Theoretical elucidation on the antioxidant mechanism of curcumin: a DFT study

[reaction: see text] Bond dissociation enthalpies (BDEs) for the curcumin-related compounds have been calculated using density functional theory (DFT) methods. It was found that the antioxidant mechanism of curcumin was a H-atom abstraction from the phenolic group, not from the central CH2 group in the heptadienone link. Curcumin, methylcurcumin, and half-curcumin had similar O-H BDEs, indicating that the two phenolic groups in curcumin were independent of each other.     

On the antioxidant mechanism of curcumin: classical methods are needed to determine antioxidant mechanism and activity

[reaction: see structure] The antioxidant activity of curcumin (1, 7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) was determined by inhibition of controlled initiation of styrene oxidation. Synthetic nonphenolic curcuminoids exhibited no antioxidant activity; therefore, curcumin is a classical phenolic chain-breaking antioxidant, donating H atoms from the phenolic groups not the CH(2) group as has been suggested (Jovanovic et al. J. Am. Chem. Soc. 1999, 121, 9677). The antioxidant activities of o-methoxyphenols are decreased in hydrogen bond accepting media.     

Analysis of amino acid neurotransmitters by capillary electrophoresis and laser-induced fluorescence using a new fluorescein-derived label

A capillary electrophoresis laser-induced fluorescence detection method (CE-LIF) was developed for the separation of eight neurotransmitters tagged on their amino function with 6-oxy-(N-succinimidyl acetate)-9-(2′-methoxycarbonyl) fluorescein (SAMF), a new fluorescent reagent synthesized in our lab. Derivatization was performed in boric acid buffer (pH = 7.75) at 37 °C over 15 min. The pH-independent fluorescence of SAMF (pH 4–9) permits background buffers over a wide range of pH. It was demonstrated that an acidic running buffer offers a better resolution compared to basic medium in terms of resolution and peak shapes. Employing Cu²⁺ as the additive, the molecules were baseline-separated using a running buffer consisting of 40 mM sodium acetate and 2 mM Cu²⁺ (pH 6.0). The detection limits ranged from 1 to 2 × 10⁻¹⁰ M. The method has been validated for the characterization of lymphocyte samples. The results obtained illustrate the advantages of combining SAMF derivatization with CE-LIF for determining neurotransmitters.     

DNA binding,DNA cleavage,and cellular imaging of a copper(II) complex based on curcumin

Binding property between CT-DNA and a Cu(II) complex, namely CuL₂, where HL = 1,7-bis(4-butoxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione, was determined by UV–Vis absorption, fluorescence spectroscopy, and viscosity measurements. The results showed that the binding of the complex with CT-DNA was through the intercalative mode and the binding constant (K_b) value was found to be 3.82 × 10⁴ M. DNA cleavage studies showed that CuL₂ exhibited effective cleavage activity on pBR322 plasmid DNA in absence of external agents. Additionally, cellular imaging studies also indicated that CuL₂ has a higher toxicity to MCF-7 cell lines compared with its corresponding ligand HL.     

Synthesis of a new metal chelating amino acid: Terpyridyl-alanine

In past years, terpyridine-containing substances have been found useful in polynucleotide chemistry and enzymatic engineering applications. Therefore, the construction of a noncanonical amino acid with a terpyridine side chain may offer promising features for in vitro and in vivo applications, such as the direct bio-expression of proteins with these substances as building blocks. The first step towards these goals is to establish a synthetic protocol for a terpyridine analog bearing an amino acid moiety. Here, we demonstrate the synthesis of terpyridyl-alanine for the first time in five steps and an overall yield of 50%. A metal complex with Fe(II) ions was prepared by crystallization of a protected terpyridyl-alanine derivative and analyzed by X-ray crystallography. Complex formation in aqueous solution was studied by ¹H-NMR, UV/Vis and fluorescence spectroscopy. The comparison of five transition metal ions revealed a metal dependent shift in the UV-absorption and a strong fluorescence in the presence of Zn(II) ions.     

