Targeting UBE2T Potentiates Gemcitabine Efficacy in Pancreatic Cancer by Regulating Pyrimidine Metabolism and Replication Stress.

BACKGROUND & AIMS: Although small patient subsets benefit from current targeted strategies or immunotherapy, gemcitabine remains the first-line drug for pancreatic cancer (PC) treatment. However, gemcitabine resistance is widespread and compromises long-term survival. Here, we identified ubiquitin-conjugating enzyme E2T (UBE2T) as a potential therapeutic target to combat gemcitabine resistance in PC. METHODS: Proteomics and metabolomics were combined to examine the effect of UBE2T on pyrimidine metabolism remodeling. Spontaneous PC mice (LSL-KrasG12D/+, LSL-Trp53R172H/+, Pdx1-Cre; KPC) with Ube2t-conditional knockout, organoids, and large-scale clinical samples were used to determine the effect of UBE2T on gemcitabine efficacy. Organoids, patient-derived xenografts (PDX), and KPC mice were used to examine the efficacy of the combination of a UBE2T inhibitor and gemcitabine. RESULTS: Spontaneous PC mice with Ube2t deletion had a marked survival advantage after gemcitabine treatment, and UBE2T levels were positively correlated with gemcitabine resistance in clinical patients. Mechanistically, UBE2T catalyzes ring finger protein 1 (RING1)-mediated ubiquitination of p53 and relieves the transcriptional repression of ribonucleotide reductase subunits M1 and M2, resulting in unrestrained pyrimidine biosynthesis and alleviation of replication stress. Additionally, high-throughput compound library screening using organoids identified pentagalloylglucose (PGG) as a potent UBE2T inhibitor and gemcitabine sensitizer. The combination of gemcitabine and PGG diminished tumor growth in PDX models and prolonged long-term survival in spontaneous PC mice. CONCLUSIONS: Collectively, UBE2T-mediated p53 degradation confers PC gemcitabine resistance by promoting pyrimidine biosynthesis and alleviating replication stress. This study offers an opportunity to improve PC survival by targeting UBE2T and develop a promising gemcitabine sensitizer in clinical translation setting.

Mechanism of the Visible-Light-Promoted C(sp3)-H Oxidation via Uranyl Photocatalysis.

Uranyl cation, as an emerging photocatalyst, has been successfully applied to synthetic chemistry in recent years and displayed remarkable catalytic ability under visible light. However, the molecular-level reaction mechanisms of uranyl photocatalysis are unclear. Here, we explore the mechanism of the stepwise benzylic C-H oxygenation of typical alkyl-substituted aromatics (i.e., toluene, ethylbenzene, and cumene) via uranyl photocatalysis using theoretical and experimental methods. Theoretical calculation results show that the most favorable reaction path for uranyl photocatalytic oxidation is as follows: first, hydrogen atom transfer (HAT) from the benzyl position to form a carbon radical ([R•]), then oxygen addition ([R•] + O2 → [ROO•]), then radical-radical combination ([ROO•] + [R•] → [ROOR] → 2[RO•]), and eventually [RO•] reduction to produce alcohols, of which 2° alcohol would further be oxidized to ketones and 1° would be stepwise-oxygenated to acids. The results of the designed verification experiments and the capture of reactive intermediates were consistent with those of theoretical calculations and the previously reported research that the active benzylic C-H would be stepwise-oxygenated in the presence of uranyl. This work deepens our understanding of the HAT mechanism of uranyl photocatalysis and provides important theoretical support for the relevant application of uranyl photocatalysts in organic transformation.

Quantitative kinetics reveal that reactions of HO2 are a significant sink for aldehydes in the atmosphere and may initiate the formation of highly oxygenated molecules via autoxidation.

