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We explore the potential of fluorine-containing small Mn 2+ chelates as alternatives to perfluorinated nanoparticles, widely used as 19 F MRI probes. In MnL1, the cyclohexanediamine skeleton and two piperidine rings, involving each a metal-coordinating amide group and an appended CF 3 moiety, provide high rigidity to the complex. This allows for good control of the Mn-F distance (r MnF =8.2±0.2 Å determined from 19 F relaxation data), as well as for high kinetic inertness (a dissociation half-life of 1285 h is estimated for physiological conditions). The paramagnetic Mn 2+ leads to a ~150-fold acceleration of the longitudinal 19 F relaxation, with moderate line-broadening effect, resulting in T 2 /T 1 ratios of 0.8 (9.4 T). Owing to its inner sphere water molecule, MnL1 is a good 1 H relaxation agent as well (r 1 =5.36 mM -1  s -1 at 298 K, 20 MHz). MnL1 could be readily visualized in 19 F MRI by using fast acquisition techniques, both in phantom images and living mice following intramuscular injection, with remarkable signal-to-noise ratios and short acquisition times. While applications in targeted imaging or cell therapy monitoring require further optimisation of the molecular structure, these results argue for the potential of such small, monohydrated and fluorinated Mn 2+ complexes for combined 19 F and 1 H MRI detection., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

A new concept for the synthesis of dialkyl chloronium cations [R-Cl-R] + is described (R=CH 3 , CH 2 CF 3 ), that allows the formation of fluorinated derivatives. By utilizing the xenonium salt [XeOTeF 5 ][M(OTeF 5 ) n ] (M=Sb, n=6; M=Al, n=4) chlorine atoms of chloroalkanes or the deactivated chlorofluoroalkane CH 2 ClCF 3 are oxidized and removed as ClOTeF 5 leading to the isolation of the corresponding chloronium salt. Since the resulting highly electrophilic cation [Cl(CH 2 CF 3 ) 2 ] + is able to alkylate weak nucleophiles, this compound can be utilized for the introduction of a fluorinated alkyl group to those. In addition, the fluorinated alkyl chloronium cation displays a high hydride ion affinity, enabling the activation of linear hydrocarbons by hydride abstraction even at low temperatures ultimately leading to the formation of branched carbocations., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

By integrating TiO 2 with rare earth upconversion nanocrystals (NaREF 4 ), efficient energy transfer can be achieved between the two subunits under near-infrared (NIR) excitation, which hold tremendous potential in the fields of photocatalysis, photodynamic therapy (PDT), etc. However, in the previous studies, the combination of TiO 2 with NaREF 4 is a non-epitaxial random blending mode, resulting in a diminished energy transfer efficiency between the NaREF 4 and TiO 2 . Herein, we present a fluorine doping-mediated epitaxial growth strategy for the synthesis of TiO 2 -NaREF 4 heteronanocrystals (HNCs). Due to the epitaxial growth connection, NaREF 4 can transfer energy through phonon-assisted pathway to TiO 2 , which is more efficient than the traditional indirect secondary photon excitation. Additionally, F doping brings oxygen vacancies in the TiO 2 subunit, which further introduces new impurity energy levels in the intrinsic band gap of TiO 2 subunit, and facilitates the energy transfer through phonon-assisted method from NaREF 4 to TiO 2 . As a proof of concept, TiO 2 -NaGdF 4  : Yb,Tm@NaYF 4 @NaGdF 4  : Nd@NaYF 4 HNCs were rationally constructed. Taking advantage of the dual-model up- and downconversion luminescence of the delicately designed multi-shell structured NaREF 4 subunit, highly efficient photo-response capability of the F-doped TiO 2 subunit and the efficient phonon-assisted energy transfer between them, the prepared HNCs provide a distinctive nanoplatform for bioimaging-guided NIR-triggered PDT., (© 2024 Wiley-VCH GmbH.)

The Lewis superacid Ga(OTeF 5 ) 3 has been synthesized and characterized, revealing a monomeric structure in solution and a dimeric structure in the solid state. Isolated adducts of Ga(OTeF 5 ) 3 with strong and weak Lewis bases have been characterized spectroscopically as well as by single-crystal X-ray diffractometry. The Lewis acidity of this new species has been evaluated by means of different experimental and theoretical methods, which has allowed to classify it as one of only a few examples of a gallium-based Lewis superacid. The high Lewis acidity of Ga(OTeF 5 ) 3 was used to amplify the strength of the Brønsted acid HOTeF 5 , leading to the protonation of diethyl ether. Furthermore, Ga(OTeF 5 ) 3 was utilized to access the strong oxidizing system Ga(OTeF 5 ) 3 /Xe(OTeF 5 ) 2 in SO 2 ClF, which was successfully employed in the synthesis of the dimethyl chloronium salt [Cl(CH 3 ) 2 ][Ga(OTeF 5 ) 4 ], a strong electrophilic methylation reagent., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

Ligand binding hotspots are regions of protein surfaces that form particularly favourable interactions with small molecule pharmacophores. Targeting interactions with these hotspots maximises the efficiency of ligand binding. Existing methods are capable of identifying hotspots but often lack assays to quantify ligand binding and direct elaboration at these sites. Herein, we describe a fragment-based competitive 19 F Ligand Based NMR (LB-NMR) screening platform that enables routine, quantitative ligand profiling focused at ligand-binding hotspots. As a proof of concept, the method was applied to 4'-phosphopantetheine adenylyltransferase (PPAT) from Mycobacterium abscessus (Mabs). X-ray crystallographic characterisation of the hits from a 960-member fragment screen identified three ligand-binding hotspots across the PPAT active site. From the fragment hits a collection of 19 F reporter candidates were designed and synthesised. By rigorous prioritisation and use of optimisation workflows, a single 19 F reporter molecule was generated for each hotspot. Profiling the binding of a set of structurally characterised ligands by competitive 19 F LB-NMR with this suite of 19 F reporters recapitulated the binding affinity and site ID assignments made by ITC and X-ray crystallography. This quantitative mapping of ligand binding events at hotspot level resolution establishes the utility of the fragment-based competitive 19 F LB-NMR screening platform for hotspot-directed ligand profiling., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Covalent organic frameworks (COFs) have emerged as potential light‐emitting polymers for optoelectronic and optical devices, but their smart responsiveness to environmental stimuli has seldom been explored particularly for alkene‐linked conjugated COFs, which limits their application scope in “smart” systems. Herein, fluorine chemistry coupled with acrylonitrile linkage is introduced as a “one‐stone‐three‐bird” strategy to produce a smart COF with rapid pH‐responsive absorption and fluorescence, high fluorescence quantum yield (QY), and good crystallinity. In addition to increased crystallinity, the newly designed fluorinated acrylonitrile‐linked COF (TF‐COF) produces 20% enhancement in fluorescence QY and more rapid responsiveness of absorption and fluorescence under acid–base induction compared to the nonfluorinated counterpart. Impressively, the yielded QY reaches 33.6% in solid states and 41.0% in tetrahydrofuran dispersion, surpassing most existing COF materials. The synergy effect of fluorine chemistry induced charge redistribution and acrylonitrile linkage enabled reversible C═C bonds contributes to the rapid responsiveness, high fluorescence QY, and good crystallinity. The developed TF‐COF can be utilized as a responsive phosphor to endow image encryption with high coloration and good reversibility, and as an encryption data carrier via simple handwriting.

