Enzymic Formation of β-D-Fructofuranosides from Sucrose: Activity and Selectivity of Inventase in Mixtures of Water and Alcohol

Abstract

Invertase-catalysed alcoholysis of sucrose in water - primary alcohol mixtures containing up to 70% organic solvent shows 5-40% alkyl β-D-fructofuranoside formation. No formation of fructosides was observed under anhydrous conditions. The kinetics of the competing reactions of water and primary alcohol as fructosyl acceptors with sucrose as fructosyl donor were studied in order to establish the scope and limitations of the method. On a molar basis, water was a relatively unreactive acceptor. 6-Kestose formation due to sucrose itself as a fructosyl acceptor was suppressed by the presence of aliphatic alcohols. The results have been explained by assuming an nonspecific non-polar binding site to be present in the enzyme cavity near the specific polar binding site for the β-D-fructofuranosyl group of the substrate.     

Study on the Selectivity of Benzoylation of Metal Chelates of Sucrose1

Abstract

A study of the selectivity of metal chelate-directed benzoylation of sucrose dianion, relative to unchelated sucrose anion, was conducted as part of a study on new synthetic approaches to the high-potency sweetener sucralose. Ionic complexes of sucrose with various metal ions were prepared in DMF and the resulting complexes reacted at low temperature with benzoic anhydride. Cobalt and manganese salts directed esterification mostly to the 3′-OH on the fructosyl portion. Unchelated sucrose anion and other metals favored esterification at the 2-OH of the glucosyl portion. Migration of the benzoate ester along the glucose portion was observed in the direction O-2 to O-6 at moderate temperature, but at higher temperature transannular migration was observed from the glucose to the fructose ring. Reaction mixtures were analyzed by HPLC and monobenzoates identified by retention times relative to standards. Six of eight possible monobenzoates of sucrose were isolated from mixtures and identified by their ¹H NMR spectra.     

Synthesis of Some Novel Glucosyl Triazoles from 2,3,4,6-Tetra-O-pivaloyl-D-glucopyranosyl Azide

In the present study, we have synthesized a series of novel glucosyl triazoles for the first time. The glucosyl triazoles 4a–e were synthesized by reaction of some azidoglycosides with various terminal alkynes via a copper-catalyzed [3+2] cycloaddition (“click chemistry”) and were deprotected to afford the corresponding glucosyl triazoles 5a–e in good yields. The structures of the new compounds were determined by IR, NMR spectroscopy, and mass spectrometry. The antitumor (human cervical cancer cell) activity was evaluated for the target compounds.     

SYNTHESIS OF THE TETRASACCHARIDE Glc α (1→3) Man α (1→2) Man α (1→2) Man α (OMe) AS INHIBITOR OF CALNEXIN BINDING TO GlcMan 9GlcNAc 2 a

Tetrasaccharide GlcMan ₃ is an inhibitor of GlcMan ₉GlcNAc ₂ binding to calnexin, a chaperone protein involved in CFTR-ΔF 508 retention. A convergent route to its methyl glycoside, the title tetrasaccharide, was developed. The key building block Glc α (1→3) Man 6 was stereoselectively obtained by condensation of a trichloroacetimidate glucosyl donor with an ethyl thiomannopyranoside acceptor. Di-mannose moiety 10 and final compound 12 resulted from thioglycoside activations.     

A Proline-Based Aminophosphinic Acid Ligand and It’s Vanadyl Complex: Synthesis,Characterization and In Vitro Inhibitory Effects on α-Amylase And α-Glucosidase

Abstract

A proline-based aminophosphinic acid ligand and it's vanadium complex have been synthesized and characterized by spectroscopic techniques. The inhibitory activity on pancreatic α-amylase and Baker's yeast α-glucosidase has been examined in vitro. The novel complex showed more inhibitory potency against pancreatic α-amylase and Baker's yeast α-glucosidase compared to acarbose as an antidiabetic drug.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Immobilization ofAzacrown Ligand onto a Fluorophore

Geometric immobilization of azacrown ligand onto a fluorophore is expected to change their binding properties toward ion discrimination. An immobilized azacrown ligand 1 onto anthracene fluorophore senses Al(III), Cu(II) and Ga(III) in ethanol among the metal ions examined. In 100% aqueous solution, ligand 1 shows large CHEF effects with Al(III) and Ga(III) and large CHEQ effect with Hg(II). By comparison, non-immobilized azacrown ligand 2 showed large CHEF effects with Al(III), Ce(III), Ga(III), La(III) and Zn(II) in ethanol.     

