The sensing mechanism underlying the ultraselective and highly sensitive ethylene detection in the unique bilayer sensor is systematically investigated with regard to the location, configuration, and thickness of the catalytic Cr2O3 overlayer. The mechanism involves the effective catalytic oxidation of interfering gases into less‐ or non‐reactive species, without limiting the analyte gas transport. The sensor exhibits a promising potential for achieving a precise quantitative assessment of the ripening of five different fruits.A highly selective and sensitive detection of the plant hormone ethylene, particularly at low concentrations, is essential for controlling the growth, development, and senescence of plants, as well as for ripening of fruits. However, this remains challenging because of the non‐polarity and low reactivity of ethylene. Herein, a strategy for detecting ethylene at a sub‐ppm‐level is proposed by using oxide semiconductor chemiresistors with a nanoscale oxide catalytic overlayer. The SnO 2 sensing layer and a catalytic Cr2O3 overlayer is proposed as a novel solution enabling the exclusive detection of sub‐ppm‐level ethylene, which is a representative plant hormone. The sensor can be applied in a wide range of applications that require the real‐time and onsite assessment of fruit freshness/ripening or the control of plant growth/development.A bilayer sensor with a SnO For the detection of ethylene with low reactivity, metal oxide semiconductors that operate at elevated temperatures (200–400 °C) are more advantageous than CNT‐ and graphene‐based chemiresistors, which are generally operated at room temperature or mildly heated conditions.Various methods and instruments have been used to detect ethylene, including gas chromatography, photoluenching, fluores probes,, 10 andometers. However oxides,, 18, 19 (CNTs),, 21, 22aterials, 24, 25 this is despite the strong demand from the agricultural industry. It is considered that this problem is related to ethylene being relatively stable and thus less reactive than other highly reactive interfering gases ; further, its high bond energy and non‐polarity are unfavorable for controlling the adsorption of a specific gas.However, the simple sensing mechanism often provides similar chemiresistive variations for a wide range of gases; this mechanism is based on a surface reaction between the target gas and the ionized surface oxygen. Therefore, the highly selective and sensitive detection of ethylene has remained a challenge since the introduction of metal oxide semiconductor gas sensors in 1960s; this isfic gas., 27, 28 this has frequently been accompanied by an increase in the responses to interfering gases and/or an increase in sensor resistance beyond the measurable range; consequently, this has hampered selective ethylene detection and/or resistance measurements, when using a conventional electric circuit. In addition, although sensor arrays consisting of multiple oxide‐based sensors have been investigated, their ability to discriminate and quantify sub‐ppm‐levels of ethylene is still insufficient for utilization in practical applications and for assessing fruit freshness.Studies on ethylene sensing using oxide semiconductor chemiresistors are currently in the nascent stage. Although catalyst loading/doping has been employed to enhance the response to ethylene,, 30, 31 sensors have be2 sensing film that is coated with a nanoscale Cr2O3 catalytic overlayer. The key concept of this intriguing bilayer sensor is the catalytic oxidation of highly reactive interfering gases into non‐ or less‐reactive species, such as CO2 and H2O, which was achieved without sacrificing the transport of the analyte gas to the lower sensing region and without affecting the sensor resistance. To demonstrate this concept and for securing a high ethylene response even after the selective catalytic filtering of gases, the micro‐thick films of SnO2 hollow spheres to exhibit high and comparable responses to a range of reducing gases have been used as sensing layers and Cr2O3 has been selected as the catalytic overlayer materials to reduce the effect of interference gas from the preliminary studies. The gas sensing characteristics of SnO2 sensing films with different configurations of the nanoscale Cr2O3 catalytic overlayer were studied and the potential of the proposed sensor for use in assessing fruit freshness is confirmed by investigating the ripening of five different fruit types . To the best of our knowledge, this paper presents the first report of a metal oxide gas sensor that enables the highly selective and sensitive detection of sub‐ppm‐levels of ethylene with negligible cross‐responses to other food‐related interfering gases , ubiquitous ethanol, and representative indoor pollutants . The main aim of this study is to elucidate the sensing mechanism that underlies the exclusive detection of ethylene in relation to the sensing film, catalytic overlayer materials, and configuration of the bilayer films.Herein, we report a novel strategy for designing highly selective and sensitive ethylene gas sensors by using a SnO22 spheres via heat treatment at 600 °C for 2 h . The average diameter of ≈100 spheres was 0.84 ± 0.36 µm. Hollow morphologies were observed in broken shells , and these were further confirmed via transmission electron microscopy (TEM) analysis. Figure S1b, Supporting Information, shows a bright contour in the central region of the sphere, which is contrasting to the dark contour observed in the outer region. The shells exhibited thicknesses of ≈34 nm, and each sphere consisted of a number of primary particles with sizes of ≈15 nm . A high‐resolution TEM (HR‐TEM) image shows lattice patterns with interplanar spacings of 2.69 and 3.31 Å, corresponding to the (101) and (110) planes of SnO2 tetragonal structures, respectively . The N2 adsorption and desorption isotherms of the SnO2 hollow spheres exhibited type IV behavior with H3 hysteresis loops, indicating the presence of abundant mesopores (size: 2–50 nm) . The Brunauer–Emmett–Teller (BET) surface area was 14.4 m2 g−1, which indicates that the SnO2 hollow spheres exhibited a highly gas‐accessible structure.Sn‐containing precursor spheres were prepared using ultrasonic spray pyrolysis and converted into SnOructure.2 hollow spheres on an Al2O3 substrate with two Au electrodes, which was followed by heat treatment at 450 °C for 3 h  evaporation  elemental mapping , and their thicknesses were both ≈22 µm , which were similar to that of the 0.3Cr2O3‐SnO2 sensor (≈21 µm). The SEM, EPMA, and TEM results clearly indicate the uniform coating of Cr2O3 layers with thicknesses of 0.05 and 0.6 µm on the thick SnO2 sensing film.Cross‐sectional and top‐view scanning electron microscopy (SEM) images of the 0.3Crs Figure . A high‐s Figure . As showg Figure . The majr Figure  coated os Figure ,d. The m2 and 0.3Cr2O3‐SnO2 sensors were characterized using X‐ray diffraction . The 0.3Cr2O3‐SnO2 specimen showed tetragonal SnO2 (ICDD #41‐1445) and rhombohedral Cr2O3 (ICDD #38‐1479) phases, and no second phase was found. The crystallite sizes of the polycrystalline SnO2 and Cr2O3 phases were calculated as 12.9 ± 0.5 and 19.5 ± 2.8 nm, respectively, by using the Scherrer's equation. No obvious peak shift was observed for the SnO2 peak of the 0.3Cr2O3‐SnO2 specimen, which indicates that Cr was not incorporated into the SnO2 lattice.The phases and crystallinities of the pure SnOFigure2 sensors (with different film thicknesses of ≈9 and ≈22 µm) and the 0.3Cr2O3‐SnO2 sensor (SnO2 film thickness of ≈21 µm) to 2.5 ppm ethylene, trimethylamine (TMA), dimethylamine (DMA), ammonia (NH3), ethanol, formaldehyde (HCHO), and carbon monoxide (CO) at 350–450 °C. All three sensors (with and without the Cr2O3 overlayer) exhibited the typical chemiresistive variations of n‐type oxide semiconductor gas sensors; there were decreases and recoveries of sensor resistance upon exposure to reducing gas and air, respectively . Accordingly, the gas response (S) was defined as follows: Ra/Rg – 1.2 sensor with a film thickness of ≈9 µm  in the upper part of the sensing film with catalytic activity. Both reasons are possible, considering the increase in the sensing‐film thickness and the fact that SnO2 is a good catalytic material for the oxidation of reducing gases. However, it is worth noting that the increase in the thickness of the SnO2 sensor had barely any effect on the response to ethylene, whereas this change significantly decreased the responses to all the other gases . The negligible change in the ethylene response, despite the increase in film thickness, suggested that gas transport was not the critical limiting step for ethylene; thus, ethylene could diffuse to the lower part of the sensing film without significant oxidation. This explanation is plausible, considering that ethylene is a very stable gas; hence, its oxidation is relatively difficult. In contrast, the decrease in the gas responses to TMA, DMA, NH3, ethanol, HCHO, and CO could be attributed to the oxidative consumption of these gases in the thick SnO2 sensing film. However, as shown in Figure For the thin SnOm Figure , the resm Figure . The higm Figure  were conerature., 37, 38m Figure , the resm Figure . We consg gases., 40 Howfficult., 30 In 2O3 overlayer on the SnO2 sensing film  and showed excellent selectivity toward ethylene over a wide range of sensing temperatures (350–450 °C). The bilayer sensor used in the present study consists of a catalytic overlayer and a sensing film, and two electrodes are located beneath the sensing film. In this configuration, the responses to the analyte gases are determined by the following: gas oxidation and/or reforming in the upper catalytic layer, gas transport to the lower sensing region, and the sensing reaction between the gas and negatively charged oxygen ions on the oxide semiconductor surfaces. Limiting the diffusion of gas by coating the Cr2O3 catalytic overlayer could be excluded as a possible reason for the decrease in responses to most gases (with the exception of ethylene); this is because the Cr2O3 overlayer (thickness: ≈0.3 µm) is significantly thinner than the SnO2 sensing film (thickness: ≈21 µm). Therefore, it was suggested that the selective catalytic filtering of gases was the probable reason for the high ethylene selectivity; this was because the catalytic Cr2O3 overlayer barely oxidized the relatively stable ethylene, but facilitated the oxidation of the more reactive interfering gases. However, it is worth noting that the response to ethylene at 350 °C was observed to slightly increase from 12.2 to 16.8 due to the coating of the Cr2O3 overlayer  was calculated, and results were plotted as a function of temperature . The SEthylene/STMA, SEthylene/SEthanol, and SEthylene/SHCHO values increased with an increase in the thickness of the SnO2 sensing film ; these values increased further after coating with the Cr2O3 catalytic overlayer. For the 0.3Cr2O3‐SnO2 sensor, all