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Polycyclic aromatic hydrocarbons (PAHs) are major environmental organic pollutants. Some metabolites of PAHs show greater toxicity to humans while the others do not. It is highly important to decipher PAHs' regioselective activation mechanism and identify the major metabolites to accurately evaluate their public health risk. Here, we have performed a thorough computational study of benzo[a]anthracene (BA) metabolized by P450 1A1 by employing molecular docking, molecular dynamics simulations, quantum chemical calculation, and quantum mechanics/molecular mechanics calculations. Our findings show that highly-reactive species such as 3,4-epoxide, 8,9-epoxide, 3,4-diol-1,2-epoxide, and 8,9-diol-10,11-epoxide were major metabolites, which can efficiently react with guanine and damage DNA with extremely low energy barrier, therefore, supports the regioselective metabolism of BA. The origin of this selective activation is mainly contributed to both the oxygen‑carbon distance and previously overlooked enzyme's intrinsic electric field. Consequently, based on the resolved activation selectivity of BA. We built a high-throughput strategy to efficiently predict the metabolites of other PAHs. The accuracy of the strategy is validated by studying 16 PAHs on the priority control list. Hopefully this will aid the accurate evaluation of public health risks associated with PAH emissions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Recently there are increasing interests in accurately evaluating the health effects of heterocyclic PAHs. However, the activation mechanism and possible metabolites of heterocyclic PAHs catalyzed by human CYP1A1 is still elusive to a great extent. Here, leveraged to high level QM/MM calculations, the corresponding activation pathways of a representative heterocyclic PAHs, carbazole, were systematically explored. The first stage is electrophilic addition or hydrogen abstraction from N-H group. Electrophilic addition was evidenced to be more feasible and regioselectivity at C3 and C4 sites were identified. Correlations between energy barriers and key structural/electrostatic parameters reveal that O-Cα distance and Fe-O-Cα angle are the main origin for the catalytic regioselectivity. Electrophilic addition was determined as the rate-determining step and the subsequent possible reactions include epoxidation, NIH shift (the hydrogen migration from the site of hydroxylation to the adjacent carbon) and proton shuttle. The corresponding products are epoxides, ketones and hydroxylated carbazoles, respectively. The main metabolites (hydroxylated carbazoles) are estimated to be more toxic than carbazole. The regioselectivity of carbazole activated by CYP1A1 is different from the environmental processes (gas and aqueous phase). Collectively, these results will inform the in-depth understanding the metabolic processes of heterocyclic PAHs and aid the accurate evaluation of their health effects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Polycyclic Aromatic Hydrocarbon (PAHs) presents one of the most abundant class of environmental pollutants. Recent study shows a lab-synthesized PAHs derivative, helicenium, can selectively kill cancer cells rather than normal cells, calling for the in-depth understanding of the metabolic process. However, the origin of metabolites diversity and selectivity of P450 catalyzed PAHs metabolic activation is still unclear to a great extent. Here we systematically investigated P450 enzymes catalyzed activation mechanism of a representative PAHs, benzo[a]pyrene (BaP), and found the corresponding activation process mainly involves two elementary steps: electrophilic addition and epoxidation. Electrophilic addition step is evidenced to be rate determining step. Two representative binding modes of BaP with P450 were found, which enables the electrophilic addition of Heme (FeO) to almost all the carbons of BaP. This electrophilic addition was proposed to be accelerated by the P450 enzyme environment when compared with the gas phase and water solvent. To dig deeper on the origin of metabolites diversity, we built several linear regression models to explore the structural-energy relationships. The selectivity was eventually attributed to the integrated effects of structural (e.g. O-C distance and O-C-Fe angle) and electrostatic parameters (e.g. charge of C and O) from both BaP and P450., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Benzofuran (BF), benzothiophene (BT), indole (IN), dibenzofuran (DBF), dibenzothiophene (DBT), and carbazole (CA) are typical heterocyclic aromatic compounds (NSO-HETs), which can coexist with polycyclic aromatic hydrocarbons (PAHs) in combustion and pyrolysis conditions. In this work, quantum chemical calculations were carried out to investigate the formation of DBF, DBT, and CA from the reactions of BF, BT, and IN with a cyclopentadienyl radical (CPDyl) by using the hybrid density functional theory (DFT) at the MPWB1K/6-311+G(3df,2p)//MPWB1K/6-31+G(d,p) level. The rate constants of crucial elementary steps were deduced over 600-1200 K, using canonical variational transition state theory with a small-curvature tunneling contribution (CVT/SCT). This paper showed that the production of DBF, DBT, and CA from the reactions of BF, BT, and IN with CPDyl involved six elementary steps: the addition reaction, ring closure, the first H shift, C-C cleavage, the second H shift, and elimination of CH 3 or H. The cleavage of the C-C bond was regarded as the rate-determining step for each pathway due to the extremely high barrier. The 1-methyl substituted products were more easily formed than the 4-methyl substituted products. The main products were DBF and 1-methyl-DBF, DBT and 1-methyl-DBT, and CA and 1-methyl-CA for reactions of BF, BT, and IN with CPDyl, respectively. The ranking of DBF, DBT, and CA formation potential was as follows: DBT and methyl-DBT formation > DBF and methyl-DBF formation > CA, and methyl-CA formation. Comparison with the reaction of naphthalene with CPDyl indicated that the reactions of CPDyl attacking a benzene ring and a furan/thiophene/pyrrole ring could be inferred to be comparable under high temperature conditions.

