Merging bioinspired incubation with supramolecular photocatalysis for Michaelis CO2 reduction beyond enzymes

Merging bioinspired incubation with supramolecular photocatalysis for Michaelis CO2 reduction beyond enzymes | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Merging bioinspired incubation with supramolecular photocatalysis for Michaelis CO 2 reduction beyond enzymes Chunying Duan, Xin Xu, Junkai Cai, Qiaojia Guo, Peng Wang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8521926/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract The conversion of carbon dioxide into chemicals and fuels via photoreduction represents a groundbreaking opportunity to forge a sustainable and carbon-neutral future, but the low concentration of photosensitized transition species and the related sluggish reaction kinetics significantly hindered the current energy efficiency toward industrial application. Herein, a bioinspired incubation to pretreat artificial cofactor BIH with photocatalyst is reported to enrich photogenerated reactive species for saturating the pocket of Fe III -porphyrin-modified capsule, and facilitating an ultra-fast photocatalytic CO 2 -to-CO conversion via a promisingly saturated enzymatic kinetics. The strategy included preincubating of photosensitizer, Ir(ppy) 3 with cofactor mimicking BIH for sufficiently producing reactive anionic Ir II (ppy) 3 species initially, followed by the thermodynamically favored abstraction of the species inside the cationic lantern-shaped capsule to facilitate the enzymatic conversion under saturated conditions and compatible substrate-product exchange kinetics. The improved and synergistic dynamics of both the iron-based CO 2 reduction and photosensitization bestow the bioinspired system with a turnover number (TON) about 180,000 and an ultrafast turnover frequency (TOF) about 165 s −1 in targeted CO 2 to CO conversion, surpassed most of reported photocatalytic CO 2 -to-CO systems and typical CO 2 reductases. This pseudo-enzymatic transformation allows concurrent intramolecular cyclic dehydrogenation of imines and CO 2 reduction, unlocking new opportunities for facilitating the conversion of high-energy-barrier photocatalysis under mild condition. Physical sciences/Chemistry Physical sciences/Chemistry/Supramolecular chemistry/Molecular capsules Physical sciences/Chemistry/Inorganic chemistry Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction The conversion of carbon dioxide into fuels and valuable chemicals through visible light-driven processes holds the promise of becoming a transformative technology with profound implications for future generations and a significant contribution toward net-zero carbon economy. 1,2 Recent breakthroughs have led to the creation of numerous techniques, which skillfully integrate essential functional components to accomplish photocatalytic reduction of CO 2 and innovative photo-redox catalytic methods to synthesize organic chemicals. 3,4 Among the various CO 2 reduction reactions, the formation of CO is notably one of the more straightforward processes to achieve during catalysis, as it requires fewer electrons and photons compared to other carbon-containing products. 5,6 Notwithstanding the best technology reported to date have yielded CO with a turnover number (TON) reaching up to 100,000 per mole of catalyst, these systems generally rely on ultra-low catalyst concentration (below nanomolar), which are significantly constrained by the extremely low concentration (far below nanomolar) of photosensitized transient intermediates with inherently short lifespans. 7–1 0 Fine-tuning the longevity and reactivity of the sequence of photoinduced transient intermediates is crucial for optimizing efficiency and selectivity at elevated catalyst concentration, while simultaneously addressing the complexities presented by competitive side reactions. 11 Natural photosynthesis converts CO 2 into energy-rich chemicals including sugars and fossil fuels by harnessing solar energy, providing foundational principles for photo-redox catalysis. 12,13 Notably, there is no lack of oxido-reductases to pre-organize and incubate cofactors i.e. NADH around enzymatic active sites in the protein constructed pocket for forming reactive intermediates, and pursuing exquisite selectivity and kinetic enhancement. 14,15 Chemists have crafted kinds of innovative bioinspired capsules to integrate cofactors and/or photosensitizers in the confined pocket for the activation and conversion of inert molecules including CO 2 via photosynthesis. 16,17 We thought that incubating cofactor mimics with photosensitizer, combined with host-guest abstracting of the formed transient species would guarantee an effective photosynthesis manifold via a saturated Michaelis conversions. 18– 20 Considering that the opened capsules exhibited position modified interactions and promising guest exchanging kinetics, we envisioned that merging bio-inspired photoincubation with dynamic favorable enzymatic conversion would enhance substrate-product circulation with the kinetics beyond the typical concentration dependence of the transient species. Herein, we report a preequilibrium approach to merge commercial photosensitizer, tris(2-phenylpyridine)iridium, Ir(ppy) 3 , within a Fe III -porphyrin decorated lantern-shaped capsule H1 for ultrafast CO 2 photoreduction. Our approach includes the incubation of Ir(ppy) 3 and 1,3-dimethyl-2-phenyl-2,3-dihydrobenzoimidazole (BIH), under visible light irradiation to form elevated concentration of anionic Ir II (ppy) 3 , 21 an active photosensitization transient species that always has quite lower concentration in typical photo-synthesis systems. The lantern-shaped capsules abstract the species to form pre-equilibrium and saturated clathrate intermediate via π-stacking and electrostatic interactions. The system efficiently facilitates the CO 2 -to-CO conversion with the initial rate exhibiting zero-order dependence on the concentration of both Ir(ppy) 3 and BIH, overcoming the typical sluggish kinetics of photosensitization in photo-synthesis. The positive charged characteristic and opened-interacted manner endow H1 facilitating rapid Ir(ppy) 3 -Ir II (ppy) 3 exchanges via kick-kick manner, achieving a turnover frequency about 165 s −1 that surpasses formate dehydrogenase 22 and a TON of 180,000 that outperforms the reported CO 2 -to-CO photoreduction systems. 23–25 The superiority of the approach enables the intramolecular C−X (X = N or S) cyclic dehydrogenation, concurrently with CO 2 reduction, demonstrating a new fashion for converting high-energy-barrier reactions under mild conditions. Results and discussion Characterization of cages and host-guest species The crystalline coordination cage H1 was constructed by assembling an ortho -dicarboxylate modified Fe III -porphyrin-based ligand (denoted as H 2 L Fe ) and bis(cyclopentadienyl) zirconium dichloride in DMF/THF solution (Supplementary Fig. 8 − 11). X-ray diffraction analysis of H1 revealed a lantern-shaped capsule consisting of two C 3 -symmetric Cp 3 Zr 3 ( µ 3 -O)( µ 2 -OH) 3 ( Cp 3 Zr 3 ) clusters distributed on the top and bottom, and three H 2 L Fe ligands strategically positioned along the sides (Fig. 2 a). H1 had a height of 21.1 Å, with an average Fe···Zr distance of 12.0 Å and an Fe···Fe distance of 15.7 Å. Crucially, the assembly features three large rhombic openings (15.7 × 16.2 Å 2 ), readily accessible for the binding suitable guest with high but dynamic active affinity that was favorable for fast preequilibrium between the association and dissociation (Supplementary Fig. 1 − 6). 26 Electrospray ionization mass spectra analysis of H1 with an intense peak at m/z = 1720.4890 assigned to [( Cp 3 Zr 3 ) 2 · L Fe 3 ] 2+ species, exhibited high stability and integrity of H1 in solution (Supplementary Fig. 14 − 16). The addition of commercial photosensitizer Ir(ppy) 3 into H1 solution, aroused a new peak at m/z = 2047.0673, which was assigned to the [ H1 ·Ir(ppy) 3 ] 2+ complex species by comparing the simulation results based on natural isotopic abundances (Fig. 2 c and Supplementary Fig. 17). UV − vis spectra of H1 (5.0 µM) solution upon the addition of Ir(ppy) 3 resulted in weakened Soret band of L Fe modules on H1 , and generated an isosbestic point at 420 nm. Hill plot fitting of the titration profile in 1:1 binding model provided an associated constant K ass as high as 1.33 × 10 5 M − 1 (Fig. 2 d). 27 Ir(ppy) 3 exhibited bright emission centered at 520 nm, and the emission intensity was quenched directly, upon the addition of H1 into the solution, fitting of the titration profile gave a 1:1 host-guest complexation behaviour with the association constant calculated as 1.05 × 10 5 M − 1 (Fig. 2 e and Supplementary Fig. 18). 27 , 28 Density functional theory calculations (DFT) of the host-guest complex revealed that the Ir(ppy) 3 guest spontaneously positioned at cleft binding sites of the host, and was stabilized by π-stacking interactions. 29 Remarkably, beyond the π-stacking separation (3.26 Å) between phenyl-pyridine moiety on Ir(ppy) 3 and porphyrin plane on H1 , C–H···O hydrogen bonds (2.70 Å) between phenyl-pyridine moiety and an oxygen atom from the zirconium clusters (Supplementary Fig. 7) was found to stabilize the complexation. This strategic interplay of the conductive π-channel enhanced the electron communication between the photosensitizer and its active reduced form for CO 2 reduction, 30,31 while allowed the fast pre-equilibrium between guest desorption and complexation for catalytic purpose (Fig. 2 b and Supplementary Fig. 7). Cyclic voltammetry of H1 displayed three pairs of redox peaks at − 0.25, − 1.05, and − 1.65 V ( vs . Ag/AgCl), assigned to the Fe III /Fe II , Fe II /Fe I , and Fe I /Fe 0 couples, 32 respectively (Supplementary Fig. 38). Adding Et 3 N·HCl into the H1 solution induced a proton-reduction peak at − 1.40 V ( vs . Ag/AgCl) (Fig. 3 a and Supplementary Fig. 39). Introducing CO 2 into the H1 solution triggered the peak related to Fe II /Fe I couple toward the more anodic side, and the potential shift exhibited a saturated behavior with the prolonged CO 2 bubbling (Fig. 3 a, Supplementary Fig. 40 − 42). 33 Notably, the introduction of CO 2 into the ligand L Fe solution caused little variation of the potential (Supplementary Fig. 41), we deduced that the Fe II /Fe I couple in the porphyrin decorated capsule was able to activate CO 2 through capsule shielding effect, at the time suitable photosensitizer was conducted to avoid a high energy barrier for reducing Fe II /Fe I couple. 