Enantioseparation of mandelic acid and substituted derivatives by high-performance liquid chromatography with hydroxypropyl-ß-cyclodextrin as chiral mobile additive and evaluation of inclusion complexes by molecular dynamics.

The enantioseparation and resolution mechanism of mandelic acid (MA), 4-methoxymandelic acid (MMA), and 4-propoxymandelic acid (PMA) were investigated by reversed-phase high-performance liquid chromatography (HPLC) with 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) as a chiral mobile-phase additive and molecular dynamics simulation. The suitable chromatographic conditions for the enantioseparation of MA, MMA, and PMA were obtained. Under the selected chromatographic conditions, these enantiomers could achieve baseline separation. The results of thermodynamic parameter analysis revealed that the main driven forces for the enantioseparation of MA, MMA, and PMA could be van der Waals forces and hydrogen-bonding interactions and the chromatographic retention of these chiral compounds was an enthalpy-driven process. The results of the molecular simulation revealed that their chiral resolution mechanism on HP-ß-CD was responsible for the formation of inclusion complexes of enantiomers with HP-ß-CD with different conformations and binding energies. And the binding energy of HP-ß-CD with (S)-isomer was larger than that with (R)-isomer, which is consistent with the experimental results of the first elution of (S)-isomer. Additionally, it is also confirmed that the interaction energies included the van der Waals energy (∆Evdw ), electrostatic energy (∆Eelec ), polar solvation energy, and SASA energy (∆Esasa ), and the separation factor (α) was closely connected with the disparity in the binding energies of optical isomers and HP-ß-CD complexes. Meanwhile, from molecular dynamics simulation, it can be found that the ∆(∆Ebinding ), (∆(∆Ebinding ) = ∆Ebinding,R - ∆Ebinding,S ) value was in order of MA-HP-ß-CD complex > MMA-HP-ß-CD complex > PMA-HP-ß-CD complex, which was consistent with the order of Δ(ΔG) values obtained from van't Hoff plot. This indicated that the molecular dynamics simulation has predictive function for chiral resolution.

Intermolecular interaction of fosinopril with bovine serum albumin (BSA): The multi-spectroscopic and computational investigation.

The intermolecular interaction of fosinopril, an angiotensin converting enzyme inhibitor with bovine serum albumin (BSA), has been investigated in physiological buffer (pH 7.4) by multi-spectroscopic methods and molecular docking technique. The results obtained from fluorescence and UV absorption spectroscopy revealed that the fluorescence quenching mechanism of BSA induced by fosinopril was mediated by the combined dynamic and static quenching, and the static quenching was dominant in this system. The binding constant, Kb , value was found to lie between 2.69 × 103 and 9.55 × 103  M-1 at experimental temperatures (293, 298, 303, and 308 K), implying the low or intermediate binding affinity between fosinopril and BSA. Competitive binding experiments with site markers (phenylbutazone and diazepam) suggested that fosinopril preferentially bound to the site I in sub-domain IIA on BSA, as evidenced by molecular docking analysis. The negative sign for enthalpy change (ΔH0 ) and entropy change (ΔS0 ) indicated that van der Waals force and hydrogen bonds played important roles in the fosinopril-BSA interaction, and 8-anilino-1-naphthalenesulfonate binding assay experiments offered evidence of the involvements of hydrophobic interactions. Moreover, spectroscopic results (synchronous fluorescence, 3-dimensional fluorescence, and Fourier transform infrared spectroscopy) indicated a slight conformational change in BSA upon fosinopril interaction.

Preparation and evaluation of a novel bonded imidazolium ionic liquid as stationary phase for gas chromatography.

1-Butyl-3-[(3-trimethoxysilyl)propyl]imidazolium chloride ionic liquid was synthesized and chemically modified onto the inner wall of a fused capillary column as a stationary phase for gas chromatography. The 1-butyl-3-[(3-trimethoxysilyl)propyl]imidazolium chloride ionic liquid bonded capillary column was evaluated in detail. The results revealed that the ionic liquid bonded capillary column exhibited high column efficiency of 1.08 × 104 plates/m, and good chromatographic separation selectivity (α) for polar and non-polar substances, and a good thermal stability between room temperature and 400°C. Moreover, the determination of thermodynamic parameters and the linear solvation energy relationship were further carried out. The results indicated that the chromatographic retention of each probe molecule on the ionic liquid bonded stationary phase was an enthalpy-driven process, and the system constants of the linear solvation energy relationship signified that the dispersion interaction, the hydrogen bonding acidity and hydrogen bonding basicity were dominant interactions between probes and stationary phase among five interactions during the chromatographic separation. However, the contribution of each specific interaction for the stationary phase is ranked as the dispersion interaction > the hydrogen bonding basicity > the hydrogen bonding acidity.

