Isabelle Gounand
email: isabelle.gounand@eawag.ch

Eric Harvey
email: eric.harvey@utoronto.ca

Chelsea J Little
email: chelseajean.little@eawag.ch

Florian Altermatt
email: florian.altermatt@eawag.ch

On embedding meta-ecosystems into a socio-ecological framework

Keywords: Metaecosystem, spatial flows, mental model, ecosystem functioning

Spatial flows of organisms and resources are increasingly recognized as key elements of ecosystem functioning [START_REF] Gounand | Worldwide cross-ecosystem carbon subsidies and their contribution to ecosystem functioning[END_REF][START_REF] Polis | Food Webs at the landscape level[END_REF]. In a previous article [START_REF] Gounand | Meta-Ecosystems 2.0 : Rooting the Theory into the Field[END_REF], we called for an update of the metaecosystem framework, a key conceptual and theoretical framework regarding spatial dynamics [START_REF] Loreau | Meta-ecosystems: a theoretical framework for a spatial ecosystem ecology[END_REF]. Specifically, we identified ways to better integrate different types of flows connecting ecosystems and their specific spatio-temporal scales in order to improve our understanding of ecosystem couplings. Building on this article, Roque et al. [START_REF] Roque | Towards a meta-socio-ecological system perspective[END_REF] wrote that, to be more predictive and operational, the meta-ecosystem framework should also explicitly include the socioecological mechanisms underlying the impacts of human societies on these flows. Their rationale is that socio-cultural mechanisms govern the way human society interacts with ecosystems and influence spatial flows connecting ecosystems. Roque et al. provide some case studies of such influence, for instance with the perception of ivory trade [6].

We see some potential value of such a socio-ecological perspective, for example to address specific questions about dynamical feedbacks between humans and the environment (e.g., on the environmental sustainability of human practices [START_REF] Lafuite | Delayed behavioural shifts undermine the sustainability of social-ecological systems[END_REF]). However, it is noteworthy that humaninduced effects on meta-ecosystem dynamics are already integrated within the variation in spatial flow values considered in meta-ecosystem models (e.g., variance and mean quantity/quality of flows) [START_REF] Loreau | Meta-ecosystems: a theoretical framework for a spatial ecosystem ecology[END_REF]. Thus, studying the effects of processes acting at different scales on ecosystem functioning can already be achieved with the existing meta-ecosystem framework while avoiding additional layers of complexity, which might reduce interpretability and understanding.

As we illustrate with a strongly human-shaped landscape in our previous article [START_REF] Gounand | Meta-Ecosystems 2.0 : Rooting the Theory into the Field[END_REF], human activities influence the spatial flows linking ecosystems in various ways. This includes increasing some flows (e.g., leaching of agricultural fertilizers to aquatic systems), regulating the species driving other spatial flows, or even modifying the landscape configuration itself. We here explain one well-known example of the role of human activities in meta-ecosystems including all these aspects (Fig. 1A): Geese populations in the southern United States massively increased following agriculture intensification in the 1960's, because the geese shifted their diets from feeding in wetlands to feeding on the augmented resources in agro-ecosystems [START_REF] Jefferies | Agricultural Food Subsidies, Migratory Connectivity and Large-Scale Disturbance in Arctic Coastal Systems: A Case Study[END_REF]. This resource augmentation was of course triggered by socio-economic changes in farming practices, and also had effects on local meta-ecosystems (i.e., runoff into waterways). In the context of global metaecosystems, the subsequent increase in flows of migratory birds dramatically affected arctic tundra ecosystems [START_REF] Jefferies | Agricultural Food Subsidies, Migratory Connectivity and Large-Scale Disturbance in Arctic Coastal Systems: A Case Study[END_REF], and this effect was partly modulated by hunting along the geese's migratory routes, in itself a socio-cultural phenomenon. Thus, along with Roque et al. [START_REF] Roque | Towards a meta-socio-ecological system perspective[END_REF] and others working on socio-ecological linkages [START_REF] Díaz | Assessing nature's contributions to people[END_REF][START_REF] Quintessence Consortium | Networking Our Way to Better Ecosystem Service Provision[END_REF], we agree that culture and mental models are central to the people-nature relationship, and a crucial link in the decision pathway leading to environmental regulation of anthropic impacts on nature (e.g., land use management, hunting rules; see Fig. 1B, arrow 1). However, accounting for these anthropic impacts can already be done by directly implementing the forcing derived from sociocultural processes on flows (e.g., in Fig. 1A adding fields and reducing migratory flow), without explicitly modelling the socio-cultural processes in the meta-ecosystem framework.

Thus, when would the additional complexity brought by integrating mental models into the metaecosystems framework be more useful than the pre-existing implicit consideration of human influences in meta-ecosystems? We find that this may depend on the questions being addressed, for example, when the focus is no longer on the meta-ecosystem dynamics themselves, but rather on the long-term consequences of feedbacks between meta-ecosystem and socio-cultural dynamics. This implies that the ecosystem services provided by meta-ecosystem dynamics ( [START_REF]Ecosystems and Human Well-Being: Synthesis[END_REF], arrow 2 in Fig. 1B) strongly feed back on mental models (arrow 3); in the geese example, this would happen if tundra loss is sufficiently important for public opinion to change agricultural or hunting practices towards "tundra-sustainable" ones. To analyse such scenarios, the metaecosystem framework could be embedded into a socio-ecological perspective in stylized models explicitly focusing on these feedback links (bold arrows in Fig. 1B), similarly to approaches proposed in the study of biodiversity -human society interactions [START_REF] Lafuite | Delayed behavioural shifts undermine the sustainability of social-ecological systems[END_REF]. In such models, however, explicit consideration of meta-ecosystem dynamics is not needed, merely the effects that these meta-ecosystem dynamics produce on ecosystem properties of values for humans.

In conclusion, to our opinion, zooming in the meta-ecosystem box (Fig. 1B), or zooming out on the socio-ecological feedback loop, relates to different questions, which might be better addressed with different modelling frameworks (meta-ecosystem versus socio-ecological). In that context, we suggest that the interactions between socio-cultural processes and meta-ecosystem dynamics should be addressed in an iterative scientific process through planned collaborations, as has been proposed for coordinating exchanges between theory and empirical work [12]. Thus, the results of one perspective can inform the other, better hypotheses can be tested, and our understanding can be bolstered by strong inference, without all processes necessarily being integrated into one framework. ). These mental models influence environmental regulation, which modulates the impact of human activities on spatial flows and meta-ecosystem dynamics (e.g., through rules on land-use or hunting; arrow 1). Meta-ecosystem dynamics affect ecosystem properties, such as productivity, or biodiversity, which provide services to people (arrow 2). Depending on the value that people attribute to these ecosystem services, change in meta-ecosystem dynamics might feedback on mental models (arrow 3), for instance (example panel A) the public opinion might shape hunting practices and regulations.

12 661 Figure 1 .

 6611 Figure 1. Meta-ecosystems in the Anthropocene. (A) The left panels show an example of

Acknowledgements

Funding is from the Swiss National Science Foundation Grant PP00P3_150698.


Chen-Chen Peng

Sheng-Yi Yang

Hong-Cheng Li

Guo-Hua Xie

Lin-Song Cui

Sheng-Nan Zou

Cyril Poriel

Zuo-Quan Jiang
email: zqjiang@suda.edu.cn

Liang-Sheng Liao
email: lsliao@suda.edu.cn.

C.-C Peng

S.-Y Yang

H.-C Li

Prof S.-N Zou

Prof Z.-Q Jiang

L.-S Liao

Dr G.-H Xie

Prof C Poriel

Dr L.-S Cui

Prof L.-S Liao

Highly Efficient Thermally Activated Delayed Fluorescence via Unconjugated Donor-Acceptor System Realizing EQE of over 30%

Keywords: fluorescence, organic light-emitting diodes, high efficiency, intramolecular spatial charge transfer, unconjugated system

thermally activated delayed

quantum efficiency (EQE) of 30.8% with a very flat efficiency roll-off of 7% at 1000 cd/m 2 .

The solution-processed OLEDs also displays an interesting EQE of 16.2%. 3tDMG shows improved solubility and solution processability as compared to 2tDMG, and thus a high EQE of 20.2% in solution-processed OLEDs is recorded. The corresponding evaporation-processed OLEDs also reach a reasonably high EQE of 26.3%. Encouragingly, this work provides a novel strategy to address the imperious demands for OLEDs with high EQE and low roll-off.