Study of Binding of Benzyl-Thiouracil to Human Serum Albumin by Gel Filtration Chromatography

Abstract

The binding of benzyl-thiouracil to human serum albumin was studied at 37°C and pH 7.4 by Sephadex filtration chromatography based upon Hummel and Dreyer's method. As the benzyl-thiouracil (ligand) was adsorbed on to the gel matrix, the free ligand concentrations had to be corrected through the ligand distribution between the stationary and mobile phases.

A good agreement was found between binding parameters—calculated by this method and by the classical method (equilibrium dialysis). Binding is characterized by one binding site with a moderate association constant (K₁ = 5.7 × 10⁴ M^-1) and two binding sites with a low association constant (K₂ = 7.8 × 10³ M^-1).     

Synthesis and structural characterization of a barium coordination polymer based on a μ2-monoatomic bridging 4-nitrobenzoate

Abstract

The synthesis, spectral characterization, crystal structure and properties of [Ba(H₂O)₂(NMF)₂(4-nba)₂], 1 (NMF = N-methylformamide; 4-nba = 4-nitrobenzoate), are reported. ¹H and ¹³C NMR spectral data reveal the presence of NMF in 1. A strong band at 1660?cm^?1 in the infrared spectrum indicates the binding of amide oxygen to Ba(II) which is confirmed by the single crystal structure. The unique Ba(II) in 1 situated on a mirror plane exhibits nine coordination and is bonded to two symmetry related monodentate terminal NMF ligands via the amide oxygen, and a terminal aqua ligand. The μ₂-monoatomic bridging binding mode of each of a crystallographically independent 4-nba ligand and a unique water ligand link the Ba(II) cations into an infinite chain extending along a, leading to the formation of a 1D coordination polymer with Ba···Ba separations of 4.2522(3) Å. In the chain, the {BaO₉} polyhedra are linked in a face sharing fashion. Thermal decomposition of 1 results in the formation of BaCO₃ residue. A comparative study of the structural chemistry of several barium coordination polymers is described.     

Synthesis,structure, and DNA-binding properties of manganese(II) and zinc(II) complexes with tris(<Emphasis Type="Italic">N</Emphasis>-methylbenzimidazol-2-ylmethyl)amine ligand

Tris(N-methylbenzimidazol-2-ylmethyl)amine (Mentb) and its two complexes, [Mn(Mentb)(DMF)(H₂O)](pic)₂ 1 and [Zn(Mentb)(pic)](pic) 2 (pic = picrate), have been synthesized and characterized by physico-chemical and spectroscopic methods. Single crystal X-ray diffraction revealed that the two complexes have different structures. In complex 1, the coordination sphere around Mn(II) is distorted octahedral, whereas in complex 2 the coordination sphere around Zn(II) is distorted trigonal bipyramidal. The DNA-binding properties of the free ligand and its two complexes have been investigated by electronic absorption, fluorescence, and viscosity measurements. The results suggest that the ligand and its two complexes bind to DNA via an intercalation binding mode, and their binding affinity for DNA follows the order 1 > 2 > ligand.     

