Complexation of a tripodal amine-catechol ligand tris((2,3-dihydroxybenzylamino)ethyl)amine towards Al(III), Ga(III), and In(III)

Abstract  

The complexation of a tripodal amine-catechol ligand tris((2,3-dihydroxybenzylamino)ethyl)amine (TRENCAT, L) with group-13 metal ions, viz., Al(III), Ga(III), and In(III), were investigated by means of potentiometric titrations and spectrophotometric measurements in an aqueous medium of 0.1 M KCl at 25 ± 1 °C. The ligand shows the potential to form various monomeric complexes of the types MLH₃, MLH₂, MLH, and ML. At low pH, the ligand is coordinated through three more acidic ortho-catecholic O-atoms to give MLH₃ species. With the rise in pH, the species MLH₃ releases three protons in steps from the meta-catecholic O-atoms to form MLH₂, MLH, and ML. The order of stability Ga(III) > Al(III) > In(III) for the species MLH₃ and MLH₂ is changed into Al(III) > Ga(III) > In(III) for the species MLH and ML. The coordination modes, binding ability, selectivity, and the change in stability order were explained with the help of experimental evidence, molecular modeling calculations, and available literature.     

Effects of the ancillary ligands of polypyridyl cobalt(II) complexes on pH-induced spectral properties and DNA binding properties

Abstract  

Two new Co(II) complexes [Co(ipH)₂(bdipH)]²⁺ and [Co(8-HQ)₂(bdipH)] (ipH = imidazo[4,5-f][1,10]phenanthroline, bdipH = 2-(benzo[d][1,3]dioxol-4-yl)-1H-imidazo[4,5-f][1,10]phenanthroline, 8-HQ = 8-hydroxyquinoline) were synthesized and characterized in detail by elemental analysis, IR, and UV–Vis spectroscopic techniques. The effects of pH on the UV–Vis absorption and emission spectra of the complex were studied. The interaction of the two complexes with calf thymus DNA was explored by using viscosity measurements, electronic absorption titration, competitive binding experiments, and cyclic voltammetry. The experimental results show that complex [Co(ipH)₂(bdipH)]²⁺ exhibits pH-sensitive emission, the two complexes can bind to DNA in an intercalation mode, and the DNA binding affinity of complex [Co(ipH)₂(bdipH)]²⁺ (K _b = 2.11 × 10⁵ M⁻¹) is greater than that of complex [Co(8-HQ)₂(bdipH)] (K _b = 1.76 × 10⁵ M⁻¹). The results show that the size and shape of the ancillary ligand have significant effects on the binding affinity of DNA and complexes.     

Synthesis, structural characterization, and magnetic properties of the metallamacrocycle [Fe6(C11H11N2O3)6(C4H9NO)6]

Abstract  

The 18-metallacrown-6 metallamacrocycle [Fe₆(pmshz)₆(C₄H₉NO)₆] has been synthesized by the self-assembly reaction of iron ions with N-substituted salicylhydrazide ligands. Six Fe(III) ions and six deprotonated N-propanoyl-4-methylsalicylhydrazide (H₃ pmshz) ligands construct a planar 18-membered ring based on Fe–N–N–Fe linkage. Because of the coordination, the ligand enforces the stereochemistry of the Fe(III) ions as a propeller shape with alternating …ΔΛΔΛ… configurations. There is a strong antiferromagnetic exchange interaction between the paramagnetic iron centers.     

Functional group interactions of a 5-HT3R antagonist

Background  

Lerisetron, a competitive serotonin type 3 receptor (5-HT₃R) antagonist, contains five functional groups capable of interacting with amino acids in the 5-HT₃R binding site. Site directed mutagenesis studies of the 5-HT_3AR have revealed several amino acids that are thought to form part of the binding domain of this receptor. The specific functional groups on the ligand that interact with these amino acids are, however, unknown. Using synthetic analogs of lerisetron as molecular probes in combination with site directed mutagenesis, we have identified some of these interactions and have proposed a model of the lerisetron binding site.     

A ~35 kDa polypeptide from insect cells binds to yeast ACS like elements in the presence of ATP

Background  

The S. cerevisiae origin recognition complex binds to the ARS consensus sequence in an ATP dependent fashion. Recently, the yeast Cdc6 has been reported to have DNA binding activity. Conservation of replication proteins among different species strongly supports their functional similarity. Here we report the results of an investigation into the DNA binding activity of human Cdc6 protein. Cdc6 was expressed and purified from baculovirus infected Sf9 (Spodoptera frugiperda) insect cells as GST fusion protein (GST-Cdc6) and its DNA binding activity was tested.     