three selectivity values were maximized at 375 °C . Accordingly, considering both the gas selectivity and gas response, the optimal sensor operation temperature for ethylene detection was identified as 375 °C, although the higher gas response could be obtained at a lower sensing temperature (<375 °C).The selectivity toward ethylene over the key interfering gases  , the oxidative filtering of the interfering gases due to the film thickening was insufficient for achieving ethylene selectivity  Cr2O3 overlayer led to relatively high cross‐responses to interfering gases, probably because oxidation of interfering gases was less effective , and the gas‐sensing characteristics were measured . The Cr2O3 overlayer was ≈1 µm thick. Interestingly, the response to ethylene (S = 7.3) was significantly higher than that of the interfering gases (S = 1.1–4.3). This result again confirms that the Cr2O3 coating, regardless of the overlayer configuration, is promising for utilization in the highly selective detection of ethylene.To examine the effect of the Cr2 spheres uniformly loaded with Cr2O3 was also prepared; this was achieved via loading of Cr2O3 nanoparticles on the entire surface of the SnO2 hollow spheres (1.0 at% Cr2O3), screen printing a slurry, and a heat treatment at 600 °C. The resulting sensor was referred to as the “Cr2O3‐loaded SnO2 sensor,” and its gas‐sensing characteristics were compared with those of the thick SnO2 and 0.3Cr2O3‐SnO2 sensors . The results showed that the response of Cr2O3‐loaded SnO2 sensor to 2.5 ppm ethylene (S = 1.1) at 375 °C was significantly lower than that of the 0.3Cr2O3‐SnO2 sensor (S = 12.1). This negligibly low gas response of the Cr2O3‐loaded SnO2 sensor can be explained by the excessive oxidation of ethylene during its transport through the thick and highly catalytic Cr2O3‐loaded SnO2 film. To confirm the effect of Cr2O3 on the gas‐sensing characteristics, a Cr2O3 thin film (0.3 µm thick) was prepared via e‐beam evaporation, and its gas‐sensing characteristics were measured at 375 °C . The pure Cr2O3 sensing film showed negligibly low gas responses to all the analyte gases, including ethylene, indicating that Cr2O3 alone cannot be used for ethylene detection. Thus, separating the catalytic and sensing reactions by using the bilayer design can provide superior controllability of the gas‐sensing characteristics.To elucidate the role of the bilayer sensor design used in the present study, a sensing film (thickness: ≈20 µm) comprising SnORa) for the thick SnO2 and 0.3Cr2O3‐SnO2 sensors were similar (200–300 kΩ), whereas the Ra value for the Cr2O3‐loaded SnO2 sensor was significantly higher (2.3 MΩ) . This significant increase in sensor resistance for the Cr2O3‐loaded SnO2 sensor could be associated with aliovalent doping or the charge transfer from SnO2 to Cr2O3. It is also worth noting that if the sensor resistance becomes excessively high by loading the catalysts on the entire sensing materials, performing resistance measurements by using a conventional electric circuit can become difficult; this can hamper the ability to provide cost‐effective resistance measurements for actual applications. In contrast, for the present bilayer sensor design, the conduction along the lower part of the SnO2 sensing film near the electrodes is barely affected by the outlying Cr2O3 catalytic overlayer; this enables the control of gas‐sensing characteristics without affecting the sensor resistance. Therefore, the bilayer sensor design with the nanoscale catalytic overlayer offers various distinctive advantages, namely: an excellent gas selectivity that arises due to the oxidative filtering of interfering gases, a high gas response that arises due to the negligible limitation of gas transport, an effective separation of sensing and catalytic reactions, and the facile control of gas‐sensing characteristics without altering the sensor resistance.It should be noted that the values of the sensor resistance in air (o Cr2O3. It is ares and τrecov) of the sensors  were calculated; these results are shown in Figure S11, Supporting Information. Note that the τres and τrecov values for ethylene sensing were similar; this was true even after coating with the Cr2O3 catalytic overlayer; however, those values for the interfering gases were observed to decrease significantly with the Cr2O3 coating. This again indicates that the majority of the interfering gases were oxidized in the Cr2O3 catalytic overlayer and that employing the bilayer sensor design caused no deterioration in the response and recovery kinetics for ethylene sensing.The effects of the catalytic overlayer on the response and recovery kinetics of the sensor were investigated. For this, the 90% response and recovery times  due to the Cr2O3 overlayer coating were significantly larger than those of the responses to ethanol and HCHO . Borck et al. reported that methylamine with lone‐pair electrons on the nitrogen atom can be adsorbed favorably on the Cr2O3 surface by donating an electron to the partially empty cation orbital. Moreover, it has been reported that Cr2O3 promotes the decomposition of NH3 and the oxidation of methyl groups in TMA and DMA. Therefore, the Cr2O3 overlayer promotes both the adsorption and oxidation of amine‐containing gases and accelerates the oxidative filtering of TMA, DMA, and NH3, and the substantial reductions in the responses to amine‐related gases when applying the 0.3‐µm‐thick Cr2O3 overlayer coating can be attributed to the facile adsorption of amine compounds as well as effective gas oxidation. All these findings support the fact that in the present study, the interfering gases were successfully filtered via catalytic oxidation in the nanoscale Cr2O3 overlayer, and this enabled the high selectivity to ethylene.The results in Figures O Figure ,d. Cr2O3eaction, and is ng HCHO. This stO Figure ,d, and t (Cr3+). Borck ek et al. reporte of NH3 and theand DMA. Therefo For example, it is known that a very low concentration of ethylene (0.1–1 ppm) is produced during the ripening of climacteric fruits, and that emitted ethylene can further accelerate ripening. Accordingly, the amount of ethylene emitted from fruit can not only be employed as a useful measure to monitor fruit ripening, but it can also provide valuable information for managing fruit storage. Moreover, in “smart farming,” the ethylene concentration provides key information that is used to control the development and growth processes of plants, such as seed germination, flowering, leaf abscission, fruit formation, and senescence. In such an industry, it is essential to precisely detect and manage low concentrations of ethylene. However, the responses of metal oxide semiconductor gas sensors to ethylene are generally significantly lower than the responses to more reactive interfering gases, including food‐related gases , ubiquitous ethanol, and indoor air pollutants (HCHO and CO). Accordingly, it is very challenging to detect ethylene in a highly selective and sensitive manner in the presence of the aforementioned interfering gases.Ethylene is a key plant hormone, and its detection is used to determine the development and growth of climacteric fruits., 3, 4 Fipening., 6 Accoand CO)., 49, 503‐loaded SnO2 nanoparticles, Pt‐doped SnO2 nanoparticles, Pd/rGO‐loaded Fe2O3 hierarchical nanostructures, and Pd‐doped SnO2 nanoparticles. However, most of these sensors exhibited relatively low gas responses (S < 9) to high concentrations of ethylene (ranging from 10–100 ppm). The sensing transients of the 0.3Cr2O3‐SnO2 sensor to 0.1–2.5 ppm ethylene at 375 °C were measured . The ethylene response in the present sensor is also superior to those of other sensors using catalyst‐loaded SnO2 nanoparticles with similar or higher operational temperature (≥ 350 °C) in the literature. This can be attributed to the effective separation and tailoring of the catalytic and sensing reaction using bilayer design as well as highly gas accessible sensing materials with hollow morphology. The sensor exhibited highly reproducible sensing and recovery upon repeated exposure to 2.5 ppm ethylene and showed good long‐term stability over 15 days  was also examined. The response to 2.5 ppm ethylene was barely affected by the coexistence of 0.01–2.5 ppm TMA or ethanol , which indicates that this sensor can be used in real applications in mixed gas environments.As previously mentioned, many attempts have been made to enhance ethylene sensing properties, for example, using WOrticles, Pt‐doperticles, Pd/rGO‐uctures, and Pd‐rticles. Howeverg Figure . The eth ., 53 Theerature., 32, 52s Figure ,d. The e2O3‐SnO2 sensor for assessing fruit freshness, we investigated time‐dependent changes in the ethylene concentration emitted from various fruit types  with similar weights (≈100 g)  Figure7. For ) Figure, and sen.In actual applications, fruit is often stored with meat or fish, which emit biogenic amines such as TMA, DMA, and NH The humidity‐dependent changes in sensor resistance and gas response in this study are consistent with those present in literature. Note that the sensor showed the similar and high responses to a banana under different humidity conditions, indicating that the present sensor is suitable for use in humid conditions or conditions in which humidity changes.The effect of ambient humidity on the gas sensing characteristics, which is also important for practical applications, was investigated by measuring the sensing transients upon exposure to the same banana under different humidity conditions in an acrylic chamber (inner volume: 40 cm × 30 cm × 12 cm) containing a miniaturized humidifier . The decrease of sensor resistance and gas response was observed with an increase in humidity from r.h. 21% to r.h. 37%. The former is associated with the generation of electrons due to the reaction between ionized oxygen on the surface and water vapor, and the latter is attributed to the decrease of ionized oxygen available for gas sensing due to formation of surface hydroxyl groups., 57 Theerature. Note th2O3‐SnO2 bilayer sensor for use in real‐time and onsite fruit freshness monitoring, a portable sensing module wirelessly connected to a mobile phone was developed . The SnO2 sensors with the Cr2O3 overlayer exhibit ultrahigh selectivity and responses to ethylene, whereas SnO2 sensors without the overlayer showed similar responses to a variety of gases. The exceptional sensing properties, such as ultra‐selectivity and highly sensitive ethylene detection, are attributed to the oxidation of food‐related interfering gases , ubiquitous ethanol, and indoor pollutants (HCHO and CO) into less‐ or non‐ reactive species by the nanoscale catalytic Cr2O3 overlayer. In addition, the bilayer sensor design enables the sensing and catalytic reactions to be separated into independent processes, which allows gas selectivity to be precisely controlled. The outlying nano‐thin catalytic overlayer is advantageous for avoiding the limitation of gas transport