Large aldehydes are widespread in the atmosphere and their oxidation leads to secondary organic aerosols. The current understanding of their chemical transformation processes is limited to hydroxyl radical (OH) oxidation during daytime and nitrate radical (NO3) oxidation during nighttime. Here, we report quantitative kinetics calculations of the reactions of hexanal (C5H11CHO), pentanal (C4H9CHO), and butanal (C3H7CHO) with hydroperoxyl radical (HO2) at atmospheric temperatures and pressures. We find that neither tunneling nor multistructural torsion anharmonicity should be neglected in computing these rate constants; strong anharmonicity at the transition states is also important. We find rate constants for the three reactions in the range 3.2-7.7 × 10-14 cm3 molecule-1 s-1 at 298 K and 1 atm, showing that the HO2 reactions can be competitive with OH and NO3 oxidation under some conditions relevant to the atmosphere. Our findings reveal that HO2-initiated oxidation of large aldehydes may be responsible for the formation of highly oxygenated molecules via autoxidation. We augment the theoretic studies with laboratory flow-tube experiments using an iodide-adduct time-of-flight chemical ionization mass spectrometer to confirm the theoretical predictions of peroxy radicals and the autoxidation pathway. We find that the adduct from HO2 + C5H11CHO undergoes a fast unimolecular 1,7-hydrogen shift with a rate constant of 0.45 s-1. We suggest that the HO2 reactions make significant contributions to the sink of aldehydes.

Rapid Atmospheric Reactions between Criegee Intermediates and Hypochlorous Acid.

Hypochlorous acid (HOCl) is a paramount compound in the atmosphere due to its significant contribution to both tropospheric oxidation capacity and ozone depletion. The main removal routes for HOCl are photolysis and the reaction with OH during the daytime, while these processes are unimportant during the nighttime. Here, we report the rapid reactions of Criegee intermediates (CH2OO and anti/syn-CH3CHOO) with HOCl by using high-level quantum chemical methods as the benchmark; their accuracy is close to coupled cluster theory with single, double, and triple excitations and quasiperturbative connected quadruple excitations with a complete basis limit by extrapolation [CCSDT(Q)/CBS]. Their rate constants have been calculated by using a dual-level strategy; this combines conventional transition state theory calculated at the benchmark level with variational transition state theory with small-curvature tunneling by a validated density functional method. We find that the introduction of the methyl group into Criegee intermediates not only affects their reactivities but also exerts a remarkable influence on anharmonicity. The calculated results uncover that anharmonicity increases the rate constants of CH2OO + HOCl by a factor of 18-5, while it is of minor importance in the anti/syn-CH3CHOO + HOCl reaction at 190-350 K. The present findings reveal that the loose transition state for anti-CH3CHOO and HOCl is a rate-determining step at 190-350 K. We also find that the reaction of Criegee intermediates with HOCl contributes significantly to the sink of HOCl during the nighttime in the atmosphere.

Dual-level strategy for quantitative kinetics for the reaction between ethylene and hydroxyl radical.

The atmospheric reactions are mainly initiated by hydroxyl radical (OH). Here, we choose the C2H4 + OH reaction as a model reaction for other reactions of OH with alkenes. We use the GMM(P).L//CCSD(T)-F12a/cc-pVTZ-F12 theoretical method as the benchmark results close to the approximation of CCSDTQ(P)/CBS accuracy to investigate the C2H4 + OH reaction. The rate constants for the C2H4 + OH reaction at high-pressure limit were calculated by using the dual-level strategy. It integrates the transition state theory rate constant calculated by GMM(P).L//CCSD(T)-F12a/cc-pVTZ-F12 with the canonical variational transition state theory containing small-curvature tunneling (CVT/SCT) calculated by using the M11-L functional method with the MG3S basis set. The rate constants of C2H4 + OH at different pressures were obtained by using both the system-specific quantum Rice-Ramsperger-Kassel (SS-QRRK) theory and master equation method. The calculated results uncover that both the calculated rate constants at different pressures and temperatures are quantitatively consistent with the values obtained by the experimental measurements in the C2H4 + OH reaction. We find that the post-CCSD(T) contributions to the barrier height for the C2H4 + OH reaction are significant with the calculated value of -0.38 kcal/mol. We also find that the rate determining step is only dominated by the tight transition state under atmospheric conditions, whereas previous investigations indicated that the rate constants were controlled by both the loose and tight transition states in the C2H4 + OH reaction. The present findings unravel that it is an important factor for the effect of torsional anharmonicity on quantitative kinetics.

