Electron-withdrawing Trifluoromethyl Research Articles

Designing Novel Solvents for High Voltage Li-Ion Batteries

The pursuit of higher energy density in lithium-ion batteries has led to the development of new cathode materials that can operate at elevated voltages and provide increased specific capacities. [1-2] One such class of materials is the nickel-rich layered oxide cathodes known as LiNixMnyCozO2 (NMC). These cathodes offer high specific capacities and demonstrate electrochemical stability at high cutoff voltages, making them promising candidates for advanced lithium-ion batteries. [3-4] However, NMC cathodes face a significant challenge in the form of capacity fading during cycling. This issue primarily arises from the voltage instability of the conventional carbonate-based electrolytes used in lithium-ion batteries, which are typically designed for the 4-V lithium-ion chemistry. [5-6] As a result, researchers and scientists have directed extensive efforts toward developing new and improved electrolyte systems that can withstand the high voltage requirements of NMC cathodes and other high-energy applications. [7-8]Designing and synthesizing new molecules for use as electrolyte solvents in lithium-ion batteries is indeed a complex and challenging task. Researchers often focus on optimizing one specific property, which can lead to the development of molecules that excel in that aspect while potentially overlooking other crucial features that are necessary for stable battery cycling. For example, the development of α-fluorinated sulfones as electrolyte solvents was driven by their exceptional anodic stability. [9] This stability is achieved by introducing strong electron-withdrawing trifluoromethyl groups directly attached to the sulfonyl group. However, while this electron-withdrawing effect enhances anodic stability, it can also significantly increase the reduction potential of α-fluorinated sulfones. This heightened reduction potential renders them unstable when used with graphite anodes, highlighting the delicate balance required in designing electrolyte solvents that perform well across various aspects of battery operation.In this presentation, we embraced the concept of a "golden middle way" when designing and synthesizing new electrolyte solvents. The recently developed β-fluorinated sulfone, TFPMS, doesn't claim to be the best in any single property, but it strikes a balance across various key characteristics. This equilibrium has proven to be highly effective in ensuring the long-term stability of high-voltage graphite||NMC622 full cells. Positioned at the β site of the sulfone molecule, the strong electron-withdrawing trifluoromethyl group renders β-fluorinated sulfone sufficiently stable against the high-voltage NMC622 cathode, even if it possesses a slightly lower oxidation potential compared to its α-fluorinated counterparts. Furthermore, its reduction potential is lower than that of α-fluorinated sulfone, making it considerably more stable when paired with the graphite anode. While it may not possess the same high lithium solvating power as the typical sulfone (EMS), the lithium solvating capacity of β-fluorinated sulfone falls somewhere in between, mitigating transition metal dissolution and deposition in the graphite||NMC622 full cell that utilizes a β-fluorinated sulfone-based electrolyte. As a result, the full cell equipped with TFPMS-based electrolyte demonstrates superior cycling performance, with a significantly higher average capacity than cells using regular sulfone or α-fluorinated sulfone-based electrolytes. In summary, our approach exemplifies the successful application of the "golden middle way" in designing and synthesizing new electrolyte solvents.Reference: Santhanam, R.; Rambabu, B., Power Sources 2010, 195, 5442.Lin, F.; Markus, I. M.; Nordlund, D.; Weng, T.-C.; Asta, M. D.; Xin, H. L.; Doeff, M. M., Commun. 2014, 5, 3529.Li, W.; Song, B.; Manthiram, A., Chemical Society Reviews 2017, 46 (10), 3006.Xu, J.; Lin, F.; Doeff, M. M.; Tong, W., Journal of Materials Chemistry A 2017, 5 (3), 874.Xia, J.; Petibon, R.; Xiong, D.; Ma, L.; Dahn, J., Journal of Power Sources 2016, 328, 124.Chen, S.; Wen, K.; Fan, J.; Bando, Y.; Golberg, D., Journal of Materials Chemistry A 2018, 6 (25), 11631.Zheng, J.; Lochala, J. A.; Kwok, A.; Deng, Z. D.; Xiao, J., Advanced Science 2017, 4 (8), 1700032.Yamada, Y.; Wang, J.; Ko, S.; Watanabe, E.; Yamada, A., Nature Energy 2019, 4 (4), 269.Su, C.-C.; He, M.; Redfern, P. C.; Curtiss, L. A.; Shkrob, I. A.; Zhang, Z., Environ. Sci. 2017, 10 (4), 900.

