Late-stage Deuteration of Arenes in D2O Exclusively Driven by Single-atom Pt Sites under Visible Light

Late-stage Deuteration of Arenes in D2O Exclusively Driven by Single-atom Pt Sites under Visible Light | 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 Late-stage Deuteration of Arenes in D2O Exclusively Driven by Single-atom Pt Sites under Visible Light Yi-Tao Dai, Jie Xu, Xin-Yuan Wu, Rui Cao, Da Zhao, Xi-Zhong Song, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9071548/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 Deuterated arenes play crucial roles in medicinal chemistry and materials science (e.g., psychotropic drugs and deuterated OLEDs). However, the desired late-stage deuteration via conventional hydrogen isotope exchange (HIE) methods always demands expensive isotopic reagents (e.g., D2, C6D6, or C2H5OD), metal complex catalysts, or harsh conditions (≥120 oC, 20 bar H2). Here, we report a single-atom photocatalytic strategy for efficient HIE of electron-rich arenes using D2O as the deuterium source. Under visible light irradiation at ambient temperature in an inert atmosphere, a single-atom photocatalyst (Pt1/TiO2) afforded high deuterium incorporation across 54 electron-rich arene substrates. The protocol is mild, sustainable, and scalable: gram-scale synthesis of deuterated arenes (11.98 g, 100 mmol) was successfully realized. Mechanistic studies indicate that the catalytically active sites are primarily Pt–O coordinate bonds, whose light-modulated charge distribution facilitates a possible electrophilic platinization pathway for C–H activation before H/D exchange. Physical sciences/Chemistry/Catalysis/Photocatalysis Physical sciences/Energy science and technology/Renewable energy/Solar energy Physical sciences/Chemistry/Organic chemistry/Synthetic chemistry methodology Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Main Text Deuterium (D) labeled compounds have demonstrated extensive applications across various fields (Fig. 1a), such as studies of reaction mechanisms 1 , deuterated drug molecules 2 , standard reagents for mass spectrometry studies 3 , deuterium metabolic imaging 4 , and optoelectronic devices 5 , etc. Biologically active molecules labeled with D can help to shed light on their metabolic profile and toxicity 6 , which plays an important role in medicinal chemistry. Furthermore, deuterium-labeled pharmaceuticals may show improved pharmacokinetic and pharmacodynamic properties 7 . Notably, in 2017 U.S. FDA approved the first deuterated drug, Austedo (deutetrabenazine), to treat both tardive dyskinesia and Huntington's disease chorea 8 . In addition, donafenib, as a multikinase inhibitor, was approved in China in 2021 to treat advanced hepatocellular carcinoma 9 . Until now, dozens of deuterated compounds have been tested as clinical candidates to discover new drugs 2 . Meanwhile, recent studies have demonstrated the dramatic enhancement of emission quantum yield and stability of OLED devices by introducing deuterated emitters (e.g., deuterated diphenylamine or phenoxy groups) 10,11 . Given promising applications of D-labeling in medicine and materials, the challenging discovery of new drugs underscores the urgent demand for efficient and selective deuteration of organic molecules. In this context, practical labeling methodologies for arenes, which are employed as common building blocks in many small-molecule drugs 12 , are of increasing significance. Traditionally, deuteration of arenes involves multi-step synthetic routes, requiring pre-functionalization (e.g., halogenation, diazotization, borylation, thianthrenation) followed by de-functionalization steps (e.g., dehalogenation, hydrodediazonation, deborylation, or decarbonylation) 13-19 . Instead, hydrogen isotope exchange (HIE) affords a single-step and more efficient protocol for deuteration, especially by employing cheap heavy water D 2 O as an isotopic source 20,21 . Among diverse catalytic techniques for HIE reactions, acid or base catalysis is a well-known effective tool for labeling arenes (Fig. 1b left) 22 . Unfortunately, erosive strong acids or bases or high temperatures (≥180 o C) are typically required to synthesize deuterated arenes (e.g., aniline and phenols) 23,24 , leading to poor tolerances of functional groups in pharmaceuticals and high safety risks during operation. Based on advances in homogeneous metal-catalyzed C–H activation, a variety of organometallic complexes have evolved for catalytic HIE reactions of arenes 25 . For instance, an iron-based complex catalyst has been developed by Chirik and co-workers in 2016 to label aromatic C( sp 2 )–H sites of pharmaceuticals by using high-cost D 2 gas 26 . Similarly, other transition-metal (e.g., Pd, Ir, Ru, and Ni) complexes have achieved exciting success in the deuteration of C( sp 2 )–H bonds in various (hetero)arenes by use of expensive D-sources (e.g., D 2 , C 6 D 6 , and acetic acid- d 4 ) under mild conditions 19,27-31 . Besides, in 2024 an efficient phenolate-type molecule-based photocatalyst has been reported to realize HIE of arenes in KO t Bu-C2H5OD solution under visible light 32 . As far as we know, aromatic HIE in D 2 O was successfully driven by limited homogeneous catalysts, usually requiring prolonged reaction time (up to 72 h) or elevated temperatures (110-120 °C) in the presence of noble-metal complexes (Fig. 1b middle) 33-35 . Thus, the main concerns involve the consumption of expensive deuterium sources and the difficult separation between products and homogeneous catalysts, immensely hindering their broad applications. In contrast, heterogeneous catalytic systems are portraying unexpectedly efficient and robust performance in HIE reactions with the benefits of facile separation and reusability. For example, the HIE of arenes (e.g., phenols, anilines, and benzoic acid) with D 2 O was successfully promoted by commercial 5-10 wt.% Pt/C or Pd/C in 1 bar H 2 atmosphere at room temperature (r.t.) to 180 o C for 24 h (Fig. 1b right) 36,37 . Furthermore, recently noble-metal-free Fe/Fe₃C nanoparticles (NPs) and Mn@Starch-1000 catalysts were developed to realize selective HIE of (hetero)arenes with D₂O in the presence of pressured H 2 (10-20 bar) at 120-140 o C (Fig. 1b right) 38,39 . However, the dangerous and severe conditions (involving H 2 and high temperature) suppressed their practical applications. On the other hand, Ir NPs stabilized by N -heterocyclic carbene ligands were employed to successfully label (hetero)arenes and related pharmaceuticals in 1 bar D 2 gas at a lower temperature (55-80 o C) 40,41 . Additionally, in 2025 Ir NPs supported on SiO 2 have been reported to well deuterate C( sp 2 )–H bonds of arenes with diverse functional groups (e.g., ketone, amide, alkene, ester, ether, halide, aniline, phenol, and heterocyclic units) in C 6 D 6 at 80 o C 42 . The apparent drawback of requiring high-cost D 2 or C 6 D 6 may be an obstacle to large-scale production. Thus, to facilitate the practical applications of catalytic techniques in deuteration, designing a scalable and stable heterogeneous catalyst for H/D exchange of arenes with D 2 O under mild and safe conditions is still challenging and urgent. In this study, we fabricated a single-atom (SA) photocatalyst of Pt 1 /TiO 2 , which realized the challenging HIE reactions of C–H bonds in electron-rich arenes with D 2 O under visible light and 1 bar Ar atmosphere at r.t. (Fig. 1c). Moreover, our SA photocatalytic synthesis tool presented several merits, involving the usage of low Pt loadings (0.7 wt.%), decent reusability, wide substrate scope (54 electron-rich arenes) and gram-scale synthesis (11.98 g, 100 mmol) of deuterated arenes. Results Photocatalyst characterizations and photocatalytic HIE Firstly, a SA photocatalyst sample of Pt 1 /TiO 2 -h with atomically dispersed Pt sites was constructed through a photo-deposition process with as-prepared anatase TiO 2 (TiO 2 -h, 15-25 nm in size, Supplementary Figs. 1-3) as the support 43 . According to the data of scanning transmission electron microscopy (STEM) with energy-dispersive X-ray spectroscopy (EDS) (Fig. 2a), uniform distribution of Pt species on the TiO 2 -h support was verified without the observation of Pt NPs. Furthermore, X-ray absorption near-edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) analysis were conducted to explore the coordination environment and electronic state of Pt species (Fig. 2b, Supplementary Figs. 4 and 5). The Pt L 3 -edge EXAFS Fourier transform (FT) profile of Pt 1 /TiO 2 -h presented a prominent peak at 1.6 Å, which can correspond to Pt–O contribution 44,45 . Instead, no discernible peaks at 2.6 and 3.0 Å relating to the Pt–Pt and Pt–Ti contribution were exhibited 45 . It suggested that Pt was atomically deposited on the surface of TiO 2 , coinciding well with aberration-corrected STEM analysis (Fig. 2c), where SA Pt sites were directly observed as the dominant species in Pt 1 /TiO 2 -h. Besides, the white line intensity of Pt 1 /TiO 2 -h was much higher than that of Pt foil, but apparently lower in contrast to PtO 2 (XANES spectra in Supplementary Fig. 4), confirming the intermediate oxidation state of Pt δ+ (0 < δ < 4) 44 . Based on the fitting data of EXAFS (Supplementary Table 1), interfacial Pt–O bonds were probably formed with a coordination number of 4.6. As expected, Pt 1 /TiO 2 -h showed the same optical bandgap (3.23 eV) with pristine TiO 2 -h (Supplementary Fig. 6). Moreover, the loading of Pd species enhanced the electron reservoir capability of the photocatalyst with promoted charge separation and diffusion, indicated from suppressed photoluminescence and higher photocurrent (Supplementary Figs. 7-9). Initially, we chose 4-methoxyphenol as the model substrate and D 2 O as the deuterium source to explore the catalytic properties of the SA photocatalyst Pt 1 /TiO 2 -h for HIE reactions by use of homemade batch-mode autoclave photoreactors (Supplementary Fig. 10). As shown in Fig. 2d, this SA photocatalyst achieved selective deuteration at the ortho position of the phenolic hydroxyl group with a satisfactory D incorporation of 95% under blue light irradiation (450 nm LED) at r.t. with inert atmosphere (1 bar Ar). The control experiments (no photocatalyst, no light, no Pt deposition, or in air, Supplementary Table 2) showed the HIE of arenes was inherently driven by SA photocatalysis. Additionally, only a trace level of D incorporation (5%) was observed even with external heating at 100 °C in the dark. Moreover, a measurable amount of HDO (0.3 mmol) in D 2 O was detected after HIE reaction, which further evidenced that the H/D exchange step took place between 4-methoxyphenol and D 2 O. In contrast, when TiO 2 -h was loaded with other noble metals (e.g., Pd, Rh, Ir, and Au), no deuteration was observed in HIE reactions. Similarly, the deposition of Pt on other semiconductors (including rutile TiO 2 , Nb 2 O 5 , SrTiO 3 , C 3 N 4 , In 2 O 3 , BiVO 4 , and BiOCl) resulted in no photocatalytic activity for HIE reactions. Meanwhile, commercially available 10 wt.