Oxidative fluorination with Selectfluor: A convenient procedure for preparing hypervalent iodine(V) fluorides.

The ability to investigate hypervalent iodine(V) fluorides has been limited primarily by their difficult preparation traditionally using harsh fluorinating reagents such as trifluoromethyl hypofluorite and bromine trifluoride. Here, we report a mild and efficient route using Selectfluor to deliver hypervalent iodine(V) fluorides in good isolated yields (72-90%). Stability studies revealed that bicyclic difluoro(aryl)-λ5-iodane 6 was much more stable in acetonitrile-d 3 than in chloroform-d 1, presumably due to acetonitrile coordinating to the iodine(V) centre and stabilising it via halogen bonding.

Fluorine-Modulated MXene-Derived Catalysts for Multiphase Sulfur Conversion in Lithium-Sulfur Battery.

Fluorine owing to its inherently high electronegativity exhibits charge delocalization and ion dissociation capabilities; as a result, there has been an influx of research studies focused on the utilization of fluorides to optimize solid electrolyte interfaces and provide dynamic protection of electrodes to regulate the reaction and function performance of batteries. Nonetheless, the shuttle effect and the sluggish redox reaction kinetics emphasize the potential bottlenecks of lithium-sulfur batteries. Whether fluorine modulation regulate the reaction process of Li-S chemistry? Here, the TiOF/Ti3C2 MXene nanoribbons with a tailored F distribution were constructed via an NH4F fluorinated method. Relying on in situ characterizations and electrochemical analysis, the F activates the catalysis function of Ti metal atoms in the consecutive redox reaction. The positive charge of Ti metal sites is increased due to the formation of O-Ti-F bonds based on the Lewis acid-base mechanism, which contributes to the adsorption of polysulfides, provides more nucleation sites and promotes the cleavage of S-S bonds. This facilitates the deposition of Li2S at lower overpotentials. Additionally, fluorine has the capacity to capture electrons originating from Li2S dissolution due to charge compensation mechanisms. The fluorine modulation strategy holds the promise of guiding the construction of fluorine-based catalysts and facilitating the seamless integration of multiple consecutive heterogeneous catalytic processes.

Gas Delivery Relevant to Human Health using Porous Materials.

Gases are essential for various applications relevant to human health, including in medicine, biomedical imaging, and pharmaceutical synthesis. However, gases are significantly more challenging to safely handle than liquids and solids. Herein, we review the use of porous materials, such as metal-organic frameworks (MOFs), zeolites, and silicas, to adsorb medicinally relevant gases and facilitate their handling as solids. Specific topics include the use of MOFs and zeolites to deliver H2S for therapeutic applications, 129Xe for magnetic resonance imaging, O2 for the treatment of cancer and hypoxia, and various gases for use in organic synthesis. This Perspective aims to bring together the organic, inorganic, medicinal, and materials chemistry communities to inspire the design of next-generation porous materials for the storage and delivery of medicinally relevant gases.

Hypervalent Iodine-Catalyzed Fluorination of Diene-Containing Compounds: A Computational Study.

Studies have shown that the incorporation of fluorine into materials can improve their properties, but C-F bonds are not readily formed in nature. Although some researchers have studied the reaction of fluorinating alkenes catalyzed by hypervalent iodine, far too little attention has been paid to its reaction mechanism. This study aimed to explore the mechanism of the hypervalent iodine-catalyzed 1,4-difluorination of dienes. We found that the catalyst is favorable for the activation of C1=C2 double bonds through halogen bonds, and then two HFs interact with one F atom in the catalyst via hydrogen bonds, resulting in the cleavage of I-F bonds and the formation of [F-H∙∙∙F]-. Subsequently, the catalyst interacts with C1, and the roaming [F-H···F]- attacks C4 from the opposite side of the catalyst. After the fluorination step is completed, the nucleophile F- substitutes the catalyst via the SN2 mechanism. Our calculations demonstrated that the interaction between HF and F- is favorable for the stabilization of the transition state within the fluorination process for which the presence of two HFs in the reaction is the best. We also observed that [F-H∙∙∙F]- attacking C4 from the opposite side of the catalyst is more advantageous than attacking from the same side. This study therefore offers a novel perspective on the mechanism of the hypervalent iodine-catalyzed fluoridation of dienes.

Benzylic C(sp3)-H fluorination.