In the past decade, the development of organic light-emitting diodes (OLEDs) was reshaped by thermally activated delayed fluorescence (TADF) which can fully utilize both singlet/triplet manifold excitons through reverse intersystem crossing (RISC) and remove heavy metal by using environmentally benign pure organic molecules. [1] Now, the cuttingedge TADF materials can exceed 30% external quantum efficiency (EQE) in electroluminescent devices, but these highly efficient TADF materials are basically limited to donor (D)-π-acceptor (A) molecular architecture. [2] This type of molecular design, firstly proposed by Adachi et al. for TADF, [1a] can tune their D or/and A groups, geometries and steric hindrance between them to generate twisted induced charge-transfer (TICT)-type emission. [3] The twisted dihedral angle between D and A units can minimize the singlet-triplet splitting energy (ΔE ST ) for fast RISC, [1c, 4] but the resulted TADF OLEDs still need to be significantly improved, notably in terms of efficiency roll-off at high brightness and concentration quenching because of the π-π intermolecular interactions in the solid-state. [5] Another way to achieve TADF is to use D/A complex, in which the D/A blocks are spatially isolated, but their forming exciplexes are far less efficient than D-π-A analogues and the resulting OLEDs also display severe efficiency roll-off. [6] Recently, researchers conceptually consider that the intramolecular noncovalent interaction between D/A units in face-to-face alignment could be a new option to realize TADF. [7] Constructing TADF materials in this unconjugated way has the potential to combine the small ΔE ST value with substantial transition dipole and achieve high luminescent efficiency. [8] These two electron-rich and electron-poor π-systems need to be held close in space to form homoconjugation. In this regard, dozens of molecular frameworks have been employed but the performances remain around 10%~20% EQE, [7,8] similar to those of D/A complexes. The problem may probably account for the D/A geometry not only the D/A distance. In other words, short D/A distance is essential for TADF but cannot ensure high efficiency which is more challenged and determinant for material and device performance. In addition, restriction of intramolecular motion (RIM) should also be taken into account in regard to enhancing photoluminescence quantum yield (PLQY). [1b,5,7b,9] However, in previously reported structures, it is noted that both D and A units are extended in single bonds, indicating the molecular conrotatory motion cannot be thoroughly restricted. [4,7c,7d] Even though these D/A units exist in a short distance and the excitation process is completed, the emission energy may be lost in free rotation.

In this work, we designed highly efficient TADF materials based on D/A intramolecular noncovalent interaction; the key design rules include not only the short D/A distance but also the fixation of the D/A geometry. We connected the D/A units via a rigid linker, thereby confining them into a closely-packed coplanar configuration (Figure 1a). [10] In light of the molecular construction, the target TADF materials could achieve very small ΔE ST and high PLQY simultaneously. Besides, we also introduced t-butyl groups to improve the solubility of the TADF emitters. For the acceptor, the 2,4,6-triphenyl-1,3,5-triazine (TPZ) is a nearly planar structure because of strong hydrogen bonding, and the rigid structure contributes to space charge transfer and reduced molecular vibration leads to enhanced PLQY. Two greenish-blue TADF emitters, 2-(tert-butyl)-10-(4-(tert-butyl)phenyl)-1'- (4-(4,6-diphenyl-1,3,5-triazin-2-yl)phenyl)-10H-spiro[acridine-9,9'-fluorene] (2tDMG) and 2,7-di-tert-butyl-10-(4-(tert-butyl)phenyl)-1'- (4-(4,6-diphenyl-1,3,5-triazin-2-yl)phenyl)-10H-spiro[acridine-9,9'-fluorene] (3tDMG), were applied in both evaporation-processed and solution-processed TADF OLEDs. 2tDMG achieved an extremely high EQE of 30.8% (evaporation-process) with efficiency roll-off while 3tDMG also obtained a high EQE of 20.2% (solution-process) because of its better solubility. These excellent results open new avenues for the study of spatial electronic interactions in organic emissive materials.

The TADF materials of 2tDMG and 3tDMG can be facilely prepared through efficient threestep reactions (Supporting Information, Scheme S1). Although the overall yield of the optimized route is high, it should be noted that the reaction sequence is quite critical. We once tried to append the donor, the t-butyl substituted triphenylamine, at C9 site of fluorene to form spiro structure and then linked it with the acceptor, TPZ, to afford the target molecules. But due to the great steric hindrance at C1 site of fluorene, [11] the last-step Pd-catalyzed coupling gave no product. The synthetic failure is an important hint: in previous reports, [12] the researchers had not met similar difficulty when they introduced D/A units in short spatial distance via coupling reaction, indicating other molecular backbones to hold close D/A units were still somewhat flexible. But in our cases, the bulky and robust spiro-backbone prevented coupling reaction from happening at the adjacent C1 site.

The conjecture about D/A special conformation hinted by the above steric hindrance is confirmed by the single crystal structures of 2tDMG and 3tDMG (Supporting Information, S1). Significantly, the presence of rigid spiro structure fixes the donor and refrains the acceptor from rotational and vibrational movement to a large extent. It indicates a short distance between donor and acceptor and a well D/A cofacial conformation, which are beneficial for spatial D/A charge transfer. [7b,13] The minimum distances between A and the best fit plane of D are 3.09 Å of 2tDMG and 3.11 Å of 3tDMG which are similar to the inter-ring distance (3.09 Å) of [2.2]paracyclophane, [14] the closest stacked aromatic rings reported to date. Then, dihedral angles between the planes of the fluorene and the TPZ are 72.48° and 69.57° for 2tDMG and 3tDMG, respectively, indicating D/A planes in 2tDMG are in more parallel conformation.

Following the fascinating cofacial D/A configuration seen in the crystal structure, the D/A interaction was further understood by the computational simulation. Ground-state and excitedstate geometries at the B3LYP-D3BJ [15,16] /def2-SVP [17,18] and wb97xd [19] /def2-SVP [17,18] levels are respectively performed (Supporting Information, Figure S4, Table S2). In lowlying singlet (S 1 ) state, the hole/electron are separated to the donor and acceptor respectively, but in low-lying triplet (T 1 ) state, the hole/electron are localized on the fluorene linker, because the fluorene segment has the lowest triplet energy (Supporting Information, Figure S5). The calculation also shows a significant separation of the highest occupied molecular orbitals (HOMOs) and the lowest unoccupied molecular orbitals (LUMOs). For both 2tDMG and 3tDMG, the HOMO is mainly located on the t-butyl substituted triphenylamine units and the LUMO is mostly situated at TPZ segments (Figure 1b,c). Because of the similar acceptor, 2tDMG and 3tDMG have similar LUMO energy levels of -2.091 and -2.093 eV, respectively.

Meanwhile, 3tDMG has a relatively higher HOMO (-4.896 eV) than 2tDMG (-4.968 eV) owing to the stronger donor ability of the triphenylamine unit with one more t-butyl group.

The detailed information is collected in Table S2. On the other side, the functions of reduced density gradient (RDG) and Sign (λ 2 )ρ were calculated to show the intramolecular noncovalent interactions in 2tDMG (Figure 1d,f) and 3tDMG (Figure 1e,g). The green region and brown region of RDG analysis show the presence of obvious attractive interactions and large steric hindrance between D and A moieties respectively, which could be beneficial for suppressing the intramolecular vibrations and reducing energy loss of the excited molecules. [20] 2tDMG and 3tDMG were analyzed by ultraviolet-visible (UV-vis) absorption and photoluminescence (PL) measurements in the toluene solution (Figure 2a). In the absorption spectra, 2tDMG and 3tDMG both show strong absorption at nearly 300 nm attributed to the local π-π * transitions. On the other hand, they also exhibited an intramolecular charge transfer (ICT) transition band around 400 nm displaying weak absorption between 370 and 440 nm, indicating a non-trivial level of interaction between the D/A moieties. Then, based on the absorption edges, the corresponding optical bandgaps can be calculated to be 2.75 eV for 2tDMG, and 2.66 eV for 3tDMG,respectively. When excited at 340 nm in the toluene solution at room temperature, a strong emission is observed for both 2tDMG and 3tDMG, at 502 and 505 nm respectively. We can obtain the S 1 energies and the T 1 energies of 2tDMG and 3tDMG from the fluorescence spectra and phosphorescent spectra in toluene at 77 K (Supporting Information, Figure S6). Therefore, the ΔE ST s of 2tDMG and 3tDMG were calculated to be 0.03 and 0.01 eV, respectively. The ΔE STs are quite small and would be beneficial for the efficient RISC process. respectively, meanwhile, the delayed sections of these two TADF materials are respectively 3.43 and 2.28 μs measured at 300 K. With the temperature decreasing from 300 to 100 K, the delayed sections were reduced gradually. Because the delayed fluorescence emission process is triggered by RISC of TADF materials which is a thermally activated process, it reaffirms the TADF nature of 2tDMG and 3tDMG. To further compare exciton utilization, PLQY was measured under nitrogen atmosphere and the PLQY of 2tDMG: DPEPO film (87%) is slightly higher than 3tDMG: DPEPO film (86%) (Supporting Information, Table S3).