% Pt/C failed to drive HIE of arenes under the same reaction conditions. These reaction results may imply that SA Pt species serve as the main active sites for photocatalytic HIE of arenes in D 2 O. Then, the photocatalysts were comprehensively analyzed by STEM-EDS and UV-Vis absorption spectroscopy (Supplementary Figs. 11-13). When Pt was replaced by other noble metals (Rh, Ir, and Au), NPs were loaded on the TiO 2 -h surface (Supplementary Figs. 11). Only the case of Pd demonstrated the deposition of atomically dispersed Pd sites on TiO 2 -h, agreeing with our recent study 46 . On the other hand, when the anatase TiO 2 -h support was substituted with a rutile phase (TiO 2 -R), only Pt NPs (1-10 nm) were observed (Supplementary Fig. 12). Analogously, Pt NPs were detected on other common semiconductors with bandgaps from 2.5 to 3.4 eV (such as Nb 2 O 5 , SrTiO 3 , C 3 N 4 , In 2 O 3 , BiVO 4 , and BiOCl) after the same photo-deposition procedure (Supplementary Figs. 12 and 13). Based on these characterization results, the decoration of SA sites or NPs via the photo-deposition method highly relied on both the metal elements and the support materials. For closer comparison, we prepared a control sample by depositing Pt NPs (1-5 nm) on TiO 2 -h via high-energetic UV irradiation (Pt n /TiO 2 -h, Supplementary Fig. 11A). However, no photocatalytic activity appeared for HIE of arenes in the presence of Pt n /TiO 2 -h (Fig. 2d). Consequently, it seemed that noble-metal NPs (Pt, Rh, Ir, and Au) and SA Pd sites were inactive for photocatalytic HIE of arenes in D 2 O. It should be pointed out that SA Pd sites were reported to be highly active for the HIE of N-heteroarenes (e.g., 2-aminopyrimidine) under 410 nm LED irradiation by our group very recently 46 . In comparison, the inert behavior of SA Pd sites for phenols could be ascribed to the side reactions based on IR (Supplementary Fig. 14). Moreover, no deuteration of anilines was also observed in the case of Pd 1 /TiO 2 -h. Because SA Pd sites required the N-heteroarene motif to achieve the configuration alignment between substrate and SA coordination environment for C–H activation. Furthermore, when the light wavelengths of irradiation were extended to 500-600 nm, no deuteration occurred over the photocatalyst of Pt 1 /TiO 2 -h because of its limited light absorption (500, 530, and 600 nm, Fig. 2e). It should be mentioned that the attachment of arenes with hydroxyl groups (e.g., phenols) onto Pt 1 /TiO 2 -h extended the light absorption tail to 470 nm in contrast to the clean photocatalyst (Supplementary Fig. 6C,D). This behavior mainly originated from the surface complexation between heteroatom-containing substrates (e.g., O, N, or S) and TiO 2 support 47 . Unexpectedly, despite pronounced UV light absorption from this SA photocatalyst, a low D incorporation (56%) was recorded under UV light illumination (365 nm, Fig. 2e). According to the in situ analysis of gaseous products using mass spectrometry, a tiny amount of D 2 (0.5-1.0 μmol) was detected under UV or 410 nm illumination, while no D 2 was detected under 450 nm LED illumination (Supplementary Fig. 15). Moreover, the control experiments indicated that the introduction of D 2 (~8 μmol) has no negative or positive effect on the HIE reaction for SA Pt sites (Supplementary Table S2, Entry 6). Thus, the activation of C–H bonds would not involve Pt–D species in our SA Pt photocatalytic system. Meanwhile, the appearance of Pt clusters was observed for the used Pt 1 /TiO 2 -h sample after UV light irradiation, based on the DRIFTS analysis of CO adsorption and AC HAADF-STEM images (Supplementary Fig. 15D,F). Instead, no changes were exhibited in DRIFTS analysis of CO adsorption for the used photocatalyst after 450 nm LED irradiation. Thus, we reasoned that more energetic UV irradiation caused the aggregation of SA Pt sites into Pt clusters, which consequently led to a low D incorporation under UV light (365 nm). In addition, up to 97% D incorporation of 4-methoxyphenol was obtained after systematic optimization of the SA photocatalytic system, including parameters of light intensity, irradiation duration, Pt loading, and photocatalyst amount (Supplementary Figs. 16-19). Remarkably, even in the case the substrate concentration was scaled up to 15 folds (from 0.1 to 1.5 mmol in 2 mL D 2 O), high deuteration (95% D incorporation) was maintained by facilely strengthening the light intensity and irradiation time (Supplementary Fig. 20). In terms of reusability, the SA Pt 1 /TiO 2 -h photocatalyst exhibited decent stability, with only a slight decline in D incorporation from 95% to 91% after five consecutive test cycles (Fig. 2f). This minor decrease can be attributed to slight Pt leaching during prolonged stirring in D 2 O, as confirmed by ICP-MS analysis (Supplementary Table 3). Moreover, the nanostructures, crystallinity, and optical properties of the used Pt 1 /TiO 2 -h photocatalyst were well preserved in comparison with the fresh sample via thorough SEM, TEM, STEM-EDS, XRD, UV-Vis DRS, and DRIFTS analysis (Supplementary Figs. 21-26). Mechanistic investigations Regarding the roles of photo-generated charges (electrons and holes) and intermediates (e.g., hydroxyl radicals), sacrificial electron acceptors/donors and other additives were introduced for investigations. As shown in Fig. 2g, the addition of sacrificial electron acceptors such as CCl₄ and K₂S₂O₈ prohibited the HIE reaction, indicating the decisive role of photo-generated electrons in the photocatalytic process. Furthermore, TEMPO presented the quenching effect as well, which usually behaved as a radical trap or oxidant 48 . Meanwhile, efficient deuteration was observed after the addition of BHT, suggesting the absence of carbon-centered radicals as intermediates. Accordingly, it is more likely that TEMPO served as the oxidant to eliminate the reductive intermediates, which agreed well with the prohibition from O 2 in air (Supplementary Table 2). On the other hand, the presence of sacrificial electron donors (isopropanol and oxalate) or t BuOH demonstrated a minor influence on the D incorporation. These slight impacts implied that the photo-generated holes and reactive oxygen species (ROS, hydroxyl radicals) may play roles in rapid steps of the HIE process, rather than the rate-determining steps. Consequently, the results from scavenger control experiments precluded the radical-controlled mechanism for C–H activation from holes or ROS. To further explore the photocatalytic mechanisms, kinetic isotope effect (KIE) experiments were performed. A significantly slower reaction rate emerged when isotope exchange between phenol- d 5 and H 2 O was run over Pt 1 /TiO 2 -h. Correspondingly, a k H /k D value of 3.7 pointed to a primary KIE (Fig. 3a), inferring that the cleavage of C( sp 2 )–H bonds rather than D 2 O activation aligned with the rate-determining step 49 . Additionally, the switch-on/off light irradiation test demonstrated that continuous photon input was essential to sustain the HIE process (Fig. 3b). It suggested that intermediate redox active species were consumed during one round of HIE reaction and then regenerated by light illumination to initiate the next round. Besides, the hot filtration test also confirmed the heterogeneous nature of our SA photocatalytic system (Supplementary Fig. 27), ruling out the active species dissolved in D 2 O. To reveal the active sites of the SA photocatalyst Pt 1 /TiO 2 -h, CO as a probe molecule was adsorbed in a controlled manner with the analysis of diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). There was only one dominant IR band at 2087 cm -1 ascribed to the linear CO adsorption at SA Pt δ+ sites (Fig. 3c) 50-52 . In contrast, the bands at 2050 and 1830 cm -1 corresponding to the linear and multiple-bonded CO adsorption at Pt NPs were observed for the Pt n /TiO 2 sample (Supplementary Fig. 28) 52 . Typically, higher oxidation state of SA Pt sites offered the less redshifted CO absorption bands in contrast to the free CO gas (2143 cm -1 ) due to declined Pt d-electron back-donation to the CO π* antibonding orbital (e.g., ~2128 cm -1 for SA Pt 4+ and ~2062 cm -1 for SA Pt 0 in alloy) 53-55 . Thus, the IR band position of CO adsorption at Pt 1 /TiO 2 -h suggested that the oxidation state of Pt δ+ was between zero and 4+, consistent with the XANES analysis. Notably, the photocatalytic HIE reaction was quenched when Pt 1 /TiO 2 -h was adsorbed with CO (Fig. 3d). This stark contrast further indicated SA Pt δ+ as active sites in HIE reactions. To further track the dynamic changes of SA photocatalysts and substrate molecules during the HIE process, in situ DRIFTS experiments were conducted (Supplementary Fig. 29). Firstly, the coordination between Pt and phenol substrate was evidenced by a red shift for the C–O stretching vibration (shifted from 1280 to 1264 cm -1 , Supplementary Fig. 30). Then, a prominent red shift in the CO adsorption IR band (shifted from 2087 to 2075 cm -1 ) appeared under light illumination (Fig. 3e), corresponding to CO interaction with SA Pt sites. This change implied that partially reduced SA Pt δ* sites with richer electrons were formed when the photo-generated electrons diffused from the conduction band (CB) level of TiO 2 to Pt δ+ sites during light irradiation 56 . In analogy to the photo-induced ligand-to-metal charge transfer (LMCT) process 57,58 , the oxygen sites of Pt–O bonds in the SA photocatalyst may simultaneously experience a lower electron-density state due to dynamic charge transfer 59,60 . It is related to the fact that O 2p orbitals predominantly contribute to the valence band (VB) of TiO 2 61 . In addition, the control experiment showed that the presence of H + or OH - strongly prohibited the HIE reaction (supplementary Table 4), which may originate from the breakage of active Pt–O coordinate bonds. The results also ruled out the electrophilic substitution mechanism catalyzed by acid for HIE in our system. Furthermore, the light irradiation of phenol adsorbed on Pt 1 /TiO 2 -h weakened the absorption band intensity at 3070 cm -1 (u s (C–H)) (Fig. 3f), which corresponded to aromatic C( sp 2 )–H bonds. Switching the light off could recover the IR band intensity of u s (C–H), suggesting the reversible formation of transition states triggered by light. Accordingly, the activation of C–H bonds may undergo an electrophilic platinization step mediated by active Pt–O coordinate bonds with modulated charge under light excitation 62,63 . After the introduction of D 2 O into the DRIFTS cell, the IR band at 3070 cm -1 gradually declined under light irradiation due to the H/D exchange step (Fig. 3f and Supplementary Fig. 31A). However, due to the overlap from CO 2 and D 2 O signals, the IR bands corresponding to C–D bonds could not be directly observed (Supplementary Figs. 31-33). Instead, no changes occurred under light irradiation for the case of Pt n /TiO 2 -h with phenol and D 2 O adsorbed (Supplementary Fig. 31B). Based on the above mechanistic studies and previous reports 62-65 , a plausible catalytic cycle for the HIE of arenes in D 2 O over SA photocatalyst Pt 1 /TiO 2 -h was proposed (Fig. 3g). Firstly, the aromatic substrates were attached to SA Pt δ+ sites via coordination of hydroxyl or amino groups. Upon visible-light excitation, photo-generated electrons were transferred from the CB level of TiO 2 to the SA Pt centers, regulating the charge state of Pt–O coordinate bonds. Later, the excited Pt–O sites facilitated the activation of nearby aromatic C( sp 2 )–H bonds via a possible electrophilic platinization pathway. Subsequently, the proposed four-membered transition state underwent an H/D exchange step with D 2 O, accompanied by the generation of HOD. Finally, the desired deuterated arenes were yielded with the release of Pt–O sites, which could be tuned back to ground state by photo-generated holes or hydroxyl radicals (Supplementary Fig. 34). Substrate scope tests To assess the substrate scope and functional group tolerance of the SA photocatalytic system for HIE reactions, diverse electron-rich (hetero)arenes were examined (Figs. 4 and 