Binding Mechanism of Nitro Musks to Human Lactoferrin: Multispectral Approach, Docking and Molecular Dynamics Simulation.

Nitro musks are highly bioaccumulative and potentially carcinogenic, commonly used as additives in fabric softeners, detergents, and other household products. Furthermore, these substances have been detected in breast milk and human adipose tissue, posing a risk of direct exposure to pregnant women and infants. Human lactoferrin (HLF) is abundant in colostrum, and plays an important role in the non-specific immune system of the human body. In this study, the mechanisms of action of two nitro musk compounds, typical examples of synthetic musks, with HLF were investigated using molecular docking, dynamics simulation and multispectral methods. The fluorescence findings demonstrated that nitro musks quenched the intrinsic fluorescence of human lactoferrin through static quenching. Thermodynamic analysis of the binding parameters suggested that hydrophobic interactions acted synergistically in the formation of the complex. Moreover, analyses utilizing multispectral techniques, such as Fourier transform infrared (FTIR) spectroscopy, validated that the microenvironment and structure of HLF were altered in the presence of nitro musks. Finally, molecular docking and molecular dynamics simulations were employed to explore the specific binding mode of nitro musks with HLF and to assess the stability of the complex. These findings may provide a reference for assessing health risks to pregnant women and infants.

Interactions between polycyclic musks and human lactoferrin: Multi-spectroscopic methods and docking simulation.

Galaxolide (1,3,4,6,7,8-hexahydro-4,6,6,7,8-hexamethylcyclopenta-γ-2-benzopyrane; HHCB) and Tonalide (7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene; AHTN) are "pseudo-persistent" pollutants that can cause DNA damage, endocrine disruption, organ toxicity, and reproductive toxicity in humans. HHCB and AHTN are readily enriched in breast milk, so exposure of infants to HHCB and AHTN is of concern. Here, the molecular mechanisms through which HHCB and AHTN interact with human lactoferrin (HLF) are investigated using computational simulations and spectroscopic methods to identify indirectly how HHCB and AHTN may harm infants. Molecular docking and kinetic simulation studies indicated that HHCB and AHTN can interact with and alter the secondary HLF structure. The fluorescence quenching of HLF by HHCB, AHTN was static with the forming of HLF-HHCB, HLF-AHTN complex, and accompanied by non-radiative energy transfer and that 1:1 complexes form through interaction forces. Time-resolved fluorescence spectroscopy indicated that binding to small molecules does not markedly change the HLF fluorescence lifetime. Three-dimensional fluorescence spectroscopy indicated that HHCB and AHTN alter the peptide chain backbone structure of HLF. Ultraviolet-visible absorption spectroscopy, simultaneous fluorescence spectroscopy, Fourier-transform infrared spectroscopy, and circular dichroism spectroscopy indicated that HHCB and AHTN change the secondary HLF conformation. Antimicrobial activity experiments indicated that polycyclic musks decrease lactoferrin activity and interact with HLF. These results improve our understanding of the mechanisms involved in the toxicities of polycyclic musks bound to HLF at the molecular level and provide theoretical support for mother-and-child health risk assessments.

Interaction between laccase and diethylstilbestrol based on multispectral and chromatography analyses.

Diethylstilbestrol (DES) is a synthetic form of oestrogen that does not easily degrade in the environment and can be harmful to human health. Herein, the mechanism of the interaction between laccase and DES was investigated by various spectroscopic means and high-performance liquid chromatography (HPLC). The results of fluorescence experiments showed that the quenching of intrinsic fluorescence of laccase by DES was due to a static quenching, forming a binding site. According to the Förster non-radiative energy transfer theory (FRET), the action distance R0 between DES and laccase was 4.708 nm, r was 5.81 nm, and the energy transfer efficiency E was 22.08%, respectively. Both UV-Vis absorption spectra and FT-IR spectra indicated changes in the conformation and surroundings of the enzyme and changed in the secondary structure of laccase. Multispectral synthesis showed that the interaction of laccase with DES caused a change in the secondary structure of laccase. The degradation experiments showed that laccase could degrade DES, and the DES content decreased with time. This study provides a new theoretical basis and experimental method for further research on the reaction mechanism of the laccase degradation of DES. It may also provide a reference basis for human biological and environmental safety evaluations.