The HOMO energy levels of 2tDMG and 3tDMG are determined by the onset of the first oxidation wave (Supporting Information, Figure S7), and the LUMO energy level can be calculated from the optical bandgap based on UV-vis absorption spectra and the HOMO energy level. The HOMO energy level of 2tDMG is estimated to be -5.12 eV, and 3tDMG has a higher HOMO of -5.03 eV corresponding to the more t-butyl groups. For comparison, the spirophenylacridine-fluorene compound, not bearing t-butyl groups displays a lower HOMO energy level (-5.33 eV obtained from E 1/2 ). [21] This translates the significant impact of the number of t-butyl groups located at the donor for HOMO energy level. The LUMO energy levels of 2tDMG and 3tDMG are both estimated to be -2.37 eV as their acceptor is identical.

Therefore, the electrochemical bandgaps (E g s) of 2tDMG and 3tDMG are calculated to be 2.75 and 2.66 eV, respectively.

Thermal and morphological stabilities are fundamental to the fabrication and operation of OLED. To investigate the thermal stability, thermogravimetric analysis (TGA) was carried out under a nitrogen atmosphere. As presented in Figure S8, the decomposition temperatures (T d ) of 2tDMG and 3tDMG with 5% weight loss are recorded at 369 and 375 °C, respectively. Diff erential scanning calorimetry (DSC) of 2tDMG and 3tDMG have also been measured showing high glass transition temperatures of 165 and 154 °C, respectively (Supporting Information, Figure S9). The results of TGA and DSC suggest that these two TADF materials can be fabricated in vacuum deposition and solution process for OLED manufacture because of great morphological stability. All these energy levels and physical properties are summarized in Table 1.

To investigate the electroluminescence (EL) properties of 2tDMG and 3tDMG, we fabricated the devices using these materials as emitters (Device 1-6). The OLED devices based on DPEPO as the host material exhibited a high efficiency at driving voltages lower than 3 V, (Figure S10-S15). There is a trend that the operating voltages decrease as the doping ratios increase, implying charge-carrier transport property of TADF emitters is better than that of the DPEPO host material. Then, we added the hole and exciton blocking layers and fabricated device 1 (2tDMG) and 2 (3tDMG). The optimal device performance achieved with this structure of: ITO/ 1, 4,5,8,9,11- host utilized as the emitting layer (EML); TCTA was used as the exciton blocking layer, and the high T 1 of mCP and DPEPO can confine triplet excitons within the EMLs. Figure 3 shows the performances of the vacuum-deposited OLEDs based on 2tDMG and 3tDMG and the EL maximum peaks are 504 and 518 nm respectively, agreeing well with their photoluminescence behaviors. The best EL efficiency is found with 2tDMG (device 1: 30.8%, 88.5 cd/A, 71.8 lm/W) whereas 3tDMG displays lower performance (device 2: 26.3%, 85.0 cd/A, 73.9 lm/W) and both devices show a small roll-off. 2tDMG has much shorter D/A distance, meanwhile, the fit planes of donor and acceptor are near to parallel which is beneficial for space charge transfer. Then, we also designed devices 3 and 4, in which mCP was used as host instead of DPEPO, device structure: ITO/ HAT-CN (10 nm)/ TAPC (40 nm)/ TCTA (8 nm)/ mCP: emitters (20 nm, 30 wt% for 2tDMG, 20 wt% for 3tDMG)/ TmPyPB (40 nm)/ Liq (2 nm)/ Al (100 nm). However, the EL efficiencies of 2tDMG and 3tDMG were lower than those using DPEPO. Actually, it is believed that n-type hosts, such as DPEPO, are suitable to realize stable delayed fluorescence organic electroluminescent devices. [22] Because of the t-butyl groups, 2tDMG and 3tDMG have the potential for solution-processed OLEDs. Therefore, we fabricated solution-processed OLEDs (Device 5-6) as shown in TmPyPB (50 nm)/ Liq (1 nm) / Al (100 nm). In these devices, PEDOT:PSS and Liq acted as the hole-injection layer and electron-injection layer respectively, TmPyPB served as the electron-transporting layer, and CzAcSF was selected as the host. DPEPO was used as the hole-blocking layer to optimize the devices (Supporting Information, Figure S16,S17). These solution-processed OLEDs show blue-shift EL emission peaks, 486 (2tDMG) and 504 nm (3tDMG), compared to the vacuum-processed devices. Moreover, these solution-processed OLEDs achieve competitive high efficiencies with maximum EQEs of 16.2% (2tDMG) and 20.2% (3tDMG). It is believed that the better solubility of 3tDMG than 2tDMG due the presence of two t-butyl groups is one of the reasons of its better device performance in solution process OLEDs (Figure S18). To our best knowledge, this is also the first time reaching 20% EQE threshold out of the traditional D-π-A TADF series. [7a,7c,23] All the device performances of 2tDMG and 3tDMG are summarized in Table 2.

In summary, we designed and synthesized greenish-blue TADF emitters based unconjugated D/A blocks interacted in confined space. These materials rely on the rigid backbone and short D/A distance which in turn restrict the free rotations of constitutional blocks and impose D/A to adopt a favorable cofacial conformation. t-butyl groups are introduced to make the TADF emitters 2tDMG and 3tDMG suitable for both evaporation and solution processed devices.

As a result, both materials show small ΔE ST and high PLQY as well as high T g because of the rigid backbone. In evaporation-processed TADF devices, 2tDMG and 3tDMG achieve 30.8% and 26.3% EQEs respectively; notably, the efficiency can retain as high as 28.5% and 23.2% at the 1000 cd/m 2 respectively, indicating very flat efficiency roll-offs. In solution-processed OLEDs, the maximum EQEs are 16.2% and 20.2% for 2tDMG and 3tDMG respectively. These excellent performances clearly demonstrate a disruptive motif in constructing highly efficient TADF materials out of conventional D-π-A architecture. We thus believe our results could shed a new light on the development of optoelectronic functional materials in noncovalent interactions.

[ CCDC-1992381 (2tDMG) and CCDC-1992382 (3tDMG) [nm] 8, 28.5, 24.6 71.8, 55.5, 38.8 88.5, 81.9, 70.3 (0.24 8, 18.4, 15.6 45.0, 32.7, 24.4 58.0, 51.8, 43.8 (0.24

λem a) [nm] S1 b) [eV] T1 b) [eV] EST [eV] HOMO c) [eV] LUMO c) [eV] Tg d) [ o C]

The table of contents entry:

The thermally activated delayed fluorescence emitter 2tDMG is designed and synthesized based on donor (D)/acceptor (A) spatially intramolecular noncovalent interaction. The D/A units are connected via a rigid linker, thereby confining them into a close-packed coplanar configuration for small singlet-triplet splitting energy (ΔE ST ). 2tDMG achieves a high external quantum efficiency of 30.8% with a low efficiency roll-off in evaporation-processed.

Keyword

Figure

  Figure S1-S3, TableS1). Significantly, the presence of rigid spiro structure fixes the donor

  Figure 2b shows transient PL decay curves which were measured by vacuum-deposited process. Transient PL measurements of 2tDMG and 3tDMG dispersed in bis[2-(diphenylphosphino)phenyl]ether oxide (DPEPO) host material were investigated to analyze the excited-state lifetime for the delayed PL emission. The doped films exhibited a prompt decay component and a delayed emission decay profile. The prompt decays of 2tDMG and 3tDMG doped film with lifetimes of 106 and 91 ns are observed

  hexaazatriphenylenehexacarbonitrile (HAT-CN, 10 nm)/ 1,1bis[(di-4-tolylamino)phenyl]cyclohexane (TAPC, 40 nm)/ 4,4',4''-tris-(carbazol-9-yl)triphenylamine (TCTA, 8 nm)/ 1,3-di(9H-carbazol-9-yl)benzene (mCP, 8 nm)/ DPEPO: 40 wt% emitters (20 nm)/ DPEPO (8 nm)/ 1,3,5-tri[(3-pyridyl)-phen-3-yl]benzene (TmPyPB, 40 nm)/ 8-hydroxyquinolinolato-lithium (Liq, 2 nm)/ Al (100 nm). The device configuration and molecular structures of functional materials are shown in Figure S10. HAT-CN and Liq were employed as the hole and electron-injection materials, respectively; TAPC and TmPyPB served as the hole-transporting layer and electron-transporting layer; emitter doped in DPEPO

Figure 3 ,

 3 Figure 3, and the best structure was: ITO/ poly(3,4-ethylenedioxythiophene)-poly(styrene

  contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.online: ((will be filled in by the editorial staff)) [22] L.-S. Cui, S.-B. Ruan, F. Bencheikh, R. Nagata, L. Zhang, K. Inada, H. Nakanotani, L.-S. Liao, C. Adachi, Nat. Commun. 2017, 8, 2250.[23] Z. Yang, Z. Mao, Z. Xie, Y. Zhang, S. Liu, J. Zhao, J. Xu, Z. Chi, M. P. Aldred, Chem.Soc. Rev. 2017, 46, 915.

Figure 1 .