The reactivity of carbamoyl radicals, generated in situ from sodium oxamate salts, has been investigated in the context of radical carbofluorination reactions of olefins and α-fluoroolefins, respectively. Both transformations are catalyzed by silver salts and required the presence of potassium persulfate (K 2 S 2 O 8 ) and Selectfluor TM as a radicophilic fluorine source. The reported methods provide a direct access to β-fluoroamides and β,β-difluoroamides., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

The DNA-guided (gDNA) Argonaute from Thermus thermophilus (TtAgo) has little potential for nucleic acid detection and gene editing due to its poor dsDNA cleavage activity at relatively low temperature. Herein, the dsDNA cleavage activity of TtAgo is enhanced by using 2'-fluorine (2'F)-modified gDNA and developes a novel nucleic acid testing strategy. This study finds that the gDNA with 2'F-nucleotides at the 3'-end (2'F-gDNA) can promote the assembly of the TtAgo-guide-target ternary complex significantly by increasing its intermolecular force to target DNA and TtAgo, thereby providing ≈40-fold activity enhancement and decreasing minimum reaction temperature from 65 to 60 °C. Based on this outstanding advance, a novel nucleic acid testing strategy is proposed, termed FAST, which is performed by using the 2'F-gDNA/TtAgo for target recognition and combining it with Bst DNA polymerase for nucleic acid amplification. By integrating G-quadruplex and Thioflavin T, the FAST assay achieves one-pot real-time fluorescence analysis with ultra-sensitivity, providing a limit of detection up to 5 copies (20 µL reaction mixture) for miR-21 detection. In summary, an atom-modification-based strategy has been developed for enhancing the cleavage activity of TtAgo efficiently, thereby improving its practicability and establishing a TtAgo-based nucleic acid testing technology with ultra-sensitivity and high-specificity., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

This work demonstrates the low-temperature operation of solid-state lithium metal batteries (LMBs) through the development of a fluorinated and plastic-crystal-embedded elastomeric electrolyte (F-PCEE). The F-PCEE is formed via polymerization-induced phase separation between the polymer matrix and plastic crystal phase, offering a high mechanical strain (≈300%) and ionic conductivity (≈0.23 mS cm -1 ) at -10 °C. Notably, strong phase separation between two phases leads to the selective distribution of lithium (Li) salts within the plastic crystal phase, enabling superior elasticity and high ionic conductivity at low temperatures. The F-PCEE in a Li/LiNi 0.8 Co 0.1 Mn 0.1 O 2 full cell maintains 74.4% and 42.5% of discharge capacity at -10 °C and -20 °C, respectively, compared to that at 25 °C. Furthermore, the full cell exhibits 85.3% capacity retention after 150 cycles at -10 °C and a high cut-off voltage of 4.5 V, representing one of the highest cycling performances among the reported solid polymer electrolytes for low-temperature LMBs. This work attributes the prolonged cycling lifetime of F-PCEE at -10 °C to the great mechanical robustness to suppress the Li-dendrite growth and ability to form superior LiF-rich interphases. This study establishes the design strategies of elastomeric electrolytes for developing solid-state LMBs operating at low temperatures and high voltages., (© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.)

Fluorinated non-natural amino acids are attracting considerable research interest, especially in the biomedical field and in materials science, thanks to their ability to self-assemble into peculiar supramolecular structures. The conformational changes induced by the presence of fluorine atoms obviously affect their functions, as well as the biological activity of the deriving peptides and proteins. Here, we will briefly describe the main effects of fluorination on the aggregation behavior of such building blocks, focusing in particular on their improved tendency to form fibrils, and gels therefrom. Our aim is to underline the promising potential of fluorination as a tool to affect the self-assembly features of amino acids, both when used alone and when inserted into polypeptide sequences. The ability of fluorine to influence physical, chemical, and structural properties of these substrates offers the possibility to engineer bioinspired materials with specific and tunable functions., (© 2024 Wiley-VCH GmbH.)