Artificial Intelligence-Assisted Prescription Determination for Orthokeratology Lens Fitting: From Algorithm to Clinical Practice.

OBJECTIVES: To explore the potential of artificial intelligence (AI) to assist prescription determination for orthokeratology (OK) lenses. METHODS: Artificial intelligence algorithm development followed by a real-world trial. A total of 11,502 OK lenses fitting records collected from seven clinical environments covering major brands. Records were randomly divided in a three-way data split. Cross-validation was used to identify the most accurate algorithm, followed by an evaluation using an independent test data set. An online AI-assisted system was implemented and assessed in a real-world trial involving four junior and three senior clinicians. RESULTS: The primary outcome measure was the algorithm's accuracy (ACC). The ACC of the best performance of algorithms to predict the targeted reduction amplitude, lens diameter, and alignment curve of the prescription was 0.80, 0.82, and 0.83, respectively. With the assistance of the AI system, the number of trials required to determine the final prescription significantly decreased for six of the seven participating clinicians (all P <0.01). This reduction was more significant among junior clinicians compared with consultants (0.76±0.60 vs. 0.32±0.60, P <0.001). Junior clinicians achieved clinical outcomes comparable to their seniors, as 93.96% (140/149) and 94.44% (119/126), respectively, of the eyes fitted achieved unaided visual acuity no worse than 0.8 ( P =0.864). CONCLUSIONS: AI can improve prescription efficiency and reduce discrepancies in clinical outcomes among clinicians with differing levels of experience. Embedment of AI in practice should ultimately help lessen the medical burden and improve service quality for myopia boom emerging worldwide.

Ammonolysis of Glyoxal at the Air-Water Nanodroplet Interface.

The reactions of glyoxal (CHO)2 ) with amines in cloud processes contribute to the formation of brown carbon and oligomer particles in the atmosphere. However, their molecular mechanisms remain unknown. Herein, we investigate the ammonolysis mechanisms of glyoxal with amines at the air-water nanodroplet interface. We identified three and two distinct pathways for the ammonolysis of glyoxal with dimethylamine and methylamine by using metadynamics simulations at the air-water nanodroplet interface, respectively. Notably, the stepwise pathways mediated by the water dimer for the reactions of glyoxal with dimethylamine and methylamine display the lowest free energy barriers of 3.6 and 4.9 kcal ⋅ mol-1 , respectively. These results showed that the air-water nanodroplet ammonolysis reactions of glyoxal with dimethylamine and methylamine were more feasible and occurred at faster rates than the corresponding gas phase ammonolysis, the OH+(CHO)2 reaction, and the aqueous phase reaction of glyoxal, leading to the dominant removal of glyoxal. Our results provide new and important insight into the reactions between carbonyl compounds and amines, which are crucial in forming nitrogen-containing aerosol particles.

Kinetics of Sulfur Trioxide Reaction with Water Vapor to Form Atmospheric Sulfuric Acid.