 1 Figure 1. Configuration and molecular structures (a) of 2tDMG and 3tDMG; HOMO and

Figure 2 .

 2 Figure 2. (a) UV-vis absorption, fluorescence (298 K) of 2tDMG and 3tDMG respectively.

Figure 3 .

 3 Figure 3. OLED device performances based on different device structures (Device 1-6). (a, d,

:

  thermally activated delayed fluorescence; organic light-emitting diodes; high efficiency; intramolecular spatial charge transfer; spiro structure C.-C. Peng, S.-Y. Yang, H.-C. Li, G.-H. Xie, L.-S. Cui, S.-N. Zou, C. Poriel, Z.-Q. Jiang*, L.-S. Liao* High Performance Organic Light Emitting Diode with over 30% External Quantum Efficiency by Using Thermally Activated Delayed Fluorescence

Table 1 .

 1 Summary of photophysical, electrochemical and thermal properties of 2tDMG and 3tDMG.

	Compounds	λabs a)

Table 2 .

 2 Summary of device performances utilizing 2tDMG and 3tDMG.

	Td e)
	[ o C]

  Values of external quantum efficiency (EQE), power efficiency (PE) and current efficiency (CE) at the maximum, 1000 cd/m 2 , and 4000 cd/m 2 , respectively.

								, 0.52)
	5	solution	CzAcSF: 2tDMG	486	16.2, 7.4, 3.6	20.1, 6.4, 2.4	37.5, 17.2, /	(0.22, 0.37)
	6	solution	CzAcSF: 3tDMG	504	20.1, 6.7, 4.9	21.1, 5.1, 2.9	53.6, 17.9, 12.0	(0.28, 0.46)
	a)

Acknowledgements

The authors acknowledge financial support from the National Key R&D Program of China (No. 2016YFB0400700), the National Natural Science Foundation of China (Nos. 51773141, 51873139 and 21572152) and the Natural Science Foundation of Jiangsu Province of China (BK20181442). This project is also funded by Collaborative Innovation Centre of Suzhou Nano Science & Technology, the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), the 111 Project of The State Administration of Foreign Experts Affairs of China.

Supporting Information

Supporting Information is available from the Wiley Online Library or from the author.


Noémie Emmanuel

Pauline Bianchi

Julien Legros

Jean-Christophe M Monbaliu
email: jc.monbaliu@uliege.bewww.citos.uliege.

A safe, green and compact flow platform for the neutralization of a mustard gas simulant with air and light

A low footprint, mobile, robust and frugal chemical neutralization technology is reported for the oxidative neutralization of a mustard gas simulant. It relies on the inherent properties of a highly engineered continuous flow setup and carefully optimized and simple, yet robust, experimental conditions. The neutralization protocol uses only non-toxic, widely available and cheap chemicals. The continuous flow setup integrates a singlet oxygen generator and exploits its oxidative power to neutralize 2-chloroethyl ethyl sulfide (CEES), the most common thioether mustard gas simulant. The flow reactor can be connected to either pressurized oxygen or air and handles CEES as a 1 M solution in EtOH containing a trace amount (0.06 mol%) of a non-toxic and widely available photosensitizer (Methylene Blue). Upon irradiation with visible light (orange or white light), total and highly selective neutralization towards the corresponding non-toxic sulfoxide (1chloro-2-(ethylsulfinyl)ethane, CEESO) is obtained with reactor effluents containing less than 1% of the corresponding potentially toxic sulfone (1-chloro-2-(ethylsulfonyl)ethane, CEESO2). With a low footprint (L x W x H 94 x 42 x 40 cm), this neutralization technology can be embarked on a vehicle for on-site interventions, localized at a neutralization facility or both. The experimental work is also supported with a computational rationalization of the reactivity of CEES towards singlet oxygen.

Introduction

Chemical warfare agents (CWAs, Figure 1) were conceived in the darkest converging alleys of Science and Industry to optimize debilitating, incapacitant or lethal activity for maintaining military superiority.

1 World War II stressed the emergence of much more redoubtable nuclear warfare, even though large stockpiles of CWAs were maintained worldwide and new chemical agents were developed. Since WWII, CWAs were sporadically used for armed conflicts with the last reports dating back to 2017-2018 in the Middle East. The tragedy with CWAs remains that it also affects civilians who lack protection gears and antidotes.

The Chemical Weapons Convention (CWC) entered in force in 1997 with the ambition to prohibit the possession, manufacture and use of CWAs and was ratified by 193 countries.

3 Besides prohibition, it also aims at developing resources, procedures and capacities to treat the consequences of a CWA attack and to supervise the destruction of stockpiles, related equipment and infrastructure. There are still large inventories of CWAs reminiscent of previous conflicts, either as a latent, still usable threat or as spoiled ammunitions. Besides, the availability of various chemicals on small to medium scale as well as emerging process technologies with a very low footprint have also raised significant concerns with the potential local production of CWAs for chemical terrorism. [START_REF] Gérardy | [END_REF] Following the inception of the CWC, a total of 8 countries declared CWAs, 7 of which have now completed the destruction of 97% of the declared inventories worldwide. The USA has announced the destruction of 90% of its total inventory and aims at a complete destruction by 2023. Please do not adjust margins Please do not adjust margins Among CWAs, 1-chloro-2-[(2-chloroethyl)sulfanyl]ethane (CAS 505-60-2) commonly referred to as mustard gas or HD is a Schedule I CWA with cytotoxic and vesicant properties.

8 HD is considered as the parent molecule of sulfur mustards. The unique reactivity and toxicity profile of sulfur mustards arise from the combination of donor lone pairs n S on the sulfur atom in the vicinity of two σ* C-Cl acceptors, hence potentially forming strongly alkylating and toxic episulfonium species epi-HD (Figure 2a). 9 The most common method of destruction of HD relies on incineration, 10,11 although such a method raises significant safety concerns not only for the emission of toxic gaseous or liquid emissions upon thermal treatment but also for the transportation risk.

12 Chemical neutralization methods 10,11 (methods 1-3, Figure 2b) for sulfur mustards such as HD or its most common simulant CEES (2-chloroethyl ethyl sulfide) typically target either one of the lone pairs n S on sulfur through selective oxidation towards a sulfoxide (method 1) or the σ* C-Cl acceptors through hydrolysis or displacement with a strong nucleophile (method 2). 13 A third alternative method of chemical neutralization relies on dehydrohalogenation protocols (method 3). Although these oxidative neutralization methods seem straightforward, the complex reaction profile of HD/CEES makes them very cumbersome. For instance, the overoxidation of HD/CEES leads to the formation of a strong Michael acceptor sulfone CEVSO 2 /EVSO 2 , [14][15][16] the toxicity of which is comparable to the parent mustard. In all instances, its formation must thus be limited to trace amounts. The selectivity of the oxidation is therefore a critical parameter for the validation of a neutralization method. The lipophilic nature of HD/CEES typically renders aqueous oxidation protocols inefficient, hence often imposing surfactants 14 or organic solvents as carriers. 15 Primary oxidizers typically include hydrogen peroxide, 14,16-22 peracids 15 or oxygen [22][23][24][25] in the presence of homogeneous 26 or heterogeneous catalysts. [16][17][18][27][28][29][30][31] Other oxidizers were also reported such as Niodosuccinimide/water (Table 1).

32

The oxidative neutralization methods relying on reactive oxygen species are very attractive, especially when molecular oxygen is the primary oxidant source (Table 1). Zeolites 2 and MOF-based heterogeneous materials and fibers were also reported and successfully tested for the UV photooxidation of CEES and actual samples of HD. 23,28,[33][START_REF] Howarth | Please do not adjust margins[END_REF][35][36] These photooxidations typically proceed with complete conversion and high to complete selectivity towards the sulfoxide HDO with a catalytic amount (typ. 1-2 mol%). 23,28 The heterogeneous MOF photocatalyst can be easily recovered after neutralization and is potentially reusable. 35 Photoactive ferrocene-conjugated microporous polymers were also reported. 24,25 Despite excellent results, these methods have only been reported on the milligram scale and would face additional challenges for reaching larger scales. Organic homogeneous photosensitizers were also considered under aerobic conditions such as Riboflavin tetraacetate (RFTA) or riboflavin (vitamin B2). 37,38 Under irradiation with blue LEDs (450 nm) with 2 mol% RFTA at room temperature, CEES was quantitatively and selectively converted into CEESO in 10 min of irradiation. Borondipyrromethene (BODIPY) PSs were assessed for the photooxidation of CEES and actual samples of HD under blue light irradiation in solution or impregnated on PVDF films and textiles, providing CEES half-life down to 0.8 min.