Herein we report a general access to silver(i) perfluoroalcoholates, their structure in the solid state and in solution, and their use as transfer reagents. The silver(i) perfluoroalcoholates are prepared by the reaction of AgF with the corresponding perfluorinated carbonyl compounds in acetonitrile and are stable for a prolonged time at -18 °C. X-ray analysis of single crystals of perfluoroalcoholate species showed that two Ag(i) centers are bridged by the alcoholate ligands. In acetonitrile solution, Ag[OCF 3 ] forms different structures as indicated by IR spectroscopy. Furthermore, the silver(i) perfluoroalcoholates can be used as easy-to-handle transfer reagents for the synthesis of Cu[OCF 3 ], Cu[OC 2 F 5 ], [PPh 4 ][Au(CF 3 ) 3 (OCF 3 )], and fluorinated alkyl ethers., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Theranostics is a novel paradigm integrating therapy and diagnostics, thereby providing new prospects for overcoming the limitations of traditional treatments. In this context, perfluorocarbons (PFCs) are the most widely used tracers in preclinical fluorine-19 magnetic resonance ( 19 F MR), primarily for their high fluorine content. However, PFCs are extremely hydrophobic, and their solutions often display reduced biocompatibility, relative instability, and subpar 19 F MR relaxation times. This study aims to explore the potential of micellar 19 F MR imaging (MRI) tracers, synthesized by polymerization-induced self-assembly (PISA), as alternative theranostic agents for simultaneous imaging and release of the non-steroidal antileprotic drug clofazimine. In vitro, under physiological conditions, these micelles demonstrate sustained drug release. In vivo, throughout the drug release process, they provide a highly specific and sensitive 19 F MRI signal. Even after extended exposure, these fluoropolymer tracers show biocompatibility, as confirmed by the histological analysis. Moreover, the characteristics of these polymers can be broadly adjusted by design to meet the wide range of criteria for preclinical and clinical settings. Therefore, micellar 19 F MRI tracers display physicochemical properties suitable for in vivo imaging, such as relaxation times and non-toxicity, and high performance as drug carriers, highlighting their potential as both diagnostic and therapeutic tools., (© 2024 The Authors. Macromolecular Bioscience published by Wiley‐VCH GmbH.)

This work demonstrates the use of jute stick extract as a reducing and stabilizing agent for the synthesis of spherical gold nanoparticles (AuNPs). In UV-Vis spectroscopy, peak at 550 nm was used to confirm the formation of AuNPs. The spherical surface morphology of AuNPs was determined through SEM and TEM analysis. While XRD investigation revealed the crystallinity of the prepared AuNPs. To ensure the biocompatibility of synthesized AuNPs, a bacterial investigation was conducted with negative results towards bacterial strain. The, modified FTO with AuNPs were able to detect glucose in CV analysis and the constructed sensor displayed a wide linear range of 50 μM to 40 mM with a detection limit of 20 μM. Scan rate analysis was performed to determine the charge transfer coefficient (0.42) and Tafel slope (102 mV/decade). Furthermore, the interfacial surface mechanism is illustrated to understand the interaction of glucose with the electrode surface in an alkaline medium and the product formation through the dehydrogenation and hydrolysis process. The prepared sensor also showed good stability, reproducibility, and anti-interference capabilities. In the case of real sample analysis, we used a blood serum sample. A low RSD value (<10 %) suggests the practical use of AuNPs/FTO in real-life applications., (© 2024 Wiley-VCH GmbH.)

Fluorine, the tiny robust atom, with its unique features has captured the attention of scientists in recent times, especially in drug discovery with its integration in small molecules, peptides, and proteins. However, studies to understand the 'fluorine effects' on the conformation of molecules that follow 'beyond the rule of 5' are in the infancy yet significant in molecular design and function. For the first time, using short hybrid peptide sequence as an appropriate model, we examined the substitution effect (size, stereoelectronic effect, and hydrogen bonding) using X-ray diffraction, 2D-NMR, and CD studies. The comparative study on their folding patterns with hydrogen-substituted analogs can provide valuable insights into fluorinated substrates' design., (© 2024 Wiley‐VCH GmbH.)

Owing to its unique physical properties, fluorine is often used to open up new reaction channels. In this report, we establish a cooperation of [5,5]-rearrangement and fluorine-assisted temporary dearomatization for arene multi-functionalization. Specifically, the [5,5]-rearrangement of fluoroaryl sulfoxides with β,γ-unsaturated nitriles generates an intriguing dearomatized sulfonium species which is short-lived but exhibits unusually high electrophilicity and thus can be instantly trapped by nucleophiles and dienes at a remarkably low temperature (-95 °C) to produce four types of valuable multi-functionalized benzenes, respectively, involving appealing processes of defluorination, desulfurization, and sulfur shift. Mechanistic studies indicate that the use of fluorine on arenes not only circumvents the generally inevitable [3,3]-rearrangement but also impedes the undesired rearomatization process, thus provides a precious space for constructing and elaborating the temporarily dearomatized fluorinated sulfonium species., (© 2023 Wiley-VCH GmbH.)

A comprehensive study of physicochemical properties (pK a , LogP, and intrinsic microsomal clearance) within the series of mono- and difluorinated azetidine, pyrrolidine, and piperidine derivatives was performed. While the number of fluorine atoms and their distance to the protonation center were the major factors defining the compound's basicity, both pK a and LogP values were affected considerably by the conformational preferences of the corresponding derivatives. For example, features of "Janus face" (facially polarized) cyclic compounds (i. e., unusually high hydrophilicity) were identified for cis-3,5-difluoropiperidine, preferring a diaxial conformation. Intrinsic microsomal clearance measurements demonstrated high metabolic stability of the compounds studied (with a single exception of the 3,3-difluoroazetidine derivative). According to pK a - LogP plots, the title compounds provide a valuable extension of the fluorine-containing (e. g., fluoroalkyl-substituted) saturated heterocyclic amine series as building blocks for rational optimization studies in early drug discovery., (© 2023 Wiley-VCH GmbH.)

Here, we report a general approach to the synthesis of the difluoroalkyl bicycloalkanes (CF 2 -BCAs), as structural surrogates of aryl ketones and ethers. The chemistry is driven by a dihydrobenzoacridine photocatalyst, that engages in a catalytic electron-donor acceptor (EDA) complex, or directly reduces the fluorinated substrate. These two convergent manifolds lead to the generation of the R-CF 2 radical, that reacts with the [1.1.1]- or [3.1.1.]-propellane. The method is extremely general, and extendable to complex bioactive molecules (30 examples, up to 87 % yield). The structural features of the CF 2 -BCP hybrid bioisostere were investigated by single crystal X-ray. Finally, we synthesised a CF 2 -BCP analogue of a Leukotriene A 4 hydrolase inhibitor, replacing the original aryl ether motif. In silico docking studies indicated that this new analogue maintains the same arrangement within the enzyme pocket, profiling the use of the CF 2 -BCA hybrid bioisostere in medicinal chemistry settings., (© 2023 The Authors. Published by Wiley-VCH GmbH.)