23 , 24 Supramolecular catalytic performance of host We then displayed the reduction of CO 2 upon addition of the electron donors into the acetonitrile solution containing Ir(ppy) 3 (0.1 mM) and H1 (0.1 µM) with typical proton donor trifluoroethanol (TFE, 0.25 M) under CO 2 atmosphere. Of typical electron donors including ascorbic acid, sodium ascorbate, triethylamine, triethanolamine, BIH (0.5 mM) aroused significant CO production (510 µL) without any side product. Control experiments without H1 , BIH, CO 2 , and light, respectively, manifested no CO generated (Supplementary Fig. 46), and a feeble catalytic performance was observed in the absence of Ir(ppy) 3 or TFE. The optimized condition facilitated a turnover number (TON) of 45,000 after 30 min irradiation and an initial turnover frequency (TOF, within the first 10 min) more than 40 s − 1 for the selective CO 2 -to-CO conversion (Supplementary Fig. 19 and Supplementary Table 5). Luminescence titration of the Ir(ppy) 3 solution upon the addition of BIH demonstrated a strong emission quenching with Volmer constant calculated about 1.78 × 10 4 M − 1 , 28 but other electron donors exhibited lower quenching constants (Supplementary Fig. 23 − 26 and Supplementary Table 5). Time-dependence emission measurements revealed a significant lifetime diminishing of Ir(ppy) 3 upon addition of electron donors, wherein BIH (50 mM) aroused the shortest lifetime (0.42 µs) (Supplementary Figs. 21 and 27). As capsule H1 exhibited lower quenching efficiency, we attributed the high efficiency to the quenching pathway that the excited state of Ir(ppy) 3 reduced by the electron donor dominated the photosynthesis, and the reductive Ir(ppy) 3 further reduced iron centers for CO 2 reduction. When pre-reacting Ir(ppy) 3 with BIH upon light for 15 min, no CO was observed, but the subsequent introduction of the cationic capsule H1 led to a 4-fold enhancement in initial TOF CO compared to the one-pot reaction without pre-incubation (Supplementary Fig. 48 and Supplementary Table 6). Under optimized conditions, about 1630 µL of CO was produced after 30 min of irradiation with > 99% selectivity and an initial TOF ca . 165 s − 1 based on the concentration of H1 (Fig. 3 d, Supplementary Fig. 48 and Supplementary Table 6). Continuous 1 h reaction formed 2075 µL CO, with a TON reached 180,000 based on the concentration of H1 (Supplementary Figs. 45 and 53). To the best of our knowledge, this value represents the most effective CO 2 -to-CO conversion with high selectivity, and unprecedented TOF higher than all reported catalysts (Supplementary Fig. 47 and Supplementary Table 16) and even 29 times higher than that of formate dehydrogenase (FDH, TOF: 5.6 s − 1 ) and 3 times higher than typical TOF reported for carbon monoxide dehydrogenase (CODH, TOF: 45 s − 1 ). 22,34 Experiments with 13 C-labeled CO 2 revealed a dominant signal at m/z = 29 exclusively corresponding to 13 CO, confirming that the CO 2 (g) feedstock was the ultimate carbon source of CO (Supplementary Fig. 60). 25 We also recognized that the reaction of Ir(ppy) 3 (0.1 mM) with BIH (50.0 mM) upon light irradiation aroused obvious Ir(ppy) 3 fluorescence quenching and formation of BI + which was detected by 1 H NMR assay (Supplementary Fig. 12, 20, and 22). UV − vis spectral tracing of the reaction solution exhibited the absorbance increase at 280 nm (the characteristic band of BI + ) and absorbance decrease at 310 nm (the band of BIH) with an obvious isosbestic point at 300 nm (Fig. 3 b). 35 The variation of the two absorbances both exhibited a linear relationship with irradiation time, and reached a plateau after 15 min (Supplementary Fig. 35). While subsequent addition of the pre-reaction mixture to H1 solution unequivocally aroused a H1 -Ir(ppy) 3 combination characteristic isosbestic point at 415 nm, accompanied with new absorptions corresponding to Fe II and even Fe I species (Fig. 3 b and Supplementary Fig. 36). 36 We attributed the absorption to the pre-reaction of Ir(ppy) 3 with BIH to form the enriched anionic Ir II (ppy) 3 , which was abstracted into the pocket of cationic H1 , proceeding the reduction of the Fe III center for further fast CO 2 reduction. 37 Kinetic experiments revealed that the initial conversion rate (within 10 min) showed a first-order dependence on the TFE concentration, but a zero-order dependence on the Ir(ppy) 3 concentration and BIH concentration (Fig. 3 e, 3 f, Supplementary Fig. 50 − 54) under standard conditions. Control experiments without pre-incubation revealed a first-order regime to the concentration of Ir(ppy) 3 . It is likely that the unique pre-activation process endowed the generation of anionic active Ir II (ppy) 3 species with elevated concentration, enabled the formation of saturated clathrate of Ir II (ppy) 3 with H1 . 19,20 The concentration independence of the photosensitizer Ir(ppy) 3 and the active intermediate Ir II (ppy) 3 delivered the sluggish kinetics of the photosensitization process that restrict the photo-catalytic CO 2 reduction efficiency (Fig. 3 e and Supplementary Fig. 35). Controlled experiments of the catalytic performance of molecular Fe-porphyrin ( i.e. , the building block of H1 , H 2 L Fe ) under identical conditions revealed the negligible activity for CO 2 reduction. The pre-incubation strategy enhanced the catalytic efficiency, but the photo-catalysis kinetics of the Fe-porphyrin monomer suggested a first-order dependence of the initial rate on the Ir(ppy) 3 concentration (Supplementary Figs. 49 and 55). In all cases, the capsule H1 exhibited superiority over the equal amounts of the Fe-porphyrin fragment. We then engineered a recirculating continuous-flow photo-reactor featuring an integrated microfluidic system (Fig. 3 c and Supplementary Fig. 56 − 58). Precise modulation of CO 2 (0.8 mL·min − 1 ) and liquid (2.0 mL·min − 1 ) flow rates enabled a yield of 65 mL CO under standardized catalytic conditions: H1 (0.1 µM), Ir(ppy) 3 (0.1 mM) with BIH (50.0 mM) in CH 3 CN upon a 15-min pre-incubation. Critically, this reactor achieved a TON of 362,000—surpassing tubular reactors in efficiency for 2 h irradiation. From the mechanism point of view, light incubation enabled the formation of sufficient Ir II (ppy) 3 species, generating a saturated Ir II (ppy) 3 involved clathrate with Fe-porphyrin decorated capsule, followed by the reduction of Fe center and the reduction of CO 2 into a intermediate Fe II COOH, and finally to gain a proton and ultimately generates H 2 O and CO (Supplementary Fig. 61). 23 , 38 In situ fourier transform infrared (FTIR) spectroscopy probed the key intermediates during photocatalysis (Supplementary Fig. 59), especially the *COOH species with a prominent band at 1600 cm − 1 , suggesting the CO 2 -to-CO pathway reported in the literature. 39 Investigation into the mechanism and scope of C–X cyclization The superiority of the unique electron transfer mode enabled oxidative cyclizations of imine-based C − X coupling motifs to form N -substituted and S -substituted aromatic chemicals subsequently. These heterocycles are important structural motifs due to their biological and therapeutic activities. However, the preparation of benzimidazole and benzothiazole compounds from easily prepared substituted imine still face marked challenges. 40 Incubating Ir(ppy) 3 (0.1 mM) with N -substituted substrate 1a (10.0 mM) upon light irradiation under CO 2 atmosphere aroused an obvious emission quenching and the formation of cyclo-addition intermediate, which was detected by the 1 H NMR tracing (Supplementary Figs. 13 and 28). UV − vis spectral tracing of the reaction mixture exhibited the absorbance increase at 290 nm and decrease at 385 nm with an obvious isosbestic point at 320 nm (Fig. 4 c and Supplementary Fig. 37). Notably, the similar substrate S -substituted substrate 2a quenched the emission of Ir(ppy) 3 significantly, but the O -substituted substrate 3a did not (Fig. 4 d and Supplementary Fig. 28). The square wave voltammetry (SWV) provided the oxidation potential about 0.45, 0.22 and 0.71 V for the N -substituted substrate 1a , S -substituted substrate 2a and O -substituted substrate 3a , respectively, and presented a positive correlation with that of the quenching efficiency (Supplementary Figs. 43 and 44). We then deduced a typical PET reaction from the substrate to the excited state of Ir(ppy) 3 , forming Ir II (ppy) 3 for further reduction conversion (Supplementary Fig. 29). 41 Most importantly, luminescence titration of dye-loaded capsule clathrate upon addition of 1a did not recover the emission of Ir(ppy) 3 , but led to further quenching of the emission (Fig. 4 e and Supplementary Fig. 30). It is likely that the presence of 1a could not squeeze the dye in the cavity, but enforced a closed proximity to dye-loaded capsule for an enhanced molarity of reactants, therefore benefitting the further reaction acceleration. 17 When 2-NH 2 substituted imine derivative substrates with different functional groups were used, the dehydrogenated C − N coupling took place, and the product yield was enhanced with electron donating groups, but diminished when the electron accepting groups were present. The square wave voltammetry exhibited the electron donating groups caused a cathodic shift of the oxidation potential, but the electron accepting group caused an anodic shift of the potential related to the imine substrates. Hammett plot suggested a statistically negative linear correlation between Hammett substituent constant σ p values and substrate conversion(Fig. 4 b and Supplementary Fig. 63), 42 reflecting that the electronic effects governed the electron transfer process. This trend was mechanistically consistent with the reduction quenching pathway, wherein electron-donating groups boosted the quenching efficiency (Supplementary Fig. 65), enhancing the thermodynamic driving force for the electron communication between substrates and photosensitizers. 43 When 2-SH substituted imine derivative substrate 2a (prepared in situ by mixing the aldehyde and amino compound) was chosen, the oxidation potential of the 2a involved clathrate was around 0.22 V (vs Ag/AgCl), which was the lowest among these imine-substrates and led to the most efficient C − S coupling. Alternatively, the C − O coupling hardly took place, when 2-OH substituted imine derivative substrate 3a was used (Fig. 4 a and Supplementary Fig. 62). We then inferred that the formation of substrate-involving clathrate was important to trigger the chemical conversion, and the oxidation potential of substrate involving transition controlled the yield of the chemical conversion. With the photon power energy increased from P 1 = 125 mW·cm − 2 to P 2 = 250 mW·cm − 2 , we found a 4.1-fold increase of the 4a yield, showing the quadratic relationship dependence of the initial rate of the 1a oxidation with different photon power (Fig. 4 f and Supplementary Fig. 64). These results suggested a combination of the two photons energy to successively drive two one-electron transfer per catalytic cycle: the first photoinduced electron transfer (PET) triggered the initial ring-forming reaction, while the second PET dehydrogenated the cyclized intermediate. In all cases the Ir II (ppy) 3 species reduced the Fe-porphyrin site for CO 2 reduction. 