In the crystal engineering area,it is important to clearly demonstrating the relationship of structure and certain functionality.Herein,we present the study of the relationship of structure with phosphorescent nature ...In the crystal engineering area,it is important to clearly demonstrating the relationship of structure and certain functionality.Herein,we present the study of the relationship of structure with phosphorescent nature for two new room temperature phosphorescence(RTP) coordination polymers(CPs).[Pb(FDA)(H_(2)O)](1) and [NH_(3)(CH_(3))NH_(2)(CH_(3))_(2)][Pb_(4)(FDA)_(5)](2),where H_(2) FDA is 2,5-furandicarboxylic acid,have been synthesized by solvothermal method using different solvents and Pb^(2+) sources and characterized by microanalysis,powderX-ray diffraction(PXRD),thermogravimetric(TG),IR and UV-vis spectra.The Pb^(2+)ions adopt bicapped triangle prism coordination sphere in 1 and 2,which are connected together via FDA^(2-) ligands into bilayer structure in 1 while pillared-layer framework in 2.The FDA^(2-) ligands show different bridging modes in 1 and 2,leading to distinct coordination interactions between Pb^(2+) ion and FDA^(2-) ligand in both CPs.Both 1 and 2 emit ligand-centered RTP due to the heavy atom of Pb^(2+) ion,with a lifetime and quantum yield of 0.62 ms and 14.9% in 1 versus 1.69 ms and 15.7% in 2.The emission peak shows significant redshift(79 nm) in 2 regarding 1,which arises from their distinction of coordination interactions between Pb^(2+) ion and FDA^(2-) ligand in both CPs.展开更多
The binding mode of the amino acid ethyl esters(vip) by 5 (2 carboxylphenyl) 10,15,20 triphenylporphyrinatozinc(Ⅱ)(host 1) was studied by means of 1H NMR spectra. The binding mode is the hydrogen bonding between th...The binding mode of the amino acid ethyl esters(vip) by 5 (2 carboxylphenyl) 10,15,20 triphenylporphyrinatozinc(Ⅱ)(host 1) was studied by means of 1H NMR spectra. The binding mode is the hydrogen bonding between the amino group of the vip and the carboxyl group of host 1 plus the coordination between the zinc atom of porphyrinatozinc(Ⅱ) and the carbonyl group of the vip. This is a novel binding mode of the metalloporphyrin to amino acid derivatives.展开更多
The binding mode and configuration of cisplatin with F-actin were studied on the basis of charge transfer bands of cisplatin-F-actin complex The binding mode was discussed on the basis of the results of LMCT.Raman and...The binding mode and configuration of cisplatin with F-actin were studied on the basis of charge transfer bands of cisplatin-F-actin complex The binding mode was discussed on the basis of the results of LMCT.Raman and fluorescence spectra.展开更多
Aggregation of the amyloid b-peptide (A b) into insoluble fibrils is a key pathologi-cal event in Alzheimers disease. Zn(II) ion induces significant Ab aggregation at nearly physio-logical concentrations in vitro. In ...Aggregation of the amyloid b-peptide (A b) into insoluble fibrils is a key pathologi-cal event in Alzheimers disease. Zn(II) ion induces significant Ab aggregation at nearly physio-logical concentrations in vitro. In order to explore the induce mechanism, the possible binding modes of Zn(II) in Ab peptide are studied by molecular modeling method. First, the Ab species containing 1,2,4 and 12 peptides are established respectively. And next a Zn(II) ion is manually hold the different sits of the Ab species based on the experimental data and subsequently the coordinate atom and number are assigned. Finally, the optimum binding site is found by the system energy minimization. Modeling results show that in soluble Zn(II) complex, Nt of imidazole ring of His14, O of carbonyl of main-chain, and two O of water occupy the four ligand positions of the tetrahedral complex; in the aggregation of Ab, the His13(Nt)-Zn(II)-His14(Nt) bridges are formed by Zn(II) cross-linking action. Therefore, the possible Zn(II) binding mode obtained by the studies will be helpful to reveal the form mechanism of pathogenic aggregates in brain.展开更多
The wide use of quaternary ammonium cationic surfactants(QACs)results in their release into the environment.Most surfactants have significant biotoxicity.However,existing toxicity data on QACs are still lacking,especi...The wide use of quaternary ammonium cationic surfactants(QACs)results in their release into the environment.Most surfactants have significant biotoxicity.However,existing toxicity data on QACs are still lacking,especially regarding the joint toxic effects of their mixtures.In computer simulation technology,molecular docking technology is commonly used for studying the mode of action of receptors docking with ligands.The research of QACs mixture interaction is relatively rare,and the binding mode of QACs is unknown.In this study,molecular docking technology was applied to explore the QAC binding mode,and the concentration addition(CA)and independent action(IA)models were applied for predicting the mixture toxicity.Firefly luciferase(FLuc)was used as a macromolecular receptor,and five typical QACs:benzalkonium bromide(BLB),tetraethylammonium bromide(TLB),N,N,N-trimethyl-1-tetradecyl ammonium bromide(CTE),tetrabutylammonium chloride(TAC),and dodecyltrimethylammonium chloride(DTC)were used as