Biomimetic nanosystems harnessing NIR-II photothermal effect and hypoxia-responsive prodrug for self-amplifying and synergistic tumor treatment

Tumor microenvironment-activated prodrugs have emerged as a promising strategy in precision medicine. However, the endogenous stimuli in the tumor microenvironment are often insufficient and unevenly distributed, impeding efficient and rapid prodrug conversion, necessitating the incorporation of complementary therapeutic strategies to amply treatment effectiveness. This study presents a self-synergistic therapeutic approach that combines hypoxia-activated paclitaxel prodrug (pro-PTX) with near-infrared-II (NIR-II) light-triggered photothermal therapy (PTT) for boosted tumor treatment. Initially, an organic polymer with strong NIR-II light harvesting capability, efficient photo-to-heat conversion, and excellent photostability was meticulously synthesized by introducing electron-withdrawing trifluoromethyl substituent. The high-performance NIR-II photothermal polymer then served as the matrix to encapsulate the hypoxia-responsive pro-PTX prodrug, forming the nanocore, on which the cell membrane derived from natural killer (NK) cells was further cloaked. The biomimetic nanopaltform exhibited a superior affinity towards tumor cells compared to normal cells, owing to the inherent tumor-recognition capability of NK cell membrane proteins. Upon exposure to NIR-II laser, the photothermal agent induced localized hyperthermia, facilitating not only direct tumor eradication but also exacerbating hypoxia within the tumor microenvironment. This, in turn, expedited the release of hypoxia-responsive prodrugs. Consequently, the synergistic effect of NIR-II PTT and chemotherapy efficiently induced cancer cell apoptosis and inhibited tumor growth. The developed nanoplatform, integrating hypoxia-responsive prodrug, high-performance NIR-II PTT agent-mediated complementary phototherapy, and NK cell-inspired active targeting, represents a promising strategy for precise and boosted tumor treatment.

Acceleration of Photoinduced Electron Transfer by Modulating Electronegativity of Substituents in Stable Zr-Metal-Organic Frameworks to Boost Photocatalytic CO2 Reduction.

Photoreduction of CO2 with water into chemical feedstocks of fuels provides a green way to help solve both the energy crisis and carbon emission issues. Metal-organic frameworks (MOFs) show great potential for CO2 photoreduction. However, poor water stability and sluggish charge transfer could limit their application. Herein, three water-stable MOFs functionalized with electron-donating methyl groups and/or electron-withdrawing trifluoromethyl groups are obtained for the CO2 photoreduction. Compared with UiO-67-o-CF3-CH3 and UiO-67-o-(CF3)2, UiO-67-o-(CH3)2 achieves excellent performance with an average CO generation rate of 178.0 μmol g-1 h-1 without using any organic solvent or sacrificial reagent. The superior photocatalytic activity of UiO-67-o-(CH3)2 is attributed to the fact that compared with trifluoromethyl groups, methyl groups could not only elevate CO2 adsorption capacity and reduction potential but also promote photoinduced charge separation and migration. These are evidenced by gas physisorption, photoluminescence, time-resolved photoluminescence, electrochemical impedance spectroscopy, transient photocurrent characteristics, and density functional theory calculations. The possible working mechanisms of electron-donating methyl groups are also proposed. Moreover, UiO-67-o-(CH3)2 demonstrates excellent reusability for the CO2 reduction. Based on these results, it could be affirmed that the strategy of modulating substituent electronegativity could provide guidance for designing highly efficient photocatalysts.