Visualization of biomolecules, cells, and tissues, as well as metabolic processes in vivo is significant for studying the associated biological activities. Fluorine magnetic resonance imaging ( 19 F MRI) holds potential among various imaging technologies thanks to its negligible background signal and deep tissue penetration in vivo. To achieve detection on the targets with high resolution and accuracy, requirements of high-performance 19 F MRI probes are demanding. An ideal 19 F MRI probe is thought to have, first, fluorine tags with magnetically equivalent 19 F nuclei, second, high fluorine content, third, adequate fluorine nuclei mobility, as well as excellent water solubility or dispersity, but not limited to. This review summarizes the research progresses of 19 F MRI probes and mainly discusses the impacts of structures on in vitro and in vivo imaging performances. Additionally, the applications of 19 F MRI probes in ions sensing, molecular structures analysis, cells tracking, and in vivo diagnosis of disease lesions are also covered in this article. From authors' perspectives, this review is able to provide inspirations for relevant researchers on designing and synthesizing advanced 19 F MRI probes., (© 2023 Wiley-VCH GmbH.)

Fluorous tagged peptides have shown promising features for biomedical applications such as drug delivery and multimodal imaging. The bioconjugation of fluoroalkyl ligands onto cargo peptides greatly enhances their proteolytic stability and membrane penetration via a proposed "fluorine effect". The tagged peptides also efficiently deliver other biomolecules such as DNA and siRNA into cells via a co-assembly strategy. The fluoroalkyl chains on peptides with antifouling properties enable efficient gene delivery in the presence of serum proteins. Besides intracellular biomolecule delivery, the amphiphilic peptides can be used to stabilized perfluorocarbon-filled microbubbles for ultrasound imaging. The fluorine nucleus on fluoroalkyls provides intrinsic probes for background-free magnetic resonance imaging. Labeling of fluorous tags with radionuclide 18 F also allows tracing the biodistribution of peptides via positron emission tomography imaging. This mini-review will discuss properties and mechanism of the fluorous tagged peptides in these applications., (© 2023 Wiley-VCH GmbH.)

C-F Insertion reactions represent an attractive approach to prepare valuable fluorinated compounds. The high strength of C-F bonds and the low reactivity of the fluoride released upon C-F bond cleavage, however, mean that examples of such processes are extremely scarce in the literature. Here we report a reaction system that overcomes these challenges using hydrogen bond donors that both activate C-F bonds and allow for downstream reactions with fluoride. In the presence of hexafluoroisopropanol, benzyl and propargyl fluorides undergo efficient formal C-F bond insertion across α-fluorinated styrenes. This process, which does not require any additional fluorinating reagent, occurs under mild conditions and delivers products featuring the gem-difluoro motif, which is attracting increasing interest in medicinal chemistry. Moreover, readily available organic bromides can be engaged directly in a one-pot process that avoids the isolation of organic fluorides., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

The imaging of hydrogel scaffolds by 19 F magnetic resonance imaging (MRI) represents an attractive tool for straightforward and noninvasive monitoring of their morphology and in vivo fate. However, their further applications are significantly limited by a dilemma of insufficient signal resolution with low 19 F content, and/or hydrophobic aggregation of fluorine moieties-induced signal attenuation with high 19 F content. Herein, a novel label-free fluorinated hydrogel (PFCB) is fabricated with high fluorine content to realize noninvasive monitoring through 19 F MRI under ultrahigh scanning resolution (1 mm of scanning thickness). The integration of a zwitterionic unit into each fluorine moiety completely overcame the hydrophobic aggregation-induced signal attenuation, manifesting as high 19 F content and imaging performance. Importantly, 3D reconstruction of the PFCB hydrogel in vivo can be facilely and accurately performed with background free signals, providing detailed biological information of the implanted hydrogel. Additionally, PFCB hydrogel showed adjustable and high mechanical performance, and exhibited minimum foreign body reaction after implantation. As a proof of concept, PFCB hydrogel could be further applied as gel electrodes and wireless flexible sensors for healthcare monitoring. Overall, such label-free fluorinated PFCB hydrogel is an ideal flexible scaffold for eventual clinical applications integrating 19 F MRI-guided unequivocally 3D reconstruction and healthcare monitoring., (© 2022 Wiley-VCH GmbH.)

Studies of protein structure and dynamics are usually carried out in dilute buffer solutions, conditions that differ significantly from the crowded environment in the cell. The double electron-electron resonance (DEER) technique can track proteins' conformations in the cell by providing distance distributions between two attached spin labels. This technique, however, cannot access distances below 1.8 nm. Here, we show that Gd III - 19 F Mims electron-nuclear double resonance (ENDOR) measurements can cover part of this short range. Low temperature solution and in-cell ENDOR measurements, complemented with room temperature solution and in-cell Gd III - 19 F PRE (paramagnetic relaxation enhancement) NMR measurements, were performed on fluorinated GB1 and ubiquitin (Ub), spin-labeled with rigid Gd III tags. The proteins were delivered into human cells via electroporation. The solution and in-cell derived Gd III - 19 F distances were essentially identical and lie in the 1-1.5 nm range revealing that both, GB1 and Ub, retained their overall structure in the Gd III and 19 F regions in the cell., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

The pentafluoroorthotellurate group (teflate, OTeF 5 ) is able to form species, for which only the fluoride analogues are known. Despite nickel fluorides being widely investigated, nickel teflates have remained elusive for decades. By reaction of [NiCl 4 ] 2- and neat ClOTeF 5 , we have synthesized the homoleptic [Ni(OTeF 5 ) 4 ] 2- anion, which presents a distorted tetrahedral structure, unlike the polymeric [NiF 4 ] 2- . This high-spin complex has allowed the study of the electronic properties of the teflate group, which can be classified as a weak/medium-field ligand, and therefore behaves as the fluoride analogue also in ligand-field terms. The teflate ligands in [NEt 4 ] 2 [Ni(OTeF 5 ) 4 ] are easily substituted, as shown by the formation of [Ni(NCMe) 6 ][OTeF 5 ] 2 by dissolving it in acetonitrile. Nevertheless, careful reactions with other conventional ligands have enabled the crystallization of nickel teflate complexes with different coordination geometries, i.e. [NEt 4 ] 2 [trans-Ni(OEt 2 ) 2 (OTeF 5 ) 4 ] or [NEt 4 ][Ni(bpyMe 2 )(OTeF 5 ) 3 ]., (© 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