Combined spectroscopies and molecular docking approach to characterizing the binding interaction of enalapril with bovine serum albumin.

The binding interaction between bovine serum albumin (BSA) and enalapril (ENPL) at the imitated physiological conditions (pH = 7.4) was investigated using UV-vis absorption spectroscopy (UV-vis), fluorescence emission spectroscopy (FES), synchronous fluorescence spectroscopy (SFS), Fourier transform infrared spectroscopy (FT-IR), circular dichroism (CD) and molecular docking methods. It can be deduced from the experimental results from the steady-state fluorescence spectroscopic titration that the intrinsic BSA fluorescence quenching mechanism induced by ENPL is static quenching, based on the decrease in the BSA quenching constants in the presence of ENPL with increase in temperature and BSA quenching rates >1010  L mol-1  sec-1 . This result indicates that the ENPL-BSA complex is formed through an intermolecular interaction of ENPL with BSA. The main bonding forces for interaction of BSA and ENPL are van der Waal's forces and hydrogen bonding interaction based on negative values of Gibbs free energy change (ΔG0 ), enthalpic change (ΔH0 ) and entropic change (ΔS0 ). The binding of ENPL with BSA is an enthalpy-driven process due to |ΔH°| > |TΔS°| in the binding process. The results of competitive binding experiments and molecular docking confirm that ENPL binds in BSA sub-domain IIA (site I) and results in a slight change in BSA conformation, but BSA still retains its α-helical secondary structure.

Probing into the binding interaction between medroxyprogesterone acetate and bovine serum albumin (BSA): spectroscopic and molecular docking methods.

To further understand the mechanism of action and pharmacokinetics of medroxyprogesterone acetate (MPA), the binding interaction of MPA with bovine serum albumin (BSA) under simulated physiological conditions (pH 7.4) was studied using fluorescence emission spectroscopy, synchronous fluorescence spectroscopy, circular dichroism and molecular docking methods. The experimental results reveal that the fluorescence of BSA quenches due to the formation of MPA-BSA complex. The number of binding sites (n) and the binding constant for MPA-BSA complex are ~1 and 4.6 × 10(3)  M(-1) at 310 K, respectively. However, it can be concluded that the binding process of MPA with BSA is spontaneous and the main interaction forces between MPA and BSA are van der Waals force and hydrogen bonding interaction due to the negative values of ΔG(0) , ΔH(0) and ΔS(0) in the binding process of MPA with BSA. MPA prefers binding on the hydrophobic cavity in subdomain IIIA (site II'') of BSA resulting in a slight change in the conformation of BSA, but BSA retaining the α-helix structure. Copyright © 2016 John Wiley & Sons, Ltd.

Combined spectroscopies and molecular docking approach to characterizing the binding interaction between lisinopril and bovine serum albumin.

To further understand the mode of action and pharmacokinetics of lisinopril, the binding interaction of lisinopril with bovine serum albumin (BSA) under imitated physiological conditions (pH 7.4) was investigated using fluorescence emission spectroscopy, synchronous fluorescence spectroscopy, Fourier transform infrared spectroscopy (FTIR), circular dichroism (CD) and molecular docking methods. The results showed that the fluorescence quenching of BSA near 338 nm resulted from the formation of a lisinopril-BSA complex. The number of binding sites (n) for lisinopril binding on subdomain IIIA (site II) of BSA and the binding constant were ~ 1 and 2.04 × 10(4) M(-1), respectively, at 310 K. The binding of lisinopril to BSA induced a slight change in the conformation of BSA, which retained its α-helical structure. However, the binding of lisinopril with BSA was spontaneous and the main interaction forces involved were van der Waal's force and hydrogen bonding interaction as shown by the negative values of ΔG(0), ΔH(0) and ΔS(0) for the binding of lisinopril with BSA. It was concluded from the molecular docking results that the flexibility of lisinopril also played an important role in increasing the stability of the lisinopril-BSA complex.

