Order Of Binding Constants Research Articles

Binding Affinity and Mechanism of Six PFAS with Human Serum Albumin: Insights from Multi-Spectroscopy, DFT and Molecular Dynamics Approaches.

Per- and Polyfluoroalkyl Substances (PFAS) bioaccumulate in the human body, presenting potential health risks and cellular toxicity. Their transport mechanisms and interactions with tissues and the circulatory system require further investigation. This study investigates the interaction mechanisms of six PFAS with Human Serum Albumin (HSA) using multi-spectroscopy, DFT and a molecular dynamics approach. Multi-spectral analysis shows that perfluorononanoic acid (PFNA) has the best binding capabilities with HSA. The order of binding constants (298 K) is as follows: "Perfluorononanoic Acid (PFNA, 7.81 × 106 L·mol-1) > Perfluoro-2,5-dimethyl-3,6-dioxanonanoic Acid (HFPO-TA, 3.70 × 106 L·mol-1) > Perfluorooctanoic Acid (PFOA, 2.27 × 105 L·mol-1) > Perfluoro-3,6,9-trioxadecanoic Acid (PFO3DA, 1.59 × 105 L·mol-1) > Perfluoroheptanoic Acid (PFHpA, 4.53 × 103 L·mol-1) > Dodecafluorosuberic Acid (DFSA, 1.52 × 103 L·mol-1)". Thermodynamic analysis suggests that PFNA and PFO3DA's interactions with HSA are exothermic, driven primarily by hydrogen bonds or van der Waals interactions. PFHpA, DFSA, PFOA, and HFPO-TA's interactions with HSA, on the other hand, are endothermic processes primarily driven by hydrophobic interactions. Competitive probe results show that the main HSA-PFAS binding site is in the HSA structure's subdomain IIA. These findings are also consistent with the findings of molecular docking. Molecular dynamics simulation (MD) analysis further shows that the lowest binding energy (-38.83 kcal/mol) is fund in the HSA-PFNA complex, indicating that PFNA binds more readily with HSA. Energy decomposition analysis also indicates that van der Waals and electrostatic interactions are the main forces for the HSA-PFAS complexes. Correlation analysis reveals that DFT quantum chemical descriptors related to electrostatic distribution and characteristics like ESP and ALIE are more representative in characterizing HSA-PFAS binding. This study sheds light on the interactions between HSA and PFAS. It guides health risk assessments and control strategies against PFAS, serving as a critical starting point for further public health research.

Investigating haloacetic acids - human serum albumin interactions: A comprehensive approach using multi-spectroscopy, DFT calculations, and molecular docking

Haloacetic acid (HAAs) has been shown in studies to be teratogenic and mutagenic. The toxicity of HAAs to macromolecules and their mechanism of action are still unclear. To further explore the potential impact of HAAs on organisms, this study used multi-spectroscopy, density functional theory (DFT), and molecular docking to analyze the characteristics and mechanisms of five typical HAAs interactions with HSA.Multispectral analysis indicates that the binding energies of the interactions between the five HAAs and HSA are weaker than other HSA-ligand complex systems. The order of binding constants at 298 K was as follows: DBAA (458.14 L mol−1) > TCAA (374.71 L mol−1) > DCAA (242.89 L mol−1) > MBAA (140.73 L mol−1) > MCAA (102.05 L mol−1). The quenching processes of the interactions between the five HAAs and HSA belong to static quenching, an exothermic reaction process. Hydrogen bonds and van der Waals forces are the main driving forces in the formation process of the HSA-HAAs complex.Molecular docking results indicate that TCAA, DBAA, and DCAA are more likely to bind with HSA. Correlation analysis based on DFT calculations reveals the intrinsic relationship between the chemical structural features of HAAs and the binding performance of HSA-HAAs. For the first time, the research discovered that among the quantum chemical descriptors, the highest ALIE maximum, the highest ESP maximum, and the maximum local electrophilic index f−(r) all correlate well with the HSA-HAAs binding constants. Their correlation coefficients are 0.83, 0.94, and -0.56, respectively, which can effectively predict the binding performance of HAAs with HSA.In-vitro toxicity experiments on LO2 cells show that within the concentration range of 0.002–10 mmol·L−1, MBAA, MCAA, and DBAA exhibit higher toxicity to normal human liver cells. In contrast, DCAA and TCAA show low or no toxicity.Through comprehensive research combining experimental and theoretical analysis, the mechanism of HSA-HAAs has been deeply revealed. This holds significant scientific value for assessing the environmental risks of HAAs and understanding their impact on biological activities.

