An allosteric mechanism for potent inhibition of SARS-CoV-2 main proteinase.

The main proteinase (Mpro) of SARS-CoV-2 plays a critical role in cleaving viral polyproteins into functional proteins required for viral replication and assembly, making it a prime drug target for COVID-19. It is well known that noncompetitive inhibition offers potential therapeutic options for treating COVID-19, which can effectively reduce the likelihood of cross-reactivity with other proteins and increase the selectivity of the drug. Therefore, the discovery of allosteric sites of Mpro has both scientific and practical significance. In this study, we explored the binding characteristics and inhibiting process of Mpro activity by two recently reported allosteric inhibitors, pelitinib and AT7519 which were obtained by the X-ray screening experiments, to probe the allosteric mechanism via molecular dynamic (MD) simulations. We found that pelitinib and AT7519 can stably bind to Mpro far from the active site. The binding affinity is estimated to be -24.37 ± 4.14 and - 26.96 ± 4.05 kcal/mol for pelitinib and AT7519, respectively, which is considerably stable compared with orthosteric drugs. Furthermore, the strong binding caused clear changes in the catalytic site of Mpro, thus decreasing the substrate accessibility. The community network analysis also validated that pelitinib and AT7519 strengthened intra- and inter-domain communication of Mpro dimer, resulting in a rigid Mpro, which could negatively impact substrate binding. In summary, our findings provide the detailed working mechanism for the two experimentally observed allosteric sites of Mpro. These allosteric sites greatly enhance the 'druggability' of Mpro and represent attractive targets for the development of new Mpro inhibitors.

The influence of a single water molecule on the reaction of BrO + HO2.

The influence of a single water molecule on the BrO + HO2 hydrogen extraction reaction has been explored by taking advantage of CCSD(T)/aug-cc-pVTZ//B3LYP/6-311 + + G(d,p) method. The reaction in the absence of water have two distinct kinds of H-extraction channels to generate HOBr + O2 (1Δg) and HBr + O3, and the channel of generation of HOBr + O2 (1Δg) dominated the BrO + HO2 reaction. The rate coefficient of the most feasible channel for the BrO + HO2 reaction in the absence of water is estimated to be 1.44 × 10-11 cm3 molecule-1 s-1 at 298.15 K, which is consistent with the experiment. The introduction of water made the reaction more complex, but the products are unchanged. Four distinct channels, beginning with HO2…H2O with BrO, H2O…HO2 with BrO, BrO…H2O with HO2, H2O…BrO with HO2 are researched. The most feasible channels, stemming from H2O…HO2 with BrO, and BrO…H2O with HO2, are much slower than the reaction of BrO + HO2 without water, respectively. Thus, the existence of water molecule takes a negative catalytic role for BrO + HO2 reaction.

A theoretical study of the gas-phase reactions of propadiene with NO3: mechanism, kinetics and insights.

In this study, the conversion mechanisms and kinetics of propadiene (CH2[double bond, length as m-dash]C[double bond, length as m-dash]CH2) induced by NO3 were researched using density functional theory (DFT) and transition state theory (TST) measurements. The NO3-addition pathways to generate IM1 (CH2ONO2CCH2) and IM2 (CH2CONO2CH2) play a significant role. P3 (CH2CONOCHO + H) was the dominant addition/elimination product. Moreover, the results manifested that one H atom from the -CH2- group has to be abstracted by NO3 radicals, leading to the final product h-P1 (CH2CCH + HNO3). Due to the high barrier, the H-abstraction pathway is not important for the propadiene + NO3 reaction. In addition, the computed ktot value of propadiene reacting with NO3 at 298 K is 3.34 × 10-15 cm3 per molecule per s, which is in accordance with the experimental value. The computed lifetime of propadiene oxidized by NO3 radicals was assessed to be 130.16-6.08 days at 200-298 K and an altitude of 0-12 km. This study provides insights into the transformation of propadiene in a complex environment.

Understanding the insight into the mechanisms and dynamics of the OH-initiated oxidation of CHF2CF2OCHF2 and the subsequent reactions in the presence of NO and O2.

