Theoretical studies on the aqueous phase and graphene heterogeneous degradation of acrylamide and acrylonitrile by HO, ClO, and BrO radicals.

The newly discovered ClO• and BrO• contribute to pollutant degradation in advanced oxidation processes, while acrylamide (AM) and acrylonitrile (ACN) are always the focus of scientists concerned due to their continuous production and highly toxic effects. Moreover, various particles with a graphene-like structure are the companions of AM/ACN in dry/wet sedimentation or aqueous phase existence, which play an important role in heterogeneous oxidation. Thus, this work focuses on the reaction mechanism and environmental effect of AM/ACN with ClO•/BrO•/HO• in the water environment under the influence of graphene (GP). The results show that although the reactivity sequence of AM and ACN takes the order of with HO• > with BrO• > with ClO•, the easiest channel always occurs at the same C-position of the two reactants. The reaction rate constants (k) of AM with three radicals are 2 times larger than that with ACN, and amide groups have a better ability to activate CC bonds than cyanide groups. The existence of GP can accelerate the target reaction, and the k increased by 9-13 orders of magnitude. The toxicity assessment results show that the toxic effect of most products is lower than that of parent compounds, but the environmental risk of products from ClO•/BrO•-adducts is higher than those from HO•-adducts. The oxidative degradation process based on ClO• and BrO• deserves special attention, and the catalytic effect of GP and its derivatives on the oxidation process is non-negligible.

Chlorination of Aromatic Amino Acids: Elucidating Disinfection Byproducts, Reaction Kinetics, and Influence Factors.

In the face of ongoing water pollution challenges, the intricate interplay between dissolved organic matter and disinfectants like chlorine gives rise to potentially harmful disinfection byproducts (DBPs) during water treatment. The exploration of DBP formation originating from amino acids (AA) is a critical focus of global research. Aromatic DBPs, in particular, have garnered considerable attention due to their markedly higher toxicity compared to their aliphatic counterparts. This work seeks to advance the understanding of DBP formation by investigating chlorination disinfection and kinetics using tyrosine (Tyr), phenylalanine (Phe), and tryptophan (Trp) as precursors. Via rigorous experiments, a total of 15 distinct DBPs with accurate molecular structures were successfully identified. The chlorination of all three AAs yielded highly toxic chlorophenylacetonitriles (CPANs), and the disinfectant dosage and pH value of the reaction system potentially influence chlorination kinetics. Notably, Phe exhibited the highest degradation rate compared to Tyr and Trp, at both the CAA:CHOCl ratio of within 1:2 and a wide pH range (6.0 to 9.0). Additionally, a neutral pH environment triggered the maximal reaction rates of the three AAs, while an acidic condition may reduce their reactivity. Overall, this study aims to augment the DBP database and foster a deeper comprehension of the DBP formation and relevant kinetics underlying the chlorination of aromatic AAs.

Chloramine Disinfection of Levofloxacin and Sulfaphenazole: Unraveling Novel Disinfection Byproducts and Elucidating Formation Mechanisms for an Enhanced Understanding of Water Treatment.

The unrestricted utilization of antibiotics poses a critical challenge to global public health and safety. Levofloxacin (LEV) and sulfaphenazole (SPN), widely employed broad-spectrum antimicrobials, are frequently detected at the terminal stage of water treatment, raising concerns regarding their potential conversion into detrimental disinfection byproducts (DBPs). However, current knowledge is deficient in identifying the potential DBPs and elucidating the precise transformation pathways and influencing factors during the chloramine disinfection process of these two antibiotics. This study conducts a comprehensive analysis of reaction pathways, encompassing piperazine ring opening/oxidation, Cl-substitution, OH-substitution, desulfurization, and S-N bond cleavage, during chloramine disinfection. Twelve new DBPs were identified in this study, exhibiting stability and persistence even after 24 h of disinfection. Additionally, an examination of DBP generation under varying disinfectant concentrations and pH values revealed peak levels at a molar ratio of 25 for LEV and SPN to chloramine, with LEV contributing 11.5% and SPN 23.8% to the relative abundance of DBPs. Remarkably, this research underscores a substantial increase in DBP formation within the molar ratio range of 1:1 to 1:10 compared to 1:10 to 1:25. Furthermore, a pronounced elevation in DBP generation was observed in the pH range of 7 to 8. These findings present critical insights into the impact of the disinfection process on these antibiotics, emphasizing the innovation and significance of this research in assessing associated health risks.