The review covers various aspects of fluorinated cycloalkyl (C 3 -C 7 ) building blocks for drug discovery, including their synthesis, key physicochemical properties, and biological and medicinal applications of their derivatives. The discussed synthetic methods include classical nucleophilic fluorinations of various substrates, the addition of fluorine and another heteroatom to double bonds, cycloadditions and other transformations of fluorine-containing substrates, as well as some newer reactions like fluorination of non-activated and remotely activated C-H bonds, decarboxylative and deborylative fluorinations, etc. The known data on the effect of introducing the fluorinated cycloalkyl groups on the compound's key in vitro parameters (such as acidity/basicity, lipophilicity, conformational behavior, and short contact capabilities) are surveyed. Finally, applications of fluorinated cycloalkyl building block derivatives in the design of biologically active compounds (including marketed drugs Maraviroc, Ivosidenib, and Sitafloxacin) are covered, with a focus on the fluorination impact., (© 2022 Wiley-VCH GmbH.)

Pentafluorosulfanyl (SF 5 )-containing compounds and corresponding analogs are a highly valuable class of fluorine-containing building blocks owing to their unique properties. The reason for that is the set of peculiar and tremendously beneficial characteristics they can impart on molecules once introduced onto them. Despite this, their application in distinct scientific fields remains modest, given the extremely harsh reaction conditions needed to access such compounds. The recent synthetic approaches via S-F, and C-SF 5 bond formation as well as the use of SF 5 -containing building blocks embody a "stairway-to-heaven" loophole in the synthesis of otherwise-inaccessible chemical scaffolds only a few years ago. Herein, we report and evaluate the properties of the SF 5 group and analogs, by summarizing synthetic methodologies available to access them as well as following applications in material science and medicinal chemistry since 2015., (© 2022 Wiley-VCH GmbH.)

Preparation and characterization of the dimeric Lewis superacid [Al(OTeF 5 ) 3 ] 2 and various solvent adducts is presented. The latter range from thermally stable adducts to highly reactive, weakly bound species. DFT calculations on the ligand affinity of these Lewis acids were performed in order to rank their remaining Lewis acidity. An experimental proof of the Lewis acidity is provided by the reaction of solvent-adducts of Al(OTeF 5 ) 3 with [PPh 4 ][SbF 6 ] and OPEt 3 , respectively. Furthermore, their reactivity towards chloride and pentafluoroorthotellurate salts as well as (CH 3 ) 3 SiCl and (CH 3 ) 3 SiF is shown. This includes the formation of the dianion [Al(OTeF 5 ) 5 ] 2- ., (© 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

The physicochemical properties (pK a (H), log P, and aqueous solubility) of fluoroalkyl-substituted heterocyclic amines were profiled to facilitate the amines' rational application in medicinal chemistry research. The features of fluorine-containing compounds were compared to those of the corresponding parent non-fluorinated heterocycles and the corresponding fluorinated n-alkylamines. Amine basicity was observed to change in a monotonic fashion depending on the fluorination pattern. Although the introduction of fluoroalkyl groups had complex effects on the lipophilicity and aqueous solubility of the compounds, possible contributions of the fluorination pattern, ring size, and conformation of the substituent in the ring were addressed for a series of derivatives. The summarized data provide a useful guideline for the application of fluorinated motifs for fine-tuning a compound's properties related to drug discovery., (© 2022 Wiley-VCH GmbH.)

The development of multifunctional nanoplatforms for bioimaging and therapy has attracted extensive attention in recent decades. As an emerging magnetic resonance imaging (MRI) technique, 19 F MRI effectively complements the limit of 1 H MRI owing to trace amount of 19 F atoms existing in the human body, affording high specificity. In this work, a novel molecule (CFO) containing hydrophilic fluorine fragments was synthesized using amino acids as starting materials, which could self-assemble into small nanoprobes via hydrophobic interactions of oleic acid moiety. The as-prepared nanoprobes displayed good relaxation performances thanks to the carboxylate group and sulfoxide group nearby. The nanoprobes successfully demonstrated its capacity for in-vivo 19 F MRI. In addition, CFO could be used as a general fluorine labeling agent for surface functionalization of nanoparticles, which provided a universal method for constructing water-soluble multifunctional nanoplatforms., (© 2022 Wiley-VCH GmbH.)

Ligand-based 19 F NMR screening is a highly effective and well-established hit-finding approach. The high sensitivity to protein binding makes it particularly suitable for fragment screening. Different criteria can be considered for generating fluorinated fragment libraries. One common strategy is to assemble a large, diverse, well-designed and characterized fragment library which is screened in mixtures, generated based on experimental 19 F NMR chemical shifts. Here, we introduce a complementary knowledge-based 19 F NMR screening approach, named 19 Focused screening, enabling the efficient screening of putative active molecules selected by computational hit finding methodologies, in mixtures assembled and on-the-fly deconvoluted based on predicted 19 F NMR chemical shifts. In this study, we developed a novel approach, named LEFshift, for 19 F NMR chemical shift prediction using rooted topological fluorine torsion fingerprints in combination with a random forest machine learning method. A demonstration of this approach to a real test case is reported., (© 2022 Wiley-VCH GmbH.)

Fluorine is a critical element for the design of bioactive compounds, driving advances in selective and sustainable fluorination. However, stereogenic tertiary fluorides pose a synthetic challenge and are thus present in only a few approved drugs (fluticasone, solithromycin, and sofosbuvir). The aldol reaction of fluorinated donors provides an atom-economical approach to asymmetric C-F motifs via C-C bond formation. We report that the type II pyruvate aldolase HpcH and engineered variants perform addition of β-fluoro-α-ketoacids (including fluoropyruvate, β-fluoro-α-ketobutyrate, and β-fluoro-α-ketovalerate) to diverse aldehydes. The reactivity of HpcH towards these fluoro-donors grants access to enantiopure secondary or tertiary fluorides. In addition to representing the first synthesis of tertiary fluorides via biocatalytic carboligation, the afforded products could improve the diversity of fluorinated building blocks and enable the synthesis of fluorinated drug analogs., (© 2022 Wiley-VCH GmbH.)