Efficient and safe coumarin-carbazole-based oxime esters for one/two-photon polymerization of LEDs/NIR light

Photocuring has developed rapidly in recent years owing to its unique “5E” characteristics, especially in the industrial and manufacturing fields, where photoinitiators (PIs) are essential components of the polymerization system. However, most PIs have limited applications in fields that directly contact the human body, such as food packaging or biomedicine, due to migration stability and toxicity. Here, four oxime esters were designed as PIs by using coumarin-carbazole as the conjugate structure, and their properties were optimized by multisite modification of the molecular structure. First, substituents with different electronic properties were introduced at the 4-position of coumarin. The introduction of electron-withdrawing trifluoromethyl redshifted the molecule and better matched the light-emitting diode (LED) emission spectra (i.e., 365–450 nm). In addition, the introduction of long and branched alkyl chains on carbazole increased the solubility of the four PIs. The initiation efficiency of the PIs was improved by inserting long or cyclized alkyl chains at the α-position of C = N double bond. The experimental results demonstrated that these four PIs are superior to the commercial oxime ester OXE 02 in terms of light absorption and initiation ability under LED irradiation. The migration stability and cytocompatibility of these PIs were validated, ensuring a green and safe application in photocuring applications. Furthermore, these PIs exhibited a considerable writing speed and remarkable nanopatterning capabilities under 780 nm laser in two-photon polymerization. These outstanding properties indicated their great potential for applications in diverse areas of photocuring, especially in food packaging, bio-3D printing, tissue engineering, and nano-additive manufacturing.

Regulating Lateral Adsorbate Interaction for Efficient Electroreforming of Bio-polyols.

Tailoring the selectivity at the electrode-electrolyte interface is one of the greatest challenges for heterogeneous electrocatalysis, and complementary strategies to catalyst structural designs need to be developed. Herein, we proposed a new strategy of controlling the electrocatalytic pathways by lateral adsorbate interaction for the bio-polyol oxidation. Redox-innocent 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) anion possesses the alcoholic property that facilely adsorbs on the nickel oxyhydroxide catalyst, but is resistant to oxidation due to the electron-withdrawing trifluoromethyl groups. The alien HFIP adsorbents can compete with bio-polyols and form a mixed adsorbate layer that creates lateral adsorbate interaction via hydrogen bonding, which achieved a >2-fold enhancement of the oxalate selectivity to 55 % for the representative glycerol oxidation and can be extended to various bio-polyol substrates. Through in situ spectroscopic analysis and DFT calculation on the glycerol oxidation, we reveal that the hydrogen-bonded adsorbate interaction can effectively tune the adsorption energies and tailor the oxidation capabilities toward the targeted products. This work offers an additional perspective of tuning electrocatalytic reactions via introducing redox-innocent adsorbates to create lateral adsorbate interactions.

Fluorescence quenching of deprotonated phenylurea through twisting motion induced by an electron-donating substituent group.

The excited-state proton transfer (ESPT) reaction between anthracen-2-yl-3-phenylurea (PUA) derivatives and tetrabutylammonium acetate (TBAAc) in dimethyl sulfoxide (DMSO) solvent was theoretically investigated using time-dependent density functional theory. The electron-donating methoxy group (OMe) and electron-withdrawing trifluoromethyl group (CF3) were bonded to 2PUA to form OMe-2PUA and CF3-2PUA, respectively. Two hydrogen bonds formed in the 1 : 1 hydrogen-bonded complexes between the 2PUA derivative and acetate ion (AcO-), namely N1-H1⋯O1 and N2-H2⋯O2. Strong charge transfer (CT) due to the electron-donating OMe group led to H1 transfer in the S1 state for the OMe-2PUA:AcO- hydrogen-bonded complex. On the contrary, weak CT due to the electron-withdrawing CF3 group led to H2 transfer in the S1 state for CF3-2PUA. After the ESPT reaction, the binding energies of the hydrogen-bonded complexes strongly decreased in both cases, and this promoted the separation of contact-ion pairs (CIPs*) and formed different types of anionic species. CF3-2PUA- could keep its nearly planar structure in the S1 state and emit "abnormal" fluorescence. On the other hand, the anionic OMe-2PUA- underwent a twisting motion to form a twisted structure in the S1 state with very low energy, and this led to a rapid internal conversion (IC) to quench long-wave fluorescence in the emission spectra.

