Colorimetric and fluorescence sensing of anions using thiourea based coumarin receptors

Thiourea-containing coumarins 1, 2 have been designed and synthesized via reaction of 6-aminomethylcoumarin and the corresponding isothiocyanates. Their anion-binding ability has been examined using UV-vis, fluorescence and ¹H NMR. The anion recognition takes place through charge neutral thiourea receptor sites with concomitant fluorescence quenching of the coumarin moiety with 1 showing a strong binding to C₆H₅COO⁻ over F⁻ with a distinct change in color.     

A benzthiazole-based simple receptor in fluorescence sensing of biotin ester and urea

A benzthiazole-based receptor 1 has been designed and synthesized for recognition of biotin ester and urea in CHCl₃ containing 1% CH₃CN. The receptor binds biotin methyl ester and urea with moderate binding constant values and shows significant increase in emission of benzthiazole motif. The emission characteristics of 1 upon complexation clearly distinguishes biotin methyl ester and urea from thiourea and N,N′-dimethylurea. Characterization and sensing properties of the receptor 1 were evaluated by ¹H NMR, UV-vis, and fluorescence spectroscopic methods.     

药物-蛋白结合作用的分析方法研究

综述了定性和定量研究药物-蛋白结合作用的部分方法,包括色谱、毛细管电泳、核磁共振光谱、质谱等方法及一些传统方法如平衡透析、超滤等方法,并讨论了各自的优点和局限性。     

癸二酸—二苯并—18—冠—6共聚物的络合特性

以溶剂萃取的方法研究了癸二酸-二苯并-18-冠-6共聚物（CEP－1）的离子络合效率和选择性，测定了苦味酸盐在水与二氯甲烷中的平衡浓度，求得了草取平衡常数，并与其小分子模型物及酚醛树脂型冠醚聚合物（CEP-2）作了对比。结果表明，酮型冠醚聚合物虽然在离子萃取能力上有所下降，但其对K 却显示出更大的选择性。     

中性红与小牛胸腺DNA相互作用机理的电化学和紫外-可见光谱研究

静电作用;嵌插作用;中性红与小牛胸腺DNA相互作用机理的电化学和紫外-可见光谱研究     

Metal(II) complexes of bioactive aminonaphthoquinone-based ligand: synthesis,characterization and BSA binding,DNA binding/cleavage,and cytotoxicity studies

An aminonaphthoquinone ligand, L, and its metal complexes of general formula [MLCl₂] {M = Co(II), Ni(II), Cu(II) and Zn(II)} have been synthesized and characterized by analytical and spectral techniques. Tetrahedral geometry has been assigned to Ni(II) and Zn(II) complexes and square planar geometry to Co(II) and Cu(II) complexes on the basis of electronic spectral and magnetic susceptibility data. The binding of complexes with bovine serum albumin (BSA) is relatively stronger than that of free ligand and alters the conformation of the protein molecule. Interaction of these complexes with CT-DNA has been investigated using UV-Vis and fluorescence quenching experiments, which show that the complexes bind strongly to DNA through intercalative mode of binding (K_app 10⁵ M^?1). Molecular docking studies reiterate the mode of binding of these compounds with DNA, proposed by spectral studies. The ligand and its complexes cleave plasmid DNA pUC18 to nicked (Form II) and linear (Form III) forms in the presence of H₂O₂ oxidant. The in vitro cytotoxicity screening shows that Cu(II) complex is more potent against MCF-7 cells and Zn(II) complex exhibits marked cytotoxicity against A-549 cells equal to that of cisplatin. Cell imaging studies suggested apoptosis mode of cell death in these two chosen cell lines.     

Oxovanadium complex as potential nucleic acid binder

DNA binding study of a vanadium(V) complex, Oxo-chloro-bis-N-phenylbenzohydroxamto-vanadium(V), derived from N-phenylbenzohydroxamic acid(PBHA) form a violet color complex with vanadium (V) in presence of hydrochloric acid is performed using absorption, fluorescence and viscometric techniques. The binding parameters of the PBHA-V(V) complex using calf thymus DNA (ct-DNA) and torula yeast RNA (t-RNA) have been determined. The complex shows the ability of cooperatively minor groove binding with ct-DNA as indicated by remarkable hyperchromicity and a blue shift of the absorption spectra. Quenching of metal complex calculation was carried out with Stern-Volmer equation and K_sv was found to be 2.32 ± 0.18 × 10⁴ M^?1, while in the case of t-RNA, enhancement is observed and that means the compound was not able to displace the Ethidium Bromide(EB)-t-RNA complex. Molecular docking was also applied to predict the mode of interaction of the hydroxamic acid with ct-DNA and t-RNA. DNA binding results of the complex are compared with those of the parent ligand.     