Polycyclic aromatic hydrocarbons (PAHs) are highly toxic, mutagenic and/or carcinogenic to humans. To reduce the emission of PAHs, it's significant and indispensable to explore the PAH formation mechanism. In the present work, the growth mechanism of PAHs from the reactions of anthracene and phenanthrene with cyclopentadienyl and indenyl radicals was investigated with the aid of high-accuracy quantum chemistry calculation. The rate constants of key elementary steps were calculated by meaning of the canonical variation transition-state (CVT) theory with the small curvature tunneling (SCT) correction over the temperature range of 400-1400 K. The mechanism of the PAH formation involves in six elementary steps, addition reaction, ring closure, intramolecular H-shift, cleavage of CC bond, intramolecular H-shift and unimolecular elimination of CH 3 or H. The cleavage of CC bond is the rate-determining step due to the high barrier. The formation of PAHs from the reactions of anthracene with cyclopentadienyl and indenyl radicals is easier than that from the reactions of phenanthrene., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Polycyclic aromatic hydrocarbons (PAHs) are globally concerned atmospheric particle-bound pollutants due to their toxicities. A mechanistic understanding of their formation from other environmental sources is of crucial importance for successful prevention of PAH. In the present work, the formation and growth mechanism of PAHs from the reactions of naphthalene with the cyclopentadienyl and indenyl radicals was investigated by using the hybrid density functional theory (DFT) at the MPWB1K/6-311+G(3df,2p)//MPWB1K/6-31+G(d,p) level. The rate constants for the crucial elementary steps were deduced with the aid of the canonical variational transition-state (CVT) theory with the small curvature tunneling (SCT) contribution. The formation of PAHs was involved in six elementary processes including: the addition reaction, ring closure, intramolecular H-shift, C-C cleavage, intramolecular H-shift and unimolecular elimination of CH3 or H. The C-C cleavage steps were revealed as the rate determining steps due to the extremely high barrier. At high temperature conditions like the combustion and pyrolysis of many hydrocarbons, the main products are phenanthrene, 4-methyl-phenanthrene and 1-methyl-phenanthrene from the reactions of naphthalene and cyclopentadienyl, and benzo(a)anthracene, 12-methyl-phenanthrene and 7-methyl-phenanthrene from the reactions of naphthalene and indenyl radicals. The reaction of naphthalene with indenyl radical is slightly more difficult than the reaction of naphthalene with cyclopentadienyl radical because of the bigger HOMO-LUMO orbital energy difference of naphthalene with indenyl relative to that of naphthalene with cyclopentadienyl., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Chlorinated polycyclic aromatic hydrocarbons (ClPAHs) have become a serious environmental concern due to their widespread occurrence and dioxin-like toxicities. In this work, the mechanism of the OH-initiated atmospheric oxidation degradation of 9,10-dichlorophenanthrene (9,10-Cl₂Phe) was investigated by using high-accuracy quantum chemistry calculations. The rate constants of the crucial elementary reactions were determined by the Rice-Ramsperger-Kassel-Marcus (RRKM) theory. The theoretical results were compared with the available experimental data. The main oxidation products are a group of ring-retaining and ring-opening compounds including chlorophenanthrols, 9,10-dichlorophenanthrene-3,4-dione, dialdehydes, chlorophenanthrenequinones, nitro-9,10-Cl₂Phe and epoxides et al. The overall rate constant of the OH addition reaction is 2.35 × 10(-12)cm(3) molecule(-1)s(-1) at 298 K and 1 atm. The atmospheric lifetime of 9,10-Cl₂Phe determined by OH radicals is about 5.05 days. This study provides a comprehensive investigation of the OH-initiated oxidation degradation of 9,10-Cl₂Phe and should contribute to clarifying its atmospheric fate., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Nitro-PAHs are globally worrisome air pollutants because their high direct-acting mutagenicity and carcinogenicity. A mechanistic understanding of their formation is of crucial importance for successful prevention of their atmospheric pollution. Here, the formation of nitro-PAHs arising from the OH-initiated and NO3-initiated atmospheric reactions of PAHs was investigated by using quantum chemical calculations. It is widely assumed that OH or NO3 radicals attack on the C atoms of the aromatic rings in the PAH molecule, followed by the addition of NO2 to the OH-PAH or NO3-PAH adducts at the ortho position and the loss of water or nitric acid to form nitro-PAHs. However, calculations show that the direct loss of water from the OH-NO2-PAH adducts via the unimolecular decomposition is energetically unfavorable. This study reveals for the first time that water molecule plays an important catalytic effect on the loss of water from the OH-NO2-PAH adducts and promotes the formation of nitro-PAHs. In addition, the introduction of water unwraps new formation pathway through the addition of NO2 to the OH-PAH or NO3-PAH adduct at the para position. The individual and overall rate constants for the addition reactions of PAHs with OH and NO3 radicals were deduced by using the Rice-Ramsperger-Kassel-Marcus (RRKM) theory.