Insight on the microscopic binding mechanism of bisphenol compounds (BPs) with transthyretin (TTR) based on multi-spectroscopic methods and computational simulations.

Thyroid hormones are involved in numerous physiological processes as regulators of metabolism, regulating organ growth, and mental state. Bisphenol compounds (BPs) are recognized as chemicals that interfere with endocrine balance. Because BPs have a similar structure to thyroxine, they can compete for binding to thyroid protein and disrupt the normal physiological activity of the thyroid system. In this study, three typical bisphenol compounds were selected to explore the interaction between BPs and TTR by computer simulations and multi-spectroscopic methods. The results revealed that BPs quenched the endogenous fluorescence of TTR via the combination of static quenching and non-radiative energy transfer, and the van der Waals forces and hydrogen bonding played a synergistic role in the binding process of BPs and TTR. Furthermore, the three-dimensional fluorescence spectroscopy, UV-vis spectroscopy, and Fourier transform infrared (FT-IR) spectroscopy, which were employed to determine the conformation of protein, revealed that binding of BPs with TTR could induce conformational changes in TTR. In addition, the binding sites and the residues surrounding the BPs within the TTR were determined through molecular docking and molecular dynamics simulation. Therefore, this work provides new insights into the interaction between BPs and TTR to evaluate the potential toxicity of BPs.

Exploring the toxic effects and mechanism of methoxylated polybrominated diphenyl ethers (MeO-PBDEs) on thyroxine-binding globulin (TBG): Synergy between spectroscopic and computations.

The interaction mechanism between thyroxine-binding globulin (TBG) and three methoxylated polybrominated diphenyl ethers (MeO-PBDEs) was analyzed by steady-state fluorescence, ultraviolet-visible (UV-visible) spectroscopy, circular dichroism (CD), molecular docking and molecular dynamics simulation methods. The results of the molecular docking technique revealed that 2'-MeO-BDE-3, 5-MeO-BDE-47, and 3-MeO-BDE-100 combined with TBG at the active site. The steady-state fluorescence spectra displayed that MeO-PBDEs quenched the endogenous fluorescence of TBG through static quenching mechanism, and complex formation between MeO-PBDEs and TBG was further indicated by UV-vis spectroscopy. The thermodynamic quantities showed that the binding process is spontaneous, and the major forces responsible for the binding are hydrogen bonding and hydrophobic interactions, which are consistent with the results of molecular docking to a certain extent. The results of CD confirmed that the secondary structure of TBG was changed after combining with MeO-PBDEs. The dynamic simulation results illustrated that the protein structure is more compact and changes in the secondary structure of TBG after binding to MeO-PBDEs. Additionally, we also utilized the molecular mechanics/Poisson-Boltzmann surface area (MM-PBSA) method to analyze the binding free energy of TBG and MeO-PBDEs. The results suggest that van der Waals force plays an essential role in the combination.

Fluorescent kinetics combined with fourth-order calibration for the determination of diclofenac sodium in environmental water.

A method that combines five-way fluorescence kinetics with fourth-order calibration for interference-free quantification of diclofenac sodium in river water was proposed and tested. Traditional fluorescence methods may not be suitable for such measurements since the fluorescence properties of the analyte are highly dependent on both pH and irradiation time in situ. In the method considered here, a five-way emission-excitation-time-pH data array was obtained from the samples by introducing the pH level and irradiation time as two extra modes. Then the data array was resolved by three fourth-order calibration algorithms: alternating fitting weighted residue quinquelinear decomposition (AFWRQQLD), five-way parallel factor analysis (five-PARAFAC), and alternating quinquelinear decomposition (AQQLD). The average recoveries and detection limits calculated for diclofenac sodium in a set of analyte-spiked river water samples using AFWRQQLD, five-PARAFAC, and AQQLD were 97.2 ± 3.2% and 1.9 ng mL-1, 96.8 ± 3.0% and 4.0 ng mL-1, and 92.6 ± 2.7% and 2.5 ng mL-1, respectively. A study of other figures of merit, statistical analysis, an elliptical joint confidence region test, and a t-test were additionally carried out to validate the analytical performance of the proposed method in detail. The results demonstrated that this new method required only two steps (fluorescence measurement and algorithm analysis) to determine the analyte concentration. It could therefore provide the basis for developing novel reliable and sensitive approaches for the accurate detection of pharmaceutical pollutants with unstable fluorescence properties in real complex matrices such as environmental water samples. Graphical Abstract ᅟ.

