Unlocking the NIR-II AIEgen for High Brightness through Intramolecular Electrostatic Locking.

Fluorescent imaging and biosensing in the near-infrared-II (NIR-II) window holds great promise for non-invasive, radiation-free, and rapid-response clinical diagnosis. However, it's still challenging to develop bright NIR-II fluorophores. In this study, we report a new strategy to enhance the brightness of NIR-II aggregation-induced emission (AIE) fluorophores through intramolecular electrostatic locking. By introducing sulfur atoms into the side chains of the thiophene bridge in TSEH molecule, the molecular motion of the conjugated backbone can be locked through intramolecular interactions between the sulfur and nitrogen atoms. This leads to enhanced NIR-II fluorescent emission of TSEH in both solution and aggregation states. Notably, the encapsulated nanoparticles (NPs) of TSEH show enhanced brightness, which is 2.6-fold higher than TEH NPs with alkyl side chains. The in vivo experiments reveal the feasibility of TSEH NPs in vascular and tumor imaging with a high signal-to-background ratio and precise resection for tiny tumors. In addition, polystyrene nanospheres encapsulated with TSEH are utilized for antigen detection in lateral flow assays, showing a signal-to-noise ratio 1.9-fold higher than the TEH counterpart in detecting low-concentration antigens. This work highlights the potential for developing bright NIR-II fluorophores through intramolecular electrostatic locking and their potential applications in clinical diagnosis and biomedical research.

An ultra-small organic dye nanocluster for enhancing NIR-II imaging-guided surgery outcomes.

PURPOSE: The accuracy of surgery for patients with solid tumors can be greatly improved through fluorescence-guided surgery (FGS). However, existing FGS technologies have limitations due to their low penetration depth and sensitivity/selectivity, which are particularly prevalent in the relatively short imaging window (< 900 nm). A solution to these issues is near-infrared-II (NIR-II) FGS, which benefits from low autofluorescence and scattering under the long imaging window (> 900 nm). However, the inherent self-assembly of organic dyes has led to high accumulation in main organs, resulting in significant background signals and potential long-term toxicity. METHODS: We rationalize the donor structure of donor-acceptor-donor-based dyes to control the self-assembly process to form an ultra-small dye nanocluster, thus facilitating renal excretion and minimizing background signals. RESULTS: Our dye nanocluster can not only show clear vessel imaging, tumor and tumor sentinel lymph nodes definition, but also achieve high-performance NIR-II imaging-guided surgery of tumor-positive sentinel lymph nodes. CONCLUSION: In summary, our study demonstrates that the dye nanocluster-based NIR-II FGS has substantially improved outcomes for radical lymphadenectomy.

Donor-Acceptor Modulating of Ionic AIE Photosensitizers for Enhanced ROS Generation and NIR-II Emission.

Photosensitizers (PSs) with aggregation-induced emission (AIE) characteristics are competitive candidates for bioimaging and therapeutic applications. However, their short emission wavelength and nonspecific organelle targeting hinder their therapeutic effectiveness. Herein, a donor-acceptor modulation approach is reported to construct a series of ionic AIE photosensitizers with enhanced photodynamic therapy (PDT) outcomes and fluorescent emission in the second near-infrared (NIR-II) window. By employing dithieno[3,2-b:2',3'-d]pyrrole (DTP) and indolium (In) as the strong donor and acceptor, respectively, the compound DTP-In exhibits a substantial redshift in absorption and fluorescent emission reach to NIR-II region. The reduced energy gap between singlet and triplet states in DTP-In also increases the reactive oxygen species (ROS) generation rate. Further, DTP-In can self-assemble in aqueous solutions, forming positively charged nanoaggregates, which are superior to conventional encapsulated nanoparticles in cellular uptake and mitochondrial targeting. Consequently, DTP-In aggregates show efficient photodynamic ablation of 4T1 cancer cells and outstanding tumor theranostic in vivo under 660 nm laser irradiation. This work highlights the potential of molecular engineering of donor-acceptor AIE PSs with multiple functionalities, thereby facilitating the development of more effective strategies for cancer therapy.

Stabilizing *CO2 Intermediates at the Acidic Interface using Molecularly Dispersed Cobalt Phthalocyanine as Catalysts for CO2 Reduction.