Abstract: Polycyclic aromatic hydrocarbons (PAHs) are widespread and toxic pollutants. Naphthalene is the most abundant PAH found in polluted urban areas. In this Letter, we studied the mechanism for the NO3-initiated atmospheric oxidation reactions of naphthalene, using high-level molecular orbital theory. Geometries of the reactants, intermediates, transition states, and products have been optimized at the BB1K level with the 6-31+G(d,p) basis set. The single-point energy calculations have been carried out at the BB1K/6-311+G(3df,2p) level. Several energetically favorable reaction pathways were revealed for the first time. The calculated results were compared with the available experimental observation. [Copyright &y& Elsevier]

Abstract: Naphthalene is the most abundant polycyclic aromatic hydrocarbon found in polluted urban areas. Its most important atmospheric loss process is the reaction with OH radicals. In this Letter, we studied the mechanism for the OH-initiated atmospheric photooxidation of naphthalene in the presence of O2 and NO x , using high-level molecular orbital theory. The profile of the potential energy surface was constructed, and all of the possible product channels were discussed. The theoretical results were compared with the experimental observation. [Copyright &y& Elsevier]

Polycyclic aromatic hydrocarbons (PAHs) have induced large-scale and long-term environmental contamination due to heavy emissions, toxicity, and persistence. The investigation of the ultimate sink of PAHs in the atmosphere is very important. In this work, using quantum chemistry methods, the reaction mechanism of hydroxyl radical-initiated oxidation of benzo[a]anthracene (BaA) in the atmosphere was studied. The products resulted from the gas-phase reaction of BaA with hydroxyl radical include benzo[a]anthracenols, dialdehydes, ketones, epoxides, etc. Applying Rice-Ramsperger-Kassel-Marcus (RRKM) theory, the overall rate constant for reactions of •OH addition to BaA was estimated to be 4.82 × 10−11 cm3 molecule−1 s−1 at 298 K and 1 atm. The lifetime of BaA in the atmosphere with respect to hydroxyl radical was calculated to be 5.92 h. [ABSTRACT FROM AUTHOR]