Combining Donor Strength and Oxidative Stability in Scorpionates: A Strongly Donating Fluorinated Mesoionic Tris(imidazol-5-ylidene)borate Ligand.

Strongly donating scorpionate ligands support the study of high-valent transition metal chemistry; however, their use is frequently limited by oxidative degradation. To address this concern, we report the synthesis of a tris(imidazol-5-ylidene)borate ligand featuring trifluoromethyl groups surrounding its coordination pocket. This ligand represents the first example of a chelating poly(imidazol-5-ylidene) mesoionic carbene ligand, a scaffold that is expected to be extremely donating. The {NiNO}10 complex of this ligand, as well as that of a previously reported strongly donating tris(imidazol-2-ylidene)borate, has been synthesized and characterized. This new ligand's strong donor properties, as measured by the υNO of its {NiNO}10 complex and natural bonding orbital second-order perturbative energy analysis, are at par with those of the well-studied alkyl-substituted tris(imidazol-2-ylidene)borates, which are known to effectively stabilize high-valent intermediates. The good donor properties of this ligand, despite the electron-withdrawing trifluoromethyl substituents, arise from the strongly donating imidazol-5-ylidene mesoionic carbene arms. These donor properties, when combined with the robustness of trifluoromethyl groups toward oxidative decomposition, suggest this ligand scaffold will be a useful platform in the study of oxidizing high-valent transition-metal species.

Photoisomerization of "Partially Embedded Dihydropyridazine" with a Helical Structure.

Herein, we report the synthesis of two "partiallyembedded fused-dihydropyridazine N-aryl aza[5]helicene derivatives" (PDH) and the demonstration of their intrinsic photo-triggered multi-functional properties based on a Kekulé biradical structure. Introducing bulky electron-withdrawing trifluoromethyl or pentafluoroethyl groups into the aza[5]helicene framework (PDH-CF3 and -C2F5) gives PDH axial chirality based on the helicity of the P and M forms, even at room temperature. Upon photo-irradiation of PDH-CF3 in a frozen solution, an ESR signal from the triplet biradical with zero-field splitting values, generated by N-N bond dissociation, was observed. However, when the irradiation was turned off, the ESR signal became silent, indicating the existence of two equilibriums, between the biradical and quinoidal forms based on the Kekulé structure, and between N-N bond cleavage and recombination. The observed photo- and thermally induced behaviors indicate that T-type photochromic molecules are involved in the photoisomerization mechanism involving the two equilibriums. Inspired by the photoisomerization, chirality control of PDH by photoracemization was achieved. Multiple functionalities, such as T-type photochromism, photo-excitation-mediated triplet biradical formation, and photoracemization, which are attributed to the "partiallyembedded dihydropyridazine" structure, are demonstrated.

