Quantifying CO-release from a photo-CORM using 19F NMR: An investigation into light-induced CO delivery.

Carbon monoxide (CO) is an innate signaling molecule that can regulate immune responses and interact with crucial elements of the circadian clock. Moreover, pharmacologically, CO has been substantiated for its therapeutic advantages in animal models of diverse pathological conditions. Given that an excessive level of CO can be toxic, it is imperative to quantify the necessary amount for therapeutic use accurately. However, estimating gaseous CO is notably challenging. Therefore, novel techniques are essential to quantify CO in therapeutic applications and overcome this obstacle precisely. The classical Myoglobin (Mb) assay technique has been extensively used to determine the amount of CO-release from CO-releasing molecules (CORMs) within therapeutic contexts. Nevertheless, specific challenges arise when applying the Mb assay to evaluate CORMs featuring innovative molecular architectures. Here, we report a fluorinated photo-CORM (CORM-FBS) for the photo-induced CO-release. We employed the 19F NMR spectroscopy approach to monitor the release of CO as well as quantitative evaluation of CO release. This new 19F NMR approach opens immense opportunities for researchers to develop reliable techniques for identifying molecular structures, quantitative studies of drug metabolism, and monitoring the reaction process.

Effects of swine manure and straw biochars on fluorine adsorption-desorption in soils.

With increasing global awareness of soil health, attention must be paid to fluorine exposure in soils, which poses a threat to human health. Therefore, this study aimed to study the fluorine adsorption characteristics of swine manure and straw biochars and their impact on fluorine adsorption-desorption in soil with batch experiments. The biochar samples originated from high-temperature anaerobic cracking of swine manure (350°C, 500°C, and 650°C) and straw (500°C). Results indicated that the adsorption of soil fluorine reached adsorption equilibrium at around 4 h after the mixing of swine manure and straw biochar. Fluorine adsorption kinetics using these biochars conformed to the quasi-two-stage kinetic model. The fluorine adsorption kinetics for biochar-treated soils conformed to the double-constant equation and the Elovich equation, and the soil treated with straw biochar showed the fastest fluorine adsorption rate. The adsorption isotherms of fluorine for biochars and biochar-treated soils could be fitted by the isothermal adsorption model of Langmuir and Freundlich. The maximal equilibrium quantity of fluorine was 73.66 mg/g for swine manure biochar. The soil, adding with 2% of swine manure biochar achieved with showed at 650°C had the smallest adsorption. This study also shows that the adsorption of fluorine by biochar gradually decreased with the increase of pH. Comparing with other factors, the mixture pH with biochars added had a significant effect on fluorine adsorption. The decreased fluorine adsorption capacities for soils treated with swine manure and straw biochars were closely related to the increased pH in soils after adding biochars. Considering the fluorine threat in soil, this study provides a theoretical basis for the application of biochars on soil fluorine adsorption.

A V-shaped bis-coumarin based fluorescence probe for F- detection in tea infusions and potable water and bioimaging applications in living systems.

Fluorine (F) is a pivotal element in the formation of human dental and skeletal tissues, and the consumption of water and tea constitutes a significant source of fluoride intake. However, prolonged ingestion of water and tea with excessive fluoride content can lead to fluorosis, which poses a serious health hazard. In this manuscript, a novel turn-on fluorescent probe DCF synthesized by bis-coumarin and tert-butyldiphenylsilane (TBDPS) was introduced for detecting F- in potable water and tea infusions. By leveraging the unique chemical affinity between fluoride and silicon, F- triggers the silicon-oxygen bond cleavage in DCF, culminating in a conspicuous emission of yellow fluorescence. Validated through a succession of optical tests, this probe exhibits remarkable advantages in terms of superior selectivity, a low detection limit, a large Stokes shift, and robust interference resistance when detecting inorganic fluoride. Moreover, it can serve as portable test strips for on-site real-time identification and quantitative analysis of F-. Furthermore, the application of DCF for in-situ monitoring and imaging of F- in zebrafish and soybean root tissues proved its significant value for F- detection in both animal and plant systems. This probe potentially functions as an efficient instrument for delving into the toxic mechanisms of fluoride in physiological processes.