The atmospheric oxidation of polycyclic aromatic hydrocarbons (PAHs) can generate toxic derivatives which contribute to the carcinogenic potential of particulate organic matter. In this work, the mechanism of the OH-initiated atmospheric oxidation of fluoranthene (Flu) was investigated by using high-accuracy molecular orbital calculations. All of the possible oxidation pathways were discussed, and the theoretical results were compared with the available experimental observation. The rate constants of the crucial elementary reactions were evaluated by the Rice–Ramsperger–Kassel–Marcus (RRKM) theory. The main oxidation products are a range of ring-retaining and ring-opening chemicals containing fluoranthols, fluoranthones, fluoranthenequinones, nitro-fluoranthenes, dialdehydes and epoxides. The overall rate constant of the OH addition reaction is 1.72 × 10 − 11 cm 3 molecule − 1 s − 1 at 298 K and 1 atm. The atmospheric lifetime of Flu determined by OH radicals is about 0.69 days. This work provides a comprehensive investigation of the OH-initiated oxidation of Flu and should help to clarify its atmospheric conversion. [ABSTRACT FROM AUTHOR]

• The formation mechanism of dinitro-pyrenes initiated by OH radicals was investigated. • The role of water molecule in the water loss process was proposed. • The rate constants of mononitro-pyrenes reacting with OH radicals were calculated. • The lifetime of mononitro-pyrenes in the presence of OH radicals was estimated. Nitrated polycyclic aromatic hydrocarbons are more mutagenic and carcinogenic than parent PAHs. The formation mechanism of dinitro-pyrenes initiated by OH from mononitro-pyrenes was conducted by quantum chemical calculations. The products are 1,2-, 1,7-, 2,4-, 2,5- and 2,7- dinitropyrenes. Water molecules can decrease the Gibbs activation barriers of water loss step of NO 2 -OH-nitropyrene. By canonical variational transition state theory with small curvature tunneling correction, the calculated overall rate constants for 1-, 2- and 4-nitropyrene are 8.13 × 10−13 cm3 molecule−1 s−1, 8.90 × 10−13 cm3 molecule−1 s−1 and 1.50 × 10−12 cm3 molecule−1 s−1 at 298 K and 1 atm, respectively. [ABSTRACT FROM AUTHOR]

Phenanthrene is a polycyclic aromatic hydrocarbon from fossil fuel combustion with toxic properties. The products arising from atmospheric reaction can be more mutagenic and carcinogenic compared to unmodified phenanthrene, and are therefore important to be studied. The products of the specific NO 3 -radical reactions with phenanthrene where therefore investigated in this study by means of Density Functional Theory (DFT). The results show that the main products are proposed to be 10-(nitrooxy)-10-hydro-phenanthrene-9-one, 2,2′-diformylbiphenyl, 9,10-phenanthrenequinone, 9-fluorenone and dibenzopyranone. 10-(nitrooxy)-10-hydro-phenanthrene-9-one and 2,2′-diformylbiphenyl are classified as first-generation products which are subject to secondary reactions to produce 9,10-phenanthrenequinone, 9-fluorenone and dibenzopyranone. The rate constants of elementary reactions were assessed by Rice-Ramsperger-Kassel-Marcus (RRKM) theory. The atmospheric lifetime of Phe determined by the gas-phase reaction with NO 3 is estimated to be 1.8 h, based on the calculated overall rate constant of 3.04 × 10 −13 cm 3 molecule −1 s −1 at 298 K and 1 atm. Combined with available experimental observation, this work should help to clarify the transformation and potential health risk of Phe in the atmosphere. [ABSTRACT FROM AUTHOR]

The degradation of polycyclic aromatic hydrocarbons (PAHs) in the atmosphere can lead to toxic derivatives which contribute to the carcinogenic potential of particulate organic matter. This paper aimed to investigate the mechanism of the OH-initiated oxidation degradation of benzo[α]pyrene (BaP), a cancer risk indicator. High-accuracy molecular orbital calculations were carried out, and all of the possible degradation pathways were discussed. The theoretical results were compared with the available experimental observation. The possible secondary reactions were also investigated. The rate constants of the crucial elementary steps were evaluated by using the Rice–Ramsperger–Kassel–Marcus (RRKM) theory. The dominant degradation products involve benzo[α]pyren-ol, nitro-benzo[α]pyrene, benzo[α]pyrene-7,10-dione as well as several ring-opened products such as alkyl substituted benzanthraldehyde et al. In particular, water plays an important role in the degradation pathways leading to the formation of nitro-benzo[α]pyrene. This work provides a comprehensive investigation of the OH-initiated degradation of BaP and should help to clarify its potential risk. [ABSTRACT FROM AUTHOR]