Prediction study on the distribution of polycyclic aromatic hydrocarbons and their halogenated derivatives in the atmospheric particulate phase.

Polycyclic aromatic hydrocarbons (PAHs) and their halogenated derivatives (X-PAHs), which generally produced from photochemical and thermal reactions of parent PAHs, widely exist in the environment. They are semi-volatile organic chemicals (SVOCs) and the partitioning between gas/particulate phases affects their environmental migration, transformation and fate, which further impacts their toxicity and health risk to human. However, there is a large data missing of the experimental distribution ratio in the atmospheric particulate phase (f), especially for X-PAHs. In this study, we first checked the correlation between experimental f values of 53 PAH derivatives and their octanol-air partitioning coefficients (log KOA), which is frequently used to characterize the distribution of chemicals in organic phase, and yielded R2 = 0.803. Then, quantum chemical descriptors derived from molecular structural optimization by M06-2X/6-311 +G (d,p) method were further employed to develop Quantitative Structure-Property Relationship (QSPR) model. The model contains two descriptors, the average molecular polarizability (α) and the equilibrium parameter of molecular electrostatic potential (τ), and yields better performance with R2 = 0.846 and RMSE = 0.122. The mechanism analysis and validation results by different strategies prove that the model can reveal the molecular properties that dominate the distribution between gas and particulate phases and it can be used to predict f values of other PAHs/X-PAHs, providing basic data for their environmental ecological risk assessment.

Predictive Models of Gas/Particulate Partition Coefficients (KP) for Polycyclic Aromatic Hydrocarbons and Their Oxygen/Nitrogen Derivatives.

Polycyclic aromatic hydrocarbons (PAHs) and their oxygen/nitrogen derivatives released into the atmosphere can alternate between a gas phase and a particulate phase, further affecting their environmental behavior and fate. The gas/particulate partition coefficient (KP) is generally used to characterize such partitioning equilibrium. In this study, the correlation between log KP of fifty PAH derivatives and their n-octanol/air partition coefficient (log KOA) was first analyzed, yielding a strong linear correlation (R2 = 0.801). Then, Gaussian 09 software was used to calculate quantum chemical descriptors of all chemicals at M062X/6-311+G (d,p) level. Both stepwise multiple linear regression (MLR) and support vector machine (SVM) methods were used to develop the quantitative structure-property relationship (QSPR) prediction models of log KP. They yield better statistical performance (R2 > 0.847, RMSE < 0.584) than the log KOA model. Simulation external validation and cross validation were further used to characterize the fitting performance, predictive ability, and robustness of the models. The mechanism analysis shows intermolecular dispersion interaction and hydrogen bonding as the main factors to dominate the distribution of PAH derivatives between the gas phase and particulate phase. The developed models can be used to predict log KP values of other PAH derivatives in the application domain, providing basic data for their ecological risk assessment.

Computational Insight into Biotransformation Profiles of Organophosphorus Flame Retardants to Their Diester Metabolites by Cytochrome P450.

Biotransformation of organophosphorus flame retardants (OPFRs) mediated by cytochrome P450 enzymes (CYPs) has a potential correlation with their toxicological effects on humans. In this work, we employed five typical OPFRs including tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), tris(1-chloro-2-propyl) phosphate (TCIPP), tri(2-chloroethyl) phosphate (TCEP), triethyl phosphate (TEP), and 2-ethylhexyl diphenyl phosphate (EHDPHP), and performed density functional theory (DFT) calculations to clarify the CYP-catalyzed biotransformation of five OPFRs to their diester metabolites. The DFT results show that the reaction mechanism consists of Cα-hydroxylation and O-dealkylation steps, and the biotransformation activities of five OPFRs may follow the order of TCEP ≈ TEP ≈ EHDPHP > TCIPP > TDCIPP. We further performed molecular dynamics (MD) simulations to unravel the binding interactions of five OPFRs in the CYP3A4 isoform. Binding mode analyses demonstrate that CYP3A4-mediated metabolism of TDCIPP, TCIPP, TCEP, and TEP can produce the diester metabolites, while EHDPHP metabolism may generate para-hydroxyEHDPHP as the primary metabolite. Moreover, the EHDPHP and TDCIPP have higher binding potential to CYP3A4 than TCIPP, TCEP, and TEP. This work reports the biotransformation profiles and binding features of five OPFRs in CYP, which can provide meaningful clues for the further studies of the metabolic fates of OPFRs and toxicological effects associated with the relevant metabolites.