Unveiling the versatility of novel oxacalix[4]arene platform: Systematic screening and comparative study on biological and antioxidant potency

Calixarene, a third generation supramolecule, have made their signature in biomedical applications through their unique physicochemical characteristics. Oxacalixarene, a class of heteracalixarene, is less explored in this respect though it has manifested its potentiality in earlier very few reports. Here we are reporting for the first time a systematic and comparative study of biological activities of different oxacalix[4]arene(OC) systems. For this purpose, very common functional groups that are available in biomacromolecules like phenolic OH (DHOC), amine (DNOC), ester (DEOC) and amide (DAOC) have been considered for functionalization to basic OC platform and the newly synthesized compounds are characterized with state-of-the-art spectroscopic techniques. Analysis of DNA cleavage, DNA binding, cell cytotoxicity and antioxidant activity studies nicely define the diversity of OC in DNA protection or DNA damage phenomena. DHOC is able to protect oxidative cleavage of DNA up to 47 % against Fenton reagents. The order of binding constant (∼105) is observed in the following order: DHOC (phenolic OH) > DNOC (amine) > DAOC (amide). The article also reports the antioxidant activity of oxacalix[4]arene compounds for the first time, observed by DPPH inhibition assay. All the compounds possess antioxidant activities. Among those, DHOC shows maximum antioxidant activity, comparable to standard antioxidant ascorbic acid at 100 µM (DPPH: 60 µM). Indeed, the observed structure-function relationship of OC systems can be tailored in the future to design molecules that are specifically targeted for biomedical applications.

Investigating sulfonamides - Human serum albumin interactions: A comprehensive approach using multi-spectroscopy, DFT calculations, and molecular docking

The environmental and health risks associated with sulfonamide antibiotics (SAs) are receiving increasing attention. Through multi-spectroscopy, density functional theory (DFT), and molecular docking, this study investigated the interaction features and mechanisms between six representative SAs and human serum albumin (HSA).Multi-spectroscopy analysis showed that the six SAs had significant binding capabilities with HSA. The order of binding constants at 298 K was as follows: sulfadoxine (SDX): 7.18 × 105 L mol−1 > sulfamethizole (SMT): 6.28 × 105 L mol−1 > sulfamerazine (SMR): 2.70 × 104 L mol−1 > sulfamonomethoxine (SMM): 2.54 × 104 L mol−1 > sulfamethazine (SMZ): 3.06 × 104 L mol−1 > sulfadimethoxine (SDM): 2.50 × 104 L mol−1. During the molecular docking process of the six SAs with HSA, the binding affinity range is from −7.4 kcal mol−1 to −8.6 kcal mol−1. Notably, the docking result of HSA-SDX reached the maximum of −8.6 kcal mol−1, indicating that SDX may possess the highest binding capacity to HSA. HSA-SDX binding, identified as a static quenching and exothermic process, is primarily driven by hydrogen bonds (H bonds) or van der Waals (vdW) interactions. The quenching processes of SMR/SMZ/SMM/SDX/SMT to HSA are a combination of dynamic and static quenching, indicating an endothermic reaction. Hydrophobic interactions are primarily accountable for SMR/SMZ/SMM/SDX/SMT and HSA binding. Competition binding results revealed that the primary HSA-SAs binding sites are in the subdomain IB of the HAS structure, consistent with the results of molecule docking.The correlation analysis based on DFT calculations revealed an inherent relationship between the structural chemical features of SAs and the binding performance of HSA-SAs. The dual descriptor (DD) and the electrophilic Fukui function were found to have a significant relationship (0.71 and −0.71, respectively) with the binding constants of HSA-SAs, predicting the binding performance of SAs and HSA. These insights have substantial scientific value for evaluating the environmental risks of SAs as well as understanding their impact on biological life activities.

Interaction of vanadium metal complexes with protein tyrosine phosphatase-1B enzyme along with identification of active site of enzyme by molecular modeling

Evidence from biochemical, genetic, and pharmacological studies strongly suggest that inhibition of Protein Tyrosine Phosphatase-1B (PTP-1B) enzyme could address both diabetes and obesity and thus making PTP-1B as an exciting target for drug development. It has been proven vanadyl compounds have an inhibitory action on PTP-1B. Owing to the importance of vanadium metal complexes in biology, we have synthesized and characterized various vanadium metal complexes using substituted acetyl acetones. The purpose of this investigation is to check the ability of these complexes to act as “inhibitors” on enzyme PTP-ases to reduce the serum glucose. Before performing inhibitory studies on PTP-1B enzyme, we thought it would be better to have studies on the interaction of these complexes with PTP-1B and to understand whether these metal complexes bind with protein (PTP-1B), if so, how strongly they bind, also to know the order of binding with different metal complexes. Fluorescence spectroscopy is used to study the interaction of the enzyme with vanadium metal complexes. The binding parameters Stern-Volmer constant (Ksv), Quenching rate constant (Kq), binding constant (Kb), No. of binding sites for the complex on the enzyme (n) are evaluated. From these results, it is concluded that various metal complexes do binds with PTP-1B enzyme. And we also evaluated the IC50 values for these compounds on interaction with the enzyme as a potent inhibitor. Other supporting studies like molecular modeling were also done to support the obtained results. The order of binding constants, IC50 values and results of molecular modeling concerning various vanadium complexes are in consistent with each other.