A combined spectroscopic and molecular docking approach to characterize binding interaction of megestrol acetate with bovine serum albumin.

The binding interactions between megestrol acetate (MA) and bovine serum albumin (BSA) under simulated physiological conditions (pH 7.4) were investigated by fluorescence spectroscopy, circular dichroism and molecular modeling. The results revealed that the intrinsic fluorescence of BSA was quenched by MA due to formation of the MA-BSA complex, which was rationalized in terms of a static quenching procedure. The binding constant (Kb ) and number of binding sites (n) for MA binding to BSA were 2.8 × 10(5) L/mol at 310 K and about 1 respectively. However, the binding of MA with BSA was a spontaneous process due to the negative ∆G(0) in the binding process. The enthalpy change (∆H(0) ) and entropy change (∆S(0) ) were - 124.0 kJ/mol and -295.6 J/mol per K, respectively, indicating that the major interaction forces in the binding process of MA with BSA were van der Waals forces and hydrogen bonding. Based on the results of spectroscopic and molecular docking experiments, it can be deduced that MA inserts into the hydrophobic pocket located in subdomain IIIA (site II) of BSA. The binding of MA to BSA leads to a slight change in conformation of BSA but the BSA retained its secondary structure, while conformation of the MA has significant change after forming MA-BSA complex, suggesting that flexibility of the MA molecule supports the binding interaction of BSA with MA.

Characterization of intermolecular interaction between cyanidin-3-glucoside and bovine serum albumin: spectroscopic and molecular docking methods.

The intermolecular interaction between cyanidin-3-glucoside (Cy-3-G) and bovine serum albumin (BSA) was investigated using fluorescence, circular dichroism and molecular docking methods. The experimental results revealed that the fluorescence quenching of BSA at 338 nm by Cy-3-G resulted from the formation of Cy-3-G-BSA complex. The number of binding sites (n) for Cy-3-G binding on BSA was approximately equal to 1. The experimental and molecular docking results revealed that after binding Cy-3-G to BSA, Cy-3-G is closer to the Tyr residue than the Trp residue, the secondary structure of BSA almost not change, the binding process of Cy-3-G with BSA is spontaneous, and Cy-3-G can be inserted into the hydrophobic cavity of BSA (site II') in the binding process of Cy-3-G with BSA. Moreover, based on the sign and magnitude of the enthalpy and entropy changes (ΔH(0) = - 29.64 kcal/mol and ΔS(0) = - 69.51 cal/mol K) and the molecular docking results, it can be suggested that the main interaction forces of Cy-3-G with BSA are Van der Waals and hydrogen bonding interactions.

Comprehending the intermolecular interaction of dacomitinib with bovine serum albumin: experimental and theoretical approaches.

Dacomitinib (DAC), as a member of tyrosine kinase inhibitors is primarily used to treat non-small cell lung cancer. The intermolecular interaction between DAC and bovine serum albumin (BSA) was comprehended with the help of experiments and theoretical simulations. The outcomes indicated that DAC quenched the endogenous fluorescence of BSA through static quenching mode. In the binding process, DAC was preferentially inserted into the hydrophobic cavity of BSA subdomain IA (site III), and a fluorescence-free DAC-BSA complex with molar ratio of 1:1 was generated. The outcomes confirmed that DAC had a stronger affinity on BSA and the non-radiative energy transfer occurred in the combination process of two. And, it can be inferred from the outcomes of thermodynamic parameters and competition experiments with 8-aniline-1-naphthalenesulfonic acid (ANS) and D-(+)- sucrose that hydrogen bonds (H-bonds), van der Waals forces (vdW) and hydrophobic forces had a significant impact in inserting DAC into the hydrophobic cavity of BSA. The outcomes from multi-spectroscopic measurements that DAC could affect the secondary structure of BSA, that was, α-helix content decreased slightly from 51.0% to 49.7%. Moreover, the combination of DAC and BSA led to a reduction in the hydrophobicity of the microenvironment around tyrosine (Tyr) residues in BSA while had little influence on the microenvironment of around tryptophan (Trp) residues. The outcomes from molecular docking and molecular dynamics (MD) simulation further demonstrated the insertion of DAC into site III of BSA and hydrogen energy and van der Waals energy were the dominant energy of DAC-BSA stability. In addition, the influence of metal ions (Fe3+, Cu2+, Co2+, etc.) on the affinity of the system was explored.Communicated by Ramaswamy H. Sarma.

