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Biomolecules Mar 2021Bones are metabolically active organs. Their reconstruction is crucial for the proper functioning of the skeletal system during bone growth and remodeling, fracture... (Review)
Review
Bones are metabolically active organs. Their reconstruction is crucial for the proper functioning of the skeletal system during bone growth and remodeling, fracture healing, and maintaining calcium-phosphorus homeostasis. The bone metabolism and tissue properties are influenced by trace elements that may act either indirectly through the regulation of macromineral metabolism, or directly by affecting osteoblast and osteoclast proliferation or activity, or through becoming part of the bone mineral matrix. This study analyzes the skeletal impact of macroelements (calcium, magnesium, phosphorus), microelements (fluorine), and heavy metals (lead), and discusses the concentration of each of these elements in the various bone tissues.
Topics: Animals; Bone Density; Bone and Bones; Calcium; Fluorine; Humans; Lead; Magnesium; Phosphorus
PubMed: 33800689
DOI: 10.3390/biom11040506 -
Molecules (Basel, Switzerland) Feb 2021The synthesis of fluorine-containing small molecules has had numerous benefits of improving the quality and efficiency of many applications of these compounds. For... (Review)
Review
The synthesis of fluorine-containing small molecules has had numerous benefits of improving the quality and efficiency of many applications of these compounds. For example, fluorine adds promising functionalities in various areas of imaging (MRI, PET, and NIR); gives cell-targeting properties; and has demonstrated improvements in cell permeability, solubility, and other pharmacologic properties. For these and other numerous reasons, fluorination of molecules has grown in popularity in various fields of chemistry. Many reports show the effects observed from increasing the number of fluorine atoms on a fluorophore scaffold. This report will cover the most significant applications and improvements that fluorine has contributed to in various dye scaffolds such as BODIPY, rhodamine, phthalocyanine, and cyanine in the recent decade.
Topics: Fluorescent Dyes; Fluorine; Molecular Structure
PubMed: 33671600
DOI: 10.3390/molecules26041160 -
Molecules (Basel, Switzerland) Dec 2022The development of diversity-oriented synthesis based on fluorine-containing building blocks has been one of the hot research fields in fluorine chemistry.... (Review)
Review
The development of diversity-oriented synthesis based on fluorine-containing building blocks has been one of the hot research fields in fluorine chemistry. -CF-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 -, -, and -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 -CF-1,3-enynes, providing a detailed overview of the current state of the art.
Topics: Fluorine; Stereoisomerism
PubMed: 36558151
DOI: 10.3390/molecules27249020 -
Chemical Reviews Apr 2021Over 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... (Review)
Review
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.
Topics: Environmental Pollutants; Environmental Pollution; Fluorine; Hydrocarbons, Fluorinated
PubMed: 33723999
DOI: 10.1021/acs.chemrev.0c01263 -
Angewandte Chemie (International Ed. in... Jun 2022(Hetero)arylsulfur compounds where the S atom is in the oxidation state VI represent a large percentage of the molecular functionalities present in organic chemistry.... (Review)
Review
(Hetero)arylsulfur compounds where the S atom is in the oxidation state VI represent a large percentage of the molecular functionalities present in organic chemistry. More specifically, (hetero)aryl-S fluorides have recently received enormous attention because of their potential as chemical biology probes, as a result of their reactivity in a simple, modular, and efficient manner. Whereas the synthesis and application of the level 1 fluorination at S atoms (sulfonyl and sulfonimidoyl fluorides) have been widely studied and reviewed, the synthetic strategies towards higher levels of fluorination (levels 2 to 5) are somewhat more limited. This Minireview evaluates and summarizes the progress in the synthesis of highly fluorinated aryl-S compounds at all levels, discussing synthetic strategies, reactivity, the advantages and disadvantages of the synthetic procedures, the proposed mechanisms, and the potential upcoming opportunities.
Topics: Fluorides; Halogenation; Oxidation-Reduction
PubMed: 35303387
DOI: 10.1002/anie.202200904 -
Applied Microbiology and Biotechnology Nov 2021Fluorinated compounds are widely used in the fields of molecular imaging, pharmaceuticals, and materials. Fluorinated natural products in nature are rare, and the... (Review)
Review
Fluorinated compounds are widely used in the fields of molecular imaging, pharmaceuticals, and materials. Fluorinated natural products in nature are rare, and the introduction of fluorine atoms into organic compound molecules can give these compounds new functions and make them have better performance. Therefore, the synthesis of fluorides has attracted more and more attention from biologists and chemists. Even so, achieving selective fluorination is still a huge challenge under mild conditions. In this review, the research progress of enzymatic synthesis of fluorinated compounds is summarized since 2015, including cytochrome P450 enzymes, aldolases, fluoroacetyl coenzyme A thioesterases, lipases, transaminases, reductive aminases, purine nucleoside phosphorylases, polyketide synthases, fluoroacetate dehalogenases, tyrosine phenol-lyases, glycosidases, fluorinases, and multienzyme system. Of all enzyme-catalyzed synthesis methods, the direct formation of the C-F bond by fluorinase is the most effective and promising method. The structure and catalytic mechanism of fluorinase are introduced to understand fluorobiochemistry. Furthermore, the distribution, applications, and future development trends of fluorinated compounds are also outlined. Hopefully, this review will help researchers to understand the significance of enzymatic methods for the synthesis of fluorinated compounds and find or create excellent fluoride synthase in future research.Key points• Fluorinated compounds are distributed in plants and microorganisms, and are used in imaging, medicine, materials science.• Enzyme catalysis is essential for the synthesis of fluorinated compounds.• The loop structure of fluorinase is the key to forming the C-F bond.