to the sensing region and for preventing significant sensor resistance changes up to an unmeasurable range, which are often observed when a sensor is uniformly loaded with a catalyst. The exclusive ethylene detection capability of the unique bilayer sensor enables the monitoring of the ripening of five different climacteric fruit types in a precise and quantitative manner, and its development can be utilized in a wide range of agricultural applications that benefit from the plant‐hormone control.In this study, a novel bilayer sensor with a SnO42 hollow spheres were prepared via one‐pot ultrasonic spray pyrolysis . The spray‐pyrolysis system consisted of six piezoelectric droplet generators (resonance frequency: 1.7 MHz), a tubular reactor, and a powder‐collecting chamber. Tin (II) chloride dihydrate , citric acid monohydrate , and a diluted hydrochloric acid solution  (4 mL) were dissolved in 200 mL of distilled water, with stirring for 1 h. The concentrations of tin chloride and citric acid were 0.1 and 0.25 m, respectively. Large quantities of droplets were generated by ultrasonic transducers and these were transferred into a high‐temperature (700 °C) tubular quartz reactor  by air at a flow rate of 20 L·min−1. The Sn‐containing precursor powder was collected through a Teflon bag filter in a particle‐collection chamber and was converted into SnO2 hollow spheres via heat treatment at 600 °C for 2 h.SnO2 hollow spheres with a terpineol‐based ink vehicle  at a ratio of 1:3 (by weight). The sensing film was screen‐printed on alumina substrates  with two Au electrodes on the upper surface (electrode gap: 0.2 mm) and a micro‐heater on the lower surface. The thicknesses of the SnO2 films were controlled by changing the emulsion thickness of the screen mask. After screen printing, the sensing film was heat‐treated at 450 °C for 3 h to remove organic components. Subsequently, catalytic Cr2O3 overlayers were deposited on the SnO2 sensing film via the e‐beam evaporation of polycrystalline Cr2O3 grains  in a vacuum environment (base pressure = 2 × 10−6 Torr).The slurry for the film coating was prepared by mixing SnO2 film coated with a Cr2O3 overlayer was investigated using field‐emission EPMA . HR‐TEM and elemental‐mapping images of the SnO2 and Cr2O3‐coated SnO2 nanospheres were obtained using JEM‐ARM200F . For the TEM analysis, the spheres were detached from the uppermost region of the sensing film, dispersed in an ethanol solution, and subsequently deposited onto Cu grids . The phases and crystal structures were investigated using X‐ray diffraction  with CuKα radiation (λ = 1.5418 Å), and the surface area and pore‐size distribution of the SnO2 hollow spheres were analyzed using N2 adsorption via the BET method Field‐emission SEM  was conducted to examine the morphologies and microstructures of the materials and sensing films. The composition of the SnO3), and the gas atmosphere was controlled using an automatic four‐way valve. The flow rate of the gas was fixed at 50 cm3·min−1. The direct‐current two‐probe resistance was measured using an electrometer  interfaced with a computer. The analyte gas concentration was controlled by changing the mixing ratio between the analyte gas and synthetic air. The sensing transients to 2.5 ppm ethylene, TMA, DMA, NH3, ethanol, HCHO, and CO were measured at 350–450 °C in a dry atmosphere .The sensors were heated at 500 °C for 2 h for stabilization prior to measurement. They were placed in a quartz tube (inner volume: 1.5 cmThe authors declare no conflict of interest.Supporting InformationClick here for additional data file.Supplemental Video 1Click here for additional data file.Supplemental Video 2Click here for additional data file.


The data collection involved field sampling of water samples in 23 sampling stations spatially distributed in the basin during nine seasons from July/2016 to May/2018. The hydro-chemical data was generated from the Laboratory analysis of the water samples using the ion chromatogram. Samples for nitrate isotope  analysis were prepared via the bacterial denitrification method and analysed using Isotope Ratio Mass Spectrometer. The data, which is categorised in different land use zones and seasons, is important for understanding the spatiotemporal variation in nitrate and solute concentrations and the role of land use on the river water quality. In addition, the δ15N-, δ18O‒NO3− and δ11B values are key for elucidating nitrate pollution sources and potential biogeochemical processes for the management and control of nutrient pollution and eutrophication of the Lake Victoria. Furthermore, the dataset can be of great use in water quality models for understanding non-point pollution dynamics in tropical basins. This article is related to This article presents hydro-chemical and isotopic (δ Specifications Table•The data is important for revealing nitrate pollution sources and potential biogeochemical processes for the management and control of nutrient pollution sources in tropical sub-Saharan African (SSA) river basins•The physicochemical dataset is quite useful in understanding water types, origin and processes governing dissolution of solutes in the basin.•This data is key to researchers, managers and policy makers involved in water and environmental resources management especially in the tropics.•15N-, δ18O‒NO3− & δ11B) is rare in tropical SSA river basins. Therefore, further analysis of this pioneer dataset can give new ideas for future research in the region.Similar isotope data  and isotopic  parameters of water samples from the Nyando river basin in Kenya obtained during nine seasons of field monitoring. The spatial distribution of the sampling stations in the basin is presented in The data presented consists of hydro-chemical . In addition, sampling was done for potential NO3− end members  for the determination of their δ15N‒, δ18O‒ NO3− and δ11B‒B values. Sewage effluents were sampled from the inlet point of sewage treatment plants located in key towns like Kisumu, Kericho, Muhoroni, and Chemelil. Manure samples were taken from cow, goat and sheep droppings in the basin. Samples of the commonly used mineral fertilizers in the basin  were purchased from farmers and suppliers. Rainfall samples were collected from stations located in Ahero, Kakamega and Kericho towns, while soil N samples were collected by filtering suspended soil sediments in river water using 11 µm filters . Before laboratory analysis for δ15N‒ and δ18O‒NO3−,samples were filtered again through 0.45 µm membrane filters and stored frozen (-17°C). Laboratory analysis of the hydro-chemical parameters  was carried out using an ion chromatograph .Field monitoring was undertaken in 23 spatially distributed sampling stations located in the main river channel and its two major tributaries . The fie15N‒ and δ18O‒NO3− were carried out using the “Bacterial denitrification method” as adopted from 15N and δ18O in N2O produced from the conversion of NO3− by the denitrifying bacteria, Pseudomonas aureofaciens. Pseudomonas aureofaciens (recently reclassified as a strain of Pseudomonas chlororaphis) are ideal bacteria for simultaneous 15N and 18O analyses because they naturally lack N2O-reductase activity (the enzyme that reduces N2O to N2) and therefore provide information for both N and O isotopes. This method is applicable for seawater and freshwater samples at the natural-abundance level. Bacterial cultures were grown for 6–10 days in amended tryptic soy broth (TSB), divided into centrifuge tubes of 40 mL aliquots and centrifuged. After centrifugation, the supernatant was decanted, reserved and 4 mL of the TSB were pipetted back into the tubes to obtain a 10-fold concentration of bacteria. These tubes were then vortexed to ensure homogenized cultures and transferred as 2 × 2 mL aliquots into 20 mL headspace vials. The vials were crimp-sealed with Teflon-backed silicone septa. To ensure anaerobic conditions, a reduced blank effect and removal of N2O produced prior to sample injection, the headspace vials were purged with N2 gas for 3 hours. Samples of dissolved NO3− (100 nmol) were then injected into the headspace vials and incubated overnight to allow for complete conversion of NO3− to N2O. The next day, 0.1 mL of 10 N NaOH were injected into the headspace vials to stop bacterial activity and to scrub any CO2 gas in the vial which can interfere with the N2O measurement. The δ15N and δ18O analyses of the produced N2O were carried out using a trace gas preparation unit , coupled to an isotope ratio mass spectrometer (IRMS) . The N2O sample was flushed out of the sample vial using a double-hole needle on an auto-sampler. Water was removed using a combination of a nafion dryer and MgClO4 scrubber. The N2O was compressed onto a capillary column  at 35°C by cryogenic trapping and focusing and subsequently analyzed by IRMS. Individual samples were ran in triplicate and the resultant isotope data is normally expressed as delta (δ) units in per mil (‰) notation, relative to international reference standards. This is expressed as:15N/14N or 18O/16O ratio of the sample and the standard for δ15N and δ18O, respectively. δ15N and δ18O values are reported relative to atmospheric N2 and Vienna Standard Mean Ocean Water (VSMOW) respectively. Three international reference standards, USGS32 , USGS34 , and USGS35 , were used to normalize the raw δ15N‒ and δ18O‒NO3− values (based on a N2O reference gas tank) to the AIR and VSMOW scale. USGS32 and USGS34 were used for normalization of the δ15N value and USGS34 and USGS35 for the δ18O. NO3− content in samples and references were harmonized (i.e. 20 nmol), this corrects for nonlinearity of the IRMS and blanks associated with the procedure. As a quality control measure, an in-house KNO3 laboratory standard  was analyzed together with the samples. Measurement batches were only accepted if measured δ15N and δ18O values of the laboratory standard were within 0.4 and 0.5 ‰ of our accepted values, respectively. Incase standard deviation on replicate samples was higher than 0.3 and 0.4 for δ15N and δ18O, respectively, the sample was reanalyzed. More details about this technique are covered in Analysis for δ11B was carried out as explained in 4OH (20%), the purified B was loaded again on a small 100 ml resin Teflon PFA® column. B was collected with 2 ml of HCl 2N. An aliquot corresponding to 2 mg of B was then evaporated below 70°C with mannitol (C6H8(OH)6) in order to avoid B loss during evaporation 11B values were then determined by measuring the Cs2BO2+ ion 11B=38.6±1.7‰). Similar to N and O, B isotope ratios were expressed in delta (δ) units and a per mil (‰) notation relative to an international standard, NBS951.The water analysis technique for B and δThe authors agree upon the standards of the expected ethical behaviourThe authors declare that they have no known competing financial interests or personal relationships which have or could be perceived to have influenced the work reported in this article.


