Stereoselective and driving-force-dependent photoinduced electron-transfer reactions of zinc myoglobin with optically active N,N′-dimethylcinchoninium and N,N′-dimethylcinchonidinium ions

In order to understand the detailed mechanism of the stereoselective photoinduced electron-transfer (ET) reactions of zinc-substituted myoglobin (ZnMb) with optically active molecules by flash photolysis, we designed and prepared new optically active agents, such as N,N′-dimethylcinchoninium diiodide ([MCN]I₂) and N,N′-dimethylcinchonidinium diiodide ([MCD]I₂). The photoexcited triplet state of ZnMb, ³(ZnMb)*, was successfully quenched by [MCN]²⁺ and [MCD]²⁺ ions to form the radical pair of ZnMb cation (ZnMb^·+) and reduced [MCN]^·+ and [MCD]^·+, followed by a thermal back ET reaction to the ground state. The rate constants (k _q) for the ET quenching at 25 °C were obtained as k _q(MCN)=(1.9±0.1)×10⁶ M⁻¹ s⁻¹ and k _q(MCD)=(3.0±0.2)×10⁶ M⁻¹ s⁻¹, respectively. The ratio of k _q(MCD)/k _q(MCN)=1.6 indicates that the [MCD]²⁺ preferentially quenches ³(ZnMb)*. The second-order rate constants (k _b) for the thermal back ET reaction from [MCN]^·+ and [MCD]^·+ to ZnMb^·+ at 25 °C were k _b(MCN)=(0.79±0.04)×10⁸ M⁻¹ s⁻¹ and k _b(MCD)=(1.0±0.1)×10⁸ M⁻¹ s⁻¹, respectively, and the selectivity was k _q(MCD)/k _q(MCN)=1.3. Both quenching and thermal back ET reactions are controlled by the ET step. In the quenching reaction, the energy differences of ΔΔH ^≠(MCD–MCN) and ΔΔS ^≠(MCD–MCN) at 25 °C were obtained as −1.1 and 0 kJ mol⁻¹, respectively. On the other hand, ΔΔH ^≠(MCD–MCN)=11±2 kJ mol⁻¹ and TΔΔS ^≠(MCD–MCN)=−10±2 kJ mol⁻¹ were given in the thermal back ET reaction. The highest stereoselectivity of 1.7 for [MCD]^·+ found at low temperature (10 °C) was due to the ΔΔS ^≠ value obtained in the thermal back ET reaction. Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.     

Formation of the thioester,N,S-diacetylcysteine,from acetaldehyde and N,N′diacetylcystine in aqueous solution with ultraviolet light

Summary The thioester, N,S-diacetylcysteine, is formed during the illumination of phosphate buffered (pH 7.0) aqueous solutions of acetaldehyde and N,N-diacetylcystine with ultraviolet light. The yield of N,S-diacetylcysteine relative to N-acetylcysteine and unidentified products progressively increases as ultraviolet light below 239 nm, 253 nm and 281 nm is cut off with optical filters. When ultraviolet light below 320 nm is removed with an optical filter, there is no detectable reaction. Illumination of 0.025 M N,N-diacetylcystine with 0.5 M and 1.0 M acetaldehyde with filtered ultraviolet light gives, respectively, 20% and 80% yields of N,S-diacetylcysteine. In the reaction with 1.0 M acetaldehyde, N-acetylcysteine forms early in the reaction and later decreases with its conversion to N,S-diacetylcysteine. The prebiotic significance of these reactions is discussed.Abbreviations Ac-Cys N-acetylcysteine - Ac-Cys(Ac) N,S-diacetylcysteine - Ac-Cys N,N-diacetylcystine     

N2 fixation,and the relative contribution of fixed N,in corals from Curaçao and Hawaii

Coral Reefs - Corals from Hawaii (Montipora capitata) and the Caribbean (brown and orange morphs of Montastraea cavernosa) have previously been shown to harbor symbiotic bacteria capable of fixing...     