Although experimental methods can be used to obtain the quantitative kinetics of atmospheric reactions, experimental data are often limited to a narrow temperature range. The reaction of SO3 with water vapor is important for elucidating the formation of sulfuric acid in the atmosphere; however, the kinetics is uncertain at low temperatures. Here, we calculate rate constants for reactions of sulfur trioxide with two water molecules. We consider two mechanisms: the SO3···H2O + H2O reaction and the SO3 + (H2O)2 reaction. We find that beyond-CCSD(T) contributions to the barrier heights are very large, and multidimensional tunneling, unusually large anharmonicity of high-frequency modes, and torsional anharmonicity are important for obtaining quantitative kinetics. We find that at lower temperatures, the formation of the termolecular precursor complexes, which is often neglected, is rate-limiting compared to passage through the tight transition states. Our calculations show that the SO3···H2O + H2O mechanism is more important than the SO3 + (H2O)2 mechanism at 5-50 km altitudes. We find that the rate ratio between SO3···H2O + H2O and SO3 + (H2O)2 is greater than 20 at altitudes between 10 and 35 km, where the concentration of SO3 is very high.

Quantitative kinetics of the atmospheric reaction between isocyanic acid and hydroxyl radicals: post-CCSD(T) contribution, anharmonicity, recrossing effects, torsional anharmonicity, and tunneling.

Hydroxyl radicals (OH) are the most important atmospheric oxidant, initiating atmospheric reactions for the chemical transformation of volatile organic compounds. Here, we choose the HNCO + OH reaction as a prototype reaction because it contains the fundamental reaction processes for OH radicals: H-abstraction reaction by OH and OH addition reaction. However, its kinetics are unknown under atmospheric conditions. We investigate the reaction of HNCO with OH by using the GMM(P).L method close to the accuracy of single, double, triple, and quadruple excitations and noniterative quintuple excitations with a complete basis set (CCSDTQ(P)/CBS) as benchmark results and a dual-level strategy for kinetics calculations. The calculated rate constant of HNCO + OH is in good agreement with the experimental data available at the temperatures between 620 and 2500 K. We find that the rate constant cannot be correctly obtained by using experimental data to extrapolate the atmospheric temperature ranges. We find that the post-CCSD(T) contribution is very large for the barrier height with the value of -0.85 kcal mol-1 for the H-abstraction reaction, while the previous investigations were done up to the CCSD(T) level. Moreover, we also find that recrossing effects, tunneling, torsional anharmonicity, and anharmonicity are important for obtaining quantitative kinetics in the OH + HNCO reaction.

Oxidative Modification of miR-184 Enables It to Target Bcl-xL and Bcl-w.

MicroRNAs (miRNAs) are small non-coding RNAs, and they bind to complementary sequences in the three prime untranslated regions (3' UTRs) of target mRNA transcripts, thereby inhibiting mRNA translation or promoting mRNA degradation. Excessive reactive oxygen species (ROS) can cause cell-damaging effects through oxidative modification of macromolecules leading to their inappropriate functions. Such oxidative modification is related to cancers, aging, and neurodegenerative and cardiovascular diseases. Here we report that miRNAs can be oxidatively modified by ROS. We identified that miR-184 upon oxidative modification associates with the 3' UTRs of Bcl-xL and Bcl-w that are not its native targets. The mismatch of oxidized miR-184 with Bcl-xL and Bcl-w is involved in the initiation of apoptosis in the study with rat heart cell line H9c2 and mouse models. Our results reveal a model of ROS in regulating cellular events by oxidatively modifying miRNA.

Pre-anesthesia ultrasound monitoring of subclavian vein diameter changes induced by modified passive leg raising can predict the occurrence of hypotension after general anesthesia: a prospective observational study.