44 The efficient dual-photon process validates our strategy: the pre-incubation protocol ensures a high concentration of Ir II (ppy) 3 , while the capsule H1 serves as a versatile platform that managed sequential electron transfers for concurrent conversions. Collectively, a new paradigm by merging bioinspired incubation with dynamic favorable enzymatic conversion was developed to overcome challenges of sluggish photo-sensitization kinetics for CO 2 photoreduction, delivering fast CO 2 -to-CO conversion with the record-setting metrics (> 165 s − 1 TOF, > 99.9% selectivity). This seamless lab-to-process translation underscores the industrial viability of integrating enzymatic kinetics with light incubation pre-activation technique for overcoming persistent energy barriers in challenging transformations. Methods General methods and materials The crystal data were collected on the Bruker D8 Venture X-ray diffractometer in Bruker AXS, Germany. The fluorescence spectra were measured on the Horiba FL-3 fluorescence spectrophotometer at room temperature. The fluorescence lifetimes were measured employing time correlated single photon counting on an Edinburgh FLS1000 instrument. Ultraviolet − visible (UV − vis) data were collected by Shimadzu UV3600 spectrometer. A typical three-electrode system was used to collect electrochemical data on CHI 760F electrochemical workstation. Nuclear magnetic resonance (NMR) data were obtained on Bruker Avance Ⅲ 400M spectrometer, and the peak frequency was based on the internal standard (tetramethylsilane, TMS) shift of 0.0 ppm. Electrospray ionization mass (ESI-MS) spectra were obtained by Thermo Fisher Q Exactive mass spectrometer, and methanol or acetonitrile was used as the mobile phase with a flow rate of 0.20 mL·min − 1 . The gas chromatography data were obtained by Techcomp GC 7900 gas chromatograph. In situ FTIR experiments were conducted on a Nicolet IS50-FTIR spectrometer (Thermo Scientific) equipped with a mercury cadmium telluride detector and a custom-designed gas-tight reaction cell. Isotopically labeled reaction products were analyzed by gas chromatography-mass spectrometry (GC-MS, QP2020N, Shimadzu Corporation) equipped with a high-sensitivity quadrupole mass analyzer. The continuous-flow photoreactor system was engineered with technical support from Beijing Roger Tech, Ltd., featuring an integrated helical microfluidic module constructed from fluorinated ethylene propylene (FEP) tubing (standard o.d. 1.6 mm, i.d. 0.8 mm; residence volume: 8 mL). Synthesis of ligand L Fe Compound L H (0.17 g, 0.24 mmol) and FeCl 2 ·4H 2 O (0.48 g, 2.4 mmol) were dissolved in DMF (80 mL). The reaction mixture was heated at 130°C for 12 h under nitrogen atmosphere. After cooling to room temperature, the solvent was removed in vacuo. The crude product was washed with warm water (50°C) until the filtrate was colorless and dried in vacuo. The resulting purple solid was dissolved in methanol, filtered, and concentrated in vacuo to afford L Fe as a purple solid (0.15 g, 78.3%). ESI-MS: calculated for C 46 H 27 ClFeN 4 O 4 [ L Fe − H] − , m/z = 790.11, found: 790.11. Synthesis of metal-organic capsule H1 Cp 2 ZrCl 2 (0.04 mmol, 11.7 mg) was dissolved in H 2 O (0.3 mL) under ultrasonication for 10 min. To this solution was added a mixture of ligand L Fe (0.02 mmol, 15.9 mg) in DMF (2.0 mL) and THF (1.0 mL). After additional ultrasonication (10 min), the reaction mixture was heated at 65°C for 12 h. Upon cooling to room temperature, the product was washed with DMF, affording purple block-shaped crystals H1 . The crystals were subsequently washed with Et 2 O and dried in vacuo for a yield of 60.6%. ESI-MS: calculated for C 168 H 115 N 12 O 20 Zr 6 Fe 3 Cl 3 [ H1 ] 2+ , m/z = 1720.4902, found: 1720.4905. Crystal data for H1 C 168 H 115 N 12 O 20 Zr 6 Fe 3 Cl 3 , M r = 3440.978, rhombohedral, dark-purple block, space group monoclinic , a = 37.098(2) Å, b = 29.5954(16) Å, c = 23.5807(13) Å, V = 25251(2) Å 3 , α = 90°, β = 102.756(3)°, γ = 90°, Z = 2, µ (Cu-Kα) = 0.830 mm − 1 , T = 193(2) K. R reflections [R int = 0.0683]. Final R 1 [with I > 2σ(I)] = 0.0754, wR 2 (all data) = 0.2253. CCDC No. 2454987. General methods for the catalytic CO reduction Photocatalytic CO 2 reduction experiments were performed in septum-sealed 15 mL quartz reactors equipped with a magnetic stir bar and water cooling. A standard reaction contained BIH (56.0 mg, 50.0 mM), trifluoroethanol (TFE, 90.0 µL, 0.25 M), and tris(2-phenylpyridine)iridium (III) (Ir(ppy) 3 , 0.10 mM) in CH 3 CN solution (4.91 mL). The reactor was sealed with a rubber plug and purged with CO 2 for 20 min. The mixture was then pre-irradiated (420 nm LED) under vigorous stirring at 25℃ for 15 min photoactivation prior to catalyst injection (named incubation). After activation, H1 (10.0 µL, 0.05 mM in methanol) was injected through the septum with a microsyringe. Headspace gas (100.0 µL aliquots) was periodically sampled using a gastight syringe and analyzed by GC-FID. General procedure for photocatalytic oxidative cyclization All photocatalytic reactions were conducted under irradiation from blue LEDs (λ = 420 nm) and maintained at 25℃ through a circulating water bath. Reaction progress was quantitatively monitored by 1 H NMR spectroscopy (400 MHz) with periodic sampling (200 µL aliquots withdrawn at 20 min intervals) using 1,3,5-trimethoxy-benzene as an internal standard. Spectral analysis enabled the determination of oxidative cyclization product formation efficiency, with all 1 H NMR measurements performed immediately after sample collection to ensure analytical fidelity. The C–X (X = O, N) coupling reaction was conducted in septum-sealed 15 mL quartz reactors equipped with a magnetic stir bar and water cooling. A solution of 2-substituted imine derivatives (10.0 mM, −OH or − NH 2 ), Ir(ppy) 3 (0.10 mM) and TFE (0.25 M) in CH 3 CN solution (5.0 mL) was degassed by CO 2 purging 20 min. The mixture was photo-incubated upon 420 nm LED irradiation (15 min). H1 was then injected, and the irradiation was continued for 2 h. The C–S coupling reaction followed the above procedure using substituted 2-aminothiophenol (10.0 mM) and benzaldehyde derivative (10.0 mM) as substrates. After the mixture was photo-incubated (15 min, vigorous stirring), H1 was subsequently injected, and continuously irradiated for 2 h. Data availability Detailed experimental procedures, computational details, characterization data for new compounds, and Cartesian coordinates of the calculated structures are available from the Supporting Information files and source data. The authors declare that the data supporting the manuscript are included in the manuscript, supplementary information, and supplementary data. All data are available from the corresponding author upon request. Source data are provided with this paper. Declarations Acknowledgements This work was supported by National Natural Science Foundation of China (92361201, 22201129, and 22571148), China Post-doctoral Science Foundation (2022M711550), Jiangsu Funding Program for Excellent Postdoctoral Talent (2022ZB26), and Shanghai Synchrotron Radiation Facility, instrument BL18U1 (proposal 2023-NFPS-PT-500404). Author contributions C.Y.D. and J.K.C. conceived the project, designed the experiments and supervised the work. X.X. carried out the main experiments, collected and interpreted the data, and wrote the original draft. J.K.C. solved and refined the X-ray single-crystal structures. Q.J.G. offered the help in the experiments and data analysis. P. W. performed the DFT calculations. 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Rev. 113 , 5322–5363 (2013). Glaser, F., Kerzig, C., Wenger, O. S. Multi-Photon Excitation in Photoredox Catalysis: Concepts, Applications, Methods. Angew. Chem. Int. Ed. 59 , 10266–10284 (2020). Additional Declarations There is NO Competing Interest. Supplementary Files H1checkcif.pdf checkcif file for H1 H1.cif cif file for H1 SupportingInformation.docx Supporting Information Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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11:51:58","extension":"html","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":133417,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8521926/v1/d009467d7b01a38f6aaece8f.html"},{"id":100398216,"identity":"3f6386d0-6ea4-4ecb-b76e-4dacd2564eba","added_by":"auto","created_at":"2026-01-16 11:52:18","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":354129,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSchematic illustration of the kinetic enhancement strategy.\u003c/strong\u003e \u003cstrong\u003ea\u003c/strong\u003e Low concentration of photosensitization transient species and related sluggish kinetics constrained by inefficient quenching between photosensitizer (PS), catalyst (Cat), electron donor (ED), in general homogeneous photocatalysis. \u003cstrong\u003eb\u003c/strong\u003e Our strategy: Merging pre-incubation with capsule photocatalysis for elevated concentration \u003cem\u003evia\u003c/em\u003epre-incubation to form saturated photosensitizer-capsule clathrate, reinforcingdirected photo-induced electron transfer and catalytic conversion via enzymatic kinetics.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8521926/v1/c6767d9511634a72ec609b10.png"},{"id":100398200,"identity":"936dd37d-c853-4fc6-bfbc-f79336f89fc7","added_by":"auto","created_at":"2026-01-16 11:52:07","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":336845,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eStructural and spectroscopic evidence for the formation of the H1⊃Ir(ppy)\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/sub\u003e\u003cstrong\u003e host–guest complex.\u003c/strong\u003e \u003cstrong\u003ea\u003c/strong\u003e The crystal structure of the coordination capsule \u003cstrong\u003eH1\u003c/strong\u003e and \u003cstrong\u003eb\u003c/strong\u003e DFT optimized structure of the host-guest species \u003cstrong\u003eH\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003eIr\u003c/strong\u003e\u003c/sub\u003e. \u003cstrong\u003ec\u003c/strong\u003e ESI-MS spectra of \u003cstrong\u003eH1\u003c/strong\u003e and of \u003cstrong\u003eH1\u003c/strong\u003e upon addition of Ir(ppy)\u003csub\u003e3\u003c/sub\u003e equivalently, the inserts show the measured and simulated isotopic patterns of the peaks mentioned. \u003cstrong\u003ed\u003c/strong\u003e UV−vis spectra of \u003cstrong\u003eH1\u003c/strong\u003e (5.0 μM) solution upon addition of Ir(ppy)\u003csub\u003e3\u003c/sub\u003e (total 3.0 μM). Inset shows the Hill plot of the titration curve at 412 nm. \u003cstrong\u003ee\u003c/strong\u003e Fluorescence spectra of Ir(ppy)\u003csub\u003e3\u003c/sub\u003e (blue line) upon addition of \u003cstrong\u003eH1\u003c/strong\u003e and BIH (red line), the inert shows the Hill plot of the titration curve at 525 nm.