small molecule ligands.Molecular docking technology was used to investigate the binding mode of macromolecules and small molecules.The luminescence inhibitory effects of individual compounds and binary mixture on FLuc were determined by microplate toxicity assay of luciferase.The prediction of mixture toxicity was performed by CA and IA.The results showed that the relative toxicity follows:TLB<TAC<DTC<BLB<CTE.TLB and TAC showed the BS-Ⅱbinding mode,and BLB,CTE and DTC showed the BS-Ⅲbinding mode.The toxicity of compounds with binding mode BS-Ⅱwas less than that of those with BS-Ⅲbinding mode.Not all mixtures with the same binding mode could be predicted by CA model,and the IA model did not effectively predict the toxicity of mixtures with compound with different binding modes.The mixture toxicities of QACs with the same binding mode mostly presented additive and synergistic effects,while the mixture toxic effects of QACs with different binding modes presented additive or antagonistic effects.展开更多
The interaction of pinacyanol chloride (PC) with nucleic acids has been investigated by a series of experiments. Extensive hypochromism, appreciable peak shifts, isosbestic points and new peaks of the product of bindi...The interaction of pinacyanol chloride (PC) with nucleic acids has been investigated by a series of experiments. Extensive hypochromism, appreciable peak shifts, isosbestic points and new peaks of the product of binding to nucleic acids in the spectra were observed. They showed that the interaction between PC and nucleic acids occurred. The results from absorption spectra of DNA, DNA melting, electrophoresis and fluorescence polarization studies have indicated that PC binds to DNA in nonintercalative way. Consistent with the nonintercalation, the studies of fluorescence titration and absorption titration specified that the binding of PC to nucleic acids occurred by an outside stacking binding, in which nucleic acids served for acting templates. The fact that the new absorption peaks of bound PC at ca. 485 nm are just close to the absorption bands of H aggregate of PC at high concentrations without DNA further supports the outside stacking binding mode. In addition, other evidence indicated that the interaction between PC and nucleic acids is not purely electrostatic.展开更多
In order to analyze and explain the mechanism of the two small inhibitors （ADS-JI and ADS-J2） binding to HIV-1 gp41, a computational study is carried out to help identifying possible binding modes by docking these c...In order to analyze and explain the mechanism of the two small inhibitors （ADS-JI and ADS-J2） binding to HIV-1 gp41, a computational study is carried out to help identifying possible binding modes by docking these compounds onto the hydrophobic pocket on gp41 and characterize structures of binding complexes. The binding interactions of gp41-molecule and free energies of binding are obtained through molecular dynamics simulation and molecular mechanic/Poisson- Boitzmann surface area （ MM/PBSA ） calculation. Specific molecular interactions in the gp41-inhibitor complexes are identified. The present computational study complements the corresponding experimental investigation and helps establish a good starting point tbr further refinement of small molecular gp41 inhibitors.展开更多
Absorbance and fluorescence methods were used to study the interaction of - and A-tris (phenanthroline) nickel ( Ⅱ) complex with calf thymus DNA. It was con- cluded that -Ni(phen). preferentially bound to DNA. Espec...Absorbance and fluorescence methods were used to study the interaction of - and A-tris (phenanthroline) nickel ( Ⅱ) complex with calf thymus DNA. It was con- cluded that -Ni(phen). preferentially bound to DNA. Especially the fluorescence Scatchard plots were discussed for the binding of EthBr to calf thymus DNA in the presence of varying concentrations of the metal complex. Theses studies indicated that both the isomers bound to DNA by two acting types , namely , intercalative and electrostatic bound modes.展开更多
Three dinucleotides containing L-isonucleosides at 5＇-end were synthesized by an elegant phosphoramidite one-pot method. Their binding modes with HIV integrase were simulated and their anti-HIV activities in pseudoty...Three dinucleotides containing L-isonucleosides at 5＇-end were synthesized by an elegant phosphoramidite one-pot method. Their binding modes with HIV integrase were simulated and their anti-HIV activities in pseudotyped virus system were examined.展开更多
Natural product bufotenine(5)which could be isolated from Venenum Bufonis,has been widely used as a tool in central nervous system(CNS)studies.We present here its quaternary ammonium salt(6)which was synthesized with ...Natural product bufotenine(5)which could be isolated from Venenum Bufonis,has been widely used as a tool in central nervous system(CNS)studies.We present here its quaternary ammonium salt(6)which was synthesized with high yields using 5-benzyloxyindole as raw materials,and we firstly discover its analgesic effects in vivo.The analgesic evaluation showed that compounds 5 and 6 had stronger effects on the behavior of formalin induced pain in mice.Moreover,the combination of compound 6 and morphine has a synergistic effect.We intended to explain the molecular mechanism of this effect.Therefore,36 analgesic-related targets(including 15 G protein-coupled receptors,6 enzymes,13 ion channels,and 2 others)were systemically evaluated using reverse docking.The results indicate that bufotenine and its derivatives are closely related to acetyl cholinesterase(AChE)orα_(4)β_(2) nicotinic acetylcholine receptor(nAChR).This study provides practitioners a new insight of analgesic effects.展开更多