BACKGROUND: Perioperative hypotension increases postoperative complication rates and prolongs postoperative recovery time. Whether Passive Leg Raising test (PLR) and Subclavian Vein Diameter (DSCV) can effectively predict post-anesthesia hypotension remains to be tested. This study aimed to identify specific predictors of General Anesthesia (GA)induced hypotension by measuring DSCV in the supine versus PLR position. METHODS: A total of 110 patients who underwent elective gynecological laparoscopic surgery under general anesthesia, were enrolled in this study. Before anesthesia, DSCV and theCollapsibility Index of DSCV(DSCV-CI) were measured by ultrasound, and the difference in maximal values of DSCV between supine and PLR positions was calculated, expressed as ΔDSCV. Hypotension was defined as Mean Blood Pressure (MBP) below 60mmhg or more than 30% below the baseline. Patients were divided into two groups according to the presence (Group H) or absence (Group N) of postanesthesia hypotension. The area under the receiver operating characteristic curve (ROC) and logistic regression analyses were used to evaluate the predictability of DSCV and other parameters for predicting preincision hypotension. RESULTS: Three patients were excluded due to unclear ultrasound scans, resulting in a total of 107 patients studied. Twenty-seven (25.2%) patients experienced hypotension. Area under the ROC curve of ΔDSCV was 0.75 (P < 0.001) with 95% confidence interval (0.63-0.87), while DSCV and DSCV-CI were less than 0.7. The odds ratio (OR)of ΔDSCV was 1.18 (P < 0.001, 95%CI 1.09-1.27) for predicting the development of hypotension. ΔDSCV is predictive of hypotension following induction of general anesthesia. CONCLUSIONS: ΔDSCV has predictive value for hypotension after general anesthesia. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry on 04/10/2021.

Quantitative Kinetics of HO2 Reactions with Aldehydes in the Atmosphere: High-Order Dynamic Correlation, Anharmonicity, and Falloff Effects Are All Important.

Kinetics provides the fundamental parameters for elucidating sources and sinks of key atmospheric species and for atmospheric modeling more generally. Obtaining quantitative kinetics in the laboratory for the full range of atmospheric temperatures and pressures is quite difficult. Here, we use computational chemistry to obtain quantitative rate constants for the reactions of HO2 with HCHO, CH3CHO, and CF3CHO. First, we calculate the high-pressure-limit rate constants by using a dual-level strategy that combines conventional transition state theory using a high level of electronic structure wave function theory with canonical variational transition state theory including small-curvature tunneling using density functional theory. The wave-function level is beyond-CCSD(T) for HCHO and CCSD(T)-F12a (Level-A) for XCHO (X = CH3, CF3), and the density functional (Level-B) is specifically validated for these reactions. Then, we calculate the pressure-dependent rate constants by using system-specific quantum RRK theory (SS-QRRK) and also by an energy-grained master equation. The two treatments of the pressure dependence agree well. We find that the Level-A//Level-B method gives good agreement with CCSDTQ(P)/CBS. We also find that anharmonicity is an important factor that increases the rate constants of all three reactions. We find that the HO2 + HCHO reaction has a significant dependence on pressure, but the HO2 + CF3CHO reaction is almost independent of pressure. Our findings show that the HO2 + HCHO reaction makes important contribution to the sink for HCHO, and the HO2 + CF3CHO reaction is the dominant sink for CF3CHO in the atmosphere.

Large Pressure Effects Caused by Internal Rotation in the s-cis-syn-Acrolein Stabilized Criegee Intermediate at Tropospheric Temperature and Pressure.

Criegee intermediates are important atmospheric oxidants, and quantitative kinetics for stabilized Criegee intermediates are key parameters for atmospheric modeling but are still limited. Here we report barriers and rate constants for unimolecular reactions of s-cis-syn-acrolein oxide (scsAO), in which the vinyl group makes it a prototype for Criegee intermediates produced in the ozonolysis of isoprene. We find that the MN15-L and M06-2X density functionals have CCSD(T)/CBS accuracy for the unimolecular cyclization and stereoisomerization of scsAO. We calculated high-pressure-limit rate constants by the dual-level strategy that combines (a) high-level wave function-based conventional transition-state theory (which includes coupled-cluster calculations with quasiperturbative inclusion of quadruple excitations because of the strongly multiconfigurational character of the electronic wave function) and (b) canonical variational transition-state theory with small-curvature tunneling based on a validated density functional. We calculated pressure-dependent rate constants both by system-specific quantum Rice-Ramsperger-Kassel theory and by solving the master equation. We report rate constants for unimolecular reactions of scsAO over the full range of atmospheric temperature and pressure. We found that the unimolecular reaction rates of this larger-than-previously studied Criegee intermediate depend significantly on pressure. Particularly, we found that falloff effects decrease the effective unimolecular cyclization rate constant of scsAO by about a factor of 3, but the unimolecular reaction is still the dominant atmospheric sink for scsAO at low altitudes. The large falloff caused by the inclusion of the stereoisomerization channel in the master equation calculations has broad implications for mechanistic analysis of reactions with competitive internal rotations that can produce stable rotamers.