The selective fluorination of C(sp3)-H bonds is an attractive target, particularly for pharmaceutical and agrochemical applications. Consequently, over recent years much attention has been focused on C(sp3)-H fluorination, and several methods that are selective for benzylic C-H bonds have been reported. These protocols operate via several distinct mechanistic pathways and involve a variety of fluorine sources with distinct reactivity profiles. This review aims to give context to these transformations and strategies, highlighting the different tactics to achieve fluorination of benzylic C-H bonds.

Engineering of a Malonyl-CoA Ligase for Production of Fluorinated Polyketide Extender Units.

Enzymatic platforms for producing malonyl-CoA-based extender units required for polyketide biosynthesis are often based on malonyl-CoA ligases such as MatB from Rhizobium trifolii and Rhodopseudomonas palustris. However, despite broad interest in the fluorination of polyketides and prior success with engineering MatB homologs, the suitability of MatB for accessing the tertiary substituted fluoromethylmalonyl-CoA needed to produce flurithromycin and solithromycin has not yet been reported. Herein, we report the structure-guided engineering of a MatB homolog to optimize the production of fluoromethylmalonyl-CoA, resulting in a variant with increased conversion and providing a platform to produce a suitable building block mixture for fluorinated macrolide production. Additionally, the mutant demonstrated broad utility for various substituted malonyl-CoAs. The MatB mutant sets the stage to access fluorinated macrolides by coupling it with altered PKS machinery to install fluorinated malonyl-CoA into macrolide scaffolds.

Modular Prodrug-Engineered Oxygen Nano-Tank With Outstanding Nanoassembly Performance, High Oxygen Loading, and Closed-Loop Tumor Hypoxia Relief.

The clinical translation of tumor hypoxia intervention modalities still falls short of expectation, restricted by poor biocompatibility of oxygen-carrying materials, unsatisfactory oxygen loading performance, and abnormally high cellular oxygen consumption-caused insufficient hypoxia relief. Herein, a carrier-free oxygen nano-tank based on modular fluorination prodrug design and co-assembly nanotechnology is elaborately exploited, which is facilely fabricated through the molecular nanoassembly of a fluorinated prodrug (FSSP) of pyropheophorbide a (PPa) and an oxygen consumption inhibitor (atovaquone, ATO). The nano-tank adeptly achieves sufficient oxygen enrichment while simultaneously suppressing oxygen consumption within tumors for complete tumor hypoxia alleviation. Significant, the fluorination module in FSSP not only confers favorable co-assemblage of FSSP and ATO, but also empowers the nanoassembly to readily carry oxygen. As expected, it displays excellent oxygen carrying capacity, favorable pharmacokinetics, on-demand laser-triggerable ATO release, closed-loop tumor hypoxia relief, and significant enhancement to PPa-mediated PDT in vitro and in vivo. This study provides a novel nanotherapeutic paradigm for tumor hypoxia intervention-enhanced cancer therapy.

Electrochemical Decarboxylative Cross-Coupling with Nucleophiles.

Decarboxylative cross-coupling reactions are powerful tools for carbon-heteroatom bonds formation, but typically require pre-activated carboxylic acids as substrates or heteroelectrophiles as functional groups. Herein, we present an electrochemical decarboxylative cross-coupling of carboxylic acids with structurally diverse fluorine, alcohol, H2O, acid, and amine as nucleophiles. This strategy takes advantage of the ready availability of these building blocks from commercial libraries, as well as the mild and oxidant-free conditions provided by electrochemical system. This reaction demonstrates good functional-group tolerance and its utility in late-stage functionalization.

Control of Multi-Fluorination Number and Position in D-π-A Type Polymers and Their Impact on High-Voltage Organic Photovoltaics.

Exploring the structure-performance relationship of high-voltage organic solar cells (OSCs) is significant for pushing material design and promoting photovoltaic performance. Herein, we chose a D-π-A type polymer composed of 4,8-bis(thiophene-2-yl)-benzo[1,2-b:4,5-b']dithiophene (BDT-T) and benzotriazole (BTA) units as the benchmark to investigate the effect of the fluorination number and position of the polymers on the device performance of the high-voltage OSCs, with a benzotriazole-based small molecule (BTA3) as the acceptor. F00, F20, and F40 are the polymers with progressively increasing F atoms on the D units, while F02, F22, and F42 are the polymers with further attachment of F atoms to the BTA units based on the above three polymers. Fluorination positively affects the molecular planarity, dipole moment, and molecular aggregations. Our results show that VOC increases with the number of fluorine atoms, and fluorination on the D units has a greater effect on VOC than on the A unit. F42 with six fluorine atom substitutions achieves the highest VOC (1.23 V). When four F atoms are located on the D units, the short-circuit current (JSC) and fill factor (FF) plummet, and before that, they remain almost constant. The drop in JSC and FF in F40- and F42-based devices may be attributed to inefficient charge transfer and severe charge recombination. The F22:BTA3 system achieves the highest power conversion efficiency of 9.5% with a VOC of 1.20 V due to the excellent balance between the photovoltaic parameters. Our study provides insights for the future application of fluorination strategies in molecular design for high-voltage organic photovoltaics.