4-Hydrophenylpyruvate dioxygenase(HPPD),a key enzyme involved in tyrosine catabolism,has long been considered a promising target for herbicides and drugs.Several types of HPPD inhibitors have been developed as high-po...4-Hydrophenylpyruvate dioxygenase(HPPD),a key enzyme involved in tyrosine catabolism,has long been considered a promising target for herbicides and drugs.Several types of HPPD inhibitors have been developed as high-potency drugs or herbicides.Understanding the structural basis of the binding of these inhibitors with HPPD will be beneficial for the development of inhibitors containing novel scaffolds.However,only limited structural information regarding the binding of triketone and pyrazole derivatives with HPPD has been reported.Here,the crystal structures of HPPD complexed with inhibitors containing different scaffolds,including triketone,pyrazole,isoxazole,heterocyclic amide,and quinazolindione derivatives,were comprehensively analyzed.Detailed binding modes of isoxazole and heterocyclic amide derivatives with HPPD were first revealed,facilitating further structural optimization.The binding mode of compound 2 with HPPD suggests that both oxygen and nitrogen atoms can mediate coordination with the metal ion.These results will provide the structure-based rational design of novel HPPD inhibitors.展开更多
A new monometallic complex [Co(phen)_2tpphz]^(3+) (where tpphz is tetrapyrido [3,2-a:2′,3′-c:3″,2″-h:2′″,3′″-j] phenazine) was synthesized by the reaction of 5, 6-diamino-1,10-phenanthroline with [Co(phen)_2(p...A new monometallic complex [Co(phen)_2tpphz]^(3+) (where tpphz is tetrapyrido [3,2-a:2′,3′-c:3″,2″-h:2′″,3′″-j] phenazine) was synthesized by the reaction of 5, 6-diamino-1,10-phenanthroline with [Co(phen)_2(phendione)]^(3+). It was characterized by elemental analysis, molar conductivity, IR, ~1H NMR, ultraviolet and fluorescence spectroscopy. The interaction of the complex with DNA was also investigated. The complex shows the absorption hypochromicity, fluorescence enhancement, the specific viscosity increased when bound to calf thymus DNA. The cyclic voltammetry (CV) measurement showed a change in peak current with the addition of DNA. All the results provide the support for the intercalative binding mode of the mononuclear complex.展开更多
Inhibition of 11βHSD1 （11-beta-hydroxysteroid dehydrogenase 1） is a promising strategy in drug treatment of diabetes. Several 11βHSDI inhibitors have been proposed; however, their selectivity to 11βHSD1 over its ...Inhibition of 11βHSD1 （11-beta-hydroxysteroid dehydrogenase 1） is a promising strategy in drug treatment of diabetes. Several 11βHSDI inhibitors have been proposed; however, their selectivity to 11βHSD1 over its isozyme 11βHSD2 （11-beta-hydroxysteroid dehydrogenase 2） has not been fully reported. The authors sought to provide a short list of top potent and selective compounds along with their detailed binding modes and pharmacophore models, Molecular docking was used for initial screening of a set of 23 potent inhibitors reported by previous experimental studies. After that, selected promising entries were reassessed by molecular dynamics simulations, followed by hydrogen bond analysis. Pharmacophore models of all drug candidates and binding modes of some selected drugs were analyzed. Among the 23 compounds, only four inhibitors were identified as potent and selective drug candidates. Binding energies, 3D pharmacophores and binding modes of the four compounds with 11βHSDI are also discussed in detail in this study.展开更多
The binding of Co(bpy)2dppz3+ to calf thymus DNA was investigated by using absorption and emission spectroscopy,DNA melting techniques,cyclic voltammetry,viscosity and electro-phoresis measurements,where bpy is 2,2...The binding of Co(bpy)2dppz3+ to calf thymus DNA was investigated by using absorption and emission spectroscopy,DNA melting techniques,cyclic voltammetry,viscosity and electro-phoresis measurements,where bpy is 2,2'-bipyridyl,dppz is dipyrido[3,2-o:2',3'-c] phenazine.The binding compound shows absorption hypochromicity,fluorescence enhancement,and increasing of DNA melting temperature and the specific viscosity.CV measurement shows the shifts in oxidation-reduction potential and change in peak current with addition of DNA.The compound is also shown to be more efficient photosensitisers for strand breaks in plasmid DNA.展开更多
