Synthesis of new chiral organosulfur donors with hydrogen bonding functionality and their first charge transfer salts

The syntheses of a range of enantiopure organosulfur donors with hydrogen bonding groups are described including TTF related materials with two, four, six and eight hydroxyl groups and multiple stereogenic centres and a pair of chiral N-substituted BEDT-TTF acetamides. Three charge transfer salts of enantiopure poly-hydroxy-substituted donors are reported, including a 4:1 salt with the meso stereoisomer of the dinuclear [Fe₂(oxalate)₅]⁴⁻ anion in which both cation and anion have chiral components linked together by hydrogen bonding, and a semiconducting salt with triiodide.     

Oxyfunctionalization products of terpenoids with dimethyldioxirane and their biological activity

Oxyfunctionalization of the bioactive terpenoids, ursolic acid acetate (1), oleanolic acid acetate (5), lupeol acetate (12), and kaurenic acid (17), with dimethyldioxirane (DMDO) was investigated. Treatment of the terpenoids with DMDO under mild conditions afforded a variety of oxidation and oxydegradation products to yield naturally occurring and/or novel compounds in one step. After chromatographic separation, the structures of the individual isolated products were determined using spectroscopic methods including several homonuclear (1H-1H) and heteronuclear (1H-13C) shift-correlated 2D-NMR techniques. The inhibitory activity of the terpenoid derivatives against alpha-glucosidase was investigated and compounds 1, 3, 7, and 9 were found to exhibit potent activity.     

Functionalization of multi-walled carbon nanotubes with coumarin derivatives and their biological evaluation

We report the synthesis and the characterization of different multi-walled carbon nanotubes (MWCNTs) linked to natural molecules, 5,7-coumarins and/or oleic acid, obtained from purified pristine MWCNTs by a cascade of chemical functionalization. The activities of these modified MWCNTs were investigated in vitro on human umbilical vein endothelial cells (HUVECs) by evaluating their ability to influence cell viability and to induce cell apoptosis. Our data showed that pristine MWCNTs are markedly cytotoxic; conversely, the carboxylated carbon nanotubes, much more readily dispersed in aqueous solutions and CNT-Link, the key intermediate designed by us for the drug anchorage, are biocompatible at the tested concentrations (1 and 10 μg ml(-1)).     

Interaction models of the Si(OH)2 functionality with Zn2+ cation in simplified biological environments: a DFT study

We report a DFT study (M06L/cc-pVDZ) of the interactions between the Si(OH)₂ group in three simplified gem-silanediols [i.e., N-[dihydroxy(methyl)silyl] methyl}formamide (DHSF), 3-[dihydroxy (methyl) silyl] propanamide (DHSP), and 3,3′-(dihydroxysilanediyl)dipropanamide (DHSDP)], which have a similar structure to silanediol-based inhibitors of metalloproteases, and simplified active site models: [Zn(Imdz)₃–OH₂]²⁺ and [Zn(Imdz)₂R–OH₂]²⁺, where R can be a formaldehyde, an acetone, or an acetic acid molecule. These models partly resemble the structure of the first coordination sphere of some metalloproteases (e.g., angiotensin I converting enzyme and thermolysin). Different types of bonding patterns were found for the systems into study. The three related silanediols may coordinate with the zinc dication in monodentate, pseudo-bidentate, and pseudo-tridentate way. Pseudo-bidentate interaction was reported to be that corresponding to the silanediol transition-state-analog of the thermolysin enzyme as confirmed by the X-ray structural study (Juers et al., Biochemistry 44:16524–16528, 2005). The binding ability of the mentioned silanediols was determined as the energy of the water displacement reaction for the mentioned active sites models in gas phase and in water solution (PCM model). The calculated binding energies point out to the higher strength of the pseudo-bidentate Zn²⁺–MBG interaction. Moreover, DHSDP ligand is calculated to be the strongest MBG for Zn²⁺ in both active sites models. NBO population analysis and the AIM methodology were implemented as a tool for evaluating electronic structure of the complexes. The results obtained may point out to the fact that the higher the electronic delocalization around the metal center is, the stronger the interaction between the MBG and the active site, bringing about a higher binding energy.     

