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.

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.

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.

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.

Enantioselective metabolism of novel chiral insecticide Paichongding by human cytochrome P450 3A4: A computational insight.

As a novel chiral neonicotinoid insecticide, Paichongding (IPP) has been widely applied in agriculture due to its excellent insecticidal activity. However, the enantioselective metabolism of IPP stereoisomers (5R7R-IPP, 5S7S-IPP, 5R7S-IPP, and 5S7R-IPP) mediated by enzymes in non-target organisms, especially the cytochrome P450s (CYPs), remains unknown. To address this knowledge gap, we developed an integrated computational framework to elucidate the binding interactions and enantioselective metabolism of IPP stereoisomers in human CYP3A4. The results reveal that 5R7R-IPP shows much stronger binding affinity to CYP3A4 than 5S7S-IPP, while enantiomers 5R7S-IPP and 5S7R-IPP have no essential difference in their binding potential, owing to their specific interactions with key CYP3A4 residues. Although enantiomers 5R7R-IPP and 5S7S-IPP feature distinct binding modes resulting from the chiral differences, their transformation activities are slightly different, with C5 and C13 being the primary metabolic sites, respectively. In contrast, CYP3A4 preferably metabolizes 5R7S-IPP over 5S7R-IPP. The metabolism of epimers 5R7R-IPP and 5R7S-IPP share C5-hydroxylation routes due to the conserved 5R-conformaitons, but differ with the transformation routes at C11/C13 and C3 sites. The 7R-chirality of 5S7R-IPP significantly reduces the metabolic potency compared to 5S7S-IPP. CYP3A4-catalyzed hydroxylation and desaturation of IPP stereoisomers generate various chiral metabolites, with C5- and C13-hydroxyIPPs further transforming into depropylated products. Furthermore, the toxicity assessment reveals that IPP, along with the majority of its hydroxylated, desaturated, and depropylated metabolites, can potentially induce adverse effects on human health, specifically hepatotoxicity, respiratory toxicity, and carcinogenicity. This study provides valuable insights into the enantioselective fate of chiral IPP metabolism by CYP3A4, and the identified metabolites can serve as potential biomarkers for monitoring IPP exposure and associated health risk in human body.

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.

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.

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.

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.

Computational insight into biotransformation of halophenols by cytochrome P450: Mechanism and reactivity for epoxidation.

Halophenols (XPs) have aroused great interests due to their high toxicity and low biodegradability. Previous experimental studies have shown that XPs can be catalytically transformed into epoxides and haloquinones by cytochrome P450 enzymes (CYPs). However, these metabolites have never been detected directly. Moreover, the effects of the reaction site and the type and number of halogen substituents on the biotransformation reactivity of halophenols still remain unknown. In this work, we performed density functional theory (DFT) calculations to simulate the CYP-mediated biotransformation of 36 XPs with mono-, di-, and tri-halogen (F, Cl, and Br) substitutions to unravel the mechanism and relevant kinetics of XPs epoxidation. The whole epoxidation process consists of initial rate-determining O-addition and subsequent ring-closure steps. The simulation results show that the epoxidation in low-spin (LS) state is kinetically preferred over that in high-spin (HS) state, and the formation of epoxide metabolite is strongly exothermic. For all XPs, the epoxidation reactivity follows the order of ortho/para O-addition > meta O-addition. Moreover, the O-addition with higher energy barriers roughly corresponds to chlorophenols and fluorophenols with more halogen atoms. Compared with dichlorophenols, the additional ortho-Cl substitution on trichlorophenols can slightly increase the energy barriers of meta O-addition. By contrast, the additional inclusion of an ortho-Cl to monochlorophenols enhances the meta O-addition reactivity of dichlorophenols. Overall, the present work clarifies the biotransformation routes of XPs to produce epoxides, and identifies the key factors affecting the epoxidation reactivity, which are beneficial in understanding comprehensively the metabolic fate and toxicity of XPs.

Investigating the molecular mechanism of hydroxylated bromdiphenyl ethers to inhibit the thyroid hormone sulfotransferase SULT1A1.

Hydroxylated bromodiphenyl ethers (OH-BDEs) have raised great concern due to their potential endocrine disrupting effects on humans. In vitro experiments have indicated OH-BDEs can inhibit the activity of thyroid hormone (TH) sulfotransferases (SULTs); however, the molecular mechanism has not been investigated in depth. In this work, we employed 17 OH-BDEs with five or fewer Br atoms, and performed integrated computational simulations to unravel the possible inhibition mechanism of OH-BDEs on human SULT1A1. The molecular docking results demonstrate that OH-BDEs form hydrogen bonds with residues Lys106 and His108, and the neutral OH-BDEs show comparable binding energies with their anionic counterparts. The further hybrid quantum mechanical/molecular mechanical (QM/MM) calculations unravel a metabolic mechanism of OH-BDEs comprised by proton abstraction and sulfation steps. This mechanism is involved in the SULT1A1 inhibition by some OH-BDEs comprised of three or fewer Br atoms, while other OH-BDEs likely only form ternary complexes to competitively inhibit SULT1A1 activity. Moreover, the effect of the hydroxyl group of OH-BDEs on SULT1A1 inhibition potential follows the order of ortho-OH BDE > meta-OH BDE > para-OH BDE. These results provide an insight into the inhibition mechanism of OH-BDEs to SULT1A1 at the molecular level, which are beneficial in illuminating the molecular initiating events involved in the TH disruption of OH-BDEs.