Determination of amino acid neurotransmitters in rat hippocampi by HPLC‐UV using NBD‐F as a derivative

A simple, rapid and accurate high‐performance liquid chromatography method with ultraviolet–visible detection was developed for the determination of five amino acid neurotransmitters – aspartate, glutamic acid, glycine, taurine and γ‐aminobutyric acid – in rat hippocampi with pre‐column derivatization with 4‐fluoro‐7‐nitrobenzofurazan. Several conditions which influenced derivatization and separation, such as pH, temperature, acetonitrile percentage mobile phase and flow rate, were optimized to obtain a suitable protocol for amino acids quantification in samples. The separation of the five neurotransmitter derivatives was performed on a C₁₈ column using a mobile phase consisting of phosphate buffer (0.02 mol/L, pH 6.0)–acetonitrile (84:16, v/v) at a flow rate of 1.0 mL/min with the column temperature at 30°C. The detection wavelength was 472 nm. Without gradient elution, the five neurotransmitter derivatives were completely separated within 15 min. The linear relation was good in the range from 0.50 to 500 µmol/L, and the correlation coefficients were ≥0.999. Intra‐day precision was between 1.8 and 3.2%, and inter‐day precision was between 2.4 and 4.7%. The limits of detection (signal‐to‐noise ratio 3) were from 0.02 to 0.15 µmol/L. The established method was used to determine amino acid neurotransmitters in rat hippocampi with satisfactory recoveries varying from 94.9 to 105.2%. Copyright © 2013 John Wiley & Sons, Ltd.     

Cytotoxic activity and DNA binding of naphthalimide derivatives with amino acid and dichloroacetamide functionalizations

A series of novel naphthalimide derivatives modified by amino acids and their dichloroacetamide derivatives at the 3-position have been synthesized. Their cytotoxic activities were preliminarily evaluated against Hela, A549 and K562 cells, which showed that the length of the side chains of the amino acids influenced the cytotoxic activities. Moreover, compound 7d showed a very good cytotoxic activity against A549 cells with an IC50 value of 4.78 mmol Là1. Furthermore, the UV–vis, fluorescence,and circular dichroism(CD) spectroscopies and thermal denaturation experiment indicated that compounds 6a, 6d and 7a, 7d, as DNA intercalators, exhibited binding affinities with calf-thymus DNA(Ct-DNA).     

Enantioselective recognition of phenylalanine by a chiral amphiphilic macrocycle at the air-water interface: a copper-mediated mechanism

The synthesis of a new chiral amphiphilic calix[4]resorcinarene, tetrakis(N-methylprolyl)tetraundecylcalix[4]resorcinarene (L-RA-Pro), bearing four L-prolyl moieties at the macrocyclic upper rim and four undecyl chains at the lower rim is described. This synthesis has been carried out via a Mannich-type reaction of L-proline and formaldehyde. It has been shown by means of Langmuir balance technique that L-RA-Pro self-assemble as well-defined monomolecular layers at the air-water interface. The effect of various cations on the stability of these monolayers has been studied. The experiments reveal that while there is a slight stabilization effect of K+, Cd2+, Co2+, Mg2+, and Ni2+, there is a high decrease in the collapse pressure in the presence of Cu(II) cation, showing that monolayers of L-RA-Pro, formed at the air-water interface, have a certain selectivity for copper(II) ions with regard to other cations tested. This supramolecular complex exhibits enantioselective recognition properties vs phenylalanine; the mechanism of this interaction is discussed.     

Synthesis,characterization and in vitro DNA binding studies of a new copper(II) complex containing antioxidant ferulic acid

A mononuclear Cu(II) complex, [Cu(FA)₂(NO₃)₂], in which FA is ferulic acid ((E)-3-(4-hydroxy-3-methoxy-phenyl)prop-2-enoic acid), was synthesized and characterized by spectroscopic methods. The main structures of the ligand and its complexes with Cu²⁺ were optimized by QM calculations. The calculations on the structures of the [Cu(FA)₂(NO₃)₂] complexes forms and the intercalating with DNA profile were undertaken by UHF/PM6 and MMFF94 methods, respectively. In vitro studies (UV-vis spectroscopy, emission titration, circular dichroism techniques, and viscometry) under physiological conditions (Tris-HCl buffer solutions, pH 7.4) showed that the complex interacts with calf-thymus DNA (ct-DNA) via an intercalative binding mode. The thermodynamic parameters, enthalpy change (ΔH), and entropy change (ΔS) showed that the acting forces between Cu(II) complex and ct-DNA mainly included van der Waals interactions and hydrogen bonds. Methylene blue (MB) displacement studies revealed that Cu(II) complex can substitute MB probe in the MB-DNA complex which was indicative of intercalative binding. The theoretical data confirm the experimental results with respect to the mechanism of binding.     