Physico-chemical properties important to drug discovery (pK a , LogP, and aqueous solubility), as well as metabolic stability, were studied for a series of functionalized gem-difluorinated cycloalkanes and compared to those of non-fluorinated and acyclic counterparts to evaluate the impact of the fluorination. It was found that the influence of the CF 2 moiety on the acidity/basicity of the corresponding carboxylic acids and amines was defined by inductive the effect of the fluorine atoms and was nearly the same for acyclic and cyclic aliphatic compounds. Lipophilicity and aqueous solubility followed more complex trends and were affected by the position of the fluorine atoms, ring size, and even the nature of the functional group present; also, significant differences were found for the acyclic and cyclic series. Also, gem-difluorination either did not affect or slightly improved the metabolic stability of the corresponding model derivatives. The presented results can be used as a guide for rational drug design employing fluorine and establish the first chapter in a catalog of the key in vitro properties of fluorinated cycloalkanes., (© 2022 Wiley-VCH GmbH.)

Fluorine-18 remains the most widely clinically utilized radionuclide globally for positron emission tomography (PET). The emergence of therapeutic isotopes for the management of disease has produced a pronounced interest in matched, theranostic isotope pairs that can be employed in tandem for the diagnosis and stratification of patients for subsequent radiotherapy. 18 F, however, does not have a suitable therapeutic isotopologue. Here, we demonstrate that the formation of [ 18 F][Sc-F] ternary complexes is feasible under mild, aqueous conditions, producing chemically robust radiopharmaceuticals in high radiochemical yield and specific activity. A corresponding in vivo study with a cancer-targeting [ 18 F][Sc-F] tracer indicates excellent in vivo stability and produces exquisite PET image quality, rendering the 18 F/ 47 Sc isotope pair an unusual, yet chemically matched theranostic pair with excellent potential for clinical translation., (© 2021 Wiley-VCH GmbH.)

A systematic study of halogenate(I/III) anions with polyatomic ligands is presented. The bis(perfluoro-tert-butoxy) halogenates(I) [X(OC 4 F 9 ) 2 ] - , X=Cl, Br, I, of chlorine, bromine, and iodine are prepared as their tetraethylammonium salts and characterized with IR, Raman, and NMR spectroscopic methods, as well as single-crystal X-ray diffraction analyses. Spectroscopical data are supported by quantum-chemical calculations. Additionally, the bonding situation of the species in question are analyzed and discussed. Furthermore, the oxidation to the corresponding halogenate(III) derivatives was studied. For [Br(OC 4 F 9 ) 2 ] - , oxidation with elemental fluorine gave [BrF 2 (OC 4 F 9 ) 2 ] - . Iodide was directly oxidized by ClOC 4 F 9 to the I III species [I(OC 4 F 9 ) 4 ] - , which is a surprisingly inert anion that might be used as a weakly coordinating anion (WCA) in the future. For [Cl(OC 4 F 9 ) 2 ] - , the decomposition products of the synthetic approaches towards a chlorine(III) system were analyzed., (© 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

The insertion of fluorine atoms and/or fluoroalkyl groups can lead to many beneficial effects in biologically active molecules, such as enhanced metabolic stability, bioavailability, lipophilicity, and membrane permeability, as well as a strengthening of protein-ligand binding interactions. However, this "magic effect" of fluorine atom(s) insertion can often be meaningless. Taking advantage of the wide range of data coming from the quest for carbonic anhydrase (CA) fluorinated inhibitors, this Minireview attempts to give "general guidelines" on how to wisely insert fluorine atom(s) within an inhibitor moiety to precisely enhance or disrupt ligand-protein interactions, depending on the target location of the fluorine substitution in the ligand. Multiple approaches such as ITC, kinetic and inhibition studies, X-ray crystallography, and NMR spectroscopy are useful in dissecting single binding contributions to the overall observed effect. The exploitation of innovative directions made in the field of protein and ligand-based fluorine NMR screening is also discussed to avoid misconduct and finely tune the exploitation of selective fluorine atom insertion in the future., (© 2021 Wiley-VCH GmbH.)

To create innovative materials, efficient control and engineering of pore sizes and their characteristics, crystallinity and stability is required. Eight hybrid Tri 4 Di 6 imine cages with a tunable degree of fluorination and one fully fluorinated Tri 4 Di 6 imine cage are investigated. Although the fluorinated and the non-fluorinated building blocks used herein differ vastly in reactivity, it was possible to gain control over the outcome of the self-assembly process, by carefully controlling the feed ratio. This represents the first hybrid material based on fluorinated/hydrogenated porous organic cages (POCs). These cages with unlimited miscibility in the solid state were obtained as highly crystalline samples after recrystallization and even showed retention of the crystal lattice, forming alloys. All mixtures and the fully fluorinated Tri 4 Di 6 imine cage were analyzed by MALDI-MS, single-crystal XRD, powder XRD and in regard to thermal stability (TGA)., (© 2021 The Authors. Published by Wiley-VCH GmbH.)

Protein-glycan interactions mediate important biological processes, including pathogen host invasion and cellular communication. Herein, we showcase an expedite approach that integrates automated glycan assembly (AGA) of 19 F-labeled probes and high-throughput NMR methods, enabling the study of protein-glycan interactions. Synthetic Lewis type 2 antigens were screened against seven glycan binding proteins (GBPs), including DC-SIGN and BambL, respectively involved in HIV-1 and lung infections in immunocompromised patients, confirming the preference for fucosylated glycans (Le x , H type 2, Le y ). Previously unknown glycan-lectin weak interactions were detected, and thermodynamic data were obtained. Enzymatic reactions were monitored in real-time, delivering kinetic parameters. These results demonstrate the utility of AGA combined with 19 F NMR for the discovery and characterization of glycan-protein interactions, opening up new perspectives for 19 F-labeled complex glycans., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Emerging evidence suggests that microRNAs (miRNAs) play key roles in the regulation of multiple biological processes, including the differentiation of osteoblasts. Although miRNA-based gene therapy holds immense potential in the treatment of a variety of diseases, the intracellular delivery of miRNA remains challenging owing to the lack of efficient and safe gene carriers. In this study, a fluoropolymer (FP) is constructed through the modification of polyamidoamine (PAMAM) using heptafluorobutyric anhydride and then is used as a carrier for miR-23b transfection to induce osteocyte differentiation of osteoblasts. The derivative FP is found to facilitate miR-23b transfection due to its favorable endosomal escape from the "proton sponge" effect. Compared to PAMAM/miR-23b, the FP/miR-23b nanocomplex efficiently promotes the differentiation of osteoblasts and formation of calcified nodules, attributable to enhanced expression of various osteogenesis genes (runt-related transfection factor 2 [RUNX2], alkaline phosphatase [ALP], osteopontin [OPN], and osteocalcin [OCN]). Thus, FP-mediated miR-23b transfection may be used as an effective strategy to facilitate osteogenic differentiation., (© 2021 Wiley-VCH GmbH.)