Synthesis of some novel imidazolidine derivatives and their metal complexes with biological and antitumor activity

Halogenated imidazo(pyrazine,[1,4]diazocine and quinoxaline), 9,10‐anthraquinone‐ [6,7‐e], phenanthroline[5,6‐e] {imidazo[4,5‐b]pyrazine}, and naphtho[1,8‐ef]imidazo[4,5‐b][1,4] diazipen were obtained through interaction of imidazolidineiminothiones with the corresponding diamino compounds. Imidazo[4,5‐e] triazine and pyrrolo[2,3‐d]imidazole were prepared when the iminothiones were reacted with thiocarbohydrazide and with ethylphenyl acetate, separately. Some of the synthesized compounds exhibited better biological and antitumor activities. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:634–647, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20244     

Effect of the structure of ethylene oxide-propylene oxide block copolymers on their interaction with biological membranes

Partition coefficients of ethylene oxide-propylene oxide block copolymers between the lipid phase and water have been estimated via equilibrium dialysis. It has been shown that for the triblock copolymer (Pluronic L61), the partition coefficient is 45 ± 9, while for the diblock copolymer (REP), this parameter is as high as 78 ± 17. The effect of the copolymers on the permeation of the charged organic ion carboxyfluorescein across the lecithin bilayer membrane changes in the same direction. Even though the triblock copolymer binding is weaker, it shows a stronger effect on the rate of transbilayer migration of lipids and on the permeation of the uncharged substance (doxorubicin). The incorporation of cholesterol into the membrane decreases its sensitivity to the action of copolymers; however, the character of changes induced by both copolymers remains invariable. The experimental data of this study indicate that the triblock structure of amphiphilic macromolecules is responsible for their higher ability to disturb lipid bilayer membranes.     

Milk fat globules enveloped by their biological membrane: Unique colloidal assemblies with a specific composition and structure

Milk fat globules are the natural colloidal assemblies secreted by the mammary epithelial cells to provide lipids and other bioactive molecules in the gastrointestinal tract of newborns. They are also consumed by human adults in food products such as cream and cheeses. These biological entities (about 4 μm diameter) have a complex architecture composed of a core rich in triacylglycerols (TAGs) enveloped by a biological membrane, the milk fat globule membrane (MFGM). Although their utmost importance for infants and their functional and nutritional role in dairy products, milk fat globules remain the least understood aspect of milk. This paper provides an overview of recent knowledge with emphasis on milk fat globule origin, size heterogeneities, fatty acid and TAG composition. The crystallisation properties are reported. Recent studies focusing on the MFGM including characterisation of its composition, probing of its structure, and accumulation of scientific evidence of MFGM nutritional and health properties are also discussed. The unique composition and structure of milk fat globules leading to specific functionalities are highlighted.     

Coordination polymers of glutaraldehyde with glycine metal complexes: synthesis,spectral characterization,and their biological evaluation

Glycine metal complexes were prepared by the reaction of glycine with Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) in 1?:?2 molar ratio. Thereafter their condensation polymerization was done with glutaraldehyde to obtain polymer metal complexes. All the synthesized polymer metal complexes were characterized by elemental analysis, FT-IR, ¹H-NMR, and UV-Vis spectrometry, magnetic susceptibility, and thermogravimetric studies. The analytical data of all the polymers agreed with 1?:?1 molar ratio of metal complex to glutaraldehyde and magnetic moment data suggest that PGG–Mn(II), PGG–Co(II), PGG–Ni(II), and PGG–Cu(II) have an octahedral geometry around the metal atom, whereas the tetrahedral geometry was proposed for PGG–Zn(II) polymer. The PGG–Mn(II) and PGG–Cu(II) showed octahedral geometry. Thermal behavior of the polymer metal complexes was obtained at a heating rate of 10°C?min^?1 under nitrogen atmosphere from 0°C to 800°C. The antimicrobial activities of synthesized polymers were investigated against Streptococcus aureus, Escherichia coli, Bacillus sphaericus, Salmonella sp. (Bacteria), Fusarium oryzae, Candida albicans, and Aspergillus niger (Yeast).     