Anion and cation binding by a new indole/pyridine/amine-based ion-pair receptor

A new ion-pair receptor bis(3-bromoindol-2-ylmethyl)(2-pyridylmethyl)amine (1) was synthesized and studied for its anion and cation binding behavior using ESI-MS and ¹H NMR spectroscopy. Among halides, 1 exhibits the strongest binding with Cl⁻ to form a 1:1 adduct (K_a = 1042 ± 21 in CD₃CN). Among alkali metal ions, Li⁺ and Na⁺ showed the strongest binding in the formation of a 1·M⁺ complex. The simultaneous binding of Cl⁻ and Li⁺ to 1 was confirmed by ¹H NMR titration of a 1:1 mixture of 1 and Cl⁻ with LiPF₆ in 83:17 v/v mixture of CDCl₃ and DMSO-d₆. DFT-optimized structures of 1·Cl⁻, 1·Li⁺, and 1·Li⁺·Cl⁻ are consistent with the chemical shift changes observed in ¹H NMR studies.     

多吡啶钌配合物作为DNA结构探针的研究

本文对多吡啶钌配合物作为DNA荧光或结构探针的研究背景、研究技术及其特点、钌配合物与DNA的键合模式及其结合力大小的影响因素、钌配合物与DNA键合的异构选择性及不同键合速率、非放射性核酸标记及DNA分子光开关等方面进行了简要述评     

中空纤维液相微萃取同时快速研究6种黄酮类药物与蛋白的结合特性

将中空纤维液相微萃取(HFLPME)-高效液相色谱法(HPLC)与Bjerrum或Scatchard法结合,同时、快速研究了6种黄酮类化合物的蛋白结合率、结合常数和结合位点数.最佳萃取条件为:聚偏氟乙烯作为有机溶剂载体,正庚醇作为萃取相,搅拌速度900 r/min,萃取时间2h.在最佳条件下,二氢杨梅素、杨梅素、槲皮素...     

Ligand–Receptor Binding Affinities from Saturation Transfer Difference (STD) NMR Spectroscopy: The Binding Isotherm of STD Initial Growth Rates

The direct evaluation of dissociation constants (K_D) from the variation of saturation transfer difference (STD) NMR spectroscopy values with the receptor–ligand ratio is not feasible due to the complex dependence of STD intensities on the spectral properties of the observed signals. Indirect evaluation, by competition experiments, allows the determination of K_D, as long as a ligand of known affinity is available for the protein under study. Herein, we present a novel protocol based on STD NMR spectroscopy for the direct measurements of receptor–ligand dissociation constants (K_D) from single‐ligand titration experiments. The influence of several experimental factors on STD values has been studied in detail, confirming the marked impact on standard determinations of protein–ligand affinities by STD NMR spectroscopy. These factors, namely, STD saturation time, ligand residence time in the complex, and the intensity of the signal, affect the accumulation of saturation in the free ligand by processes closely related to fast protein–ligand rebinding and longitudinal relaxation of the ligand signals. The proposed method avoids the dependence of the magnitudes of ligand STD signals at a given saturation time on spurious factors by constructing the binding isotherms using the initial growth rates of the STD amplification factors, in a similar way to the use of NOE growing rates to estimate cross relaxation rates for distance evaluations. Herein, it is demonstrated that the effects of these factors are cancelled out by analyzing the protein–ligand association curve using STD values at the limit of zero saturation time, when virtually no ligand rebinding or relaxation takes place. The approach is validated for two well‐studied protein–ligand systems: the binding of the saccharides GlcNAc and GlcNAcβ1,4GlcNAc (chitobiose) to the wheat germ agglutinin (WGA) lectin, and the interaction of the amino acid L ‐tryptophan to bovine serum albumin (BSA). In all cases, the experimental K_D measured under different experimental conditions converged to the thermodynamic values. The proposed protocol allows accurate determinations of protein–ligand dissociation constants, extending the applicability of the STD NMR spectroscopy for affinity measurements, which is of particular relevance for those proteins for which a ligand of known affinity is not available.     

