In Situ Ozone Generated on the Surface of Water Microdroplets Mediates Selective Aromatic Oxidation

In Situ Ozone Generated on the Surface of Water Microdroplets Mediates Selective Aromatic Oxidation | 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 In Situ Ozone Generated on the Surface of Water Microdroplets Mediates Selective Aromatic Oxidation Kaiyu Geng, Lian Xue, Boyu Zhu, Peng Zheng, Jiao Geng, Xingbang Hu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7417699/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Microdroplet-mediated ozone (O 3 ) oxidation offers an alternative route for organic transformations compared to the commonly studied hydrogen peroxide (H 2 O 2 )-dominated systems. Here, we demonstrate efficient O 3 oxidation at the microdroplet interface, achieving selective conversion of naphthalene (NA) to dimethyl phthalate (DP) with 11.6% yield. When an aqueous methanol solution of NA is atomized into ~ 7.0 µm microdroplets under O 2 atmosphere, the system operates without external catalysts or oxidants while outperforming typical microdroplet oxidation methods. The generation of O 3 is unequivocally confirmed by indigo disulfonate spectrophotometry and high-resolution mass spectrometry. Combined with radical trapping experiments and DFT calculations, these results establish a surface-activated O 3 -mediated oxidation mechanism. Key intermediates were further confirmed by mass spectrometry. This work not only advances microdroplet O 3 chemistry beyond analytical detection to preparative synthesis, but also provides new insights into interfacial oxidative processes. Physical sciences/Chemistry/Green chemistry Physical sciences/Nanoscience and technology/Other nanotechnology microdroplets ozone naphthalene oxidation mechanism Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 INTRODUCTION In recent years, microdroplet chemistry, realized by atomizing aqueous solutions into micron-sized droplets, has emerged as a powerful platform for accelerating chemical reactions under ambient and mild conditions 1–3 . Microdroplets possess physicochemical properties distinct from bulk phases, including high surface-to-volume ratios 4 , partial solvation 5 , strong interfacial electric fields 6 , which together enable unique reactivities that are often inaccessible in bulk. Among these, oxidation reactions in aqueous microdroplets have drawn increasing attention, particularly those mediated by reactive oxygen species (ROS) 7–13 . To date, most studies on microdroplet oxidation have focused on the generation of hydrogen peroxide (H 2 O 2 ) at the air-water interface to drive redox processes (Scheme 1a) 14–18 . It has been proposed that hydroxide ions at the microdroplet surface undergo decomposition into hydroxyl radicals and electrons, leading to the in-situ formation of H 2 O 2 12, 14, 19–27 and enabling oxidation of solutes inside the microdroplet 23, 28–31 . Various H 2 O 2 -mediated oxidative reactions have been reported. For example, Zare and co-workers demonstrated the oxidation of methane to methanol using water microdroplets 23 . Rao et al. further found that thiols and thioethers accumulate at the interface and proposed that their spontaneous oxidation is driven by highly reactive radicals formed at or near the microdroplet surface 32 . In our previous work, we also showed that styrene can be efficiently oxidized to styrene oxide in microdroplets without the use of any catalysts 24 . Beyond H 2 O 2 -mediated pathways, recent studies have demonstrated that ozone (O 3 ) can also be generated at the interface of water microdroplets 8, 33, 34 . Banerjee and colleagues detected O 3 radical cations (m/z = 48) at the microdroplet interface using mass spectrometry, establishing the feasibility of ozone generation in aqueous aerosols 33 . Also, Zare et al. introduced the concept of “microlightning” to describe transient electrical discharge events at the microdroplet interface that generate reactive oxidants, including O 3 8 . While these pioneering studies significantly advanced our mechanistic understanding, they primarily focused on detecting oxidants such as O 3 or dioxygen-derived species using mass spectrometry or isotopic labeling. Based on these foundational studies, Meng’s group showed that pure water microdroplets can induce triple bond cleavage in alkynes via microlightning and in-situ ozone generation 34 , although the reported product yields remained extremely low, often detectable only by high-sensitivity methods. Motivated by these advances, we sought to explore whether microdroplet-generated O 3 could be harnessed to perform synthetically useful bond transformations, which is a key step for the practical application of microdroplet chemistry. Here, we report a catalyst-free transformation of naphthalene (NA) to dimethyl phthalate (DP) under ambient conditions (Scheme 1b). The reaction proceeds efficiently in a recirculating ultrasonic atomization system under an O 2 atmosphere and is driven by oxygen activation at the microdroplet interface. Notably, the oxidation yields a single major product (DP) with a measurable yield of 11.6%, which is readily detected by both GC-MS and NMR, highlighting the synthetic practicality of this microdroplet-based method. Direct evidence for ozone formation at the microdroplet interface was obtained via indigo disulfonate (IDS) colorimetry and high-resolution mass spectrometry. Furthermore, density functional theory (DFT) calculations indicate that the ozone-mediated oxidation pathway at the microdroplet interface exhibits significantly reduced energy barriers, further supporting the catalytic potential of interfacial ozone. In summary, this study builds upon previous reports of microdroplet-generated O 3 and uniquely demonstrates its synthetic utility in performing selective, preparative-scale oxidations. By expanding the oxidative repertoire of microdroplet chemistry beyond H 2 O 2 and into O 3 -mediated transformations, our findings offer new insights into interfacial redox reactivity and present a promising strategy for catalyst-free, green oxidation processes under mild conditions. RESULTS AND DISCUSSION Microdroplet oxidation has frequently been associated with the generation of hydrogen peroxide (H 2 O 2 ), which is widely considered as a key oxidant in such systems. Most previous studies have focused on the oxidative behavior of H 2 O 2 in microdroplet environments 12, 14-27, 32, 35-39 . However, while investigating naphthalene (NA) oxidation under microdroplet conditions, we observed a reaction pathway that could not be explained by the conventional H 2 O 2 mechanism. The experiments began with the preparation of a homogeneous methanol-water solution of NA ( Figure S1a ), which was then atomized into microdroplets using a 20W ultrasonic nebulizer ( Figure S1b ). The microdroplets had an average diameter of approximately 7.0 μm, as determined by high-speed camera system and a microscopic measurement system ( Figure 1 ) 29, 31, 40 . After continuous spraying for 4 hours under an air atmosphere, gas chromatography-mass spectrometry (GC-MS) analysis revealed the formation of dimethyl phthalate (DP) as the primary oxidation product. As shown in Figure 2a , NA exhibited a retention time of approximately 7.1 min, with a mass-to-charge ratio (m/z) of 128.2 ( Figure 2c ), while DP had a retention time of about 9.0 min, with an m/z