糖苷配合物与DNA作用机理的电化学研究进展

本文综述了糖苷配合物的合成、表征、生物功能及糖化学研究现状，并对糖苷功能配合物与DNA的作用机理及生物功能的电分析化学研究进行了探讨。着重讨论了应用电分析化学、谱学方法、单晶X-射线衍射分析来研究糖苷功能配合物。引用文献39篇。     

Why voltage-gated Ca(2+) and bacterial Na(+) channels with the same EEEE motif in their selectivity filters confer opposite metal selectivity

Voltage-gated sodium (Na(v)) and calcium (Ca(v)) channels, which play essential biological roles, are characterized by their ability to discriminate the "native" ion from other competing cations. Surprisingly, Na(+)-selective bacterial Na(v) and high voltage-activated Ca(2+)-selective Ca(v) channels both exhibit selectivity filters (the narrowest part of the open pore) lined by four Glu residues that interact specifically with the permeating ions. This raises the intriguing question why selectivity filters with the same EEEE motif are Na(+)-selective in Na(v) channels but Ca(2+)-selective in Ca(v) channels. We show that the different degree of metal hydration inside the pore, which is related to the pore size and rigidity, can account for the opposite ion selectivity in Na(v) and Ca(v) channels with identical EEEE selectivity filters. The results are consistent with experimental estimates of the metal hydration structure in Na(v) and Ca(v) channels with the EEEE motif. They suggest that the protein matrix, which can enhance or attenuate ion-protein interactions relative to ion-solvent interactions by controlling the pore's solvent accessibility, size/rigidity, and charge state, is a key determinant of Ca(2+)vs. Na(+) selectivity in EEEE selectivity filters.     

Capillary zone electrophoresis with UV-scanning detection for the analysis of metal species and their organic binding partners in biological systems

A capillary zone electrophoretic method with UV-scanning detection for the separation and identification of both free ligands and metal species is presented. The electrophoretic behavior of naturally occurring binding partners such as organic acids and amino acids was studied and compared with their metal-complexes. Copper(II) complexes of citrate and amino acids showed decreased electrophoretic mobilities and altered UV spectra. The optimized method was validated on ultrafiltered cow's milk and human milk samples. In cow's milk six low molecular weight substances, including citrate, orotate, and hippurate, could be separated. Metal supplementation with Cu(II), Ni(II), or Zn(II) decreased not only the citrate peak but also the orotate signal and in the case of copper(II) supplementation a new signal for the copper(II)-citrate complex appeared. In human milk samples various amino acids such as glutamate, phenylalanine, tyrosine, and tryptophan could be identified besides citrate. The electrophoretic mobilites and peak areas of the amino acids were also influenced by the metal supplementation.     

Design,synthesis, and biological evaluation of novel benzimidazole derivatives and their interaction with calf thymus DNA and synergistic effects with clinical drugs

A series of new benzimidazole derivatives was synthesized and characterized by IR,1H NMR,13C NMR,MS,and HRMS spectra.All the new compounds were screened for their antimicrobial activities in vitro by a twofold serial dilution technique.The bioactive evaluation showed that 3,5-bis(trifluoromethyl)phenyl benzimidazoles were comparably or even more strongly antibacterial and antifungal than the reference drugs Chloromycin,Norfloxacin,and Fluconazole.The combination of2,4-difluorobenzyl benzimidazole derivative 5l and its hydrochloride 7 respectively with the antibacterials Chloromycin,Norfloxacin,and the antifungal Fluconazole was more sensitive to methicillin-resistant MRSA and Fluconazole-insensitive A.flavus.In addition,the interaction of compound 5l with calf thymus DNA demonstrated that this compound could effectively intercalate into DNA to form a compound 5l-DNA complex that might block DNA replication and thereby exert good antimicrobial activity.     