Binding and Metabolism of Brominated Flame Retardant ß-1,2-Dibromo-4-(1,2-dibromoethyl)cyclohexane in Human Microsomal P450 Enzymes: Insights from Computational Studies.

The emerging brominated flame retardant, 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (TBECH), has recently attracted strong interest due to its extensive detection in the environment and potential toxicological effects on humans. Previous in vitro experiments have shown that the technical mixture of TBECH and the pure ß-isomer (ß-TBECH) can be metabolized by cytochrome P450 enzymes (CYPs) into multiple metabolites, but the specific CYP isoforms involved in TBECH metabolism and the relevant metabolic regioselectivity remain unknown. Here, we, for the first time, investigated the binding patterns and affinities of ß-TBECH in human CYPs 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, and 3A4, through molecular dynamics (MD) simulations. The binding affinities of ß-TBECH in CYPs, which are estimated by the calculated binding free energies, follow the order of 2A6 > 2C9 > 2B6 > 2E1 > 3A4 ≈ 2C19 ≈ 1A2 > 2D6. Although all CYPs are important ß-TBECH receptors, only 2A6, 2C19, 2E1, and 3A4 are responsible for metabolizing ß-TBECH. Specially, 2A6 and 2E1 may selectively hydroxylate the C1 and C7 sites of ß-TBECH, while 2C19 and 3A4 show metabolic preference for C7- and C8-hydroxylations, respectively. The three hydroxylation routes proposed by the further density functional theory (DFT) calculations generate C1-, C7-, and C8-hydroxylated metabolites, while the latter two may further undergo debromination to yield the respective ketone and aldehyde as additional metabolites. The results provide meaningful insight into the binding and metabolism of ß-TBECH by human CYPs, which is helpful for understanding the metabolic fate and toxicity mechanism of this chemical.

Molecular Basis for Metabolic Regioselectivity and Mechanism of Cytochrome P450s toward Carcinogenic 4-(Methylnitrosamino)-(3-pyridyl)-1-butanone.

As an abundantly present tobacco component, carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) has also been detected in atmospheric particulate matter, suggesting the ineluctable exposure risk of this contaminant. NNK metabolic activation by cytochrome P450 enzymes (CYPs) is a prerequisite to exerting its genotoxicity, but the metabolic regioselectivity and mechanism are still unknown. Here the binding feature and regioselectivity of CYPs 1A1, 1A2, 2A6, 2A13, 2B6, and 3A4 toward NNK are unraveled through molecular docking and molecular dynamics (MD) simulations. Binding mode analyses reveal that 1A2 and 2B6 have definite preferences for NNK α-methyl hydroxylation, while the other four CYPs preferentially catalyze α-methylene hydroxylation. The binding affinities between NNK and CYPs evaluated by the binding free energies follow the order 2A13 > 2B6 > 1A2 > 2A6 > 1A1 > 3A4. Density functional theory (DFT) calculations are further performed to characterize the mechanism of NNK biotransformation. Results show that the α-hydroxyNNK generated from α-hydroxylation may undergo nonenzymatic decomposition to form genotoxic diazohydroxide and aldehyde, and further oxidation by P450 to yield nitrosamide, which mainly contributes to NNK toxification capacity. Meanwhile the pyridine N-oxidation and denitrosation of Cα-radical intermediate play an important role in detoxifying NNK. Overall, the present study provides the molecular basis for CYP-catalyzed regioselectivity and mechanism of NNK biotransformation, which can enable the identification of metabolites for assessing the health risk of individual NNK exposure.

In silico study for inhibiting thyroid hormone sulfotransferase activity by halogenated phenolic chemicals.