Multi-spectroscopic and molecular dynamics simulations investigation of the binding mechanism of polybrominated diphenyl ethers to hen egg white lysozyme.

Three PBDEs (BDE25, BDE47, and BDE154) were selected to investigate the interactions between PBDEs and hen egg white lysozyme (HEWL) by molecular modeling, fluorescence spectroscopy, and FT-IR spectra. The docking results showed that hydrogen bonds were formed between BDE25 and residue TRP63 and between BDE47 and TRP63 with bond lengths of 2.178 Å and 2.146 Å, respectively. The molecular dynamics simulations indicated that van der Waals forces played a predominant role in the binding of three PBDEs to HEWL. The observed fluorescence quenching can be attributed to the formation of complexes between HEWL and PBDEs, and the quenching mechanism is a static quenching. According to Förster's non-radiative energy transfer theory, the binding distances r were < 7 nm, indicating a high probability of energy transfer from HEWL to the three PBDEs. The synchronous fluorescence showed that the emission maximum wavelength of tryptophan (TRP) residues emerged a red-shift. FT-IR spectra indicated that BDE25, BDE47 and BDE154 induced the α-helix percentage of HEWL decreased from 32.70% ± 1.64% to 28.27% ± 1.41%, 27.50% ± 1.38% and 29.78% ± 1.49%, respectively, whereas the percentage of random coil increased from 26.67% ± 1.33% to 27.60% ± 1.38%, 29.18% ± 1.46% and 30.59% ± 1.53%, respectively.

The mechanism and conformational changes of polybrominated diphenyl ethers to TTR by fluorescence spectroscopy, molecular simulation, and quantum chemistry.

Extracellular deposition of transthyretin (TTR) as amorphous aggregates and amyloid fibrils is genetically and biochemically linked to a number of human diseases characterized by nervous system or organ dysfunction. The interaction mechanism of TTR with different polybrominated diphenyl ethers (PBDEs), such as BDE49, BDE108 and BDE155, was studied by a variety of spectroscopic techniques and computer simulations. The results of steady-state fluorescence, time-resolved fluorescence and UV-Vis spectroscopy showed that BDE49, BDE108 and BDE155 could cause fluorescence quenching of TTR, which was mainly static quenching and Förster's resonance energy transfer. Molecular docking and thermodynamic analysis further confirmed that the binding of PBDEs to TTR was mainly hydrophobic and formed a cation-π with the residue LYS15 in the TTR. Quantum chemistry and energy contribution analysis of the ligand and residue LYS15 revealed that the binding was mainly due to the cation-π formed by the C atom of the benzene ring and the polar residue LYS15 (NH3+) of TTR. Moreover, the energy contributions of BDE49, BDE108 and BDE155 to the residue LYS15 (B Chain and D Chain) are relatively large which enables their combination to be more stable. Therefore, the residue LYS15 in TTR plays a crucial role in various physiological activities in the human body.

Binding of hydroxylated polybrominated diphenyl ethers with human serum albumin: Spectroscopic characterization and molecular modeling.