Developing orally available small molecule inhibitors of HIV-1 fusion has attracted significant interest over many years. Frey had recently reported several synthetic compounds which are experimentally shown to inhibi...Developing orally available small molecule inhibitors of HIV-1 fusion has attracted significant interest over many years. Frey had recently reported several synthetic compounds which are experimentally shown to inhibit cell-cell fusion in the low micromolar range. We carried out computational study to help identify possible binding modes by docking these compounds onto the hydrophobic pocket on gp41 and to characterize structures of binding complexes. The detailed gp41-molecule binding interactions and free energies of binding are obtained through mo- lecular dynamics simulation and MM-PBSA calculation. Specific molecular interactions in the gp41-inhibitor com- plexes are identified. The present computational study complements the corresponding experimental investigation and helps establish a good starting point for further refinement of small molecular gp41 inhibitors.展开更多
Various molecular docking software packages are available for modeling interactions between small molecules and proteins.However,there have been few reports of modeling the interactions between metal ions and metallop...Various molecular docking software packages are available for modeling interactions between small molecules and proteins.However,there have been few reports of modeling the interactions between metal ions and metalloproteins.In this study,the AutoDock package was employed to example docking into a di-iron binding protein,bacterioferritin.Each binding site of this protein was tested for docking with iron ions.Blind docking experiments showed that all docking conformations converged into two clusters,one for internal iron binding in sites within the metalloprotein and the other for external iron binding on the protein surface.Local docking experiments showed that there were significant differences between two internal iron binding sites.Docking at one site gave a reasonable root-mean-square deviation(RMSD) distribution with relatively low binding energy.Analysis of the binding mode quality for this site revealed that more than half of the docking conformations were categorized as having good binding geometry,while no good conformations were found for the other site.Further investigations indicated that coordinating water molecules contributed to the stability of binding geometries.This study provides an empirical approach towards the study of molecular docking in metalloproteins.展开更多
A novel complex [Co(phen)2HPlP]Cl3[phen= phenanethroline, HPIP=2-(2-hydroxyphenyl) imidazo [4,5-f][l,10]phenanethroline] has been synthesized and structurally characterized by elemental analysis, UV, IR and 1H NMR spe...A novel complex [Co(phen)2HPlP]Cl3[phen= phenanethroline, HPIP=2-(2-hydroxyphenyl) imidazo [4,5-f][l,10]phenanethroline] has been synthesized and structurally characterized by elemental analysis, UV, IR and 1H NMR spectroscopies. The interaction of the complex with calf thymus DNA (CT DNA) has been studied using absorption and emission spectroscopy, DNA melting techniques and cyclic voltammetry. The compound shows absorption hypochromicity, fluorescence enhancement and DNA melting temperature increment when binding to CT DNA. CV measurement shows a shift in reduction potential and a change in peak current with addition of DNA. These results prove mat the compound inserts into DNA base pairs. The shift of peak potential indicates the ion interaction mode between the complex and DNA. The binding constant of the compound to DNA is 4.37 × 104. The complex also seems to be an efficient photocleavage reagent.展开更多
Masks modified asphalt(MMA)provides a potential solution to pollution from discarded medical masks.Mixing temperature significantly affects storage stability and rheological performance of MMA.Traditional selection me...Masks modified asphalt(MMA)provides a potential solution to pollution from discarded medical masks.Mixing temperature significantly affects storage stability and rheological performance of MMA.Traditional selection method overly relies on trial-and-error experiment,neglecting the convenience offered by computational chemistry.Furthermore,previous literature lacks precise elucidation of MMA’s physical modification mechanism,especially concerning the binding mode and energy composition.To address these issues,the optimal mixing temperature for MMA was recommended based on molecular dynamics(MD).The rationality of recommended temperature was validated through laboratory tests,simultaneously investigating the impact of heating time.Fluorescence microscopy and multi-band spectroscopy were employed to acquire the microstructure.Binding modes in MMA were determined using binding sites exploration,evaluating the energy composition of each binding mode through quantum chemistry(QC).The interaction mechanism was explained based on surface properties of isolated molecules.Results indicated that 170℃was the recommended optimal mixing temperature derived from mixing free energy and Flory-Huggins interaction parameter.The fluctuations in softening point difference(DTR&B)and separation ratio(R_(S))concurrently tended towards stability,thereby validating the reliability of recommended temperature.Moreover,even after 72 h heating,MMA prepared at recommended temperature remained within a reasonable range concerning DTR&B,RS,and microscopic structure.Perpendicular,parallel,toroidal,and spherical modes emerged in MMA.Perpendicular and parallel modes exhibited the highest binding energy,while circular mode demonstrated the lowest.Binding energy is primarily governed by van der Waals interaction,attributed to the dominance of dispersion term on MMA’s molecular surface.Besides,due to the presence of polycyclic aromatic hydrocarbons in asphalt molecules,electrostatic interaction contributed to specific molecular bindings.展开更多