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Other critical parameters are the compactness, robustness and inherent safety related to the neutralization method. Indeed, the neutralization setup must be transportable and compact for rapid deployment on site. It must also provide consistent neutralization with high selectivity yet relying on simple, non-toxic, cheap and widely available chemicals. While most of the oxidative procedures rely on batch setups, several authors have considered continuous flow conditions and flow reactors as process technologies endowed with unique inherent features that could be exploited for the efficient oxidation of CEES specifically r for the use of oxygen and related reactive species. [40][START_REF] Hone | The Use of Molecular Oxygen for Liquid Phase Aerobic Oxidations in Continuous Flow[END_REF][START_REF] Kassin | [END_REF][43][44][45] In particular, photocatalysis in flow has attracted significant attention both for the preparation of advanced chemical structures and for the chemical destruction (neutralization) of pollutants. 46 Flow protocols relying on either homogeneous or heterogeneous photocatalysts [47][48][49][50][51][52] benefit from the synergistic combination of flow and photochemistry: uniform irradiation with accurately controlled irradiations times, hence leading to intensified reactions with shorter and more selective reaction pathways. 46,[53][54][START_REF] Ishitani | Chapter 1: Recent Perspectives in Catalysis under Continuous Flow[END_REF] Flow conditions are also typically considered as scale-independent and easier to scale-up than conventional batch setups.

46,53-56

Seeberger was actually one of first to report the catalytic photooxidation of thiodiglycol TDG (0.25 M) under continuous flow conditions. 58 The authors used tetraphenylporphyrin (TPP, 2 mM) in chloroform as a photosensitizer. The reactor was operated at room temperature under 6.9 bar of . The oxidation was carried out with the hydrogen peroxide/urea complex (UHP) in methanol with methanesulfonic acid as promotor. The authors reported complete and selective oxidation mustard gas simulant CEES within 3.9 min of residence time, and overoxidation to the sulfone was avoided by collecting the reaction effluents in a quenching solution. Despite its effectiveness, their procedure imposes the availability and transportation of explosive and corrosive reagents along with the reactor setup. Moreover, the use of UHP releases stoichiometric amounts of urea in the effluents to be further disposed.

Based upon our expertise in the design of flow processes and in particular for the generation and handling of reactive oxygen species 5,59-61 , a compact flow system (L x W x H 94 x 42 x 40 cm) was devised for enabling rapid deployment on site and effective oxidative neutralization with frugal and benign resources. We report herein an advanced continuous flow setup for the selective oxidation of simulant CEES and further document the reactivity of such thioethers through MP2 and Natural Bond Order (NBO) computations. The combination of both experimental and theoretical approaches led to a more refined understanding of the unique features of the photooxidation of thioethers. This process is unique compared to the prior Art (Table 1, entry 16) since (a) it relies on the unique features of a highly engineered continuous flow setup using intensified and user-friendly conditions; (b) it uses the powerful combination of oxygen (or air), visible light and trace amounts (0.06 mol%) of a non-toxic, cheap and widely available organic photosensitizer (Methylene Blue); (c) only environmental and user-friendly reagents are involved, including the solvent (EtOH); (d) the reactor setup is mobile and can be embarked on a vehicle for on-site neutralization with minimal resources and it can be integrated with in-line analysis for process monitoring and increased safety; (e) quantitative conversion of simulant CEES is obtained with high selectivity within 4 min of irradiation time under mild process conditions (20 °C, 9 bar) with unprecedented concentrations (1 M in ethanol); (f) the process is virtually scaled-independent since it relies on intensified flow conditions that can be transposed to much larger scales with larger commercial fluidic reactors. It provides the most cost effective, operatorfriendly and low footprint process with high atom economy reported so far for the oxidative neutralization of mustard gas simulant CEES. .

Experimental section

General information

Conversion, selectivity and yield were determined by Gas Chromatography coupled to Flame Ionization Detection (GC-FID) or Mass Spectrometry (GC-MS) or by High Performance Liquid Chromatography coupled to Diode-Array Detection (HPLC-DAD). GC and HPLC conversions and yields were determined using external calibration curves established with commercial standards (2-chloroethylethyl sulfide, 2chloroethylethyl sulfone, ethyl vinyl sulfide, ethyl vinyl sulfone, methyl vinyl sulfone, methyl phenyl sulfide, methyl phenyl sulfoxide, methyl phenyl sulfone, dipropyl sulfide, dipropyl sulfone, thiodipropionic acid, dibenzyl sulfide, dibenzyl sulfoxide, dibenzyl sulfone, diphenyl sulfide, diphenyl sulfoxide, diphenyl sulfone, tetrahydrothiophene sulfide, tetrahydrothiophene sulfoxide, tetrahydrothiophene sulfone, benzyl phenyl sulfide, diethyl sulfide, benzyl methyl sulfide, benzyl methyl sulfone, dibenzothiophene, dibenzothiophene sulfone) or with synthesized reference samples following reported procedures (see Supporting Information Section 2.2.4 for experimental procedures). 19,30,35,39 Structural identity was confirmed by 1 H and 13 C NMR spectroscopy (400 MHz Bruker Avance spectrometer) in CDCl 3 (Supporting Information Sections 2.4 and 2.5). Ethanol, acetonitrile, water, Rose Bengal, Methylene Blue, 9,10-dicyanoanthracene, oxygen and air were obtained from commercial sources, and used without additional purification.

CAUTION:

1-chloro-2-(ethylsulfinyl)ethane (CEES) is a highly toxic and severe vesicant. It must be handled with great care under a fume hood. The access to 1-chloro-2-[(2-chloroethyl)sulfanyl]ethane (mustard gas or HD) is subjected to military clearance under very strict conditions.

Computations

Computations were performed at the MP2/6-31+G** or B3LYP/6-31+G** level of theory with the Gaussian 09 package of programs (Revision D.01) with implicit solvent (PCM, ε = 24.852, ethanol). Stationary points were optimized with gradient techniques (tight optimization convergence). Transition states were localized using the Newton-Raphson algorithm, and the nature of the stationary points was determined by analysis of the Hessian matrix. Intrinsic reaction coordinate (IRC) calculations were performed on representative transition states. NBO calculations and population analysis were performed at the B3LYP/6-31+G**level on the optimized structures (MP2/6-31+G**). Graphical representations of the HOMO of thioethers were obtained through the FormChk utility in Gaussian 09 62 . , and both streams were conveyed through PFA tubing to the first glass fluidic module of the Corning® Advanced-Flow™ LF/G1 skid Photo Reactor upon irradiation at 610 nm (full intensity, 300 LEDs) at 20° C (9 bar of counterpressure) (Figure 6). The reactor effluent was collected at steady state, diluted with EtOH and analyzed by GC/FID (99% conversion, 99% selectivity, see Table 1).

Experimental

Results and Discussion

The photooxidation of thioethers has been widely discussed in the literature through mechanistic and computational studies, and various mechanisms were postulated and assessed.

63-77

Depending on the photosensitization, the oxidation can proceed either through the addition of the thioether substrate onto singlet oxygen or through electron transfer (ET) involving the superoxide anion. 66,78 The photooxidation of thioethers with singlet oxygen is consensually recognized as a complex reaction sequence leading to various oxidations products, among which the corresponding sulfoxides are typically the major product, along with variable amounts of sulfones and oxidative fragmentation products. 65,69,74,76 The process goes through the formation of several key intermediates (Figure 3), the first of which being a weakly bound peroxysulfoxide intermediate A that forms upon the addition of the nucleophilic thioether substrate onto electrophilic singlet oxygen. Intermediate A was actually never isolated. The fate of the later determines the output of the photochemical process.

Intermediate A typically undergoes physical quenching in apolar aprotic solvents, while it is stabilized in protic solvents, hence drastically improving the efficiency of the photooxidation.

73,79

The exact nature of the second intermediate B has fed intense debate in the literature; advanced mechanistic and computations studies pointed towards hydroperoxysulfonium ylide B 2 rather than thiadioxirane B 1 . [63][64][65][66][67][68][69][70][71][72][73][74][75][76][77] The reaction of each molecule of singlet oxygen can potentially result in 2 equiv. of sulfoxide.

64,73

Fig. 3. Commonly accepted intermediates and mechanism for the reaction of thioethers with singlet oxygen under photosensitized conditions. Singlet oxygen is typically generated from ground state molecular oxygen upon irradiation in the presence of a photosensitizer (PS). A common organic PS is Methylene Blue.

The access to HD is subjected to military clearance under very strict conditions, while small inventories of its most widely accepted simulant (CEES) can be purchased. CEES is however still a very toxic and severe vesicant that must be handled with great care, hence precluding its direct use for large-scale optimization. Decision was made to undertake a preliminary computational study on the reactivity of HD and CEES towards singlet oxygen for comparison with other widely available non-toxic thioethers, the handling of which for preliminary experiments with singlet oxygen would not raise a significant safety hazard. Obviously, the model thioethers must echo the peculiar inherent reactivity of HD/CEES for enabling fast transposition with minimal readjustments to CEES. The rationale behind such an approach was to limit the exposure to extremely toxic chemicals upon the optimization of the process conditions. In silico modeling enables to compute quantitative or semi-quantitative models and data, which are particularly relevant when high toxicity chemicals are at stakes.