Three hydroxylated polybrominated diphenyl ethers (OH-PBDEs), 3-OH-BDE-47, 5-OH-BDE-47, and 6-OH-BDE-47, were selected to investigate the interactions between OH-PBDEs with human serum albumin (HSA) under physiological conditions. The observed fluorescence quenching can be attributed to the formation of complexes between HSA and OH-PBDEs. The thermodynamic parameters at different temperatures indicate that the binding was caused by hydrophobic forces and hydrogen bonds. Molecular modeling and three-dimensional fluorescence spectrum showed conformational and microenvironmental changes in HSA. Circular dichroism analysis showed that the addition of OH-PBDEs changed the conformation of HSA with a minor reduction in α-helix content and increase in ß-sheet content. Furthermore, binding distance r between the donor (HSA) and acceptor (three OH-PBDEs) calculated using Förster's nonradiative energy transfer theory was <7 nm; therefore, the quenching mechanisms for the binding between HSA and OH-PBDEs involve static quenching and energy transfer. Combined with molecular dynamics simulations, the binding free energies (ΔGbind ) were calculated using molecular mechanics/Poisson - Boltzmann surface area method, and the crucial residues in HSA were identified.

[Study of the Detection of Histidine Based on "On-Off" Fluorescence Probe of Carbon Dots].

An new type of switch "On-Off" fluorescence probe was constructed based on fluorescence carbon dots as a novel strategy to analyze trace histidine(His) which was proposed for the first time. In water solution with pH 7.6, the fluorescence of CDs was quenched with Ru3+ due to the formation of ground state compound through electrostatic attraction, and the system was thus "turned-off". The fluorescence intensity of CDs was "turned-on" due to the competition between His and Ru towards the surface of CDs. The effect of critical parameters including pH, buffer solutions, reaction temperature and time needed to grow the fluorescence intensity of CDs was studied. Results show thatin water solution with pH 7.6, and when the temperature was between 20~25 ℃, the fluorescence intensity of the released CDs displayed a linear relationship in the range of (6.5~219.3)×10-6 mol·L-1 of captopril. Lower limit of detection for His, at the signal-to-noise ratio of 3/(3δ), was 2.15×10-6 mol·L-1. The methodology was successfully applied for the determination of His in Compound Amino Acid Injections, with the RSD≤2.07%, and the recovery rate was between 95.7%～102.4%. The result of the experiment was satisfactory. On the one hand, the excellent optical character CDs was acted as "On-Off" fluorescence probe, which could be extent the application of CDs, on the other hand, the excellent performance of the proposed fluorescence probe shows that this method possesses the potential for practical application.

Analysis of Binding Modes between Three Perfluorosulfonates and GPER Based on Computational Simulation and Multiple Spectral Methods.

Perfluorinated compounds (PFCs) belong to a significant category of global environmental pollutants. Investigating the toxicological effects of PFCs within biological systems is of critical significance in various disciplines such as life sciences, environmental science, chemistry, and ecotoxicology. In this study, under simulated human physiological conditions (pH = 7.4), a combination of multiple spectroscopic techniques and computational simulations was employed to investigate the impact of perfluorinated compounds (PFCs) on the G protein-coupled estrogen receptor (GPER). Additionally, the research focused on exploring the binding modes and toxicological mechanisms between PFCs and GPER at the molecular level. All three perfluorinated sulfonic acids (PFSAs) can induce quenching of GPER fluorescence through static quenching and non-radiative energy transfer. Steady-state fluorescence calculations at different temperatures revealed apparent binding constants in the order of 106, confirming a strong binding affinity between the three PFSAs and GPER. Molecular docking studies indicated that the binding sites of PFSAs are located within the largest hydrophobic cavity in the head region of GPER, where they can engage in hydrogen bonding and hydrophobic interactions with amino acid residues within the cavity. Fourier transform infrared spectroscopy, three-dimensional fluorescence, and molecular dynamics simulations collectively indicate that proteins become more stable upon binding with small molecules. There is an overall increase in hydrophobicity, and alterations in the secondary structure of the protein are observed. This study deepens the comprehension of the effects of PFCs on the endocrine system, aiding in evaluating their potential impact on human health. It provides a basis for policy-making and environmental management while also offering insights for developing new pollution monitoring methods and drug therapies.

Exploring the mechanism of interaction between TBG and halogenated thiophenols: Insights from fluorescence analysis and molecular simulation.