Electrochemical investigations of DNA-Intercalation potency of bisnitrophenoxy compounds with different alkyl chain lengths

In this study, the binding tendency of bisnitrophenoxy compounds (BN) having different methylene (–CH2–)n spacer groups (n = 8–11) with fish sperm double stranded deoxyribonucleic acid (dsDNA) was explored. Cyclic voltammetry (CV) was used to evaluate various kinetic and binding parameters (Ks,h, Do, Kb and binding site sizes). Performed electrochemical studies designated strong contact of these symmetric molecules with dsDNA in threading intercalation mode of binding. The number (n) of methylene spacer group in the molecular structure of bisnitrophenoxy compounds, e.g., BN-8 (1-nitro-4-(8-(4-nitrophenoxy)octyloxy)benzene, was observed to have a strong influence on their binding affinity. Decreased peak current values and positively shifted peak potentials recorded via cyclic voltammetry clearly depicted that bisnitrophenoxy compounds can intercalate with dsDNA. Results demonstrated the following order of binding constants; Kb (M−1): BN-8 (2.32 × 104) < BN-9 (5.73 × 104) < BN-10 (8.97 × 104) < BN-11 (17.34 × 104). The order of increasing binding sites from BN-8 (0.13) to BN-11 (1.38), revealed the maximum threading intercalation strength by bisnitrophenoxy compound having the longest methylene spacer (n = 11). Thermodynamic studies augmented the strong binding of BN-11 with dsDNA as compared to BN-8 because of the long-chain, –CH2- spacer in its structure. The spontaneity of dsDNA-binding was revealed by the negative ΔG values for interaction of all the compounds. Moreover, binding parameters from thermodynamic and kinetic studies also corresponded to the threading intercalation mode of interaction, which itself points to the potency of the envisioned drug-like molecules.

DNA/BSA Binding, Molecular Docking, Nuclease Activity and Cytotoxicity Studies of Hydrazide Based Schiff Base Complexes

A new series of hydrazide based Schiff base metal Cu(II)/Zn(II) complexes of the type [Cu(L1-L4)2] and [Zn(L1-L4)2] has been synthesized and characterized by various analytical and spectral techniques. The proposed geometry of metal complexes, square planar for Cu2+ ion and tetrahedral for Zn2+ ion was confirmed by the spectral and analytical results. DNA interaction with metal complexes was explored by spectral and molecular docking analysis. The results obtained indicates that Cu(II)/Zn(II) complexes interaction with DNA via an intercalative binding mode and its respective intrinsic binding constant (Kb) was found in the order of 7 &gt; 8 &gt; 5 &gt; 6 &gt; 3 &gt; 4 &gt; 1 &gt; 2. Further, similar interactions of these metal complexes with BSA were found in the same order of binding constant. Furthermore, the complexes showed moderate cleavage ability with pUC19 DNA. Cytotoxicity studies confirmed the biological importance of the Schiff base complexes.

Synthesis, characterization, and binding assessment with human serum albumin of three bipyridine lanthanide(III) complexes

In this work, the terbium(III), dysprosium(III), and ytterbium(III) complexes containing 2, 2′-bipyridine (bpy) ligand have been synthesized and characterized using CHN elemental analysis, FT-IR, UV–Vis and 1H-NMR techniques and their binding behavior with human serum albumin (HSA) was studied by UV–Vis, fluorescence and molecular docking examinations. The experimental data indicated that all three lanthanide complexes have high binding affinity to HSA with effective quenching of HSA fluorescence via static mechanism. The binding parameters, the type of interaction, the value of resonance energy transfer, and the binding distance between complexes and HSA were estimated from the analysis of fluorescence measurements and Förster theory. The thermodynamic parameters suggested that van der Waals interactions and hydrogen bonds play an important role in the binding mechanism. While, the energy transfer from HSA molecules to all these complexes occurs with high probability, the order of binding constants (BpyTb > BpyDy > BpyYb) represents the importance of radius of Ln3+ ion in the complex-HSA interaction. The results of molecular docking calculation and competitive experiments assessed site 3 of HSA, located in subdomain IB, as the most probable binding site for these ligands and also indicated the microenvironment residues around the bound mentioned complexes. The computational results kept in good agreement with experimental data.