Optoelectronic Response to the Fluor Ion Bond on 4-(4,4,5,5-Tetramethyl-1,3,2-dioxoborolan-2-yl)benzaldehyde.

Boronate esters are a class of compounds containing a boron atom bonded to two oxygen atoms in an ester group, often being used as precursors in the synthesis of other materials. The characterization of the structure and properties of esters is usually carried out by UV-visible, infrared, and nuclear magnetic resonance (NMR) spectroscopic techniques. With the aim to better understand our experimental data, in this article, the density functional theory (DFT) is used to analyze the UV-visible and infrared spectra, as well as the isotropic shielding and chemical shifts of the hydrogen atoms 1H, carbon 13C and boron 11B in the compound 4-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)benzaldehyde. Furthermore, this study considers the change in its electronic and spectroscopic properties of this particular ester, when its boron atom is coordinated with a fluoride anion. The calculations were carried out using the LSDA and B3LYP functionals in Gaussian-16, and PBE in CASTEP. The results show that the B3LYP functional gives the best approximation to the experimental data. The formation of a coordinated covalent B-F bond highlights the remarkable sensitivity of the NMR chemical shifts of carbon, oxygen, and boron atoms and their surroundings. Furthermore, this bond also highlights the changes in the electron transitions bands n → π* and π → π* during the absorption and emission of a photon in the UV-vis, and in the stretching bands of the C=C bonds, and bending of BO2 in the infrared spectrum. This study not only contributes to the understanding of the properties of boronate esters but also provides important information on the interactions and responses optoelectronic of the compound when is bonded to a fluorine atom.

Synthesis of Fluorinated Nucleosides/Nucleotides and Their Antiviral Properties.

The FDA has approved several drugs based on the fluorinated nucleoside pharmacophore, and numerous drugs are currently in clinical trials. Fluorine-containing nucleos(t)ides offer significant antiviral and anticancer activity. The insertion of a fluorine atom, either in the base or sugar of nucleos(t)ides, alters its electronic and steric parameters and transforms the lipophilicity, pharmacodynamic, and pharmacokinetic properties of these moieties. The fluorine atom restricts the oxidative metabolism of drugs and provides enzymatic metabolic stability towards the glycosidic bond of the nucleos(t)ide. The incorporation of fluorine also demonstrates additional hydrogen bonding interactions in receptors with enhanced biological profiles. The present article discusses the synthetic methodology and antiviral activities of FDA-approved drugs and ongoing fluoro-containing nucleos(t)ide drug candidates in clinical trials.

Development of Ln(III) Derivatives as 19F Parashift Probes.

19F parashift probes with paramagnetically shifted reporter nuclei provide attractive platforms to develop molecular imaging probes. These probes enable ratiometric detection of molecular disease markers using a direct detection technique. Here, we describe a series of trivalent lanthanide (Ln(III)) complexes that are structural analogues of the clinically approved MR contrast agent (CA) ProHance to obtain LnL 19F parashift probes. We evaluated trans-gadolinium paramagnetic lanthanides compared to diamagnetic YL for 19F chemical shift and relaxation rate enhancement. The paramagnetic contribution to chemical shift (δPCS) for paramagnetic LnL exhibited either shifts to lower frequency (δPCS < 0 for TbL, DyL, and HoL) or shifts to higher frequency (δPCS > 0 for ErL, TmL, and YbL) compared to YL 19F spectroscopic signal. Zero-echo time pulse sequences achieved 56-fold sensitivity enhancement for DyL over YL, while developing probe-specific pulse sequences with fast delay times and acquisition times achieved 0.6-fold enhancement in limit of detection for DyL. DyL provides an attractive platform to develop 19F parashift probes for ratiometric detection of enzymatic activity.