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8521926/v1/414d04498a297e5b157d9d39.png"},{"id":100398146,"identity":"2bcb4be6-c802-4826-b3e6-f1922b427f00","added_by":"auto","created_at":"2026-01-16 11:51:39","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":319070,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMechanistic investigations and catalytic performance.\u003c/strong\u003e \u003cstrong\u003ea\u003c/strong\u003e Cyclic voltammetry of \u003cstrong\u003eH1\u003c/strong\u003e (0.25 mM) with increasing Et\u003csub\u003e3\u003c/sub\u003eN·HCl. Inset: Linear sweep voltammograms of \u003cstrong\u003eH1\u003c/strong\u003e solution upon bubbling of CO\u003csub\u003e2\u003c/sub\u003e. \u003cstrong\u003eb\u003c/strong\u003e UV−vis spectra of the solution containing Ir(ppy)\u003csub\u003e3 \u003c/sub\u003e(0.10 mM) and BIH (50.0 mM) upon light irradiation. The insert shows the spectral variation of \u003cstrong\u003eH1\u003c/strong\u003e (3.0 μM) with BIH (30.0 mM)/Ir(ppy)\u003csub\u003e3\u003c/sub\u003e (10.0 μM) upon light irradiation. \u003cstrong\u003ec\u003c/strong\u003e Schematic of continuous-flow photoreactor with pre-incubation. A: recirculating reaction vessel; B: KOH(sat. aq.)/CO\u003csub\u003e2\u003c/sub\u003e scrubber; C: drainage gas collection device (sat. KOH aq.); D: peristaltic pump; E: in-line dynamic gas-liquid mixer; F: coiled continuous-flow photoreactor. \u003cstrong\u003ed\u003c/strong\u003e Time-dependent TON of \u003cstrong\u003eH1\u003c/strong\u003e with/without pre-incubation. The inset compares the corresponding initial TOF. \u003cstrong\u003ee\u003c/strong\u003e Kinetic analysis with pre-incubation with the variation of [Ir(ppy)\u003csub\u003e3\u003c/sub\u003e] from 50 to 125 μM, showing 1st-to-0th order transition; \u003cstrong\u003ef\u003c/strong\u003e and changing [Ir(ppy)\u003csub\u003e3\u003c/sub\u003e] from 50 to 100 μM without pre-incubation under standard conditions.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8521926/v1/7460db0f89e5816dec536d30.png"},{"id":100421398,"identity":"cbfff8b2-7b6f-4d75-b42a-139aae89b858","added_by":"auto","created_at":"2026-01-16 13:32:53","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":397929,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMechanistic insights and substrate scope of the photocatalytic intramolecular C−X (N, S, O) coupling.\u003c/strong\u003e \u003cstrong\u003ea\u003c/strong\u003e Time tracing of the yield of the intramolecular C−X coupling of substrates with different heteroatoms N, \u003cstrong\u003e1a\u003c/strong\u003e; S, \u003cstrong\u003e2a; \u003c/strong\u003eand O, \u003cstrong\u003e3a\u003c/strong\u003e. The inset shows the normalized SWV oxidation peaks of the substrates mentioned. \u003cstrong\u003eb\u003c/strong\u003e Kinetic parameter vs. Hammett \u003cem\u003eσ\u003c/em\u003e\u003csub\u003ep\u003c/sub\u003e. of the intramolecular C−N coupling. The inset shows the normalized SWV of the substrates \u003cstrong\u003e1a\u003c/strong\u003e−\u003cstrong\u003e1f\u003c/strong\u003e. \u003cstrong\u003ec\u003c/strong\u003e UV−vis spectra of \u003cstrong\u003e1a\u003c/strong\u003e (10.0 mM) solution under CO\u003csub\u003e2\u003c/sub\u003e atmosphere during photo-incubation. The inset shows the time-dependent absorbance at 380 nm. \u003cstrong\u003ed\u003c/strong\u003e Fluorescence quenching (λ\u003csub\u003eem\u003c/sub\u003e = 525 nm) of Ir(ppy)\u003csub\u003e3\u003c/sub\u003e with \u003cstrong\u003e1a\u003c/strong\u003e/\u003cstrong\u003e2a\u003c/strong\u003e/\u003cstrong\u003e3a\u003c/strong\u003e upon light irradiation. \u003cstrong\u003ee\u003c/strong\u003e Emission changes of the dye-loaded capsule (10.0 μM) upon addition of \u003cstrong\u003e1a\u003c/strong\u003e, the inert shows the Hill plot of the titration curve at 525 nm. \u003cstrong\u003ef\u003c/strong\u003e The yields of \u003cstrong\u003e1a\u003c/strong\u003e with the light power of 250 and 125 mW·cm\u003csup\u003e−2\u003c/sup\u003e, respectively. \u003cstrong\u003eg\u003c/strong\u003e Substrate scope: Intramolecular C−X (N/S) bond formation under standard reaction conditions: \u003cstrong\u003eH1\u003c/strong\u003e (1.0 μM), Ir(ppy)\u003csub\u003e3\u003c/sub\u003e (100 μM), substrate (10.0 mM).\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-8521926/v1/90d3888819ca6018ef91ed4a.png"},{"id":100796070,"identity":"f5bc7fba-42ca-4819-bc6d-64eb35d4b391","added_by":"auto","created_at":"2026-01-21 13:38:11","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2331627,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8521926/v1/1baf7fd9-e3af-4e17-bef9-5a0d59c624e9.pdf"},{"id":100398199,"identity":"8fa54ef6-299f-47e7-a458-85f831491730","added_by":"auto","created_at":"2026-01-16 11:52:06","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":106685,"visible":true,"origin":"","legend":"checkcif file for H1","description":"","filename":"H1checkcif.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8521926/v1/4ba6a45aa83eac215b2de2db.pdf"},{"id":100398251,"identity":"f4a9e576-1be4-4717-b4d0-62d40e8ebae1","added_by":"auto","created_at":"2026-01-16 11:52:38","extension":"cif","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":16204836,"visible":true,"origin":"","legend":"cif file for H1","description":"","filename":"H1.cif","url":"https://assets-eu.researchsquare.com/files/rs-8521926/v1/621266a976bc6ac494451de4.cif"},{"id":100398249,"identity":"52a66481-4a8d-4e04-b4f5-ffd3953d0502","added_by":"auto","created_at":"2026-01-16 11:52:37","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":26611964,"visible":true,"origin":"","legend":"Supporting Information","description":"","filename":"SupportingInformation.docx","url":"https://assets-eu.researchsquare.com/files/rs-8521926/v1/2d55d551c18e07d4d8cbce1b.docx"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"\u003cp\u003eMerging bioinspired incubation with supramolecular photocatalysis for Michaelis CO\u003csub\u003e2\u003c/sub\u003e reduction beyond enzymes\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe conversion of carbon dioxide into fuels and valuable chemicals through visible light-driven processes holds the promise of becoming a transformative technology with profound implications for future generations and a significant contribution toward net-zero carbon economy.\u003csup\u003e1,2\u003c/sup\u003e Recent breakthroughs have led to the creation of numerous techniques, which skillfully integrate essential functional components to accomplish photocatalytic reduction of CO\u003csub\u003e2\u003c/sub\u003e and innovative photo-redox catalytic methods to synthesize organic chemicals.\u003csup\u003e3,4\u003c/sup\u003e Among the various CO\u003csub\u003e2\u003c/sub\u003e reduction reactions, the formation of CO is notably one of the more straightforward processes to achieve during catalysis, as it requires fewer electrons and photons compared to other carbon-containing products.\u003csup\u003e5,6\u003c/sup\u003e Notwithstanding the best technology reported to date have yielded CO with a turnover number (TON) reaching up to 100,000 per mole of catalyst, these systems generally rely on ultra-low catalyst concentration (below nanomolar), which are significantly constrained by the extremely low concentration (far below nanomolar) of photosensitized transient intermediates with inherently short lifespans.\u003csup\u003e7\u0026ndash;1\u003c/sup\u003e\u003csup\u003e0\u003c/sup\u003e Fine-tuning the longevity and reactivity of the sequence of photoinduced transient intermediates is crucial for optimizing efficiency and selectivity at elevated catalyst concentration, while simultaneously addressing the complexities presented by competitive side reactions.\u003csup\u003e11\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eNatural photosynthesis converts CO\u003csub\u003e2\u003c/sub\u003e into energy-rich chemicals including sugars and fossil fuels by harnessing solar energy, providing foundational principles for photo-redox catalysis.\u003csup\u003e12,13\u003c/sup\u003e Notably, there is no lack of oxido-reductases to pre-organize and incubate cofactors \u003cem\u003ei.e.\u0026nbsp;\u003c/em\u003eNADH around enzymatic\u0026nbsp;active sites in\u0026nbsp;the protein constructed pocket\u0026nbsp;for forming\u0026nbsp;reactive intermediates, and pursuing\u0026nbsp;exquisite selectivity and kinetic enhancement.\u003csup\u003e14,15\u003c/sup\u003e Chemists have crafted kinds of innovative bioinspired capsules to integrate cofactors and/or photosensitizers in the confined pocket for the activation and conversion of inert molecules including CO\u003csub\u003e2\u003c/sub\u003e \u003cem\u003evia\u003c/em\u003e photosynthesis.\u003csup\u003e16,17\u003c/sup\u003e We thought that incubating cofactor mimics with photosensitizer, combined with host-guest abstracting of the formed transient species would guarantee an effective photosynthesis manifold \u003cem\u003evia\u003c/em\u003e a saturated Michaelis conversions.\u003csup\u003e18\u0026ndash;\u003c/sup\u003e\u003csup\u003e20\u003c/sup\u003e Considering that the opened capsules exhibited position modified interactions and promising guest exchanging kinetics, we envisioned that merging bio-inspired photoincubation with dynamic favorable enzymatic conversion would enhance substrate-product circulation with the kinetics beyond the typical concentration dependence of the transient species.\u003c/p\u003e\n\u003cp\u003eHerein, we report a preequilibrium approach to merge commercial photosensitizer, tris(2-phenylpyridine)iridium, Ir(ppy)\u003csub\u003e3\u003c/sub\u003e, within a Fe\u003csup\u003eIII\u003c/sup\u003e-porphyrin decorated lantern-shaped capsule \u003cstrong\u003eH1\u003c/strong\u003e for ultrafast CO\u003csub\u003e2\u003c/sub\u003e photoreduction. Our approach includes the incubation of Ir(ppy)\u003csub\u003e3\u003c/sub\u003e and 1,3-dimethyl-2-phenyl-2,3-dihydrobenzoimidazole (BIH), under visible light irradiation to form elevated concentration of anionic Ir\u003csup\u003eII\u003c/sup\u003e(ppy)\u003csub\u003e3\u003c/sub\u003e,\u003csup\u003e21\u003c/sup\u003e an active photosensitization transient species that always has quite lower concentration in typical photo-synthesis systems. The lantern-shaped capsules abstract the species to form pre-equilibrium and saturated clathrate intermediate \u003cem\u003evia\u003c/em\u003e \u0026pi;-stacking and electrostatic interactions. The system efficiently facilitates the CO\u003csub\u003e2\u003c/sub\u003e-to-CO conversion with the initial rate exhibiting zero-order dependence on the concentration of both Ir(ppy)\u003csub\u003e3\u003c/sub\u003e and BIH, overcoming the typical sluggish kinetics of photosensitization in photo-synthesis. The positive charged characteristic and opened-interacted manner endow \u003cstrong\u003eH1\u003c/strong\u003e facilitating rapid Ir(ppy)\u003csub\u003e3\u003c/sub\u003e-Ir\u003csup\u003eII\u003c/sup\u003e(ppy)\u003csub\u003e3\u003c/sub\u003e exchanges \u003cem\u003evia\u003c/em\u003e kick-kick manner, achieving a turnover frequency about 165 s\u003csup\u003e\u0026minus;1\u003c/sup\u003e that surpasses formate dehydrogenase\u003csup\u003e22\u003c/sup\u003e and a TON of 180,000 that outperforms the reported CO\u003csub\u003e2\u003c/sub\u003e-to-CO photoreduction systems.