Protodefluorinated Selectfluor® Aggregatively Activates Selectfluor® for Efficient Radical C(sp3)-H Fluorination Reactions.

Efficient fluorination reactions are key in the late-stage functionalization of complex molecules in medicinal chemistry, in upgrading chemical feedstocks, and in materials science. Radical C(sp3)-H fluorinations using Selectfluor® - one of the most popular fluorination agents - allow to directly engage unactivated precursors under mild photochemical or thermal catalytic conditions. However, H-TEDA(BF4)2 to date is overlooked and discarded as waste, despite comprising 95% of the molecular weight of Selectfluor®. We demonstrate that the addition of H-TEDA(BF4)2 at the start of fluorination reactions markedly promotes their rates and accesses higher overall yields of fluorinated products (~3.3x higher on average across the cases studied) than unpromoted reactions. Several case studies showcase generality of the promotor, for photochemical, photocatalytic and thermal radical fluorination reactions. Detailed mechanistic investigations reveal the key importance of aggregation changes in Selectfluor® and H-TEDA(BF4)2 to fill gaps of understanding in how radical C(sp3)-H fluorination reactions work. This study exemplifies an overlooked reaction waste product being upcycled for a useful application.

Recent Progress of Fluorinated Conjugated Polymers.

In recent years, conjugated polymers have received widespread attention due to their characteristic advantages of light weight, favorable solution processability, and structural modifiability. Among various conjugated polymers, fluorinated ones have developed rapidly to achieve high-performance n-type or ambipolar polymeric semiconductors. The uniqueness of fluorinated conjugated polymers contains the high coplanarity of their structures, lower frontier molecular orbital energy levels, and strong nonbonding interactions. In this review, first the fluorinated building blocks, including fluorinated benzene and thiophene rings, fluorinated B←N bridged units, and fluoroalkyl side chains are summarized. Subsequently, different synthetic methods of fluorinated conjugated polymers are described, with a special focus on their respective advantages and disadvantages. Then, with these numerous fluorinated structures and appropriate synthetic methods bear in mind, the properties and applications of the fluorinated conjugated polymers, such as cyclopentadithiophene-, amide-, and imide-based polymers, and B←N embedded polymers, are systematically discussed. The introduction of fluorine atoms can further enhance the electron-deficiency of the backbone, influencing the charge carrier transport performance. The promising fluorinated conjugated polymers are applied widely in organic field-effect transistors, organic solar cells, organic thermoelectric devices, and other organic opto-electric devices. Finally, the outlook on the challenges and future development of fluorinated conjugated polymers is systematically discussed.

Precise Helium Sieving from Hydrogen Using Fluorine-Decorated Carbon Hollow Fiber Membranes.

Separating helium (He) and hydrogen (H2), two gases that are extremely similar in molecular size and condensation properties, presents a formidable challenge in the helium industry. The development of membranes capable of precisely differentiating between these gases is crucial for achieving large-scale, energy-efficient He/H2 separation. However, the limited selectivity of current membranes has hindered their practical application. In this study, we propose a novel approach to overcome this challenge by engineering submicroporous membranes through the fluorination of partially carbonized hollow fibers. We demonstrate that the fluorine substitution on the inner rim of the micropore walls within the carbon hollow fibers enables tunability of the microporous architecture. Furthermore, it enhances interactions between H2 molecules and the micropore walls through the polarization and hydrogen bonding induced by C-F bonds, resulting in simultaneous improvements in both He/H2 diffusivity and solubility selectivities. The fluorinated HFM-550-F-1 min membrane exhibits exceptional mixed-gas separation performance, with a binary mixed-gas He/H2 selectivity of 10.5 and a ternary mixed-gas He/(H2+CO2) selectivity of 20.8, at 40 bar feed pressure and 35 °C, surpassing all previously reported polymer-based gas separation membranes, and remarkable plasticization resistance and long-term continuous stability over 30 days.