of 194.0 ( Figure 2d ). These results confirmed the conversion of NA to DP. Being different from most of the previous microdroplet oxidation reactions which only gave trace amount of product 16, 35, 36, 41, 42 , the product amount obtained in the circulating spray ultrasonic atomization microdroplet system was high enough to be detected by nuclear magnetic resonance (NMR) and the NMR result can further support the formation of dimethyl phthalate ( Figures 2e, S4 and S7 ). To investigate whether this reaction proceeded via an H 2 O 2 -dependent pathway, we conducted a series of control experiments comparing bulk and microdroplet environments under identical conditions. Notably, no detectable DP formed in bulk solutions exposed to air, while NA was efficiently converted to DP in microdroplets ( Figure 3 ). This stark contrast highlights the crucial role of the microdroplet environment in enabling oxidation, likely due to the high interfacial electric field at the microdroplet surface 25-27, 43-45 . The nature of this oxidation process became particularly intriguing when we modified the reaction conditions. Under a N 2 atmosphere, DP formation was completely suppressed ( Figure 2b and 3a ), whereas in pure O 2 , the DP yield increased significantly from 9.4% (under air) to 11.6% ( Figure 3b ), indicating that the oxidation process directly depended on molecular oxygen. However, the increase in DP yield with higher O 2 concentration alone does not directly prove that H 2 O 2 is the primary oxidant, as other reactive oxygen species (ROS) could also contribute to the oxidation. To further probe the mechanism, we added H 2 O 2 directly to the microdroplet system under a N 2 atmosphere. Based on previous reports, it is generally believed that hydroxyl radicals (·OH) form under high electric fields and lead to the generation of H 2 O 2 , which then participates in oxidation reactions 12, 14, 19-24, 46, 47 . However, in our experiment, despite the presence of H 2 O 2 , we observed almost no conversion of NA into DP ( Figure 3a ). This finding strongly suggests that the oxidation process does not follow the conventional pathway involving H 2 O 2 but instead proceeds through an alternative oxidation mechanism. In addition, in order to exclude the possibility that metal parts in the spray device may participate in the reaction or cause the same background peak due to corrosion, we have designed and adopted an inverted spray device (as shown in the Figure S8 ), so that the reaction liquid does not contact with the metal throughout the process. The experimental results showed that the same DP product was still observed in GC-MS detection, indicating that the metal components did not have a significant impact on the reaction process. Given that the reaction from NA to DP involves the cleavage of carbon-carbon double bonds and the formation of carbonyl groups, which is the characteristic of ozonolysis, this led us to start considering the possibility of O 3 involvement in the oxidation process. O 3 is a well-known oxidant that reacts efficiently with unsaturated compounds, but its generation typically requires high-voltage discharges (10-20 kV) to ionize O 2 , corresponding to electric field strengths of 10 6 -10 7 V/m 48-52 . However, the electric field at the microdroplet interface can reach up to 10 9 V/m 43-45 , far exceeding the threshold required for O 3 formation. Therefore, we hypothesize that the ultra-high electric field at the microdroplet interface can directly ionize oxygen (O 2 ), forming oxygen atoms (O), which then combine with O 2 to generate O 3 , thereby driving the oxidation of NA. To verify the presence of O 3 in the microdroplet environment, we employed indigo disulfonate sodium (IDS) as a colorimetric probe. O 3 oxidizes the carbon-carbon double bonds in IDS, disrupting its conjugated structure and leading to decolorization ( Figure 4a ) 53, 54 . Such ozone-indigo disulphonate spectrophotometry experiment has been established as a standardized method for detecting the presence of ozone 54, 55 . To further confirm the response characteristics of IDS to O 3 , an experiment was conducted by introducing O 3 into the IDS solution. The results showed that after contact with O 3 , the characteristic absorption peak at 610 nm of IDS rapidly disappeared and dropped to the background level within only 0.1 hour ( Figure 4b ). This phenomenon verifies the high sensitivity of this method, further supporting its applicability as an O 3 probe. When applied to the microdroplet system under an O 2 atmosphere, ultraviolet-visible spectroscopy (UV-Vis) show that the characteristic absorption peak of IDS at 610 nm decreases rapidly with reaction time 55, 56 , with noticeable decolorization occurring within about 1.25 hours, turning the solution from deep blue to almost colorless ( Figure 4a ) 57 . In contrast, under the same concentration of H 2 O 2 , even when the reaction time is extended to 10 hours, the change in absorption intensity is minimal, with almost no noticeable decolorization. Although hydrogen peroxide (H 2 O 2 ) can also induce the decolorization of IDS under specific conditions, its reaction rate is much slower than that of O 3 . Previous literature reports that during the first 6 hours after reagent addition, the influence of H 2 O 2 is negligible 55 , ensuring that the observed decolorization phenomenon is primarily attributed to the oxidation by O 3 . To further quantify the differences, we defined the change in absorption as Δh = A t -A 0 (where A 0 is the initial absorbance at 610 nm, and A t is the absorbance at time t). The results show that only in the presence of O 3 or microdroplet in O 2 atmosphere, Δh increases significantly ( Figure 4b ), effectively ruling out significant interference from H 2 O 2 and further confirming that O 3 is the dominant oxidative species in the process. Additionally, electrospray ionization mass spectrometry (ESI-MS) detected a product peak at m/z = 226.0, corresponding to the oxidation product of IDS by O 3 ( Figure 4c and S10 ), providing strong evidence for O 3 formation at the microdroplet interface. To optimize the oxidation reaction, we systematically investigated the effects of temperature, atomization power, and ultrasound. The yield of DP increased with the temperature ( Figure 5a ). This suggests that moderate heating accelerates solvent evaporation, reducing microdroplet size and enhancing the surface concentration of the reactants. However, excessive heating may disrupt the solution composition and affect the reaction progress. Higher atomization power produced smaller microdroplets, leading to an increased interfacial area and improved activation efficiency of O 2 at the microdroplet interface, thereby promoting O 3 generation and enhancing the overall oxidation rate ( Figure 5b ). Notably, ultrasound further enhanced DP yield, likely due to its synergy with cavitation effects in microdroplets 24, 58 , which promote O 2 activation and O 3 formation ( Figure S11 ). However, when ultrasound was applied without microdroplet spraying, no DP wasdetected ( Figure S11 ), confirming that the oxidation was inherently linked to the microdroplet environment rather than ultrasound alone ultrasound was applied without microdroplet spraying, no DP wasdetected ( Figure S1 1 ), confirming that the oxidation was inherently linked to the microdroplet environment