Topics: Aldehyde-Lyases; Catalysis; Fluorine; Halogenation; Transaminases
PubMed: 34625820
DOI: 10.1007/s00253-021-11608-0 -
Chemical Society Reviews Jul 2020Fluorochemicals are a widely distributed class of compounds and have been utilized across a wide range of industries for decades. Given the environmental toxicity and... (Review)
Review
Fluorochemicals are a widely distributed class of compounds and have been utilized across a wide range of industries for decades. Given the environmental toxicity and adverse health threats of some fluorochemicals, the development of new methods for their decomposition is significant to public health. However, the carbon-fluorine (C-F) bond is among the most chemically robust bonds; consequently, the degradation of fluorinated hydrocarbons is exceptionally difficult. Here, metalloenzymes that catalyze the cleavage of this chemically challenging bond are reviewed. These enzymes include histidine-ligated heme-dependent dehaloperoxidase and tyrosine hydroxylase, thiolate-ligated heme-dependent cytochrome P450, and four nonheme oxygenases, namely, tetrahydrobiopterin-dependent aromatic amino acid hydroxylase, 2-oxoglutarate-dependent hydroxylase, Rieske dioxygenase, and thiol dioxygenase. While much of the literature regarding the aforementioned enzymes highlights their ability to catalyze C-H bond activation and functionalization, in many cases, the C-F bond cleavage has been shown to occur on fluorinated substrates. A copper-dependent laccase-mediated system representing an unnatural radical defluorination approach is also described. Detailed discussions on the structure-function relationships and catalytic mechanisms provide insights into biocatalytic defluorination, which may inspire drug design considerations and environmental remediation of halogenated contaminants.
Topics: Carbon; Fluorine; Metalloproteins
PubMed: 32510080
DOI: 10.1039/c9cs00740g -
Molecules (Basel, Switzerland) Sep 2023Glycomimetics, which are synthetic molecules designed to mimic the structures and functions of natural carbohydrates, have been developed to overcome the limitations... (Review)
Review
Glycomimetics, which are synthetic molecules designed to mimic the structures and functions of natural carbohydrates, have been developed to overcome the limitations associated with natural carbohydrates. The fluorination of carbohydrates has emerged as a promising solution to dramatically enhance the metabolic stability, bioavailability, and protein-binding affinity of natural carbohydrates. In this review, the fluorination methods used to prepare the fluorinated carbohydrates, the effects of fluorination on the physical, chemical, and biological characteristics of natural sugars, and the biological activities of fluorinated sugars are presented.
Topics: Fluorine; Drug Discovery; Carbohydrates; Sugars; Biological Availability; Halogenation
PubMed: 37764416
DOI: 10.3390/molecules28186641 -
Angewandte Chemie (International Ed. in... Jan 2023Automated glycan assembly (AGA) on solid support has become invaluable in reconciling the biological importance of complex carbohydrates with the persistent challenges...
Automated glycan assembly (AGA) on solid support has become invaluable in reconciling the biological importance of complex carbohydrates with the persistent challenges associated with reproducible synthesis. Whilst AGA platforms have transformed the construction of many natural sugars, validation in the construction of well-defined (site-selectively modified) glycomimetics is in its infancy. Motivated by the importance of fluorination in drug discovery, the biomedical prominence of 2-fluoro sugars and the remarkable selectivities observed in fluorine-directed glycosylation, fluorine-directed automated glycan assembly (FDAGA) is disclosed. This strategy leverages the fluorine atom for stereocontrolled glycosylation on solid support, thereby eliminating the reliance on O-based directing groups. The logical design of C2-fluorinated mannose building blocks, and their application in the fully (α-)stereocontrolled automated assembly of linear and branched fluorinated oligomannosides, is disclosed. This operationally simple strategy can be integrated into existing AGA and post-AGA protocols to augment the scope of programmed carbohydrate synthesis.
Topics: Fluorine; Polysaccharides; Carbohydrates; Glycosylation; Sugars
PubMed: 36331042
DOI: 10.1002/anie.202213304 -
Nature Chemistry Sep 2022Modification of polyketides with fluorine offers a promising approach to develop new pharmaceuticals. While synthetic chemical methods for site-selective incorporation...
Modification of polyketides with fluorine offers a promising approach to develop new pharmaceuticals. While synthetic chemical methods for site-selective incorporation of fluorine in complex molecules have improved in recent years, approaches for the biosynthetic incorporation of fluorine in natural compounds are still rare. Here, we report a strategy to introduce fluorine into complex polyketides during biosynthesis. We exchanged the native acyltransferase domain of a polyketide synthase, which acts as the gatekeeper for the selection of extender units, with an evolutionarily related but substrate tolerant domain from metazoan type I fatty acid synthase. The resulting polyketide-synthase/fatty-acid-synthase hybrid can utilize fluoromalonyl coenzyme A and fluoromethylmalonyl coenzyme A for polyketide chain extension, introducing fluorine or fluoro-methyl units in polyketide scaffolds. We demonstrate the feasibility of our approach in the chemoenzymatic synthesis of fluorinated 12- and 14-membered macrolactones and fluorinated derivatives of the macrolide antibiotics YC-17 and methymycin.
Topics: Acyltransferases; Animals; Coenzyme A; Fluorine; Polyketide Synthases; Polyketides
PubMed: 35879443
DOI: 10.1038/s41557-022-00996-z