Preparation and Characterization of Fluorine-Containing Polyimide Films with Enhanced Output Performance for Potential Applications as Negative Friction Layers for Triboelectric Nanogenerators

Nanotechnologies are being increasingly widely used in advanced energy fields. Triboelectric nanogenerators (TENGs) represent a class of new-type flexible energy-harvesting devices with promising application prospects in future human societies. As one of the most important parts of TENG devices, triboelectric materials play key roles in the achievement of high-efficiency power generation. Conventional polymer tribo-negative materials, such as polytetrafluoroethylene (PTFE), polyvinylidene difluoride (PVDF), and the standard polyimide (PI) film with the Kapton® trademark based on pyromellitic anhydride (PMDA) and 4,4′-oxydianiline (ODA), usually suffer from low output performance. In addition, the relationship between molecular structure and triboelectric properties remains a challenge in the search for novel triboelectric materials. In the current work, by incorporating functional groups of trifluoromethyl (–CF3) with strong electron withdrawal into the backbone, a series of fluorine-containing polyimide (FPI) negative friction layers have been designed and prepared. The derived FPI-1 (6FDA-6FODA), FPI-2 (6FDA-TFMB), and FPI-3 (6FDA-TFMDA) resins possessed good solubility in polar aprotic solvents, such as the N,N-dimethylacetamide (DMAc) and N-methyl-2-pyrrolidone (NMP). The PI films obtained via the solution-casting procedure showed glass transition temperatures (Tg) higher than 280 °C with differential scanning calorimetry (DSC) analyses. The TENG prototypes were successfully fabricated using the developed PI films as the tribo-negative layers. The electron-withdrawing trifluoromethyl (–CF3) units in the molecular backbones of the PI layers provided the devices with an apparently enhanced output performance. The FPI-3 (6FDA-TFMDA) layer-based TENG devices showcased an especially impressive open-circuit voltage and short-circuit current, measuring 277.8 V and 9.54 μA, respectively. These values were 4~5 times greater when compared to the TENGs manufactured using the readily accessible Kapton® film.

Inductive Effects on Intramolecular Hydrogen Bond Strength: An Investigation of the Effect of an Electron-Withdrawing CF3 Group Adjacent to an Alcohol Hydrogen Bond Donor.

This combined experimental and theoretical study seeks to determine the role that inductive effects have on hydrogen bonds by an investigation into the change in intramolecular hydrogen bond strength in 2-amino-1-trifluoromethylethanol (2ATFME) relative to that in 2-aminoethanol (2AE). Toward this end, the rotational spectra of the normal, 13C, and 15N isotopologues have been measured using Fourier transform microwave spectroscopy and fit to the rotational, quadrupole coupling, and centrifugal distortion constants of the Watson A-reduction Hamiltonian. Structural parameters used to characterize the strength of the intramolecular hydrogen bond have been determined from the experimental structures of both 2ATFME and 2AE as well as from MP2/6-311++G(d,p) calculations. A comparison of these parameters in 2ATFME with those of 2AE indicates that the electron-withdrawing trifluoromethyl CF3 group strengthens the hydrogen bond. These include a 4% decrease in the distance between the donor and acceptor heavy atoms of the hydrogen bond, a 6% increase toward linearity of the OH···N angle, and a 23% decrease of the COH···N torsional angle toward planarity in 2ATFME relative to 2AE. This trend toward increased intramolecular hydrogen bond strength in 2ATFME is also observed within the ab initio structures.

Nucleophilic Carbenes Derived from Dichloromethane.

Nickel PyBox catalysts promote nucleophilic cyclopropanation reactions using CH2 Cl2 as a methylene source and Mn as a stoichiometric reductant. The substrate scope includes a broad range of alkenes bearing electron-withdrawing substituents, including esters, amides, ketones, nitriles, sulfones, phosphonate esters, trifluoromethyl groups, and electron-deficient arenes. Enantioselective cyclopropanations of α,β-unsaturated esters have been developed using chiral PyBox ligands. Mechanistic studies suggest the intermediacy of a (PyBox)Ni=CH2 species, which adds to the alkene by a stepwise [2+2]-cycloaddition/C-C reductive elimination mechanism. DFT models provide a rationale for the nucleophilic character of the nickel carbene and the sense of enantioinduction.

Arene Insertion with Pincer-Supported Molybdenum-Hydrides: Determination of Site Selectivity, Relative Rates, and Arene Complex Formation.