rather than ultrasound alone Mechanisms Based on the above experimental observations, we propose a mechanistic pathway for ozone (O 3 ) formation at the microdroplet interface and its subsequent ozonation of NA. Previous reports suggest that the electric field at the microdroplet interface can reach up to 10 9 V/m 43-45 , which is far higher than that required for O 2 dissociation 48-52 . O 2 may undergo dissociation into two oxygen atoms (O) under the strong interfacial electric field 8 . One of the dissociative O reacts with atmospheric O 2 to form O 3 59-65 . The in situ generated O 3 subsequently reacts with NA in the microdroplet. The proposed mechanism is shown in Figure 6a. The reaction follows a five-step radical-driven pathway: (1) [3+2] cycloaddition of O 3 with NA to generate primary ozonide (POZ); (2) cleavage of the POZ to form a Criegee intermediate; (3) hydrogen abstraction to generate a carbon-centered radical; (4) intramolecular rearrangement to a more stable ester-type radical; and (5) coupling with methyl radicals to yield the final product (DP). In addition, through high-resolution mass spectrometry, we detected intermediates 3 (Figure 6b), which directly proves that the reaction mechanism follows the ozone oxidation mechanism rather than the hydrogen peroxide oxidation mechanism. To further substantiate the reaction mechanism, DFT calculations were conducted. The computed Gibbs free energy profiles under microdroplet and bulk-phase conditions are shown in Figures 6c and 6d , respectively. The reaction initiates with a [3+2] cycloaddition between ozone and the conjugated π-system of NA, forming a POZ. This step is highly exergonic, releasing 47.4-49.8 kcal/mol. The retained energy within the adduct drives rapid decomposition of POZ via homolytic cleavage of the C-C and O-O bonds, affording a Criegee intermediate (Int7) and acetaldehyde 66, 67 . The interfacial electric field notably lowers the activation barriers of TS3 and TS4, from 15.1 and 8.3 kcal/mol to 11.1 and 6.6 kcal/mol, respectively. Subsequent hydrogen abstraction at the carbonyl α-position, mediated by abundant hydroxyl radicals (·OH), generates an α-carbonyl radical with an activation barrier of 2.2 kcal/mol under microdroplet conditions. The radical then undergoes intramolecular rearrangement to form a thermodynamically stable ester-type radical (Int12). In the final step, methyl radicals (·CH 3 ), produced via field-induced ionization of methanol 68-70 , couple with the ester radical to form DP. This methylation step (TS7) constitutes the rate-determining step, with a barrier of 25.8 kcal/mol under bulk-phase conditions, reduced to 15.3 kcal/mol in microdroplets. Overall, the electric field not only facilitates radical generation but also reduces the key activation barriers, thereby enhancing the overall reaction efficiency. Detection of methyl radicals by electron paramagnetic resonance (EPR) and high-resolution mass spectrometry ( Figures 7 and S12 ) strongly supports the proposed radical-driven mechanism, wherein microdroplet-generated ozone drives the oxidative transformation of NA to DP. To confirm that the methyl radical signal originates from microdroplet induction rather than methanol oxidation, we conducted a control experiment in which DMPO was used to trap pure methanol without the microdroplet setup. As shown in Figure S13 , no EPR signal was detected. CONCLUSIONS In summary, this study demonstrates that O 3 can be effectively generated at the interface of aqueous microdroplets under ambient conditions and can serve as a potent oxidant for promoting synthetically meaningful organic transformations. Through combined experimental and theoretical investigations, we show that the strong interfacial electric field facilitates the activation of molecular O 2 , leading to the in situ formation of O 3 . The generated O 3 drives the selective oxidation of NA to DP via a radical-mediated pathway involving Criegee intermediates and methyl radical coupling. DFT calculations reveal that the microdroplet environment substantially lowers the energy barriers of key transition states, thereby enhancing the overall reaction kinetics. EPR spectroscopy and high-resolution mass spectrometry provide direct evidence of free radical species, supporting the proposed mechanism pathway. Collectively, these findings establish O 3 as a viable and efficient oxidant in microdroplet systems, extending the role of microdroplet chemistry from analytical detection to preparative synthesis. Moreover, this work highlights the broader potential of field-induced microdroplet phenomena, such as microlightning, for enabling green, catalyst-free oxidation strategies under mild conditions. Declarations AUTHOR CONTRIBUTIONS L. Xue: conceptualization, data curation, investigation, methodology, and writing - original draft; B. Y. Zhu: Density Functional Theory Calculations (DFT); P. Zheng: investigation; K. Y. Geng: investigation, methodology, software, and writing - review and editing; J. Geng: methodology and supervision; X. B. Hu: project administration, conceptualization, resources, funding acquisition, writing - review and editing, and supervision. CONFLICTS OF INTERESTS There are no conflicts to declare. 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J. Water Process. Eng. 56 , 104393 (2023). Hao, R. et al. Synchronous oxidation-removal of CO and NO using microwave-ultraviolet co-catalysis of H 2 O/O 2 mixture. Chem. Eng. Sci. 285 , 119556 (2024). Johnson, D. M., G. The gas-phase ozonolysis of unsaturated volatile organic compounds in the troposphere. Chem. Soc. Rev. 37 , 699-716 (2008). Park, J. K., H. Theoretical Study on the Reaction of p-Cymene with Ozone. Bull. Korean Chem. Soc. 42 , 832-835 (2021). Jasper, A. W. K., S. J.; Harding, L. B.; Ruscic, B. Kinetics of the Reaction of Methyl Radical with Hydroxyl Radical and Methanol Decomposition. J. Phys. Chem. A 111 , 3932-3950 (2007). Morgan, C. U. Decay Kinetics of the Methyl Radical Produced by Ultraviolet Irradiation of Methanol-Water Matrices at 77°K. J. Am. Chem. Soc. 91 , 1599-1602 (1969). Hama, T. Y., M.; Yabushita, A.; Kawasaki, M.; Wickramasinghe, P.; Guo, W.; Loock, H. P.; Ashfold, M. N. R.; Western, C. M. Translational and internal energy distributions of methyl and hydroxyl radicals produced by 157 nm photodissociation of amorphous solid methanol. J. Chem. Phys. 131 , 224512 (2009). Scheme 1 Scheme 1 is available in the Supplementary Files section. Additional Declarations There is NO Competing Interest. Supplementary Files SupportingInformation.docx In Situ Ozone Generated on the Surface of Water Microdroplets Mediates Selective Aromatic Oxidation TOCGraphic.png TOC Scheme1.png Scheme 1. (a) Traditional single spray H 2 O 2 microdroplet oxidation system. (b) Circulating spray ozone ultrasonic atomization microdroplet oxidation system developed in this study. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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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-7417699","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":512021782,"identity":"368bf748-3e63-42c2-8bdb-af302f6f0f4a","order_by":0,"name":"Kaiyu Geng","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA40lEQVRIiWNgGAWjYBACCQbGBgiLHUQbWJCihecASIsEMVrgrARUPk4g2X64TYLhl02efOTzqxt+FEgw8Ld3J+DVIs2T2CbB2JdWbHg7p+xmD9BhEmfObsCrRY4BpKXncOLG2TlpN3iAWgwkcglo4X8I0vI/cePMM2k3/xCjRVoCaAvDjwOJ8yXYj90myhbJGQ+bLRIbkhM38OSw3ZYxkOAh6BeJ8+kPb3z4Y5c4v/34s5tv/tjI8bf34tcCBCxAtwEj8QCPAYjHQ0g5CDB/YPjDwCDfwP6AGNWjYBSMglEwAgEAXKdKOId1IYcAAAAASUVORK5CYII=","orcid":"","institution":"Nanjing University","correspondingAuthor":true,"prefix":"","firstName":"Kaiyu","middleName":"","lastName":"Geng","suffix":""},{"id":512021783,"identity":"ad033b3b-cbd3-4257-98a6-ad1e5d4d4548","order_by":1,"name":"Lian Xue","email":"","orcid":"","institution":"Nanjing University","correspondingAuthor":false,"prefix":"","firstName":"Lian","middleName":"","lastName":"Xue","suffix":""},{"id":512021784,"identity":"a8525d13-2ac2-401d-a16f-a75856ad32d7","order_by":2,"name":"Boyu Zhu","email":"","orcid":"","institution":"Nanjing University","correspondingAuthor":false,"prefix":"","firstName":"Boyu","middleName":"","lastName":"Zhu","suffix":""},{"id":512021785,"identity":"c26c695b-6c95-461d-a255-3dbd40b31a7e","order_by":3,"name":"Peng Zheng","email":"","orcid":"","institution":"Nanjing University","correspondingAuthor":false,"prefix":"","firstName":"Peng","middleName":"","lastName":"Zheng","suffix":""},{"id":512021786,"identity":"3fbfe2cf-3a2d-4a3f-898c-fced08ba4133","order_by":4,"name":"Jiao Geng","email":"","orcid":"","institution":"Nanjing University","correspondingAuthor":false,"prefix":"","firstName":"Jiao","middleName":"","lastName":"Geng","suffix":""},{"id":512021787,"identity":"109c816b-a48a-4bf1-9834-672f1749416f","order_by":5,"name":"Xingbang Hu","email":"","orcid":"https://orcid.org/0000-0002-2995-9704","institution":"Nanjing University","correspondingAuthor":false,"prefix":"","firstName":"Xingbang","middleName":"","lastName":"Hu","suffix":""}],"badges":[],"createdAt":"2025-08-20 12:55:58","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7417699/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7417699/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90933416,"identity":"e98bb0c5-599f-4c38-96ed-8660c1d0ebb0","added_by":"auto","created_at":"2025-09-09 16:40:00","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":106172,"visible":true,"origin":"","legend":"\u003cp\u003eMorphological characteristics of microdroplets in a 20W spraying device. (a) Size distribution of microdroplets measured by optical microscopy (inset: microdroplet image under the microscope). (b) Morphology of airborne microdroplets captured by a high-speed camera.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7417699/v1/33471ca1fe5350f9307be82c.png"},{"id":90933418,"identity":"7324fae0-2d6c-470c-83dc-5a5d899ad3b8","added_by":"auto","created_at":"2025-09-09 16:40:01","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":132006,"visible":true,"origin":"","legend":"\u003cp\u003eGas chromatogram of the spontaneous oxidation of naphthalene microdroplets (a) in an air atmosphere and (b) in an N\u003csub\u003e2\u003c/sub\u003e atmosphere. Mass spectra of (c) naphthalene and (d) dimethyl phthalate. (e) \u003csup\u003e13\u003c/sup\u003eC NMR spectra of naphthalene oxidation to dimethyl phthalate in cyclic microdroplets reaction.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7417699/v1/8ba83f6cfba2b5f9f2828afd.png"},{"id":90933417,"identity":"244437db-f1ca-49a2-a5a5-9672ce517ecc","added_by":"auto","created_at":"2025-09-09 16:40:01","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":74977,"visible":true,"origin":"","legend":"\u003cp\u003e(a) The yield of dimethyl phthalate produced by naphthalene under air, N\u003csub\u003e2\u003c/sub\u003e and N\u003csub\u003e2 \u003c/sub\u003e+ H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e systems in both bulk and microdroplet (Md) reactions. (b) Kinetic curves of the spontaneous oxidation reaction of O\u003csub\u003e2\u003c/sub\u003e and Air atmospher in the bulk reaction and microdroplet reaction. (The error bars in the figure were determined from three replicates).\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7417699/v1/c164a89434b9ae67ac50db75.png"},{"id":90933421,"identity":"60d77896-8b3e-4c6e-9cd6-6aa498e8c98e","added_by":"auto","created_at":"2025-09-09 16:40:01","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":167603,"visible":true,"origin":"","legend":"\u003cp\u003e(a) Schematic illustration of the oxidation reaction of IDS in microdroplets (inset: color change of IDS-O\u003csub\u003e2\u003c/sub\u003e-Microdroplet (Md)). (b) The trend of Δ h variation with time for IDS-O\u003csub\u003e3\u003c/sub\u003e, IDS-O\u003csub\u003e2\u003c/sub\u003e and IDS-H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e (Δh represents the absorbance change at 610 nm, defined as Δh=A\u003csub\u003et\u003c/sub\u003e-A\u003csub\u003e0, \u003c/sub\u003et (t =0.25 h, 0.5 h, 0.75 h, 1 h, 1.25 h, 4 h, 8 h, 10 h), A\u003csub\u003e0\u003c/sub\u003e is the absorbance at 0 h (\u003cstrong\u003eFigure S9\u003c/strong\u003e). (c) High resolution mass spectrometry of the solution before and after IDS oxidation reaction in microdroplets.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7417699/v1/04968b95f623e90d75356f1a.png"},{"id":90935153,"identity":"43377f5c-389f-4c15-b531-0ba4a68b44e6","added_by":"auto","created_at":"2025-09-09 16:56:01","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":66490,"visible":true,"origin":"","legend":"\u003cp\u003e(a) Effect of temperature on DP yield during self-oxidation. (b) Microdroplet size distribution at different atomization powers and its impact on DP yield.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-7417699/v1/6b4f21ce7ac3131e4c708f1a.png"},{"id":90933422,"identity":"9a864047-ad03-4156-86b4-4d055040ec95","added_by":"auto","created_at":"2025-09-09 16:40:01","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":186061,"visible":true,"origin":"","legend":"\u003cp\u003e(a) The proposed mechanism for the reaction; (b) High resolution mass spectrometry of reaction intermediates; (c)-(d) the energy profile (in kcal/mol) with and without microdroplets for the reaction.\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-7417699/v1/5291db36bb5ca6a1d3a0bc9d.png"},{"id":90935158,"identity":"f2d83092-8f77-40da-9f2c-3c4fb5c5e5e1","added_by":"auto","created_at":"2025-09-09 16:56:01","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":112755,"visible":true,"origin":"","legend":"\u003cp\u003e(a) Schematic of \u003csup\u003e\u003cstrong\u003e.\u003c/strong\u003e\u003c/sup\u003eCH\u003csub\u003e3\u003c/sub\u003e trapping by DMPO; (b) EPR spectrum of \u003csup\u003e\u003cstrong\u003e.\u003c/strong\u003e\u003c/sup\u003eCH\u003csub\u003e3\u003c/sub\u003e-DMPO produced by microdroplets; (c) High resolution mass spectrometry of \u003csup\u003e\u003cstrong\u003e.\u003c/strong\u003e\u003c/sup\u003eCH\u003csub\u003e3\u003c/sub\u003e-DMPO produced by microdroplets.