QSPR models for predicting the adsorption capacity for microplastics of polyethylene, polypropylene and polystyrene.

Microplastics have become an emerging concerned global environmental pollution problem. Their strong adsorption towards the coexisting organic pollutants can cause additional environmental risks. Therefore, the adsorption capacity and mechanisms are necessary information for the comprehensive environmental assessments of both microplastics and organic pollutants. To overcome the lack of adsorption information, five quantitative structure-property relationship (QSPR) models were developed for predicting the microplastic/water partition coefficients (log Kd) of organics between polyethylene/seawater, polyethylene/freshwater, polyethylene/pure water, polypropylene/seawater, and polystyrene/seawater. All the QSPR models show good fitting ability (R2 = 0.811-0.939), predictive ability (Q2ext = 0.835-0.910, RMSEext = 0.369-0.752), and robustness (Qcv2 = 0.882-0.957). They can be used to predict the Kd values of organic pollutants (such as polychlorinated biphenyls, chlorobenzene, polycyclic aromatic hydrocarbons, antibiotics perfluorinated compounds, etc.) under different pH conditions. The hydrophobic interaction has been indicated as an important mechanism for the adsorption of organic pollutants to microplastics. In sea waters, the role of hydrogen bond interaction in adsorption is considerable. For polystyrene, π-π interaction contributes to the partitioning. The developed models can be used to quickly estimate the adsorption capacity of organic pollutants on microplastics in different types of water, providing necessary information for ecological risk studies of microplastics.

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.

N-doped mixed Co, Ni-oxides with petal structure as effective catalysts for hydrogen and oxygen evolution by water splitting.

Developing electrocatalytic nanomaterials for green H2 energy is inseparable from the exploration of novel materials and internal mechanisms for catalytic enhancement. In this work, nano-petal N-doped bi-metal (Ni, Co) and bi-valence (+2, +3) (Ni1-x Co x )2+Co2 3+O4 compounds have been in situ grown on the surface of Ni foam. The N3- atoms originate from the amino group in urea and doped in the compound during annealing. The as-synthesized N-doped (Ni1-x Co x )2+Co2 3+O4 nano-petals demonstrate commendable hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) bi-functional catalytic efficiency and stability. Electrochemical measurements confirm that the nitrogen doping significantly improves the catalytic kinetics and the surface area. Density functional theory calculations reveal that the improved HER and OER kinetics is not only due to the synergistic effect of bi-metal and bi-valence, as well as the introduction of defects such as oxygen vacancies, but also it more depends on the shortened bond length between the nitrogen N3- atoms and the metal atoms, and the increased electron density of the metal atoms attached to the N3- atoms. In other words, the change of lattice parameters caused by nitrogen doping is more conducive to the catalytic enhancement than the synergistic effect brought by bi-metal. This study provides an experimental and theoretical reference for the design of bi-functional electrocatalytic nanomaterials.

Precursors for brominated haloacetic acids during chlorination and a new useful indicator for bromine substitution factor.

Brominated haloacetic acids (HAAs) are much more cytotoxic and genotoxic than chlorinated one, yet little information is available for their organic precursors. In the present study, 8 water samples were collected in East China: 2 from lakes, 2 from rivers, 2 from reservoirs, a well and a mountain spring. Dissolved organic carbon (DOC), UV absorbance at 254 (UVA), specific UVA (SUVA) and chlorophyll a (Chl-a) were determined in raw water samples; formation of 9 HAA species as well as bromine substitution factor (BSF) were measured in chlorinated water samples. Results showed that water samples located in city generally contained higher levels of DOC (6.4-12.2mg/L) and UVA (0.124-0.194/cm), while those in the country side, low DOC (2.4-5.9mg/L) and UVA (0.061-0.109/cm) levels were observed. Negative relationship (p<0.01) was found between SUVA values and Chl-a levels. Among 9 HAA species, 4 brominated HAA were detected. As for BAA and DBAA (i.e. Br-HAAs), their yields (µg/L) were significant related (p<0.05) with DOC; In terms of BCAA and BDCAA (i.e. ClBr-HAAs), they were not only related with DOC, but also with UVA. These two results were quite different from DCAA and TCAA (Cl-HAAs), whose yields (µg/mg C) were only correlated with SUVA values, suggesting that precursors of Cl-HAA, Br-HAA and ClBr-HAA were different from each other, and their aromaticity/hydrophobicity may be in the order of Br-HAA

Effects of surface morphology on alginate adhesion: Molecular insights into membrane fouling based on XDLVO and DFT analysis.

While surface morphology is the key parameter affecting membrane performance, its exact roles on membrane fouling have not well unveiled. In this study, effects of membrane surface roughness on fouling caused by alginate adhesion were investigated by thermodynamic techniques of the extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) approach and density functional theory (DFT). The energy of a single typical alginate chain adhering to rough membrane surface was figured out to be 0.5-3.0 kJ/mol for the first time. Whereas, the related bending energy at typical bending angle was calculated to be over 13.0 kJ/mol based on DFT calculations. The big energy gap suggested that the alginate chain in solution would not change its configuration to fit membrane surface morphology, and tended to directly adhere to membrane surface. The thermodynamic analyses predicted that the direct adhesion pathway was favorable in energy when an alginate chain approaching to rough membrane surface. As a result, as compared to the smooth membrane, rough membrane corresponds to less alginate adhesion and adhesive fouling. Combination of XDLVO and DFT techniques provided not only molecular insights into membrane fouling, but also a new way for fouling research.