The synthesis of phosphino(oxazoline)pyridine-supported molybdenum(0) cycloocta-1,5-diene complexes is described. Exposure of these complexes to dihydrogen in the presence of an arene resulted in insertion of the substrate into the molybdenum hydride bond and afforded the corresponding molybdenum cyclohexadienyl hydrides. For mono- and disubstituted arenes, the site selectivity for insertion of the most substituted bond increases with increasing size of the substituent from methyl to ethyl, iso-propyl, and tert-butyl. In contrast, 1,3,5-trisubstituted arenes underwent insertion with exclusive site selectivity. Relative rates of insertion were determined by competition experiments and established faster insertions for electron-rich arenes. Introduction of electron-withdrawing trifluoromethyl groups on the arene resulted in decreased relative rates of insertion and an increased rate for H2 reductive elimination, favoring formation of the corresponding molybdenum η6-arene complex. Studies on the reductive elimination of the cyclohexadienyl ligand with the hydride enabled the synthesis of an enantioenriched cyclohexa-1,3-diene. This study provides new insights into the ligand requirements for catalytic arene hydrogenation and a new strategy for selective arene reduction.

Mechanistic Investigations of Thermal Decomposition of Perfluoroalkyl Ether Carboxylic Acids and Short-Chain Perfluoroalkyl Carboxylic Acids.

In this study, we investigated the thermal decomposition mechanisms of perfluoroalkyl ether carboxylic acids (PFECAs) and short-chain perfluoroalkyl carboxylic acids (PFCAs) that have been manufactured as replacements for phased-out per- and polyfluoroalkyl substances (PFAS). C-C, C-F, C-O, O-H, and C═C bond dissociation energies were calculated at the M06-2X/Def2-TZVP level of theory. The α-C and carboxyl-C bond dissociation energy of PFECAs declines with increasing chain length and the attachment of an electron-withdrawing trifluoromethyl (-CF3) group to the α-C. Experimental and computational results show that the thermal transformation of hexafluoropropylene oxide dimer acid to trifluoroacetic acid (TFA) occurs due to the preferential cleavage of the C-O ether bond close to the carboxyl group. This pathway produces precursors of perfluoropropionic acid (PFPeA) and TFA and is supplemented by a minor pathway (CF3CF2CF2OCFCF3COOH → CF3CF2CF2· + ·OCFCF3COOH) through which perfluorobutanoic acid (PFBA) is formed. The weakest C-C bond in PFPeA and PFBA is the one connecting the α-C and the β-C. The results support (1) the C-C scission in the perfluorinated backbone as an effective PFCA thermal decomposition mechanism and (2) the thermal recombination of radicals through which intermediates are formed. Additionally, we detected a few novel thermal decomposition products of studied PFAS.

Altering the Site of Electron Abstraction in Cobalt Corroles via meso-Trifluoromethyl Substituents

A mono-DMSO cobalt meso-CF3 corrole, formulated as (CF3)3CorCo(DMSO), where (CF3)3Cor is the trianion of 5,10,15-tris(trifluoromethyl)corrole, was synthesized and characterized as to its spectral and electrochemical properties in nonaqueous media with a focus on its coordination chemistry and electronic structure. Cyclic voltammetric measurements showed more facile reductions and difficult oxidations compared to the cobalt triarylcorrole possessing p-CF3Ph units at the meso-positions, a result consistent with the enhanced inductive effect of the electron-withdrawing trifluoromethyl substituents linked directly at the meso-carbon atoms of the macrocycle. The effects of DMSO, pyridine, and cyanide anions (CN-) on the electrochemistry and spectral properties of the compound were investigated, and it was found that only two molar equivalents are needed to form the bis-CN adduct, which exhibited two 1-electron oxidations at 0.27 and 0.95 V vs saturated calomel electrode (SCE) in CH2Cl2/0.1 M TBAP. The sites of electron transfer in the first oxidation and reduction were investigated by spectroelectrochemistry and confirmed that the first electron addition affords a Cor3-CoII complex under all solution conditions independent of the initial coordination and/or electronic configuration (i.e., innocent Cor3-CoIII or noninnocent Cor•2-CoII). In contrast, data for the first oxidation suggests that the site of electron abstraction (ligand or metal) depended upon coordination of the neutral and in situ generated complexes under the various solution conditions, leading to a Co(IV)-corrole3- product for both the bis-pyridine and bis-cyanide adducts.