Synthesis, Crystal Structure, Photophysical Properties, and DFT Calculations of a Bis(tetrathia-calix[4]arene) Tetracadmium Complex

Abstract  

Thiacalix[4]arenes are a unique family of polydentate ligands that offer a combination of four soft sulfur atoms together with four hard phenol oxygen atoms for binding to metal ions. In this study, the tetranuclear cadmium (II) complex Cd₄^II(tca)₂·1.5CH₂Cl₂ (tca⁴⁻ = tetra-anionic p-tert-butylthiacalix[4]arene) (1) was synthesized by reaction of a deprotonated p-tert-butylthiacalix[4]arene and various Cd^II salts. The structure of 1 was established by single crystal X-ray diffraction analysis. The neutral complex 1 contains a square arrangement of four cadmium (II) ions sandwiched between two tca⁴⁻ ligands that have a ‘cone’ conformation similar to that of the free ligand. The absorption and emission properties of the free ligand H₄tca and complex 1 have been recorded and explained by DFT calculations of the molecular orbitals and electronic transitions between them.     

Analysis of fluorescently labeled substance P analogs: binding, imaging and receptor activation

Background  

Substance P (SP) is a peptide neurotransmitter found in central and peripheral nerves. SP is involved in the control of smooth muscle, inflammation and nociception. The amino acid sequence of SP is Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH₂. Five different forms of fluorescently labeled SP have recently been synthesized, in which Alexa 488, BODIPY Fl, fluorescein, Oregon Green 488 or tetramethylrhodamine has been covalently linked to SP at Lys³. Here, these novel analogs are characterized as to their ligand binding, receptor activation and fluorescence labeling properties.     

Heck-type reaction of aryldiazonium silica sulfates

Abstract  

Aryldiazonium silica sulfates were employed as new and efficient reagents for Heck-type arylation reactions with styrene and methyl acrylate. The reactions were carried out in an organic solvent, in the presence of Pd(OAc)₂ as precatalyst without use of base and free ligand. The trans isomers of desired products, methyl cinnamates and stilbenes, were obtained with full conversion. Use of a catalytic amount of Pd(OAc)₂ produced the corresponding products in short reaction times and excellent yields.     

Thermodynamic data for lanthanoid(III) sequestration by phytate at different temperatures

Abstract  

The results of an investigation on the interactions between phytate ion (myo-inositol hexaphosphate, Phy) and some lanthanoid cations (La³⁺, Nd³⁺, Sm³⁺, Dy³⁺, and Yb³⁺) are reported. The stability constants of various LnH _j Phy species (Ln = generic lanthanoid) were determined by potentiometry (ISE-H⁺ glass electrode) in NaCl_aq at I = 0.15 mol dm⁻³ and t = 25 °C, and the corresponding formation enthalpies by calorimetric titration. The thermodynamic data obtained were used to provide a speciation scheme for the lanthanoid(III)–phytate systems at different temperatures. The sequestering ability of this ligand toward Ln³⁺ was also evaluated by calculation of pL₅₀ values (the total concentration of ligand necessary to bind 50% of a cation present in trace amounts) under different conditions, and equations were formulated to model their dependence on temperature and pH.     

Synthesis, characterization, and crystal structure of two zinc(II) halide complexes with the symmetrical bidentate Schiff-base ligand (3,4-MeO-ba)2en

Abstract  

In this study two zinc(II) halide complexes with the Schiff-base ligand (3,4-MeO-ba)₂en [N,N′-bis(3,4-dimethoxybenzylidene)ethane-1,2-diamine] have been synthesized and characterized by elemental analyses (CHN), single-crystal X-ray diffraction, Fourier-transform infrared (FT-IR), and ¹H nuclear magnetic resonance (NMR) spectroscopy. The metal-to-ligand ratio was found to be 1:1 within the formula ZnX₂((3,4-MeO-ba)₂en) (X = Br, I). Crystal structure analysis reveals that the coordination geometry around the zinc(II) ions in the two isotypic complexes is distorted tetrahedral. The Schiff-base ligand (3,4-MeO-ba)₂en acts as a chelating ligand and coordinates via two N atoms to the metal center and adopts an (E,E) conformation. The coordination spheres of the metal atoms are completed by the two halide atoms, which are also involved in weak non-classical hydrogen-bonding interactions of the type C–H···X–Zn.     

Protonation of electroneutral p-tert-butylcalix[4]arenetetraacetic acid

Abstract  

Using ¹H NMR spectroscopy together with density functional theoretical calculations, it is shown that electroneutral p-tert-butylcalix[4]arenetetraacetic acid forms an equimolar complex with a proton in the form of the H₃O⁺ ion in nitrobenzene-d ₅. Protons were offered by hydrogen bis(1,2-dicarbollyl)cobaltate and converted to hydroxonium ions by traces of water. In the resulting complex, the H₃O⁺ cation is bound by strong hydrogen bonds to two phenoxy oxygen atoms of the parent calix[4]arene ligand and to one carbonyl oxygen of the corresponding COOH group of this ligand.     

Orthophosphate binding at the dimer interface of <Emphasis Type="Italic">Corynebacterium callunae</Emphasis> starch phosphorylase: mutational analysis of its role for activity and stability of the enzyme

Background  

Orthophosphate recognition at allosteric binding sites is a key feature for the regulation of enzyme activity in mammalian glycogen phosphorylases. Protein residues co-ordinating orthophosphate in three binding sites distributed across the dimer interface of a non-regulated bacterial starch phosphorylase (from Corynebacterium callunae) were individually replaced by Ala to interrogate their unknown function for activity and stability of this enzyme.     