5). First, various phenols and anilines bearing ortho- , meta- , or para- methyl/methoxy/ethoxy/ethyl substituents underwent efficient HIE with satisfactory D incorporation ( 1b - 1 3b ). In most cases, the C( sp 2 )–H bonds at the ortho and para positions of hydroxyl or amino groups were well labeled (D incorporation >80%), due to the chelation effect from directing groups of –OH and –NH 2 . In contrast, the presence of methyl/methoxy groups in the meta position of the directing groups inhibits the D incorporation of its ortho and para positions ( 3b , 6b , 1 1b , 12b , 15b , 20b , 22b ), which may be related to the steric hindrance of the substituents. Next, we examined substrates containing two hydroxyl or amino groups, all of which could be deuterated with excellent D incorporation (≥99% for 14b - 18b ) at the ortho or para positions of functional groups. Halogenated phenols and anilines, including –F ( 19b - 20b , 23b ), –Cl ( 21b , 24b ), and –Br ( 22b ), were well tolerated in our SA photocatalytic system. These substrates afforded decent D incorporation at the ortho positions of hydroxyl or amino groups (≥94%), highlighting their potential for further derivatization. Besides, for the case of halogen groups located at the ortho positions of hydroxyl groups, high-level deuteration (≥91%) was also observed at the meta positions of –OH ( 20b , 22b ). It is worth noting that, when the meta position of the directing group was replaced by –Cl ( 21b , 24b ), suppressed D incorporation at the ortho position of directing groups appeared. It may be due to the electron-withdrawing effect of halogen atoms. In contrast, for substrate 19b, where the –F is located at the meta positions of hydroxyl groups, the deuteration at the ortho positions of –OH was not suppressed due to the possible “ ortho -fluorine effect” 66 . Other functional groups, such as –CF 3 ( 25b ), –Ph ( 26b ), and morpholino ( 27b-29b ), were also highly compatible for HIE reactions with D incorporation varying from 80 to 99% at the ortho positions of –OH or –NH 2 . However, medium D incorporation of 45% appeared for the substituent of linear alkyl alcohol ( 30b ). Notably, a fused aromatic amine delivered the corresponding deuterated product with high D incorporation (85%, 31b ). Moreover, N -alkyl substituted arenes could be labeled with deuterium as well ( 32b and 33b ). Additionally, electron-rich 1,3,5-trimethoxybenzene was tolerated by yielding 34b with D incorporation of 64%. On the other hand, neither arenes substituted with electron-withdrawing groups (–COOH/CF 3 /CN) nor electron-deficient N-heteroarenes were compatible with the SA photocatalytic system (Supplementary Table 2). It contradicted the substrate scope of the oxidative addition mechanism proposed in our recent study, which could cover the electron-deficient C–H bonds 46 , 67 . Therefore, the requirement of electron-rich substrates favored the proposed electrophilic platinization mechanism. Delightedly, the deuteration of some N-heteroarenes in the presence of hydroxyl or amino groups, such as pyridines and quinolines ( 35b-38b ), was successfully driven with D incorporation ranging from 79% to 99%. Furthermore, the late-stage deuteration of representative natural products and drugs was investigated over the Pt 1 /TiO 2 -h photocatalyst (Fig. 5). Natural products, for instance, guaiacol, olivetol, cianidanol, resveratrol, phloretin, arbutin, and NSC 87909, were labeled dominantly at the ortho positions of –OH or –NH 2 groups with satisfactory D incorporation (≥91% for 39b-43b and 45b ; 76% for 44b ). Several commercial small-molecule drugs (e.g., aminoglutethimide, benzocaine, procaine, 5-HIAA, and tacrine), used to treat cancer/vascular/heart/alzheimer diseases and viral/bacterial infections, were efficiently deuterated via SA photocatalysis (D incorporation of 78-96% for 46b-50b ). Overall, 86% of tested substrates (including 1a - 29a , 31a , 35a - 36a , 38a , 39a - 43a , 45a - 47a , 49a - 50a ) offered satisfactory D incorporation (>80%), demonstrating the broad substrate scope of Pt-based SA photocatalysis. In addition, slight deuteration was also observed for relatively labile C( sp 3 )–H bonds at the benzylic sites or ortho positions to carbonyl groups (e.g., 13b , 43b , 46b , 50b ). Gram-scale synthesis and synthetic applications To evaluate the practicability of this SA photocatalytic system, gram-scale synthesis experiments were performed. The reactant with amount scaled up to 1000 times (100 mmol, 12 g) was labeled in a homemade glass photoreactor (250 mL, Fig. 6a) charged with 5 g SA photocatalysts and 180 mL D 2 O. After 48 h irradiation (410 nm LED strips) in 1 bar Ar atmosphere, up to 99% D incorporation was achieved without external heating. It should be mentioned that the temperature of suspensions in the photoreactor gradually rose from r.t. to ~65 o C due to the visible irradiation for a long time. After facile photocatalyst separation and solvent evaporation, a highly pure deuterated product (2,6-dimethylaniline-3,4,5- d 3 ) was obtained with an isolation yield of 97% (11.98 g; 1 H NMR-based purity >99%). Considering the successful reproducible deuteration of N-heteroarenes using a home-made photoreactor bed equipped with dozens of glass reactors in our laboratory recently 46 , we believe this SA photocatalytic system can be easily scaled up to kilogram-level synthesis of deuterated arenes. Furthermore, the deuterated anilines can be efficiently converted to N -acylated compounds with high-level D labeling, whose direct late-stage deuteration is usually challenging (D incorporation <15%). For instance, deuterated lidocaine 51b , nefiracetam 52b , herbicides chlortoluron 53b, and fluometuron 54b were conveniently synthesized with corresponding deuterated aniline precursors (Fig. 6b). It is worth noting that nefiracetam has entered phase III clinical trials for the treatment of Alzheimer’s disease. These results demonstrated that deuterated aniline products from SA photocatalytic HIE reactions would have potential applications in the synthesis of D-labeling pharmaceuticals. Discussion In summary, we establish a single-atom (SA) photocatalytic mechanism for hydrogen-deuterium exchange of electron-rich arenes using D 2 O under visible light at ambient temperature and inert atmosphere; nanoparticle (NP) sites were ineffective. The Pt 1 /TiO 2 SA photocatalyst enables late-stage deuteration of highly functionalized natural products and pharmaceuticals, displays good reusability, and tolerates a broad substrate scope (54 electron-rich arenes). The developed photocatalytic deuteration method is mild, scalable (gram-scale: 11.98 g, 100 mmol), and operationally simple, demonstrating the practicability of SA photocatalysis. We anticipate this approach will provide an economical, selective, and robust route for preparing deuterated small-molecule drugs and functional materials. Methods Catalyst preparation For the preparation of SA photocatalyst Pt 1 /TiO 2 -h : Firstly, as-prepared 500 mg TiO 2 -h and 7.35 mg H 2 PtCl 6 ·xH 2 O were added to a 20 mL water-isopropanol solution (volume ratio of deionized water : i -PrOH was 5 : 1) under stirring for 30 min. Then the mixture was irradiated with a 410 nm LED lamp under Ar atmosphere at room temperature. After 10 h irradiation, the light grey solids were collected via centrifugation and further washed with water. After drying in a vacuum oven, the sample Pt 1 /TiO 2 -h was obtained, which was directly used for characterizations and photocatalytic tests. The loading amount of Pt was tuned by introducing different amounts of H 2 PtCl 6 ·xH 2 O. Photocatalytic HIE reaction In a 7 mL glass vial with a fitted magnetic stirring bar, Pt 1 /TiO 2 -h (50 mg) and substrate (0.1 mmol) were added. After adding the solvent D 2 O (2.0 mL), the vial was placed into a 20 mL stainless-steel autoclave with a quartz window. The autoclave was purged with Ar at 10 bar and then degassed to the ambient pressure (1 bar). It was repeated 6 times to remove O 2 maximally. Next, it was seated into an aluminum cooling jacket with water circulating from the chiller to keep the room temperature (25 o C). Later, the monochromatic LED lamp (light wavelength of 365 nm, 410 nm, 450 nm, 500 nm, 530 nm, or 600 nm) was placed on top of the autoclave and irradiated the suspension through the quartz window for 6 h. After the photocatalytic HIE reaction, the suspension was transferred from the autoclave to a centrifuge tube and then centrifuged to obtain the supernatant. The deuterium incorporation (D incorporation) and selectivity of products can be obtained by 1 H NMR analysis of the supernatant (see below for calculation equations). For the product isolation, after the removal of all D 2 O in vacuo, the desired products were obtained. Declarations Data availability All the data that support the findings of this study are available within the main text and the Supplementary Information. Details about materials, photocatalyst preparation, experimental procedures, characterization data, and NMR spectra are available in the Supplementary Information. Acknowledgments We appreciate the financial support from the National Natural Science Foundation of China (22479141), Gusu Innovation and Entrepreneurship Leading Talents Program (ZXL2022468), Youth Fund Project of Natural Science Foundation of Jiangsu Province (BK20220287), Science and Technology Program of Suzhou (SWY2022003), and Jiangxi Provincial Double Thousand Plan-Leading Innovative Talents Program (No. jxsq2023101011). We thank professional service from characterization platforms. The characterization work was partially conducted at the Instruments Center for Physical Science, University of Science and Technology of China, and Physical and Chemical Analysis Center at Suzhou Institute for Advanced Research (University of Science and Technology of China). We thank the BL14W1 XAFS beamline of the Shanghai Synchrotron Radiation Facility (SSRF) for providing beamtime. Author contributions Y.-T.D. supervised the project and conceived the research. J.X. and Y.-T.D. designed the experiments. J.X., X.-Y.W., R.C., and Y.-T.D. performed experiments and characterizations. J.X. and Y.-T.D. interpreted the data and generated figures. D.Z., X.-Z.S., H.C., W.-W.L., T. P., K.M.L., and F.B. provided valuable suggestions throughout this study. J.X. wrote the initial draft and Y.-T.D. finalized it. All authors contributed to revising the paper. Competing interests The authors declare no competing interests. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9071548","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":604778328,"identity":"4fcd719f-2020-493c-961e-ceea536ccbff","order_by":0,"name":"Yi-Tao 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(\u003cstrong\u003eb\u003c/strong\u003e) HIE of arenes with D\u003csub\u003e2\u003c/sub\u003eO via reported catalytic systems. (\u003cstrong\u003ec\u003c/strong\u003e) Our SA photocatalytic route for HIE of electron-rich arenes in D\u003csub\u003e2\u003c/sub\u003eO. EDG, electron-donating groups. \u0026nbsp;\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9071548/v1/ff2ca70e65c637939fdafb9e.jpg"},{"id":104544517,"identity":"e1a947d2-0eb9-4f51-a129-d05b955926e2","added_by":"auto","created_at":"2026-03-13 06:58:52","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":353483,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eStructural characterizations of Pt\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/sub\u003e\u003cstrong\u003e/TiO\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/sub\u003e\u003cstrong\u003e-h and HIE of 4-methoxyphenol in D\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/sub\u003e\u003cstrong\u003eO via photocatalysis.