are crucial for our health. In many cases, however, their exact biological role is still not fully understood. 

This chapter deals with modifications of the physical and chemical properties of an organic molecule, which are induced by the replacement of hydrogen atoms by fluorines. These changes in the physicochemical properties play an important role in the behavior of the molecule when it is put into a biological environment. 

While the amino acid, which has been replaced by its fluorinated analogue, is essential for the functionality of the protein, some biological consequences can occur. Thus, incorporation of 2-F-His into mammalian proteins (4-F-His cannot be incorporated), in cell culture or invivo, is accompanied by inhibition of the induction of several enzymes (e.g., inhibition of acetyltransferase activity of the pineal gland). This probably stems from the formation of defective or inactive enzymes. Indeed, histidine plays an important role in the nucleophilic and acid-base processes connected to the catalytic activity of numerous enzymes. 

This example of the toxicity of fluoroacetate shows that interpreting a biological effect at the enzymological level requires long and complex studies. Thus, we must remember that explanations about the role of fluorine in the inhibition of enzymes should be considered with caution. In most cases, they must be considered as hypotheses. 

In Chapter 1, the main effects resulting from the introduction of fluorine atoms into a molecule are recalled. Chapter 2 focuses on the specific methods used to prepare fluorinated compounds, while Chapter 3 surveys the potential role of fluorine atoms in the biological activity of a molecule. 

Despite the quantity of collected data over the last fifty years, many questions remain about the effects induced by the presence of fluorine atoms on biologically active molecules. Indeed, the frequency of fluorine in pharmaceuticals has generally stemmed from structure-activity studies rather than rational predictions. In this book we attempt to rationalize and comprehend the role of fluorine in bioactivity. 

The simplicity and efficiency of the click chemistry is attractive to fluorine-18 chemistry, where time plays an important role in synthesis due to the relative short half-life of fluorine-18. This one-pot reaction provides a versatile tool for coupling drug-like fragments in high yield and under mild conditions. The product 1,2,3-triazole formed from cycloaddition is biologically stable with polarity and size similar to an amide group that is a common functional group in many radiopharmaceuticals [77],... 

Amino acids, peptides and proteins play essential roles in living systems. As chemists, we have the ability to fabricate new structures of great complexity. Yet frequently the synthesis and application of even the simplest chemical structures can contribute substantial information on living systems. This has certainly been true for the application of fluorine chemistry to the synthesis of fluorinated amino acids [1, 2], These molecules are not only interesting in their own right but may act as potent mechanism-based enzyme inhibitors that may have application in medicine or diagnostics, or they can be valuable probes that, incorporated into peptides or proteins, elucidate fundamental biological chemistry or uncover new aspects of biochemical structure and function [3-5],... 

Accordingly, I believe that it is the right time for us to review the recent advances and envision the new and exciting developments in the future. This book has a focus on the unique and significant roles that fluorine plays in medicinal chemistry and chemical biology, but also covers new and efficient synthetic methods for medicinal chemistry, 18F PET, and expanding applications of 19F NMR spectroscopy to biomedical research. 

Fluorine (F) is the second most active chemical element after astatine. It was isolated in 1886 by Henri Moisson in Paris (BriH 1995), and five years later, F. Erhardt in Germany recommended that pregnant women and children should take fluorine pastilles at second dentition. Moreover, F. Erhardt was the first to observe that fluorine fortified dogs dental enamel (Anke 1991). However surprising it is, now as before, the plastic role of fluorine is beyond doubt. Nevertheless, in spite of the availability of a wide class of flu-orous compounds with a pronounced physiological activity, some of the aspects of its biological effects are still not clear. 

The C-l Hydroxyl. We examined the role of the C-l hydroxyl in binding the receptor based on the activity of a fluorinated probe. Fluorination of biologically active compounds is useful for studying the... 

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