\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-7417699/v1/7738147d45ecc0f95892ede1.png"},{"id":94599554,"identity":"d85fbb6f-0400-4cd7-a992-05d29dee5cbe","added_by":"auto","created_at":"2025-10-28 19:06:20","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1441678,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7417699/v1/4711c216-dc89-409b-a08f-c01d9bcd107e.pdf"},{"id":90933434,"identity":"5781b48f-8082-4a46-89c9-4ce768e8c9ca","added_by":"auto","created_at":"2025-09-09 16:40:01","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":4169615,"visible":true,"origin":"","legend":"In Situ Ozone Generated on the Surface of Water Microdroplets Mediates Selective Aromatic Oxidation","description":"","filename":"SupportingInformation.docx","url":"https://assets-eu.researchsquare.com/files/rs-7417699/v1/67208d5a2932f52e42e58daa.docx"},{"id":90933740,"identity":"4cd02ca0-4598-4772-9461-a414ea9abc14","added_by":"auto","created_at":"2025-09-09 16:48:01","extension":"png","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":269722,"visible":true,"origin":"","legend":"\u003cp\u003eTOC\u003c/p\u003e","description":"","filename":"TOCGraphic.png","url":"https://assets-eu.researchsquare.com/files/rs-7417699/v1/993d732789d6d5cfddf011bc.png"},{"id":90936908,"identity":"41555770-c7c1-4b7d-b145-4cbf258d12de","added_by":"auto","created_at":"2025-09-09 17:12:01","extension":"png","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":216115,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eScheme 1.\u003c/strong\u003e (a) Traditional single spray H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e microdroplet oxidation system. (b) Circulating spray ozone ultrasonic atomization microdroplet oxidation system developed in this study.\u003c/p\u003e","description":"","filename":"Scheme1.png","url":"https://assets-eu.researchsquare.com/files/rs-7417699/v1/2f57842a6eebc3390e0516e5.png"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"In Situ Ozone Generated on the Surface of Water Microdroplets Mediates Selective Aromatic Oxidation","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eIn recent years, microdroplet chemistry, realized by atomizing aqueous solutions into micron-sized droplets, has emerged as a powerful platform for accelerating chemical reactions under ambient and mild conditions\u003csup\u003e1\u0026ndash;3\u003c/sup\u003e. Microdroplets possess physicochemical properties distinct from bulk phases, including high surface-to-volume ratios\u003csup\u003e4\u003c/sup\u003e, partial solvation\u003csup\u003e5\u003c/sup\u003e, strong interfacial electric fields\u003csup\u003e6\u003c/sup\u003e, which together enable unique reactivities that are often inaccessible in bulk. Among these, oxidation reactions in aqueous microdroplets have drawn increasing attention, particularly those mediated by reactive oxygen species (ROS)\u003csup\u003e7\u0026ndash;13\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eTo date, most studies on microdroplet oxidation have focused on the generation of hydrogen peroxide (H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e) at the air-water interface to drive redox processes (Scheme 1a)\u003csup\u003e14\u0026ndash;18\u003c/sup\u003e. It has been proposed that hydroxide ions at the microdroplet surface undergo decomposition into hydroxyl radicals and electrons, leading to the in-situ formation of H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e \u003csup\u003e12, 14, 19\u0026ndash;27\u003c/sup\u003e and enabling oxidation of solutes inside the microdroplet\u003csup\u003e23, 28\u0026ndash;31\u003c/sup\u003e. Various H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e-mediated oxidative reactions have been reported. For example, Zare and co-workers demonstrated the oxidation of methane to methanol using water microdroplets\u003csup\u003e23\u003c/sup\u003e. Rao et al. further found that thiols and thioethers accumulate at the interface and proposed that their spontaneous oxidation is driven by highly reactive radicals formed at or near the microdroplet surface\u003csup\u003e32\u003c/sup\u003e. In our previous work, we also showed that styrene can be efficiently oxidized to styrene oxide in microdroplets without the use of any catalysts\u003csup\u003e24\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eBeyond H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e-mediated pathways, recent studies have demonstrated that ozone (O\u003csub\u003e3\u003c/sub\u003e) can also be generated at the interface of water microdroplets\u003csup\u003e8, 33, 34\u003c/sup\u003e. Banerjee and colleagues detected O\u003csub\u003e3\u003c/sub\u003e radical cations (m/z\u0026thinsp;=\u0026thinsp;48) at the microdroplet interface using mass spectrometry, establishing the feasibility of ozone generation in aqueous aerosols\u003csup\u003e33\u003c/sup\u003e. Also, Zare et al. introduced the concept of \u0026ldquo;microlightning\u0026rdquo; to describe transient electrical discharge events at the microdroplet interface that generate reactive oxidants, including O\u003csub\u003e3\u003c/sub\u003e\u003csup\u003e8\u003c/sup\u003e. While these pioneering studies significantly advanced our mechanistic understanding, they primarily focused on detecting oxidants such as O\u003csub\u003e3\u003c/sub\u003e or dioxygen-derived species using mass spectrometry or isotopic labeling. Based on these foundational studies, Meng\u0026rsquo;s group showed that pure water microdroplets can induce triple bond cleavage in alkynes via microlightning and in-situ ozone generation\u003csup\u003e34\u003c/sup\u003e, although the reported product yields remained extremely low, often detectable only by high-sensitivity methods.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eMotivated by these advances, we sought to explore whether microdroplet-generated O\u003csub\u003e3\u003c/sub\u003e could be harnessed to perform synthetically useful bond transformations, which is a key step for the practical application of microdroplet chemistry. Here, we report a catalyst-free transformation of naphthalene (NA) to dimethyl phthalate (DP) under ambient conditions (Scheme 1b). The reaction proceeds efficiently in a recirculating ultrasonic atomization system under an O\u003csub\u003e2\u003c/sub\u003e atmosphere and is driven by oxygen activation at the microdroplet interface. Notably, the oxidation yields a single major product (DP) with a measurable yield of 11.6%, which is readily detected by both GC-MS and NMR, highlighting the synthetic practicality of this microdroplet-based method. Direct evidence for ozone formation at the microdroplet interface was obtained via indigo disulfonate (IDS) colorimetry and high-resolution mass spectrometry. Furthermore, density functional theory (DFT) calculations indicate that the ozone-mediated oxidation pathway at the microdroplet interface exhibits significantly reduced energy barriers, further supporting the catalytic potential of interfacial ozone.\u003c/p\u003e\n\u003cp\u003eIn summary, this study builds upon previous reports of microdroplet-generated O\u003csub\u003e3\u003c/sub\u003e and uniquely demonstrates its synthetic utility in performing selective, preparative-scale oxidations. By expanding the oxidative repertoire of microdroplet chemistry beyond H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e and into O\u003csub\u003e3\u003c/sub\u003e-mediated transformations, our findings offer new insights into interfacial redox reactivity and present a promising strategy for catalyst-free, green oxidation processes under mild conditions.\u003c/p\u003e"},{"header":"RESULTS AND DISCUSSION","content":"\u003cp\u003eMicrodroplet oxidation has frequently been associated with the generation of hydrogen peroxide (H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e), which is widely considered as a key oxidant in such systems. Most previous studies have focused on the oxidative behavior of H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e in microdroplet environments\u003csup\u003e12, 14-27, 32, 35-39\u003c/sup\u003e. However, while investigating naphthalene (NA) oxidation under microdroplet conditions, we observed a reaction pathway that could not be explained by the conventional H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e mechanism.