Thyroid hormones (THs) are essential to proper growth and development of human bodies. Inhibiting the sulfation metabolism of THs has been demonstrated to be an important way for some environmental pollutants, such as halogenated phenolic compounds, to interfere THs homeostasis, thereby causing health problems. However, the important property characteristics that govern the sulfation inhibition of these chemicals are not well understood, and the experimental data on inhibition potential is limited. In this work, an in silico approach was developed to investigate the structure-activity relationship for their sulfotransferases (SULTs) inhibition. A series of quantum chemical descriptors that quantify the electronic and energy properties of 22 halogenated phenolic compounds have been calculated to establish a predictive model and analyzed their corresponding contributions to SULTs inhibition. Density functional theory (DFT) B3LYP/6-31G** has been employed to optimize molecular geometries to obtain a total of 15 descriptors for every compound. The implementation of linear regression shows three descriptors that represent molecular mass, positive charges on hydrogen atoms, and energy of frontier orbitals strongly correlate with SULTs inhibition potential. This indicates molecular size, hydrogen-bond strength, and nucleophilic-electrophilic reactivity may play important roles in SULTs inhibition. The derived regression model has good statistical performance (r2 = 0.84, rms = 0.35), and different validation strategies indicate it can serve as an efficient predictive tool for other chemicals in application domain but with no experimental data, consequently assisting in their THs sulfation inhibition and health risk assessment.

Developing Predictive Models for Carrying Ability of Micro-Plastics towards Organic Pollutants.

Microplastics, which have been frequently detected worldwide, are strong adsorbents for organic pollutants and may alter their environmental behavior and toxicity in the environment. To completely state the risk of microplastics and their coexisting organics, the adsorption behavior of microplastics is a critical issue that needs to be clarified. Thus, the microplastic/water partition coefficient (log Kd) of organics was investigated by in silico method here. Five log Kd predictive models were developed for the partition of organics in polyethylene/seawater, polyethylene/freshwater, polyethylene/pure water, polypropylene/seawater, and polystyrene/seawater. The statistical results indicate that the established models have good robustness and predictive ability. Analyzing the descriptors selected by different models finds that hydrophobic interaction is the main adsorption mechanism, and π-π interaction also plays a crucial role for the microplastics containing benzene rings. Hydrogen bond basicity and cavity formation energy of compounds can determine their partition tendency. The distinct crystallinity and aromaticity make different microplastics exhibit disparate adsorption carrying ability. Environmental medium with high salinity can enhance the adsorption of organics and microplastics by increasing their induced dipole effect. The models developed in this study can not only be used to estimate the log Kd values, but also provide some necessary mechanism information for the further risk studies of microplastics.

Theoretical Insights into the Mechanism and Stereoselectivity of Olefin Cyclopropanation Catalyzed by Two Engineered Cytochrome P450 Enzymes.

Engineered P450s can catalyze some non-natural reactions with high efficiency and excellent selectivity, such as the carbine transfer, nitrene transfer, C-H insertion, and C-H amination, opening alternative routes for sustainable production of chemicals. Recent experiments revealed that two engineered cytochrome P450 enzymes (P450BM3-CIS and P411BM3-CIS) show different efficiencies and stereoselectivities in the olefin cyclopropanation, but key factors that affect the activity remain unclear. In this work, both quantum mechanics (QM) and QM/molecular mechanics (MM) methods were employed to explore the catalytic reactions and selectivity of these two engineered cytochrome P450 enzymes. On the basis of our results, the cyclopropanation of styrene is suggested to mainly occur on the open-shell singlet (OSS) and triplet state surfaces, which contain two elementary steps. The reactive iron(III)-porphyrin carbene (IPC) radical first attacks the terminal alkenyl group of styrene to form a C-radical intermediate, which then undergoes a cyclization reaction affording the cyclopropanation products. Importantly, it is found that the stereoselectivity of cyclopropanations is elucidated only if considering the real protein environment, and the stereoselectivity is determined by multiple factors, such as the relative orientation of IPC to styrene, the binding affinity of the substrate, and the reaction barriers of rate-limiting steps. It is the enzymatic environment that makes the reaction highly stereoselective, which provides useful clues for designing whole-cell catalysts for non-natural chemical reactions.