The efficiency of singlet oxygen oxidation of thioethers is not only very sensitive to reaction conditions, but it also critically depends on the inherent structural and stereoelectronic features of the thioether substrate. The availability of the non-bonding n S orbitals on the sulfur atom, which correlates to its intrinsic nucleophilicity, is thus paramount to ensure quick and efficient scavenging of singlet oxygen to form peroxysulfoxide intermediate A. Any factor that potentially decreases the availability of the non-bonding n S orbitals on the sulfur atom will therefore potentially reduce the efficiency of the reaction with singlet oxygen. As discussed in the Introduction (Figure 2a), the reactivity and toxicity profiles of sulfur mustards HD and CEES arise from the combination of a donor lone pair n S on the sulfur atom in the vicinity of two σ* C-Cl acceptors; such stereoelectronic feature might thus impact the oxidative neutralization process. It is therefore critical to have access to a metric for assessing the extent of such stereoelectronic features for supporting the rational selection of an appropriate non-toxic model thioether. This journal is © The Royal Society of Chemistry 20xx

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In order to quantify the availability of the non-bonding n S orbitals and thus to provide insights on the potential for reaction with singlet oxygen, a preliminary computational study was undertaken on a series of model thioethers with defined structural and stereoelectronic features (Figure 4). The selected model thioethers included CEES and HD, as well as other alkyl, aryl and benzyl thioethers (1a-f),more specifically, dipropyl sulfide (1a), (chloromethyl)(ethyl)sulfide (1b), benzyl methyl sulfide (1c) methyl phenyl sulfide (1d), diphenyl sulfide (1e) and dibenzothiophene (1f). Thus the selection of thioethers 1a-f included thioethers with qualitatively expected high (1a), intermediate (1c, 1d) and low (1b, 1e, 1f) availability of non-bonding n S orbitals, thus mirroring a potentially decreasing reactivity towards electrophilic singlet oxygen. This qualitative scale relies on the structural analysis of the compounds 1a-f and the identification of any potential strong stereoelectronic or delocalization effects, yet a more precise scale was required.

The structures of HD, CEES and 1a-f were optimized at the MP2/6-31+G** level of theory in ethanol. In order to have more precise information on the availability of the nonbonding n S orbitals on the sulfur atom of each of these thioethers, NBO and electronic population analyses were carried out at the B3LYP/6-31+G** level of theory on the optimized structures (MP2/6-31+G**) A second order perturbation theory analysis of the Fock matrix in the NBO basis provided a convenient metric (Figure 4) to sense stereoelectronic features that are responsible for a decreased availability of the non-bonding n S orbitals on the sulfur atom, thus indicating a lower efficiency for the reaction with singlet oxygen. Only the potential donor/acceptor interactions (E int )

involving the non-bonding n S and acceptors such as σ* C-X (X = C, Cl) or * C=C were looked at on the most stable conformers of CEES, HD and 1a-f. From the NBO and population analyses (Figure 4), it can be seen that dialkyl sulfides such as CEES, HD and 1a have welllocalized HOMO centered on the sulfur atom and are characterized by low to negligible donor/acceptor interactions (Figure 4). ) involving a neighboring σ* C-C orbital. Major differences appear for 1d and to a larger extent to 1e,f, where the delocalization of the non-bonding n S orbitals to the aromatic ring drastically affects their availability. Dibenzothiophene 1f comes with a very strong stereoelectronic interaction (E int = 18.7 kcal mol -1 for each n S orbital). The results from the NBO and population analyses are in agreement with the data from the literature, which emphasize that alkyl aryl and diaryl sulfides are considered as poor quenchers of singlet oxygen compared to dialkyl sulfides due to their HOMO only partially localized on the sulfur atom.

67

The transition state for the quenching of singlet oxygen by thioethers 1a, CEES and HD towards the corresponding peroxysulfoxide intermediates A (1Aa, CEESOO and HDOO, respectively) were located at the MP2/6-31+G** level of theory in ethanol. The structure of the targeted sulfoxides (2a, CEESO and HDO) are illustrated for the sake of comparison (Figure 5). These TSs display an orthogonal approach of singlet oxygen relative to the thioether substrates and are structurally related (Supporting Information Section 4).

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Please do not adjust margins indicative of an early transition state and strong interactions between the non-bonding n S orbitals and singlet oxygen. 77 The slightly shorter S-O bond length for TS 1 HD (1.85 Å) compared to TS 1 1a , TS 1 CEES (1.87 Å) reflects the presence of two electrons withdrawing Cl atoms. From the analysis of both NBO and TS structures, it appeared that both 1a and CEES are potentially good structural mimics of the parent HD for such transformation, hence the results collected on the photooxidation of both 1a and CEES are expected to be transposable on HD.

Based on the computational results, preliminary trials were carried out under photosensitized conditions to calibrate the singlet oxygen oxidation process. The flow setup is described in Figure 6. It consisted of 5 specialty glass fluidic modules (FMs) of 2.6 mL each connected in series for a total of 13 mL. Each glass FM features a succession of high performance static mixers to ensure high mass transfer efficiency between gaseous and liquid effluents. Each FM is integrated with a double layer heat exchanger and is sandwiched between two LED panels, each equipped with 30 high power LEDs of a defined wavelength (300 LEDs in total). The LED panels are integrated with a dedicated heat exchanger. The combination of high-efficiency static mixers and high power LEDs makes this reactor configuration particularly well suited for the generation of singlet oxygen in the presence of organic substrates. 59 The reactor setup was kept under 9 bar of counterpressure with a dome-type backpressure regulator (BPR). In-line low field NMR or IR spectrometers were optionally inserted downstream for qualitative process monitoring and samples were analyzed off-line either by GC or HPLC (Supporting Information Section 2.2.1). Solutions of representative commercial thioethers were prepared in EtOH (1 M), unless solubility issues imposed a cosolvent or a lower concentration (Supporting Information Section 2.2.3), in the presence of an organic photosensitizer (Figure 6 and Table 2). Methylene Blue (MB) was selected as organic photosensitizer for the singlet oxygen reaction with thioethers 1a-f rather than Rose Bengal for its improved resistance to photobleaching and its overall better performances as an organic photosensitizer (Supporting Information Section 3.2.3). MB is a non-toxic, stable, widely available and affordable organic photosensitizer. The liquid feed solution was mixed with oxygen upon irradiation with the appropriate wavelength at 25 °C under 9 bar of counterpressure for a total estimated residence time of 10 min (see Supporting Information Sections 2.2.3 and 3.1 for details). The first set of conditions involved MB (0.06 mol%) in conjunction with oxygen and irradiation at 610 nm (orange LEDs) for the generation of singlet oxygen (entries 1-5). Control experiments in the absence of light or in the absence of organic photosensitizer were carried out as well, and no conversion was detected. Compound 1b was not tested since it reacted quickly with the solvent under these conditions.

The experimental observations were analyzed in parallel with the computation data (Table 2). It can be concluded that thioethers 1a, 1c and 1d that are characterized by a low stereoelectronic involvement of the non-bonding n S orbitals (E int  4.1 kcal mol -1

) and a rather S-centered HOMO are efficient quenchers of singlet oxygen under intensified flow conditions, and are converted selectively and quantitatively to the corresponding sulfoxides (Table 2, entries 1-3). No traces of sulfones or other oxidative fragmentation products were detected. By contrast, diaryl thioethers 1e,f were barely reactive towards singlet oxygen (entries 4,5). Changing the photosensitizer to 9,10-dicyanoanthracene (0.06 mol%) in acetonitrile under irradiation at 395 nm (entries 6,7) led to 47 and 49% conversion for compounds 1e,f. Such conditions are typically associated with the generation of a superoxide and an electron transfer mechanism for the oxidation of thioethers hence emphasizing the differences in terms of mechanism and its implication for the oxidation of structurally diverse thioethers. The choice of the involved mechanism depends not only on the structural and stereoelectronic features of the thioether, but also on the nature of the photosensitizer, which was not evaluated with the computational approach, hence showing the interests for combining computational with experimental data. A stock solution of CEES (1 M) and Methylene Blue (560 µM) weas prepared in EtOH (Supporting Information Section 2.2.3) and the process conditions were further optimized. Given the complex reactivity profile of CEES, a variety of side products are expected according to the data of the literature. Under the experimental conditions of this report, 4 impurities were detected (Scheme 1, Table 3), among which only CEESO 2 (the corresponding overoxidized sulfone) is considered as toxic since it potentially produces electrophilic vinyl sulfone EVS (Figure 2). Impurities I-1 and I-3 are formed through the addition of EtOH on CEES and CEESO and can therefore be considered as neutralized species. Impurity I-2 is formed through the dechlorination of CEESO and is typically considered as a non-toxic chemical. The identity of all impurities was confirmed by GC, GC-MS or NMR with commercial or prepared samples.