Thyroxine-binding globulin (TBG) plays a vital role in regulating metabolism, growth, organ differentiation, and energy homeostasis, exerting significant effects in various key metabolic pathways. Halogenated thiophenols (HTPs) exhibit high toxicity and harmfulness to organisms, and numerous studies have demonstrated their thyroid-disrupting effects. To understand the mechanism of action of HTPs on TBG, a combination of competitive binding experiments, multiple fluorescence spectroscopy techniques, molecular docking, and molecular simulations was employed to investigate the binding mechanism and identify the binding site. The competition binding assay between HTPs and ANS confirmed the competition of HTPs with thyroid hormone T4 for the active site of TBG, resulting in changes in the TBG microenvironment upon the binding of HTPs to the active site. Key amino acid residues involved in the binding process of HTPs and TBG were further investigated through residue energy decomposition. The distribution of high-energy contributing residues was determined. Analysis of root-mean-square deviation (RMSD) demonstrated the stability of the HTPs-TBG complex. These findings confirm the toxic mechanism of HTPs in thyroid disruption, providing a fundamental reference for accurately assessing the ecological risk of pollutants and human health. Providing mechanistic insights into how HTPS causes thyroid diseases.

The molecular mechanisms of TRß receptor interaction with polychlorinated biphenyls: A multispectral and computational exploration.

The thyroid hormone (TH) system is susceptible to the toxic effects of polychlorinated biphenyls (PCBs). Pollutants may disrupt the TH system by binding to serum TH transport proteins or interacting with thyroid hormone receptors (TRs) in target cells. However, the molecular mechanism of interaction with the Thyroid Hormone Receptor Beta (TRß) is not fully understood. This study employed fluorescence, UV-visible absorption, three-dimensional fluorescence, and Fourier-transform infrared spectroscopy, along with molecular docking and molecular dynamics simulations, to investigate the interaction between TRß and PCBs. Moreover, molecular docking and fluorescence resonance energy transfer (FRET) findings suggest that TRß and PCBs underwent resonance energy transfer consistent with Förster's theory. The root mean square deviation (RMSD) and docking outcomes indicate that the TRß-PCB29 complex exhibited optimal structural stability. Thus, the study concludes that integrating spectroscopic data with molecular docking is essential for a comprehensive analysis. Further analysis of intermolecular interactions using quantum chemistry and reduced density gradient analysis (RDG) analysis revealed that van der Waals forces are the primary drivers of PCBs to TRß.

Anthracene-based dual channel donor-acceptor triazine-containing covalent organic frameworks for superior photoelectrochemical sensing.

Covalent organic frameworks (COFs) exhibit excellent photoelectrically active structures and serve as channels for photon capture and charge carrier transport. However, their relatively high charge-carrier recombination rates and lack of specific recognition sites limit their application in photoelectrochemical sensing. This paper reports a functionalized donor-acceptor (D-A) COF comprising electron-rich polycyclic aromatic moieties and electron-deficient triazines (Tz) incorporating boronic acid through ligand exchange. The number of aromatic rings in the polycyclic aromatic moiety is crucial for establishing an efficient D-A system within COF. In the absence of an external electron donor, the anthracene-based COF exhibited a five-fold enhancement in photocurrent compared to the naphthalene-based COF. The resulting anthracene-based D-A COF exhibited enhanced orbital overlap and electron push-pull interactions, facilitating more effective charge separation. Furthermore, introducing boronic acid enabled the selective enrichment of low-concentration external electron donors, such as dopamine, in the inner Helmholtz plane. This ingenious approach establishes a unique dual-channel D-A system that allows direct measurement of dopamine in serum. Under optimized conditions, the test platform achieves good correspondence for dopamine at 1 to 100 nM and 0.5 to 100 µM with a detecting limit of 0.36 nM (3σ/S, n = 11). This strategy introduces a novel dimension to photoelectrochemical sensing, focusing on the effect of spatial separation between the external electron donor and the photoelectrode interface that intricately shapes the behavior and enhances the performance of the photoelectric system.