CO2 electroreduction (CO2 R) operating in acidic media circumvents the problems of carbonate formation and CO2 crossover in neutral/alkaline electrolyzers. Alkali cations have been universally recognized as indispensable components for acidic CO2 R, while they cause the inevitable issue of salt precipitation. It is therefore desirable to realize alkali-cation-free CO2 R in pure acid. However, without alkali cations, stabilizing *CO2 intermediates by catalyst itself at the acidic interface poses as a challenge. Herein, we first demonstrate that a carbon nanotube-supported molecularly dispersed cobalt phthalocyanine (CoPc@CNT) catalyst provides the Co single-atom active site with energetically localized d states to strengthen the adsorbate-surface interactions, which stabilizes *CO2 intermediates at the acidic interface (pH=1). As a result, we realize CO2 conversion to CO in pure acid with a faradaic efficiency of 60 % at pH=2 in flow cell. Furthermore, CO2 is successfully converted in cation exchanged membrane-based electrode assembly with a faradaic efficiency of 73 %. For CoPc@CNT, acidic conditions also promote the intrinsic activity of CO2 R compared to alkaline conditions, since the potential-limiting step, *CO2 to *COOH, is pH-dependent. This work provides a new understanding for the stabilization of reaction intermediates and facilitates the designs of catalysts and devices for acidic CO2 R.

Aggregation-Induced Emission (AIE), Life and Health.

Light has profoundly impacted modern medicine and healthcare, with numerous luminescent agents and imaging techniques currently being used to assess health and treat diseases. As an emerging concept in luminescence, aggregation-induced emission (AIE) has shown great potential in biological applications due to its advantages in terms of brightness, biocompatibility, photostability, and positive correlation with concentration. This review provides a comprehensive summary of AIE luminogens applied in imaging of biological structure and dynamic physiological processes, disease diagnosis and treatment, and detection and monitoring of specific analytes, followed by representative works. Discussions on critical issues and perspectives on future directions are also included. This review aims to stimulate the interest of researchers from different fields, including chemistry, biology, materials science, medicine, etc., thus promoting the development of AIE in the fields of life and health.

Dispersed Nickel Phthalocyanine Molecules on Carbon Nanotubes as Cathode Catalysts for Li-CO2 Batteries.

The Li-CO2 battery has great potential for both CO2 utilization and energy storage, but its practical application is limited by low energy efficiency and short cycle life. Efficient cathode catalysts are needed to address this issue. Herein, this work reports on molecularly dispersed electrocatalysts (MDEs) of nickel phthalocyanine (NiPc) anchored on carbon nanotubes (CNTs) as the cathode catalyst for Li-CO2 batteries. The dispersed NiPc molecules efficiently catalyze CO2 reduction, while the conductive and porous CNTs networks facilitate CO2 evolution reaction, leading to enhanced discharging and charging performance compared to the NiPc and CNTs mixture. Octa-cyano substitution on NiPc (NiPc-CN) further enhances the interaction between the molecule and CNTs, resulting in better cycling stability. The Li-CO2 battery with the NiPc-CN MDE cathode shows a high discharge voltage of 2.72 V and a small discharging-charging potential gap of 1.4 V, and can work stably for over 120 cycles. The reversibility of the cathode is confirmed by experimental characterizations. This work lays a foundation for the development of molecular catalysts for Li-CO2 battery cathodes.

NIR-II Imaging and Sandwiched Plasmonic Biosensor for Ultrasensitive Intraoperative Definition of Tumor-Invaded Lymph Nodes.

Radical lymphadenectomy remains the cornerstone of preventing tumor metastasis through the lymphatic system. Current surgical resection of lymph nodes (LNs) based on fluorescence-guided surgery (FGS) suffers from low sensitivity/selectivity with only qualitative information, hampering accurate intraoperative decision-making. Herein, we develop a modularized theranostic system including NIR-II FGS and a sandwiched plasmonic chip (SPC). Intraoperative NIR-II FGS and detection of tumor-positive lymph nodes were performed on the gastric tumor to determine the feasibility of the modularized theranostic system in defining LN metastasis. Under the NIR-II imaging window, the orthotopic tumor and sentinel lymph nodes (SLNs) were successfully excised without ambient light interference in the operating room. Importantly, the SPC biosensor achieved 100% sensitivity and 100% specificity for tumor markers and realized rapid and high-throughput intraoperative SLN detection. We propose the synergetic design of combining the NIR-II FGS and suitable biosensor will substantially improve the efficiency of cancer diagnosis and therapy follow-up.