Anion-directed self-assembly of a 2,6-bis(2-anilinoethynyl)pyridine bis(amide) scaffold

Bis(sulfonamide) receptors based on the 2,6-bis(2-anilinoethynyl)pyridine scaffold form persistent dimers with water and halides in solution and in the solid-state. The structurally related bis(amide) receptor derived from 3,5-dinitrobenzoyl chloride is a dimer in the solid-state with two HCl molecules directing the self-assembly. The 2+2 dimer, with a twisted ‘S’-shaped backbone, is held together by six hydrogen bonds. Dissolution of the (H2⁺√Cl ^? )₂ adduct in CHCl₃ results, however, in a monomeric structure. DOSY and ¹H NMR experiments were used to identify the dominance of monomer in solution for both 2 and H2⁺√Cl ^? . The ‘OFF–ON’ fluorescence response of 2,6-bis(2-anilinoethynyl)pyridine is retained with amide arms.     

Superantibodies

The antibody molecule possesses a number of so-called unconventional binding sites in the variable domain that are expressed and function independently from the antigen-binding site. These sites are encoded in the germiline, predominantly in framework residues. By this definition, these sites function as part of the innate immunity, and are not subject to antigendriven mutation and maturation. In this article, we focus on the evidence for the function and utility of the self-binding domain. The self-binding or autophilic domain has been discovered on murine germline-encoded antibodies from the S107/T15 Vh family. Autophilic antibodies form self-complexes after attaching to targets, but remain monomeric in solution. A peptide has been identified that confers self-binding if chemically attached to antibodies. Because this modification enhances the overall avidity of antibodies for target binding, therapeutic and diagnostic antibodies can be biotechnologically improved. The concept of super antibodies is introduced here to describe the unique coexistence and synergism of acquired immunity with innate immunity via antigen-specific and unconventional functional domains. As not every antibody qualifies as a super antibody, biotechnology engineering can produce superantibodies with superior targeting and therapeutic properties.     

光谱分析法研究四磺酸酞菁金属配合物与牛血清白蛋白的结合作用

分别采用吸收和荧光光谱分析方法准确测定了四磺酸酞菁铝、钴、锰(AlPcS4、CoPcS4、MnPcS4)与牛血清白蛋白(BSA)的结合常数,两种方法的结果基本一致,结合常数的数量级皆为105L/mol。以氯血红素(HE)、布洛芬(IB)和L-色氨酸(TRP)为分子探针,络合竞争法确定了AlPcS4、CoPcS4和MnPcS4与BSA的结合点是SiteⅠ和SiteⅡ。     

Amphiphilic copolymers with increased affinity for substrates

The copolymers of methyl quaternized 2-dimethylaminoethyl acrylate and styrene, 2-vinyl naphthalene, acrylic acid iso-octyl ester, or acrylic acid n-butyl ester have been prepared. Studies were made of the binding of a “binding probe,” methyl orange, by the copolymers in aqueous solution. The first binding constants and the thermodynamic parameters in the course of the binding were evaluated. Furthermore, the intensity of fluorescence of a hydrophobic fluorescent probe, 2-p-toluidinylnaphthalene-6-sulfonate, in the presence of these polymers was investigated. In addition, the fluorescence spectra of monomer and excimer emissions of the polymers with aromatic residues were measured. The excimer/monomer fluorescence intensity ratio was studied in the presence of various additives such as methyl orange, urea, methanol, and NaCl to gain an insight into the nature of microdomains in the polymer. The nature and phenomena of dye binding and hydrophobic fluorescent probe binding with the polymers are discussed. © 1993 John Wiley & Sons, Inc.     

Interaction of an anticancer drug,methotrexate with amphiphilic copolymers of methyl quaternized 2-dimethylaminopropyl acrylamide and styrene

The copolymers of methyl quaternized 2-dimethylaminopropyl acrylamide and styrene have been prepared. Studies were made of the binding of an anticancer drug, methotrexate by the copolymers, bovine serum albumin, and polyvinylpyrrolidone in aqueous solution. The first binding constants and the thermodynamic parameters in the course of the binding were evaluated and compared with those of a binding probe, methyl orange and its homologs in order to gain insight into the nature of drug binding and to apply the drug-polymer complex to a drug-delivery system. The nature and phenomena of drug binding with the polymers are discussed.     