\u003c/strong\u003e (\u003cstrong\u003ea\u003c/strong\u003e) Representative STEM-EDS elemental mapping of Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h. (\u003cstrong\u003eb\u003c/strong\u003e) FT-EXAFS spectra of Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h with Pt foil as a reference at the Pt L\u003csub\u003e3\u003c/sub\u003e-edge. (\u003cstrong\u003ec\u003c/strong\u003e) Aberration-corrected high-angle annular dark-field (HAADF) STEM image of Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h with Pt atoms indicated by yellow circles. (\u003cstrong\u003ed\u003c/strong\u003e) Photocatalytic HIE of 4-methoxyphenol in D\u003csub\u003e2\u003c/sub\u003eO over different photocatalysts. Pt\u003csub\u003en\u003c/sub\u003e and TiO\u003csub\u003e2\u003c/sub\u003e-R indicate Pt NPs and rutile TiO\u003csub\u003e2\u003c/sub\u003e, respectively. (\u003cstrong\u003ee\u003c/strong\u003e) Photocatalytic HIE of 4-methoxyphenol in D\u003csub\u003e2\u003c/sub\u003eO over Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h under light irradiation with different wavelengths. (\u003cstrong\u003ef\u003c/strong\u003e) Reusability of photocatalyst Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h. (\u003cstrong\u003eg\u003c/strong\u003e) Scavenger control experiments by adding sacrificial reagents, including butylated hydroxytoluene (BHT), 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO), isopropanol, ammonium oxalate (AO), CCl\u003csub\u003e4\u003c/sub\u003e, K\u003csub\u003e2\u003c/sub\u003eS\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e8\u003c/sub\u003e, and \u003cem\u003etert\u003c/em\u003e-butanol. Standard reaction conditions: 4-methoxyphenol (0.1 mmol), photocatalyst (50 mg), D\u003csub\u003e2\u003c/sub\u003eO (2.0 mL), LED irradiation (light wavelength of 365, 410, 450, 500, 530, or 600 nm, 30 mW/cm\u003csup\u003e2\u003c/sup\u003e), Ar (1 bar), room temperature (r.t.), 6 h.\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9071548/v1/0e825f163da73e3b4a2e8002.jpg"},{"id":104544521,"identity":"1af7e629-1a6b-49d8-945e-398b815cd074","added_by":"auto","created_at":"2026-03-13 06:58:53","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":320361,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMechanistic studies of SA photocatalysis for HIE of arenes in D\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/sub\u003e\u003cstrong\u003eO.\u003c/strong\u003e (\u003cstrong\u003ea\u003c/strong\u003e) The isotopic labeling experiments. (\u003cstrong\u003eb\u003c/strong\u003e) Photocatalytic HIE reactions under switch-on/off light irradiation. (\u003cstrong\u003ec\u003c/strong\u003e) DRIFTS analysis of Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h\u003csub\u003e \u003c/sub\u003eand Pt\u003csub\u003en\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e samples with CO adsorbed. (\u003cstrong\u003ed\u003c/strong\u003e) Photocatalytic HIE reactions over Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h with/without CO adsorbed. (\u003cstrong\u003ee\u003c/strong\u003e) DRIFTS analysis of Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h with/without light excitation during CO adsorption. (\u003cstrong\u003ef\u003c/strong\u003e) \u003cem\u003eIn situ\u003c/em\u003e DRIFTS analysis of photocatalytic HIE of phenol in D\u003csub\u003e2\u003c/sub\u003eO via SA photocatalyst Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h. (\u003cstrong\u003eg\u003c/strong\u003e) Proposed catalytic mechanism for HIE of arenes in D\u003csub\u003e2\u003c/sub\u003eO over SA photocatalyst Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h under visible light irradiation.\u0026nbsp;\u003c/p\u003e","description":"","filename":"Picture3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9071548/v1/1283baabbc2b0ccdc3c1a042.jpg"},{"id":104544522,"identity":"d2f8e9e3-4f66-4978-a706-7f0e75d33680","added_by":"auto","created_at":"2026-03-13 06:58:53","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":375309,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe HIE of electron-rich (hetero)arenes via SA photocatalysis.\u003c/strong\u003e Standard reaction conditions:\u0026nbsp; Substrate (0.1 mmol), SA photocatalyst 0.7 wt.% Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h (50 mg), D\u003csub\u003e2\u003c/sub\u003eO (2.0 mL), LED irradiation (450 nm, 30 mW/cm\u003csup\u003e2\u003c/sup\u003e), Ar (1 bar), r.t., 6 h. \u003csup\u003ea\u003c/sup\u003eLED irradiation (410 nm, 60 mW/cm\u003csup\u003e2\u003c/sup\u003e), 12 h. \u003csup\u003eb\u003c/sup\u003eLED irradiation (410 nm, 95 mW/cm\u003csup\u003e2\u003c/sup\u003e). \u003csup\u003ec\u003c/sup\u003eLED irradiation (410 nm, 60 mW/cm\u003csup\u003e2\u003c/sup\u003e), 60 \u003csup\u003eo\u003c/sup\u003eC. \u003csup\u003ed\u003c/sup\u003eLED irradiation (410 nm, 60 mW/cm\u003csup\u003e2\u003c/sup\u003e), 60 \u003csup\u003eo\u003c/sup\u003eC, 12 h. \u003csup\u003ee\u003c/sup\u003eD\u003csub\u003e2\u003c/sub\u003eO (1.6 mL), acetone (0.4 mL), LED irradiation (410 nm, 60 mW/cm\u003csup\u003e2\u003c/sup\u003e), 60 \u003csup\u003eo\u003c/sup\u003eC, 12 h. \u003csup\u003ef\u003c/sup\u003e2.0 wt.% Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h, LED irradiation (410 nm, 60 mW/cm\u003csup\u003e2\u003c/sup\u003e), 60 \u003csup\u003eo\u003c/sup\u003eC, 24 h. \u003csup\u003eg\u003c/sup\u003e2.0 wt.% Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h, D\u003csub\u003e2\u003c/sub\u003eO (1.6 mL), acetone (0.4 mL), LED irradiation (410 nm, 60 mW/cm\u003csup\u003e2\u003c/sup\u003e), 60 \u003csup\u003eo\u003c/sup\u003eC, 24 h. \u003csup\u003eh\u003c/sup\u003egram-scale synthesis. The grey spots denote the positions of the C–H bonds that are labelled with the deuterium incorporation \u0026lt;15%. The pink spots and numbers denote the positions of the labeled C–H bonds and the deuterium incorporation, respectively.\u003c/p\u003e","description":"","filename":"Picture4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9071548/v1/85923a5be940a61b64f4856d.jpg"},{"id":104544519,"identity":"7fe7625c-1613-4bfd-999a-8c09e0993d67","added_by":"auto","created_at":"2026-03-13 06:58:53","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":316325,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe HIE of natural products and drugs via SA photocatalysis.\u003c/strong\u003e Standard reaction conditions: Substrate (0.1 mmol), SA photocatalyst 0.7 wt.% Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h (50 mg), D\u003csub\u003e2\u003c/sub\u003eO (2.0 mL), LED irradiation (410 nm, 60 mW/cm\u003csup\u003e2\u003c/sup\u003e), Ar (1 bar), 60 \u003csup\u003eo\u003c/sup\u003eC, 12 h. \u003csup\u003ea\u003c/sup\u003eD\u003csub\u003e2\u003c/sub\u003eO (1.6 mL), acetone (0.4 mL). \u003csup\u003eb\u003c/sup\u003e2.0 wt.% Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h, 24 h. \u003csup\u003ec\u003c/sup\u003e2.0 wt.% Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h, D\u003csub\u003e2\u003c/sub\u003eO (1.6 mL), acetone (0.4 mL), 24 h. The grey spots denote the positions of the C–H bonds that are labelled with the deuterium incorporation \u0026lt;15%. The pink spots and numbers denote the positions of the labeled C–H bonds and the deuterium incorporation, respectively. [D], deuterated.\u003c/p\u003e","description":"","filename":"Picture5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9071548/v1/6e56fb71bffad9daed9405f4.jpg"},{"id":104544518,"identity":"6a079514-e398-47f4-b4ce-0ee205bec826","added_by":"auto","created_at":"2026-03-13 06:58:52","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":193137,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eGram-scale synthesis of deuterated anilines and synthetic applications. \u003c/strong\u003eGram-scale reaction conditions: 2,6-dimethylaniline (12 g, 100 mmol), SA photocatalyst of 2.0 wt.% Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h (5.0 g), D\u003csub\u003e2\u003c/sub\u003eO (180 mL), LED irradiation (410 nm), Ar (1 bar), r.t.-65 \u003csup\u003eo\u003c/sup\u003eC, 48 h. The detailed synthetic application conditions were presented in Supplementary Methods. [D], deuterated.\u003c/p\u003e","description":"","filename":"Picture6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9071548/v1/5503ae4cb263be1e8b5bee13.jpg"},{"id":104780931,"identity":"67772a1d-d7c8-45d5-950d-1c0baed21f9b","added_by":"auto","created_at":"2026-03-17 07:54:19","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3082408,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9071548/v1/81de8136-094e-49df-be76-cf9210d64e58.pdf"},{"id":104544520,"identity":"e1a5700d-af63-418f-9b8c-f6551fe4c791","added_by":"auto","created_at":"2026-03-13 06:58:53","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":17627799,"visible":true,"origin":"","legend":"Supplementary Information","description":"","filename":"ArenesdeuterationSIsubmitFinal.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9071548/v1/45747973cf629cfca1fce882.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Late-stage Deuteration of Arenes in D2O Exclusively Driven by Single-atom Pt Sites under Visible Light","fulltext":[{"header":"Main Text","content":"\u003cp\u003eDeuterium (D) labeled compounds have demonstrated extensive applications across various fields (Fig. 1a), such as studies of reaction mechanisms\u003csup\u003e1\u003c/sup\u003e, deuterated drug molecules\u003csup\u003e2\u003c/sup\u003e, standard reagents for mass spectrometry studies\u003csup\u003e3\u003c/sup\u003e, deuterium metabolic imaging\u003csup\u003e4\u003c/sup\u003e, and optoelectronic devices\u003csup\u003e5\u003c/sup\u003e, etc. Biologically active molecules labeled with D can help to shed light on their metabolic profile and toxicity\u003csup\u003e6\u003c/sup\u003e, which plays an important role in medicinal chemistry. Furthermore, deuterium-labeled pharmaceuticals may show improved pharmacokinetic and pharmacodynamic properties\u003csup\u003e7\u003c/sup\u003e. Notably, in 2017 U.S. FDA approved the first deuterated drug, Austedo (deutetrabenazine), to treat both tardive dyskinesia and Huntington\u0026apos;s disease chorea\u003csup\u003e8\u003c/sup\u003e. In addition, donafenib, as a multikinase inhibitor, was approved in China in 2021 to treat advanced hepatocellular carcinoma\u003csup\u003e9\u003c/sup\u003e. Until now, dozens of deuterated compounds have been tested as clinical candidates to discover new drugs\u003csup\u003e2\u003c/sup\u003e.\u0026nbsp;Meanwhile,\u0026nbsp;recent studies have demonstrated the dramatic enhancement of emission quantum yield and stability of OLED devices by introducing deuterated emitters (e.g., deuterated\u0026nbsp;diphenylamine or phenoxy groups)\u003csup\u003e10,11\u003c/sup\u003e. Given promising applications of D-labeling in medicine and materials, the challenging discovery of new drugs underscores the urgent demand for efficient and selective deuteration of organic molecules. In this context, practical labeling methodologies for arenes, which are employed as common building blocks in many small-molecule drugs\u003csup\u003e12\u003c/sup\u003e, are of increasing significance.