III complex leads to efficient and high yielding fused γ‐lactam formation across a range of substituted heterocycles. Quantum calculations show that the reaction proceeds via cyclization in the triplet excited state to yield a 1,4‐diradical; intersystem crossing leads preferentially to the closed shell singlet zwitterion. This is geometrically restricted from undergoing recombination to yield a cyclobutane by the planarity of the amide substituent. A prototropic shift leads to the observed bicyclic products in what can be viewed as an interrupted [2+2] cycloaddition.The [2+2] photocycloaddition is the most valuable and intensively investigated photochemical process. Here we demonstrate that irradiation of N‐acryloyl heterocycles with blue LED light (440 nm) in the presence of an Ir III complex leads to fused γ‐lactam formation. The reaction proceeds via cyclization in the triplet excited state to yield a 1,4‐diradical; intersystem crossing leads to a singlet zwitterion that is geometrically restricted from yielding a cyclobutane. Proton transfer leads to the products in an interrupted [2+2] cycloaddition.Irradiation of N‐acryloyl heterocycles with blue LED light and an Ir N‐functionalization of heterocycles (such as indole) with an α‐aryl acryloyl derivative.−1, similar in magnitude to the triplet energies of a number of excited state photocatalysts. We envisaged that excitation to the triplet (T1) state via triplet energy transfer (TET) from an appropriate sensitizer and addition to the indole alkene would generate a 1,4‐diradical intermediate, which in a conventional [2+2] process would generate cyclobutane products via intersystem crossing (ISC) to the singlet state. Once in the singlet state, this intermediate may adopt an open shell diradical or zwitterionic closed shell electronic configuration. Both types of electronic configuration have been recognised in thermal and photochemical cyclobutane formation and in other processes.The [2+2] photocycloaddition is arguably the most important photochemical transformation in synthetic chemistry.1 through N‐acylation of 5‐cyano indole and examined its reactivity in the presence of a range of photocatalysts under irradiation with blue LED light (Table 2]PF6 (entry 3) afforded a trace of product 2. Significantly higher conversion was observed with fac‐Ir(ppy)3  and similar results were obtained using [Ir(dF(CF3)ppy)2(dtbbpy)]PF6 (81 % yield), while Ir(dFppy)3 gave complete conversion and an 85 % yield of 2. Furthermore, addition of a catalytic amount of NaOAc further increased the isolated yield to 93 %. With a working substrate synthesis and cyclization procedure in hand, we examined the scope and limitations of this visible light mediated process  and electron‐withdrawing groups such as halogens . More reactive groups such as 8‐O‐methanesulfonyl 7 also cyclize successfully, albeit in lower yield (52 %). Introducing substituents in the 7‐position does not have any deleterious effects on the reaction. Halogen substituted indoles cyclize in good to excellent yields: 7‐fluoro 8 (95 % yield), 7‐bromo 9 (94 % yield) and 7‐iodo 10 (83 % yield) groups are all well‐tolerated. Electron‐withdrawing groups such as a cyano 2 (93 % yield) or a methyl ester 11 (62 % yield) were both tolerated at C‐7 without incident, and electron rich pyrroloindoles were synthesized with equal facility . Pyrroloindoles bearing pinacol boronic acid esters were also demonstrated to be viable substrates for the reaction, cyclizing in 66 % isolated yield to afford 13. 6‐Bromo and 6‐trifluoromethyl substituted indole derivatives also cyclized effectively to afford product in good yields . We were also able to demonstrate that performing the reaction on a substrate bearing an aldehyde in the 6‐position was also possible, albeit affording product 16 in a moderate yield of 32 %; in this case the remaining material is likely consumed via polymerization of the starting acrylic acid derivative. 5‐Substitution on the pyrroloindole core was exemplified through the synthesis of the 5‐fluoro derivative 17 in 82 % yield. We were also able to perform the reaction efficiently on a series of azaindoles: 6‐azaindole derivative 18 (77 % yield), 5‐azaindole 19 (90 % yield) and 4‐azaindole 20 were all generated in good to excellent yields. The transformation is also tolerant of other changes to the backbone of the heterocycle; bicyclic pyrrole derivatives such as 21 could also be generated in 83 % yield while bicyclic imidazole derivative 22 was obtained in 21 % yield as a mixture of regioisomers. Substitution is also tolerated in the 9‐position of the pyrroloindole as demonstrated by the successful conversion of substrates bearing cyanomethyl 23 (92 % yield) and methyl ester groups . We also probed the potential to make changes to the substrate via modification of the N‐acyl portion of the molecule. Replacement of the α‐phenyl group on the N‐acyl moiety by a methoxy ether was well tolerated and led to the desired photo‐cyclised product in high yield , while modification of the phenyl group itself by the addition of a p‐OMe substituent also gave an excellent yield . Similarly, addition of a p‐tBu  and p‐CF3  are well tolerated. Addition of an alkyl substituent at the terminal end of the alkene had no deleterious effect; however, the product was obtained with minimal control over diastereoselectivity . Finally, we turned our attention to modifying more complex products containing indoles. Camalexin, a simple alkaloid that is cytotoxic against aggressive prostate cancer,30 (50 % yield) and 31 (50 % yield) respectively.We initially explored cyclization of substrates with different substituents on the indole. The parent substrate in which indole is 14 was performed. By starting with 4.6 mmol of the appropriate precursor, 1.39 g of 14 were obtained (93 %), thus demonstrating that the reaction is scalable without affecting the overall yield.To probe the practical utility of this transformation, a gram scale synthesis of 6‐bromo substrate N‐acyl 1A from the singlet (S0) to π‐π* triplet (T1) state is 52.2 kcal mol−1. This is well matched with the emissive energy of the Ir(dFppy)3 ,3)ppy)2(dtbbpy)]PF6 fac‐Ir(ppy)3 1 indicated a reduction potential of −1.62 V and an oxidation potential of 1.91 V (vs. SCE in MeCN). Both reduction and oxidation potentials are outside the redox capabilities of the optimal Ir(dFppy)3 catalyst (E1/2(M+/M*)=−1.27 V; E1/2(M*/M−)=0.35 V vs. SCE in MeCN).To probe the mechanistic profile of this transformation, we carried out computational studies with density functional theory DFT,. The cal1A to 3A), a 5‐exo‐trig cyclization takes place to produce intermediate 3B. 3B undergoes an intersystem crossing (ISC) and generates the corresponding singlet species 1B; this species is better described as a closed‐shell singlet zwitterion rather than a singlet diradical (⟨Ŝ2⟩=0 in the wavefunction stability checks). This zwitterionic species undergoes a proton transfer to form final product C. The reaction activation barriers of the main pathway, which range from 3.2 to 10.6 kcal mol−1 . The calculated energy profile also indicates the presence of a retrocyclization process (from 1B back to 1A) with an activation barrier of 9.7 kcal mol−1; this is somewhat higher than the barrier required to form the reaction product C . When we performed the reaction on substrate 1 in the presence of acetone, the adduct 32 was isolated (11 % yield), along with the pyrroloindole product, consistent with the presence of an enolate‐like intermediate. The last step of the proposed mechanism involves transformation of the zwitterion 1B into the final product C. We reasoned initially that this could occur via stepwise deprotonation/reprotonation events or by a direct hydrogen shift from C9a of 1B to C2. To probe this, we subjected deuterated substrate 33 to the reaction conditions in the presence of 20 equivalents of H2O . We did, however, observe 17 % incorporation of deuterium at C9, which is consistent with a minor 1,2‐shift pathway; this was also observed computationally . Conversely, when using D2O as co‐solvent with a non‐deuterated indole 1, the C2 position of product 35 showed significant deuterium incorporation (80 %); control experiments also demonstrated that the pyrroloindole 2 is unreactive under these conditions and no deuterium incorporation is observed. This is consistent with a pathway whereby the C2 hydrogen comes from solvent. We probed this with further calculation and found that the stepwise solvent mediated deprotonation/reprotonation pathway is feasible with a barrier of 7.6 kcal mol−1 . We also discovered an alternative lower energy pathway that could operate in the presence of water .Our proposed mechanism is pictured in Figure 1 Figure  are easiO Figure . Under tIn conclusion, we have discovered an operationally simple and functional‐group‐tolerant synthesis of pyrroloindoles that proceeds in the presence of visible light and an iridium(III) sensitizer. The reaction proceeds via cyclization in the triplet excited state to yield a 1,4‐diradical; intersystem crossing leads preferentially to a closed shell singlet zwitterion that is geometrically restricted from undergoing recombination to yield a cyclobutane, leading to the preferential formation of a 5,5‐bicyclic lactam ring system.The authors declare no conflict of interest.As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re‐organized for online delivery, but are not copy‐edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.SupplementaryClick here for additional data file.