(2S,4S)-5-Fluoroleucine, (2S,4R)-5-Fluoroleucine, and 5,5'-Difluoroleucine in Escherichia coli PpiB: Protein Production, 19F NMR, and Ligand Sensing Enhanced by the γ-Gauche Effect.

Global substitution of leucine for analogues containing CH2F instead of methyl groups delivers proteins with multiple sites for monitoring by 19F nuclear magnetic resonance (NMR) spectroscopy. The 19 kDa Escherichia coli peptidyl-prolyl cis-trans isomerase B (PpiB) was prepared with uniform high-level substitution of leucine by (2S,4S)-5-fluoroleucine, (2S,4R)-5-fluoroleucine, or 5,5'-difluoroleucine. The stability of the samples toward thermal denaturation was little altered compared to the wild-type protein. 19F nuclear magnetic resonance (NMR) spectra showed large chemical shift dispersions between 6 and 17 ppm. The 19F chemical shifts correlate with the three-bond 1H-19F couplings (3JHF), providing the first experimental verification of the γ-gauche effect predicted by [Feeney, J. J. Am. Chem. Soc. 1996, 118, 8700-8706] and establishing the effect as the predominant determinant of the 19F chemical shifts of CH2F groups. Individual CH2F groups can be confined to single rotameric states by the protein environment, but most CH2F groups exchange between different rotamers at a rate that is fast on the NMR chemical shift scale. Interactions between fluorine atoms in 5,5'-difluoroleucine bias the CH2F rotamers in agreement with results obtained previously for 1,3-difluoropropane. The sensitivity of the 19F chemical shift to the rotameric state of the CH2F groups potentially renders them particularly sensitive for detecting allosteric effects.

Fluorine-functionalized magnetic amino microporous organic network for enrichment of perfluoroalkyl substances.

Perfluoroalkyl substances (PFAS) are persistent organic pollutants that pose significant risks to human health and the environment. Efficient and selective enrichment of these compounds was crucial for their accurate detection and quantification in complex matrices. Herein, we report a novel magnetic solid-phase extraction (MSPE) method using fluorine-functionalized magnetic amino-microporous organic network (Fe3O4@MONNH2@F7) adsorbent for the efficient enrichment of PFAS from aqueous samples. The core-shell Fe3O4@MONNH2@F7 nanosphere was synthesized, featuring magnetic Fe3O4 nanoparticles as the core and a porous amino-functionalized MONs coating as the shell, which was further modified by fluorination. The synthesized adsorbent material exhibited high specific surface area, hydrophobicity, and abundant fluorine groups, facilitating efficient and selective adsorption of PFAS via electrostatic attraction, hydrophobic-hydrophobic interactions, fluorine-fluorine interactions, π-CF interactions and hydrogen bonding. Furthermore, the MSPE method coupled with ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) allowed for the rapid, sensitive, and accurate determination of ultra-trace PFAS in real water samples, human serum, and human follicular fluid. Under optimal conditions, the established MSPE method demonstrated a linear range (2 to 2000 ng L-1), with a correlation coefficient exceeding 0.9977, low limits of detection ranging from 0.54 to 1.47 ng L-1, with a relative standard deviation (RSD) < 9.1%. Additionally, the method showed excellent performance in complex real samples (recovery ratio of 81.7 to 121.6 %). The adsorption mechanism was investigated through kinetic, isotherm, and molecular simulation studies, revealing that the introduction of fluorine groups enhanced the hydrophobic interaction and fluorine-fluorine attraction between the adsorbent and PFAS. This work provides a proof-of-concept strategy for designing adsorbent materials with high efficiency and selectivity by post-modification, which has great potential for the detection and analysis of PFAS in complex samples.

Radical fluorine transfer catalysed by an engineered nonheme iron enzyme.