\u003c/p\u003e\n\u003cp\u003eTraditionally, deuteration of arenes involves multi-step synthetic routes, requiring pre-functionalization (e.g., halogenation, diazotization, borylation, thianthrenation) followed by de-functionalization steps (e.g., dehalogenation, hydrodediazonation, deborylation, or decarbonylation)\u003csup\u003e13-19\u003c/sup\u003e. Instead, hydrogen isotope exchange (HIE) affords a single-step and more efficient protocol for deuteration, especially by employing cheap heavy water D\u003csub\u003e2\u003c/sub\u003eO as an isotopic source\u003csup\u003e20,21\u003c/sup\u003e. Among diverse catalytic techniques for HIE reactions, acid or base\u0026nbsp;catalysis is a well-known effective tool\u0026nbsp;for labeling arenes\u0026nbsp;(Fig. 1b left)\u003csup\u003e22\u003c/sup\u003e.\u0026nbsp;Unfortunately,\u0026nbsp;erosive strong\u0026nbsp;acids or bases\u0026nbsp;or high temperatures (\u0026ge;180\u0026nbsp;\u003csup\u003eo\u003c/sup\u003eC) are typically required to synthesize deuterated arenes (e.g., aniline and phenols)\u003csup\u003e23,24\u003c/sup\u003e, leading to\u0026nbsp;poor tolerances\u0026nbsp;of\u0026nbsp;functional groups in pharmaceuticals\u0026nbsp;and high safety risks\u0026nbsp;during operation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBased on advances in homogeneous metal-catalyzed C\u0026ndash;H activation, a variety of organometallic complexes have evolved for catalytic HIE reactions of arenes\u003csup\u003e25\u003c/sup\u003e. For instance, an iron-based complex catalyst has been developed by Chirik and co-workers in 2016 to label aromatic C(\u003cem\u003esp\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e)\u0026ndash;H sites of pharmaceuticals by using high-cost D\u003csub\u003e2\u003c/sub\u003e gas\u003csup\u003e26\u003c/sup\u003e. Similarly, other transition-metal (e.g., Pd, Ir, Ru, and Ni) complexes have achieved exciting success in the deuteration of C(\u003cem\u003esp\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e)\u0026ndash;H bonds in various (hetero)arenes by use of expensive D-sources (e.g., D\u003csub\u003e2\u003c/sub\u003e, C\u003csub\u003e6\u003c/sub\u003eD\u003csub\u003e6\u003c/sub\u003e, and acetic acid-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e\u0026nbsp;\u003c/sub\u003eunder mild conditions\u003csup\u003e19,27-31\u003c/sup\u003e. Besides, in 2024 an efficient phenolate-type molecule-based photocatalyst has been reported to realize HIE of arenes in\u0026nbsp;KO\u003cem\u003e\u003csup\u003et\u003c/sup\u003e\u003c/em\u003eBu-C2H5OD solution under visible light\u003csup\u003e32\u003c/sup\u003e. As far as we know, aromatic HIE in D\u003csub\u003e2\u003c/sub\u003eO was successfully driven by limited homogeneous catalysts, usually requiring prolonged reaction time (up to 72 h) or elevated temperatures (110-120 \u0026deg;C) in the presence of noble-metal complexes (Fig. 1b middle)\u003csup\u003e33-35\u003c/sup\u003e. Thus, the main concerns involve the consumption of expensive deuterium sources and the difficult separation between products and homogeneous catalysts, immensely hindering their broad applications.\u003c/p\u003e\n\u003cp\u003eIn contrast, heterogeneous catalytic systems are portraying unexpectedly efficient and robust performance in HIE reactions with the benefits of facile separation and reusability. For example, the HIE of arenes (e.g., phenols, anilines, and benzoic acid) with D\u003csub\u003e2\u003c/sub\u003eO was successfully promoted by commercial 5-10 wt.% Pt/C or Pd/C in 1 bar H\u003csub\u003e2\u003c/sub\u003e atmosphere at room temperature (r.t.) to 180 \u003csup\u003eo\u003c/sup\u003eC for 24 h (Fig. 1b right)\u003csup\u003e36,37\u003c/sup\u003e. Furthermore, recently noble-metal-free Fe/Fe₃C nanoparticles (NPs) and Mn@Starch-1000 catalysts were developed to realize selective HIE of (hetero)arenes with D₂O in the presence of pressured H\u003csub\u003e2\u003c/sub\u003e (10-20 bar) at 120-140 \u003csup\u003eo\u003c/sup\u003eC (Fig. 1b right)\u003csup\u003e38,39\u003c/sup\u003e. However, the dangerous and severe conditions (involving H\u003csub\u003e2\u003c/sub\u003e and high temperature) suppressed their practical applications. On the other hand,\u0026nbsp;Ir NPs\u0026nbsp;stabilized by \u003cem\u003eN\u003c/em\u003e-heterocyclic carbene ligands were employed to successfully label (hetero)arenes and related pharmaceuticals in 1 bar D\u003csub\u003e2\u003c/sub\u003e gas at a lower temperature (55-80 \u003csup\u003eo\u003c/sup\u003eC)\u003csup\u003e40,41\u003c/sup\u003e. Additionally, in 2025 Ir NPs supported on SiO\u003csub\u003e2\u003c/sub\u003e have been reported to well deuterate C(\u003cem\u003esp\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e)\u0026ndash;H bonds of arenes with diverse functional groups (e.g., ketone, amide, alkene, ester, ether, halide, aniline, phenol, and heterocyclic units) in C\u003csub\u003e6\u003c/sub\u003eD\u003csub\u003e6\u003c/sub\u003e at 80 \u003csup\u003eo\u003c/sup\u003eC\u003csup\u003e42\u003c/sup\u003e. The apparent drawback of requiring high-cost D\u003csub\u003e2\u003c/sub\u003e or C\u003csub\u003e6\u003c/sub\u003eD\u003csub\u003e6\u003c/sub\u003e may be an obstacle to large-scale production. Thus, to facilitate the practical applications of catalytic techniques in deuteration, designing a scalable and stable heterogeneous catalyst for H/D exchange of arenes with D\u003csub\u003e2\u003c/sub\u003eO under mild and safe conditions is still challenging and urgent.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn this study, we fabricated a single-atom (SA) photocatalyst of Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e, which realized the challenging HIE reactions of C\u0026ndash;H bonds in electron-rich arenes with D\u003csub\u003e2\u003c/sub\u003eO under visible light and 1 bar Ar atmosphere at r.t. (Fig. 1c). Moreover, our SA photocatalytic synthesis tool presented several merits, involving the usage of low Pt loadings (0.7 wt.%), decent reusability, wide substrate scope (54 electron-rich arenes) and gram-scale synthesis (11.98 g, 100 mmol) of deuterated arenes.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003ePhotocatalyst characterizations and photocatalytic HIE\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFirstly, a SA photocatalyst sample of Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h with atomically dispersed Pt sites was constructed through a photo-deposition process with as-prepared anatase TiO\u003csub\u003e2\u003c/sub\u003e (TiO\u003csub\u003e2\u003c/sub\u003e-h, 15-25 nm in size, Supplementary Figs. 1-3) as the support\u003csup\u003e43\u003c/sup\u003e. According to the data of scanning transmission electron microscopy (STEM) with energy-dispersive X-ray spectroscopy (EDS) (Fig. 2a), uniform distribution of Pt species on the TiO\u003csub\u003e2\u003c/sub\u003e-h support was verified without the observation of Pt NPs. Furthermore, X-ray absorption near-edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) analysis were conducted to explore the coordination environment and electronic state of Pt species (Fig. 2b, Supplementary Figs. 4 and 5). The\u0026nbsp;Pt L\u003csub\u003e3\u003c/sub\u003e-edge\u0026nbsp;EXAFS Fourier transform (FT) profile of\u0026nbsp;Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h\u0026nbsp;presented a prominent\u0026nbsp;peak at 1.6 \u0026Aring;, which can correspond to\u0026nbsp;Pt\u0026ndash;O\u0026nbsp;contribution\u003csup\u003e44,45\u003c/sup\u003e. Instead, no discernible peaks\u0026nbsp;at 2.6\u0026nbsp;and 3.0\u0026nbsp;\u0026Aring;\u0026nbsp;relating to\u0026nbsp;the Pt\u0026ndash;Pt\u0026nbsp;and Pt\u0026ndash;Ti\u0026nbsp;contribution\u0026nbsp;were exhibited\u003csup\u003e45\u003c/sup\u003e. It suggested that Pt was atomically deposited on the surface of TiO\u003csub\u003e2\u003c/sub\u003e, coinciding well with aberration-corrected STEM analysis (Fig. 2c), where SA\u0026nbsp;Pt\u0026nbsp;sites were directly observed as the dominant species\u0026nbsp;in Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h. Besides, the\u0026nbsp;white line intensity of\u0026nbsp;Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h\u0026nbsp;was much higher than that of Pt foil, but apparently lower in contrast to PtO\u003csub\u003e2\u003c/sub\u003e (XANES spectra in Supplementary Fig. 4), confirming the intermediate oxidation state of Pt\u003csup\u003e\u0026delta;+\u003c/sup\u003e (0 \u0026lt; \u0026delta; \u0026lt; 4)\u003csup\u003e44\u003c/sup\u003e. Based on the fitting data of EXAFS (Supplementary Table 1), interfacial Pt\u0026ndash;O bonds were probably formed with a coordination number of 4.6. As expected, Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h showed the same optical bandgap (3.23 eV) with pristine TiO\u003csub\u003e2\u003c/sub\u003e-h (Supplementary Fig. 6). Moreover, the loading of Pd species enhanced the electron reservoir capability of the photocatalyst with promoted charge separation and diffusion, indicated from suppressed photoluminescence and higher photocurrent (Supplementary Figs. 7-9).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eInitially, we chose 4-methoxyphenol as the model substrate and D\u003csub\u003e2\u003c/sub\u003eO as the deuterium source to explore the catalytic properties of the SA photocatalyst Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h for HIE reactions by use of homemade batch-mode autoclave photoreactors (Supplementary Fig. 10). As shown in Fig. 2d, this SA photocatalyst achieved\u0026nbsp;selective deuteration at the \u003cem\u003eortho\u003c/em\u003e position of the phenolic hydroxyl group with a satisfactory D incorporation of 95% under blue light irradiation (450 nm LED) at r.t. with inert atmosphere (1 bar Ar). The control experiments (no photocatalyst, no light, no Pt deposition, or in air, Supplementary Table 2) showed the HIE of arenes was inherently driven by SA photocatalysis. Additionally, only a trace level of D incorporation (5%) was observed even with external heating at 100 \u0026deg;C in the dark. Moreover, a measurable amount of HDO (0.3 mmol) in D\u003csub\u003e2\u003c/sub\u003eO was detected after HIE reaction, which further evidenced that the H/D exchange step took place between 4-methoxyphenol and D\u003csub\u003e2\u003c/sub\u003eO. In contrast, when TiO\u003csub\u003e2\u003c/sub\u003e-h was loaded with other noble metals (e.g., Pd, Rh, Ir, and Au), no deuteration was observed in HIE reactions. Similarly, the deposition of Pt on other semiconductors (including rutile TiO\u003csub\u003e2\u003c/sub\u003e, Nb\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e5\u003c/sub\u003e, SrTiO\u003csub\u003e3\u003c/sub\u003e, C\u003csub\u003e3\u003c/sub\u003eN\u003csub\u003e4\u003c/sub\u003e, In\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e, BiVO\u003csub\u003e4\u003c/sub\u003e, and BiOCl) resulted in no photocatalytic activity for HIE reactions. Meanwhile, commercially available 10 wt.% Pt/C failed to drive HIE of arenes under the same reaction conditions. These reaction results may imply that SA Pt species serve as the main active sites for photocatalytic HIE of arenes in D\u003csub\u003e2\u003c/sub\u003eO.