Analysis of amino acid neurotransmitters in hypothalamus of rats during cerebral ischemia-reperfusion by microdialysis and capillary electrophoresis

In this work, focal cerebral ischemia and reperfusion were induced by the model of middle cerebral artery occlusion. The dialysate of extracellular fluid in the hypothalamus of rats were obtained by using brain microdialysis technique. An efficient and sensitive MEKC method for the simultaneous determination of multiple amino acid neurotransmitters in microdialysate was developed by capillary electrophoresis with laser-induced fluorescence detection and 5-(4, 6-dichloro-s-triazin-2-ylamino) fluorescein derivatization. Different parameters that influenced derivatization reaction and CE separation were studied and optimized. This method was used to investigate the dynamic change of fourteen amino acid neurotransmitters in microdialysates during cerebral ischemia/reperfusion period. Our results reveal that MCAO and reperfusion elicited significant increases in the extracellular levels of Arg, Lys, Trp, Phe, Gln, GABA, Asn, Pro, Ser, Ala, Tau, Gly, Glu and Asp. The excitatory/inhibitory neurotransmitter balance was disturbed during ischemia/reperfusion. The dynamic changes and functional status of releasable neurotransmitters during ischemia/reperfusion were discussed.     

Novel Schiff base metal complexes: synthesis,characterization, DNA binding,DNA cleavage and molecular docking studies

A novel Schiff base, 3-(((1H-1,2,4-triazol-3-yl)imino)methyl)-4H-chromen-4-one (L) was synthesized and used as ligand for the synthesis of Co(II), Ni(II), Cu(II), Zn(II) and Pd(II) complexes. The structural characterization of the ligand and its metal complexes was determined by using various physicochemical and spectroscopic methods. The IR data show that the Schiff base ligand acts as a bidentate donor coordinating through the oxygen atom of the chromone and nitrogen atom of the imine group. Based on all spectral data, tetrahedral geometry has been proposed for all the metal complexes except Cu(II) and Pd(II) complexes. However, square-planar geometry has been proposed for Cu(II) and Pd(II) complexes. DNA binding interaction of the ligand and its metal complexes was investigated by using UV–visible absorption, fluorescence and molecular docking studies. The binding constants were in the order of 10⁴ M^?1 suggesting good binding affinity towards CT-DNA. The DNA cleavage activity of the synthesized compounds was investigated by using agarose gel electrophoresis. In vitro antimicrobial activity of the synthesized compounds were screened against two gram-positive bacteria (Bacillus subtilis, Staphylococcus aureu) and two gram-negative bacteria (Escherichia coli, Proteus vulgaris) and one fungi strain Candida albicans using disc diffusion method. Antioxidant activity was carried out by DPPH radical scavenging method. In vitro anti-proliferative activity of the ligand and its metal complexes was also carried on the HEK-293, HeLa, IMR-32 and MCF-7 cancer cell lines using MTT assay.     

Induced and photoinduced DNA damage by quinolones: ciprofloxacin, ofloxacin and nalidixic acid determined by comet assay

Quinolones are degraded by light with loss of their antimicrobial activity, generating active species or radicals. Evidence exists that some fluoroquinolones (lomefloxacin, fleroxacin and enoxacin) induce damage to the cellular membrane and DNA cleavage by photosensitization. In this study, the genotoxic potential of the quinolones ofloxacin, nalidixic acid and ciprofloxacin (three antimicrobials frequently used in therapy) was evaluated upon irradiation with UV light by using the comet assay on cells of the Jurkat line. The results demonstrate that there are significant differences between the control groups (positive control with 50 microM H2O2, negative controls without drug and with and without irradiation) and the groups of irradiated quinolones (ofloxacin 2.76 x 10(-5) M, nalidixic acid 2.15 x 10(-4) M and ciprofloxacin 2.01 x 10(-5) M), indicating that, at the dose of irradiation employed (necessary to produce 50% photodegradation), the photodecomposition of the quinolones enhanced DNA damage. The unirradiated drugs also exhibited genotoxicity significantly different from that of the negative control.     

Synthesis,characterization, DNA binding,antibacterial, and antioxidant activity of new bis-phthalimides

New bis-phthalimides were synthesized by 2: 1 condensation of phthalic anhydride and tetrachlorophthalic anhydride with 1,2,4-triazole-3,5-diamine, pyridine-2,6-diamine, and 4-hydroxypyrimidine- 2,6-diamine. The synthesized compounds were characterized by elemental analyses and IR, ¹H NMR, and mass spectra. Their interaction with calf thymus DNA (ct-DNA) was studied by UV-Vis spectrophotometry, cyclic voltammetry, and viscosity measurements, which revealed intercalative mode of binding to ct-DNA. Antibacterial activity of the synthesized compounds against Escherichia coli and Streptococcus mutans was assessed in vitro by the agar well diffusion method. The antioxidant activity of these compounds was estimated by DPPH assay.     