Furan Donor for NIR-II Molecular Fluorophores with Enhanced Bioimaging Performance.

The second near-infrared (NIR-II, 1,000 to 1,700 nm) molecular fluorophores containing donor-acceptor-donor conjugated backbone have attracted substantial attention due to their outstanding advantages, such as stable emission and facilely tuned photophysical properties. However, it is still challenging for them to simultaneously achieve high brightness and red-shifted absorption and emission. Herein, furan is adopted as the D unit to construct NIR-II fluorophores, demonstrating red shift of absorption, enhanced absorption coefficient, and fluorescent quantum yield when compared with the generally used thiophene counterparts. The high brightness and desirable pharmacokinetics of the optimized fluorophore, IR-FFCHP, endows improved performance for angiography and tumor-targeting imaging. Furthermore, dual-NIR-II imaging of tumor and sentinel lymph nodes (LNs) has been achieved with IR-FFCHP and PbS/CdS quantum dots, enabling the in vivo imaging navigated LN surgery in tumor-bearing mice. This work demonstrates the potential of furan for constructing bright NIR-II fluorophores for biological imaging.

Low-Dose NIR-II Preclinical Bioimaging Using Liposome-Encapsulated Cyanine Dyes.

Fluorescence imaging in the second near-infrared window (NIR-II, 1000-1700 nm) provides a powerful tool for in vivo structural and functional imaging in deep tissue. However, the lack of biocompatible contrast agents with bright NIR-II emission has hindered its application in fundamental research and clinical trials. Herein, a liposome encapsulation strategy for generating ultrabright liposome-cyanine dyes by restricting dyes in the hydrophobic pockets of lipids and inhibiting the aggregation, as corroborated by computational modeling, is reported. Compared with free indocyanine green (ICG, an US Food and Drug Administration-approved cyanine dye), liposome-encapsulated ICG (S-Lipo-ICG) shows a 38.7-fold increase in NIR-II brightness and enables cerebrovascular imaging at only one-tenth dose over a long period (30 min). By adjusting the excitation wavelength, two liposome-encapsulated cyanine dyes (S-Lipo-ICG and S-Lipo-FD1080) enable NIR-II dual-color imaging. Moreover, small tumor nodules (2-5 mm) can be successfully distinguished and removed with S-Lipo-ICG image-guided tumor surgery in rabbit models. This liposome encapsulation maintains the metabolic pathway of ICG, promising for clinical implementation.

Regulating Morphological Features of Nickel Single-Atom Catalysts for Selective and Enhanced Electroreduction of CO2.

Single-atom catalysts (SACs) are of interest for chemical transformations of significant energy and environmental relevance because of the envisioned efficient use of active sites and the flexibility in tuning their coordination environment. Future advancement in this vein hinges upon the ability to further increase the number and accessibility of active sites in addition to fine-tuning their chemical environment. In this work, a Ni SAC is reported with a unique hierarchical hollow structure (Ni/HH) that allows increased accessibility of the active sites. The successful obtainment of such a uniquely structured catalyst was enabled by the judiciously chosen solvent mixtures for the preparation of the precursor whose hierarchical feature is maintained during the subsequent pyrolysis and etching of the pyrolysis product. Comparative catalytic and mechanistic studies with reference to three closely related but more compact Ni SACs established the superior performance of Ni/HH for selective electroreduction of CO2 to CO. Experimental analyses by in situ attenuated total reflection surface-enhanced infrared spectroscopy reveal that it is the facilitated formation of the *COOH intermediate in the rate-determining step that leads to the enhanced reaction kinetics and the overall catalytic performance.

Multiplexed evaluation of immunity against SARS-CoV-2 variants using surface enhanced fluorescence from a nanostructured plasmonic chip.