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThen, the photocatalysts were comprehensively analyzed by STEM-EDS and UV-Vis absorption spectroscopy (Supplementary Figs. 11-13). When Pt was replaced by other noble metals (Rh, Ir, and Au), NPs were loaded on the TiO\u003csub\u003e2\u003c/sub\u003e-h surface (Supplementary Figs. 11). Only the case of Pd demonstrated the deposition of atomically dispersed Pd sites on TiO\u003csub\u003e2\u003c/sub\u003e-h, agreeing with our recent study\u003csup\u003e46\u003c/sup\u003e. On the other hand, when the anatase TiO\u003csub\u003e2\u003c/sub\u003e-h support was substituted with a rutile phase (TiO\u003csub\u003e2\u003c/sub\u003e-R), only Pt NPs (1-10 nm) were observed (Supplementary Fig. 12). Analogously, Pt NPs were detected on other common semiconductors with bandgaps from 2.5 to 3.4 eV (such as\u0026nbsp;Nb\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e5\u003c/sub\u003e,\u0026nbsp;SrTiO\u003csub\u003e3\u003c/sub\u003e, C\u003csub\u003e3\u003c/sub\u003eN\u003csub\u003e4\u003c/sub\u003e, In\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e, BiVO\u003csub\u003e4\u003c/sub\u003e, and BiOCl) after the same photo-deposition procedure (Supplementary Figs. 12 and 13). Based on these characterization results, the decoration of SA sites or NPs via the photo-deposition method highly relied on both the metal elements and the support materials. For closer comparison, we prepared a control sample by depositing Pt NPs (1-5 nm) on TiO\u003csub\u003e2\u003c/sub\u003e-h via high-energetic UV irradiation (Pt\u003csub\u003en\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h, Supplementary Fig. 11A). However, no photocatalytic activity appeared for HIE of arenes in the presence of Pt\u003csub\u003en\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h (Fig. 2d). Consequently, it seemed that noble-metal NPs (Pt, Rh, Ir, and Au) and SA Pd sites were inactive for photocatalytic HIE of arenes in D\u003csub\u003e2\u003c/sub\u003eO. It should be pointed out that SA Pd sites were reported to be highly active for the HIE of N-heteroarenes (e.g., 2-aminopyrimidine) under 410 nm LED irradiation by our group very recently\u003csup\u003e46\u003c/sup\u003e. In comparison, the inert behavior of SA Pd sites for phenols could be ascribed to the side reactions based on IR (Supplementary Fig. 14). Moreover, no deuteration of anilines was also observed in the case of Pd\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h. Because SA Pd sites required the N-heteroarene motif to achieve the configuration alignment between substrate and SA coordination environment for C\u0026ndash;H activation.\u003c/p\u003e\n\u003cp\u003eFurthermore, when the light wavelengths of irradiation were extended to 500-600 nm, no deuteration occurred over the photocatalyst of Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h because of its limited light absorption (500, 530, and 600 nm, Fig. 2e). It should be mentioned that the attachment of arenes with hydroxyl groups (e.g., phenols) onto Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h extended the light absorption tail to 470 nm in contrast to the clean photocatalyst (Supplementary Fig. 6C,D). This behavior mainly originated from the surface complexation between heteroatom-containing substrates (e.g., O, N, or S) and TiO\u003csub\u003e2\u003c/sub\u003e support\u003csup\u003e47\u003c/sup\u003e. Unexpectedly, despite pronounced UV light absorption from this SA photocatalyst, a low D incorporation (56%) was recorded under UV light illumination (365 nm, Fig. 2e). According to the \u003cem\u003ein situ\u003c/em\u003e analysis of gaseous products using mass spectrometry, a tiny amount of D\u003csub\u003e2\u003c/sub\u003e (0.5-1.0 \u0026mu;mol) was detected under UV or 410 nm illumination, while no D\u003csub\u003e2\u003c/sub\u003e was detected under 450 nm LED illumination (Supplementary Fig. 15). Moreover, the control experiments indicated that the introduction of D\u003csub\u003e2\u003c/sub\u003e (~8 \u0026mu;mol) has no negative or positive effect on the HIE reaction for SA Pt sites (Supplementary Table S2, Entry 6). Thus, the activation of C\u0026ndash;H bonds would not involve Pt\u0026ndash;D species in our SA Pt photocatalytic system. Meanwhile, the appearance of Pt clusters was observed for the used Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h sample after UV light irradiation, based on the DRIFTS analysis of CO adsorption and AC HAADF-STEM images (Supplementary Fig. 15D,F). Instead, no changes were exhibited in DRIFTS analysis of CO adsorption for the used photocatalyst after 450 nm LED irradiation. Thus, we reasoned that more energetic UV irradiation caused the aggregation of SA Pt sites into Pt clusters, which consequently led to a low D incorporation under UV light (365 nm).\u003c/p\u003e\n\u003cp\u003eIn addition, up to 97% D incorporation of 4-methoxyphenol was obtained after systematic optimization of the SA photocatalytic system, including parameters of light intensity, irradiation duration, Pt loading, and photocatalyst amount (Supplementary Figs. 16-19). Remarkably, even in the case the substrate concentration was scaled up to 15 folds (from 0.1 to 1.5 mmol in 2 mL D\u003csub\u003e2\u003c/sub\u003eO), high deuteration (95% D incorporation) was maintained by facilely strengthening the light intensity and irradiation time (Supplementary Fig. 20). In terms of reusability, the SA Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h photocatalyst exhibited decent stability, with only a slight decline in D incorporation from 95% to 91% after five consecutive test cycles (Fig. 2f). This minor decrease can be attributed to slight Pt leaching during prolonged stirring in D\u003csub\u003e2\u003c/sub\u003eO, as confirmed by ICP-MS analysis (Supplementary Table 3). Moreover, the nanostructures, crystallinity, and optical properties of the used Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h photocatalyst were well preserved in comparison with the fresh sample via thorough SEM, TEM, STEM-EDS, XRD, UV-Vis DRS, and DRIFTS analysis (Supplementary Figs. 21-26).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMechanistic investigations \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRegarding the roles of photo-generated charges (electrons and holes) and intermediates (e.g., hydroxyl radicals), sacrificial electron acceptors/donors and other additives were introduced for investigations. As shown in Fig. 2g, the addition of sacrificial electron acceptors such as CCl₄ and K₂S₂O₈ prohibited the HIE reaction, indicating the decisive role of photo-generated electrons in the photocatalytic process. Furthermore, TEMPO presented the quenching effect as well, which usually behaved as a radical trap or oxidant\u003csup\u003e48\u003c/sup\u003e. Meanwhile, efficient deuteration was observed after the addition of BHT, suggesting the absence of carbon-centered radicals as intermediates. Accordingly, it is more likely that TEMPO served as the oxidant to eliminate the reductive intermediates, which agreed well with the prohibition from O\u003csub\u003e2\u003c/sub\u003e in air (Supplementary Table 2). On the other hand, the presence of sacrificial electron donors (isopropanol and oxalate) or \u003cem\u003e\u003csup\u003et\u003c/sup\u003e\u003c/em\u003eBuOH demonstrated a minor influence on the D incorporation. These slight impacts implied that the photo-generated holes and reactive oxygen species (ROS, hydroxyl radicals) may play roles in rapid steps of the HIE process, rather than the rate-determining steps. Consequently, the results from scavenger control experiments precluded the radical-controlled mechanism for C\u0026ndash;H activation from holes or ROS.\u003c/p\u003e\n\u003cp\u003eTo further explore the photocatalytic mechanisms, kinetic isotope effect (KIE) experiments were performed. A significantly slower reaction rate emerged when isotope exchange between phenol-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e5\u003c/sub\u003e and H\u003csub\u003e2\u003c/sub\u003eO was run over Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h. Correspondingly, a k\u003csub\u003eH\u003c/sub\u003e/k\u003csub\u003eD\u003c/sub\u003e value of 3.7 pointed to a primary KIE (Fig. 3a), inferring that the cleavage of C(\u003cem\u003esp\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e)\u0026ndash;H bonds rather than D\u003csub\u003e2\u003c/sub\u003eO activation aligned with the rate-determining step\u003csup\u003e49\u003c/sup\u003e. Additionally, the switch-on/off light irradiation test demonstrated that continuous photon input was essential to sustain the HIE process (Fig. 3b). It suggested that intermediate redox active species were consumed during one round of HIE reaction and then regenerated by light illumination to initiate the next round. Besides, the hot filtration test also confirmed the heterogeneous nature of our SA photocatalytic system (Supplementary Fig. 27), ruling out the active species dissolved in D\u003csub\u003e2\u003c/sub\u003eO.\u003c/p\u003e\n\u003cp\u003eTo reveal the active sites of the SA photocatalyst Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h, CO as a probe molecule was adsorbed in a controlled manner with the analysis of diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). There was only one dominant IR band at 2087 cm\u003csup\u003e-1\u003c/sup\u003e ascribed to the linear CO adsorption at SA Pt\u003csup\u003e\u0026delta;+\u003c/sup\u003e sites (Fig. 3c)\u003csup\u003e50-52\u003c/sup\u003e.\u0026nbsp;In contrast, the bands at 2050 and 1830 cm\u003csup\u003e-1\u003c/sup\u003e corresponding to the linear and multiple-bonded CO adsorption at Pt NPs were observed for the Pt\u003csub\u003en\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e sample (Supplementary Fig. 28)\u003csup\u003e52\u003c/sup\u003e. Typically, higher oxidation state of SA Pt sites offered the less redshifted CO absorption bands in contrast to the free CO gas (2143 cm\u003csup\u003e-1\u003c/sup\u003e) due to declined Pt d-electron back-donation to the CO \u0026pi;* antibonding orbital (e.g., ~2128 cm\u003csup\u003e-1\u003c/sup\u003e for SA Pt\u003csup\u003e4+\u003c/sup\u003e and ~2062 cm\u003csup\u003e-1\u003c/sup\u003e for SA Pt\u003csup\u003e0\u003c/sup\u003e in alloy)\u003csup\u003e53-55\u003c/sup\u003e. Thus, the IR band position of CO adsorption at Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h suggested that the oxidation state of Pt\u003csup\u003e\u0026delta;+\u003c/sup\u003e was between zero and\u0026nbsp;4+, consistent with the XANES analysis. Notably, the photocatalytic HIE reaction was quenched when Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h was adsorbed with CO (Fig. 3d). This stark contrast further indicated SA Pt\u003csup\u003e\u0026delta;+\u003c/sup\u003e as active sites in HIE reactions.