Insight into intermolecular binding mechanism of apatinib mesylate and human alpha-1-acid glycoprotein: combined multi-spectroscopic approaches with in silico.

Apatinib mesylate (APM), an oral tyrosine kinase inhibitor, has a good anti-tumor activity in the treatment of various cancers, particularly in advanced non-small cell lung cancer. In this study, the intermolecular binding mechanism between APM and human alpha-1-acid glycoprotein (HAG) was investigated by combining multi-spectroscopic approaches with in silico techniques. The findings revealed that APM gave rise to the fluorescence quenching of HAG by forming a ground-state complex between APM and HAG with a stoichiometric ratio of 1:1, and APM has a moderate affinity for HAG as the binding constant of APM and HAG of approximately 105 M-1, which was larger than the APM-HAG complex. The findings from thermodynamic parameter analysis indicated that the dominant driving forces for the formation of the APM-HAG complex were van der Waals forces, hydrogen bonding and hydrophobic interactions, which were also verified with site-probe studies and molecular docking. The findings from in silico study indicated that APM inserted into the opening of the hydrophobic cavity of HAG, leads to a slight conformational change in the HAG, which was verified by circular dichroism (CD) measurements, that was, the beta sheet level of HAG decreased. Additionally, the results of synchronous and 3D fluorescence spectroscopies confirmed the decline in hydrophobicity of the microenvironment around Trp and Tyr residues. Moreover, some common metal ions such as Cu2+, Mg2+, Fe3+, Ca2+, and Zn2+ could cause the alteration in the binding constant of APM with HAG, leading to the change in the efficacy of APM. It will be expected that these study findings are to provide useful information for further understanding pharmacokinetic and structural modifications of APM.Communicated by Ramaswamy H. Sarma.

In vitro investigation of the binding characteristics of dacomitinib to human α 1-acid glycoprotein: Multispectral and computational modeling.

Dacomitinib is a highly selective second-generation tyrosine kinase inhibitor that can irreversibly bind to tyrosine kinase and is mainly used in the treatment of lung cancer. The binding characteristics of dacomitinib with human α 1-acid glycoprotein (HAG) were analyzed by multispectral and computational simulation techniques. The fluorescence spectra showed that dacomitinib can quench the fluorescence of HAG by forming the HAG-dacomitinib complex with a molar ratio of 1:1 (static quenching). At the temperature similar to that of the human body, the affinity of dacomitinib to HAG (8.95 × 106 M-1) was much greater than that to BSA (3.39 × 104 M-1), indicating that dacomitinib will give priority to binding onto HAG. Thermodynamics parameters analysis and driving force competition experiments showed that hydrogen bonding and hydrophobic forces were the major sources for keeping the complex of HAG-dacomitinib stable. The experimental outcomes also showed that the binding of dacomitinib can lead to the loosening of the skeleton structure of HAG, which led to a slight change in the secondary structure, and also reduces the hydrophobicity of the microenvironment of Trp and Tyr residues. The binding sites of dacomitinib on HAG and the contribution of key amino acid residues to the binding reaction were determined by molecular docking and molecular dynamics (MD) simulation. In addition, it was found that there was a synergistic effect between dacomitinib and Mg2+ and Co2+ ions. Mg2+ and Co2+ could increase the Kb of dacomitinib to HAG and prolong the half-life of dacomitinib.

Comprehending the inhibition mechanism of indole-based bis-acylhydrazone compounds on α-glucosidase: Spectral and theoretical approaches.