The mechanism and dynamics of CHF2CF2OCHF2 initiated by OH radical evaluated through the density functional theory and variflex code. The solvation pattern of PCM was utilized to analyze the influence of water on the CHF2CF2OCHF2 + OH reaction. The most feasible reaction channel is resulting in the product CF2CF2OCHF2 with H2O by hydrogen abstraction. The computed rate coefficient is consistent with the experimental data. The results turned out that aqueous water act as a disincentive to the title reaction. In the atmosphere, the computation results testified that OH, H2O, NH3 and HCOOH could not accelerate the degradation of the CHF2CF2OCHF2 through OH-initiated in view of the Gibbs free barriers. The research of the follow-up oxidation procedure of the products CHF2CF2OCF2 and CF2CF2OCHF2 with O2/NO reactions indicated that CF2O and CHF2 were the most feasible products. The atmospheric lifetimes of CHF2CF2OCHF2 were in the scope of 71.10-4.74 years in altitude of 0-12 km and at 200-300 K. This research supplies discernment into the conversion of CHF2CF2OCHF2 in a complex environment.

Crystal Structure, Photophysical Study, Hirshfeld Surface Analysis, and Nonlinear Optical Properties of a New Hydroxyphenylamino Meldrum's Acid Derivative.

The structural, photophysical, and vibrational properties of a new hydroxyphenylamino Meldrum's acid derivative, 3-((2-hydroxyphenylamino)methylene)-1,5-dioxaspiro[5.5]undecane-2,4-dione (HMD), were studied. The comparison of experimental and theoretical vibrational spectra can help understand basic vibration patterns and provides a better interpretation of IR spectra. The UV-Vis spectrum of HMD was computed using density functional theory (DFT)/B3LYP/6-311 G(d,p) basis set in the gas state, and the maximum wavelength was in accord with the experimental data. The molecular electrostatic potential (MEP) and Hirshfeld surface analysis confirmed O(1)-H(1A)···O(2) intermolecular hydrogen bonds in the HMD molecule. The natural bond orbital (NBO) analysis provided delocalizing interactions between π→π* orbitals and n→σ*/π* charge transfer transitions. Finally, the thermal gravimetric (TG)/differential scanning calorimeter (DSC) and the non-linear optical (NLO) properties of HMD were also reported.

Degradation of mevinphos and monocrotophos by OH radicals in the environment: A computational investigation on mechanism, kinetic, and ecotoxicity.

Known organophosphorus pesticides are used widely in agriculture to improve the production of crops. Based on the literature, the degradation of some organophosphorus pesticides was studied theoretically. However, the mechanisms and variation of toxicity during the degradation of mevinphos and monocrotophos are still unclear in the environment, especially in wastewater. In this study, the reaction mechanisms for the degradation of the two representative organophosphorus pesticides (i.e., mevinphos and monocrotophos) in presence of OH radicals in the atmosphere and water are proposed using quantum chemical methods wB97-XD/6-311 + +G(3df,2pd)//wB97-XD/6-311 + +G(d,p). Result shows that the dominant channel is OH-addition to the C atom in CC bond with energy barriers being 15.6 and 14.7 kJ/mol, in the atmosphere and water, respectively, for mevinphos. As for monocrotophos, H-abstraction from NH group via barriers of 8.2 and 10.6 kJ/mol is more feasible in both the atmosphere and water. Moreover, the subsequent reactions of the major products in the atmosphere with NO and O2 were also studied to evaluate the atmospheric chemistry of mevinphos and monocrotophos. Kinetically, the total rate constant is 2.68 × 10-9 and 3.86 × 10-8 cm3 molecule-1·s-1 for mevinphos and monocrotophos in the atmosphere and 4.91 × 1010 and 7.77 × 1011 M-1 s-1 in the water at 298 K, thus the lifetime is estimated to be 36.46-364.60 s (2.53-25.31 s) in the atmosphere, and 1.41 × 10-2 - 1.41 × 10-1 s (8.92 ×10-4 - 8.92 ×10-3 s) in the advanced oxidation processes (AOPs) system. Furthermore, ecotoxic predictions for rats and three aqueous organisms imply their toxicity are reduced during degradation by using ECOSAR and T.E.S.T program based quantitative structure and activity relationship (QSAR) method.

OH-initiated degradation of 1,2,3-trimethylbenzene in the atmosphere and wastewater: Mechanisms, kinetics, and ecotoxicity.