\u003csup\u003e23\u0026ndash;25\u003c/sup\u003e The superiority of the approach enables the intramolecular C\u0026minus;X (X = N or S) cyclic dehydrogenation, concurrently with CO\u003csub\u003e2\u003c/sub\u003e reduction, demonstrating a new fashion for converting high-energy-barrier reactions under mild conditions.\u003c/p\u003e"},{"header":"Results and discussion","content":"\u003cdiv id=\"Sec2\" class=\"Section2\"\u003e \u003ch2\u003eCharacterization of cages and host-guest species\u003c/h2\u003e \u003cp\u003eThe crystalline coordination cage \u003cb\u003eH1\u003c/b\u003e was constructed by assembling an \u003cem\u003eortho\u003c/em\u003e-dicarboxylate modified Fe\u003csup\u003eIII\u003c/sup\u003e-porphyrin-based ligand (denoted as H\u003csub\u003e2\u003c/sub\u003e\u003cb\u003eL\u003c/b\u003e\u003csup\u003e\u003cb\u003eFe\u003c/b\u003e\u003c/sup\u003e) and bis(cyclopentadienyl) zirconium dichloride in DMF/THF solution (Supplementary Fig.\u0026nbsp;8\u0026thinsp;\u0026minus;\u0026thinsp;11). X-ray diffraction analysis of \u003cb\u003eH1\u003c/b\u003e revealed a lantern-shaped capsule consisting of two \u003cem\u003eC\u003c/em\u003e\u003csub\u003e3\u003c/sub\u003e-symmetric Cp\u003csub\u003e3\u003c/sub\u003eZr\u003csub\u003e3\u003c/sub\u003e(\u003cem\u003e\u0026micro;\u003c/em\u003e\u003csub\u003e3\u003c/sub\u003e-O)(\u003cem\u003e\u0026micro;\u003c/em\u003e\u003csub\u003e2\u003c/sub\u003e-OH)\u003csub\u003e3\u003c/sub\u003e (\u003cb\u003eCp\u003c/b\u003e\u003csub\u003e\u003cb\u003e3\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eZr\u003c/b\u003e\u003csub\u003e\u003cb\u003e3\u003c/b\u003e\u003c/sub\u003e) clusters distributed on the top and bottom, and three H\u003csub\u003e2\u003c/sub\u003e\u003cb\u003eL\u003c/b\u003e\u003csup\u003e\u003cb\u003eFe\u003c/b\u003e\u003c/sup\u003e ligands strategically positioned along the sides (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea). \u003cb\u003eH1\u003c/b\u003e had a height of 21.1 \u0026Aring;, with an average Fe\u0026middot;\u0026middot;\u0026middot;Zr distance of 12.0 \u0026Aring; and an Fe\u0026middot;\u0026middot;\u0026middot;Fe distance of 15.7 \u0026Aring;. Crucially, the assembly features three large rhombic openings (15.7 \u0026times; 16.2 \u0026Aring;\u003csup\u003e2\u003c/sup\u003e), readily accessible for the binding suitable guest with high but dynamic active affinity that was favorable for fast preequilibrium between the association and dissociation (Supplementary Fig.\u0026nbsp;1\u0026thinsp;\u0026minus;\u0026thinsp;6).\u003csup\u003e26\u003c/sup\u003e Electrospray ionization mass spectra analysis of \u003cb\u003eH1\u003c/b\u003e with an intense peak at \u003cem\u003em/z\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1720.4890 assigned to [(\u003cb\u003eCp\u003c/b\u003e\u003csub\u003e\u003cb\u003e3\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eZr\u003c/b\u003e\u003csub\u003e\u003cb\u003e3\u003c/b\u003e\u003c/sub\u003e)\u003csub\u003e2\u003c/sub\u003e\u0026middot;\u003cb\u003eL\u003c/b\u003e\u003csup\u003e\u003cb\u003eFe\u003c/b\u003e\u003c/sup\u003e\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e2+\u003c/sup\u003e species, exhibited high stability and integrity of \u003cb\u003eH1\u003c/b\u003e in solution (Supplementary Fig.\u0026nbsp;14\u0026thinsp;\u0026minus;\u0026thinsp;16). The addition of commercial photosensitizer Ir(ppy)\u003csub\u003e3\u003c/sub\u003e into \u003cb\u003eH1\u003c/b\u003e solution, aroused a new peak at \u003cem\u003em/z\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2047.0673, which was assigned to the [\u003cb\u003eH1\u003c/b\u003e\u0026middot;Ir(ppy)\u003csub\u003e3\u003c/sub\u003e]\u003csup\u003e2+\u003c/sup\u003e complex species by comparing the simulation results based on natural isotopic abundances (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ec and Supplementary Fig.\u0026nbsp;17).\u003c/p\u003e \u003cp\u003eUV\u0026thinsp;\u0026minus;\u0026thinsp;vis spectra of \u003cb\u003eH1\u003c/b\u003e (5.0 \u0026micro;M) solution upon the addition of Ir(ppy)\u003csub\u003e3\u003c/sub\u003e resulted in weakened Soret band of \u003cb\u003eL\u003c/b\u003e\u003csup\u003e\u003cb\u003eFe\u003c/b\u003e\u003c/sup\u003e modules on \u003cb\u003eH1\u003c/b\u003e, and generated an isosbestic point at 420 nm. Hill plot fitting of the titration profile in 1:1 binding model provided an associated constant \u003cem\u003eK\u003c/em\u003e\u003csub\u003eass\u003c/sub\u003e as high as 1.33 \u0026times; 10\u003csup\u003e5\u003c/sup\u003e M\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed).\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e Ir(ppy)\u003csub\u003e3\u003c/sub\u003e exhibited bright emission centered at 520 nm, and the emission intensity was quenched directly, upon the addition of \u003cb\u003eH1\u003c/b\u003e into the solution, fitting of the titration profile gave a 1:1 host-guest complexation behaviour with the association constant calculated as 1.05 \u0026times; 10\u003csup\u003e5\u003c/sup\u003e M\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ee and Supplementary Fig.\u0026nbsp;18).\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e,\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e Density functional theory calculations (DFT) of the host-guest complex revealed that the Ir(ppy)\u003csub\u003e3\u003c/sub\u003e guest spontaneously positioned at cleft binding sites of the host, and was stabilized by π-stacking interactions.\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e Remarkably, beyond the π-stacking separation (3.26 \u0026Aring;) between phenyl-pyridine moiety on Ir(ppy)\u003csub\u003e3\u003c/sub\u003e and porphyrin plane on \u003cb\u003eH1\u003c/b\u003e, C\u0026ndash;H\u0026middot;\u0026middot;\u0026middot;O hydrogen bonds (2.70 \u0026Aring;) between phenyl-pyridine moiety and an oxygen atom from the zirconium clusters (Supplementary Fig.\u0026nbsp;7) was found to stabilize the complexation. This strategic interplay of the conductive π-channel enhanced the electron communication between the photosensitizer and its active reduced form for CO\u003csub\u003e2\u003c/sub\u003e reduction,\u003csup\u003e30,31\u003c/sup\u003e while allowed the fast pre-equilibrium between guest desorption and complexation for catalytic purpose (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb and Supplementary Fig.\u0026nbsp;7).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eCyclic voltammetry of \u003cb\u003eH1\u003c/b\u003e displayed three pairs of redox peaks at \u0026minus;\u0026thinsp;0.25, \u0026minus;\u0026thinsp;1.05, and \u0026minus;\u0026thinsp;1.65 V (\u003cem\u003evs\u003c/em\u003e. Ag/AgCl), assigned to the Fe\u003csup\u003eIII\u003c/sup\u003e/Fe\u003csup\u003eII\u003c/sup\u003e, Fe\u003csup\u003eII\u003c/sup\u003e/Fe\u003csup\u003eI\u003c/sup\u003e, and Fe\u003csup\u003eI\u003c/sup\u003e/Fe\u003csup\u003e0\u003c/sup\u003e couples,\u003csup\u003e32\u003c/sup\u003e respectively (Supplementary Fig.\u0026nbsp;38). Adding Et\u003csub\u003e3\u003c/sub\u003eN\u0026middot;HCl into the \u003cb\u003eH1\u003c/b\u003e solution induced a proton-reduction peak at \u0026minus;\u0026thinsp;1.40 V (\u003cem\u003evs\u003c/em\u003e. Ag/AgCl) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea and Supplementary Fig.\u0026nbsp;39). Introducing CO\u003csub\u003e2\u003c/sub\u003e into the \u003cb\u003eH1\u003c/b\u003e solution triggered the peak related to Fe\u003csup\u003eII\u003c/sup\u003e/Fe\u003csup\u003eI\u003c/sup\u003e couple toward the more anodic side, and the potential shift exhibited a saturated behavior with the prolonged CO\u003csub\u003e2\u003c/sub\u003e bubbling (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea, Supplementary Fig.\u0026nbsp;40\u0026thinsp;\u0026minus;\u0026thinsp;42).\u003csup\u003e33\u003c/sup\u003e Notably, the introduction of CO\u003csub\u003e2\u003c/sub\u003e into the ligand \u003cb\u003eL\u003c/b\u003e\u003csup\u003e\u003cb\u003eFe\u003c/b\u003e\u003c/sup\u003e solution caused little variation of the potential (Supplementary Fig.\u0026nbsp;41), we deduced that the Fe\u003csup\u003eII\u003c/sup\u003e/Fe\u003csup\u003eI\u003c/sup\u003e couple in the porphyrin decorated capsule was able to activate CO\u003csub\u003e2\u003c/sub\u003e through capsule shielding effect, at the time suitable photosensitizer was conducted to avoid a high energy barrier for reducing Fe\u003csup\u003eII\u003c/sup\u003e/Fe\u003csup\u003eI\u003c/sup\u003e couple.\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e,\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSupramolecular catalytic performance of host\u003c/h2\u003e \u003cp\u003eWe then displayed the reduction of CO\u003csub\u003e2\u003c/sub\u003e upon addition of the electron donors into the acetonitrile solution containing Ir(ppy)\u003csub\u003e3\u003c/sub\u003e (0.1 mM) and \u003cb\u003eH1\u003c/b\u003e (0.1 \u0026micro;M) with typical proton donor trifluoroethanol (TFE, 0.25 M) under CO\u003csub\u003e2\u003c/sub\u003e atmosphere. Of typical electron donors including ascorbic acid, sodium ascorbate, triethylamine, triethanolamine, BIH (0.5 mM) aroused significant CO production (510 \u0026micro;L) without any side product. Control experiments without \u003cb\u003eH1\u003c/b\u003e, BIH, CO\u003csub\u003e2\u003c/sub\u003e, and light, respectively, manifested no CO generated (Supplementary Fig.\u0026nbsp;46), and a feeble catalytic performance was observed in the absence of Ir(ppy)\u003csub\u003e3\u003c/sub\u003e or TFE. The optimized condition facilitated a turnover number (TON) of 45,000 after 30 min irradiation and an initial turnover frequency (TOF, within the first 10 min) more than 40 s\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e for the selective CO\u003csub\u003e2\u003c/sub\u003e-to-CO conversion (Supplementary Fig.\u0026nbsp;19 and Supplementary Table\u0026nbsp;5).\u003c/p\u003e \u003cp\u003eLuminescence titration of the Ir(ppy)\u003csub\u003e3\u003c/sub\u003e solution upon the addition of BIH demonstrated a strong emission quenching with Volmer constant calculated about 1.78 \u0026times; 10\u003csup\u003e4\u003c/sup\u003e M\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e,\u003csup\u003e28\u003c/sup\u003e but other electron donors exhibited lower quenching constants (Supplementary Fig.