Fluorination/Dearomatization of C6F5 Groups: An FLP Route to an Electrophilic Borane and Non-Coordinating Anions.

B(C6F5)3 and the corresponding anion [B(C6F5)4]- are ubiquitous in main group and transition metal chemistry. Known derivatives are generally limited to the incorporation of electron donating substituents. Herein we describe electrophilic fluorination and dearomatization of such species using XeF2 in the presence of BF3 or Lewis acidic cations. In this fashion the anions [HB(C6F5)3]-, [B(C6F5)4]- and [(C6F5)3BC≡NB(C6F5)3]-, are converted to [FB(C6F7)3]-, [B(C6F7)4]-, and [(C6F7)3BC≡NB(C6F7)3]-, respectively. Similarly, the borane adducts (L)B(C6F7)3 (L=MeCN, OPEt3) are produced. These rare examples of electrophilic attack of electron deficient rings proceed as [XeF][BF4] acts as a frustrated Lewis pair effecting fluorination and dearomatization of C6F5 rings.

α-Fluorination of tropane compounds and its impact on physicochemical and ADME properties.

Using an electrochemical C(sp3)-H fluorination reaction, a series of α-fluorinated tropane compounds were synthesized and their druglikeness parameters were assessed to compare with the parent compounds. Improvements were observed in membrane permeability, P-gp liability, and inhibitory effects on hERG and Nav1.5 channels, accompanied with a trend of decreased aqueous solubility and microsomal stability. It was also revealed that α-fluorination reduced the basicity of tropane nitrogen atom for about 1000-fold.

First-Principles Study of Adsorption of CH4 on a Fluorinated Model NiF2 Surface.

Electrochemical fluorination on nickel anodes, also known as the Simons' process, is an important fluorination method used on an industrial scale. Despite its success, the mechanism is still under debate. One of the proposed mechanisms involves higher valent nickel species formed on an anode acting as effective fluorinating agents. Here we report the first attempt to study fluorination by means of first principles investigation. We have identified a possible surface model from the simplest binary nickel fluoride (NiF2). A twice oxidized NiF2(F2) (001) surface exhibits higher valent nickel centers and a fluorination source that can be best characterized as an [F2]- like unit, readily available to aid fluorination. We have studied the adsorption of CH4 and the co-adsorption of CH4 and HF on this surface by means of periodic density functional theory. By the adsorption of CH4, we found two main outcomes on the surface. Unreactive physisorption of CH4 and dissociative chemisorption resulting in the formation of CH3F and HF. The co-adsorption with the HF gave rise to four main outcomes, namely the formation of CH3F, CH2F2, CH3 radical, and also physisorbed CH4.

Boosting the Electrochemical Performance of Primary and Secondary Lithium Batteries with Mn-Doped All-Fluoride Cathodes.

Transition metal fluorides are potentially high specific energy cathode materials of next-generation lithium batteries, and strategies to address their low conductivity typically involve a large amount of carbon coating, which reduces the specific energy of the electrode. In this study, MnyFe1-yF3@CFx was generated by the all-fluoride strategy, converting most of the carbon in MnyFe1-yF3@C into electrochemical active CFx through a controllable NF3 gas phase fluorination method, while still retaining a tightly bound graphite layer to provide initial conductivity, which greatly improved the energy density of the composite. This synergistic effect of nonfluorinated residual carbon (∼11%) and Mn doping ensures the electrochemical kinetics of the composite. The loading mass of the active substance had been increased to 86%. The theoretical and actual discharge capacity of MnyFe1-yF3@CFx composite was up to 765 mAh g-1 (pure FeF3 is 712 mAh g-1) and 728 mAh g-1, respectively. The discharge capacity at the high-voltage (3.0 V) platform was more than three times higher than that of the non-Mn-doped composite (FeF3@CFx).

Fluorination effects on non-covalent binding forces: A rotational study on the 2-(trifluoromethyl)acrylic acid-water complex.

This study explores the effects of the -CF3 group on non-covalent interactions through a comprehensive rotational investigation of the 2-(trifluoromethyl)acrylic acid-water complex. Employing Fourier transform microwave spectroscopy complemented by quantum chemical calculations, two isomers, i.e., s-cis and s-trans structures, have been observed in the pulsed jet. Based on relative intensity measurements, the s-cis to the s-trans population ratio was experimentally estimated to be âˆ¼ 1:1.2. Subsequently, a comparison of the non-covalent interactions was carried out between the three similar complexes, acrylic acid-water, methacrylic acid-water, and 2-(trifluoromethyl)acrylic acid-water, offering quantitative insights into fluorination affecting the strength of the formed hydrogen bonds important, e.g., in molecular recognition.