N2) and base‐induced elimination (E2). A Lewis base acting as a strong nucleophile is needed for SN2 reactions, whereas a Lewis base acting as a strong protophile  is required for E2 reactions. A complicating factor is, however, the fact that a good nucleophile is often a strong protophile. Nevertheless, a sound, physical model that explains, in a transparent manner, when an electron‐rich Lewis base acts as a protophile or a nucleophile, which is not just phenomenological, is currently lacking in the literature. To address this fundamental question, the potential energy surfaces of the SN2 and E2 reactions of X−+C2H5Y model systems with X, Y = F, Cl, Br, I, and At, are explored by using relativistic density functional theory at ZORA‐OLYP/TZ2P. These explorations have yielded a consistent overview of reactivity trends over a wide range in reactivity and pathways. Activation strain analyses of these reactions reveal the factors that determine the shape of the potential energy surfaces and hence govern the propensity of the Lewis base to act as a nucleophile or protophile. The concepts of “characteristic distortivity” and “transition state acidity” of a reaction are introduced, which have the potential to enable chemists to better understand and design reactions for synthesis.The concepts of nucleophilicity and protophilicity are fundamental and ubiquitous in chemistry. A case in point is bimolecular nucleophilic substitution  or protophile (E2) and the novel concepts of “characteristic distortivity” and “transition state acidity” are introduced. N2) and base‐induced elimination (E2).[N2 reactions  are in principle always in competition with E2 reactions , which opens the possibility and the necessity to actively tune reactivity toward the desired pathway to maximize the formation of the targeted compound and to avoid unwanted side products  paves the way to such design and may lead to the discovery of new chemistry. Two prototypical reactions in organic chemistry that feature in many routes in organic synthesis are bimolecular nucleophilic substitution (Sion (E2).1, 2 SN2 and E2 reactivity, as well as the nature of the reactions’ potential energy surfaces.N2 and E2 pathways for a range of anionic Lewis bases reacting with ethyl chloride. They consolidated our earlier finding that the unfavorably high activation strain, ΔE≠strain, of the E2 pathway can be overruled by a strongly stabilizing transition state (TS) interaction, ΔE≠int, eventually leading to a preference for E2 over SN2.N2 reactions have been related to various properties of X− (the nucleophile) and Y (the leaving group),N2 reaction barriers is directly determined by the stability of the nucleophile's (X−) highest occupied molecular orbital (HOMO) and by the strength of the substrate's carbon–leaving group bond (C−Y): a higher electron‐donating capability of the X− HOMO or a weaker C−Y bond leads to a lower barrier and vice versa.N2 barrier depends on the vertical ionization energy of the nucleophile (IX:–) minus the electron affinity of the C−Y bond (AC−Y).[IX:– is directly related to the energy of the HOMO and AC−Y is dominated by the strength of the C−Y bond.Over the past decades, valuable insights have emerged from experimentalN2 substitution, anti‐E2 elimination (E2‐a), and syn‐E2 elimination (E2‐s) reactions of X−+C2H5Y, with X, Y = F, Cl, Br, I, and At, by using relativistic density functional theory (DFT) at ZORA‐OLYP/TZ2P.2H5Y substrate allows us to probe the direct competition between SN2 and E2, and our findings can be extended to any substrate where the acidic hydrogen and the leaving group are electronically coupled. In the first place, these explorations provide us with a consistent overview of reactivity trends over a wide range of reactivities and pathways. More importantly, analyses of these consistent reactivity data based on the activation strain model (ASM) of reactivity[α‐leaving group bond. In the course of our analyses, we develop the concepts of “intrinsic nucleophilicity”, “apparent nucleophilicity”, and “transition state acidity”, which are associated with a particular type of reaction. These concepts will provide chemists with rational design principles that will enable the design of selective synthetic routes to targeted products.Herein, we develop, based on quantum chemical analyses, a unified model that provides chemists with the tools to readily understand the duality of Lewis bases, that is their nucleophilic or protophilic character. To this end, we have explored and analyzed the potential energy surfaces along the reaction coordinates of the Seactivity4c, 10N2 and E2 reactions in Scheme The results of our ZORA‐OLYP/TZ2P computations on the SN2, anti‐E2, and syn‐E2 model reactions proceed via a reactant complex (RC) and a transition state (TS) towards a product complex (PC), which may eventually dissociate into products  constitutes the actual elimination process and leads to an intermediate complex (INT) in which the conjugated acid forms an X‐H⋅⋅⋅π complex with the newly formed ethylene and the leaving group Y− hydrogen binds to an ethylene Cα−H bond . From here, migration of XH to the leaving group leads, via a second transition state (TS2), to the PC, H2C=CH‐H⋅⋅⋅−YHX, which, for our model reactions,syn‐E2 elimination. In all cases, TS1 is higher in energy than TS2 and, therefore, rate‐determining for the overall anti‐E2 pathway. The energetically favored products for both anti‐E2 and syn‐E2 pathways are C2H4+YHX−, that is, the olefin plus the leaving group, microsolvated by the conjugate acid. A number of clear and general trends in reactivity can be discerned. Reaction barriers always increase as the Lewis base X− becomes less basic, along F−, Cl−, Br−, I−, and At− . This trend can be found for all of the C2H5Y substrates. As a consequence, the preferred reaction pathway switches from anti‐E2, in the cases where F− attacks the substrate, to SN2 for the heavier halide anions. For example, along F−, Cl−, Br−, I−, and At−+C2H5Cl, the SN2 reaction barrier  theory, that strong Lewis bases prefer the E2 pathway.syn‐E2 pathway is in all cases less reactive than anti‐E2.In most cases, the S state TS constitu state TS constitu state TS constitu state TS constituN2 barriers for X−+C2H5Y are consistently a few kcal mol−1 higher than the corresponding barriers for X−+CH3Y obtained at the same level of theory in an earlier study.−, Cl−, Br−, and I−+CH3Cl, the SN2 barrier increases comparatively moderately from −19.2 to −0.2, +4.1, and +7.9 kcal mol−1.N2 reactions of C2H5X compared with those of CH3X.N2 and anti‐E2 pathways as the leaving group Y in the substrate C2H5Y varies along F, Cl, Br, I, and At. Thus, along Cl−+C2H5F, C2H5Cl, C2H5Br, C2H5I, and C2H5At, the SN2 barrier  but an enhanced apparent nucleophilicity . The origin of these trends is analyzed and explained later on, on the basis of the activation strain model (ASM) of reactivity[Our computations show that less basic halides, that is, those with a lower proton affinity, are both worse nucleophiles and worse protophiles, in the sense that they lead to higher barriers for substitution (nucleophilic attack) as well as for elimination (protophilic attack) reactions along the series Feactivity4c, 10N2 versus E2 reactivity hold for all reaction systems. But the precise shape of the PES differs in a few instances to the extent that the process becomes spontaneous, the reverse barrier disappears, or the product complex becomes labile and leads to a spontaneous follow‐up reaction.The prior discussed trends in S− and C2H5Br, C2H5I, or C2H5At, the barrier for the anti‐E2 pathway disappears and F− spontaneously abstracts a β‐proton from C2H5X  to form the product complex E2‐a‐PC, C2H4⋅⋅⋅−YHX, without the occurrence of a stable reactant complex or transition state. The latter has become a shoulder on the PES along the reaction coordinate, as schematically depicted in Figure N2 reaction has also disappeared for these reactants, which is in line with our previously obtained results for the SN2 reactions F−+CH3Br and CH3I.−+C2H5X reactants leads into the anti‐E2 and not the SN2 channel.In the case of the rather exothermic reactions that occur between F−, I−, and At−+C2H5F have, by symmetry, no reverse barrier . This transition state is achieved after the actual substitution stage, as the reaction systems begin to deviate from the actual SN2 path. What happens is that the emerging leaving group, Y−=F−, is a relatively strong Lewis base, which induces a barrier‐free E2 elimination from the comparatively reactive C2H5X molecule  formed in the SN2 reaction  are collected in Figure E) into two distinct energy terms, namely, the strain energy (ΔEstrain) and the interaction energy (ΔEint). The strain energy results from the deformation of the individual reactants and the interaction energy between the deformed reactants along the reaction coordinate, defined, in this case, as the stretch of the α‐carbon–leaving group (Cα−Y) bond. This critical reaction coordinate undergoes a well‐defined change during the reaction from the reactant complex via the transition state to the product and is shown to be a valid reaction coordinate for studying substitution reactions.