1,2,3-Trimethylbenzene (1,2,3-TMB) is an important volatile organic compound (VOC) present in petroleum wastewater and the atmosphere. This compound can be degraded by OH radicals via abstraction, addition and substitution mechanisms. Results show that the addition mechanism is dominant and H-abstraction is subdominant, while methyl abstraction and substitution mechanisms are negligible in the gas and aqueous phases. Moreover, H-abstraction products undergo further reactions with O2, NO, NO2, H2O, and OH radicals in the atmosphere. Time-dependent density functional theory (TDDFT) calculations show that the degraded products, including 2,3,4-trimethylphenyl-nitroperoxoite, 1,2,3-trimethyl-4-nitrobenzene, 1,2,3-trimethyl-5-nitrobenzene, 2,6-dimethylbenzyl nitroperoxoite, 2,3-dimethylphenyl nitroperoxoite, 2,6-dimethylbenzaldehyde, and 2,3-dimethylbenzaldehyde, can photolyze under the sunlight. Kinetically, the calculated total rate constant is 5.57 × 10-11 cm3 molecule-1·s-1 at 1 atm and 298 K, which is consistent with available experimental values measured in the atmosphere. In addition, the calculated total reaction rate constant in water is close to that in the gas phase. In terms of ecotoxicity, all degradation products are less toxic than the initial reactant to fish, green algae and daphnia. For mammals represented by rats, 1,2,3-TMB and its products are moderately toxic, except for 2,3-dimethylphenol and 2,6-dimethylphenol, which are slightly toxic.

The influence of (H2O)1-2 in the HOBr + HO2 gas-phase reaction.

The HOBr + HO2 reaction in the absence of water has three different channels for the abstraction of H to generate the corresponding products. The dominant channel is the generation of BrO + H2O2. The introduction of water molecules influences this dominant reaction via the way the reactants interact with the water molecules. The addition of water molecules decreases the energy barrier and increases the rate coefficient of the reaction. Interestingly, water works as a catalyst and we obtain BrO + H2O2, like in the reaction without water, or the water works as a reactant and we obtain products other than BrO + H2O2. The rate coefficients of the HOBr + HO2 reaction in the presence of water are calculated to be faster than the reaction in the absence of water. However, other pathways in the presence of water are slower than the reaction in the absence of water. The water-assisted effective rate coefficients for the HOBr + HO2 reaction are also larger than those for the reaction in the absence of water. The influence of a water dimer is not as important when compared with one water molecule. In summary, a single water molecule has a positive catalytic influence in enhancing the HOBr + HO2 reaction.

Role of monomolecular water and bimolecular water in IO + CH2O reaction.

A CCSD(T)//B3LYP method was employed to research the influence of monomolecular and bimolecular water molecules on the IO + CH2O reaction. H-abstraction and addition/elimination mechanisms have been located, and the H-abstraction mechanism occupied the whole reaction without water. The introduction of water complicates the reaction, but the final product remains unchanged. Water molecules influence each reaction pathway in six different pathways with monomolecular water and two different pathways with bimolecular water, respectively. The present calculations manifested that water has a positive influence on the IO + CH2O reaction with monomolecular water molecule, and plays negative catalytic influence on the IO + CH2O reaction with bimolecular water molecule. The effective rate constants are much lower than the IO + CH2O reaction without water.

Synthesis, Crystal Structures, and Density Functional Theory Studies of Two Salt Cocrystals Containing Meldrum's Acid Group.

Two salt cocrystals, C31H34N4O8 (DDD) and C17H20N2O8 (MDD), were synthesized and their structures were determined by single-crystal X-ray diffraction. DDD is made up of one (C13H13O8)- anion, one (C9H11N2)+ cation, and one 5,6-dimethyl-1H-benzo[d]imidazole molecule. MDD consists of one (C4H7N2)+ cation and one (C13H13O8)- anion. DDD and MDD belong to the monoclinic, P21/c space group and triclinic, P-1 space group, respectively. A 1D-chained structure of DDD was constituted by N-H···N and N-H···O hydrogen bonds. However, a 1D-chained structure of MDD was bridged by N-H···O hydrogen bonds. Their density functional theory-optimized geometric structures with a B3LYP/6-311G(d,p) basis set fit well with those of crystallographic studies. By calculating their thermodynamic properties, the correlation equations of C 0 p,m , S 0 m , H 0 m , and temperature T were obtained. By comparing the experimental electronic spectra with the calculated electronic spectra, it is found that the PBEPBE/6-311G(d,p) method can simulate the UV-Vis spectra of DDD and MDD. In addition, the fluorescence spectra in the EtOH solution analysis show that the yellowish-green emission occurs at 570 nm (λex = 310 nm) for DDD and the purplish-blue emission occurs at 454 nm (λex = 316 nm) for MDD.

The influence of a single water molecule on the reaction of BrO + HONO.