Importance of aliphatic C–H hydrogen bonding on anion recognition

We have designed and synthesised new anion receptors 1 and 2, both of their C–H groups were at the α positions to carbonyl groups and further polarised by the attached polarising substituents. This enabled us to study hydrogen bonding donor ability of C–H bonds. The polarising substituents are electron withdrawing cyano group for host 1, while charged pyridinium group for host 2. As expected from charge effects, host 2 shows roughly an order of magnitude higher binding constants against various anion guests than those of receptor 1. Since the magnitude of polarisation change should be greatest for C–H group among various hydrogen bonding groups, this indicates the importance of C–H hydrogen bonding. In contrast, the relative order of binding constants was the same for both host 1 and 2. The order of association constants was found to be (CH3)2POO− > CH3COO− > C6H5COO− > Cl− > Br−. DFT calculation results were in good agreement with experimental binding constants and confirmed the importance of charged group substitution. In addition, receptor 1 showed the highest association constant for dimethyl phosphinate, which is implicated in many metabolic diseases.

Heavy metal detoxification by recombinant ferritin from Apostichopus japonicus

Ferritin fromApostichopus japonicasshowed better ability in heavy metal detoxification than horse spleen ferritin.

Voltammetric and impedance study of the binding of ferrocene derivatives to a sulfonated calix[6]arene host in aqueous solutions

This report describes the effect of host–guest complexation on the thermodynamic and kinetic parameters of ferrocene redox reactions in aqueous media. The formal potentials of the ferrocene/ferrocenium couples examined shifted to less positive values with increasing calixarene concentration, because of the formation of a 1:1 inclusion compound. The order of binding constants was cationic ferrocene≫non-charged ferrocene>anionic ferrocene. The oxidized form with a higher positive charge was bound more strongly to the host than was the corresponding reduced form. The result was contrary to that observed for β-cyclodextrin. The inclusion compounds formed by sulfonated calix[6]arene were greatly stabilized by an electrostatic interaction between the negatively charged host and cationic guest. Fast-scan voltammetric behavior suggested that inclusion-ejection processes practically attain equilibrium in the scan-rate range below 2 V s −1. Randles plots for the Faradaic impedance of the electrode reaction virtually comprised two nearly parallel straight lines with a small separation over the frequency range of 10 2−10 −3 Hz, indicating negligible chemical reaction impedance. As the host concentration increased, the mean diffusion coefficient of the (ferrocenylmethyl)trimethylammonium cation decreased inversely proportionally from 6.0×10 −6 cm 2 s −1 of the free ion to (2.1±0.2)×10 −6 cm 2 s −1 of the corresponding inclusion complex. The result of the impedance analysis suggests that the included guest exchanges no electrons directly with the electrode.

Synthesis of polymeric crown ethers and thermoregulated ion complexation effects

AbstractThe alkylation of catechol with (chloromethyl)styrene–divinylbenzene copolymer 1 produces the polymer‐bound catechol 2, which upon reaction with a series of polyglycol dihalides affords macrocyclic polymeric benzo crown ethers 3, in fair yields. The alkylation of polybenzylamine 4 with polyglycol dihalides leads to diazapolymeric pseudocrown ethers 5. The degree of conversion of the catechol groups into macrocyclic ether groups and the residual concentration of diol groups were estimated from elemental analysis, weight‐gain data, and the analysis of bis‐2,4‐dinitrophenyl derivatives of the residual diol groups. The ion‐coordination patterns for the polymeric crowns were determined using distribution and column techniques. Equilibrium distribution values in methanol in the temperature range 20–60°C, for the perchlorate, thiocyanate, or bromide salts, have led to the following conclusions: (1) The spheric recognition patterns, typical of crown ethers in solution, are fully reproduced in the polymeric analogs. (2) The order of binding constants is K &gt; Cs &gt; Na &gt; Li for polymeric benzocrown‐6 (3Hc) and benzocrown‐8 (3Hd) and K &gt; Cs ≅ Na &gt; Li for polymeric benzocrown‐4 (3Ha) and benzocrown‐5 (3Hb). (3) The polymers bind alkali metal cations by two mechanisms: the residual diol groups by ion exchange mechanism, and the crown groups by a salt‐coordination mechanism; the second mechanism is temperature‐dependent. Consequently, a thermal increase of 40°C causes a spontaneous elution, by “thermal shock,” and a three‐fold increase in the eluent of the original ion concentration. (4) Quantitative release of all the bound salt is observed.