Nonheme iron enzymes stand out as one of the most versatile biocatalysts for molecular functionalization. They facilitate a wide array of chemical transformations within biological processes, including hydroxylation, chlorination, epimerization, desaturation, cyclization, and more. Beyond their native biological functions, these enzymes possess substantial potential as powerful biocatalytic platforms for achieving abiological metal-catalyzed reactions, owing to their functional and structural diversity and high evolvability. To this end, our group has recently engineered a series of nonheme iron enzymes to employ non-natural radical-relay mechanisms for abiological radical transformations not previously known in biology. Notably, we have demonstrated that a nonheme iron enzyme, (S)-2-hydroxypropylphosphonate epoxidase from Streptomyces viridochromogenes (SvHppE), can be repurposed into an efficient and selective biocatalyst for radical fluorine transfer reactions. This marks the first known instance of a redox enzymatic process for C(sp3)F bond formation. This chapter outlines the detailed experimental protocol for engineering SvHPPE for fluorination reactions. Furthermore, the provided protocol could serve as a general guideline that might facilitate other engineering endeavors targeting nonheme iron enzymes for novel catalytic functions.

Synthesis of fluorinated amino acids by low-specificity, promiscuous aldolases coupled to in situ fluorodonor generation.

Fluorine (F) is an important element in the synthesis of molecules broadly used in medicine, agriculture, and materials. F addition to organic structures represents a unique strategy for tuning molecular properties, yet this atom is rarely found in Nature and approaches to produce fluorometabolites (such as fluorinated amino acids, key building blocks for synthesis) are relatively scarce. This chapter discusses the use of L-threonine aldolase enzymes (LTAs), a class of enzymes that catalyze reversible aldol addition to the α-carbon of glycine. The C-C bond formation ability of LTAs, together with their known substrate promiscuity, make them ideal for in vitro F biocatalysis. Here, we describe protocols to harness the activity of the low-specificity LTAs isolated from Escherichia coli and Pseudomonas putida on 2-fluoroacetaldehyde to efficiently synthesize 4-fluoro-L-threonine in vitro. This chapter also provides a comprehensive account of experimental protocols to implement these activities in vivo. These methods are illustrative and can be adapted to produce other fluorometabolites of interest.

Defluorination as the key trait to gauge the biodegradability of fluorinated pollutants in environmental microbial communities.

Research on microbial defluorination is largely centred on controlled experiments using axenic or well defined microbial inocula. These approaches serve a relevant purpose in the field, offering fundamental biochemical and mechanistic insights on the intricacies of biological defluorination. However, they fail to account for the effective contribution of environmental microbial communities in the recycling of fluoroorganic pollutants, a highly relevant perspective from an environmental risk assessment standpoint, while also missing an important outlook on how community-wide dynamics can leverage the breakdown of C─F bonds in these recalcitrant compounds. With that in mind, this chapter provides experimental and methodological insights on the study of microbial defluorination in wild environmental communities, using this critical catabolic step as the de facto endpoint to evolve, select and cultivate microorganisms with improved defluorination performances.

4,4-Difluoroproline as a Unique 19F NMR Probe of Proline Conformation.