Quantum chemical computations and transition state theory are employed to systematically research the influence of a single molecule water on the BrO + HONO reaction. Two distinct reactions, namely BrO + trans-HONO and BrO + cis-HONO are explored for the reaction in the absence of water, which is mainly decided by the configuration of HONO. With introduction a single water molecule to the reaction, the rate coefficient of the channel starting from BrO + cis-HONO and BrO + trans-HONO are 2.43 × 10-19 and 5.22 × 10-22 cm3 molecule-1 s-1, which is larger than the reaction in the absence of water. For further comprehend the impact of water on the BrO + HONO reaction, it is necessary to compute the effective rate coefficient by taking into account the concentration of water. The water-assisted effective rate coefficients for the BrO + HONO reaction are smaller than that the reaction in the absence of water. The reaction of BrO with cis-HONO is feasible both in absence and existence of water.

Investigations on mechanisms, kinetics, and ecotoxicity in OH-initiated degradation of 1,2,4,5-tetramethylbenzene in the environment.

As one of the volatile organic compounds (VOCs) in the environment, 1,2,4,5-tetramethylbenzene (1,2,4,5-TeMB) present in oily wastewater, and it can occur substitution, abstraction, and addition reactions with OH radicals in the atmosphere and wastewater. Electrostatic potential (ESP) and average local ionization energy (ALIE) prediction indicate that H atoms from CH3 group and the benzene ring are the most active sites in 1,2,4,5-TeMB. The result shows that potential energy surfaces (PESs) in the gas and aqueous phase are similar, and the relevant barriers in the latter one are higher. The dominant channel is H abstraction from the benzene ring, and the subdominant one is OH radical addition to the benzene ring. Furthermore, subsequent reactions of dominant products with O2, NO2, NO, and OH radicals in the atmosphere are studied, as well. The total reaction rate constant is calculated to be 2.36×10-10 cm3 molecule-1 s-1 at 1 atm and 298 K in the atmosphere, which agrees well with the experimental data. While the total rate constant in the aqueous phase is much lower than that in the gas phase. Ecologic toxicity analysis shows that 1,2,4,5-TeMB is very toxic to fish, daphnia, and green algae; and OH-initiated degradation in the environment will reduce its toxicity.

Structural and energetic features of the dimerization of the main proteinase of SARS-CoV-2 using molecular dynamic simulations.

The COVID-19 pandemic caused by SARS-CoV-2 has been declared a global health crisis. The development of anti-SARS-CoV-2 drugs heavily depends on the systematic study of the critical biological processes of key proteins of coronavirus among which the main proteinase (Mpro) dimerization is a key step for virus maturation. Because inhibiting the Mpro dimerization can efficiently suppress virus maturation, the key residues that mediate dimerization can be treated as targets of drug and antibody developments. In this work, the structure and energy features of the Mpro dimer of SARS-CoV-2 and SARS-CoV were studied using molecular dynamics (MD) simulations. The free energy calculations using the Generalized Born (GB) model showed that the dimerization free energy of the SARS-CoV-2 Mpro dimer (-107.5 ± 10.89 kcal mol-1) is larger than that of the SARS-CoV Mpro dimer (-92.83 ± 9.81 kcal mol-1), indicating a more stable and possibly a quicker formation of the Mpro dimer of SARS-CoV-2. In addition, the energy decomposition of each residue revealed 11 key attractive residues. Furthermore, Thr285Ala weakens the steric hindrance between the two protomers of SARS-CoV-2 that can form more intimate interactions. It is interesting to find 11 repulsive residues which effectively inhibit the dimerization process. At the interface of the Mpro dimer, we detected three regions that are rich in interfacial water which stabilize the SARS-CoV-2 Mpro dimer by forming hydrogen bonds with two protomers. The key residues and rich water regions provide important targets for the future design of anti-SARS-CoV-2 drugs through inhibiting Mpro dimerization.

New theoretical investigation of mechanism, kinetics, and toxicity in the degradation of dimetridazole and ornidazole by hydroxyl radicals in aqueous phase.