Tryptophan receptors containing acridine-based thiourea

Four derivatives of acridine and acridinium compounds (L1, L2, L1H and L2H) comprised thiourea-binding sites were synthesised. The binding abilities of receptors L1, L2, L1H and L2H towards amino acids (l-Trp, l-Phe, l-Leu, l-Ala and l-Gly) were studied by ¹H NMR spectroscopy, UV–vis and fluorescence spectrophotometry. Hydrogen bonding interactions between thiourea-binding site of the ligand and the carboxylate groups in zwitterionic amino acids were found to be the main interactions driving complexation to take place. The stoichiometry of 1:1 ligand to amino acid was observed in all cases. Neutral ligands L1 and L2 showed weak binding towards all studied amino acids. The cyclic ligand L1 showed better binding ability towards tryptophan (Trp) than the acyclic ligand L2 did (K for Trp is 307 and 266 M^? 1 for L1 and L2, respectively). Interestingly, binding abilities of the protonated ligands, L1H and L2H, towards studied amino acids, especially Trp (K for Trp is 3157 and 2873 M^? 1 for L1H and L2H, respectively), were increased due to R–COO^? …H…N⁺–acridinium interactions. Calculated structures of L1H·Trp and L2H·Trp showed that the polyglycol moiety in L1H provided a hydrophobic cavity for binding Trp resulting in a stronger binding affinity of L1H over L2H.     

Advances in the synthesis of homochiral (-)-1-azafagomine and (+)-5-epi-1-azafagomine. 1-N-phenyl carboxamide derivatives of both enantiomers of 1-azafagomine: Leads for the synthesis of active α-glycosidase inhibitors

A new expeditious preparation of homochiral (-)-1-azafagomine and (+)-5-epi-1-azafagomine has been devised. Stoodley's diastereoselective cycloaddition of dienes bearing a 2,3,4,6-tetraacetyl glucosyl chiral auxiliary to 4-phenyl-1,2,4-triazole-3,5-dione was merged with Bols's protocol for functionalizing alkenes into molecules bearing a glucosyl framework. Homochiral (+)-5-epi-1-azafagomine was synthetized for the first time. Partial reductive cleavage of the phenyltriazolidinone moiety afforded new homochiral 1-N-phenyl carboxamide derivatives of 1-azafagomine. Both enantiomers of these derivatives were synthetized and tested, displaying a very good enzymatic inhibition toward baker's yeast α-glucosidase. The molecular recognition mechanism of the 1-N-phenyl carboxamide derivative of 1-azafagomine by α-glucosidase from baker's yeast was studied by molecular modeling. The efficient packing of the aromatic ring of the 1-N-phenyl carboxamide moiety into a hydrophobic subsite (pocket) in the enzyme's active site seems to be responsible for the improved binding affinity in relation to underivatized (-)-1-azafagomine and (+)-1-azafagomine.     

Antifungal activity,DNA and lysozyme binding affinity of Pd(II) and Pt(II) complexes bearing N,N-pyridylbenzimidazole ligand

Abstract

The lysozyme- and DNA-binding affinities of the biologically active cisplatin analogues, Pd(II) (1) and Pt(II) (2) complexes of functionalized N,N-pyridylbenzimidazole ligand, are reported. The electronic transitions were studied by time-dependent density functional theory. Complex 1 exhibits interesting antifungal activity against Candida albicans (MIC?=?32?μg?mL^?1; 64?nM) and Cryptococcus neoformans (MIC?=?16?μg?mL^?1, 32?nM). Complex 1 is covalently bound to DNA and lysozyme via the elimination of the chloride ligand(s). When complex 2 interacts with lysozyme, two adduct peaks are observed in the mass spectrum corresponding to binding of Pt(II) ion to lysozyme.     

Synthesis,structure, and DNA-binding properties of manganese(II) and nickel(II) complexes with tris(N-ethylbenzimidazol-2-ylmethyl)amine ligand

Tris(N-ethylbenzimidazol-2-ylmethyl)amine (Etntb), [Mn(Etntb)(DMF)(H₂O)](pic)₂ (1), and [Ni(Etntb)(DMF)(H₂O)](pic)₂ (2) (pic?=?picrate) have been synthesized and characterized by elemental analyses, molar conductivities, UV–Visible spectra, and IR spectra. Single-crystal X-ray diffraction revealed that the complexes have the same arrangement with distorted octahedral coordination geometries. DNA-binding properties of the free ligand, 1, and 2 have been investigated by electronic absorption, fluorescence, and viscosity measurements. The results suggest that the ligand and its complexes bind DNA via intercalation, and their binding affinity for DNA follows the order 2?>?1?> ligand.     