Binding specificity of Bacillus thuringiensis Cry1Aa for purified, native Bombyx mori aminopeptidase N and cadherin-like receptors

Background  

To better understand the molecular interactions of Bt toxins with non-target insects, we have examined the real-time binding specificity and affinity of Cry1 toxins to native silkworm (Bombyx mori) midgut receptors. Previous studies on B. mori receptors utilized brush border membrane vesicles or purifed receptors in blot-type assays.     

Biochemical evidence for the tyrosine involvement in cationic intermediate stabilization in mouse β-carotene 15, 15'-monooxygenase

Background  

β-carotene 15,15'-monooxygenase (BCMO1) catalyzes the crucial first step in vitamin A biosynthesis in animals. We wished to explore the possibility that a carbocation intermediate is formed during the cleavage reaction of BCMO1, as is seen for many isoprenoid biosynthesis enzymes, and to determine which residues in the substrate binding cleft are necessary for catalytic and substrate binding activity. To test this hypothesis, we replaced substrate cleft aromatic and acidic residues by site-directed mutagenesis. Enzymatic activity was measured in vitro using His-tag purified proteins and in vivo in a β-carotene-accumulating E. coli system.     

Theoretical studies of 1,4-dihydropyridine-3,5-dicarboxamides as possible inhibitors of Mycobacterium tuberculosis enoyl reductase

Abstract  

The binding affinity of some novel 1,4-dihydropyridine-3,5-dicarboxamides to enoyl-ACP reductase (InhA) from M. tuberculosis was studied by the docking method. A molecular dynamics simulation lasting 230 ns in total was performed for 19 ligand–enzyme complexes to calculate the binding free energies of these ligands to the enzyme. All of the studied compounds stayed in the active site. An energetics analysis revealed that the van der Waals share is more important than electrostatic in binding of all ligands to the active site.     

Analysis of DNA relaxation and cleavage activities of recombinant Mycobacterium tuberculosis DNA topoisomerase I from a new expression and purification protocol

Background  

Mycobacterium tuberculosis DNA topoisomerase I is an attractive target for discovery of novel TB drugs that act by enhancing the accumulation of the topoisomerase-DNA cleavage product. It shares a common transesterification domain with other type IA DNA topoisomerases. There is, however, no homology between the C-terminal DNA binding domains of Escherichia coli and M. tuberculosis DNA topoisomerase I proteins.     

Nonnatural amino acid incorporation into the methionine 214 position of the metzincin <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> alkaline protease

Background  

The alkaline protease from Pseudomonas aeruginosa(AprA) is a member of the metzincin superfamily of metalloendoproteases. A key feature of these proteases is a conserved methionine-containing 1,4-tight β turn at the base of the active site zinc binding region.     

A 2D network silver coordination polymer with the multimodal ligand 2-pyrazyl methyl ketazine

Abstract  

A two-dimensional coordination polymer {Ag(PMK)(OTf)·MeCN} _n (1) based on multi-modal bridging ligand, namely N,N′-bis[1-(pyrazin-2-yl)ethylidene]-hydrazine or 2-pyrazyl methyl ketazine (PMK), and AgOTf salt has been synthesized and characterized by ESI-MS, ¹H-NMR, ATR-IR, and single crystal X-ray diffraction. The PMK shows distinct binding sites, both chelating and monodentate, and bridging modes in 1 where each silver(I) centre is five coordinate, and bound to one bidentate pyrazylketimine and a monodentate pyrazine through the peripheral N atom from another ligand, and also a bridging pyrazine through the peripheral N atom of the adjacent chelating unit from another ligand, and to triflate anion to feature one-dimensional infinite chain. The triflate anions have effectively increased the 1D coordination polymers to a 2D network via H-bonding interactions. These 2D planes are stacked together building up channels (1D tube) in which the acetonitrile solvent molecules reside and form very weak contacts with the triflates and the pyrazylketimine units via C–H···O and C–H···N, respectively. In addition, the fluorescent spectrum of 1 in the solid state exhibits two emission maxima at 496 and 522 nm. The ESI-MS, IR, and ¹H-NMR confirm the structure.     

Use of 3D QSAR to investigate the mode of binding of pyrazinones to HIV-1 RT

Abstract  

Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) based on the docked conformation were performed for 24 pyrazinone derivatives. All compounds were docked into the wild-type HIV-1 RT binding pocket and the lowest-energy docked configurations were used to construct the 3D QSAR models. The CoMFA and CoMSIA models enable good prediction of inhibition by the pyrazinones, with r_\textcv² r_{\text{cv}}^{2}  = 0.703 and 0.735. Results obtained from CoMFA and CoMSIA based on the docking conformation of the pyrazinones are, therefore, powerful means of elucidating the mode of binding of pyrazinones and suggesting the design of new potent NNRTIs.     

Identification of archaeal proteins that affect the exosome function in vitro

Background  

The archaeal exosome is formed by a hexameric RNase PH ring and three RNA binding subunits and has been shown to bind and degrade RNA in vitro. Despite extensive studies on the eukaryotic exosome and on the proteins interacting with this complex, little information is yet available on the identification and function of archaeal exosome regulatory factors.