The impact of various process parameters (irradiation time, primary source of singlet oxygen, light intensity and nature) on the efficiency and the selectivity of the photooxidation was assessed (Table 3 and Supporting Information Section 3.2). In this process, the highest conversion of CEES must be reached within a short residence time, and the oxidation must be selective enough to produce low amounts of CEESO 2. The emergence of other impurities such as I-1, I-2 and I-3 does not impact negatively the process, since they are considered as neutralized species as CEESO. Scheme 1. Oxidative neutralization of CEES under optimized continuous flow conditions (see also Table 3).

The irradiation time can be reduced from 10 to 4 min upon irradiation at 610 nm with full intensity in the presence of oxygen while still reaching almost quantitative conversion of CEES (entries 1 and 7, >99% and 92%, respectively) towards mainly CEESO and other minor impurities (Scheme 1). A further decrease to 2 min nevertheless left about 18% of unreacted CEES in the reactor effluent (82% conversion). The amount of CEESO 2 increased with the conversion of CEES to CEESO, yet it remained under 1%: 0.1% (2 min), 0.4% (4 min) and 0.9% (10 min). Impurities I-1 (3%), I-2 (1%) and I-3 (3%) were present in the reactor effluent from the experiment at 4 min of irradiation time.

Please do not adjust margins Please do not adjust margins At 10 min of irradiation time, only impurities I-2 (1%) and I-3 (3%) were detected besides CEESO 2 . It is expected that the longer irradiation time oxidized completely I-1 towards I-3. At the shortest residence time (2 min), impurity I-3 was not detected while impurities I-1 and I-2 reached 2% and 1%, respectively. These observations indicate a potential filiation between I-3 and I-1, as well as I-2 (EVSO) and CEESO, although other reaction paths might be incriminated (See Supporting Information Section 2.2.4). Impurity I-2 is also believed to arise from the specific reactivity of the corresponding hydroperoxysulfonium ylide B 2 intermediate (Figure 3). Impurity I-1 most likely arises from a slow reaction between the substrate CEES and the solvent upon storage of the feed solution. Such reaction was not significant upon standing in the feed, and is likely to be accelerated in the flow reactor with the local heat generated by the LEDs (Supporting Information Section 2.2.4).

The efficiency of the photooxidation is typically greater with pure oxygen rather than air. This is logical and explainable as the proportion of oxygen is simply lower in air. Within 4 min of irradiation at 610 nm (full intensity), the conversion of CEES reached 99% with pure oxygen while it decreased to 51% with air under the same conditions. For the longest irradiation time (10 min), either oxygen or air gave a similar conversion (99%). The reactor effluent from the experiment with air within 4 min of irradiation was exempt from CEESO 2 , although this is most likely related to the low conversion of CEES than to the nature of the primary source of singlet oxygen. The amount of impurity I-1, was slightly higher for the experiment with air (4%) than for the experiment with oxygen (3%). Impurity I-3 was absent from the reaction with air, while 3% were formed in the presence of oxygen.

The intensity and the nature of the light source were also looked at (Supporting Information Section 3.2.4). Decreasing the LEDs intensity typically led to lower conversions, and the maximum intensity was used for most of the trials. With oxygen or air at the longest irradiation time (10 min), either orange LEDs (610 nm) or white LEDs (4000K) provided >99.9% conversion of CEES. The reactor effluent from the experiment with the 610 nm LEDs contained 95% of CEESO, and traces of CEESO 2 (0.6%), I-1 (0.5%), I-2 (2%) and I-3 (1%). The reactor effluent from the experiment with white LEDs had a similar composition with 96% of CEESO, and traces of CEESO 2 (1%), I-2 (1%) and I-3 (3%). Decreasing the residence time to 4 min still afforded quantitative conversion of CEES under white LEDs irradiation. In the latter case, the crude reactor effluent contained 98% of CEESO along with 0.5% of CEESO 2 and less than 2% of I-2. Pure oxygen could be replaced with air, although the concentration of the solution had to be decreased 10-fold to maintain full conversion within 10 min of residence time. Within 4 min of irradiation in the presence of air, white LEDs gave better photooxidation performances than the orange LEDs, affording 68% conversion in CEES (51% under irradiation at 610 nm). Both samples were free of CEESO 2.

To summarize the optimization of the chemical oxidative neutralization of CEES, the best results involved process conditions relying on oxygen under 4 min irradiation either at 610 nm or under white light at room temperature and 9 bar of counterpressure. Under these conditions, only a trace amount of CEESO 2 is formed. Air can also be utilized for the neutralization of CEES, affording complete conversion of CEES yet with a longer irradiation time (10 min).

Conclusion

This work illustrates the development of a low footprint, mobile, robust and frugal chemical neutralization technology for the oxidative neutralization of a mustard gas simulant. It relies on the unique features of a highly engineered continuous flow setup and robust conditions using non-toxic and widely available chemicals. The experimental work is also supported with a computational rationalization of the reactivity of selected thioethers towards singlet oxygen. The optimized conditions use concentrated solutions of CEES in

2 , 4 Fig. 1 .

 241 Fig. 1. Representative examples of Schedule I CWAs.

6,7 2 |

 2 J. Name., 2012, 00, 1-3 This journal is © The Royal Society of Chemistry 20xx

Fig. 2 .

 2 Fig. 2. a. Reactivity and toxicity of HD; b. General chemical neutralization methods for mustard gas (HD) and its most common simulant (CEES).

  neutralization of CEES with oxygen. The pump used to deliver the solution of 2-chloroethyl ethyl sulfide (CEES, 1 M) and Methylene Blue (560 µM) in EtOH was set to 1 mL min -1 . The mass flow controller used to deliver oxygen was set to 20 mL N min -1

Fig. 4 .

 4 Fig. 4. Selection of model thioethers 1a-f for the computational study. The stereoelectronic interaction between a donor non-bonding nS and a vicinal acceptor (σ*C-X (X = C, Cl) or *C=C were looked at on the most stable conformers of CEES, HD and 1a-f) is expressed in kcal mol -1 . HOMO (isovalue 0.02) are represented for thioethers CEES, HD and 1a-f. By contrast, chloromethyl ethyl sulfide (1b) features a strongly interacting non-bonding n S in the direct vicinity of a σ* C-Cl acceptor and a less localized HOMO. Benzyl methyl sulfide (1c) features a medium stereoelectronic effect (E int = 4.0 kcal mol -1

Fig. 5 .

 5 Fig. 5. Structural features of the transition states for the reaction of thioethers 1a, CEES, and HD with singlet oxygen, of the corresponding peroxysulfoxide intermediates A and of the final sulfoxides. See Supporting Information Section 4 for details. The corresponding S-O and O-O bond lengths are listed here (values in Å): TS 1 1a (S-O: 1.88, O-O: 1.36), TS 1 CEES (S-O: 1.87, O-O: 1.36), TS 1 HD (S-O: 1.85, O-O: 1.36), 1Aa (S-O: 1.63, O-O: 1.46), CEESOO (S-O: 1.63, O-O: 1.46), HDOO (S-O: 1.63, O-O: 1.46), 2a (S-O: 1.54), CEESO (S-O: 1.54), and HDO (S-O: 1.54). The structural and energetic features of these TSs are in agreement with the work of Jensen and Clennan on other dialkyl thioethers. 63-65,68,70,75-77 The TSs connecting 1a, CEES and HD (TS 1 1a , TS 1 CEES and TS 1 HD , respectively) to the corresponding peroxysulfoxide intermediates (1Aa, CEESOO and HDOO) feature a rather long S-O bond (1.85-1.87 Å)indicative of an early transition state and strong interactions between the non-bonding n S orbitals and singlet oxygen.77 The

Fig. 6

 6 Fig. 6. a. Simplified flow chart for the photooxidation of thioethers including CEES (BPR = back pressure regulator; MFC = mass flow controller; FM = fluidic module; Feed A = substrate typically 1 M in EtOH with 0.06 mol% of an organic photosensitizer; heat exchange on the reactive path and LED panels are omitted for clarity). b. Photograph of the low footprint and mobile chemical neutralization technology for the oxidative neutralization of mustard gas simulant CEES upon irradiation at 610 nm (Corning® Advanced-Flow TM G1/LF skid Photo Reactor; Courtesy of Corning®). The footprint of the setup is L x W x H 94 x 42 x 40 cm. c. Details of a glass fluidic module with the LED panels removed.

Table 1 .