\u003c/p\u003e\n\u003cp\u003eThe experiments began with the preparation of a homogeneous methanol-water solution of NA (\u003cstrong\u003eFigure S1a\u003c/strong\u003e), which was then atomized into microdroplets using a 20W ultrasonic nebulizer (\u003cstrong\u003eFigure S1b\u003c/strong\u003e). The microdroplets had an average diameter of approximately 7.0 \u0026mu;m, as determined by high-speed camera system and a microscopic measurement system (\u003cstrong\u003eFigure 1\u003c/strong\u003e)\u003csup\u003e29, 31, 40\u003c/sup\u003e. After continuous spraying for 4 hours under an air atmosphere, gas chromatography-mass spectrometry (GC-MS) analysis revealed the formation of dimethyl phthalate (DP) as the primary oxidation product. As shown in \u003cstrong\u003eFigure 2a\u003c/strong\u003e, NA exhibited a retention time of approximately 7.1 min, with a mass-to-charge ratio (m/z) of 128.2 (\u003cstrong\u003eFigure 2c\u003c/strong\u003e), while DP had a retention time of about 9.0 min, with an m/z of 194.0 (\u003cstrong\u003eFigure 2d\u003c/strong\u003e). These results confirmed the conversion of NA to DP. Being different from most of the previous microdroplet oxidation reactions which only gave trace amount of product\u003csup\u003e16, 35, 36, 41, 42\u003c/sup\u003e, the product amount obtained in the circulating spray ultrasonic atomization microdroplet system was high enough to be detected by nuclear magnetic resonance (NMR) and the NMR result can further support the formation of dimethyl phthalate (\u003cstrong\u003eFigures 2e, S4\u0026nbsp;\u003c/strong\u003eand\u003cstrong\u003e\u0026nbsp;S7\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eTo investigate whether this reaction proceeded via an H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e-dependent pathway, we conducted a series of control experiments comparing bulk and microdroplet environments under identical conditions. Notably, no detectable DP formed in bulk solutions exposed to air, while NA was efficiently converted to DP in microdroplets (\u003cstrong\u003eFigure 3\u003c/strong\u003e). This stark contrast highlights the crucial role of the microdroplet environment in enabling oxidation, likely due to the high interfacial electric field at the microdroplet surface\u003csup\u003e25-27, 43-45\u003c/sup\u003e. The nature of this oxidation process became particularly intriguing when we modified the reaction conditions. Under a N\u003csub\u003e2\u003c/sub\u003e atmosphere, DP formation was completely suppressed (\u003cstrong\u003eFigure 2b\u0026nbsp;\u003c/strong\u003eand\u003cstrong\u003e\u0026nbsp;3a\u003c/strong\u003e), whereas in pure O\u003csub\u003e2\u003c/sub\u003e, the DP yield increased significantly from 9.4% (under air) to 11.6% (\u003cstrong\u003eFigure 3b\u003c/strong\u003e), indicating that the oxidation process directly depended on molecular oxygen. However, the increase in DP yield with higher O\u003csub\u003e2\u003c/sub\u003e concentration alone does not directly prove that H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e is the primary oxidant, as other reactive oxygen species (ROS) could also contribute to the oxidation.\u003c/p\u003e\n\u003cp\u003eTo further probe the mechanism, we added H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e directly to the microdroplet system under a N\u003csub\u003e2\u003c/sub\u003e atmosphere. Based on previous reports, it is generally believed that hydroxyl radicals (\u0026middot;OH) form under high electric fields and lead to the generation of H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e, which then participates in oxidation reactions\u003csup\u003e12, 14, 19-24, 46, 47\u003c/sup\u003e. However, in our experiment, despite the presence of H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e, we observed almost no conversion of NA into DP (\u003cstrong\u003eFigure 3a\u003c/strong\u003e). This finding strongly suggests that the oxidation process does not follow the conventional pathway involving H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e but instead proceeds through an alternative oxidation mechanism. In addition, in order to exclude the possibility that metal parts in the spray device may participate in the reaction or cause the same background peak due to corrosion, we have designed and adopted an inverted spray device (as shown in the\u003cstrong\u003e\u0026nbsp;Figure S8\u003c/strong\u003e), so that the reaction liquid does not contact with the metal throughout the process. The experimental results showed that the same DP product was still observed in GC-MS detection, indicating that the metal components did not have a significant impact on the reaction process.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGiven that the reaction from NA to DP involves the cleavage of carbon-carbon double bonds and the formation of carbonyl groups, which is the characteristic of ozonolysis, this led us to start considering the possibility of O\u003csub\u003e3\u003c/sub\u003e involvement in the oxidation process. O\u003csub\u003e3\u003c/sub\u003e is a well-known oxidant that reacts efficiently with unsaturated compounds, but its generation typically requires high-voltage discharges (10-20 kV) to ionize O\u003csub\u003e2\u003c/sub\u003e, corresponding to electric field strengths of 10\u003csup\u003e6\u003c/sup\u003e-10\u003csup\u003e7\u003c/sup\u003e V/m\u003csup\u003e48-52\u003c/sup\u003e.\u0026nbsp;However, the electric field at the microdroplet interface can reach up to 10\u003csup\u003e9\u003c/sup\u003e V/m\u003csup\u003e43-45\u003c/sup\u003e,\u0026nbsp;far exceeding the threshold required for O\u003csub\u003e3\u003c/sub\u003e formation. Therefore, we hypothesize that the ultra-high electric field at the microdroplet interface can directly ionize oxygen (O\u003csub\u003e2\u003c/sub\u003e), forming oxygen atoms (O), which then combine with O\u003csub\u003e2\u003c/sub\u003e to generate O\u003csub\u003e3\u003c/sub\u003e, thereby driving the oxidation of NA.\u003c/p\u003e\n\u003cp\u003eTo verify the presence of O\u003csub\u003e3\u003c/sub\u003e in the microdroplet environment, we employed indigo disulfonate sodium (IDS) as a colorimetric probe. O\u003csub\u003e3\u003c/sub\u003e oxidizes the carbon-carbon double bonds in IDS, disrupting its conjugated structure and leading to decolorization (\u003cstrong\u003eFigure 4a\u003c/strong\u003e)\u003csup\u003e53, 54\u003c/sup\u003e. Such ozone-indigo disulphonate spectrophotometry experiment has been established as a standardized method for detecting the presence of ozone\u003csup\u003e54, 55\u003c/sup\u003e. To further confirm the response characteristics of IDS to O\u003csub\u003e3\u003c/sub\u003e, an experiment was conducted by introducing O\u003csub\u003e3\u003c/sub\u003e into the IDS solution. The results showed that after contact with O\u003csub\u003e3\u003c/sub\u003e, the characteristic absorption peak at 610 nm of IDS rapidly disappeared and dropped to the background level within only 0.1 hour (\u003cstrong\u003eFigure 4b\u003c/strong\u003e). This phenomenon verifies the high sensitivity of this method, further supporting its applicability as an O\u003csub\u003e3\u003c/sub\u003e probe.