Computational Insight into the Activation Mechanism of Carcinogenic N'-Nitrosonornicotine (NNN) Catalyzed by Cytochrome P450.

Tobacco-specific N'-nitrosonornicotine (NNN), a genotoxic nitrosamine classified as Group 1 carcinogen, is also present in atmospheric particulate matter and has even been detected as a new disinfection byproduct in wastewaters. NNN generally requires metabolic activation by cytochrome P450 enzymes to exert its genotoxicity, but the respective biotransformation pathways have not been described in detail. In this work, we performed density functional theory (DFT) calculations to unravel possible NNN activation pathways including α-hydroxylation, ß-hydroxylation, pyridine N-oxidation, and norcotinine formation. The results reveal an initial rate-determining Hα-atom abstraction step for α-hydroxylation, followed by an unexpected kinetic competition between denitrosation and OH rebound, leading to ( iso-)myosmine as a detoxified product and α-hydroxyNNNs as the precursor of carcinogenic diazohydroxides, respectively. Further detoxification routes are given by ß-hydroxylation with relative high reaction barrier and N-oxidation with comparable barrier to the toxifying α-hydroxylation. Moreover, we show for the first time how norcotinine can be generated as a minor NNN metabolite that is formed from iso-myosmine through a unique porphyrin-assisted H atom 1,2-transfer mechanism. These results demonstrate that the carcinogenic potential of NNN is subject to a kinetic competition between activating and deactivating metabolic routes, and identify respective biomarkers to inform about the individual risk associated with NNN exposure.

Development and evaluation of predictive model for bovine serum albumin-water partition coefficients of neutral organic chemicals.

The binding of organic chemicals to serum albumin can significantly reduce their unbound concentration in blood and affect their biological reactions. In this study, we developed a new QSAR model for bovine serum albumin (BSA) - water partition coefficients (KBSA/W) of neutral organic chemicals with large structural variance, logKBSA/W values covering 3.5 orders of magnitude (1.19-4.76). All chemical geometries were optimized by semi-empirical PM6 algorithm. Several quantum chemical parameters that reflect various intermolecular interactions as well as hydrophobicity were selected to develop QSAR model. The result indicates the regression model derived from logKow, the most positive net atomic charges on an atom, Connolly solvent excluded volume, polarizability, and Abraham acidity could explain the partitioning mechanism of organic chemicals between BSA and water. The simulated external validation and cross validation verifies the developed model has good statistical robustness and predictive ability, thus can be used to estimate the logKBSA/W values for chemicals in application domain, accordingly to provide basic data for the toxicity assessment of the chemicals.

QM/MM studies on the calcium-assisted ß-elimination mechanism of pectate lyase from bacillus subtilis.

Pectate lyase utilizes the anti-ß-elimination chemistry to catalyze the cleavage of α-1,4 glycosidic bond between D -galacturonate regions during the degradation of plant polysaccharide pectin. We report here detailed mechanistic studies of the Bacillus subtilis pectate lyase (BsPel) using QM/MM calculations. It was found that the residue Arg279 serves as the catalytic base to abstract the α-proton from C52 atom of substrate Ada2 subsite, forming an unstable carbanion intermediate. The glycosidic bond of this intermediate is scissile to generate the 4,5-unsaturated digalacturonate product and a negatively charged ß-leaving group. Two active site residues (Lys247 and Arg279) and two Ca2+ ions (Ca2 and Ca3) form hydrogen-bonding and coordination interactions with C52 COO- of Ada2, respectively, which facilitate the proton abstraction and stabilize the generated carbanion intermediates. Arg284 is not the potential proton donor to saturate the leaving group. Actually, the proton source of leaving group is the solvent water molecule rather than any active site acidic residues. In addition, the calculation results suggest that careful selections of QM- and Active-regions are essential to accurately explore the enzymatic reactions. Proteins 2016; 84:1606-1615. © 2016 Wiley Periodicals, Inc.

Water promoting electron hole transport between tyrosine and cysteine in proteins via a special mechanism: double proton coupled electron transfer.