Investigations on the binding properties of hydroxylated polybrominated diphenyl ethers with lysozyme using the multispectral techniques and molecular modeling.

As a kind of phenolic chemical with endocrine disrupting potency, hydroxylated polybrominated diphenyl ethers (OH-PBDEs) cause a latent threat to human health from their residue in the environment. Their binding efficiency with lysozyme (LYSO) was studied by molecular simulation combined with fluorescence, UV-vis absorption and circular dichroism (CD), so as to assess their toxicity at the molecular level. Molecular docking data indicate that van der Waals force is the principal interaction force between OH-PBDEs and LYSO. The binding site for 5'-OH-BDE-25 in LYSO is ascertained as the active site, which interaction with the TRP63 and TRP108 residues of LYSO to take shape a strong face-to-face stacked rank (F-shaped). Both 4'-OH-BDE-99 and 3'-OH-BDE-154 display a certain degree of deviation from the active site. Nevertheless, their F-shaped interaction with TRP63 conduce to bind LYSO and stabilize the docking conformation. Combined with dynamics simulation and spectral analysis, the secondary structure of LYSO can be induced by the three kinds of OH-PBDEs. CD spectrum shows that the combination of LYSO and OH-PBDEs will make α- Helix content increased. The combination of OH-PBDEs and LYSO touch upon a static quenching mechanism as a result of steady state fluorescence. The energy decomposition analysis exhibited that LYSO-OH-PBDEs binding site was stable by van der Waals and hydrophobic interaction. As enzyme activity experiments demonstrate that OH-PBDEs can inhibit the activity of LYSO, which is helpful to clarify the molecular toxicity mechanism of OH-PBDEs.

Thyroid hormone transporters binding affinity of methoxypoly chlorinated biphenyls: Insights from molecular simulations and fluorescence competitive binding experiment.

Triiodothyronine (T3) and thyroxine (T4) are essential for regulating cell metabolic rate and promoting the development and differentiation of brain tissue, especially in fetuses and newborns. In particular, it has been proved that MeO-PCBs have high binding to thyroid hormone transporters and can competitively bind to thyroid carrier proteins, thus destroying the transport of the thyroid hormone. Fluorescence competition binding experiments and docking results showed that the binding affinity decreased with the increase in number of chlorine atoms of MeO-PCBs. The interaction mechanism of MeO-PCBs with thyroid transporter (TTR) and thyroid binding globulin (TBG) was compared by computational simulation and the binding free energies were calculated by the molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) method. Electrostatic potential analysis, Hirshfeld surface analysis and electron density difference maps confirmed the existence of electrostatic interactions. Secondly, noncovalent interaction (NCI) analysis further indicated that the main driving force for the combination of MeO-PCBs to TTR and TBG were electrostatic interaction and van der Waals interaction. The conformational changes of the protein after binding were studied by a molecular dynamic simulation.

A QSAR study of environmental estrogens based on a novel variable selection method.

A large number of descriptors were employed to characterize the molecular structure of 53 natural, synthetic, and environmental chemicals which are suspected of disrupting endocrine functions by mimicking or antagonizing natural hormones and may thus pose a serious threat to the health of humans and wildlife. In this work, a robust quantitative structure-activity relationship (QSAR) model with a novel variable selection method has been proposed for the effective estrogens. The variable selection method is based on variable interaction (VSMVI) with leave-multiple-out cross validation (LMOCV) to select the best subset. During variable selection, model construction and assessment, the Organization for Economic Co-operation and Development (OECD) principles for regulation of QSAR acceptability were fully considered, such as using an unambiguous multiple-linear regression (MLR) algorithm to build the model, using several validation methods to assessment the performance of the model, giving the define of applicability domain and analyzing the outliers with the results of molecular docking. The performance of the QSAR model indicates that the VSMVI is an effective, feasible and practical tool for rapid screening of the best subset from large molecular descriptors.

Combined toxicity of the mixtures of phenol and aniline derivatives to Vibrio qinghaiensis sp.-Q67.