A Novel β-cyclodextrin dimer,2,2′-o-phenylenediseleno-bridgedbis（β-cyclodextrin）（2）,has been synthesized by reaction ofmono-[2-O-（p-tolylsulfonyl）]-β-cyclodextrin and poly（o-phenylenediselenide）.The comple...A Novel β-cyclodextrin dimer,2,2′-o-phenylenediseleno-bridgedbis（β-cyclodextrin）（2）,has been synthesized by reaction ofmono-[2-O-（p-tolylsulfonyl）]-β-cyclodextrin and poly（o-phenylenediselenide）.The complexation stability constants（Ks）and Gibbs free energy changes（-ΔG°）of dimer 2 with fourfluorescence dyes,that is,ammonium 8-anilino-1-naphthalene-sulfonate（ANS）,sodium 6-（p-toluidino）-2-naphthalenesul-fonate（TNS）,Acridine Red（AR）and Rhodamine B（RhB）have been determined in aqueous phosphate buffer solution(pH=7.2,0.1 mol·L-1at 25℃ by means of fluorescence spec-展开更多
Dinitrogen(N_(2)) is the major component of the atmosphere and many factors bring about dinitrogen inertness with low reactivity. Dinitrogen activation on metal complexes and clusters under ambient condition is the lo...Dinitrogen(N_(2)) is the major component of the atmosphere and many factors bring about dinitrogen inertness with low reactivity. Dinitrogen activation on metal complexes and clusters under ambient condition is the long-standing goal in the modern chemistry. In this review,an attempt has been made to survey the mechanistic aspects of dinitrogen activation and functionalization based on different coordination binding modes of dinitrogen. Our goal is to provide a comprehensive survey of dinitrogen activation in order to guide the relevant research in the future.展开更多
基金the National Natural Science Foundation of China (No.21901116)。
文摘In the crystal engineering area,it is important to clearly demonstrating the relationship of structure and certain functionality.Herein,we present the study of the relationship of structure with phosphorescent nature for two new room temperature phosphorescence(RTP) coordination polymers(CPs).[Pb(FDA)(H_(2)O)](1) and [NH_(3)(CH_(3))NH_(2)(CH_(3))_(2)][Pb_(4)(FDA)_(5)](2),where H_(2) FDA is 2,5-furandicarboxylic acid,have been synthesized by solvothermal method using different solvents and Pb^(2+) sources and characterized by microanalysis,powderX-ray diffraction(PXRD),thermogravimetric(TG),IR and UV-vis spectra.The Pb^(2+)ions adopt bicapped triangle prism coordination sphere in 1 and 2,which are connected together via FDA^(2-) ligands into bilayer structure in 1 while pillared-layer framework in 2.The FDA^(2-) ligands show different bridging modes in 1 and 2,leading to distinct coordination interactions between Pb^(2+) ion and FDA^(2-) ligand in both CPs.Both 1 and 2 emit ligand-centered RTP due to the heavy atom of Pb^(2+) ion,with a lifetime and quantum yield of 0.62 ms and 14.9% in 1 versus 1.69 ms and 15.7% in 2.The emission peak shows significant redshift(79 nm) in 2 regarding 1,which arises from their distinction of coordination interactions between Pb^(2+) ion and FDA^(2-) ligand in both CPs.
文摘The binding mode of the amino acid ethyl esters(vip) by 5 (2 carboxylphenyl) 10,15,20 triphenylporphyrinatozinc(Ⅱ)(host 1) was studied by means of 1H NMR spectra. The binding mode is the hydrogen bonding between the amino group of the vip and the carboxyl group of host 1 plus the coordination between the zinc atom of porphyrinatozinc(Ⅱ) and the carbonyl group of the vip. This is a novel binding mode of the metalloporphyrin to amino acid derivatives.
文摘The binding mode and configuration of cisplatin with F-actin were studied on the basis of charge transfer bands of cisplatin-F-actin complex The binding mode was discussed on the basis of the results of LMCT.Raman and fluorescence spectra.
基金This work was supported by the National Natural Science Foundation of China (Grant No. 20171031).
文摘Aggregation of the amyloid b-peptide (A b) into insoluble fibrils is a key pathologi-cal event in Alzheimers disease. Zn(II) ion induces significant Ab aggregation at nearly physio-logical concentrations in vitro. In order to explore the induce mechanism, the possible binding modes of Zn(II) in Ab peptide are studied by molecular modeling method. First, the Ab species containing 1,2,4 and 12 peptides are established respectively. And next a Zn(II) ion is manually hold the different sits of the Ab species based on the experimental data and subsequently the coordinate atom and number are assigned. Finally, the optimum binding site is found by the system energy minimization. Modeling results show that in soluble Zn(II) complex, Nt of imidazole ring of His14, O of carbonyl of main-chain, and two O of water occupy the four ligand positions of the tetrahedral complex; in the aggregation of Ab, the His13(Nt)-Zn(II)-His14(Nt) bridges are formed by Zn(II) cross-linking action. Therefore, the possible Zn(II) binding mode obtained by the studies will be helpful to reveal the form mechanism of pathogenic aggregates in brain.