N,N′-Dicyclohexylcarbodiimide Inhibition of Dunaliella Growth,and Restoration by Some Adenine Nucleotides and Plant Growth Regulators

N,N′-Dicyclohexylcarbodiimide (DCCD), an inhibitor of membrane-bound ATPase, strongly inhibited the growth, as measured by an increase in cell number, of Dunaliella tertiolecta. However, this inhibition was reversed by simultaneous application of adenosine 5′-triphosphate (ATP) or adenosine 2′-monophosphate (2′-AMP). Adenosine and adenosine 5′-diphosphate (ADP) were ineffective in restroration of the DCCD-inhibited growth. Gibberellin A₃ (GA₃) and 2,4- dichlorophenoxyacetic acid (2,4-D) also reversed the inhibition of DCCD on D. tertiolecta growth, although these plant growth regulators did not promote an increase in cell number.     

Interactions of Bovine Brain Tubulin with Pyridostigmine Bromide and N,N′-Diethyl-m-Toluamide

Pyridostigmine bromide (PB), an inhibitor of acetylcholinesterase, has been used as a prophylactic for nerve gas poisoning. N,N-diethyl-m-toluamide (DEET) is the active ingredient in most insect repellents and is thought to interact synergistically with PB. Since PB can inhibit the binding of organophosphates to tubulin and since organophosphates inhibit microtubule assembly, we decided to examine the effects of PB and DEET on microtubule assembly as well as their interactions with tubulin, the subunit protein of microtubules. We found that PB binds to tubulin with an apparent K _d of about 60 M. PB also inhibits microtubule assembly in vitro, although at higher concentrations PB induces formation of tubulin aggregates of high absorbance. Like PB, DEET is a weak inhibitor of microtubule assembly and also induces formation of tubulin aggregates. Many tubulin ligands stabilize the conformation of tubulin as measured by exposure of sulfhydryl groups and hydrophobic areas and stabilization of colchicine binding. PB appears to have very little effect on tubulin conformation, and DEET appears to have no effect. Neither compound interferes with colchicine binding to tubulin. Our results raise the possibility that PB and DEET may exert some of their effects in vivo by interfering with microtubule assembly or function, although high intracellular levels of these compounds would be required.     

Dioxo-, oxothio- and dithio-tungsten(VI) and tungsten(V) complexes of the ligand N,N′-Dimethyl-N,N′-bis(2-mercaptophenyl)ethylenediamine

Synthesis of complexes cis,cis-W^VOXL (X=Cl, NCS), cis,trans-W^VOXL (X=Cl, OPh, SPh) and cis,trans-W^VIE₂L (E₂=O₂, OS, S₂) of the title ligand LH₂ are reported. cis,cis-W^VOCIL crystallises in space group P2₁/c with a=13.6541(9) Å, b=7.1555(11) Å, c=18.198(2) Å, β=95.294(6)°, V=1770.4(3) ų and Z=4 while the cis,trans isomer crystallises in space group P2₁/n with a=10.361(3) Å, b=14.141(4) Å, c=12.213(5) Å, β=102.56(3)°, V=1747(2) ų and Z=4. cis,trans-W^VIS₂L crystallises in space group P2₁/n with a=10.645(2) Å, b=13.929(2) Å, c=12.189(2) Å, β=103.14(2)°, V=1760(1) ų and Z=4. A short CH₃···Cl distance of 3.067(7) Å and an acute OWCl angle of 94.1(2)° are seen in cis,cis-W^VOClL, which converts to the cis,trans form on heating in MeCN. The latter isomer features a CH₃···Cl distance of 3.38(2) Å and an OWCl angle of 105.1(8)°. Electrochemical and EPR data are reported. In particular, cis,trans-W^VIE₂L may be reduced to [W^VE₂L]^–. EPR properties of these anions and those of complexes W^VOXL are discussed in the context of W^V centres in tungsten enzymes.     