Synthesis of Fluorenones and Xanthones through Intramolecular C–F Arylation

Abstract Facile methods to synthesize fluorenones and xanthones through C–F cleavages are disclosed. Transition-metal-catalyzed coupling reactions of 2-halogenated benzotrifluorides with arylboronic acids and phenols and following intramolecular carbonylative arylation of trifluoromethyl group afforded fluorenones and xanthones. A wide variety of cyclic ketones can be prepared by the cross-coupling/C–F arylation approach since electron-withdrawing trifluoromethyl groups facilitated deprotonated transformations at neighboring moieties realizing an efficient synthesis of 2-halogenated benzotrifluorides.

Tumor killing by a dietary curcumin mono-carbonyl analog that works as a selective ROS generator via TrxR inhibition

In comparison with normal cells, cancer cells feature intrinsic oxidative stress, thereby being more vulnerable to further production of reactive oxygen species (ROS) by pro-oxidative anticancer agents (PAAs). However, PAAs also inevitably generate ROS in normal cells, resulting in their narrow therapeutic window and toxic side effects that greatly limit their clinical application. To develop PAAs that generate ROS selectively in cancer cells over in normal cells, we rationally designed three series of 21 dietary curcumin 5-carbon mono-carbonyl analogs differentiated by either placement of the cyclohexanone, piperidone, and methylpiperidone linkers, or introduction of electron-withdrawing trifluoromethyl and electron-donating methoxyl groups on its two aromatic rings in the ortho, meta, or para position to the linkers. From the designed molecules, 2c, characterized of the presence of the meta-CF3-substituted mode and the piperidone linker, was identified as a potent selective ROS-generating agent, allowing its ability to kill selectively human non-small cell lung cancer NCI–H460 (IC50 = 0.44 μM) over human normal lung MRC-5 cells with a selectivity index of 32.0. Additionally, it was more potent and selective than the conventional chemotherapeutic agents (5-fluorouracil and camptothecin) did. Mechanistical investigation reveals that by means of its Michael acceptor unit and structure characteristics as described above, 2c could covalently modify the Sec-498 residue of intracellular thioredoxin reductase (TrxR) to generate ROS selectively, resulting in ROS-dependent apoptosis and ferroptosis of NCI–H460 cells. Noticeably, 2c inhibited significantly the growth of NCI–H460 cell xenograft tumor in nude mice without obvious toxicity to liver and kidney. Together, this work highlights a practical strategy of targeting TrxR overexpressed in cancer cells to develop PAAs capable of generating ROS selectively, as evidenced by the example of 2c.

Engineering piperlongumine-inspired analogs as Nrf2-dependent neuroprotectors against oxidative damage by an electrophilicity-based strategy.

Oxidative stress contributes significantly to the development of neurodegenerative diseases, thus developing nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent neuroprotectors is highly required for either prevention or treatment of these diseases. This work highlights an electrophilicity-based strategy that allows finding more active Nrf2-dependent neuroprotectors than natural piperlongumine (PL). Electrophilic modification was applied on both the exocylic and endocyclic Michael acceptors of PL, which includes placement of an electron-withdrawing trifluoromethyl group on its aromatic ring in the ortho, meta, or para position to the exocyclic olefin, and further introduction of an electron-withdrawing α-chlorine on its lactam ring. From a panel of PL analogs, we identified PLCl-4CF3, characterized by the presence of p-trifluoromethyl group and α-chlorine, to be significantly superior to the parent PL in protecting PC12cells from oxidative damage induced by 6-hydroxydopamine hydrochloride. Mechanistic studies reveal that the increased electrophilicity of PLCl-4CF3 in its two Michael acceptors allows its ability to covalently modify Cys-151 at Keap1, facilitating inhibition against Nrf2 ubiquitination, translocation of Nrf2 into the nucleus, induction of phase 2 enzymes and final protection of PC12cells from oxidative damage.