基金Financially supported from the National Natural Science Foundation of China (21667013 and 21866010)Natural Science Foundation of Guangxi Province (2018GXNSFAA281156)+2 种基金Guilin Scientific Research and Technology Development Program (20180107-5)Special Funding for Guangxi’BaGui Scholar’Construction ProjectsGuangxi Key Laboratory of Environmental Pollution Control Theory and Technology for Science and Education Combined with Science and Technology Innovation Base。
文摘The wide use of quaternary ammonium cationic surfactants(QACs)results in their release into the environment.Most surfactants have significant biotoxicity.However,existing toxicity data on QACs are still lacking,especially regarding the joint toxic effects of their mixtures.In computer simulation technology,molecular docking technology is commonly used for studying the mode of action of receptors docking with ligands.The research of QACs mixture interaction is relatively rare,and the binding mode of QACs is unknown.In this study,molecular docking technology was applied to explore the QAC binding mode,and the concentration addition(CA)and independent action(IA)models were applied for predicting the mixture toxicity.Firefly luciferase(FLuc)was used as a macromolecular receptor,and five typical QACs:benzalkonium bromide(BLB),tetraethylammonium bromide(TLB),N,N,N-trimethyl-1-tetradecyl ammonium bromide(CTE),tetrabutylammonium chloride(TAC),and dodecyltrimethylammonium chloride(DTC)were used as small molecule ligands.Molecular docking technology was used to investigate the binding mode of macromolecules and small molecules.The luminescence inhibitory effects of individual compounds and binary mixture on FLuc were determined by microplate toxicity assay of luciferase.The prediction of mixture toxicity was performed by CA and IA.The results showed that the relative toxicity follows:TLB<TAC<DTC<BLB<CTE.TLB and TAC showed the BS-Ⅱbinding mode,and BLB,CTE and DTC showed the BS-Ⅲbinding mode.The toxicity of compounds with binding mode BS-Ⅱwas less than that of those with BS-Ⅲbinding mode.Not all mixtures with the same binding mode could be predicted by CA model,and the IA model did not effectively predict the toxicity of mixtures with compound with different binding modes.The mixture toxicities of QACs with the same binding mode mostly presented additive and synergistic effects,while the mixture toxic effects of QACs with different binding modes presented additive or antagonistic effects.
基金ProjectsupportedbytheNationalNaturalScienceFoundationofChina (No .2 9975 0 14 )andtheResearchofEducationDepartmentofGuangxiRegionalNationalAutonomyofChina
文摘The interaction of pinacyanol chloride (PC) with nucleic acids has been investigated by a series of experiments. Extensive hypochromism, appreciable peak shifts, isosbestic points and new peaks of the product of binding to nucleic acids in the spectra were observed. They showed that the interaction between PC and nucleic acids occurred. The results from absorption spectra of DNA, DNA melting, electrophoresis and fluorescence polarization studies have indicated that PC binds to DNA in nonintercalative way. Consistent with the nonintercalation, the studies of fluorescence titration and absorption titration specified that the binding of PC to nucleic acids occurred by an outside stacking binding, in which nucleic acids served for acting templates. The fact that the new absorption peaks of bound PC at ca. 485 nm are just close to the absorption bands of H aggregate of PC at high concentrations without DNA further supports the outside stacking binding mode. In addition, other evidence indicated that the interaction between PC and nucleic acids is not purely electrostatic.
基金The National Basic Research Program of China (973 Program) (No. 2007CB936300)
文摘In order to analyze and explain the mechanism of the two small inhibitors （ADS-JI and ADS-J2） binding to HIV-1 gp41, a computational study is carried out to help identifying possible binding modes by docking these compounds onto the hydrophobic pocket on gp41 and characterize structures of binding complexes. The binding interactions of gp41-molecule and free energies of binding are obtained through molecular dynamics simulation and molecular mechanic/Poisson- Boitzmann surface area （ MM/PBSA ） calculation. Specific molecular interactions in the gp41-inhibitor complexes are identified. The present computational study complements the corresponding experimental investigation and helps establish a good starting point tbr further refinement of small molecular gp41 inhibitors.
文摘Absorbance and fluorescence methods were used to study the interaction of - and A-tris (phenanthroline) nickel ( Ⅱ) complex with calf thymus DNA. It was con- cluded that -Ni(phen). preferentially bound to DNA. Especially the fluorescence Scatchard plots were discussed for the binding of EthBr to calf thymus DNA in the presence of varying concentrations of the metal complex. Theses studies indicated that both the isomers bound to DNA by two acting types , namely , intercalative and electrostatic bound modes.
基金National Natural Science Foundation of China (Grant No. 20832008 and 21002004)
文摘Three dinucleotides containing L-isonucleosides at 5＇-end were synthesized by an elegant phosphoramidite one-pot method. Their binding modes with HIV integrase were simulated and their anti-HIV activities in pseudotyped virus system were examined.
基金supported by National Natural Science Foundation of China(No.81973171)Postgraduate Research&Practice Innovation Program of Jiangsu Province(Nos.KYCX20J561,SJCX200533).
文摘Natural product bufotenine(5)which could be isolated from Venenum Bufonis,has been widely used as a tool in central nervous system(CNS)studies.We present here its quaternary ammonium salt(6)which was synthesized with high yields using 5-benzyloxyindole as raw materials,and we firstly discover its analgesic effects in vivo.The analgesic evaluation showed that compounds 5 and 6 had stronger effects on the behavior of formalin induced pain in mice.Moreover,the combination of compound 6 and morphine has a synergistic effect.We intended to explain the molecular mechanism of this effect.Therefore,36 analgesic-related targets(including 15 G protein-coupled receptors,6 enzymes,13 ion channels,and 2 others)were systemically evaluated using reverse docking.The results indicate that bufotenine and its derivatives are closely related to acetyl cholinesterase(AChE)orα_(4)β_(2) nicotinic acetylcholine receptor(nAChR).This study provides practitioners a new insight of analgesic effects.