The proton/electron transfer reactions between cysteine residue (Cys) and tyrosinyl radical (Tyr(•)) are an important step for many enzyme-catalyzed processes. On the basis of the statistical analysis of protein data bank, we designed three representative models to explore the possible proton/electron transfer mechanisms from Cys to Tyr(•) in proteins. Our ab initio calculations on simplified models and quantum mechanical/molecular mechanical (QM/MM) calculations on real protein environment reveal that the direct electron transfer between Cys and Tyr(•) is difficult to occur, but an inserted water molecule can greatly promote the proton/electron transfer reactions by a double-proton-coupled electron transfer (dPCET) mechanism. The inserted H2O plays two assistant roles in these reactions. The first one is to bridge the side chains of Tyr(•) and Cys via two hydrogen bonds, which act as the proton pathway, and the other one is to enhance the electron overlap between the lone-pair orbital of sulfur atom and the π-orbital of phenol moiety and to function as electron transfer pathway. This water-mediated dPCET mechanism may offer great help to understand the detailed electron transfer processes between Tyr and Cys residues in proteins, such as the electron transfer from Cys439 to Tyr730(•) in the class I ribonucleotide reductase.

A Study of the Internal Deformation Fields and the Related Microstructure Evolution during Thermal Fatigue Tests of a Single-Crystal Ni-Base Superalloy.

Ni-base superalloys operate in harsh service conditions where cyclic heating and cooling introduce deformation fields that need to be investigated in detail. We used the high-angular-resolution electron backscatter diffraction method to study the evolution of internal stress fields and dislocation density distributions in carbides, dendrites, and notch tips. The results indicate that the stress concentrations decay exponentially away from the notch, and this pattern of distribution was modified by the growth of cracks and the emission of dislocations from the crack tip. Crack initiation follows crystallographic traces and is weakly correlated with carbides and dendrites. Thermal cycles introduce local plasticity around carbides, the dendrite boundary, and cracks. The dislocations lead to higher local stored energy than the critical value that is often cited to induce recrystallization. No large-scale onset of recrystallization was detected, possibly due to the mild temperature (800 °C); however, numerous recrystallized grains were detected in carbides after 50 and 80 cycles. The results call for a detailed investigation of the microstructure-related, thermally assisted recrystallization phenomenon and may assist in the microstructure control and cooling channel design of turbine blades.

Mechanistic insight into biotransformation of novel triazine-based flame retardant 1,3,5-tris(2,3-dibromopropyl)-1,3,5-triazinane-2,4,6-trione by human cytochrome P450s.

The escalating focus on the environmental occurrence and toxicology of emerging pollutants underscores the imperative need for a profound exploration of their metabolic transformations mediated by human CYP450 enzymes. Such investigations have the potential to unravel the intricate metabolite profiles, substantially altering the toxicological outcomes. In this study, we integrated the computational simulations with in vitro metabolism experiments to investigate the metabolic activity and mechanism of an emerging pollutant, 1,3,5-tris(2,3-dibromopropyl)-1,3,5-triazinane-2,4,6-trione (TDBP-TAZTO), catalyzed by human CYP450s. The results highlight the important contributions of CYP2E1, 3A4 and 2C9 to the biotransformation of TDBP-TAZTO, leading to the identification of four distinct metabolites. The effective binding conformations governing biotransformation reactions of TDBP-TAZTO within active CYP450s are unveiled. Structural instability of primary hydroxyTDBP-TAZTO products suggests three potential outcomes: (1) generation of an alcohol metabolite through successive debromination and reduction reactions, (2) formation of a dihydroxylated metabolite through secondary hydroxylation by CYP450, and (3) production of an N-dealkylated metabolite via decomposition and isomerization reactions in the aqueous environment. The formation of a desaturated debrominated metabolite may arise from H-abstraction and barrier-free Br release during the primary oxidation, potentially competing with the generation of hydroxyTDBP-TAZTO. These findings provide detailed mechanistic insight into TDBP-TAZTO biotransformation by CYP450s, which can enrich our understanding of the metabolic fate and associated health risk of this chemical.

Homogeneous and air-water interface properties of nicotine relative to aqueous aerosol: Adsorption, oxidation, and the influence for the HNCO formation.