[Display omitted] • C1 site is more reactive than C2 site. • Water cannot catalyze the intramolecular H transfer reaction of O 2 -OH-adducts. • The products include phenanthrene-9,10-dicarboxaldehyde and 2-nitrotriphenylene. • The lifetime of triphenylene determined by OH radical is 1.66 days. Triphenylene is a four-ring polycyclic aromatic hydrocarbon (PAH) with fully-benzenoid structure. The OH-initiated atmospheric oxidation of triphenylene was investigated using quantum chemical calculations at M06-2X/6–311++G(3df,2p)//M06-2X/6–311+G(d,p) level. The main products are nitro-PAHs and oxygenated PAHs. The overall rate constant of triphenylene reacting with OH radicals at 298 K and 1 atm is 7.17 × 10−12 cm3 molecule−1 s−1 and its lifetime is 1.66 days, which is longer than those of its isomers. This work helps to analyze the environmental fate and risk of triphenylene and further to build regular degradation profile of PAHs in the atmosphere. [ABSTRACT FROM AUTHOR]

Chrysene, a four-ring polycyclic aromatic hydrocarbon (PAH), is recalcitrant to biodegradation and persistent in the environment due to its low water solubility. Here, we investigated the atmospheric degradation process of chrysene initiated by OH radical in the presence of O 2 and NO X using quantum chemical calculations. The reaction mechanisms were elucidated by density functional theory (DFT) at M06–2X/6–311++G(3df,2p)//M06–2X/6-311+G(d,p) level, and the kinetics calculations were conducted with Rice-Ramsperger-Kassel-Marcus (RRKM) theory. The results show that the oxidation products of atmospheric chrysene are oxygenated PAHs (OPAHs) and nitro-PAHs (NPAHs), including nitro-chrysene, hydroxychrysene, hydroxychrysenone, 11-benzo[ a ]fluorenone and dialdehydes. Most of the products have deleterious effects on the environment and human beings due to their acute toxicity, carcinogenicity and mutagenicity. The overall rate constant for the reaction of chrysene with OH radical is 4.48 × 10−11 cm3 molecule−1 s−1 and the atmospheric lifetime of chrysene determined by OH radical is 6.4 h. The present work provided a comprehensive understanding on the degradation mechanisms and kinetics of chrysene, which could help to clarify its atmospheric fate and environmental risks. Image 1 • OH-initiated oxidation of chrysene was investigated with DFT. • Nitro-chrysene can be formed through the reaction with NO 2. • Hydroxychrysene is formed via H transfer reaction. • The OH addition to C5 and C6 will lead to the formation of benzo[a]fluorenone. • The lifetime of chrysene determined by OH radical is 6.4 h. [ABSTRACT FROM AUTHOR]

The atmospheric degradation of polycyclic aromatic hydrocarbons (PAHs) can generate organic pollutants that contribute to the formation of secondary organic aerosols (SOAs) and exacerbate their carcinogenicity. Indene is an example of styrene-like bicyclic hydrocarbons that are not fully aromatic. The OH-initiated atmospheric oxidation of indene in the presence of O 2 and NO was investigated using quantum chemical methods at M06–2X/6–311++G(3df,2p)//M06–2X/6-311+G(d,p) level. The oxidation products are oxygenated polycyclic aromatic hydrocarbons (OPAHs) containing hydroxyindene, indenone, dialdehydes and 2-(formylmethyl)benzaldehyde. Calculation results showed that 7-indene radical, which is the precursor of various PAHs, has a high production ratio that is 35.29% in the initial reaction, indicating that the OH-initiated oxidation increase the environmental risks of indene in the atmosphere. The rate constants for the crucial elementary reactions were calculated based on Rice-Ramsperger-Kassel-Marcus (RRKM) theory. The overall rate constant of the initial reaction is calculated to be 1.04 × 10−10 cm3 molecule−1 s−1 and the atmospheric lifetime of indene is determined as 2.74 h. This work provides a comprehensive understanding on the oxidation mechanisms of indene and the findings could help to clarify the fate of indene in the atmosphere. Image 1 • OH-initiated oxidation of indene was studied with DFT. • Indene radical has a high production ratio of 35.29% in the initial reaction. • The ring-opening products of indene are OPAHs. • The lifetime of indene determined by OH radical is 2.74 h. [ABSTRACT FROM AUTHOR]