基金funded in part by the National Key Research and Development Program of China(No.2021YFD1700100)National Natural Science Foundation of China(No.22007035,21837001).
文摘4-Hydrophenylpyruvate dioxygenase(HPPD),a key enzyme involved in tyrosine catabolism,has long been considered a promising target for herbicides and drugs.Several types of HPPD inhibitors have been developed as high-potency drugs or herbicides.Understanding the structural basis of the binding of these inhibitors with HPPD will be beneficial for the development of inhibitors containing novel scaffolds.However,only limited structural information regarding the binding of triketone and pyrazole derivatives with HPPD has been reported.Here,the crystal structures of HPPD complexed with inhibitors containing different scaffolds,including triketone,pyrazole,isoxazole,heterocyclic amide,and quinazolindione derivatives,were comprehensively analyzed.Detailed binding modes of isoxazole and heterocyclic amide derivatives with HPPD were first revealed,facilitating further structural optimization.The binding mode of compound 2 with HPPD suggests that both oxygen and nitrogen atoms can mediate coordination with the metal ion.These results will provide the structure-based rational design of novel HPPD inhibitors.
基金Supported by the National Natural Foundation of China and Shanxi Province.
文摘A new monometallic complex [Co(phen)_2tpphz]^(3+) (where tpphz is tetrapyrido [3,2-a:2′,3′-c:3″,2″-h:2′″,3′″-j] phenazine) was synthesized by the reaction of 5, 6-diamino-1,10-phenanthroline with [Co(phen)_2(phendione)]^(3+). It was characterized by elemental analysis, molar conductivity, IR, ~1H NMR, ultraviolet and fluorescence spectroscopy. The interaction of the complex with DNA was also investigated. The complex shows the absorption hypochromicity, fluorescence enhancement, the specific viscosity increased when bound to calf thymus DNA. The cyclic voltammetry (CV) measurement showed a change in peak current with the addition of DNA. All the results provide the support for the intercalative binding mode of the mononuclear complex.
文摘Inhibition of 11βHSD1 （11-beta-hydroxysteroid dehydrogenase 1） is a promising strategy in drug treatment of diabetes. Several 11βHSDI inhibitors have been proposed; however, their selectivity to 11βHSD1 over its isozyme 11βHSD2 （11-beta-hydroxysteroid dehydrogenase 2） has not been fully reported. The authors sought to provide a short list of top potent and selective compounds along with their detailed binding modes and pharmacophore models, Molecular docking was used for initial screening of a set of 23 potent inhibitors reported by previous experimental studies. After that, selected promising entries were reassessed by molecular dynamics simulations, followed by hydrogen bond analysis. Pharmacophore models of all drug candidates and binding modes of some selected drugs were analyzed. Among the 23 compounds, only four inhibitors were identified as potent and selective drug candidates. Binding energies, 3D pharmacophores and binding modes of the four compounds with 11βHSDI are also discussed in detail in this study.
基金Project supported by the National Natural Science Foundation of China.
文摘The binding of Co(bpy)2dppz3+ to calf thymus DNA was investigated by using absorption and emission spectroscopy,DNA melting techniques,cyclic voltammetry,viscosity and electro-phoresis measurements,where bpy is 2,2'-bipyridyl,dppz is dipyrido[3,2-o:2',3'-c] phenazine.The binding compound shows absorption hypochromicity,fluorescence enhancement,and increasing of DNA melting temperature and the specific viscosity.CV measurement shows the shifts in oxidation-reduction potential and change in peak current with addition of DNA.The compound is also shown to be more efficient photosensitisers for strand breaks in plasmid DNA.
文摘Developing orally available small molecule inhibitors of HIV-1 fusion has attracted significant interest over many years. Frey had recently reported several synthetic compounds which are experimentally shown to inhibit cell-cell fusion in the low micromolar range. We carried out computational study to help identify possible binding modes by docking these compounds onto the hydrophobic pocket on gp41 and to characterize structures of binding complexes. The detailed gp41-molecule binding interactions and free energies of binding are obtained through mo- lecular dynamics simulation and MM-PBSA calculation. Specific molecular interactions in the gp41-inhibitor com- plexes are identified. The present computational study complements the corresponding experimental investigation and helps establish a good starting point for further refinement of small molecular gp41 inhibitors.