[syn‐E2 pathway always goes with a higher reaction barrier than the anti‐E2 pathway and, therefore, is excluded from this analysis. In Figure − (left column) and the leaving group Y (right column) influences the decomposition of the potential energy surface (PES) along the reaction coordinate (ζ), cf. Eq. (1), for the SN2 reaction (upper row) and anti‐E2 reaction (lower row). The solid curves represent the PES (ΔE), whereas the dashed and dotted curves represent the strain (ΔEstrain) and interaction (ΔEint) energy, respectively. Panels (a) and (c) compare curves of F−+C2H5F (black) and Cl−+C2H5F (red) for SN2 and anti‐E2 reactions, respectively, whereas panels (b) and (d) compare curves of Cl−+C2H5F (red) and Cl−+C2H5Cl (blue) for SN2 and anti‐E2 reactions, respectively. Note that the left and right columns share reaction 1 a, that is, Cl−+C2H5F. This series is representative for the observed effects induced by Lewis base and/or leaving group variations along the various model reactions. Figure N2 reaction, a stronger nucleophile enhances, in agreement with its increased intrinsic nucleophilicity, the stabilizing interaction energy over the entire course of the reaction, whereas the strain energy is minimally affected. The reason for this more stabilizing interaction energy is the stability of the X− n p atomic orbital (AO), which decreases along At−, I−, Br−, Cl−, and F− and reduces the corresponding HOMO–LUMO energy gap with the substrate 4c, 10N2 systems, a better leaving group reduces the strain curves, as a result of the prior discussed weaker carbon–leaving group bond, whereas the stabilizing interaction energy remains nearly unchanged , F−+C2H5Cl (1 b), Cl−+C2H5F (2 a), and Cl−+C2H5Cl (2 b). Going down a column, we vary the Lewis base, and along a row, we change the nature of the leaving group. Note that, for all reactions, the strain and interaction energy curves for the E2 reaction display a profound difference compared to the SN2 analog. As mentioned above, a sudden jump in strain and interaction energy is observed during the E2 reaction. This jump can be attributed to the proton abstraction by the Lewis base, which, in E2 reactions, acts as a protophile. The deprotonation of the substrate by the protophile requires a large deformation in the geometry of the substrate but also results in a more stabilizing interaction (see below).To directly analyze and compare the SN2 pathway intrinsically has a less destabilizing strain energy than the E2 analog, because along the former reaction pathway only one bond (Cα−Y) is being broken, while for the latter two bonds are being broken (Cα−Y and Cβ−H). Thus, the distortion, characteristic for the SN2 pathway, is inherently lower than the E2 pathway. At the same time, the “characteristic distortivity” for both pathways also has direct implications on the electronic structure of the substrate. The LUMO of the substrate has antibonding character in the Cα−Y and Cβ−H bonds. The deformation along the SN2 pathway (elongation of Cα−Y) reduces the antibonding overlap for Cα−Y, which, in turn, stabilizes the LUMO . As a result, the E2 pathways will always dominate the SN2 pathway in the limit of a strong interaction (more basic Lewis base), which we have observed for the reactions where X−=F−.Our activation strain analysis reveals that, similar to the strain energy, the interaction energy may also be translated into a simple concept, that is, it corresponds directly to the strength of the Lewis acid or base.1, 20 −=F− to X−=Cl− has a profound effect on the preferred reaction pathway, shifting the preference from E2 for F−  or the preference for the SN2 pathway is reduced ; see also Table N2 and E2 limit , solvation will enhance the apparent nucleophilicity as it increases the E2 reaction barrier to a larger extent than the SN2 reaction barrier. These effects will be more pronounced when the polarity of the solvent increases.Our herein presented model also explains the effect of solvation on the S− Figure , to a we− Figure  and, hensolution.6a, 6eN2/E2 competition of the following three, commonly used, Lewis bases H3CHN−, H3CO−, and H3CS− with C2H5Cl.[3CHN− (ϵHOMO=3.3 eV), to H3CO− (ϵHOMO = 2.4 eV), to H3CS− (ϵHOMO = 1.7 eV), which indicates that the Lewis base becomes increasingly weaker. This implies that the strong Lewis base H3CHN− will be prone to undergo an E2 reaction and that the intrinsic nucleophilicity reduces along the series from H3CHN−, to H3CO−, to H3CS−.Next, we seek to test our proposed general model and have, therefore, studied the Sh C2H5Cl.7, 22 N2 and E2 reaction between H3CX−  and C2H5Cl. As predicted, based on the stability of the HOMO of the Lewis base, H3CHN− is the most reactive Lewis base, to the extent that both the SN2 and E2 reactions are barrierless. We note that the SN2 reaction occurs with a TS‐like structure at −13.7 kcal mol−1 but this is a shoulder on the reactions’ potential energy surface, as shown in Figure 3CO− is a moderate Lewis base, it is strong enough to result in a lower reaction barrier for the E2 reaction compared to the SN2 reaction, −12.1 and −9.2 kcal mol−1, respectively. Contrarily, the weakest Lewis base of the series, H3CS−, undergoes, not unexpectedly, an SN2 reaction, with a barrier that is 3 kcal mol−1 lower than the E2 reaction. Thus, changing the Lewis base from H3CHN− to H3CO− to H3CS− reduces the intrinsic nucleophilicity, as the SN2 reaction barrier steadily increases, but enhances the apparent nucleophilicity, because the SN2 reaction barrier becomes consistently more favorable compared with the E2 barrier.Table N2/E2 competition of H3CO− and H3CS−, which prefer an E2 and SN2 reaction, respectively. It can clearly be seen that the more basic Lewis base H3CO− interacts strongly with the more acidic E2 transition state, which, in turn, manifests in a more stabilizing interaction energy  of reactivity to examine if the behavior of the Lewis base, that is, nucleophilic or protophilic, is indeed determined by the Lewis acid–base‐like interaction between the Lewis base and the substrate. In Figure y Figure . As a rey Figure . As the N2; nucleophilic attack) and base‐induced elimination  reactions are both accelerated when the electron‐donating capability of the Lewis base increases, but the E2 pathway benefits more and therefore is favored in the case of stronger Lewis bases. Solvation, in general, stabilizes the HOMO, decreasing the electron‐donating capability of the Lewis base and thus reduces the preference for E2 or enhances the preference for SN2 (enhanced apparent nucleophilicity), even though the barrier of the latter is also raised (reduced intrinsic nucleophilicity). These insights emerge from a detailed and consistent quantum chemical exploration of a vast range of archetypal model systems X−+C2H5Y  displaying a wide range in reactivity and pathways.Bimolecular nucleophilic substitution , versus, low and associated with a less destabilizing strain for the SN2 pathway, in which only one bond is broken (Cα−Y). At the same time, the LUMO of the substrate is Cα−Y and Cβ−H antibonding and therefore assumes a lower orbital energy along the more distortive E2 pathway, rendering effectively a higher electron‐accepting capability. We refer to this circumstance as the “transition state acidity” of the substrate, which is stronger for E2 than SN2.We highlight the main factors determining the shape of the potential energy surface, and hence the propensity of the Lewis base to act as a nucleophile or protophile, to be the structural deformation of the substrate during the course of the reaction in combination with the nature of the Lewis base and the nature of the leaving group. Each pathway is associated with a characteristic distortivity: high and associated with a more destabilizing strain for the E2 pathway, in which two bonds are broken  in a regime of strong interaction, that is, if the Lewis base is strong, the interaction overrules the strain and determines the barrier, and this factor is always more favorable, i.e., more stabilizing, for the more distortive pathway, E2. These findings show that the nucleophilic or protophilic behavior of a Lewis base towards a Lewis‐acidic substrate is fundamentally co‐determined by the latter.Thus, the Lewis acid–base‐like interaction between the Lewis base and the substrate in the transition state determines the outcome of the competition: (i) in a regime of weak interaction, that is, if the Lewis base is weak, the strain determines the barrier and this factor is always more favorable, i.e., less destabilizing, for the less distortive pathway, SN2 reactions, and why (stronger) solvation pushes the mechanistic competition from E2 towards SN2. The insights provided herein elucidate a plethora of experimental findings and can serve as powerful tools for a more rational design of synthetic routes. We envisage that the scope of our findings extends well beyond the competition between nucleophilic and protophilic reactivity.The introduced concepts of “characteristic distortivity” and “transition state acidity”, together with the distinction between apparent and intrinsic nucleophilicity, provide a vital, qualitative approach for understanding organic reactions in the framework of both MO theory and Lewis’ theory of acids and bases.15, 20The authors declare no conflict of interest.As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re‐organized for online delivery, but are not copy‐edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.SupplementaryClick here for additional data file.