\u003c/p\u003e\n\u003cp\u003eWhen applied to the microdroplet system under an O\u003csub\u003e2\u003c/sub\u003e atmosphere, ultraviolet-visible spectroscopy (UV-Vis) show that the characteristic absorption peak of IDS at 610 nm decreases rapidly with reaction time\u003csup\u003e55, 56\u003c/sup\u003e, with noticeable decolorization occurring within about 1.25 hours, turning the solution from deep blue to almost colorless (\u003cstrong\u003eFigure 4a\u003c/strong\u003e)\u003csup\u003e57\u003c/sup\u003e. In contrast, under the same concentration of H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e, even when the reaction time is extended to 10 hours, the change in absorption intensity is minimal, with almost no noticeable decolorization. Although hydrogen peroxide (H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e) can also induce the decolorization of IDS under specific conditions, its reaction rate is much slower than that of O\u003csub\u003e3\u003c/sub\u003e. Previous literature reports that during the first 6 hours after reagent addition, the influence of H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e is negligible\u003csup\u003e55\u003c/sup\u003e, ensuring that the observed decolorization phenomenon is primarily attributed to the oxidation by O\u003csub\u003e3\u003c/sub\u003e.\u003c/p\u003e\n\u003cp\u003eTo further quantify the differences, we defined the change in absorption as \u0026Delta;h = A\u003csub\u003et\u003c/sub\u003e-A\u003csub\u003e0\u003c/sub\u003e (where A\u003csub\u003e0\u003c/sub\u003e is the initial absorbance at 610 nm, and A\u003csub\u003et\u003c/sub\u003e is the absorbance at time t). The results show that only in the presence of O\u003csub\u003e3\u0026nbsp;\u003c/sub\u003eor microdroplet in O\u003csub\u003e2\u003c/sub\u003e atmosphere, \u0026Delta;h increases significantly (\u003cstrong\u003eFigure 4b\u003c/strong\u003e), effectively ruling out significant interference from H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e and further confirming that O\u003csub\u003e3\u003c/sub\u003e is the dominant oxidative species in the process. Additionally, electrospray ionization mass spectrometry (ESI-MS) detected a product peak at m/z = 226.0, corresponding to the oxidation product of IDS by O\u003csub\u003e3\u003c/sub\u003e (\u003cstrong\u003eFigure 4c and S10\u003c/strong\u003e), providing strong evidence for O\u003csub\u003e3\u003c/sub\u003e formation at the microdroplet interface.\u003c/p\u003e\n\u003cp\u003eTo optimize the oxidation reaction, we systematically investigated the effects of temperature, atomization power, and ultrasound. The yield of DP increased with the temperature (\u003cstrong\u003eFigure 5a\u003c/strong\u003e). This suggests that moderate heating accelerates solvent evaporation, reducing microdroplet size and enhancing the surface concentration of the reactants. However, excessive heating may disrupt the solution composition and affect the reaction progress. Higher atomization power produced smaller microdroplets, leading to an increased interfacial area and improved activation efficiency of O\u003csub\u003e2\u003c/sub\u003e at the microdroplet interface, thereby promoting O\u003csub\u003e3\u003c/sub\u003e generation and enhancing the overall oxidation rate (\u003cstrong\u003eFigure 5b\u003c/strong\u003e). Notably, ultrasound further enhanced DP yield, likely due to its synergy with cavitation effects in microdroplets\u003csup\u003e24, 58\u003c/sup\u003e,\u0026nbsp;which promote O\u003csub\u003e2\u003c/sub\u003e activation and O\u003csub\u003e3\u003c/sub\u003e formation (\u003cstrong\u003eFigure S11\u003c/strong\u003e). However, when ultrasound was applied without microdroplet spraying, no DP wasdetected (\u003cstrong\u003eFigure S11\u003c/strong\u003e), confirming that the oxidation was inherently linked to the microdroplet environment rather than ultrasound alone\u0026nbsp;ultrasound was applied without microdroplet spraying, no DP wasdetected (\u003cstrong\u003eFigure S1\u003c/strong\u003e\u003cstrong\u003e1\u003c/strong\u003e), confirming that the oxidation was inherently linked to the microdroplet environment rather than ultrasound alone\u003c/p\u003e\n\u003cp\u003eMechanisms\u003c/p\u003e\n\u003cp\u003eBased on the above experimental observations, we propose a mechanistic pathway for ozone (O\u003csub\u003e3\u003c/sub\u003e) formation at the microdroplet interface and its subsequent ozonation of NA. Previous reports suggest that the electric field at the microdroplet interface can reach up to 10\u003csup\u003e9\u003c/sup\u003e V/m\u003csup\u003e43-45\u003c/sup\u003e, which is far higher than that required for O\u003csub\u003e2\u003c/sub\u003e dissociation\u003csup\u003e48-52\u003c/sup\u003e. O\u003csub\u003e2\u003c/sub\u003e may undergo dissociation into two oxygen atoms (O) under the strong interfacial electric field\u003csup\u003e8\u003c/sup\u003e. One of the dissociative O reacts with atmospheric O\u003csub\u003e2\u003c/sub\u003e to form O\u003csub\u003e3\u003c/sub\u003e\u003csup\u003e59-65\u003c/sup\u003e. The in situ generated O\u003csub\u003e3\u003c/sub\u003e subsequently reacts with NA in the microdroplet. The proposed mechanism is shown in Figure 6a. The reaction follows a five-step radical-driven pathway: (1) [3+2] cycloaddition of O\u003csub\u003e3\u0026nbsp;\u003c/sub\u003ewith NA to generate primary ozonide (POZ); (2) cleavage of the POZ to form a Criegee intermediate; (3) hydrogen abstraction to generate a carbon-centered radical; (4) intramolecular rearrangement to a more stable ester-type radical; and (5) coupling with methyl radicals to yield the final product (DP). In addition, through high-resolution mass spectrometry, we detected intermediates 3 (Figure 6b), which directly proves that the reaction mechanism follows the ozone oxidation mechanism rather than the hydrogen peroxide oxidation mechanism.\u003c/p\u003e\n\u003cp\u003eTo further substantiate the reaction mechanism, DFT calculations were conducted. The computed Gibbs free energy profiles under microdroplet and bulk-phase conditions are shown in \u003cstrong\u003eFigures 6c and 6d\u003c/strong\u003e, respectively. The reaction initiates with a [3+2] cycloaddition between ozone and the conjugated \u0026pi;-system of NA, forming a POZ. This step is highly exergonic, releasing 47.4-49.8 kcal/mol. The retained energy within the adduct drives rapid decomposition of POZ via homolytic cleavage of the C-C and O-O bonds, affording a Criegee intermediate (Int7) and acetaldehyde\u003csup\u003e66, 67\u003c/sup\u003e. The interfacial electric field notably lowers the activation barriers of TS3 and TS4, from 15.1 and 8.3 kcal/mol to 11.1 and 6.6 kcal/mol, respectively.