Indole-based bis-acylhydrazone compounds can inhibit the activity of α-glucosidase and control the concentration of blood glucose. In this paper, the characteristics of three indole-based bis-acylhydrazone compounds with different inhibitory activities of α-glucosidase as well as the interaction with α-glucosidase were studied by experiments and computational simulation techniques. Enzyme kinetic and spectral experiments showed that the indole-based bis-acylhydrazone compounds were able to inhibit enzyme activity through mixed inhibition dominated by competitive inhibition, and during the binding reaction, indole-based bis-acylhydrazone compounds can quench the intrinsic fluorescence of α-glucosidase through static quenching and an aggregation of the indole-based bis-acylhydrazone with α-glucosidase produces a stable complex with a molar ratio of 1:1, and the combination of indole-based bis-acylhydrazone compounds could lead to slight change in the conformation of α-glucosidase. The theoretical simulation demonstrated that the stability of the complex systems was positively correlated with the inhibitory activity of indole-based bis-acylhydrazone compounds, and the indole-based bis-acylhydrazone compounds occupied the active site in the multi-ligand system, resulting in a significant decrease in the binding ability of starch to active amino acids. These results suggested that indole-based bis-acylhydrazone compound was expected to be a new type of α-glucosidase inhibitor.

Assessment on binding characteristics of ethiprole and a model protein bovine serum albumin (BSA) through various spectroscopic techniques integrated with computer simulation.

To investigate the binding characteristics of pesticide ethiprole (ETP) with serum albumin is of great significance for pathological analysis of pesticide poisoning, gene mutation, and clinical detection. In present work, the binding characteristics of ETP with a model protein BSA has been estimated by means of multi-spectroscopic approaches integrated with computer simulation. The outcomes testified that the intrinsic fluorescence of BSA was mainly quenched by ETP in a static quenching mode and the stable ETP-BSA complex with the stoichiometry of 1:1 and the binding constant of 6.81 × 103 M-1 (298 K) was produced. The outcomes revealed that ETP combined preferentially to the subdomain IIA (Site I) of BSA and caused the decline in the content of α-helix of BSA and the enhancement in the hydrophobicity of environment centered on Trp residues. The outcomes of experimental and theoretical studies provide the sufficient evidence about the driving forces for the complexation of ETP with BSA, which included van der Waals forces (vdW), hydrogen bonding (H-bonding) interaction, and hydrophobicity. Simultaneously, the theoretical calculation results also confirmed the existence of the significant changes in the physicochemical natures of ETP including molecular conformation, dipole moment, frontier orbital energy, and the atomic charge distribution, which was a responsible for the complexation with BSA.Communicated by Ramaswamy H. Sarma.

Elucidation of the interaction mechanism of olmutinib with human α-1 acid glycoprotein: insights from spectroscopic and molecular modeling studies.

Olmutinib, the third-generation tyrosine kinase inhibitor, is applied in treating non-small cell lung cancer (NSCLC). The aim of this study is to elucidate the interaction mechanism of olmutinib with human α-1 acid glycoprotein (HAG), an important carrier protein, by mean of multi-spectroscopic and molecular simulation techniques. Fluorescence spectral results confirmed that the fluorescence of this carrier protein can be quenched by olmutinib in the static quenching mode, and this anticancer drug possesses a moderate binding affinity on HAG. The evidence from thermodynamic analysis, replacement interaction with ANS and sucrose, and computational simulation results showed that hydrogen bonding, hydrophobic interactions, and van der Waals forces involved the olmutinib-HAG complexation process. The results from UV-vis, 3D fluorescence and synchronous fluorescence spectroscopy proved that binding anticancer drug olmutinib caused the alteration in the microenvironment around Trp residues. And, circular dichroism spectral results provided the support for the conformational alterations in the carrier protein. The data also proved that olmutinib preferably bound to the hydrophobic cavity of HAG and the binding distance between the two was 2.21 nm. In addition, it can be found that the presence of some metal ions such as Zn2+, Ca2+, Ni2+ and Cu2+ would exert a certain extent effect on the olmutinib-HAG complexation process.Communicated by Ramaswamy H. Sarma.

Exploring the binding behaviors between nisoldipine and bovine serum albumin as a model protein by the aid of multi-spectroscopic approaches and in silico.