Reaction of SO3 with HONO2 and Implications for Sulfur Partitioning in the Atmosphere.

Sulfur trioxide is a critical intermediate for the sulfur cycle and the formation of sulfuric acid in the atmosphere. The traditional view is that sulfur trioxide is removed by water vapor in the troposphere. However, the concentration of water vapor decreases significantly with increasing altitude, leading to longer atmospheric lifetimes of sulfur trioxide. Here, we utilize a dual-level strategy that combines transition state theory calculated at the W2X//DF-CCSD(T)-F12b/jun'-cc-pVDZ level, with variational transition state theory with small-curvature tunneling from direct dynamics calculations at the M08-HX/MG3S level. We also report the pressure-dependent rate constants calculated using the system-specific quantum Rice-Ramsperger-Kassel (SS-QRRK) theory. The present findings show that falloff effects in the SO3 + HONO2 reaction are pronounced below 1 bar. The SO3 + HONO2 reaction can be a potential removal reaction for SO3 in the stratosphere and for HONO2 in the troposphere, because the reaction can potentially compete well with the SO3 + 2H2O reaction between 25 and 35 km, as well as the OH + HONO2 reaction. The present findings also suggest an unexpected new product from the SO3 + HONO2 reaction, which, although very short-lived, would have broad implications for understanding the partitioning of sulfur in the stratosphere and the potential for the SO3 reaction with organic acids to generate organosulfates without the need for heterogeneous chemistry.

Forkhead Box S1 mediates epithelial-mesenchymal transition through the Wnt/ß-catenin signaling pathway to regulate colorectal cancer progression.

BACKGROUND: Recent studies have shown that the fox family plays a vital role in tumorigenesis and progression. Forkhead Box S1 (FOXS1), as a newly identified subfamily of the FOX family, is overexpressed in certain types of malignant tumors and closely associated with patient's prognosis. However, the role and mechanism of the FOXS1 in colorectal cancer (CRC) remain unclear. METHOD: FOXS1 level in CRC tissues and cell lines was analyzed by western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemistry (IHC) was used to detect the relationship between FOXS1 expression and clinicopathological features in 136 patients in our unit. The expression of FOXS1 was knocked down in CRC cells using small interfering RNA (siRNA) technology. Cell proliferation was assessed by CCK8 assay, colony formation, and 5-Ethynyl-20-deoxyuridine (EdU) incorporation assay. Flow cytometry detected apoptosis and wound healing, and Transwell assays determined cell migration and invasion. Western blotting was used to detect the levels of proteins associated with the Wnt/ß-catenin signaling pathway. Then, we used short hairpin RNA (shRNA) to knock down FOXS1 to see the effect of FOXS1 on the proliferation, migration, invasion, and metastasis of CRC cells in vivo. Finally, we investigated the impact of Wnt activator LiCl on the proliferation, migration, invasion, and metastasis of CRC cells after FOXS1 knockdown. RESULT: Compared to those in normal groups, FOXS1 overexpressed in CRC tissues and CRC cells (P < 0.05). Upregulation of FOXS1 association with poor prognosis of CRC patients. si-FOXS1 induced apoptosis and inhibited proliferation, migration, invasion, the epithelial-mesenchymal transition (EMT), and the Wnt/ß-catenin signaling pathway in vitro; sh-FOXS1 inhibited the volume and weight of subcutaneous xenografts and the number of lung metastases in vivo. LiCl, an activator of Wnt signaling, partially reversed the effect of FOXS1 overexpression on CRC cells. CONCLUSION: FOXS1 could function as an oncogene and promote CRC cell proliferation, migration, invasion and metastasis through the Wnt/ßcatenin signaling pathway, FOXS1 may be a potential target for CRC treatment.