The Weak Cytokinins N,N′-bis-(1-naphthyl)urea and N,N′-bis-(2-naphthyl)urea may Enhance Rooting in Apple and Mung Bean

The present research investigates the possibility that 2 weak urea-type cytokinins, the N,N′-bis-(1-naphthyl)urea and the N,N′-bis-(2-naphthyl)urea, enhance adventitious root formation. The rooting activity was assessed using the stem slice test, the mung bean rooting test and the rooting of apple microcuttings. The two compounds influenced the adventitious rooting process differently as regards the bioassay used. In the stem slice test, in the presence of exogenous auxin, both compounds enhanced the rooted slice percentage. In mung bean shoots, the N,N′-bis-(1-naphthyl)urea enhanced the root formation at the lowest concentration used (0.01 μM) while the N,N′-bis-(2-naphthyl)urea enhanced rooting at higher concentrations. In the rooting test of apple microcuttings the N,N′-bis-(1-naphthyl)urea and the N,N′-bis-(2-naphthyl)urea slightly enhanced only the mean root number per microcutting.     

Unsymmetrical non-adamantyl N,N′-diaryl urea and amide inhibitors of soluble expoxide hydrolase

Incorporation of an adamantyl group in prototypical soluble expoxide hydrolase (sEH) inhibitors afforded improved enzyme potency. We explored replacement of the adamantyl group in unsymmetrical ureas and amides with substituted aryl rings to identify equipotent and metabolically stable sEH inhibitors. We found that aryl rings, especially those substituted in the para position with a strongly electron withdrawing substituent, afforded enzyme IC₅₀ values comparable to the adamantyl compounds in an ether substituted, unsymmetrical N,N′-diaryl urea or amide scaffold.     

[Zn(phen)(O,N,O)(H2O)] and [Zn(phen)(O,N)(H2O)] with O,N,O?is?2,6-dipicolinate and N,O?is?l-threoninate: synthesis, characterization, and biomedical properties

Two ternary Zn(II) complexes, with 1,10-phenanthroline (phen) as the main ligand and a carboxylate-containing ligand [dipicolinate (dipico) or L-threoninate (L-Thr)] as the subsidiary ligand, were prepared and characterized by elemental analysis, Fourier transform IR, UV, and fluorescence spectroscopy, X-ray diffraction, molar conductivity, and electrospray ionization mass spectrometry. X-ray structure analysis shows that both [Zn(phen)(dipico)(H(2)O)]·H(2)O (1) and [Zn(phen)(L-Thr)(H(2)O)Cl]·2H(2)O (2) have octahedral geometry about the Zn(II) atom. Both complexes can inhibit topoisomerase I, and have better anticancer activity than cisplatin against nasopharyngeal cancer cell lines, HK1 and HONE-1, with concentrations causing 50?% inhibition of cell proliferation (IC(50)) in the low micromolar range. Complex 2 has the highest therapeutic index for HK1. Both Zn(II) complexes can induce cell death by apoptosis. Changing the subsidiary ligand in the Zn(II) complexes affects the UV-fluorescence spectral properties of the coordinated phen ligand, the binding affinity for some DNA sequences, nucleobase sequence-selective binding, the phase at which cell cycle progression was arrested for treated cancer cells, and their therapeutic index.     

Diastereo- and Enantioselective Synthesis of 1′-C-Branched N,O-Nucleosides

Abstract

A synthetic approach towards 1′-C-branched N, O-nucleosides is reported, based on 1,3-dipolar cycloaddition of ethoxycarbonylnitrone. The asymmetric version of the process exploits the presence of a chiral auxiliary at the carbon atom of nitrone and leads to β-D and β-L nucleosides in good yields.     

Synthesis and biological evaluation of novel N,N′-bis-methylenedioxybenzyl-alkylenediamines as bivalent anti-Alzheimer disease ligands

A novel series of N,N′-bis-methylenedioxybenzyl-alkylenediamines 5a–5g have been designed, synthesized and evaluated as bivalent anti-Alzheimer’s disease ligands. The enzyme inhibition assay results indicated that compounds 5e–5g inhibit both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in the micromolar range (IC₅₀, 2.76–4.24 µM for AChE and 3.02–5.14 µM for BuChE), which was in the same potential as the reference compound rivastigmine (IC₅₀, 5.50 µM for AChE and 1.60 µM for BuChE). It was found that compounds could bind simultaneously to the peripheral and catalytic sites of AChE. β-Amyloid (Aβ) aggregation inhibition assay results showed that compound 5e exhibited highest self-mediated Aβ fibril aggregation inhibition activity (40.3%) with a similar potential as curcumin (41.6%). It was also found that 5e–5g did not affect neuroblastoma cell viability at the concentration of 50 μM.     