Synthesis,characterization, and hypoglycemic efficacy of nitro and amino acridines and 4-phenylquinoline on starch hydrolyzing compounds: an in silico and in vitro study

α-Amylase and α-Glucosidase are important therapeutic targets for type II diabetes. The present focus of our study is to elucidate the hypoglycemic activity of novel compounds through in vitro and in silico studies. Here, we synthesized the nitro acridines (3a–3c), amino acridines (4a–4c), and nitro phenylquinoline (3d) and amino phenylquinoline (4d) using a multi-step reaction protocol in good yields. All the above derivatives were screened for molecular docking, α-Amylase and α-Glucosidase inhibitory activities utilizing acarbose as standard drug. In silico studies were performed to explore the binding ability of compounds with the active site of α-Amylase and α-Glucosidase enzymes. The in vitro antihyperglycemic report of 3c exhibits the maximum inhibitory activity with IC₅₀ values of 200.61?±?9.71 μmol/mL and 197.76?±?8.22 μmol/mL against α-Amylase and α-Glucosidase, respectively. Similarly, the compound 3a exhibits IC₅₀ values of 243.78?±?13.25 μmol/mL and 296.57?±?10.66 μmol/mL, and 4c exhibits IC₅₀ values of 304.28?±?3.51 μmol/mL and 278.86?±?3.24 μmol/mL with a significant p?<?0.05 in both enzyme inhibitions. In addition, the presence of diverse functional moieties in synthesized compounds may provide a strong inhibitory action against the abovementioned enzymes compared with standard acarbose inhibition (IC₅₀, 58.74?±?3.68 μmol/mL and 49.39?±?4.94 μmol/mL). Also, the docking studies provided an excellent support for our in vitro studies. The outcome of these studies recommends that the tested compounds might be treated as potential inhibitors for the starch hydrolyzing enzymes in type II diabetes.

     

Synthesis,crystal structure,and BSA interaction with a new Co(II) complex based on 5-(trifluoromethyl)pyridine-2-carboxylic acid

Abstract

A new complex, Co(Htpc)₂(H₂O)₂ (1) (Htpc = 5-(trifluoromethyl)pyridine-2-carboxylic acid), has been synthesized and characterized by X-ray single-crystal diffraction, elemental analysis, infrared spectral analysis, and thermogravimetric analysis. Meanwhile, the optimized geometric structure of the ligand was determined using the M06-2X functional of density functional theory (DFT) with the 6-311?+?G(d, p) basis set. The gap energies ΔE between the frontier molecular orbitals were computed in different solvent media (water, methanol and ethanol) using the time dependent density functional theory (TD-DFT)/M06-2X by applying the Polarizable Continuum Model (PCM). The coordination sphere around Co(II) is distorted octahedral with two chelating tpc^- ligands and two coordinated water molecules. Bovine serum albumin (BSA) binding properties of the ligand, CoCl₂·6H₂O and 1 were investigated by fluorescence and UV–Vis absorption spectroscopy, revealing 1 exhibits higher binding affinity with BSA than free ligand and CoCl₂·6H₂O. ΔG, ΔH and ΔS at 298 and 308?K manifested that van der Waals interactions and hydrogen bonds were the main forces in the binding process.     