Light as a construction tool of metal nanoparticles: Synthesis and mechanism

The photo-induced synthesis of metal nanoparticles (NPs) was reviewed with a closer look at those based on photochemistry. Recent developments in metal NPs research, photochemistry, and photoprocessing techniques have allowed researchers to devise various photo-induced synthetic strategies to obtain metal NPs under a variety of conditions. We begin by outlining the classical method. The photochemical synthesis of metal NPs including direct photoreduction and photosensitization has been developed to achieve decent yields. We focused on stabilization and functionalization method of NPs in photochemical synthesis, which has enabled us to fabricate a variety of metal nanostructures and composite materials. In addition, we mention an alternative approach, that is, laser ablation at the solid–liquid interface. Some of the most innovative studies dealing with the three-dimensional fabrication of metal NPs are highlighted, together with new directions such as potential applications for a light-driven actuator, bioimaging, and three-dimensional processing. This review is concluded with the future perspectives for the photo-induced synthesis of metal NPs.     

Synthesis,characterization and DNA binding studies of two cyclopentadienyl ruthenium(II) complexes with amino acid ligands

Two new half-sandwich cyclopentadienyl ruthenium(II) complexes containing α-amino acids, [CpRu(PPh₃)₂(Ser)] (Ser = l-serine) and [CpRu(PPh₃)(Met)] (Met = l-methionine), were synthesized and characterized by physicochemical methods. Interactions of these two complexes with calf thymus DNA were investigated by UV–Vis absorption spectroscopy, emission spectroscopy and competitive binding studies. The results indicate that both complexes can interact with DNA, leading to the damage of the double helix. [CpRu(PPh₃)₂(Ser)] binds to DNA by intercalation, while the binding mode for [CpRu(PPh₃)(Met)] is more complicated due to the formation of an EB-DNA-complex (EB = ethidium bromide). The affinity of the Met complex for DNA is stronger than that of the Ser complex, which could be due to groove–surface combination or electrostatic interaction in addition to intercalative binding.     

Evaluation of DNA damage and antioxidant capacity of sericin by a DNA electrochemical biosensor based on dendrimer-encapsulated Au-Pd/chitosan composite

Au-Pd bimetallic nanoparticles were prepared in the presence of an amine-terminated dendrimer of a fourth generation poly(amidoamine) type. A biosensor was fabricated by immobilizing dsDNA on a thin layer of a dendrimer-encapsulated bimetallic nanoparticles (Au-Pd) in a chitosan composite on a glassy carbon electrode. The biosensor was evaluated by square wave voltammetry for the determination of the oxidative damage of immobilized DNA and the antioxidant capacity of sericin. The biosensor is shown to be suitable for the rapid detection of DNA damage and the assessment of the antioxidant capacity of sericin.     

Metallodesferals as a new class of DNA cleavers: Specificity, mechanism and targetting of DNA scission reactions

Interaction of metal complexes with nucleic acids is currently attracting wide attention due to their potential utility as drugs, regulators of gene expression and tools for molecular biology. Many metal complexes exhibit nucleolytic activity, the most important examples being Cu(II)-OP, Fe(H)-BLM, Fe(II)-EDTA, metalloporphyrins, Ru and Co complexes of 4,7-diphenyl-l,10-phenanthroline and more recently by Ni(II) complexes. Desferal, a well known siderophore and a highly effective drug in chelation therapy of iron overload diseases, forms a stable octahedral co-ordination Fe(III) complex Eerrioxamine B. We have been interested in the DNA damaging properties of metallodesferals and this paper describes the DNA cleaving ability of metallodesferals, metal-dependent base selectively in DNA scission reactions, mechanistic studies on DNA cleavage by CuDFO and targetting of DNA cutting by covalent MDFO conjugates. This paper reports the synthesis of Cu(II), Co (III) and Ni(II) complexes of a siderophore chelating drug desferal, the studies on cleavage of plasmid DNA, the sequence preference of cleavage reactions, and C1’ as the primary site of hydroxyl radical attack in the reactions. Oligonucleotides covalently linked with this molecular scissor can direct the cleavage of either single or double strand DNA’s, mediated by duplex or triple helix structures respectively. Such targetting of DNA cleavage reactions, mediated by oligonucleotide-Cu(II)/Co(III) desferal conjugates has demonstrated reasonable site specificity and efficiency     

Fluorescent cyclodextrins bearing metal binding sites and their use for chemo- and enantioselective sensing of amino acid derivatives

Ditopic receptors based on cyclodextrins bearing a metal binding site were used as enantioselective fluorescence sensors, which were able to generate different responses in the presence of d- or l-amino acids. The performances of the selectors as a function of their structure were evaluated, and the same analysis was extended to other analytes. In this work, this approach is used for the enantiomers of a series of amino acid derivatives and in particular of 2-aminocaprolactam. The results showed that the ability of these sensors to perform enantiomeric analysis can be extended to other analytes of interest in organic synthesis such as amino acid amides and α-aminolactams.