Diagnostic value of circN4BP2L2 in type I and type II epithelial ovarian cancer.

BACKGROUND: CircN4BP2L2 was previously identified to be significantly decreased in epithelial ovarian cancer (EOC) and was associated with disease progression. The aim of this study was to evaluate the diagnostic value of plasma circN4BP2L2 using the unifying model of type I and type II EOC. METHODS: A total of 540 plasma samples were obtained from 180 EOC patients, 180 benign ovarian cyst patients, and 180 healthy volunteers. CircN4BP2L2 was assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) were assessed using enzyme-linked immunosorbent assay (ELISA). Receiver operating curve (ROC), the area under the curve (AUC), sensitivity and specificity were estimated. RESULTS: Low level of circN4BP2L2 was associated with advanced tumor stage (p < 0.01) in type I EOC. Decreased circN4BP2L2 was associated with lymph node metastasis (LNM) (p = 0.04) in type II EOC. The expression level of circN4BP2L2 in type I was similar to that in type II. CircN4BP2L2 could significantly separate type I or type II from benign or normal cohort (p < 0.01). Early-stage type I or type II EOC vs. benign or normal cohort could also be distinguished by circN4BP2L2 (p < 0.01). CONCLUSION: CircN4BP2L2 might serve as a promising diagnostic biomarker for both type I and type II EOC. The diagnostic safety for circN4BP2L2 in early-stage type I or type II EOC is also acceptable. Further large-scale well-designed studies are warranted to investigate whether circN4BP2L2 is specific for all histologic subgroups.

Peroxy Radical Autoxidation and Sequential Oxidation in Organic Nitrate Formation during Limonene Nighttime Oxidation.

Limonene is an abundant monoterpene released into the atmosphere via biogenic emissions and biomass burning. However, the atmospheric oxidation and secondary organic aerosol (SOA) formation mechanisms of limonene, especially during nighttime, remain largely understudied. In this work, limonene was oxidized synergistically by ozone (O3) and nitrate radicals (NO3) in a flow tube reactor and a continuous flow stirred tank reactor. Upon oxidation, many highly oxidized organic nitrates and nitrooxy peroxy radicals (RO2) were observed in the gas phase within 1 min. Combining quantum chemical calculations with kinetic simulations, we found that the primary nitrooxy RO2 (C10H16NO5) through NO3 addition at the more substituted endocyclic double bond and at the exocyclic double bond (previously considered as minor pathways) can undergo autoxidation with rate constants of around 0.02 and 20 s-1 at 298 K, respectively. These pathways could explain a major portion of the observed highly oxidized organic nitrates. In the SOA, highly oxidized mono- and dinitrates (e.g., C10H17NO7-8 and C10H16,18N2O8-10) make up a significant contribution, highlighting nitrooxy RO2 autoxidation and sequential NO3 oxidation of limonene. The same organic nitrates are also observed in ambient aerosol during biomass burning and nighttime in the southeastern United States. Therefore, the present work provides new insights into the nighttime oxidation of limonene and SOA formation in the atmosphere.

Quantitative kinetics for the atmospheric reactions of Criegee intermediates with acetonitrile.