Despite the importance of proline conformational equilibria (trans versus cis amide and exo versus endo ring pucker) on protein structure and function, there is a lack of convenient ways to probe proline conformation. 4,4-Difluoroproline (Dfp) was identified to be a sensitive 19F NMR-based probe of proline conformational biases and cis-trans isomerism. Within model compounds and disordered peptides, the diastereotopic fluorines of Dfp exhibit similar chemical shifts (ΔδFF = 0-3 ppm) when a trans X-Dfp amide bond is present. In contrast, the diastereotopic fluorines exhibit a large (ΔδFF = 5-12 ppm) difference in chemical shift in a cis X-Dfp prolyl amide bond. DFT calculations, X-ray crystallography, and solid-state NMR spectroscopy indicated that ΔδFF directly reports on the relative preference of one proline ring pucker over the other: a fluorine which is pseudo-axial (i.e., the pro-4R-F in an exo ring pucker, or the pro-4S-F in an endo ring pucker) is downfield, while a fluorine which is pseudo-equatorial (i.e., pro-4S-F when exo, or pro-4R-F when endo) is upfield. Thus, when a proline is disordered (a mixture of exo and endo ring puckers, as at trans-Pro in peptides in water), it exhibits a small Δδ. In contrast, when the Pro is ordered (i.e., when one ring pucker is strongly preferred, as in cis-Pro amide bonds, where the endo ring pucker is strongly favored), a large Δδ is observed. Dfp can be used to identify inherent induced order in peptides and to quantify proline cis-trans isomerism. Using Dfp, we discovered that the stable polyproline II helix (PPII) formed in the denatured state (8 M urea) exhibits essentially equal populations of the exo and endo proline ring puckers. In addition, the data with Dfp suggested the specific stabilization of PPII by water over other polar solvents. These data strongly support the importance of carbonyl solvation and n → π* interactions for the stabilization of PPII. Dfp was also employed to quantify proline cis-trans isomerism as a function of phosphorylation and the R406W mutation in peptides derived from the intrinsically disordered protein tau. Dfp is minimally sterically disruptive and can be incorporated in expressed proteins, suggesting its broad application in understanding proline cis-trans isomerization, protein folding, and local order in intrinsically disordered proteins.

Synthesis and biological properties of novel glucose-based fluoro segmented macromolecular architectures.

The emergence of novel well-defined biological macromolecular architectures containing fluorine moieties displaying superior functionalities can satisfactorily address many biomedical challenges. In this research, ABA- and AB-type glucose-based biological macromolecules were synthesized using acryl-2,3,4,6-tetra-O-acetyl-D-glucopyranoside with pentafluorophenyl (FPM), pentafluorobenzyl (FBM), phenyl (PM) and benzyl (BM) methacrylate-based macro-RAFT agents following RAFT polymerization. The macro-RAFT agents and the corresponding copolymers were characterized by 19F, 1H, and 13C NMR and FTIR spectroscopic techniques to understand the chemical structure, molecular weight by size-exclusion chromatography, thermal analysis by TGA and DSC. Thermal stability (Td5%) of the FPM and FBM fluoro-based polymers was observed in the range of 219-267 °C, while the non-fluoro PM and BM polymers exhibited in the range of 216-264 °C. Among the macro-RAFT agents, PFPM (107 °C, ΔH: 0.613 J/g) and PPM (103 °C, ΔH: 0.455 J/g) showed higher Tm values, while among the block copolymers, PFBM-b-PG (123 °C, ΔH: 0.412 J/g) and PG-b-PFPM-b-PG (126 °C, ΔH: 0.525 J/g) exhibited higher Tm values. PFBMT and PPM macro-RAFT agents, PPM-b-PG and PG-b-PPM-b-PG copolymer spin-coated films showed the highest hydrophobicity (120°) among the synthesized polymers. The block copolymers exhibited self-assembled segregation by using relatively hydrophobic segments as the core and hydrophilic moieties as the corona. Synthesized biological macromolecules exhibit maximum antibacterial activity towards S. aureus than E. coli bacteria. Fluorophenyl (PFPM) and non-fluorobenzyl-based (PBMT) macro-RAFT agents exhibit low IC50 values, suggesting high cytotoxicity. All the triblock copolymers exhibit lesser cytotoxicity than the di-block polymers.

Fluorine in the pharmaceutical industry: Synthetic approaches and application of clinically approved fluorine-enriched anti-infectious medications.