\u0026nbsp;23\u0026thinsp;\u0026minus;\u0026thinsp;26 and Supplementary Table\u0026nbsp;5). Time-dependence emission measurements revealed a significant lifetime diminishing of Ir(ppy)\u003csub\u003e3\u003c/sub\u003e upon addition of electron donors, wherein BIH (50 mM) aroused the shortest lifetime (0.42 \u0026micro;s) (Supplementary Figs.\u0026nbsp;21 and 27). As capsule \u003cb\u003eH1\u003c/b\u003e exhibited lower quenching efficiency, we attributed the high efficiency to the quenching pathway that the excited state of Ir(ppy)\u003csub\u003e3\u003c/sub\u003e reduced by the electron donor dominated the photosynthesis, and the reductive Ir(ppy)\u003csub\u003e3\u003c/sub\u003e further reduced iron centers for CO\u003csub\u003e2\u003c/sub\u003e reduction.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eWhen pre-reacting Ir(ppy)\u003csub\u003e3\u003c/sub\u003e with BIH upon light for 15 min, no CO was observed, but the subsequent introduction of the cationic capsule \u003cb\u003eH1\u003c/b\u003e led to a 4-fold enhancement in initial TOF\u003csub\u003eCO\u003c/sub\u003e compared to the one-pot reaction without pre-incubation (Supplementary Fig.\u0026nbsp;48 and Supplementary Table\u0026nbsp;6). Under optimized conditions, about 1630 \u0026micro;L of CO was produced after 30 min of irradiation with \u0026gt;\u0026thinsp;99% selectivity and an initial TOF \u003cem\u003eca\u003c/em\u003e. 165 s\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e based on the concentration of \u003cb\u003eH1\u003c/b\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ed, Supplementary Fig.\u0026nbsp;48 and Supplementary Table\u0026nbsp;6). Continuous 1 h reaction formed 2075 \u0026micro;L CO, with a TON reached 180,000 based on the concentration of \u003cb\u003eH1\u003c/b\u003e (Supplementary Figs.\u0026nbsp;45 and 53). To the best of our knowledge, this value represents the most effective CO\u003csub\u003e2\u003c/sub\u003e-to-CO conversion with high selectivity, and unprecedented TOF higher than all reported catalysts (Supplementary Fig.\u0026nbsp;47 and Supplementary Table\u0026nbsp;16) and even 29 times higher than that of formate dehydrogenase (FDH, TOF: 5.6 s\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e) and 3 times higher than typical TOF reported for carbon monoxide dehydrogenase (CODH, TOF: 45 s\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e).\u003csup\u003e22,34\u003c/sup\u003e Experiments with \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003eC-labeled CO\u003csub\u003e2\u003c/sub\u003e revealed a dominant signal at \u003cem\u003em/z\u003c/em\u003e\u0026thinsp;=\u0026thinsp;29 exclusively corresponding to \u003csup\u003e13\u003c/sup\u003eCO, confirming that the CO\u003csub\u003e2\u003c/sub\u003e(g) feedstock was the ultimate carbon source of CO (Supplementary Fig.\u0026nbsp;60).\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eWe also recognized that the reaction of Ir(ppy)\u003csub\u003e3\u003c/sub\u003e (0.1 mM) with BIH (50.0 mM) upon light irradiation aroused obvious Ir(ppy)\u003csub\u003e3\u003c/sub\u003e fluorescence quenching and formation of BI\u003csup\u003e+\u003c/sup\u003e which was detected by \u003csup\u003e1\u003c/sup\u003eH NMR assay (Supplementary Fig.\u0026nbsp;12, 20, and 22). UV\u0026thinsp;\u0026minus;\u0026thinsp;vis spectral tracing of the reaction solution exhibited the absorbance increase at 280 nm (the characteristic band of BI\u003csup\u003e+\u003c/sup\u003e) and absorbance decrease at 310 nm (the band of BIH) with an obvious isosbestic point at 300 nm (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eb).\u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e The variation of the two absorbances both exhibited a linear relationship with irradiation time, and reached a plateau after 15 min (Supplementary Fig.\u0026nbsp;35). While subsequent addition of the pre-reaction mixture to \u003cb\u003eH1\u003c/b\u003e solution unequivocally aroused a \u003cb\u003eH1\u003c/b\u003e-Ir(ppy)\u003csub\u003e3\u003c/sub\u003e combination characteristic isosbestic point at 415 nm, accompanied with new absorptions corresponding to Fe\u003csup\u003eII\u003c/sup\u003e and even Fe\u003csup\u003eI\u003c/sup\u003e species (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eb and Supplementary Fig.\u0026nbsp;36).\u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e We attributed the absorption to the pre-reaction of Ir(ppy)\u003csub\u003e3\u003c/sub\u003e with BIH to form the enriched anionic Ir\u003csup\u003eII\u003c/sup\u003e(ppy)\u003csub\u003e3\u003c/sub\u003e, which was abstracted into the pocket of cationic \u003cb\u003eH1\u003c/b\u003e, proceeding the reduction of the Fe\u003csup\u003eIII\u003c/sup\u003e center for further fast CO\u003csub\u003e2\u003c/sub\u003e reduction.\u003csup\u003e\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eKinetic experiments revealed that the initial conversion rate (within 10 min) showed a first-order dependence on the TFE concentration, but a zero-order dependence on the Ir(ppy)\u003csub\u003e3\u003c/sub\u003e concentration and BIH concentration (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ee, \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ef, Supplementary Fig.\u0026nbsp;50\u0026thinsp;\u0026minus;\u0026thinsp;54) under standard conditions. Control experiments without pre-incubation revealed a first-order regime to the concentration of Ir(ppy)\u003csub\u003e3\u003c/sub\u003e. It is likely that the unique pre-activation process endowed the generation of anionic active Ir\u003csup\u003eII\u003c/sup\u003e(ppy)\u003csub\u003e3\u003c/sub\u003e species with elevated concentration, enabled the formation of saturated clathrate of Ir\u003csup\u003eII\u003c/sup\u003e(ppy)\u003csub\u003e3\u003c/sub\u003e with \u003cb\u003eH1\u003c/b\u003e.\u003csup\u003e19,20\u003c/sup\u003e The concentration independence of the photosensitizer Ir(ppy)\u003csub\u003e3\u003c/sub\u003e and the active intermediate Ir\u003csup\u003eII\u003c/sup\u003e(ppy)\u003csub\u003e3\u003c/sub\u003e delivered the sluggish kinetics of the photosensitization process that restrict the photo-catalytic CO\u003csub\u003e2\u003c/sub\u003e reduction efficiency (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ee and Supplementary Fig.\u0026nbsp;35). Controlled experiments of the catalytic performance of molecular Fe-porphyrin (\u003cem\u003ei.e.\u003c/em\u003e, the building block of \u003cb\u003eH1\u003c/b\u003e, H\u003csub\u003e2\u003c/sub\u003e\u003cb\u003eL\u003c/b\u003e\u003csup\u003e\u003cb\u003eFe\u003c/b\u003e\u003c/sup\u003e) under identical conditions revealed the negligible activity for CO\u003csub\u003e2\u003c/sub\u003e reduction. The pre-incubation strategy enhanced the catalytic efficiency, but the photo-catalysis kinetics of the Fe-porphyrin monomer suggested a first-order dependence of the initial rate on the Ir(ppy)\u003csub\u003e3\u003c/sub\u003e concentration (Supplementary Figs.\u0026nbsp;49 and 55). In all cases, the capsule \u003cb\u003eH1\u003c/b\u003e exhibited superiority over the equal amounts of the Fe-porphyrin fragment.\u003c/p\u003e \u003cp\u003eWe then engineered a recirculating continuous-flow photo-reactor featuring an integrated microfluidic system (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ec and Supplementary Fig.\u0026nbsp;56\u0026thinsp;\u0026minus;\u0026thinsp;58). Precise modulation of CO\u003csub\u003e2\u003c/sub\u003e (0.8 mL\u0026middot;min\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e) and liquid (2.0 mL\u0026middot;min\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e) flow rates enabled a yield of 65 mL CO under standardized catalytic conditions: \u003cb\u003eH1\u003c/b\u003e (0.1 \u0026micro;M), Ir(ppy)\u003csub\u003e3\u003c/sub\u003e (0.1 mM) with BIH (50.0 mM) in CH\u003csub\u003e3\u003c/sub\u003eCN upon a 15-min pre-incubation. Critically, this reactor achieved a TON of 362,000\u0026mdash;surpassing tubular reactors in efficiency for 2 h irradiation. From the mechanism point of view, light incubation enabled the formation of sufficient Ir\u003csup\u003eII\u003c/sup\u003e(ppy)\u003csub\u003e3\u003c/sub\u003e species, generating a saturated Ir\u003csup\u003eII\u003c/sup\u003e(ppy)\u003csub\u003e3\u003c/sub\u003e involved clathrate with Fe-porphyrin decorated capsule, followed by the reduction of Fe center and the reduction of CO\u003csub\u003e2\u003c/sub\u003e into a intermediate Fe\u003csup\u003eII\u003c/sup\u003eCOOH, and finally to gain a proton and ultimately generates H\u003csub\u003e2\u003c/sub\u003eO and CO (Supplementary Fig.\u0026nbsp;61).\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e,\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e \u003cem\u003eIn situ\u003c/em\u003e fourier transform infrared (FTIR) spectroscopy probed the key intermediates during photocatalysis (Supplementary Fig.\u0026nbsp;59), especially the *COOH species with a prominent band at 1600 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e, suggesting the CO\u003csub\u003e2\u003c/sub\u003e-to-CO pathway reported in the literature.\u003csup\u003e\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eInvestigation into the mechanism and scope of C–X cyclization\u003c/h3\u003e\n\u003cp\u003eThe superiority of the unique electron transfer mode enabled oxidative cyclizations of imine-based C\u0026thinsp;\u0026minus;\u0026thinsp;X coupling motifs to form \u003cem\u003eN\u003c/em\u003e-substituted and \u003cem\u003eS\u003c/em\u003e-substituted aromatic chemicals subsequently. These heterocycles are important structural motifs due to their biological and therapeutic activities. However, the preparation of benzimidazole and benzothiazole compounds from easily prepared substituted imine still face marked challenges.\u003csup\u003e\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u003c/sup\u003e Incubating Ir(ppy)\u003csub\u003e3\u003c/sub\u003e (0.1 mM) with \u003cem\u003eN\u003c/em\u003e-substituted substrate \u003cb\u003e1a\u003c/b\u003e (10.0 mM) upon light irradiation under CO\u003csub\u003e2\u003c/sub\u003e atmosphere aroused an obvious emission quenching and the formation of cyclo-addition intermediate, which was detected by the \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003eH NMR tracing (Supplementary Figs.\u0026nbsp;13 and 28). UV\u0026thinsp;\u0026minus;\u0026thinsp;vis spectral tracing of the reaction mixture exhibited the absorbance increase at 290 nm and decrease at 385 nm with an obvious isosbestic point at 320 nm (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ec and Supplementary Fig.\u0026nbsp;37).