Bovine serum albumin (BSA), a model protein was used to evaluate the binding behavior of nisoldipine and human serum albumin by a series of experiments and in silico in this article. The outcomes suggested that nisoldipine and BSA formed the nisoldipine-BSA complex with a molar ratio of 1:1, caused the fluorescence quenching of BSA, which quenching mechanism was attributable to static quenching. The binding constant of the nisoldipine-BSA complex was (1.3-3.0) × 104 M-1 at 298-310 K, indicating that nisoldipine on BSA protein had a moderate affinity. During the complexation of nisoldipine with BSA, nisoldipine can spontaneously insert into the site II (subdomain III A) of BSA and the distance of energy transfer from donor group in protein to acceptor group in nisoldipine was 3.21 nm, which led to the change in the hydrophobicity of the microenvironment surrounding Trp residues and in the secondary structure of BSA. Additionally, the findings also confirmed that the hydrogen bond and van der Waals force were responsible for forming the nisoldipine-BSA complex and the complexation process was a spontaneous exothermic process.Communicated by Ramaswamy H. Sarma.

Comprehending binding features between ibrutinib and Human Alpha-1 acid glycoprotein: Combined experimental approaches and theoretical simulations.

Human alpha-1 acidic glycoprotein (HAG) is one of the proteins widely present in the blood, and the level of HAG in patients with cancer and inflammation is significantly increased. As one of transport proteins in the blood, the ability of HAG to bind with a drug, especially alkaline drugs, affects significantly the drug content at the target site, which in turn affects the efficacy of the drug. In this study, the interaction mechanism between HAG and the first generation Bruton's tyrosine kinase (BTK) inhibitor namely ibrutinib was explored by a combination of multi-spectroscopic techniques and theoretical calculations. The findings revealed that the quenching and binding constants of the HAG-ibrutinib system both reduced as the temperature rose, demonstrating that ibrutinib quenched the intrinsic fluorescence of HAG in a static manner. It was confirmed that HAG and ibrutinib formed a 1:1 complex with moderate affinity due to the binding constant of around 105 M-1 and accompanied by Förster resonance energy transfer. It was verified by thermodynamic parameter analysis and competition assays as well as molecular simulation that the existence of hydrogen bonds, van der Waals forces, and hydrophobic forces in the complexation of HAG and ibrutinib.The findings from theoretical calculations including molecular docking and theoretical calculation simulation confirmed that ibrutinib bound to the barrel hydrophobic pocket of HAG with a binding energy of -41.9 kJ∙mol-1, and the the binding constant of around 105 M-1 and the contribution of each residue in the complexation of ibrutinib and HAG. Additionally, it can be confirmed that metal ions affected the binding interaction of ibrutinib with HAG, among them, some promoted binding while others inhibited it.

Exploring the binding characteristics of bovine serum albumin with tyrosine kinase inhibitor entrectinib: Multi-spectral analysis and theoretical calculation.

Entrectinib (ENB) is one of multi-target tyrosine kinase inhibitors, which is mainly used for treating neurotrophic tyrosine receptor kinase gene fusion positive solid tumors. The binding characteristics of ENB and bovine serum albumin (BSA) were studied by experiments and theoretical calculations. The steady-state fluorescence showed that ENB quenched the fluorescence of BSA through mixed quenching, and ENB was dominated by static quenching at low concentration. ENB and BSA had a moderate affinity, formed a complex with a stoichiometric ratio of 1:1 and the binding constant of about 105 M-1 at 298 K, and Förster non-radiative energy transfer occurs. According to the driving force competition experiment, thermodynamic parameter analysis and theoretical calculation, hydrogen bond, van der Waals force and hydrophobic force were the main factors affecting the stability of the ENB-BSA complex. Molecular docking and site markers competition showed that ENB spontaneously bound to the Site III of BSA so that ENB could make the skeleton of BSA loose, the spatial structure of BSA changed (α-helix decreased by 3.1%, random coil increased by 1.7%), and the microenvironment of Tyr and Trp residues changed. The existence of Co2+ metal ions can enhance the binding effect, thus prolonging the half-life of ENB in vivo, which may improve the efficacy of ENB, while Ca2+, Cu2+ and Mg2+ metal ions will reduce the efficacy of ENB.

Investigation on the binding behavior of human α1-acid glycoprotein with Janus Kinase inhibitor baricitinib: Multi-spectroscopic and molecular simulation methodologies.