The strategic integration of fluorine atoms into anti-infectious agents has become a cornerstone in the field of medicinal chemistry, owing to the unique influence of fluorine on the chemical and biological properties of pharmaceuticals. This review examines the synthetic methodologies that enable the incorporation of fluorine into anti-infectious drugs, and the resultant clinical applications of these fluorine-enriched compounds. With a focus on clinically approved medications, the discussion extends to the molecular mechanisms. It further outlines the specific effects of fluorination, which contribute to the heightened efficacy of anti-infective therapies. By presenting a comprehensive analysis of current drugs and their developmental pathways, this review underscores the continuing evolution and significance of fluorine in advancing anti-infectious treatment options. The insights offered extend valuable guidance for future drug design and the development of next-generation anti-infectious agents.

Genetic Encoding of Fluoro-l-tryptophans for Site-Specific Detection of Conformational Heterogeneity in Proteins by NMR Spectroscopy.

The substitution of a single hydrogen atom in a protein by fluorine yields a site-specific probe for sensitive detection by 19F nuclear magnetic resonance (NMR) spectroscopy, where the absence of background signal from the protein facilitates the detection of minor conformational species. We developed genetic encoding systems for the site-selective incorporation of 4-fluorotryptophan, 5-fluorotryptophan, 6-fluorotryptophan, and 7-fluorotryptophan in response to an amber stop codon and used them to investigate conformational heterogeneity in a designed amino acid binding protein and in flaviviral NS2B-NS3 proteases. These proteases have been shown to present variable conformations in X-ray crystal structures, including flips of the indole side chains of tryptophan residues. The 19F NMR spectra of different fluorotryptophan isomers installed at the conserved site of Trp83 indicate that the indole ring flip is common in flaviviral NS2B-NS3 proteases in the apo state and suppressed by an active-site inhibitor.

Silane and fluorine free facile hydrophobicization of water hyacinth biomass for oil-water separations.

As the adverse effects of using plastics and perfluorinated alkyl substances become more apparent, there is a growing need for sustainable hydrophobic products. Cellulose and its derivatives are the most abundant and widely used polymers, and cellulose-based products have great potential in industries where plastics and other hydrophobic polymers are used, such as stain-resistant fabrics, food packaging, and oil-water separation applications. In this study, we extracted cellulose from water hyacinth (WH) biomass, known for its negative environmental impact, and converted it into hydrophobic cellulose. This addresses the issue of managing WH waste and creating an environmentally friendly hydrophobic material. Initially, aldehyde groups were introduced through oxidation with periodate, followed by direct octadecyl amine (ODA) grafting onto dialdehyde cellulose (DAC) via a Schiff base condensation. The resulting ODA modified cellulose (ODA-C) was dispersed in ethanol and used to coat various materials, including cotton fabric, cellulose filter paper, and packaging paper. The modified materials showed excellent hydrophobicity as measured by their water contact angles (WCAs), and the application of the coating was demonstrated for oil-water separation, stain-resistant hydrophobic fabric, and paper-based packaging materials. FTIR, XRD, and WCA analysis confirmed the successful modification of cellulose. A high separation efficiency of 99% was achieved for diesel/water separation using modified filter paper (MoFP), under gravity. On application of the coating, cotton fabric became hydrophobic and resisted staining from dye, and paper-based packaging materials became more robust by becoming water-resistant. Overall, the facile synthesis, low cost, high efficiency, and use of environmentally friendly sustainable materials make this a promising strategy for hydrophobically modifying surfaces for a wide range of applications while reducing the menace of water hyacinth.

Exploring long-range fluorine-carbon J-coupling for conformational analysis of deoxyfluorinated disaccharides: A combined computational and NMR study.