To test whether the dose addition and independent action models can predict the combined toxicity of the mixtures of phenol and aniline derivatives, six phenolic and two aniline derivatives were selected as the test components. The inhibition toxicity of the derivatives and their mixtures to Vibrio qinghaiensis sp.-Q67 indicated that all dose-response relationships could be effectively described by the Weibull function with correlation coefficients greater than 0.99. The combined toxicity of two equivalent-effect concentration ratio mixtures and eight uniform design concentration ratio mixtures could be predicted successfully by the dose addition model within 95% confidence intervals. However, it was also well predicted by the independent action model, especially at lower concentrations.

Investigating the interaction between three perfluorinated carboxylic acids and the G protein-coupled estrogen receptor: spectroscopic analyses and computational simulations.

In this paper, perfluorinated compounds (PFCs), such as perfluorobutyric acid (PFBA), perfluorooctanoic acid (PFOA) and perfluorododecanoic acid (PFDoA), were selected as typical representatives of perfluorinated carboxylic acids (PFCAs) to study the effects of PFCAs on the G protein-coupled estrogen receptor (GPER). The interaction mechanism of the three types of PFCAs with the GPER was investigated using steady-state fluorescence spectroscopy, ultraviolet-visible spectroscopy, three-dimensional fluorescence spectroscopy, and Fourier transform infrared spectroscopy combined with molecular docking and molecular dynamics simulations. Among these techniques, steady-state fluorescence and ultraviolet-visible spectroscopic analyses showed that PFBA, PFOA and PFDoA quenched the endogenous GPER fluorescence by combined dynamic and static quenching and non-radiative energy transfer. The binding constants (Ka) of PFCAs on the GPER were all larger than 105 L mol-1, indicating that their affinity for the GPER was strong. Fourier transform infrared spectroscopy and three-dimensional fluorescence showed that the secondary structure of the GPER changed after binding to PFCAs. Thermodynamic analysis showed ΔG < 0, which indicated that the interaction between the GPER and PFCAs was spontaneous. For the binding of PFBA and PFOA to the GPER, ΔH > 0 and ΔS > 0, indicating that the interaction was mainly driven by hydrophobic forces; for the binding of PFDoA to the GPER, ΔH < 0 and ΔS < 0, suggesting that van der Waals force and hydrogen bonding were the main interaction forces. Molecular dynamics simulations suggested that the stability of the GPER-PFCA complexes was higher than that of the free GPER, and also that the structure and hydrophobicity of the GPER changed after binding to PFCAs. Molecular docking analysis showed that all three PFCAs could form hydrogen bonds with the GPER, which improved the stability of the complex.

Study on the binding characteristics of hydroxylated polybrominated diphenyl ethers and thyroid transporters using the multispectral technique and computational simulation.

Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) are a class of toxic environmental pollutants that are persistent, bioaccumulative, and difficult to degrade. Their structure is very similar to the thyroid hormone (T4) and uses the body's thyroid transporter (TTR) binding to interfere with the endocrine balance, disrupting the body's normal physiological activity. According to Fourier transform infrared spectroscopy and dynamics simulation of do_dssp module analysis, there are three kinds of OH-PBDEs that can induce TTR secondary structural changes. Fluorescence spectra and UV-Vis spectra show that for the three kinds of OH-PBDEs for TTR, the main methods of quenching are static quenching and non-radiative energy transfer. According to thermodynamic analysis, ΔG < 0, ΔH > 0, and ΔS > 0 combine to show that the hydrophobic interaction is the main driving force of the combination. From the molecular docking analysis, it was found that 4'-hydroxy-2,2',4,5'- tetrabromodiphenyl ether (4'-OH-BDE49) and 4 hydroxy-2,2',3,4',5,6,6'- heptabromodiphenyl ether (4-OH-BDE188) had a cationic-π interaction with TTR, whereas 4 hydroxy-2,2',3,4,5,5',6- heptabromodiphenyl ether (4-OH-BDE187) was bonded to TTR by hydrogen bonds to form stable complexes. In this paper, we highlight the consistency of spectroscopic experiments and computer simulations so as to provide a reliable analytical method for the toxicological properties of small molecule contaminants.