Asymmetric synthesis of mechanically planar chiral rotaxanes and topologically chiral catenanes has been a long-standing challenge in organic synthesis. Recently, an excellent strategy was developed based on diastereomeric synthesis of rotaxanes and catenanes with mechanical chirality followed by removal of the chiral auxiliary. On the other hand, its enantioselective approach has been quite limited. Here, we report enantioselective preparation of mechanically planar chiral rotaxanes by kinetic resolution of the racemates via remote asymmetric acylation of a hydroxy group in the axis component, which provides an unreacted enantiomer in up to >99.9% ee in 29% yield . While the rotaxane molecules are expected to have conformational complexity, our original catalysts enabled to discriminate the mechanical chirality of the rotaxanes efficiently with the selectivity factors in up to 16. Since the discovery of mechanically planar chiral rotaxanes and topologically chiral catenanes, their asymmetric synthesis has been a long-standing challenge. Here, the authors report enantioselective preparation of mechanically planar chiral rotaxanes with up to 99.9% ee in 29% yield. Even if the ring component and the axis component are not chiral by themselves, the formation of interlocked molecules consisting of ring and/or axis components brings mechanical chirality when each of the components exhibits structural dissymmetry  spectra of both enantiomers of topologically chiral catenanes and mechanically planar chiral rotaxanes obtained by high-performance liquid chromatography (HPLC) separation of the racemates with chiral stationary phases.Asymmetric synthesis of molecules with central, axial, planar, and helical chirality has been extensively developed, and the field of asymmetric synthesis is becoming a mature science. On the other hand, asymmetric synthesis of chiral mechanically interlocked molecules such as mechanically planar chiral rotaxanes and topologically chiral catenanes Fig.  has beentry Fig. . This wa5. Their synthesis and the applications to molecular devices and catalysis have been actively studied14. Since the proposal of mechanically planar chirality and topological chirality in the structure of rotaxanes and catenanes, respectively2, their enantioselective preparation has been a challenge in organic synthesis14. In most cases, the strategy largely relied on separation of enantiomers by HPLC with chiral stationary phases6. Recently, Goldup and co-workers proposed an excellent practical method for the preparation of an enantiomeric pair of mechanically planar chiral rotaxanes via separation of the corresponding diastereomers followed by removal of the chiral auxiliary16. The strategy was also applied to the stereoselective synthesis of topologically chiral catenanes17. On the other hand, a pioneering approach toward the direct catalytic enantioselective synthesis of a mechanically planar chiral rotaxane was reported by Takata and co-workers . Very recently, Leigh and co-workers achieved enantioselective synthesis of mechanically planar chiral rotaxanes in up to 50% ee by a chiral leaving group strategy19. To date, however, there have been no reports on highly enantioselective catalytic synthesis of chiral mechanically interlocked molecules. Here, we report highly enantioselective preparation of mechanically planar chiral rotaxanes by kinetic resolution of the racemates promoted by acylation catalysts ).Mechanically interlocked molecules such as rotaxanes and catenanes have attracted considerable attentions because of the non-conventional molecular frameworksers Fig. 18. An acsts Fig. . A rotax20. A problem is determining how can such remote asymmetric induction be achieved? Methods for acylative kinetic resolution of racemic alcohols have been extensively investigated, and efficient discrimination of chirality of substrate alcohols has been achieved when the reacting center (OH) in the substrate is close to the chiral center  (S25-34), temperature-dependent 1H NMR spectra (S58-60) and temperature-dependent CD spectra (S7) of 1a-OAc). On the other hand, a highly successful example for remote asymmetric acylation of a bisphenol compound with rigid conformation has been reported22. Dynamic kinetic resolution of a [2]rotaxane with point prochirality by asymmetric acylation has also been reported23.Inspired by Takata’s pioneering work in this field Fig. , we desiter Fig. 21. On thble Fig. . Further1a–c  group. According to our previous studies27, we hypothesized that use of a substrate alcohol with an NHNs group in the presence of catalyst 3 -4 took place in the presence of catalyst 3, while acylation of (5R)-4 occurred at the primary hydroxy group almost exclusively. Comparison of the contrasting chemoselectivities suggests that catalyst 3 might recognize remote chirality at C(5) of 4, even when acylation takes place at the hydroxy group at C(1). Catalyst 3 possesses uncommon structural characteristics as chiral catalysts, where chiral elements are located at a certain distance from the catalytically active site (pyridine nitrogen)28. This could be somewhat suitable for remote asymmetric acylation as shown in a possible transition state model . Based on these backgrounds and other results regarding chemoselective acylation observed in our laboratory26, we chose racemic rotaxanes 1a–c and catalyst 3 and the related catalysts for the study of the kinetic resolution.Aiming at effective kinetic resolution, we designed rotaxane a–c Fig.  that cont 3 Fig.  and the . 4 Fig. 24. Highl1a–c with various chiral 4-pyrroridinopyridine (PPY) catalysts 2  of 2.6 (entry 1). With these promising results in hand, we next examined the substrate structure. The bulkiness of the amide groups , entry 5: s = 1.9 for 1c (R = Ad), entry 6: s = 2.6 for 1a (R = Me), entry 1). After finding that catalyst 2 is the most effective for the acylative kinetic resolution of mechanically planar chiral rotaxanes, we re-investigated the reaction parameters, including the solvents, acylating agents, auxiliary bases and concentrations (Supplementary Table 1). We employed acid anhydrides as acyl donors throughout the screening because carboxylate anion generated from the anhydride and the nucleophilic catalyst was expected to be critically important for both selectivity and acceleration of the site-selective acylation32. It was found that selectivity of the acylation was strongly dependent on the substrate concentration. Since the best results were obtained with substrate 1a at 0.01 M in the presence of collidine and acetic anhydride in CHCl3 solution, further optimization of the reaction conditions was performed with the substrate concentration of 0.01 M (Table racemic1a (0.01 M) with 0.5 equivalents of acetic anhydride in the presence of 0.5 equivalents of catalyst 2 and 1.2 equivalents of collidine in CHCl3 at −60 °C for 6 h to give the acylated chiral rotaxane in 66% ee and recovered chiral rotaxane 1a in 23% ee, which corresponds to s = 6.1 at 26% conversion hydrogen bonding interaction with a catalyst for the molecular recognition process  with an s factor of >14.5  compared to the case of 1a (s = 16.1). The reaction of 10 was also found to be quite sluggish compared with that of 1a. Acylation of 1a proceeded at 44% conversion after 6 h, whereas that of 10 progressed only in 8% conversion even after 37 h under the identical conditions. This suggests that the NHNs group of 1a plays a key role in the molecular recognition process between the catalyst and the substrate as a hydrogen-bond donor. The hydrogen bonding interaction is assumed to be responsible for asymmetric induction, as well as acceleration of the acylation reaction . A diminished enantioselectivity (s = 3.6) was also observed in the kinetic resolution of 11 with CH2NHNs group instead of an NHNs group of 1a. This may suggest either that a more acidic hydrogen of the NHNs group in 1a than that in 11 serves as a better hydrogen-bond donor and/or importance of the distance between the OH and NH groups for effective chiral discrimination by the catalyst. The enhanced conformational flexibility by one-carbon elongation could also be responsible for the diminished selectivity. Based on these results and previously proposed transition state models for site-selective acylation with catalyst 2 and the related catalysts34, we propose A as a possible transition state model for remote asymmetric acylation  with constraint of hydrogen bonds indicated by yellow circles  of catalyst 2  were added a CHCl3 solution of 2,4,6-collidine  and a CHCl3 solution (1.0 ml) of racemic rotaxane 1a  at room temperature. The mixture was cooled to −60 °C. A CHCl3 solution of acetic anhydride  was added dropwise to the mixture, and the reaction mixture was stirred at −60 °C for 37 h. Then MeOH (15 ml) was added to the reaction mixture at −60 °C, and the mixture was stirred at room temperature for 30 min. The mixture was evaporated to dryness under a reduced pressure. The crude product was subjected to preparative thin layer chromatography (TLC)  to allow isolation of recovered 1a  and acylated 1a-OAc . Enantiomeric purity of the recovered rotaxane, 1a (>99.9% ee), and the acylated product, 1a-OAc (40% ee), was determined by chiral HPLC with CHIRALPAK-IC column eluted by EtOH/CH2Cl2 1/60 (0.7 ml/min) at 20 °C. Conversion  and selectivity factor  were determined according to the following equation: conversion C = ee1a/(ee1a + ee1a-OAc) and selectivity factor s = ln[(1 – C)(1 – ee1a)]/ln[(1 – C) (1 + ee1a)] = ln[1 – C(1 + ee1a-OAc)]/ln[1 – C(1 − ee1a-OAc)].To a CHClFurther information on research design is available in the Supplementary InformationPeer Review FileReporting Summary


Thermodynamic calculations and viscosity measurements were applied for studying the evaporation mechanism of fluoride. The results showed that the evaporation ratio increases with increasing Li2O content and temperature. The volatile constituents from the molten slags, mainly LiF and CaF2, were detected and their concentrations calculated. The fluoride evaporation is primarily affected by the vapour pressure of LiF and CaF2, viscosity of the slags, and melt-component activities under given experimental conditions. On the other hand, mass transfer of the gas is not the rate-controlling step that affects fluoride evaporation from the slags. The activation energy for fluoride evaporation gradually decreased from 193 ± 11 to 113 ± 3 kJ mol−1 as the Li2O content in the slags increases from 0 to 5.48 wt%. These results hold great theoretical significance for developing low-fluoride slags for electroslag remelting.The isothermal kinetics of fluoride evaporation from CaF To perform the intended functions, the slags must have some well-defined properties such as low electrical conductivity and suitable viscosity at remelting temperature7. The traditional ESR slags are CaF2–CaO–Al2O3-based slags with a high CaF2 content, and an additive such as MgO, TiO2 or SiO2 is commonly used to meet specific material requirements. However, fluoride evaporation from high CaF2-content slags is a potential health- and safety hazard. Furthermore, it would alter the chemical composition and cause changes in the metallurgical properties of the slags11. Therefore, it is important to develop low-fluoride slags and study their effect on fluoride evaporation during the ESR process.The slags in electroslag remelting (ESR) process serve as a heat source, a barrier to the atmosphere, and a medium for liquid metals refining2O3 mass ratio and substitute a small amount of oxides for CaF2 to keep the physicochemical properties stable. Several oxides including Na2O, B2O3, and Li2O are considered as potential substitutes for CaF214. Among them, a small addition of Li2O could effectively regulate the viscosity and melting temperature