Obtaining quantitative kinetics of Criegee intermediates is of paramount significance in the atmosphere. However, there are limited reports on the kinetics of Criegee intermediates. Here, by using our very recently developed dual-level strategy, we report the quantitative kinetics of the reaction of Criegee intermediates (CH2OO/anti-CH3CHOO/syn-CH3CHOO) with acetonitrile (CH3CN). The dual-level strategy combines post-CCSD(T) calculations for transition state theory with the validated M06CR/MG3S and M11-L/MG3S functional methods for direct dynamics calculations using canonical variational transition state theory with small-curvature tunneling to obtain recrossing effects and tunneling coefficients. We show that W3X-L//DF-CCSD(T)-F12b/jun-cc-pVDZ can be used to obtain quantitative enthalpies of activation at 0 K in the reactions of Criegee intermediates with CH3CN. We find that the CH2OO/anti-CH3CHOO/syn-CH3CHOO + CH3CN reactions only depend on temperature. Moreover, we also find that their rate constants are dominantly determined by the enthalpy of activation at 0 K and recrossing effects and tunneling are negligible. The present findings also show that the CH2OO/anti-CH3CHOO + CH3CN reactions have negative temperature dependence in the range of 190-350 K. In the atmosphere, we reveal that the reactions of CH2OO and anti-CH3CHOO with CH3CN are significant acetonitrile sinks, leading to the formation of N-formylacetamide and diacetamide. The present findings will be useful for obtaining quantitative kinetics of Criegee intermediates and understanding acetonitrile sinks.

Temperature-dependent kinetics of the atmospheric reaction between CH2OO and acetone.

Criegee intermediates are important oxidants produced in the ozonolysis of alkenes in the atmosphere. Quantitative kinetics of the reactions of Criegee intermediates are required for atmospheric modeling. However, the experimental studies do not cover the full relevant range of temperature and pressure. Here we report the quantitative kinetics of CH2OO + CH3C(O)CH3 by using our recently developed dual strategy that combines coupled cluster theory with high excitation levels for conventional transition state theory and well validated levels of density functional theory for direct dynamics calculations using canonical variational transition theory including tunneling. We find that the W3X-L//DF-CCSD(T)-F12b/jun-cc-pVDZ electronic structure method can be used to obtain quantitative kinetics of the CH2OO + CH3C(O)CH3 reaction. Whereas previous investigations considered a one-step mechanistic pathway, we find that the CH2OO + CH3C(O)CH3 reaction occurs in a stepwise manner. This has implications for the modeling of Criegee-intermediate reactions with other ketones and with aldehydes. In the kinetics calculations, we show that recrossing effects of the conventional transition state are negligible for determining the rate constant of CH2OO + CH3C(O)CH3. The present findings reveal that the rate ratio between CH2OO + CH3C(O)CH3 and OH + CH3C(O)CH3 has a significant negative dependence on temperature such that the CH2OO + CH3C(O)CH3 reaction can contribute as a significant sink for atmospheric CH3C(O)CH3 at low temperature. The present findings should have broad implications in understanding the reactions of Criegee intermediates with carbonyl compounds and ketones in the atmosphere.

Vacuum ultraviolet photochemistry of sulfuric acid vapor: a combined experimental and theoretical study.

We present a vacuum ultraviolet (VUV) photoionization study of the gas-phase sulfuric acid (H2SO4) molecule in the 11-14 eV energy range by using the method of synchrotron radiation-based double imaging photoelectron photoion coincidence (i2PEPICO) spectroscopy complemented with accurate theoretical calculations. The slow photoelectron spectrum (SPES) of H2SO4 has been acquired and the three electronic states of H2SO4+, X2A, A2A and B2A have been populated and assigned. The adiabatic ionization energy of the H2SO4 molecule towards the X2A cationic ground state is measured at 11.684 ± 0.006 eV, in accordance with high-level calculated findings. With increasing photon energies, the H2SO4+ cation dissociates into HSO3+ and OH fragments and their adiabatic appearance energy is measured at 13.498 ± 0.007 eV. Then, the enthalpies of formation for the species involved in the photoionization and dissociative photoionization have been determined through a thermochemical cycle.