The coordination chemistry of KrF 2 has been limited in contrast with that of XeF 2 , which exhibits a far richer coordination chemistry with main-group and transition-metal cations. In the present work, reactions of [XeF 5 ][AsF 6 ] with KrF 2 in anhydrous HF solvent afforded [F 5 Xe(FKrF)AsF 6 ] and [F 5 Xe(FKrF) 2 AsF 6 ], the first mixed krypton/xenon compounds. X-ray crystal structures and Raman spectra show the KrF 2 ligands and [AsF 6 ] - anions are F-coordinated to the xenon atoms of the [XeF 5 ] + cations. Quantum-chemical calculations are consistent with essentially noncovalent ligand-xenon bonds that may be described in terms of σ-hole bonding. These complexes significantly extend the XeF 2 -KrF 2 analogy and the limited chemistry of krypton by introducing a new class of coordination compound in which KrF 2 functions as a ligand that coordinates to xenon(VI). The HF solvates, [F 5 Xe(FH)AsF 6 ] and [F 5 Xe(FH)SbF 6 ], are also characterized in this study and they provide rare examples of HF coordinated to xenon(VI)., (© 2020 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Glycans are well established to play important roles at various stages of infection and disease, and ways to modulate these interactions have been sought as novel therapies. The use of native glycan structures has met with limited success, which can be attributed to their characteristic high polarity (e.g., low binding affinities) and inherently poor pharmacokinetic properties (e.g., short drug-target residence times, rapid renal excretion), leading to the development of 'glycomimetics'. Fluorinated drugs have become increasingly common over recent decades, with fluorinated glycomimetics offering some unique advantages. Deoxyfluorination maintains certain electrostatic interactions, while concomitantly reducing net polarity through 'polar hydrophobicity', improving residence times and binding affinities. Fluorination destabilizes the oxocarbenium transition state associated with metabolic degradation, and can restore exo- and endo-anomeric effects in C-glycosides and carbasugars. Lastly, it has shown great utility in radiotracer development and enhancement of antigenicity in glycan-based vaccines. Owing to synthetic challenges, fluorinated glycomimetics have been somewhat underutilized to date, but methodological improvements will advance their use in glycomimetic drugs., (© 2020 Wiley-VCH GmbH.)

Discovering new functional genes, designing perfect crystal structures, and developing high-performance materials are the goals being pursued by scientists. Herein, the first antimony pyrophosphate, K 2 Sb(P 2 O 7 )F, possessing an optimal layered structure, is reported, where the perfect structural arrangement induces excellent optical properties. K 2 Sb(P 2 O 7 )F not only displays a sharply enhanced birefringence (0.157@546 nm) compared to the existing phosphate optical materials, but also exhibits a strong second-harmonic generation response (4.0×KDP). Remarkably, a new bifunctional gene, the square-pyramidal SbO 4 F group, was discovered, and a unique two-dimensional arrangement of Cairo pentagonal tiling units was observed in inorganic compounds for the first time., (© 2020 Wiley-VCH GmbH.)