In this study, we investigated the potential of long-range fluorine-carbon J-coupling for determining the structures of deoxyfluorinated disaccharides. Three disaccharides, previously synthesized as potential galectin inhibitors, exhibited through-space fluorine-carbon J-couplings. In our independent conformational analysis of these disaccharide derivatives, we employed a combination of density functional theory (DFT) calculations and nuclear magnetic resonance (NMR) experiments. By comparing the calculated nuclear shieldings with the experimental carbon chemical shifts, we were able to identify the most probable conformers for each compound. A model comprising fluoromethane and methane molecules was used to study the relationship between molecular arrangements and intermolecular through-space J-coupling. Our study demonstrates the important effect of internuclear distance and molecular orientation on the magnitude of fluorine-carbon coupling. The experimental values for the fluorine-carbon through-space couplings (TSCs) of the disaccharides corresponded with values calculated for the most probable conformers identified by the conformational analysis. These results unlock the broader application of fluorine-carbon TSCs as powerful tools for conformational analysis of flexible molecules, offering valuable insights for future structural investigations.

Potential and performance of anisotropic 19F NMR for the enantiomeric analysis of fluorinated chiral active pharmaceutical ingredients.

Controlling the enantiomeric purity of chiral drugs is of paramount importance in pharmaceutical chemistry. Isotropic 1H NMR spectroscopy involving chiral agents is a widely used method for discriminating enantiomers and quantifying their relative proportions. However, the relatively weak spectral separation of enantiomers (1H Δδiso(R, S)) in frequency units at low and moderate magnetic fields, as well as the lack of versatility of a majority of those agents with respect to different chemical functions, may limit the general use of this approach. In this article, we investigate the analytical potential of 19F NMR in anisotropic chiral media for the enantiomeric analysis of fluorinated active pharmaceutical ingredients (API) via two residual anisotropic NMR interactions: the chemical shift anisotropy (19F-RCSA) and dipolar coupling ((19F-19F)-RDC). Lyotropic chiral liquid crystals (CLC) based on poly-γ-benzyl-L-glutamate (PBLG) show an interesting versatility and adaptability to enantiodiscrimination as illustrated for two chiral drugs, Flurbiprofen® (FLU) and Efavirenz® (EFA), which have very different chemical functions. The approach has been tested on a routine 300 MHz NMR spectrometer equipped with a standard probe (5 mm BBFO probe) in a high-throughput context (i.e., ≈10 s of NMR experiments) while the performance for enantiomeric excess (ee) measurement is evaluated in terms of trueness and precision. The limits of detection (LOD) determined were 0.17 and 0.16 µmol ml-1 for FLU and EFA, respectively, allow working in dilute conditions even with such a short experimental duration. The enantiodiscrimination capabilities are also discussed with respect to experimental features such as CLC composition and temperature.

Asymmetric α-Fluoroalkyl-α-Amino Acids: Recent Advances in Their Synthesis and Applications.

Due to the specific properties provided by fluorine atoms to biomolecules, amino acids with fluorinated side chains are of great interest for medicinal chemistry and chemical biology. Among them, α-fluoroalkyl-α-amino acids constitute a unique class of compounds. In this review, we outline the strategies adopted for their syntheses in enantiopure or enantioenriched forms and their incorporation into peptides. We then describe the consequences of the introduction of fluorine atoms in these compounds for the modulation of their hydrophobicity and the control of their conformation. Emerging applications are presented in the areas of enzyme inhibition, medicinal chemistry, hydrolytic stability of peptides, antimicrobial peptides, PET, and 19F NMR probes.

Genetically encoded site-specific 19F unnatural amino acid incorporation in V. natriegens for in-cell NMR analysis.

Nuclear magnetic resonance (NMR) spectroscopy NMR is a well-established technique for probing protein structure, dynamics and conformational changes. Taking advantage of the high signal sensitivity and broad chemical shift range of 19F nuclei, 19F NMR has been applied to investigate protein function at atomic resolution. In this report, we extend the unnatural amino acid site-specific incorporation into V. natriegens, an alternate protein expression system. The unnatural amino acid L-4-trifluoromethylphenylalanine (tfmF) was site-specifically introduced into the mitogen-activated protein kinase MEKK3 in V. natriegens using genetically encoded technology, which will be an extensive method for in-cell protein structure and dynamic investigation.