基金Project (No. 2011-II-010) supported by the Fundamental Research Funds for the Central Universities,China
文摘Various molecular docking software packages are available for modeling interactions between small molecules and proteins.However,there have been few reports of modeling the interactions between metal ions and metalloproteins.In this study,the AutoDock package was employed to example docking into a di-iron binding protein,bacterioferritin.Each binding site of this protein was tested for docking with iron ions.Blind docking experiments showed that all docking conformations converged into two clusters,one for internal iron binding in sites within the metalloprotein and the other for external iron binding on the protein surface.Local docking experiments showed that there were significant differences between two internal iron binding sites.Docking at one site gave a reasonable root-mean-square deviation(RMSD) distribution with relatively low binding energy.Analysis of the binding mode quality for this site revealed that more than half of the docking conformations were categorized as having good binding geometry,while no good conformations were found for the other site.Further investigations indicated that coordinating water molecules contributed to the stability of binding geometries.This study provides an empirical approach towards the study of molecular docking in metalloproteins.
基金theNationalNaturalScienceFoundationofChina (No .2 0 1710 31)andtheNaturalScienceFoundationofShanxiProvince (No .2 0 0 110 0 7)
文摘A novel complex [Co(phen)2HPlP]Cl3[phen= phenanethroline, HPIP=2-(2-hydroxyphenyl) imidazo [4,5-f][l,10]phenanethroline] has been synthesized and structurally characterized by elemental analysis, UV, IR and 1H NMR spectroscopies. The interaction of the complex with calf thymus DNA (CT DNA) has been studied using absorption and emission spectroscopy, DNA melting techniques and cyclic voltammetry. The compound shows absorption hypochromicity, fluorescence enhancement and DNA melting temperature increment when binding to CT DNA. CV measurement shows a shift in reduction potential and a change in peak current with addition of DNA. These results prove mat the compound inserts into DNA base pairs. The shift of peak potential indicates the ion interaction mode between the complex and DNA. The binding constant of the compound to DNA is 4.37 × 104. The complex also seems to be an efficient photocleavage reagent.
基金supported by the National Natural Science Foundation of China(No.52178433 and 51878499).
文摘Masks modified asphalt(MMA)provides a potential solution to pollution from discarded medical masks.Mixing temperature significantly affects storage stability and rheological performance of MMA.Traditional selection method overly relies on trial-and-error experiment,neglecting the convenience offered by computational chemistry.Furthermore,previous literature lacks precise elucidation of MMA’s physical modification mechanism,especially concerning the binding mode and energy composition.To address these issues,the optimal mixing temperature for MMA was recommended based on molecular dynamics(MD).The rationality of recommended temperature was validated through laboratory tests,simultaneously investigating the impact of heating time.Fluorescence microscopy and multi-band spectroscopy were employed to acquire the microstructure.Binding modes in MMA were determined using binding sites exploration,evaluating the energy composition of each binding mode through quantum chemistry(QC).The interaction mechanism was explained based on surface properties of isolated molecules.Results indicated that 170℃was the recommended optimal mixing temperature derived from mixing free energy and Flory-Huggins interaction parameter.The fluctuations in softening point difference(DTR&B)and separation ratio(R_(S))concurrently tended towards stability,thereby validating the reliability of recommended temperature.Moreover,even after 72 h heating,MMA prepared at recommended temperature remained within a reasonable range concerning DTR&B,RS,and microscopic structure.Perpendicular,parallel,toroidal,and spherical modes emerged in MMA.Perpendicular and parallel modes exhibited the highest binding energy,while circular mode demonstrated the lowest.Binding energy is primarily governed by van der Waals interaction,attributed to the dominance of dispersion term on MMA’s molecular surface.Besides,due to the presence of polycyclic aromatic hydrocarbons in asphalt molecules,electrostatic interaction contributed to specific molecular bindings.
基金Project supported by the National Natural Science Foundation of China(Nos.29992590-8 and 20272028),the Natural Science Fund of Tianjin(No.013613511)and Special Fund for Doctoral Program from the Ministry of Education of China(No.20010055001).
文摘A Novel β-cyclodextrin dimer,2,2′-o-phenylenediseleno-bridgedbis（β-cyclodextrin）（2）,has been synthesized by reaction ofmono-[2-O-（p-tolylsulfonyl）]-β-cyclodextrin and poly（o-phenylenediselenide）.The complexation stability constants（Ks）and Gibbs free energy changes（-ΔG°）of dimer 2 with fourfluorescence dyes,that is,ammonium 8-anilino-1-naphthalene-sulfonate（ANS）,sodium 6-（p-toluidino）-2-naphthalenesul-fonate（TNS）,Acridine Red（AR）and Rhodamine B（RhB）have been determined in aqueous phosphate buffer solution(pH=7.2,0.1 mol·L-1at 25℃ by means of fluorescence spec-
基金National Natural Science Foundation of China(21902182,22033005 and 22038002)Fundamental Research Funds for the Central Universities(2022YQHH01)The support of Guangdong Provincial Key Laboratory of Catalysis(No.2020B121201002)is also acknowledged.
文摘Dinitrogen(N_(2)) is the major component of the atmosphere and many factors bring about dinitrogen inertness with low reactivity. Dinitrogen activation on metal complexes and clusters under ambient condition is the long-standing goal in the modern chemistry. In this review,an attempt has been made to survey the mechanistic aspects of dinitrogen activation and functionalization based on different coordination binding modes of dinitrogen. Our goal is to provide a comprehensive survey of dinitrogen activation in order to guide the relevant research in the future.