Synergistic antibacterial effect between silybin and N,N′-dicyclohexylcarbodiimide in clinical Pseudomonas aeruginosa isolates

Silybin is a composition of the silymarin group as a hepatoprotective agent, and it exhibits various biological activities, including an antibacterial activity. In this study, the effects of a combination of silybin with N,N'-dicyclohexylcarbodiimide (DCCD) against clinical isolates of Pseudomonas aeruginosa were investigated. In the results of susceptibility assay, silybin showed more potent antibacterial activity in methicilin-resistant Staphylococcus aureus (MRSA) than in P. aeruginosa, but DCCD significantly increased the antibacterial activity of silybin in P. aeruginosa. The antibacterial activity of silybin was affected by the strong action of multidrug-resistant pumps rather than by a permeable disruption of lipopolysaccharide and silybin showed a remarkable synergistic activity in combination with some antibiotic agents against drug-resistant bacteria. Therefore, silybin has a potential as a combination therapeutic agent for treatment of infectious diseases by multidrug-resistant bacteria.     

Synthesis and spectroscopic studies of platinum(II) complexes of N,N′-dicyclohexylethylenediamine

The platinum(II) complexes of the formula [Pt(DCHEDA)X₂], where DCHEDA is N,N′-dicyclohexylethylenediamine and X⁻ is CL⁻, Br⁻, I⁻, 0.5C₂O₄²⁻ (oxalate), 0.5C₃H₂O₄²⁻ (malonate), 0.5C₉H₄O₆²⁻ (4-carboxyphthalate), 0.5S₂O₃²⁻ or 0.5SO₄²⁻, have been synthesized and characterized by UVVis, IR, and ¹H NMR spectral techniques. All the above complexes are non-electrolytes in DMF/H₂O, except the sulphate complex which becomes a 1:1 electrolyte after incubation for 24 h at 28 °C. The halide complexes were also studied by X-ray photoelectron spectroscopy and these data suggest that there is π-bonding from platinum to halide in these complexes. The oxalate, malonate and sulphate bind in their complexes as bidentate ligands to platinum through two oxygen atoms whereas the thiosulphate in its complex binds as a bidentate ligand to platinum through one oxygen atom and one sulphur atom.     

Membrane proteins and squalene-hydrosqualene profile in methanoarchaeon Methanothermobacter thermautotrophicus resistant to N,N′-dicyclohexylcarbodiimide

The biochemical basis of a defective bioenergetic system was attempted to be determined in N,N'-dicyclohexylcarbodiimide (DCCD)-resistant mutant of Methanothermobacter thermautotrophicus. Components participating in the maintenance of methanoarchaeal membrane structure and function, such as the composition of the mixture of squalene and its hydrosqualene derivatives and also properties of membrane-associated proteins were compared in wild-type and mutant cells. The impairment of the bioenergetic system in DCCD-resistant mutant was detectable in the membrane-protein profile; it was also accompanied by changes in proportions of squalene-hydrosqualenes.     

Antimicrobial efficiency of some N,N′-bis(alkymethyl)-1,2-ethanediamine dioxides and N,N′-bis(alkylmethyl)-1,2-propanediamine dioxides

Ten dioxide species derived from N,N′-bis(alkylmethyl)-1,2-ethanediamine and N,N′-bis(alkylmethyl)-1,2-propanediamine were tested for their activity withStaphylococcus aureus, Escherichia coli andCandida albicans. A relation between the length of the alkylchain, and/or the molecule asymmetry, and the antimicrobial activity was found. Part V of the series Amine Oxides; part IV: Mlynarciket al.: Folia Microbiol. 24, 188 (1979).     