Generated by the immune system post-infection or through vaccination, the effectiveness of antibodies against emerging SARS-CoV-2 variants is crucial for protecting individuals from the COVID-19 pandemic. Herein, a platform for the multiplexed evaluation of SARS-CoV-2 neutralizing antibodies against various variants was designed on the basis of near-infrared (NIR) surface enhanced fluorescence by nano-plasmonic gold chip (pGOLD). Antibody level across variants (Wild-type, Alpha, Beta, Delta, Omicron) was confirmed by the sera from recovered-individuals who were unvaccinated and had infected with Wild-type, Delta, Omicron variants. However, the neutralizing activity against Omicron variant was markedly decreased for individuals infected by Wild-type (~ 5.6-fold) and Delta variant (~ 19.1-fold). To the opposite, neutralizing antibody from individuals recovered from Omicron variant infection showed weak binding strength against non-Omicron variants. Antibody evolution over time was studied with individuals 196-530 days post Wild-type infection. Decreasing IgG antibody titer accompanied by increasing IgG binding avidity with elongated post-infection period were observed for the sera from Wild-type recovered-individuals with different post-infection times, suggesting that after the primary infection, a great number of antibodies were generated and then gradually decreased, while the antibody matured over time. By comparing the IgG level of individuals vaccinated for 27-51 days with individual post-infection, we found that ca. 1 month after two doses of vaccination, the antibody level was comparable to that of 500 days post-infection, and vaccination could enhance IgG avidity more efficiently. This work demonstrated a platform for the multiplexed, high-throughput and rapid screening of acquired immunity against SARS-CoV-2 variants, providing a new approach for the analysis of vaccine effectiveness, immunity against emerging variants, and related serological study.

Deciphering the selectivity descriptors of heterogeneous metal phthalocyanine electrocatalysts for hydrogen peroxide production.

The electrocatalytic 2e- oxygen reduction reaction (2e- ORR) provides an appealing pathway to produce hydrogen peroxide (H2O2) in a decentralized and clean manner, which drives the demand for developing high selectivity electrocatalysts. However, current understanding on selectivity descriptors of 2e- ORR electrocatalysts is still insufficient, limiting the optimization of catalyst design. Here we study the catalytic performances of a series of metal phthalocyanines (MPcs, M = Co, Ni, Zn, Cu, Mn) for 2e- ORR by combining density functional theory calculations with electrochemical measurements. Two descriptors (ΔG *O - ΔG *OOH and ΔG *H2O2 ) are uncovered for manipulating the selectivity of H2O2 production. ΔG *O - ΔG *OOH reflects the preference of O-O bond breaking of *OOH, affecting the intrinsic selectivities. Due to the high value of ΔG *O - ΔG *OOH, the molecularly dispersed electrocatalyst (MDE) of ZnPc on carbon nanotubes exhibits high selectivity, even superior to the previously reported NiPc MDE. ΔG *H2O2 determines the possibility of further H2O2 reduction to affect the measured selectivities. Enhancing the hydrophobicity of the catalytic layer can increase ΔG *H2O2 , leading to selectivity improvement, especially under high H2O2 production rates. In the gas diffusion electrode measurements, both ZnPc and CoPc MDEs with polytetrafluoroethylene (PTFE) exhibit low overpotentials, high selectivities, and good stability. This study provides guidelines for rational design of 2e- ORR electrocatalysts.

Sensitively detecting antigen of SARS-CoV-2 by NIR-II fluorescent nanoparticles.

Early detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is an efficient way to prevent the spread of coronavirus disease 2019 (COVID-19). Detecting SARS-CoV-2 antigen can be rapid and convenient, but it is still challenging to develop highly sensitive methods for effective diagnosis. Herein, a lateral flow assay (LFA) based on fluorescent nanoparticles emitting in the second near-infrared (NIR-II) window is developed for sensitive detection of SARS-CoV-2 antigen. Benefiting from the NIR-II fluorescence with high penetration and low autofluorescence, such NIR-II based LFA allows enhanced signal-to-background ratio, and the limit of detection is down to 0.01 ng·mL-1 of SARS-CoV-2 antigen. In the clinical swab sample tests, the NIR-II LFA outperforms the colloidal gold LFA with higher overall percent agreement with the polymerase chain reaction test. The clinical samples with low antigen concentrations (∼ 0.015-∼ 0.068 ng·mL-1) can be successfully detected by the NIR-II LFA, but fail for the colloidal gold LFA. The NIR-II LFA can provide a promising platform for highly sensitive, rapid, and cost-effective method for early diagnosis and mass screening of SARS-CoV-2 infection. Electronic Supplementary Material: Supplementary material (the operation procedure and cost of the materials needed of NIR-II lateral flow assays, the dynamic light scattering spectrum of the NIR-II nanoparticles, the components and testing principle, optimization of main parameters pertaining to the LFA performance, the colloidal gold LFA strip, the fluorescence intensity distribution curves and the T/C values of the strips for clinical samples by NIR-II LFA, and results of clinical swab samples detected by colloidal gold LFA) is available in the online version of this article at 10.1007/s12274-022-4351-1.