A novel biological role for nsLTP2 from Oriza sativa: Potential incorporation with anticancer agents,nucleosides and their analogues

Development of a protein-based drug delivery system has major impact on the efficacy and bioavailability of unstable and water insoluble drugs. In the present study, the binding modes of a nonspecific lipid transfer protein (nsLTP2) from Oryza sativa with various nucleosides and analogous molecules were identified. The 3-D structure of the protein was designed and validated using modeler 9.13, Molegro virtual docker and procheck tool, respectively. The binding affinity and strength of interactions, key contributing residues and specificity toward the substrates were accomplished by computational docking and model prediction. The protein presented high affinity to acyclovir and vidarabine as purine-analogous drugs. Binding affinity is influenced by the core template and functional groups of the ligands which are structurally different cause the variation of interaction energies with nsLTP2. Nonetheless, all the evaluated analogous drugs occupy the proximity space at the nsLTP active site with high similarity in their binding modes. Our findings hold great promise for the future applications of nsLTPs in various aspects of pharmaceutical science and molecular biology.     

The use of liquid membranes in the multi-residue extraction of stilbenes in a variety of biological matrices and their detection with LC-ES-MS

Supported liquid membrane (SLM) has been used as a sample preparation method in the simultaneous extraction of a mixture of three stilbene compounds in cow's milk, urine, bovine kidney and liver tissues matrices. The stilbene compounds analysed included, dienestrol, diethylstilbestrol and hexestrol. The liquid membrane used for trapping these compounds consisted of 5% tri-n-octylphosphine oxide (TOPO) dissolved in di-n-hexylether/n-undecane (1:1). The extraction efficiencies obtained after enrichment of 1 ng/L stilbenes in variety of biological matrices of milk, urine, liver, kidney and water, ranged from 60 - 70%, 71 - 86%, 69 - 80%, 63 - 7A% and 72 - 93% respectively. The detection limits obtained from urine extraction were 2.1 ng/L, 1.3 ng/L and 3.0 ng/L; from liver and kidney tissues were 2.9 ng/L, 1.6 ng/L and 3.8 ng/L and from milk was 3.2 ng/L, 2.5 ng/L and 4.3 ng/L for hexestrol, dienestrol and diethylstilbestrol respectively.     

Hydrothermal synthesis of highly luminescent CdTe quantum dots by adjusting precursors’ concentration and their conjunction with BSA as biological fluorescent probes

A study on hydrothermal synthesis of CdTe quantum dots, highly luminescent nanocrystals at a relatively lower temperature, via changing the concentration of the CdTe precursors, is described. The full width at half maximum ranged from 40 to 80 nm and quantum yield (QY) was detected to be 27.4% at room temperature. The as-prepared CdTe QDs were labeled with BSA for fluorescence probes without pretreatment. Conjunction experimental results suggested that the as-prepared CdTe QDs are suitable for the application of biotechnology.     

Synthesis of 5-hydroxy- and 5-acylhydrazinopyrazolidines by the reaction of β-substituted hydrazides with α,β-unsaturated aldehydes and their biological activity

The reaction of -substituted hydrazides with alkenals (acrolein, methacrolein, crotonaldehyde, and cinnamaldehyde) serves as a method for the synthesis of the corresponding 1-acyl-5-hydroxypyrazolidines and, in a number of cases, 1-acyl-5-acylhydrazinopyrazolidines. Some of the 1-acyl-5-hydroxypyrazolidines obtained have antiphlogistic activity.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 659–666, May, 1984.