Synthesis,structures and characterization of the dinuclear nickel(II) complexes containing N,N,N′,N′-tetrakis[(1-ethyl-2-benzimidazolyl)methyl]-2-hydroxy-1,3-diaminopropane and an azide ion

Two dinuclear nickel(II) complexes, [Ni₂(L-Et)(N₃)(H₂O)₃](NO₃)₂ · 2H₂O (1) and [Ni₂(L-Et)(μ-1,3-N₃)(H₂O)₂](NO₃)₂ · 4H₂O (2) containing (HL-Et = N,N,N′,N′-tetrakis[(1-ethyl-2-benzimidazolyl)methyl]-2-hydroxy-1,3-diaminopropane), have been synthesized and characterized by their IR and UV–Vis spectra and magnetic susceptibilities. The crystal structures of [Ni₂(L-Et)(N₃)(H₂O)₃](NO₃)₂ · CH₃OH (1′) and [Ni₂(L-Et)(μ-1,3-N₃)(H₂O)₂](NO₃)₂ · 2C₂H₅OH (2′) similar to 1 and 2 were determined by X-ray crystallography. In 1′, the two nickel(II) ions are bridged by only an alkoxo group of L-Et⁻, while an azido and an alkoxo connect two nickel(II) ions in 2′. Magnetic susceptibility measurements (2–300 K) showed a weak ferromagnetic exchange coupling between the two nickel(II) ions (2J = 10.1 cm⁻¹) for 1. On the other hand, antiferromagnetic interactions were observed for 2 (2J = −15.8 cm⁻¹).     

Molecular design of N-linked tetravalent glycosides bearing N-acetylglucosamine,N,N′-diacetylchitobiose and N-acetyllactosamine: Analysis of cross-linking activities with WGA and ECA lectins

Two types of nonspacer- and spacer-N-linked tetravalent glycosides bearing N-acetylglucosamine (GlcNAc), N,N′-diacetylchitobiose [(GlcNAc)₂] and N-acetyllactosamine (LacNAc) were designed and prepared as glycomimetics. The interactions of wheat germ (Triticum vulgaris) agglutinin (WGA) and coral tree (Erythrina cristagalli) agglutinin (ECA) with a series of tetravalent glycosides and related compounds were studied using a hemagglutination inhibition assay, a precipitation assay, double-diffusion test, and an optical biosensor based on surface plasmon resonance (SPR). The tetravalent glycosides were found to be capable of binding and precipitating the lectins as tetravalent ligands. Strong interactions with WGA, due to a combination of multivalency effects and spacer effects, were observed for tetravalent glycosides bearing flexible tandem GlcNAc. The chelate effect leads to large rate enhancement for the tetravalent system with favorable orientation of ligands. Our simple strategy produced multivalent glycosides with strong cross-linking activity for lectin as a specific coagulant.     

Effect of β-indoleacetic acid,maleic hydrazide,and 2,3,5-triiodobenzoic acid on N,P, K,and Ca accumulation by pea plants

A study was performed on the effect of various concentrations of IAA, 2,3,6-triiodobenzoic acid, and maleic hydrazide, supplied to Richter’s nutrient solution, on growth of pea plants in water cultures. After a 18-day cultivation growth was evaluated and in the plants gathered the content of total N, P, K, and Ca was estimated. Growth of experimental plants (as evaluated from fresh and dry weight) was affected by all three regulators in dependence on the concentration used. It was stimulated by lower concentrations and inhibited by higher, the production of both fresh and dry weight of the root system being stimulated by all IAA concentrations used. The ratio of root dry weight to that of the entire plant was markedly increased after application of IAA and 2,3,5-triiodobenzoic acid, whereas when applying maleic hydrazide it was only slightly increased in comparison with control. Stimulation or inhibition of growth induced by IAA treatment was accompanied by an accordingly increased or decreased accumulation of N, P, K, and Ca. Thus their utilization did not change in comparison with control. On the other hand, both inhibitory and stimulatory effects of 2,3,5-triiodobenzoic acid and maleic hydrazide on growth were associated with a relatively lower accumulation of the elements in question, resulting in an increased utilization. The distribution index of N, P, K, and Ca decreased with increasing concentrations of IAA, 2,3,5-triiodobenzoic acid and maleic hydrazide. Only the highest 2,3,5-triiodobenzoic acid and maleic hydrazide concentrations used brought about a more marked increase in the distribution index of potassium, simultaneously with a marked decrease in the distribution index of calcium.