Effective diagnosis of disease and its progression can be aided by 19 F magnetic resonance imaging (MRI) techniques. Specifically, the inherent sensitivity of the spin-lattice relaxation time (T 1 ) of 19 F nuclei to oxygen partial pressure makes 19 F MRI an attractive non-invasive approach to quantify tissue oxygenation in a spatiotemporal manner. However, there are only few materials with the adequate sensitivity to be used as oxygen-sensitive 19 F MRI agents at clinically relevant field strengths. Motivated by the limitations in current technologies, we report highly fluorinated monomers that provide a platform approach to realize water-soluble, partially fluorinated copolymers as 19 F MRI agents with the required sensitivity to quantify solution oxygenation at clinically relevant magnetic field strengths. The synthesis of a systematic library of partially fluorinated copolymers enabled a comprehensive evaluation of copolymer structure-property relationships relevant to 19 F MRI. The highest-performing material composition demonstrated a signal-to-noise ratio that corresponded to an apparent 19 F density of 220 mm, which surpasses the threshold of 126 mm 19 F required for visualization on a three Tesla clinical MRI. Furthermore, the T 1 of these high performing materials demonstrated a linear relationship with solution oxygenation, with oxygen sensitivity reaching 240×10 -5  mmHg -1 s -1 . The relationships between material composition and 19 F MRI performance identified herein suggest general structure-property criteria for the further improvement of modular, water-soluble 19 F MRI agents for quantifying oxygenation in environments relevant to medical imaging., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In the continuous search for multimodal systems with combined diagnostic and therapeutic functions, several efforts have been made to develop multifunctional drug delivery systems. In this work, through a covalent approach, a new class of fluorinated poly(lactic-co-glycolic acid) co-polymers (F-PLGA) were designed that contain an increasing number of magnetically equivalent fluorine atoms. In particular, two novel compounds, F 3 -PLGA and F 9 -PLGA, were synthesized and their chemical structure and thermal stability were analyzed by solution NMR, DSC, and TGA. The obtained F-PLGA compounds were proven to form in aqueous solution colloidal stable nanoparticles (NPs) displaying a strong 19 F NMR signal. The fluorinated NPs also showed an enhanced ability to load hydrophobic drugs containing fluorine atoms compared to analogous pristine PLGA NPs. Preliminary in vitro studies showed high cell viability and the NP ability to intracellularly deliver and release a functioning drug., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The absence of fluorine from most biomolecules renders it an excellent probe for NMR spectroscopy to monitor inhibitor-protein interactions. However, predicting the binding mode of a fluorinated ligand from a chemical shift (or vice versa) has been challenging due to the high electron density of the fluorine atom. Nonetheless, reliable 19 F chemical-shift predictions to deduce ligand-binding modes hold great potential for in silico drug design. Herein, we present a systematic QM/MM study to predict the 19 F NMR chemical shifts of a covalently bound fluorinated inhibitor to the essential oxidoreductase tryparedoxin (Tpx) from African trypanosomes, the causative agent of African sleeping sickness. We include many protein-inhibitor conformations as well as monomeric and dimeric inhibitor-protein complexes, thus rendering it the largest computational study on chemical shifts of 19 F nuclei in a biological context to date. Our predicted shifts agree well with those obtained experimentally and pave the way for future work in this area., (© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Structural proteomics refers to large-scale mapping of protein structures in order to understand the relationship between protein sequence, structure, and function. Chemical labeling, in combination with mass-spectrometry (MS) analysis, have emerged as powerful tools to enable a broad range of biological applications in structural proteomics. The key to success is a biocompatible reagent that modifies a protein without affecting its high-order structure. Fluorine, well-known to exert profound effects on the physical and chemical properties of reagents, should have an impact on structural proteomics. In this Minireview, we describe several fluorine-containing reagents that can be applied in structural proteomics. We organize their applications around four MS-based techniques: a) affinity labeling, b) activity-based protein profiling (ABPP), c) protein footprinting, and d) protein cross-linking. Our aim is to provide an overview of the research, development, and application of fluorine-containing reagents in protein structural studies., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The removal of 5-methyl-deoxycytidine (mdC) from promoter elements is associated with reactivation of the silenced corresponding genes. It takes place through an active demethylation process involving the oxidation of mdC to 5-hydroxymethyl-deoxycytidine (hmdC) and further on to 5-formyl-deoxycytidine (fdC) and 5-carboxy-deoxycytidine (cadC) with the help of α-ketoglutarate-dependent Tet oxygenases. The next step can occur through the action of a glycosylase (TDG), which cleaves fdC out of the genome for replacement by dC. A second pathway is proposed to involve C-C bond cleavage that converts fdC directly into dC. A 6-aza-5-formyl-deoxycytidine (a-fdC) probe molecule was synthesized and fed to various somatic cell lines and induced mouse embryonic stem cells, together with a 2'-fluorinated fdC analogue (F-fdC). While deformylation of F-fdC was clearly observed in vivo, it did not occur with a-fdC, thus suggesting that the C-C bond-cleaving deformylation is initiated by nucleophilic activation., (© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

A fluoro-substituted δ-tocotrienol derivative, DT3-F2, was synthesized. This compound was designed to stabilize the metabolically labile terminal methyl groups of δ-tocotrienol by replacing one C-H bond on each of the two methyl groups with a C-F bond. However, in vitro metabolic stability studies using mouse liver microsomes revealed an unexpected rapid enzymatic C-F bond hydrolysis of DT3-F2. To the best of our knowledge, this is the first report of an unusual metabolic hydrolysis of allylic C-F bonds., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The conjugation of hydrophilic low-fouling polymers to therapeutic molecules and particles is an effective approach to improving their aqueous stability, solubility, and pharmacokinetics. Recent concerns over the immunogenicity of poly(ethylene glycol) has highlighted the importance of identifying alternative low fouling polymers. Now, a new class of synthetic water-soluble homo-fluoropolymers are reported with a sulfoxide side-chain structure. The incorporation of fluorine enables direct imaging of the homopolymer by 19 F MRI, negating the need for additional synthetic steps to attach an imaging moiety. These self-reporting fluoropolymers show outstanding imaging sensitivity and remarkable hydrophilicity, and as such are a new class of low-fouling polymer for bioconjugation and in vivo tracking., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Solid-state 19 F NMR is a powerful method to study the interactions of biologically active peptides with membranes. So far, in labelled peptides, the 19 F-reporter group has always been installed on the side chain of an amino acid. Given the fact that monofluoroalkenes are non-hydrolyzable peptide bond mimics, we have synthesized a monofluoroalkene-based dipeptide isostere, Val-Ψ[(Z)-CF=CH]-Gly, and inserted it in the sequence of two well-studied antimicrobial peptides: PGLa and (KIGAKI) 3 are representatives of an α-helix and a β-sheet. The conformations and biological activities of these labeled peptides were studied to assess the suitability of monofluoroalkenes for 19 F NMR structure analysis., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Fragment-based drug discovery (FBDD) is a popular method in academia and the pharmaceutical industry for the discovery of early lead candidates. Despite its wide-spread use, the approach still suffers from laborious screening workflows and a limited diversity in the fragments applied. Presented here is the design, synthesis, and biological evaluation of the first fragment library specifically tailored to tackle both these challenges. The 3F library of 115 fluorinated, Fsp 3 -rich fragments is shape diverse and natural-product-like with desirable physicochemical properties. The library is perfectly suited for rapid and efficient screening by NMR spectroscopy in a two-stage workflow of 19 F NMR and subsequent 1 H NMR methods. Hits against four diverse protein targets are widely distributed among the fragment scaffolds in the 3F library and a 67 % validation rate was achieved using secondary assays. This collection is the first synthetic fragment library tailor-made for 19 F NMR screening and the results demonstrate that the approach should find broad application in the FBDD community., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Molecular alkali tetrafluorido aurate ion pairs M[AuF 4 ] (M=K, Rb, Cs) are produced by co-deposition of IR laser-ablated AuF 3 and MF in solid neon under cryogenic conditions. This method also yields molecular AuF 3 and its dimer Au 2 F 6 . The products are characterized by their Au-F stretching bands and high-level quantum-chemical calculations at the CCSD(T)/triple-ζ level of theory. Structural changes in AuF 4 - associated with the coordination of the anion to different alkali cations are proven spectroscopically and discussed., (© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)