Dimetridazole (DMZ) and ornidazole (ONZ) have been widely used to treat anaerobic and protozoal infections. The residues of DMZ/ONZ persist in the water environment. The mechanisms and kinetics of hydroxyl-initiated oxidation, the primary DMZ/ONZ degradation method, were evaluated by quantum chemical methods.·OH-induced degradation of DMZ and ONZ shared many mechanistic and kinetic characteristics. The most feasible degradation pathway involved forming OH-imidazole adducts and NO2. The OH-imidazole adducts were subsequently degraded into double·OH imidazole intermediates. The rate coefficients for·OH degradation of DMZ and ONZ were 4.32 × 109 M-1 s-1 and 4.42 × 109 M-1 s-1 at 298 K, respectively. The lifetimes of DMZ and ONZ treated with·OH at concentrations of 10-9-10-18 mol L-1 at 298 K were τDMZ = 0.231-2.31 × 108 s and τONZ = 0.226-2.26 × 108 s, respectively. Toxicity assessment showed that the first degradation products of DMZ and ONZ exhibited enhanced aquatic toxicity, whereas most of the secondary degradation products were not harmful to aquatic organisms. Some of transformation products were still developmental toxicant or mutagenicity positive.

A theoretical investigation on the degradation reactions of CH3CH2CH2NH and (CH3CH2CH2)2N radicals in the presence of NO, NO2 and O2.

The degradation reactions of propylamino and dipropylamino radicals in the presence of NO, NO2 and O2 were investigated at the CCSD(T)/6-311++G (2d, 2p)//B3LYP/6-311++G (d,p) levels of theory. Result indicates that nitrosamines, nitramines, nitroso-oxy compounds and imines can be formed at atmosphere. Time dependent density functional theory (TDDFT) calculation shows that nitrosamines and nitroso-oxy compounds can photolyze under sunlight, while nitramines cannot undergo photolysis in the daytime. Moreover, the ecotoxicity assessment result implies that the degradation of propyl-substituted amines by OH radicals, NO and NO2 will reduce their toxicity to fish, daphnia and green algae in the aquatic environment.

Theoretical investigations on mechanisms and kinetics of methylketene with O(3P) reaction in the atmosphere.

The O(3P)-initiated conversion mechanism and dynamics of CH3CHCO were researched in atmosphere by executing density functional theory (DFT) computations. Optimizations of all the species and single-point energy computations were implemented at the B3LYP/6-311++G(d,p) and CCSD(T)/cc-pVTZ level, respectively. The explicit oxidation mechanism was introduced and discussed. The results state clearly that the O(3P) association was more energetically beneficial than the abstraction of H. The rate coefficients over the probable temperature range of 200-3000 K were forecasted by implementing Rice-Ramsperger-Kassel-Marcus (RRKM) theory. Specifically, the total rate coefficient of O(3P) association reactions is 1.19 × 10-11 cm3 molecule-1 s-1 at 298 K, which is consistent with the experimental results (1.16 × 10-11 cm3 molecule-1 s-1). The rate coefficients for the O(3P) with CH2CO, CH3CHCO, and (CH3)2CCO suggest that rate coefficient of ketene derivatives increase with the increase of methylation degree. Graphical abstract.

Key residues of the receptor binding domain in the spike protein of SARS-CoV-2 mediating the interactions with ACE2: a molecular dynamics study.

The widespread coronavirus disease 2019 (COVID-19) has been declared a global health emergency. As one of the most important targets for antibody and drug developments, the Spike RBD-ACE2 interface has received extensive attention. Here, using molecular dynamics simulations, we explicitly analyzed the energetic features of the RBD-ACE2 complex of both SARS-CoV and SARS-CoV-2. Despite the high structural similarity, the binding strength of SARS-CoV-2 to the ACE2 receptor is estimated to be -16.35 kcal mol-1 stronger than that of SARS-CoV. Energy decomposition analyses identified three binding patches in SARS-CoV-2 RBD and eleven key residues (F486, Y505, N501, Y489, Q493, L455, etc.), which are believed to be the main targets for drug development. The dominating forces arise from van der Waals attractions and dehydration of these residues. Compared with SARS-CoV, we found seven mutational sites (K417, L455, A475, G476, E484, Q498 and V503) on SARS-CoV-2 that unexpectedly weakened the RBD-ACE2 binding. Interestingly, the E484 site is recognized to be the most repulsive residue at the RBD-ACE2 interface, indicating that from the energy point of view, a mutation of E484 would be beneficial to RBD-ACE2 binding. This is in line with recent findings that it is mutated by lysine (E484K mutation) in the rapidly spreading variants of COVID-19 belonging to the B.1.351 and P.1 lineages. In addition, this mutation is reported to cause virus neutralization escapes from highly neutralizing COVID-19 convalescent plasma. Thus, further efforts are required to probe its functional relevance. Overall, our results present a systematic understanding of the energetic binding features of SARS-CoV-2 RBD with the ACE2 receptor, which can provide a valuable insight for the design of SARS-CoV-2 drugs and identification of cross-active antibodies.