\u003c/p\u003e\n\u003cp\u003eSubsequent hydrogen abstraction at the carbonyl \u0026alpha;-position, mediated by abundant hydroxyl radicals (\u0026middot;OH), generates an \u0026alpha;-carbonyl radical with an activation barrier of 2.2 kcal/mol under microdroplet conditions. The radical then undergoes intramolecular rearrangement to form a thermodynamically stable ester-type radical (Int12). In the final step, methyl radicals (\u0026middot;CH\u003csub\u003e3\u003c/sub\u003e), produced via field-induced ionization of methanol\u003csup\u003e68-70\u003c/sup\u003e, couple with the ester radical to form DP. This methylation step (TS7) constitutes the rate-determining step, with a barrier of 25.8 kcal/mol under bulk-phase conditions, reduced to 15.3 kcal/mol in microdroplets. Overall, the electric field not only facilitates radical generation but also reduces the key activation barriers, thereby enhancing the overall reaction efficiency. Detection of methyl radicals by electron paramagnetic resonance (EPR) and high-resolution mass spectrometry (\u003cstrong\u003eFigures 7 and S12\u003c/strong\u003e) strongly supports the proposed radical-driven mechanism, wherein microdroplet-generated ozone drives the oxidative transformation of NA to DP. To confirm that the methyl radical signal originates from microdroplet induction rather than methanol oxidation, we conducted a control experiment in which DMPO was used to trap pure methanol without the microdroplet setup. As shown in \u003cstrong\u003eFigure S13\u003c/strong\u003e, no EPR signal was detected.\u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eIn summary, this study demonstrates that O\u003csub\u003e3\u003c/sub\u003e can be effectively generated at the interface of aqueous microdroplets under ambient conditions and can serve as a potent oxidant for promoting synthetically meaningful organic transformations. Through combined experimental and theoretical investigations, we show that the strong interfacial electric field facilitates the activation of molecular O\u003csub\u003e2\u003c/sub\u003e, leading to the in situ formation of O\u003csub\u003e3\u003c/sub\u003e. The generated O\u003csub\u003e3\u003c/sub\u003e drives the selective oxidation of NA to DP via a radical-mediated pathway involving Criegee intermediates and methyl radical coupling. DFT calculations reveal that the microdroplet environment substantially lowers the energy barriers of key transition states, thereby enhancing the overall reaction kinetics. EPR spectroscopy and high-resolution mass spectrometry provide direct evidence of free radical species, supporting the proposed mechanism pathway. Collectively, these findings establish O\u003csub\u003e3\u003c/sub\u003e as a viable and efficient oxidant in microdroplet systems, extending the role of microdroplet chemistry from analytical detection to preparative synthesis. Moreover, this work highlights the broader potential of field-induced microdroplet phenomena, such as microlightning, for enabling green, catalyst-free oxidation strategies under mild conditions.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAUTHOR CONTRIBUTIONS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eL. Xue: conceptualization, data curation, investigation, methodology, and writing - original draft; B. Y. Zhu: Density Functional Theory Calculations (DFT); P. Zheng: investigation; K. Y. Geng: investigation, methodology, software, and writing - review and editing; J. Geng: methodology and supervision; X. B. Hu: project administration, conceptualization, resources, funding acquisition, writing - review and editing, and supervision.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONFLICTS OF INTERESTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere are no conflicts to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eACKNOWLEDGMENTS \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the National Natural Science Foundation of China (no. 22478173 and 22178159).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eCooks, R. G., Holden, D. T. Breaking down microdroplet chemistry. \u003cem\u003eScience\u003c/em\u003e \u003cstrong\u003e384\u003c/strong\u003e, 958-959 (2024).\u003c/li\u003e\n \u003cli\u003eLee, J. K. et al. Condensing water vapor to droplets generates hydrogen peroxide. \u003cem\u003eProc. Natl. Acad. Sci. 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Theoretical Study on the Reaction of p-Cymene with Ozone. \u003cem\u003eBull. Korean Chem. Soc. \u003c/em\u003e\u003cstrong\u003e42\u003c/strong\u003e, 832-835 (2021).\u003c/li\u003e\n \u003cli\u003eJasper, A. W. K., S. J.; Harding, L. B.; Ruscic, B. Kinetics of the Reaction of Methyl Radical with Hydroxyl Radical and Methanol Decomposition. \u003cem\u003eJ. Phys. Chem. A\u003c/em\u003e \u003cstrong\u003e111\u003c/strong\u003e, 3932-3950 (2007).\u003c/li\u003e\n \u003cli\u003eMorgan, C. U. Decay Kinetics of the Methyl Radical Produced by Ultraviolet Irradiation of Methanol-Water Matrices at 77°K.\u003cem\u003e J. Am. Chem. Soc. \u003c/em\u003e\u003cstrong\u003e91\u003c/strong\u003e, 1599-1602 (1969).\u003c/li\u003e\n \u003cli\u003eHama, T. Y., M.; Yabushita, A.; Kawasaki, M.; Wickramasinghe, P.; Guo, W.; Loock, H. P.; Ashfold, M. N. R.; Western, C. M. Translational and internal energy distributions of methyl and hydroxyl radicals produced by 157 nm photodissociation of amorphous solid methanol.\u003cem\u003e J. Chem. Phys.\u003c/em\u003e \u003cstrong\u003e131\u003c/strong\u003e, 224512 (2009).\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Scheme 1","content":"\u003cp\u003eScheme 1 is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"microdroplets, ozone, naphthalene oxidation, mechanism","lastPublishedDoi":"10.21203/rs.3.rs-7417699/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7417699/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eMicrodroplet-mediated ozone (O\u003csub\u003e3\u003c/sub\u003e) oxidation offers an alternative route for organic transformations compared to the commonly studied hydrogen peroxide (H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e)-dominated systems. Here, we demonstrate efficient O\u003csub\u003e3\u003c/sub\u003e oxidation at the microdroplet interface, achieving selective conversion of naphthalene (NA) to dimethyl phthalate (DP) with 11.6% yield. When an aqueous methanol solution of NA is atomized into ~\u0026thinsp;7.0 \u0026micro;m microdroplets under O\u003csub\u003e2\u003c/sub\u003e atmosphere, the system operates without external catalysts or oxidants while outperforming typical microdroplet oxidation methods. The generation of O\u003csub\u003e3\u003c/sub\u003e is unequivocally confirmed by indigo disulfonate spectrophotometry and high-resolution mass spectrometry. Combined with radical trapping experiments and DFT calculations, these results establish a surface-activated O\u003csub\u003e3\u003c/sub\u003e-mediated oxidation mechanism. Key intermediates were further confirmed by mass spectrometry. This work not only advances microdroplet O\u003csub\u003e3\u003c/sub\u003e chemistry beyond analytical detection to preparative synthesis, but also provides new insights into interfacial oxidative processes.\u003c/p\u003e","manuscriptTitle":"In Situ Ozone Generated on the Surface of Water Microdroplets Mediates Selective Aromatic Oxidation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-09 16:39:56","doi":"10.21203/rs.3.rs-7417699/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"41d9b406-5a1f-4a97-8760-968bc4147b74","owner":[],"postedDate":"September 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":54382987,"name":"Physical sciences/Chemistry/Green chemistry"},{"id":54382988,"name":"Physical sciences/Nanoscience and technology/Other nanotechnology"}],"tags":[],"updatedAt":"2025-10-28T18:30:29+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-09 16:39:56","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7417699","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7417699","identity":"rs-7417699","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}