\u003c/p\u003e\n\u003cp\u003eTo further track the dynamic changes of SA photocatalysts and substrate molecules during the HIE process, \u003cem\u003ein situ\u003c/em\u003e DRIFTS experiments were conducted (Supplementary Fig. 29). Firstly, the coordination between Pt and phenol substrate was evidenced by a red shift for the C\u0026ndash;O stretching vibration (shifted from 1280 to 1264 cm\u003csup\u003e-1\u003c/sup\u003e, Supplementary Fig. 30). Then, a prominent red shift in the CO adsorption IR band (shifted from 2087 to 2075 cm\u003csup\u003e-1\u003c/sup\u003e) appeared under light illumination (Fig. 3e), corresponding to CO interaction with SA Pt sites. This change implied that partially reduced SA Pt\u003csup\u003e\u0026delta;*\u003c/sup\u003e sites with richer electrons were formed when the photo-generated electrons diffused from the conduction band (CB) level of TiO\u003csub\u003e2\u003c/sub\u003e to Pt\u003csup\u003e\u0026delta;+\u003c/sup\u003e sites during light irradiation\u003csup\u003e56\u003c/sup\u003e. In analogy to the photo-induced ligand-to-metal charge transfer (LMCT) process\u003csup\u003e57,58\u003c/sup\u003e, the oxygen sites of Pt\u0026ndash;O bonds in the SA photocatalyst may simultaneously experience a lower electron-density state due to dynamic charge transfer\u003csup\u003e59,60\u003c/sup\u003e. It is related to the fact that O 2p orbitals predominantly contribute to the valence band (VB) of TiO\u003csub\u003e2\u003c/sub\u003e\u003csup\u003e61\u003c/sup\u003e. In addition, the control experiment showed that the presence of H\u003csup\u003e+\u003c/sup\u003e or OH\u003csup\u003e-\u0026nbsp;\u003c/sup\u003estrongly prohibited the HIE reaction (supplementary Table 4), which may originate from the breakage of active\u0026nbsp;Pt\u0026ndash;O coordinate bonds. The results also ruled out the electrophilic substitution mechanism catalyzed by acid for HIE in our system. Furthermore, the light irradiation of\u0026nbsp;phenol\u0026nbsp;adsorbed on\u0026nbsp;Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h\u0026nbsp;weakened the absorption band intensity at 3070\u0026thinsp;cm\u003csup\u003e-1\u003c/sup\u003e (u\u003csub\u003es\u003c/sub\u003e(C\u0026ndash;H)) (Fig. 3f), which corresponded to aromatic C(\u003cem\u003esp\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e)\u0026ndash;H bonds. Switching the light off could recover the IR band intensity of\u0026nbsp;u\u003csub\u003es\u003c/sub\u003e(C\u0026ndash;H), suggesting the reversible formation of transition states triggered by light. Accordingly, the activation of C\u0026ndash;H bonds may undergo an electrophilic platinization step\u0026nbsp;mediated by active\u0026nbsp;Pt\u0026ndash;O coordinate bonds with modulated charge under light excitation\u003csup\u003e62,63\u003c/sup\u003e. After the introduction of D\u003csub\u003e2\u003c/sub\u003eO into the DRIFTS cell, the IR band at 3070 cm\u003csup\u003e-1\u003c/sup\u003e gradually declined under light irradiation due to the H/D exchange step (Fig. 3f and Supplementary Fig. 31A). However, due to the overlap from CO\u003csub\u003e2\u003c/sub\u003e and D\u003csub\u003e2\u003c/sub\u003eO signals, the IR bands corresponding to C\u0026ndash;D bonds could not be directly observed\u0026nbsp;(Supplementary Figs. 31-33).\u0026nbsp;Instead, no changes occurred under light irradiation for the case of Pt\u003csub\u003en\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h with phenol and D\u003csub\u003e2\u003c/sub\u003eO adsorbed (Supplementary Fig. 31B).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBased on the above mechanistic studies\u0026nbsp;and previous reports\u003csup\u003e62-65\u003c/sup\u003e, a plausible catalytic cycle for the HIE of arenes in D\u003csub\u003e2\u003c/sub\u003eO over SA photocatalyst Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h was proposed (Fig. 3g). Firstly, the aromatic substrates were attached to SA Pt\u003csup\u003e\u0026delta;+\u003c/sup\u003e sites via coordination of hydroxyl or amino groups. Upon visible-light excitation, photo-generated electrons were transferred from the CB level of TiO\u003csub\u003e2\u003c/sub\u003e to the SA Pt centers, regulating the charge state of Pt\u0026ndash;O coordinate bonds. Later, the excited Pt\u0026ndash;O sites facilitated the activation of nearby aromatic C(\u003cem\u003esp\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e)\u0026ndash;H bonds via a possible electrophilic platinization pathway. Subsequently, the proposed four-membered transition state underwent an H/D exchange step with D\u003csub\u003e2\u003c/sub\u003eO, accompanied by the generation of HOD. Finally, the desired deuterated arenes were yielded with the release of Pt\u0026ndash;O sites, which could be tuned back to ground state by photo-generated holes or hydroxyl radicals (Supplementary Fig. 34).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSubstrate scope tests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo assess the substrate scope and functional group tolerance of the SA photocatalytic system for HIE reactions, diverse electron-rich (hetero)arenes were examined\u0026nbsp;(Figs. 4 and 5).\u0026nbsp;First, various phenols and anilines bearing \u003cem\u003eortho-\u003c/em\u003e, \u003cem\u003emeta-\u003c/em\u003e, or \u003cem\u003epara-\u0026nbsp;\u003c/em\u003emethyl/methoxy/ethoxy/ethyl substituents underwent efficient HIE with satisfactory D incorporation\u0026nbsp;(\u003cstrong\u003e1b\u003c/strong\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003cstrong\u003e3b\u003c/strong\u003e).\u0026nbsp;In most cases, the C(\u003cem\u003esp\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e)\u0026ndash;H bonds at the \u003cem\u003eortho\u003c/em\u003e and \u003cem\u003epara\u003c/em\u003e positions of hydroxyl or amino groups were well labeled (D incorporation \u0026gt;80%), due to the chelation effect from directing groups of\u0026nbsp;\u0026ndash;OH and\u0026nbsp;\u0026ndash;NH\u003csub\u003e2\u003c/sub\u003e.\u0026nbsp;In contrast, the presence of methyl/methoxy groups in the \u003cem\u003emeta\u003c/em\u003e position of the directing groups inhibits the\u0026nbsp;D\u0026nbsp;incorporation of its \u003cem\u003eortho\u003c/em\u003e and \u003cem\u003epara\u003c/em\u003e positions (\u003cstrong\u003e3b\u003c/strong\u003e, \u003cstrong\u003e6b\u003c/strong\u003e,\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003cstrong\u003e1b\u003c/strong\u003e,\u003cstrong\u003e\u0026nbsp;12b\u003c/strong\u003e,\u003cstrong\u003e\u0026nbsp;15b\u003c/strong\u003e,\u003cstrong\u003e\u0026nbsp;20b\u003c/strong\u003e,\u003cstrong\u003e\u0026nbsp;22b\u003c/strong\u003e), which may be related to the steric hindrance of the substituents.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNext, we examined substrates containing two hydroxyl or amino groups, all of which could be\u0026nbsp;deuterated\u0026nbsp;with excellent D incorporation (\u0026ge;99% for\u0026nbsp;\u003cstrong\u003e14b\u003c/strong\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003cstrong\u003e18b\u003c/strong\u003e)\u0026nbsp;at the \u003cem\u003eortho\u003c/em\u003e or \u003cem\u003epara\u003c/em\u003e positions of functional groups.\u0026nbsp;Halogenated phenols and anilines, including\u0026nbsp;\u0026ndash;F (\u003cstrong\u003e19b\u003c/strong\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003cstrong\u003e20b\u003c/strong\u003e, \u003cstrong\u003e23b\u003c/strong\u003e), \u0026ndash;Cl (\u003cstrong\u003e21b\u003c/strong\u003e, \u003cstrong\u003e24b\u003c/strong\u003e), and \u0026ndash;Br (\u003cstrong\u003e22b\u003c/strong\u003e), were well tolerated in our SA photocatalytic system. These substrates afforded decent D incorporation at the \u003cem\u003eortho\u0026nbsp;\u003c/em\u003epositions of hydroxyl or amino groups (\u0026ge;94%), highlighting their potential for further derivatization. Besides, for the case of halogen groups located at the \u003cem\u003eortho\u003c/em\u003e positions of hydroxyl groups, high-level deuteration (\u0026ge;91%) was also observed at the \u003cem\u003emeta\u0026nbsp;\u003c/em\u003epositions of \u0026ndash;OH (\u003cstrong\u003e20b\u003c/strong\u003e, \u003cstrong\u003e22b\u003c/strong\u003e). It is worth noting that, when the \u003cem\u003emeta\u003c/em\u003e position of the directing group was replaced by \u0026ndash;Cl (\u003cstrong\u003e21b\u003c/strong\u003e, \u003cstrong\u003e24b\u003c/strong\u003e), suppressed D incorporation at the \u003cem\u003eortho\u003c/em\u003e position of directing groups appeared. It may be due to the electron-withdrawing effect of halogen atoms. In contrast, for substrate \u003cstrong\u003e19b,\u003c/strong\u003e where the \u0026ndash;F is located at the \u003cem\u003emeta\u003c/em\u003e positions of hydroxyl groups, the deuteration at the \u003cem\u003eortho\u0026nbsp;\u003c/em\u003epositions of \u0026ndash;OH was not suppressed due to the possible \u0026ldquo;\u003cem\u003eortho\u003c/em\u003e-fluorine effect\u0026rdquo;\u003csup\u003e66\u003c/sup\u003e. Other functional groups, such as\u0026nbsp;\u0026ndash;CF\u003csub\u003e3\u003c/sub\u003e (\u003cstrong\u003e25b\u003c/strong\u003e),\u0026nbsp;\u0026ndash;Ph (\u003cstrong\u003e26b\u003c/strong\u003e),\u0026nbsp;and morpholino (\u003cstrong\u003e27b-29b\u003c/strong\u003e), were also highly compatible for HIE reactions with D incorporation varying from 80 to 99% at the \u003cem\u003eortho\u003c/em\u003e positions of\u0026nbsp;\u0026ndash;OH or\u0026nbsp;\u0026ndash;NH\u003csub\u003e2\u003c/sub\u003e. However, medium D incorporation of 45% appeared for the substituent of linear alkyl alcohol\u0026nbsp;(\u003cstrong\u003e30b\u003c/strong\u003e). Notably, a fused aromatic amine delivered the corresponding deuterated product with high D incorporation\u0026nbsp;(85%, \u003cstrong\u003e31b\u003c/strong\u003e). Moreover, \u003cem\u003eN\u003c/em\u003e-alkyl substituted arenes\u0026nbsp;could be\u0026nbsp;labeled\u0026nbsp;with deuterium\u0026nbsp;as well (\u003cstrong\u003e32b\u003c/strong\u003e and \u003cstrong\u003e33b\u003c/strong\u003e). Additionally,\u0026nbsp;electron-rich 1,3,5-trimethoxybenzene was tolerated by yielding \u003cstrong\u003e34b\u003c/strong\u003e with D incorporation of 64%.\u003c/p\u003e\n\u003cp\u003eOn the other hand, neither arenes substituted with electron-withdrawing groups (\u0026ndash;COOH/CF\u003csub\u003e3\u003c/sub\u003e/CN) nor electron-deficient N-heteroarenes were compatible with the SA photocatalytic system (Supplementary Table 2). It contradicted the substrate scope of the oxidative addition mechanism proposed in our recent study, which could cover the electron-deficient C\u0026ndash;H bonds\u003csup\u003e46\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e67\u003c/sup\u003e. Therefore, the requirement of electron-rich substrates favored the proposed electrophilic platinization mechanism.\u0026nbsp;Delightedly,\u0026nbsp;the\u0026nbsp;deuteration of\u0026nbsp;some\u0026nbsp;N-heteroarenes\u0026nbsp;in the presence of hydroxyl or amino groups,\u0026nbsp;such as pyridines and quinolines\u0026nbsp;(\u003cstrong\u003e35b-38b\u003c/strong\u003e), was\u0026nbsp;successfully driven with D incorporation ranging from 79% to 99%.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFurthermore, the late-stage deuteration of representative natural products and drugs was investigated over the Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h photocatalyst (Fig. 5). Natural products, for instance, guaiacol, olivetol, cianidanol, resveratrol, phloretin, arbutin, and NSC 87909, were labeled dominantly at the \u003cem\u003eortho\u0026nbsp;\u003c/em\u003epositions of \u0026ndash;OH or \u0026ndash;NH\u003csub\u003e2\u003c/sub\u003e groups with satisfactory D incorporation (\u0026ge;91% for \u003cstrong\u003e39b-43b\u0026nbsp;\u003c/strong\u003eand \u003cstrong\u003e45b\u003c/strong\u003e; 76% for \u003cstrong\u003e44b\u003c/strong\u003e). Several commercial small-molecule drugs (e.g., aminoglutethimide, benzocaine, procaine, 5-HIAA, and tacrine), used to treat cancer/vascular/heart/alzheimer diseases and viral/bacterial infections, were efficiently deuterated via SA photocatalysis (D incorporation of 78-96% for \u003cstrong\u003e46b-50b\u003c/strong\u003e). Overall, 86% of tested substrates (including \u003cstrong\u003e1a\u003c/strong\u003e-\u003cstrong\u003e29a\u003c/strong\u003e, \u003cstrong\u003e31a\u003c/strong\u003e, \u003cstrong\u003e35a\u003c/strong\u003e-\u003cstrong\u003e36a\u003c/strong\u003e, \u003cstrong\u003e38a\u003c/strong\u003e, \u003cstrong\u003e39a\u003c/strong\u003e-\u003cstrong\u003e43a\u003c/strong\u003e, \u003cstrong\u003e45a\u003c/strong\u003e-\u003cstrong\u003e47a\u003c/strong\u003e,\u003cstrong\u003e\u0026nbsp;49a\u003c/strong\u003e-\u003cstrong\u003e50a\u003c/strong\u003e) offered satisfactory D incorporation (\u0026gt;80%), demonstrating the broad substrate scope of Pt-based SA photocatalysis. In addition, slight deuteration was also observed for relatively labile C(\u003cem\u003esp\u003c/em\u003e\u003csup\u003e3\u003c/sup\u003e)\u0026ndash;H bonds at the benzylic sites or \u003cem\u003eortho\u003c/em\u003e positions to carbonyl groups (e.g., \u003cstrong\u003e13b\u003c/strong\u003e, \u003cstrong\u003e43b\u003c/strong\u003e, \u003cstrong\u003e46b\u003c/strong\u003e, \u003cstrong\u003e50b\u003c/strong\u003e).