Combining ZnO and PDINO as a Thick Cathode Interface Layer for Polymer Solar Cells.

Cathode interface layers (CILs) are important for electron extraction in polymer solar cells (PSCs). Currently, the thickness of CILs is often below 15 nm due to their low electron mobility, which is not favorable for large-scale fabrication. Herein, we report a thick CIL for efficient PSCs by modifying the ZnO nanocrystals (NCs) film with perylene diimides functionalized with amino oxide (PDINO). The combined ZnO NCs/PDINO CIL inherits the high electron mobility of ZnO NCs and dense morphology of PDINO, affording higher power conversion efficiencies (PCEs) of its devices than the sole component controls. The PSCs with the ZnO NCs/PDINO CIL also exhibit good tolerance to the CIL thickness, and the PM6:Y6 and PM6:BTP-eC9 devices can achieve high PCEs of over 15% at the CIL thickness of 70 nm. Further, the ZnO NCs/PDINO devices show better stability than those with sole ZnO NCs or PDINO. Our results provide a new way to construct potential CILs for high performance PSCs.

Accessing Organonitrogen Compounds via C-N Coupling in Electrocatalytic CO2 Reduction.

Given the limited product variety of electrocatalytic CO2 reduction reactions solely from CO2 and H2O as the reactants, it is desirable to expand the product scope by introducing additional reactants that provide elemental diversity. The integration of inorganic heteroatom-containing reactants into electrocatalytic CO2 reduction could, in principle, enable the sustainable synthesis of valuable products, such as organonitrogen compounds, which have widespread applications but typically rely on NH3 derived from the energy-intensive and fossil-fuel-dependent Haber-Bosch process for their industrial-scale production. In this Perspective, research progress toward building C-N bonds in N-integrated electrocatalytic CO2 reduction is highlighted, and the electrosyntheses of urea, acetamides, and amines are examined from the standpoints of reactivity, catalyst structure, and, most fundamentally, mechanism. Mechanistic discussions of C-N coupling in these advances are emphasized and critically evaluated, with the aim of directing future investigations on improving the product yield and broadening the product scope of N-integrated electrocatalytic CO2 reduction.

Shielding Unit Engineering of NIR-II Molecular Fluorophores for Improved Fluorescence Performance and Renal Excretion Ability.

Molecular fluorophores emitting in the second near-infrared (NIR-II) window with good renal excretion ability are favorable for in vivo bio-imaging and clinical applications. So far, renally excretable fluorophores are still less studied. Understanding the influences of molecular structure on optical properties and renal excretion abilities are vital for fluorophore optimization. Herein, a series of shielding unit-donor-acceptor-donor-shielding unit (S-D-A-D-S) NIR-II molecular fluorophores are designed and synthesized with dialkoxy chains substituted benzene as the S unit. The anchoring positions of dialkoxy chains on benzene are tuned as meso-2,6, para-2,5, or ortho-3,4 to afford three fluorophores: BGM6P, BGP6P and BGO6P, respectively. Experimental and calculation results reveal that alkoxy side chains anchored closer to the conjugated backbone can provide better protection from water molecules and PEG chains, affording higher fluorescence quantum yield (QY) in aqueous solutions. Further, these side chains can enable good encapsulation of backbone, resulting in decreased binding with albumin and improved renal excretion. Thus, fluorophore BGM6P with meso-2,6-dialkoxy chains exhibits the highest quantum yield and fastest renal excretion. This work emphasizes the important roles of side chain patterns on optimizing NIR-II fluorophores with high brightness and renal excretion ability.

Heterogeneous Molecular Catalysts of Metal Phthalocyanines for Electrochemical CO2 Reduction Reactions.