A novel label-free solid-state electrochemiluminescence sensor based on the resonance energy transfer from Ru(bpy)32+ to GO for DNA hybridization detection.

Based on electrochemiluminescence resonance energy transfer (ERET) from Ru(bpy)32+ to graphene oxide (GO), a novel label-free solid-state ECL sensor for sensitive detection of DNA was proposed. First, Ru(bpy)32+/AuNPs was successfully prepared by using a simple and green method and characterized by transmission electron microscopy (TEM), Energy Dispersive X-ray (EDX), and UV-vis spectroscopy. Then, the Ru(bpy)32+/AuNPs colloid was assembled on the gold electrode surface for solid-state ECL film which also later could be used to immobilize thiol-derivatized, single-stranded DNA (HS-ssDNA) via Au-S interactions. The stepwise modification procedure was characterized by cyclic voltammetry(CV), electrochemical impedance spectroscopy (EIS), probe approach curves (PAC) and ECL, respectively. The resulting modified electrode was tested as ECL biosensor for DNA detection. Upon addition of GO, the strong noncovalent interaction between HS-ssDNA and GO led to ECL quenching because of ERET. When in the presence of target ssDNA (t-ssDNA), the distance between the HS-ssDNA and GO increased, which significantly hindered the ERET and, thus, resulted in the restoration of ECL. The ECL intensity of the biosensor increased linearly with t-ssDNA concentration in the range of 50-1000pM, and the detection limit is 20pM. To the best of our knowledge, this is the first application of solid-state ERET from Ru(bpy)32+ to GO and opens new opportunities for sensitive detection of biorecognition events.

Theoretical investigations on mechanisms and kinetics of the CH3CFClO2· with ClO· reaction in the atmosphere.

The singlet and triplet potential energy surfaces of the ClO• radical reaction with the CH3CFClO2• radical have been investigated at the CCSD(T)/cc-pVTZ level based on the optimized geometries at the B3LYP/6-311++G(d,p) level. On the singlet potential energy surfaces (PES), the possible reaction involves association-dissociation, direct H-abstraction and Nucleophilic Substitution 2 (SN2) mechanisms. On the triplet PES, SN2 displacement and direct H-abstraction reaction pathways have been investigated, which are less competitive compared with the reaction pathways on the singlet PES. The rate constants have been calculated at 10-10 to 1010 atm and 200-3,000 K by Rice-Ramsperger-Kassel-Marcus (RRKM) theory for the important product pathways. At 200-800 K, IM1 produced (CH3CFClOOOCl) by collisonal deactivation is dominant; at high temperatures, the production P1 (CH3CFO + ClOOCl) becomes dominate. The calculated rate constants for CH3CFClO2• + ClO• are good agreement with the available experimental value. The atmospheric lifetime of CH3CFClO2• in ClO• is around 3.27 h. TD-DFT computations imply that IM1 (CH3CFClOOOCl), IM2 (CH3CFClOOClO) and IM3 (CH3CFClOClO2) will photolyze under the sunlight.

Atmospheric chemistry of CFCl2O2: a theoretical study on mechanisms and kinetics of the CFCl2O2 + ClO reaction.

The gas-phase reaction between CFCl2O2 and ClO was researched by means of quantum chemical methods. B3LYP method with the 6-311++G(d,p) basis set was used to obtain the geometric parameters of all stationary points including in the CFCl2O2 + ClO reaction. The singlet and triplet potential energy surfaces were characterized at the CCSD(T)/6-311++G(2d,2p)//B3LYP/6-311++G(d,p) level. Addition/elimination and SN2 displacement reaction mechanisms were identified on the singlet PES, and only substituent reaction mechanism was located on the triplet PES. The dominant reaction takes place on the singlet PES, and the major pathways are CFCl2O2 + ClO → IM1 (CFCl2OOOCl) → IM2 (CFCl2OOClO) → IM3 (CH3OClO2) → P6 (CFClO + (ClO)2). RRKM theory was used to calculate rate constants, which is consistent with the experimental data. The atmospheric lifetime of CFCl2O2 in ClO is around 8.84 h. TD-DFT computations imply that IM1 (CFCl2OOOCl), IM2 (CFCl2OOClO), and IM3 (CFCl2OClO2) will photolyze under the sunlight. Graphical abstract.