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGram-scale synthesis and synthetic applications\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo evaluate the practicability of this SA photocatalytic system, gram-scale synthesis experiments were performed. The reactant with amount scaled up to 1000 times (100 mmol, 12 g) was labeled in a homemade glass photoreactor (250 mL, Fig. 6a) charged with 5 g SA photocatalysts and 180 mL D\u003csub\u003e2\u003c/sub\u003eO. After 48 h irradiation (410 nm LED strips) in 1 bar Ar atmosphere, up to 99% D incorporation was achieved without external heating. It should be mentioned that the temperature of suspensions in the photoreactor gradually rose from r.t. to ~65 \u003csup\u003eo\u003c/sup\u003eC due to the visible irradiation for a long time. After facile photocatalyst separation and solvent evaporation, a highly pure deuterated\u0026nbsp;product\u0026nbsp;(2,6-dimethylaniline-3,4,5-\u003cem\u003ed\u003c/em\u003e\u003csub\u003e3\u003c/sub\u003e) was obtained with an isolation yield of 97% (11.98 g; \u003csup\u003e1\u003c/sup\u003eH NMR-based purity \u0026gt;99%). Considering the successful reproducible deuteration of N-heteroarenes using a home-made photoreactor bed equipped with dozens of glass reactors in our laboratory recently\u003csup\u003e46\u003c/sup\u003e, we believe this SA photocatalytic system can be easily scaled up to kilogram-level synthesis of deuterated arenes.\u003c/p\u003e\n\u003cp\u003eFurthermore, the deuterated anilines can be efficiently converted to\u0026nbsp;\u003cem\u003eN\u003c/em\u003e-acylated\u0026nbsp;compounds with high-level D labeling, whose direct late-stage deuteration is usually challenging (D incorporation \u0026lt;15%).\u0026nbsp;For instance,\u0026nbsp;deuterated lidocaine \u003cstrong\u003e51b\u003c/strong\u003e, nefiracetam \u003cstrong\u003e52b\u003c/strong\u003e, herbicides chlortoluron \u003cstrong\u003e53b,\u003c/strong\u003e and fluometuron \u003cstrong\u003e54b\u003c/strong\u003e were conveniently synthesized with corresponding deuterated aniline precursors (Fig. 6b). It is worth noting that nefiracetam has entered phase III clinical trials for the treatment of Alzheimer\u0026rsquo;s disease. These results demonstrated that deuterated aniline products from SA photocatalytic HIE reactions would have potential applications in the synthesis of D-labeling pharmaceuticals.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn summary, we establish a single-atom (SA) photocatalytic mechanism\u0026nbsp;for hydrogen-deuterium exchange of electron-rich arenes using D\u003csub\u003e2\u003c/sub\u003eO under visible light at ambient temperature and inert atmosphere; nanoparticle (NP) sites were ineffective. The Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e SA photocatalyst enables late-stage deuteration of highly functionalized natural products and pharmaceuticals, displays good reusability, and tolerates a broad substrate scope (54 electron-rich arenes). The developed photocatalytic deuteration method is mild, scalable (gram-scale: 11.98 g, 100 mmol), and operationally simple, demonstrating the practicability of SA photocatalysis. We anticipate this approach will provide an economical, selective, and robust route for preparing deuterated small-molecule drugs and functional materials.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eCatalyst preparation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFor the preparation of SA photocatalyst \u003cstrong\u003ePt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h\u003c/strong\u003e: Firstly, as-prepared 500 mg TiO\u003csub\u003e2\u003c/sub\u003e-h and 7.35 mg H\u003csub\u003e2\u003c/sub\u003ePtCl\u003csub\u003e6\u003c/sub\u003e\u0026middot;xH\u003csub\u003e2\u003c/sub\u003eO were added to a 20 mL water-isopropanol solution (volume ratio of deionized water : \u003cem\u003ei\u003c/em\u003e-PrOH was 5 : 1) under stirring for 30 min. Then the mixture was irradiated with a 410 nm LED lamp under Ar atmosphere at room temperature. After 10 h irradiation, the light grey solids were collected via centrifugation and further washed with water. After drying in a vacuum oven, the sample \u003cstrong\u003ePt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h\u003c/strong\u003e was obtained, which was directly used for characterizations and photocatalytic tests.\u0026nbsp;The loading amount of Pt was tuned by introducing different amounts of H\u003csub\u003e2\u003c/sub\u003ePtCl\u003csub\u003e6\u003c/sub\u003e\u0026middot;xH\u003csub\u003e2\u003c/sub\u003eO.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePhotocatalytic HIE reaction\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn a 7 mL glass vial with a fitted magnetic stirring bar,\u0026nbsp;Pt\u003csub\u003e1\u003c/sub\u003e/TiO\u003csub\u003e2\u003c/sub\u003e-h (50 mg) and substrate (0.1 mmol) were added. After adding the solvent\u0026nbsp;D\u003csub\u003e2\u003c/sub\u003eO\u0026nbsp;(2.0 mL), the vial was placed into a 20 mL stainless-steel autoclave with\u0026nbsp;a quartz\u0026nbsp;window. The autoclave was\u0026nbsp;purged\u0026nbsp;with Ar at 10 bar and\u0026nbsp;then\u0026nbsp;degassed to the ambient pressure\u0026nbsp;(1 bar). It was repeated\u0026nbsp;6 times\u0026nbsp;to remove O\u003csub\u003e2\u003c/sub\u003e maximally.\u0026nbsp;Next, it was\u0026nbsp;seated\u0026nbsp;into an aluminum\u0026nbsp;cooling jacket\u0026nbsp;with water circulating\u0026nbsp;from the chiller\u0026nbsp;to keep the room temperature\u0026nbsp;(25 \u003csup\u003eo\u003c/sup\u003eC).\u0026nbsp;Later, the monochromatic LED lamp (light wavelength of 365 nm, 410 nm, 450 nm, 500 nm, 530 nm, or 600 nm) was placed on top of the autoclave and irradiated the suspension through the quartz window for 6 h. After the photocatalytic HIE reaction, the suspension was transferred from the autoclave to a centrifuge tube and then centrifuged to obtain the supernatant. The deuterium incorporation (D incorporation) and selectivity of products can be obtained by \u003csup\u003e1\u003c/sup\u003eH NMR analysis of the supernatant\u0026nbsp;(see below for calculation\u0026nbsp;equations). For the product isolation, after the removal of all D\u003csub\u003e2\u003c/sub\u003eO in vacuo, the desired products were obtained.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cimg 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\" 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\" alt=\"image\" width=\"1171\" height=\"87\"\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the data that support the findings of this study are available within the main text and the Supplementary Information. Details about materials, photocatalyst preparation, experimental procedures, characterization data, and NMR spectra are available in the Supplementary Information.\u0026nbsp;\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe appreciate the financial support from the National Natural Science Foundation of China (22479141), Gusu Innovation and Entrepreneurship Leading Talents Program (ZXL2022468), Youth Fund Project of Natural Science Foundation of Jiangsu Province (BK20220287), Science and Technology Program of Suzhou (SWY2022003), and Jiangxi Provincial Double Thousand Plan-Leading Innovative Talents Program (No. jxsq2023101011). We thank\u0026nbsp;professional service from characterization platforms. The characterization work was partially conducted at the Instruments Center for Physical Science, University of Science and Technology of China, and Physical and Chemical Analysis Center at Suzhou Institute for Advanced Research (University of Science and Technology of China). We thank the BL14W1 XAFS beamline of the Shanghai Synchrotron Radiation Facility (SSRF) for providing beamtime.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eY.-T.D. supervised the project and conceived the research. J.X. and Y.-T.D. designed the experiments. J.X., X.-Y.W., R.C., and Y.-T.D. performed experiments and characterizations. J.X. and Y.-T.D. interpreted the data and generated figures. D.Z., X.-Z.S., H.C., W.-W.L., T. P., K.M.L., and F.B. provided valuable suggestions throughout this study. J.X. wrote the initial draft and Y.-T.D. finalized it. All authors contributed to revising the paper.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003eAdditional Information\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary information\u003c/strong\u003e is available for this paper.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorrespondence and requests for materials\u003c/strong\u003e should be addressed to Yi-Tao Dai.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eReprints and permissions information\u003c/strong\u003e is available at www.nature.com/reprints.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSimmons, E. M. \u0026amp; Hartwig, J. F. On the Interpretation of Deuterium Kinetic Isotope Effects in C\u0026minus;H Bond Functionalizations by Transition-Metal Complexes. \u003cem\u003eAngew. Chem. Int. 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Transition-Metal-Catalyzed Deuteration via Hydrogen Isotope Exchange. \u003cem\u003eSynOpen\u003c/em\u003e \u003cstrong\u003e8\u003c/strong\u003e, 328\u0026ndash;359 (2024).\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-9071548/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9071548/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Deuterated arenes play crucial roles in medicinal chemistry and materials science (e.g., psychotropic drugs and deuterated OLEDs). However, the desired late-stage deuteration via conventional hydrogen isotope exchange (HIE) methods always demands expensive isotopic reagents (e.g., D2, C6D6, or C2H5OD), metal complex catalysts, or harsh conditions (≥120 oC, 20 bar H2). Here, we report a single-atom photocatalytic strategy for efficient HIE of electron-rich arenes using D2O as the deuterium source. Under visible light irradiation at ambient temperature in an inert atmosphere, a single-atom photocatalyst (Pt1/TiO2) afforded high deuterium incorporation across 54 electron-rich arene substrates. The protocol is mild, sustainable, and scalable: gram-scale synthesis of deuterated arenes (11.98 g, 100 mmol) was successfully realized. Mechanistic studies indicate that the catalytically active sites are primarily Pt–O coordinate bonds, whose light-modulated charge distribution facilitates a possible electrophilic platinization pathway for C–H activation before H/D exchange.","manuscriptTitle":"Late-stage Deuteration of Arenes in D2O Exclusively Driven by Single-atom Pt Sites under Visible Light","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-13 06:58:42","doi":"10.21203/rs.3.rs-9071548/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":"730c4a25-1969-4557-9c88-3ec38f5cda8c","owner":[],"postedDate":"March 13th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":64361115,"name":"Physical sciences/Chemistry/Catalysis/Photocatalysis"},{"id":64361116,"name":"Physical sciences/Energy science and technology/Renewable energy/Solar energy"},{"id":64361117,"name":"Physical sciences/Chemistry/Organic chemistry/Synthetic chemistry methodology"}],"tags":[],"updatedAt":"2026-03-13T06:58:42+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-13 06:58:42","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9071548","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9071548","identity":"rs-9071548","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}