Fluorine-modified polymers reduce the adsorption of immune-reactive proteins to PEGylated gold nanoparticles.

Aim: To investigate the influence of fluorine in reducing the adsorption of immune-reactive proteins onto PEGylated gold nanoparticles. Methods: Reversible addition fragmentation chain transfer polymerization, the Turkevich method and ligand exchange were used to prepare polymer-coated gold nanoparticles. Subsequent in vitro physicochemical and biological characterizations and proteomic analysis were performed. Results: Fluorine-modified polymers reduced the adsorption of complement and other immune-reactive proteins while potentially improving circulatory times and modulating liver toxicity by reducing apolipoprotein E adsorption. Fluorine actively discouraged phagocytosis while encouraging the adsorption of therapeutic targets, CD209 and signaling molecule calreticulin. Conclusion: This study suggests that the addition of fluorine in the surface coating of nanoparticles could lead to improved performance in nanomedicine designed for the intravenous delivery of cargos.

Nanomedicines are based around the delivery of therapies by tiny, nanosized delivery vehicles. This method offers a much better way of specifically targeting life-threatening diseases. For fast delivery, nanomedicines can be injected into the blood (intravenously); however, this often leads to an unwanted and exaggerated immune response. The immune system is activated by proteins in the blood that attach themselves to nanoparticles through various chemical interactions (the protein corona effect). Fluorine is a chemical routinely used in surfactants such as firefighting foam and more recently in molecular imaging and nanoparticles designed for the delivery of therapies aimed at cancer. While fluorine has great potential to improve the cellular uptake of therapies, little is known about whether it can also help camouflage the nanoparticles against the immune system responses. Here, using fluorinated polymer-coated gold nanoparticles, the authors demonstrate that fluorine reduces uptake by immune cells and is highly effective at reducing the binding of immune system-initiating proteins. This work successfully illustrates the rationale for more widespread investigation of fluorine during the development of polymer-coated nanoparticles designed for the intravenous delivery of nanomedicines.

A Fluorination Strategy and Low-Acidity Anchoring Group in Self-Assembled Molecules for Efficient and Stable Inverted Perovskite Solar Cells.

Herein, we synthesized two donor-acceptor (D-A) type small organic molecules with self-assembly properties, namely MPA-BT-BA and MPA-2FBT-BA, both containing a low acidity anchoring group, benzoic acid. After systematically investigation, it is found that, with the fluorination, the MPA-2FBT-BA demonstrates a lower highest occupied molecular orbital (HOMO) energy level, higher hole mobility, higher hydrophobicity and stronger interaction with the perovskite layer than that of MPA-BT-BA. As a result, the device based-on MPA-2FBT-BA displays a better crystallization and morphology of perovskite layer with larger grain size and less non-radiative recombination. Consequently, the device using MPA-2FBT-BA as hole transport material achieved the power conversion efficiency (PCE) of 20.32 % and remarkable stability. After being kept in an N2 glove box for 116 days, the unsealed PSCs' device retained 93 % of its initial PCE. Even exposed to air with a relative humidity range of 30±5 % for 43 days, its PCE remained above 91 % of its initial condition. This study highlights the vital importance of the fluorination strategy combined with a low acidity anchoring group in SAMs, offering a pathway to achieve efficient and stable PSCs.

Engineering Two-Dimensional Nodal Semimetals in Functionalized Biphenylene by Fluorine Adatoms.

We propose a band engineering scheme on the biphenylene network, a newly synthesized carbon allotrope. We illustrate that the electronic structure of the biphenylene network can be significantly altered by controlling conditions affecting the symmetry and destructive interference of wave functions through periodic fluorination. First, we investigate the mechanism for the appearance of a type-II Dirac fermion in a pristine biphenylene network. We show that the essential ingredients are mirror symmetries and stabilization of the compact localized eigenstates via destructive interference. While the former is used for the band-crossing point along high symmetry lines, the latter induces highly inclined Dirac dispersions. Subsequently, we demonstrate the transformation of the biphenylene network's type-II Dirac semimetal phase into various Dirac phases such as type-I Dirac, gapped type-II Dirac, and nodal line semimetals through the deliberate disruption of mirror symmetry or modulation of destructive interference by varying the concentration of fluorine atoms.