 1 Selection of procedures for the neutralization of mustard gas HD and its simulant CEES

	Entry	Author	Scale	Type	Catalyst	Oxidant	Solvent	Conditions
	1	Jackowski 57	5 mM	Batch a	Rhodococcus R. IGTS8	N.A.	H2O	30 °C, 14 d, quant. c
	2	Landry 29	5.4 mg	Batch b	V-mesoporous SiO2, 10%	t-BuOOH	CH2Cl2	r.t., 1 h, 97% d
	3	Wynne 30	0.85 mg	Batch b	ZnOPPc	Air	neat	λ, 32-34 °C, 24 h, quant. e
	4	Cibulka 38	25 mg	Batch a	riboflavin tetraacetate, 2 mol%	O2	MeCN/H2O	450 nm, r.t. 10 min; quant.
	5	Farha 28	25 mg	Batch b	NU-1000, 1 mol%	O2	MeOH	~400 nm, r.t., 15 min, quant. c
	6	Legros 20	~780 g.day -1	Flow a	methanesulfonic acid urea-H2O2 (UHP) adduct	MeOH	r.t., 3.9 min, quant. c
	7	Farha 34	25 mg	Batch b	NU-1000-PCBA, 0.7 mol%	O2	MeOH	400 nm, 14 min, quant. c
	8	Clarck 26	28.7 mg	Batch b	Cu(hfac)2.H2O, 4 mol%	t-BuOOH	CDCl3	r.t., 27 h, 50% c
	9	Zhao 22	10 mg	Batch a	/	H2O2	[BMIm]HCO3	r.t., 30 min, quant. f
	10	Karwacki 39	172 mM no info	Batch a	BODIPYs	O2	d4-MeOH	3 -30 min, quant. g
	11	Karwacki 39	2.8 mg (HD)	Batch b	BODIPY-I in fabric, 0.1 mol%	Air	neat	r.t. 30 min, quant. g
	12	Farha 33	25 mg	Batch b	PCN-222, UMCM-313, 1 mol%	O2	MeOH	395 -420 nm 12 -18 min, quant. c
	13	Farha 35	25 mg	Batch b	[Y(H9TPPA)(H2O)x]Cl2•yH2O	O2	MeOH	400 -500 nm, 28 min, quant. c
	14	Zafrani 13	50 mg	Batch b	Me-DABCOF, 6-20 wt%	N.A.	H2O	36 min -24 h, quant. c
	15	Estour 21	116,5 mg	Batch b	MIP/porphyrin, 0.25 mol%	H2O2	MeOH/H2O	r.t., 2 h, 99.3% c

16 This work 180 g day -1 Flow a Methylene Blue, 0.06 mol% O2 or air EtOH 610 nm, 4 min, >99% h

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	counterpressure and under UV irradiation (450 W medium
	pressure mercury lamp). Analog TDG was oxidized with 95%,
	yielding to a 3:1 mixture of the corresponding sulfoxide and
	sulfone. Legros reported a compact flow process with an
	integrated in-line low field NMR	20
	a Homogeneous conditions;	b heterogeneous conditions;	c no sulfone detected;	d CEESO/CEESO2 ratio of 3.1;	e trace amounts for long reaction time;	f 6% of CEESO2;	g trace
				amounts; h <1% of CEESO2
						This journal is © The Royal Society of Chemistry 20xx
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  1/8" o.d. or 1/4" o.d.) equipped with PFA or SS Swagelok connectors and ferrules. The liquid feed was handled with ThalesNano MicroHPLC pumps, and the gas feed (oxygen or air) was handled with a Bronkhorst EL FLOW Prestige mass flow controller. The reactor was maintained at reaction temperature with a LAUDA Integral XT 280 thermostat. The LED panels were maintained at 10 °C with a LAUDA RP845.

	Downstream pressure was regulated with a back pressure
	regulator from Zaiput Flow Technologies (BPR-10 or BPR-100).
	Optionally, an in-line IR (FlowIRTM from Mettler-Toledo
	equipped with a DTGS detector using HappGenzel apodization,
	a Silicon probe connected via a FlowIRTM sensor and a high
	pressure heated 10 µL cell) or NMR (43 MHz Spinsolve™
	carbon NMR spectrometer from Magritek®) was inserted
	downstream (Supporting Information Section 2.3).

setup Mesofluidic setup. Mesofluidic experiments were carried with a Corning® Advanced-Flow™ Lab Photo Reactor (1 fluidic module, 2.6 mL internal volume) and in a Corning® Advanced-Flow™ LF/G1 skid Photo Reactor (5 fluidic modules integrated with static mixers and connected in series, 13 mL total internal volume). Feed and collection lines consisted of PFA tubing Please do not adjust margins Please do not adjust margins

(

Table 2 .

 2 Calibration of the photooxidation process with singlet oxygen on model thioethers (see also Figure6for the general setup)

	Entry	Thioether Substrate	Solvent (M)	Catalyst (mol%)	Conv. (%) c
	1	1a	EtOH (1)	MB (0.06) a	>99 d
	2	1c	EtOH (1)	MB (0.06) a	>99 e
	3	1d	EtOH (1)	MB (0.06) a	>99 e
	4	1e	EtOH (1)	MB (0.06) a	5 e
	5	1f	EtOH:2MeTHF (0.1)	MB (0.06) a	0 e
	6	1e	CH3CN	DCA b	47
	7	1f	CH3CN	DCA b	49

a MB = Methylene Blue, Irradiation at 610 nm; b DCA = 9,10-dicyanoanthracene, Irradiation at 395 nm; c Conditions (see Scheme 1): 25 °C, 10 min residence time, 9 bar; the selectivity towards the corresponding sulfoxides is given in the Supporting Information (

Table S3); d Determined by GC-FID. e Determined by ARTICLE Journal Name 8 | J. Name., 2012, 00, 1-3 This journal is © The Royal Society of Chemistry 20xx

Table 3 .

 3 Optimization of the oxidative neutralization of CEES under continuous flow conditions (see also Scheme 1). 1 M solution in EtOH with 0.06 mol% Methylene Blue (Rose Bengal for entry 3), processed at 20 °C under 9 bar of counterpressure; b 0.1 M solution in EtOH with 0.06 mol% Methylene Blue, processed at 20 °C under 9 bar of counterpressure; c Determined by GC with an external calibration on commercial CEES; d Ratio of compounds determined by GC. The references for compounds CEESO, CEESO2, I-1, I-2 and I-3 were either purchased from commercial sources or synthesized in the lab. This journal is © The Royal Society of Chemistry 20xxPlease do not adjust margins Please do not adjust margins ethanol with a trace amount of Methylene Blue upon irradiation with orange or white light. Quantitative conversion was obtained within 4 min of irradiation time under mild process conditions (20 °C, 9 bar). Oxygen or air can be utilized as primary oxidant, although with air longer irradiation times or lower feed concentrations are typically required. Under optimized conditions, only trace amounts of toxic CEESO 2 are detected in the reactor effluent, hence providing an extremely cost effective, operator-friendly and low footprint process for the oxidative neutralization of CEES. The neutralization technology can be embarked on a vehicle for on-site interventions, localized at a neutralization facility or both. The ability to transpose these optimized conditions to larger scales with commercial Corning Advanced-Flow Reactors with minimal reoptimization definitively opens up new perspectives for the safe chemical neutralization of mustard gas with a minimal footprint under frugal conditions. Such a protocol of neutralization could possibly be further adapted to other Sbased CWA from the V-series (VX, VR).

	Entry	Oxidant	RT	LEDs	Conv. c		Reactor effluent composition (%) d
			(min)	(nm)	(%)	CEES	CEESO	CEESO2	I-1	I-2	I-3
	1	O2	10	610	>99 a	0	95	1	0	1	3
	2	O2	10	white	>99 a	0	96	1	0	2	1
	3	O2	10	white	>99 a	0	95	1	0	1	3
	4	Air	10	610	>99 a	0	84	1	0	1	15
	5	Air	10	610	>99 b	0	85	0	0	1	14
	6	O2	4	610	99 a	1	92	0	3	1	3
	7	Air	4	610	51 a	81	14	0	4	0	0
	8	O2	4	white	>99 a	0	98	1	0	2	0
	9	Air	4	white	68 a	41	55	0	3	1	0
	10	O2	2	610	82 a	28	68	0	2	1	0

a This journal is © The Royal Society of Chemistry 20xx

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Table of Content

 of Intensified chemical neutralization of chemical warfare agent simulant CEES with air and light under continuous flow conditions

This journal is © The Royal Society of Chemistry 20xx J. Name., 2013, 00, 1-3 | 5

This journal is © The Royal Society of Chemistry 20xx J. Name., 2013, 00, 1-3 | 7

Acknowledgments

This work was supported by the University of Liège (Welcome Grant WG-13/03, JCMM) and by the French Community of Belgium (Concerted Research Action ARC-icFlow, Integrated Continuous Flow Photoreactors). Computational resources have been provided by the "Consortium des Équipements de C l ul I " (CÉCI), funded by the "Fonds de la Recherche S qu d l qu " (F.R.S.-FNRS) under Grant No. 2.5020.11. Dr. Morgan Hans is acknowledged for carrying out the GC/MS experiments.

Notes and references

Conflicts of interest

There are no conflicts to declare.