Superhydrophobic MOFs with enhanced catalytic activity for chemical fixation of CO2.

A general approach to prepare superhydrophobic MOFs (denoted as MOFs-CF3) through a post-decorating strategy for highly efficient chemical fixation of CO2 was demonstrated. The enhanced catalytic activity of MOFs-CF3 is attributed to a synergistic effect between the Lewis acid sites of MOFs and modification of the electron-withdrawing trifluoromethyl group, which resulted in a high CO2 enrichment capacity. The possible mechanism of cycloaddition catalyzed by the MOFs-CF3 catalyst was also proposed.

Energy level tuning of push-pull porphyrin sensitizer by trifluoromethyl group for dye-sensitized solar cells

We have introduced trifluoromethyl groups into meta-positions of two meso-phenyl rings of a push-pull-type porphyrin dye (ZnP-CF[Formula: see text] to modulate the energy levels of the porphyrin dye for dye-sensitized solar cells (DSSCs). The light-harvesting ability of ZnP-CF[Formula: see text] is almost comparable to those of reference porphyrins where the trifluoromethyl groups are replaced with methyl (ZnP-CH[Formula: see text] or tert-butyl groups (YD2). We revealed that the introduction of the electron-withdrawing trifluoromethyl groups is effective to lower the excited-state oxidation potential of the porphyrin (–0.80 V vs NHE), which is consistent with the theoretical calculation. Meanwhile, DSSCs with ZnP-CF[Formula: see text] exhibited a lower power conversion efficiency ([Formula: see text] of 5.95% than DSSCs with ZnP-CH[Formula: see text] ([Formula: see text] = 7.33%) and YD2 ([Formula: see text] = 8.97%) because of the severe aggregation tendency of ZnP-CF[Formula: see text] arising from the trifluoromethyl groups. In addition, the insufficient steric bulkiness of the trifluoromethyl and methyl groups relative to tert-butyl groups would result in the lower short circuit current and open circuit voltage for ZnP-CF[Formula: see text] and ZnP-CH[Formula: see text] due to fast charge recombination between electrons in the conduction band of TiO2 and I[Formula: see text]in the electrolyte solution. Overall, introducing both trifluoromethyl groups and bulky substituents into a porphyrin core would be necessary to boost cell performance.

Fluorinated triphenylphosphonium analogs improve cell selectivity and invivo detection of mito-metformin.

Triphenylphosphonium (TPP+) conjugated compounds selectively target cancercells by exploiting their hyperpolarized mitochondrial membrane potential. Todate, studies have focused on modifying either the linker or the cargo of TPP+-conjugated compounds. Here, we investigated the biological effects ofdirect modification to TPP+ to improve the efficacy and detection of mito-metformin (MMe), a TPP+-conjugated probe we have shown to have promising preclinical efficacy against solid cancer cells. We designed, synthesized, and tested trifluoromethyl and methoxy MMe analogs (pCF3-MMe, mCF3-MMe, and pMeO-MMe) against multiple distinct human cancer cells. pCF3-MMe showed enhanced selectivity toward cancer cells compared to MMe, while retaining thesame signaling mechanism. Importantly, pCF3-MMe allowed quantitative monitoring of cellular accumulation via 19F-NMR invitro and invivo. Furthermore, adding trifluoromethyl groups to TPP+ reduced toxicity invivo while retaining anti-tumor efficacy, opening an avenue to de-risk these next-generation TPP+-conjugated compounds.