of the slags; thus, the partial substitution of CaF2 with Li2O retains the performance of the slags. Several works reported by Shi et al.15 have researched the effect of Li2O on the viscosity of CaF2–CaO–Al2O3–MgO slags, which suggested that the viscosity of slags decreased with Li2O content increasing from 0 to 4.5 wt%. Kim et al.16 measured the viscosity of CaO–Al2O3-12 wt% Na2O-12 wt% CaF2-based slags and concluded that the addition of Li2O depolymerized the large aluminate structures and decreased the slag viscosity. Additionally, Liu et al.17 studied the effect of Li2O on the properties of CaF2–CaO–Al2O3–SiO2–Na2O–Li2O slags, and discovered that adding a small account of Li2O could decrease the slag-melting temperature. The characteristic temperature experiments conducted by Qi et al.18 indicated that the melting temperature of CaO–Al2O3–Li2O–Ce2O3 slags reduced gradually with the increase of Li2O content. In conclusion, Li2O provides an optimum condition for reducing the viscosity and melting temperature. Thus, it could be selected as an effective component to design the low-fluoride slags for ESR. However, several studies have reported that Li2O could react with CaF2 resulting in the appearance of gaseous LiF20. Such a loss of the fluoride will lead to serious environmental pollution and health problems22. However, the previous studies are very limited in demonstrating the mechanism of fluoride evaporation. Thus, it is necessary to study the effect of Li2O on the fluoride evaporation from low-fluoride slags.The most common approach for developing low-fluoride slags is to control the CaO/Al2–CaO–Al2O3–MgO–TiO2–(Li2O) slags containing 0–6 wt% Li2O in the temperature range 1743–1803 K. Meanwhile, the evaporation of fluoride was qualitatively analysed using thermodynamic calculations and viscosity measurements. The influence of Li2O on the mechanism of fluoride evaporation was clarified to gain the theoretical understanding of the development of low-fluoride slags for ESR.In the present work, isothermal thermogravimetry was employed to investigate the kinetics of fluoride evaporation from CaF2 (≥ 98.5%), CaO (≥ 98.0%), Al2O3 (≥ 99.0%), MgO (≥ 98.0%), TiO2 (≥ 99.0%), and Li2O (≥ 99.9%). The initial compositions are listed in Table All slag samples were prepared from analytical-grade reagents of CaFIsothermal thermogravimetric experiments were conducted using a thermal analyser  having an accuracy of 0.2 μg at three temperatures: 1743, 1773, and 1803 K. Figure −1. To reduce the evaporation during the heating process, the samples were heated to the desired temperature at 100 K min−1 rate. The samples were held at the target temperature for 60 min. The Pt crucible was placed in an alumina crucible, which was suspended in the sample chamber and connected to the balance of the thermal analyser using a Pt wire. The length of the Pt wire was adjusted to ensure that the slags were positioned in the uniform-temperature zone. To exclude the influence of system error in the thermal analyser and buoyancy force of the gas mixtures, blank tests were conducted with empty crucibles. The slag viscosity measurements were conducted using a rotating spindle viscometer , as shown in Fig. The experiments were conducted using the pre-melted samples weighting 15 ± 0.5 mg and having a particle size less than 74 μm. The slag samples were tested in a Pt crucible having inside diameter of 5.0 mm and height of 6.0 mm and under high-purity Ar gas with a flow rate of 70 mL min23. In the present work, the equilibrium module was used to predict the evaporating species. For the calculations, the equilibrium module was employed together with the databases FToxid and FactPS. Additionally, to understand the vapour pressures of volatile fluoride from the thermodynamics perspective, the equilibrium constant (K) and the component activity in the molten slags (a) were calculated using the FactSage software’s reaction module and equilibrium module, respectively.Moreover, the thermodynamic calculations were performed with the principle of minimising Gibbs free energy using FactSage software The ratio of weight loss to the initial mass (α) is calculated from the thermogravimetric data by Eq. 1\documenm0 represents the initial slag mass. mt is the slag mass at time t. Figure Here, 2O content. The detailed discussion on the effect of Li2O on evaporation will be discussed in the next section. The maximum values of α at 1773 and 1803 K increase from 4.98 to 10.28% and 6.13 to 13.15%, respectively, when Li2O content increases from 0 to 5.48 wt%. The results suggest that α gradually increases with increasing temperature. From kinetic point of view, an increase in temperature decreases the viscosity, which accelerates the liquid phase mass transport. The weight loss process of the slags can be separated into two stages. The evaporation ratio rapidly increases in the first 500 s, and shows a slower increase at longer times. Figure The weight loss curves of the slags at different temperatures are shown in Fig. The possible reactions occurring during the isothermal experiments are as follows:2) and their quantities were calculated. The estimated weight of LiF was obviously greater than that of CaF2. The quantities of gaseous MgF2, AlF3, and AlOF generated were negligible. Therefore, Eqs.  and cations (Li+ and Ca2+) involved in Eqs. ..3).2 gas molecules.Nucleation of LiF and CaFThe transport of bubbles from the bulk liquid slag to the slag/gas interface through the liquid boundary layer.The transport of the gas from the slag/gas interface to the bulk gas flow through the stagnant gas film.Flow of the bulk gas stream from the crucible.The rate-controlling step of the fluoride evaporation process can be one or a combination of the following steps Fig. 24–26:Mas27. The equilibrium constants for Eqs.  of LiF and CaF2, respectively, and ai is the activity of the melt component i in the molten slags. KEq and ai were calculated by thermodynamic calculations of FactSage software. The vapour pressures of LiF and CaF2 were calculated by entering the equilibrium constant values and activity data into Eqs. ;;PLiF andons Eqs.  .The fluoride evaporation process is also affected by the viscosity and component activities of the slag19 The Li2O activity values calculated for various temperatures are listed in Table 2O activity of gradually increases with increasing Li2O content, which favours the formation of LiF. Moreover, increasing the temperature can promote liquid mass transfer and the transport of bubbles from bulk liquid slag to the slag/gas interface through the liquid boundary layer. Hence, σ increases with increasing temperature and Li2O content.The thermodynamic calculations of the melt component activities were performed using FactSage software according to the work reported by Zheng et al.27.By comprehensively analysing the vapour pressures, viscosity of the slags, and melts component activities, it can be concluded that step (1), (2), and (4) play a significant part in controlling the evaporation process. These results are in agreement with those reported by Liu et al.−1) is above the starvation rate, the isothermal experiments were conducted under different Ar flow rates conducted. Figure −1 did not appear to affect the fluoride evaporation rate in L4. This is because the bulk-gas flow rate of 70 mL min−1 is sufficient to carry the volatile constituents at a rate larger than that of the evaporation reaction itself. Hence, step (6) is unlikely to act the rate-controlling step.In the present study, step (5) and (6) are gas-mass transfer processes. In order to understand whether the Ar flow rate used  is rate-controlling step, the following analysis was performed based on the schematic model shown in Fig. DLiF and DCaF2 represent the diffusion coefficients of LiF and CaF2, respectively. through Ar gas (cm2 s−1). L is the distance between the surface of molten slag and the top edge of the crucible (cm). R is the gas constant [8.314 J/(mol K)]. T is the absolute temperature (K). Pi and Pb are vapour pressures at the slag/gas interface and in the bulk of the flow, respectively (atm). Pb is assumed zero under the present experiment. The diffusion coefficient is typically estimated using the Chapman–Enskog equation36Here, DAB is the mass diffusivity of A through B (cm2 s); −1σAB, ΩAB are the Lennard–Jones parameters, and the dimensionless quantity ΩAB is the collision integral, which is function of dimensionless temperature (κT/ε). MA and MB are molecular weights of component LiF or CaF2 and Ar gas, respectively. P is the absolute pressure (atm). The parameters for Ar gas are available from the literature. However, the experimental data is not available for specific gaseous species such as LiF and CaF2. Their parameters can be estimated by the following empirical relations36:Here, Tm is the melting temperature (K) and Vm is the molecular volume (cm3 mol−1). The values of ε/κ and σ for different gaseous species37 are shown in Table AB and εAB were then estimated from Eqs. Tm is the2 in Ar gas were also calculated using Eq.  is unlikely to be the rate-controlling step for the differences are too large. The findings of this research are consistent with previous studies by Li et al.2 in the present experiment. Further studies are needed to determine whether step (3) is the rate-controlling process.Based on the discussion above, step (5) and step (6) are not rate-limiting steps. However, steps (1), (2), step (4) would be the rate-controlling steps for the evaporation of LiF and CaF41The activation energy of evaporation is a critical parameter to evaluate the propensity of evaporation. The Activation energy for evaporation can be determined by fitting the Arrhenius equationk represents the rate constant, T is the reaction temperature, A is the pre-exponential factor (s−1), and Ea is the activation energy (J mol−1). It is worth mentioning that the evaporation rates appear almost linear trend in four slag samples in the first stage. Since the chemical composition of the slags changes significantly due to fluoride evaporation, the present study took the initial 500 s to calculate the activation energy of evaporation. The activation energy for evaporation of the slags with varying Li2O contents is presented in Fig. 2) obtained from the data fitting procedure is close to 1. The calculated values of activation energy decreased with the addition of Li2O to the slags. The Ea value calculated for L0 was 193 ± 11 kJ mol−1, which gradually dropped to 113 ± 3 kJ mol−1 as the Li2O content increased. It further proves that Li2O, as a network modifier, depolymerizes the intricate network structure and thus decreases the activation energy of the evaporation process.Here, 2O on the fluoride evaporation of the CaF2–CaO–Al2O3–MgO–TiO2–(Li2O) slag was investigated in the temperature range 1743–1803 K using isothermal thermogravimetry. Our results are summarised as follows:2O content and temperature.The fluoride evaporation from the molten slags occurred primarily during the initial 500 s; the process was promoted by increasing the Li2. The activation energy for the fluoride evaporation decreased from 193 ± 11 to 113 ± 3 kJ mol−1 as Li2O content increased from 0 to 5.48 wt%.The species evaporating from the molten slags mainly consisted of LiF and CaF2O in the slags. On the other hand, gas mass transfer was not the rate-controlling step under the present experimental conditions.The evaporation of fluoride was primarily affected by its vapour pressure, viscosity of the slags, and activity of Li2O can effectively regulate the viscosity of the slags and serve as an effective component in low-fluoride slags for ESR. However, harmful gaseous LiF evaporates from the molten slags when CaF2 is substituted with Li2O.A small amount of LiThe effect of Li