ConspectusMolecular catalysts, often deployed in homogeneous conditions, are favorable systems for structure-reactivity correlation studies of electrochemical reactions because of their well-defined active site structures and ease of mechanistic investigation. In pursuit of selective and active electrocatalysts for the CO2 reduction reactions which are promising for converting carbon emissions to useful fuels and chemical products, it is desirable to support molecular catalysts on substrates because heterogeneous catalysts can afford the high current density and operational convenience that practical electrolyzers require. Herein, we share our understanding in the development of heterogenized metal phthalocyanine catalysts for the electrochemical reduction of CO2. From the optimization of preparation methods and material structures for the electrocatalytic activity toward CO2 reduction to CO, we find that molecular-level dispersion of the active material and high electrical conductivity of the support are among the most important factors controlling the activity. The molecular nature of the active site enables mechanism-based optimization. We demonstrate how electron-withdrawing and -donating ligand substituents can be utilized to modify the redox property of the molecule and improve its catalytic activity and stability. Adjusting these factors further allows us to achieve electrochemical reduction of CO2 to methanol with appreciable activity, which has not been attainable by conventional molecular catalysts. The six-electron reduction process goes through CO as the key intermediate. Rapid and continuous electron delivery to the active site favors further reduction of CO to methanol. We also point out that, in homogeneous electrocatalysis where the catalyst molecules are dissolved in the electrolyte solution, even if the molecular structure remains intact, the actual catalysis may be dominated by molecules permanently adsorbed on the electrode surface and is thus heterogeneous in nature. This account uses our research on CO2 electroreduction reactions catalyzed by metal phthalocyanine molecules to illustrate our understanding about heterogeneous molecular electrocatalysis, which is also applicable to other electrochemical systems.

Nanographene-Osmapentalyne Complexes as a Cathode Interlayer in Organic Solar Cells Enhance Efficiency over 18.

Interface engineering is a critical method by which to efficiently enhance the photovoltaic performance of nonfullerene solar cells (NFSC). Herein, a series of metal-nanographene-containing large transition metal involving dπ -pπ conjugated systems by way of the addition reactions of osmapentalynes and p-diethynyl-hexabenzocoronenes is reported. Conjugated extensions are engineered to optimize the π-conjugation of these metal-nanographene molecules, which serve as alcohol-soluble cathode interlayer (CIL) materials. Upon extension of the π-conjugation, the power conversion efficiency (PCE) of PM6:BTP-eC9-based NFSCs increases from 16% to over 18%, giving the highest recorded PCE. It is deduced by X-ray crystallographic analysis, interfacial contact methods, morphology characterization, and carrier dynamics that modification of hexabenzocoronenes-styryl can effectively improve the short-circuit current density (Jsc ) and fill factor of organic solar cells (OSCs), mainly due to the strong and ordered charge transfer, more matching energy level alignments, better interfacial contacts between the active layer and the electrodes, and regulated morphology. Consequently, the carrier transport is largely facilitated, and the carrier recombination is simultaneously impeded. These new CIL materials are broadly able to enhance the photovoltaic properties of OSCs in other systems, which provides a promising potential to serve as CILs for higher-quality OSCs.

Selective and High Current CO2 Electro-Reduction to Multicarbon Products in Near-Neutral KCl Electrolytes.

Reducing CO2 to value-added multicarbon (C2+) fuels and chemicals using renewable energy is a viable way to circumvent CO2 buildup in the atmosphere and facilitate closing the carbon cycle. To date it remains a challenge to achieve high product selectivity and long-term stability of electrocatalytic carbon dioxide reduction reaction (CO2RR) especially at practically relevant high current levels >100 mA cm-2. Here, we report a simple electrodeposited Cu electrocatalyst on a hydrophobic porous gas-diffusion layer (GDL) electrode affording stable and selective CO2RR to C2+ products in near-neutral KCl electrolytes. By directing the CO2 stream to fully submerged hydrophobic GDLs in a H-cell, high C2+ partial current densities near 100 mA cm-2 were achieved. In a flow-cell setup, the Cu/GDL cathode in 2 M KCl afforded stable CO2RR superior to that in widely used KOH electrolytes. We found that Cu etching/corrosion associated with trace oxygen played a role in the catalyst instability in alkaline media under cathodic CO2RR conditions, a problem largely suppressed in near-neutral electrolyte. A two-electrode CO2 electrolyzer was constructed with a Cu/GDL cathode in KCl catholyte and an anode comprised of nickel-iron hydroxide on nickel foam (NiFe/NF) in a KOH anolyte separated by Nafion membrane. By periodically adding HCl to the KCl catholyte to compensate the increasing pH and remove accumulated (bi)carbonates, we observed little decay over ∼30 h in flow-cell CO2RR activity and selectivity at 150 mA cm-2 with a high Faradaic efficiency (FE) of ∼75% and energy efficiency of 40% for C2+ products.