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eNotably, the similar substrate \u003cem\u003eS\u003c/em\u003e-substituted substrate \u003cb\u003e2a\u003c/b\u003e quenched the emission of Ir(ppy)\u003csub\u003e3\u003c/sub\u003e significantly, but the \u003cem\u003eO\u003c/em\u003e-substituted substrate \u003cb\u003e3a\u003c/b\u003e did not (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ed and Supplementary Fig.\u0026nbsp;28). The square wave voltammetry (SWV) provided the oxidation potential about 0.45, 0.22 and 0.71 V for the \u003cem\u003eN\u003c/em\u003e-substituted substrate \u003cb\u003e1a\u003c/b\u003e, \u003cem\u003eS\u003c/em\u003e-substituted substrate \u003cb\u003e2a\u003c/b\u003e and \u003cem\u003eO\u003c/em\u003e-substituted substrate \u003cb\u003e3a\u003c/b\u003e, respectively, and presented a positive correlation with that of the quenching efficiency (Supplementary Figs.\u0026nbsp;43 and 44). We then deduced a typical PET reaction from the substrate to the excited state of Ir(ppy)\u003csub\u003e3\u003c/sub\u003e, forming Ir\u003csup\u003eII\u003c/sup\u003e(ppy)\u003csub\u003e3\u003c/sub\u003e for further reduction conversion (Supplementary Fig.\u0026nbsp;29).\u003csup\u003e\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e Most importantly, luminescence titration of dye-loaded capsule clathrate upon addition of \u003cb\u003e1a\u003c/b\u003e did not recover the emission of Ir(ppy)\u003csub\u003e3\u003c/sub\u003e, but led to further quenching of the emission (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ee and Supplementary Fig.\u0026nbsp;30). It is likely that the presence of \u003cb\u003e1a\u003c/b\u003e could not squeeze the dye in the cavity, but enforced a closed proximity to dye-loaded capsule for an enhanced molarity of reactants, therefore benefitting the further reaction acceleration.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eWhen 2-NH\u003csub\u003e2\u003c/sub\u003e substituted imine derivative substrates with different functional groups were used, the dehydrogenated C\u0026thinsp;\u0026minus;\u0026thinsp;N coupling took place, and the product yield was enhanced with electron donating groups, but diminished when the electron accepting groups were present. The square wave voltammetry exhibited the electron donating groups caused a cathodic shift of the oxidation potential, but the electron accepting group caused an anodic shift of the potential related to the imine substrates. Hammett plot suggested a statistically negative linear correlation between Hammett substituent constant \u003cem\u003eσ\u003c/em\u003e\u003csub\u003ep\u003c/sub\u003e values and substrate conversion(Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eb and Supplementary Fig.\u0026nbsp;63),\u003csup\u003e42\u003c/sup\u003e reflecting that the electronic effects governed the electron transfer process. This trend was mechanistically consistent with the reduction quenching pathway, wherein electron-donating groups boosted the quenching efficiency (Supplementary Fig.\u0026nbsp;65), enhancing the thermodynamic driving force for the electron communication between substrates and photosensitizers.\u003csup\u003e\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eWhen 2-SH substituted imine derivative substrate \u003cb\u003e2a\u003c/b\u003e (prepared \u003cem\u003ein situ\u003c/em\u003e by mixing the aldehyde and amino compound) was chosen, the oxidation potential of the \u003cb\u003e2a\u003c/b\u003e involved clathrate was around 0.22 V (vs Ag/AgCl), which was the lowest among these imine-substrates and led to the most efficient C\u0026thinsp;\u0026minus;\u0026thinsp;S coupling. Alternatively, the C\u0026thinsp;\u0026minus;\u0026thinsp;O coupling hardly took place, when 2-OH substituted imine derivative substrate \u003cb\u003e3a\u003c/b\u003e was used (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ea and Supplementary Fig.\u0026nbsp;62). We then inferred that the formation of substrate-involving clathrate was important to trigger the chemical conversion, and the oxidation potential of substrate involving transition controlled the yield of the chemical conversion. With the photon power energy increased from P\u003csub\u003e1\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;125 mW\u0026middot;cm\u003csup\u003e\u0026minus;\u0026thinsp;2\u003c/sup\u003e to P\u003csub\u003e2\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;250 mW\u0026middot;cm\u003csup\u003e\u0026minus;\u0026thinsp;2\u003c/sup\u003e, we found a 4.1-fold increase of the \u003cb\u003e4a\u003c/b\u003e yield, showing the quadratic relationship dependence of the initial rate of the \u003cb\u003e1a\u003c/b\u003e oxidation with different photon power (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ef and Supplementary Fig.\u0026nbsp;64). These results suggested a combination of the two photons energy to successively drive two one-electron transfer per catalytic cycle: the first photoinduced electron transfer (PET) triggered the initial ring-forming reaction, while the second PET dehydrogenated the cyclized intermediate. In all cases the Ir\u003csup\u003eII\u003c/sup\u003e(ppy)\u003csub\u003e3\u003c/sub\u003e species reduced the Fe-porphyrin site for CO\u003csub\u003e2\u003c/sub\u003e reduction.\u003csup\u003e\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u003c/sup\u003e The efficient dual-photon process validates our strategy: the pre-incubation protocol ensures a high concentration of Ir\u003csup\u003eII\u003c/sup\u003e(ppy)\u003csub\u003e3\u003c/sub\u003e, while the capsule \u003cb\u003eH1\u003c/b\u003e serves as a versatile platform that managed sequential electron transfers for concurrent conversions.\u003c/p\u003e \u003cp\u003eCollectively, a new paradigm by merging bioinspired incubation with dynamic favorable enzymatic conversion was developed to overcome challenges of sluggish photo-sensitization kinetics for CO\u003csub\u003e2\u003c/sub\u003e photoreduction, delivering fast CO\u003csub\u003e2\u003c/sub\u003e-to-CO conversion with the record-setting metrics (\u0026gt;\u0026thinsp;165 s\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e TOF, \u0026gt;\u0026thinsp;99.9% selectivity). This seamless lab-to-process translation underscores the industrial viability of integrating enzymatic kinetics with light incubation pre-activation technique for overcoming persistent energy barriers in challenging transformations.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eGeneral methods and materials\u003c/h2\u003e \u003cp\u003eThe crystal data were collected on the Bruker D8 Venture X-ray diffractometer in Bruker AXS, Germany. The fluorescence spectra were measured on the Horiba FL-3 fluorescence spectrophotometer at room temperature. The fluorescence lifetimes were measured employing time correlated single photon counting on an Edinburgh FLS1000 instrument. Ultraviolet\u0026thinsp;\u0026minus;\u0026thinsp;visible (UV\u0026thinsp;\u0026minus;\u0026thinsp;vis) data were collected by Shimadzu UV3600 spectrometer. A typical three-electrode system was used to collect electrochemical data on CHI 760F electrochemical workstation. Nuclear magnetic resonance (NMR) data were obtained on Bruker Avance Ⅲ 400M spectrometer, and the peak frequency was based on the internal standard (tetramethylsilane, TMS) shift of 0.0 ppm. Electrospray ionization mass (ESI-MS) spectra were obtained by Thermo Fisher Q Exactive mass spectrometer, and methanol or acetonitrile was used as the mobile phase with a flow rate of 0.20 mL\u0026middot;min\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e. The gas chromatography data were obtained by Techcomp GC 7900 gas chromatograph. In situ FTIR experiments were conducted on a Nicolet IS50-FTIR spectrometer (Thermo Scientific) equipped with a mercury cadmium telluride detector and a custom-designed gas-tight reaction cell. Isotopically labeled reaction products were analyzed by gas chromatography-mass spectrometry (GC-MS, QP2020N, Shimadzu Corporation) equipped with a high-sensitivity quadrupole mass analyzer. The continuous-flow photoreactor system was engineered with technical support from Beijing Roger Tech, Ltd., featuring an integrated helical microfluidic module constructed from fluorinated ethylene propylene (FEP) tubing (standard \u003cem\u003eo.d.\u003c/em\u003e 1.6 mm, \u003cem\u003ei.d.\u003c/em\u003e 0.8 mm; residence volume: 8 mL).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003e\u003c/h3\u003e\n\u003cdiv class=\"Heading\"\u003e\u003cb\u003eSynthesis of ligand L\u003c/b\u003e\u003csup\u003e\u003cb\u003eFe\u003c/b\u003e\u003c/sup\u003e\u003c/div\u003e \u003cp\u003eCompound \u003cb\u003eL\u003c/b\u003e\u003csup\u003e\u003cb\u003eH\u003c/b\u003e\u003c/sup\u003e (0.17 g, 0.24 mmol) and FeCl\u003csub\u003e2\u003c/sub\u003e\u0026middot;4H\u003csub\u003e2\u003c/sub\u003eO (0.48 g, 2.4 mmol) were dissolved in DMF (80 mL). The reaction mixture was heated at 130\u0026deg;C for 12 h under nitrogen atmosphere. After cooling to room temperature, the solvent was removed in vacuo. The crude product was washed with warm water (50\u0026deg;C) until the filtrate was colorless and dried in vacuo. The resulting purple solid was dissolved in methanol, filtered, and concentrated in vacuo to afford \u003cb\u003eL\u003c/b\u003e\u003csup\u003e\u003cb\u003eFe\u003c/b\u003e\u003c/sup\u003e as a purple solid (0.15 g, 78.3%). ESI-MS: calculated for C\u003csub\u003e46\u003c/sub\u003eH\u003csub\u003e27\u003c/sub\u003eClFeN\u003csub\u003e4\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e [\u003cb\u003eL\u003c/b\u003e\u003csup\u003e\u003cb\u003eFe\u003c/b\u003e\u003c/sup\u003e \u0026minus; H]\u003csup\u003e\u0026minus;\u003c/sup\u003e, \u003cem\u003em/z\u003c/em\u003e\u0026thinsp;=\u0026thinsp;790.11, found: 790.11.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eSynthesis of metal-organic capsule H1\u003c/h2\u003e \u003cp\u003eCp\u003csub\u003e2\u003c/sub\u003eZrCl\u003csub\u003e2\u003c/sub\u003e (0.04 mmol, 11.7 mg) was dissolved in H\u003csub\u003e2\u003c/sub\u003eO (0.3 mL) under ultrasonication for 10 min. To this solution was added a mixture of ligand \u003cb\u003eL\u003c/b\u003e\u003csup\u003e\u003cb\u003eFe\u003c/b\u003e\u003c/sup\u003e (0.02 mmol, 15.9 mg) in DMF (2.0 mL) and THF (1.0 mL). After additional ultrasonication (10 min), the reaction mixture was heated at 65\u0026deg;C for 12 h. Upon cooling to room temperature, the product was washed with DMF, affording purple block-shaped crystals \u003cb\u003eH1\u003c/b\u003e. The crystals were subsequently washed with Et\u003csub\u003e2\u003c/sub\u003eO and dried in vacuo for a yield of 60.6%. ESI-MS: calculated for C\u003csub\u003e168\u003c/sub\u003eH\u003csub\u003e115\u003c/sub\u003eN\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e20\u003c/sub\u003eZr\u003csub\u003e6\u003c/sub\u003eFe\u003csub\u003e3\u003c/sub\u003eCl\u003csub\u003e3\u003c/sub\u003e [\u003cb\u003eH1\u003c/b\u003e]\u003csup\u003e2+\u003c/sup\u003e, \u003cem\u003em/z\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1720.4902, found: 1720.4905.