Baricitinib is a Janus Kinase (JAK) inhibitor that is primarily used to treat moderately to severely active rheumatoid arthritis in adults and has recently been reported for the treatment of patients with severe COVID-19. This paper describes the investigation of the binding behavior of baricitinib to human α1-acid glycoprotein (HAG) employing a variety of spectroscopic techniques, molecular docking and dynamics simulations. Baricitinib can quench the fluorescence from amino acids in HAG through a mix of dynamic and static quenching, according to steady-state fluorescence and UV spectra observations, but it is mainly static quenching at low concentration. The binding constant (Kb) of baricitinib to HAG at 298 K was at the level of 104 M-1, indicating a moderate affinity of baricitinib to HAG. Hydrogen bonding and hydrophobic interactions conducted the main effect, according to thermodynamic characteristics, competition studies between ANS and sucrose, and molecular dynamics simulations. For the change in HAG conformation, the results of multiple spectra showed that baricitinib was able to alter the secondary structure of HAG as well as increase the polarity of the microenvironment around the Trp amino acid. Furthermore, the binding behavior of baricitinib to HAG was investigated by molecular docking and molecular dynamics simulations, which validated experimental results. Also explored is the influence of K+, Co2+, Ni2+, Ca2+, Fe3+, Zn2+, Mg2+ and Cu2+plasma on binding affinity.

Exploring the binding characteristics of febuxostat, an inhibitor of xanthine oxidase with calf thymus DNA: Multi-spectroscopic methodologies and molecular docking.

In this paper, the interacting characteristics of febuxostat (FBST), an inhibitor of xanthine oxidase for treating gout patients with hyperuricemia with calf thymus DNA (ctDNA) was investigated through multi-spectroscopic methodologies combined with theoretical calculation for understanding the interacting mode on ctDNA, affinity with ctDNA, interacting forces, as well as the alteration in the conformation of ctDNA after interacting FBST The experimental results demonstrated that interacting FBST with ctDNA formed 1:1 complex, the association constant was 913 M-1 at 298 K, suggesting the affinity of FBST on ctDNA was very weak, the interacting mode of FBST on ctDNA was groove binding, and it inserted into the minor groove with rich A-T region of ctDNA. Based on the results of the thermodynamic analysis and theoretical calculation, it can be inferred that the dominated interacting forces between FBST and ctDNA were van der Waals forces and hydrogen bond. And, interacting FBST with ctDNA was a spontaneous, enthalpy-driven, and exothermic process because of ΔG0 < 0, ΔH0 < 0, and |ΔH0| > T|ΔS0|. The results of the circular dichroism (CD) measurements indicated the conformation of ctDNA was weakly disturbed after interacting with FBST but still maintained B-conform. The studied results offer significant insight into further clarifying whether it has genotoxicity.

Exploring the inclusion interaction of estradiol with ß-CD and HP-ß-CD with the help of molecular dynamics simulation as well as multi-spectroscopic approaches.

The inclusion behaviors of estradiol with ß-CD and HP-ß-CD were characterized using molecular dynamics simulation combined with multi-spectroscopic approaches. The findings revealed that estradiol enclosed into the cavity of ß-CD and HP-ß-CD and produced the estradiol-ß-CD and estradiol-HP-ß-CD complexes with the stoichiometry of 1:1. The association constants of the estradiol-ß-CD and estradiol-HP-ß-CD complexes were 3.14 × 104 and 3.22 × 104 M-1 at 298 K, respectively, which declined with rising temperature. The analysis results of thermodynamic parameters confirmed that the dominate interaction forces were the hydrophobic and hydrogen-bonding interactions for stabilizing the estradiol-ß-CD complex, and were the hydrogen bonding interaction and van der Waals forces for stabilizing the estradiol-HP-ß-CD complex. Moreover, it was confirmed from the results of molecular modeling that estradiol inserted into the hydrophobic cavity of ß-CD and HP-ß-CD and form a stable estradiol-CD complexes. And, it is also observed that the phenyl moiety in estradiol is almost parallel to the central axis of ß-CD and HP-ß-CD, and the phenyl moiety was located on wider rim of ß-CD and HP-ß-CD.