1,2,3-Triazole derivatives as highly selective cannabinoid receptor type 2 (CB2) agonists

The cannabinoid receptor 2 (CB2 receptor) has attracted considerable interest, mainly due to its potential as a target for therapeutics for treating various diseases that have a neuroinflammatory or neurodegenerative component while avoiding the adverse psychotropic effects that accompany CB1 receptor-based therapies. With the appreciation that CB2-selective ligands show marked functional selectivity, there is a renewed opportunity to explore this promising area of research from both a mechanistic as well as a therapeutic perspective. In this research, we are interested in the discovery of new chemotypes as highly selective CB2 modulators, which may serve as good starting points for further optimization towards the development of CB2 therapeutics. In search of new chemotypes as CB2 selective agents, we screened a series of triazole derivatives with interesting bioactive scaffolds, which led to the discovery of two novel and highly selective ligands for CB2 receptors. Compounds 6 and 11 produced a concentration-dependent inhibition of specific [³H]-CP55,940 (CB2) binding with K_i ± SEM values of 105.3 ± 22.6 and 116.4 ± 19.5 nM, respectively, while no binding affinity towards CB1 receptors or opioid receptors was observed. The CB2 functional activity of 6 and 11, as measured by a GPCR Tango assay (G-protein independent β-arrestin translocation assay), revealed that these compounds act as CB2 agonists with EC₅₀ values ± SEM of 1.83 ± 0.16 and 1.14 ± 0.52 µM, respectively. Molecular modeling results showed that both compounds fit well into the active site of the CB2 receptor and showed strong hydrophobic interactions with key residues. In conclusion, the new triazole derivatives (6 and 11) showed promising activity towards CB2 receptors and have great potential to be developed into therapeutically useful CB2 agonists through hit-to-lead optimization.     

Insights into Modeling Approaches in Chemistry: Assessing Ligand-Protein Binding Thermodynamics Based on Rigid-Flexible Model Molecules

In the field of chemistry, model compounds find extensive use for investigating complex objects. One prime example of such object is the protein-ligand supramolecular interaction. Prediction the enthalpic and entropic contribution to the free energy associated with this process, as well as the structural and dynamic characteristics of protein-ligand complexes poses considerable challenges. This review exemplifies modeling approaches used to study protein-ligand binding (PLB) thermodynamics by employing pairs of conformationally constrained/flexible model molecules. Strategically designing the model molecules can reduce the number of variables that influence thermodynamic parameters. This enables scientists to gain deeper insights into the enthalpy and entropy of PLB, which is relevant for medicinal chemistry and drug design. The model studies reviewed here demonstrate that rigidifying ligands may induce compensating changes in the enthalpy and entropy of binding. Some “rules of thumb” have started to emerge on how to minimize entropy-enthalpy compensation and design efficient rigidified or flexible ligands.     

溴甲酚绿与血清白蛋白的结合反应

用分光光度法研究了溴甲酚绿（ＢＣＧ）与牛血清白蛋白（ＢＳＡ）在酸性溶液中的结合反应。认为ＢＣＧ与ＢＳＡ主要由于静电引力而结合，疏水作用力对结合反应也有影响。讨论了反应过程中的平衡关系，推导了求算表观结合常数，最大结合数及摩尔吸光系数的线性回归公式，考察了影响染色反应灵敏度的因素，发现溶液酸度、离子强度对染色反应有显著影响。     

Spectral and molecular docking studies of nucleic acids/protein binding interactions of a novel organometallic palladium (II) complex containing bioactive PTA ligands: Its synthesis,anticancer effects and encapsulation in albumin nanoparticles

The organometallic palladium complex with nitrogen-containing heterocycles is a potent antitumor agent. Coordination of phosphorus ligands to organometallic complexes increases their hydrophilicity, promotes ligand−DNA interactions and damage level to cancer cells, and blocks division in target cells. In this study, a phosphaadamantane palladium complex ([Pd{(C,N)- (C₁₂H₈NH₂)} (PTA) Cl], PTA = 1,3,5-Triaza-7-phosphaadamantane) ( 2 ) was synthesized via the reaction of biologically active PTA with binuclear palladacycles [Pd₂{(C,N)-(C₁₂H₈NH₂)}₂(μ-Cl)₂] ( 1 ). In vitro studies of the complex with DNA (calf-thymus) explored by UV–Vis, emission titration, circular dichroism and helix melting methods showed that the complex interacts with DNA via an intercalative mechanism. Furthermore, competitive binding studies using warfarin, digoxin and ibuprofen site markers containing definite binding sites revealed the binding of the complex to site I on bovine serum albumin. The in vitro release mechanism of the palladium complex exhibited a biphasic pattern characterized by an initial burst release followed by a slower sustained release. Ultimately, in vitro evaluation of cytotoxicity and cell death showed that the complexes were able to decrease the viability of human cancer cell lines (MCF-7 and Jurkat) in a dose-dependent manner, but lower decreases were observed in the viability of normal fibroblast cells ASF-4 at the dosages evaluated. Finally, the order of in vitro anticancer activities was found to be consistent with the DNA-binding affinities.