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eCrystal data for H1\u003c/h3\u003e\n\u003cp\u003eC\u003csub\u003e168\u003c/sub\u003eH\u003csub\u003e115\u003c/sub\u003eN\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e20\u003c/sub\u003eZr\u003csub\u003e6\u003c/sub\u003eFe\u003csub\u003e3\u003c/sub\u003eCl\u003csub\u003e3\u003c/sub\u003e, \u003cem\u003eM\u003c/em\u003e\u003csub\u003e\u003cem\u003er\u003c/em\u003e\u003c/sub\u003e = 3440.978, rhombohedral, dark-purple block, space group \u003cem\u003emonoclinic\u003c/em\u003e, \u003cem\u003ea\u003c/em\u003e\u0026thinsp;=\u0026thinsp;37.098(2) \u0026Aring;, \u003cem\u003eb\u003c/em\u003e\u0026thinsp;=\u0026thinsp;29.5954(16) \u0026Aring;, \u003cem\u003ec\u003c/em\u003e\u0026thinsp;=\u0026thinsp;23.5807(13) \u0026Aring;, \u003cem\u003eV\u003c/em\u003e\u0026thinsp;=\u0026thinsp;25251(2) \u0026Aring;\u003csup\u003e3\u003c/sup\u003e, \u003cem\u003eα\u003c/em\u003e\u0026thinsp;=\u0026thinsp;90\u0026deg;, \u003cem\u003eβ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;102.756(3)\u0026deg;, \u003cem\u003eγ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;90\u0026deg;, \u003cem\u003eZ\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2, \u003cem\u003e\u0026micro;\u003c/em\u003e(Cu-Kα)\u0026thinsp;=\u0026thinsp;0.830 mm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e, \u003cem\u003eT\u003c/em\u003e\u0026thinsp;=\u0026thinsp;193(2) K. R reflections [R\u003csub\u003eint\u003c/sub\u003e = 0.0683]. Final R\u003csub\u003e1\u003c/sub\u003e [with I\u0026thinsp;\u0026gt;\u0026thinsp;2σ(I)]\u0026thinsp;=\u0026thinsp;0.0754, wR\u003csub\u003e2\u003c/sub\u003e (all data)\u0026thinsp;=\u0026thinsp;0.2253. CCDC No. 2454987.\u003c/p\u003e\n\u003ch3\u003eGeneral methods for the catalytic CO reduction\u003c/h3\u003e\n\u003cp\u003ePhotocatalytic CO\u003csub\u003e2\u003c/sub\u003e reduction experiments were performed in septum-sealed 15 mL quartz reactors equipped with a magnetic stir bar and water cooling. A standard reaction contained BIH (56.0 mg, 50.0 mM), trifluoroethanol (TFE, 90.0 \u0026micro;L, 0.25 M), and tris(2-phenylpyridine)iridium (III) (Ir(ppy)\u003csub\u003e3\u003c/sub\u003e, 0.10 mM) in CH\u003csub\u003e3\u003c/sub\u003eCN solution (4.91 mL). The reactor was sealed with a rubber plug and purged with CO\u003csub\u003e2\u003c/sub\u003e for 20 min. The mixture was then pre-irradiated (420 nm LED) under vigorous stirring at 25℃ for 15 min photoactivation prior to catalyst injection (named incubation). After activation, \u003cb\u003eH1\u003c/b\u003e (10.0 \u0026micro;L, 0.05 mM in methanol) was injected through the septum with a microsyringe. Headspace gas (100.0 \u0026micro;L aliquots) was periodically sampled using a gastight syringe and analyzed by GC-FID.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eGeneral procedure for photocatalytic oxidative cyclization\u003c/h2\u003e \u003cp\u003eAll photocatalytic reactions were conducted under irradiation from blue LEDs (λ\u0026thinsp;=\u0026thinsp;420 nm) and maintained at 25℃ through a circulating water bath. Reaction progress was quantitatively monitored by \u003csup\u003e1\u003c/sup\u003eH NMR spectroscopy (400 MHz) with periodic sampling (200 \u0026micro;L aliquots withdrawn at 20 min intervals) using 1,3,5-trimethoxy-benzene as an internal standard. Spectral analysis enabled the determination of oxidative cyclization product formation efficiency, with all \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003eH NMR measurements performed immediately after sample collection to ensure analytical fidelity. The C\u0026ndash;X (X\u0026thinsp;=\u0026thinsp;O, N) coupling reaction was conducted in septum-sealed 15 mL quartz reactors equipped with a magnetic stir bar and water cooling. A solution of 2-substituted imine derivatives (10.0 mM, \u0026minus;OH or \u0026minus;\u0026thinsp;NH\u003csub\u003e2\u003c/sub\u003e), Ir(ppy)\u003csub\u003e3\u003c/sub\u003e (0.10 mM) and TFE (0.25 M) in CH\u003csub\u003e3\u003c/sub\u003eCN solution (5.0 mL) was degassed by CO\u003csub\u003e2\u003c/sub\u003e purging 20 min. The mixture was photo-incubated upon 420 nm LED irradiation (15 min). \u003cb\u003eH1\u003c/b\u003e was then injected, and the irradiation was continued for 2 h. The C\u0026ndash;S coupling reaction followed the above procedure using substituted 2-aminothiophenol (10.0 mM) and benzaldehyde derivative (10.0 mM) as substrates. After the mixture was photo-incubated (15 min, vigorous stirring), \u003cb\u003eH1\u003c/b\u003e was subsequently injected, and continuously irradiated for 2 h.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eData availability\u003c/h2\u003e \u003cp\u003eDetailed experimental procedures, computational details, characterization data for new compounds, and Cartesian coordinates of the calculated structures are available from the Supporting Information files and source data. The authors declare that the data supporting the manuscript are included in the manuscript, supplementary information, and supplementary data. All data are available from the corresponding author upon request. Source data are provided with this paper.\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003eAcknowledgements\u003c/p\u003e\n\u003cp\u003eThis work was supported by National Natural Science Foundation of China (92361201, 22201129, and 22571148), China Post-doctoral Science Foundation (2022M711550), Jiangsu Funding Program for Excellent Postdoctoral Talent (2022ZB26), and Shanghai Synchrotron Radiation Facility, instrument BL18U1 (proposal 2023-NFPS-PT-500404).\u003c/p\u003e\n\u003cp\u003eAuthor contributions\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eC.Y.D. and J.K.C. conceived the project, designed the experiments and supervised the work. X.X. carried out the main experiments, collected and interpreted the data, and wrote the original draft. J.K.C. solved and refined the X-ray single-crystal structures. Q.J.G. offered the help in the experiments and data analysis. P. W. performed the DFT calculations. C.Y.D. contributed materials and analysis tools. X.X., J.K.C. and C.Y.D. cowrote the paper. All authors discussed the results and commented on the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdditional information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary Information\u003c/strong\u003e accompanies this paper at https://doi.org/10.1038/xxxx.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e The authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLi, M., Han, Z., Hu, Q., Fan, W., Hu, Q., He, D., Chen, Q., Jiao, X., Xie, Y. Recent progress in solar-driven CO\u003csub\u003e2\u003c/sub\u003e reduction to multicarbon products. \u003cem\u003eChem. Soc. Rev.\u003c/em\u003e \u003cstrong\u003e53\u003c/strong\u003e, 9964\u0026ndash;9975 (2024).\u003c/li\u003e\n\u003cli\u003eGong, E., Ali, S., Hiragond, C. B., Kim, H. S., Powar, N. S., Kim, D., Kim, H., In, S. 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Ed.\u003c/em\u003e \u003cstrong\u003e59\u003c/strong\u003e, 10266\u0026ndash;10284 (2020).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8521926/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8521926/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe conversion of carbon dioxide into chemicals and fuels \u003cem\u003evia\u003c/em\u003e photoreduction represents a groundbreaking opportunity to forge a sustainable and carbon-neutral future, but the low concentration of photosensitized transition species and the related sluggish reaction kinetics significantly hindered the current energy efficiency toward industrial application. Herein, a bioinspired incubation to pretreat artificial cofactor BIH with photocatalyst is reported to enrich photogenerated reactive species for saturating the pocket of Fe\u003csup\u003eIII\u003c/sup\u003e-porphyrin-modified capsule, and facilitating an ultra-fast photocatalytic CO\u003csub\u003e2\u003c/sub\u003e-to-CO conversion \u003cem\u003evia\u003c/em\u003e a promisingly saturated enzymatic kinetics. The strategy included preincubating of photosensitizer, Ir(ppy)\u003csub\u003e3\u003c/sub\u003e with cofactor mimicking BIH for sufficiently producing reactive anionic Ir\u003csup\u003eII\u003c/sup\u003e(ppy)\u003csub\u003e3\u003c/sub\u003e species initially, followed by the thermodynamically favored abstraction of the species inside the cationic lantern-shaped capsule to facilitate the enzymatic conversion under saturated conditions and compatible substrate-product exchange kinetics. The improved and synergistic dynamics of both the iron-based CO\u003csub\u003e2\u003c/sub\u003e reduction and photosensitization bestow the bioinspired system with a turnover number (TON) about 180,000 and an ultrafast turnover frequency (TOF) about 165 s\u003csup\u003e−1\u003c/sup\u003e in targeted CO\u003csub\u003e2\u003c/sub\u003e to CO conversion, surpassed most of reported photocatalytic CO\u003csub\u003e2\u003c/sub\u003e-to-CO systems and typical CO\u003csub\u003e2\u003c/sub\u003e reductases. This pseudo-enzymatic transformation allows concurrent intramolecular cyclic dehydrogenation of imines and CO\u003csub\u003e2\u003c/sub\u003e reduction,\u003cem\u003e \u003c/em\u003eunlocking new opportunities for facilitating the conversion of high-energy-barrier photocatalysis under mild condition.\u003c/p\u003e","manuscriptTitle":"Merging bioinspired incubation with supramolecular photocatalysis for Michaelis CO2 reduction beyond enzymes","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-16 08:34:52","doi":"10.21203/rs.3.rs-8521926/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-communications","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"NCOMMS","sideBox":"Learn more about [Nature Communications](http://www.nature.com/ncomms/)","snPcode":"","submissionUrl":"https://mts-ncomms.nature.com/","title":"Nature Communications","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Communications","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"af4b5e87-2a9d-43d9-894a-0d75f002d262","owner":[],"postedDate":"January 16th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":61221026,"name":"Physical sciences/Chemistry"},{"id":61221027,"name":"Physical sciences/Chemistry/Supramolecular chemistry/Molecular capsules"},{"id":61221028,"name":"Physical sciences/Chemistry/Inorganic chemistry"}],"tags":[],"updatedAt":"2026-05-11T08:15:45+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-16 08:34:52","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8521926","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8521926","identity":"rs-8521926","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}