Fleetamine (3-O-α-d-glucopyranosyl-swainsonine): the synthesis of a hypothetical inhibitor of endo-α-mannosidase

3-O-α-d-Glucopyranosyl-swainsonine was originally proposed¹⁷ as a potential inhibitor of the mammalian enzyme endo-α-mannosidase, but its synthesis has not been reported. Herein we report the total synthesis of this enigmatic compound, utilizing a halide-ion catalysed glycosylation of a swainsonine lactam with a glucosyl iodide donor as the key step. The resulting inhibitor was evaluated as an inhibitor of human endo-α-mannosidase, and as a ligand for bacterial orthologs from Bacteroides thetaiotaomicron and Bacteroides xylanisolvens, including active-centre variants, although no evidence for binding or inhibition was observed. The surprising lack of binding was rationalized by using structural alignment with an endo-α-mannosidase inhibitor complex, which identified deleterious interactions with the swainsonine piperidine ring and an essential active site residue.     

Synthesis,structure, DNA-binding properties,and antioxidant activity of copper(II) and cobalt(II) complexes with bis(<Emphasis Type="Italic">N</Emphasis>-allylbenzimidazol-2-ylmethyl)benzylamine

Bis(N-allylbenzimidazol-2-ylmethyl)benzylamine (babb) and two of its complexes, [Cu(babb)(pic)₂]·H₂O (1) and [Co(babb)₂](pic)₂ (2) (pic = picrate), have been synthesized and characterized by physico-chemical and spectroscopic methods. Single crystal X-ray diffraction revealed that the two complexes have similar distorted octahedral structures, but the degree of distortion and the coordinated atoms are different. The DNA-binding properties of the free ligand and its two complexes have been investigated by electronic absorption, fluorescence, and viscosity measurements. The results suggest that all three compounds bind to DNA via an intercalative binding mode, and their binding affinity for DNA follows the order 2 > 1 > ligand. Additionally, both complexes exhibited potential antioxidant properties in in vitro studies, and complex 1 was the more effective.     

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.     

Role of Tyr-435 of <Emphasis Type="Italic">Vibrio harveyi</Emphasis> Chitinase A in Chitin Utilization

Vibrio harveyi chitinase A or VhChiA (EC.3.2.1.14) is a member of GH-18 chitinases that catalyzes chitin degradation from marine biomaterials. Our earlier structural data of VhChiA suggested that Tyr-435 marks the ending of subsite +2 and may influence binding of the interacting substrate at the aglycone binding sites. This study reports the effects of Tyr-435 using site-directed mutagenesis technique. Mutation of Tyr-435 to Ala (mutant Y435A) enhanced both binding and catalytic efficiency of VhChiA, whereas substitution of Tyr-435 to Trp (mutant Y435W) lessened the ability of the enzyme to bind and hydrolyze chitin substrates. The increased activity of Y435A can be explained by partial removal of a steric clash around subsite (+2), thereby allowing a chitin chain to move beyond or to access the enzyme’s active site from the aglycone side more straightforwardly.     

由2-(4'-羧基苯基)咪唑-4,5-二羧酸构筑的过渡金属配位聚合物的合成、结构及性质

在溶剂热条件下,由2-(4′-羧基苯基)咪唑-4,5-二羧酸(H_4L,C_(12)H_8N_2O_6),合成了4个配位聚合物{[M(H_3L)_2]·2H_2O}_n(M=Zn(1),Cd(2),Co(3)),[Cd(H_2L)(H_2O)]_n(4)。用元素分析、红外光谱、热重分析和单晶X射线衍射对配合物进行了表征和结构分析。结构分析结果表明:1～3是异质同晶。配体失去1个质子以H_3L~-的形式通过单齿和N,O-双齿螯合的配位模式与中心金属离子配位,构成一个略有变形的八面体结构。对于配合物4来说,配体失去2个质子以H_2L~(2-)的形式分别通过单齿和N,O-双齿螯合的配位方式与Cd~(2+)配位,中心离子采取扭曲的七配位五角双锥配位模式,并且通过配体苯环上羧基氧原子的双齿桥联作用连接2个中心离子,形成四元环的双核结构;同时呈现双节点(3,6)-连接的二维拓扑网络(4.4.4)(4.4.4.4.4.4.5.6.6.6.6.6)。测定了产物的固体荧光光谱;用EtBr荧光探针法研究了配体及配合物与ct-DNA的相互作用。