Nicotine is the most abundant alkaloid compound in cigarette smoke and a known "emerging contaminant" in gas and aqueous environments. The main environmental behavior of nicotine is to be deposited on various surfaces. Aerosol droplets have a rich specific surface area, which has a great influence on air quality and human health. However, the microscopic interaction between aqueous nanoparticles and nicotine has not been revealed. In this work, the theoretical simulation of the adsorption and reaction properties of nicotine onto aerosol droplets is performed. The strong preference for nicotine on aqueous particle surfaces is firstly proven, and its interface retention rate is about 73 %, 4-7 times larger than that in the air/water phase. The k value of the interface reaction (heterogeneous reaction) is 4.34 × 10-9 cm3 molecule-1 s-1, which is about 80 and 571 times higher than that of the gaseous and aqueous reactions (homogeneous reaction). Interface environment can promote the oxidation of nicotine by •OH, and indirectly promote the rapid generation of toxic HNCO. The reaction rate constant of nicotine with •OH decreases with the increase of aerosol acidity, subsequently impeding the formation of HNCO. Considering the larger rate constant at the interface environment, the total effect of aqueous aerosol should be to improve the formation of HNCO. This work provides insight into the adsorption and oxidation of nicotine on the surface of the aerosol and is helpful in accurately evaluating its environmental fate and risk.

Thyroid hormone activities of neutral and anionic hydroxylated polybrominated diphenyl ethers to thyroid receptor ß: A molecular dynamics study.

Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) have been identified as the strong endocrine disrupting chemicals to humans, which show structural similarity with endogenous thyroid hormones (THs) and thus disrupt the functioning of THs through competitive binding with TH receptors (TRs). Although previous studies have reported the hormone activities of some OH-PBDEs on TH receptor ß (TRß), the interaction mechanism remains unclear. Furthermore, hydroxyl dissociation of OH-PBDEs may alter their TR disrupting activities, which has not yet been investigated in depth. In this work, we selected 18 OH-PBDEs with neutral and anionic forms and performed molecular dynamics (MD) simulations to estimate their binding interactions with the ligand binding domain (LBD) of TRß. The results demonstrate that most of OH-PBDEs have stronger binding affinities to TRß-LBD than their anionic counterparts, and the hydroxyl dissociation of ligands differentiate the major driving force for their binding. More Br atoms in OH-PBDEs can result in stronger binding potential with TRß-LBD. Moreover, 5 hydrophobic residues, including Met313, Leu330, Ile276, Leu346, and Phe272, are identified to have important contributions to bind OH-PBDEs. These results clarify the binding mechanism of OH(O-)-PBDEs to TRß-LBD at the molecular level, which can provide a solid theoretical basis for accurate assessment of TH disrupting effects of these chemicals.

Cytotoxicity of nitrogenous disinfection byproducts: A combined experimental and computational study.

Nitrogenous disinfection byproducts (N-DBPs), such as halocetamides (HAcAms), haloacetonitriles (HANs) and halonitromethanes (HNMs), are emerging DBPs in drinking water. They are more toxic than currently regulated DBPs, attracting more attention to their toxic effects and mechanism. In this study, human embryonic kidney (HEK) 293T cells were employed to explore the cytotoxicity of 29 N-DBPs. The influence of molecular structures and different halogenations on cytotoxicity has been comparatively analyzed. As toxicity is the downstream of chemico-biological interactions, the thiol reactivity of 29 N-DBPs has thus been evaluated by using glutathione (GSH) as a model nucleophile, which is the most prevalent cellular thiol and acts as an antioxidant to protect cells by detoxifying electrophilic compounds. Results show that the cytotoxicity of N-DBPs follows by the order of HAcAms > HANs > HNMs, which is different from their reactivity with GSH (the median of kGSH ranks as HNMs > HAcAms > HANs). However, a significant correlation (p < 0.001) between log kGSH and log IC50 (concentration causing 50% inhibition) has been respectively observed for HAcAms and HANs subset and HNMs subset, indicating such chemical reaction is a probable trigger for these DBPs to result in cytotoxicity. Finally, two separate quantitative structure - activity relationship (QSAR) models based on HANs & HAcAms subset and HNMs subset have been developed for estimating IC50 values. The good statistical performance makes the models possible to quickly and accurately predict IC50 values of other N-DBPs, providing basic data for their health risk assessment and greatly reducing in vivo and in vitro experiments.