N,N′-bis-(2,3-methylenedioxyphenyl)urea and N,N′-bis-(3,4-methylenedioxyphenyl)urea interact with auxin in enhancing root formation of M26 apple (Malus pumila Mill.) stem slices

Stem slices cut from micropropagated cuttings of apple rootstock M26 were cultured in the presence of indole-3-butyric acid (IBA) plus N,N-bis-(2,3-methylenedioxyphenyl)urea or N,N-bis-(3,4-methylenedioxyphenyl)urea, to verify if there was an interaction between them in enhancing root formation. The N,N-bis-(methylenedioxyphenyl)ureas were supplemented after, before and in the simultaneous presence of auxin. Our data demonstrate that only the simultaneous presence of auxin and N,N-bis-(methylenedioxyphenyl)ureas in the culture medium enhanced root formation on M26 stem slices. The percentage of rooted slices obtained in the presence of the mixtures was significantly different from that obtained in the presence of low auxin concentration alone (1µM). Moreover both the percentage of rooted slices and the number of roots per slice obtained in these culture conditions was not significantly different to that of the optimal auxinic treatment in which the auxin concentration was threefold higher.     

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.     

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.     

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 and evaluation of (S,S)-N,N′-bis-[3-(2,2′,6,6′-tetramethylbenzhydryloxy)-2-hydroxy-propyl]-ethylenediamine (S2824) analogs with anti-tuberculosis activity

In order to identify new and potent candidate drugs to treat tuberculosis, a library of compounds was screened, and (S,S)-N,N′-bis-[3-(2,2′,6,6′-tetramethylbenzhydryloxy)-2-hydroxy-propyl]-ethylenediamine (S2824) was identified as a hit in the screen. This research discusses our efforts to synthesize and test 30 analogs of this hit for activity against Mycobacterium tuberculosis. Two compounds with homopiperazine ring possess high in vitro activity against drug sensitive and resistant M. tuberculosis with MICs 0.78–3.13 μg/mL (or 1.22–4.88 μM).     

Exploration of secondary and tertiary pharmacophores in unsymmetrical N,N′-diaryl urea inhibitors of soluble epoxide hydrolase

The impact of various secondary and tertiary pharmacophores on in vitro potency of soluble epoxide hydrolase (sEH) inhibitors based on the unsymmetrical urea scaffold 1 is discussed. N,N′-Diaryl urea inhibitors of soluble epoxide hydrolase exhibit subtle variations in inhibitory potency depending on the secondary pharmacophore but tolerate considerable structural variation in the second linker/tertiary pharmacophore fragment.     

Syntheses and antitumor activities of N′1,N′3-dialkyl-N′1,N′3-di-(alkylcarbonothioyl) malonohydrazide: The discovery of elesclomol

A series of N′¹,N′³-dialkyl-N′¹,N′³-di(alkylcarbonothioyl) malonohydrazides have been designed and synthesized as anticancer agents by targeting oxidative stress and Hsp70 induction. Structure–activity relationship (SAR) studies lead to the discovery of STA-4783 (elesclomol), a novel small molecule that has been evaluated in a number of clinical trials as an anticancer agent in combination with Taxol.     

The oxidation of N,N′-bis(4-aminophenyl)-N,N′-dimethylethylenediamine (BED) by rat liver

We have examined the oxidation of N,N′-bis(4-aminophenyl)-N,N′-dimethylethylenediamine (BED) by tissue homogenates and fractions of liver homogenates. We find that this agent both gives osmiophilic deposits in tissue blocks and readily increases the uptake of oxygen by hepatic homogenates. The highest activity was in the mitochondrial and, next, in the microsomal fractions. Kinetic evidence indicates that the former represents two enzymatic activities while the latter is only a single site. The activity was greatest in the outer membrane of the mitochondria, in agreement with electron micrographic studies and in the rough microsomal fraction. Further, it was very sensitive to both formaldehyde and detergents. The activity was not well associated with either monamine oxidase (benzylamine substrate) or xanthine oxidase activities. Activity was observed in a large number of tissues.     

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.     

The reaction of amines with N,N′-ethylenebis(salicylideneiminato)(nitrato)-iron(III) and related complexes

The title compound, Fe(salen)NO₃, was reacted with imidazole, 1-methylimidazole, piperidine, and morpholine in either chloroform or dichloromethane solution. The reactions were monitored with proton NMR and electronic spectra and conductance measurements. The imidazole bases appeared to react with the complex in a 2:1 fashion with displacement of the nitrate, producing a high-spin iron(III) complex. The secondary amines promoted hydrolysis with any trace water present to form [Fe(salen)]₂O. The chloro complex, Fe(salen)Cl, did not react with the imidazole bases, but did form the μ-oxo complex when a large excess of piperidine was present. The N,N′-phenylenebis-(salicylideneimine) complex, Fe-(salphen)NO₃, was found to precipitate from an imidazole (im) chloroform solution as the high-spin complex, Fe(salphen)NO₃·2im.     

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.     

Biodegradabilities of Ethylenediamine-N,N′-disuccinic Acid (EDDS) and Other Chelating Agents

Biodegradabilities of chelating agents were tested with activated sludge. Ethylenediaminetetraacetic acid (EDTA) remained intact in the effluent even after acclimation for 100 days, but propanediamine-N,N′-disuccinic acid (PDDS) and nitrilotriacetic acid (NTA) were biodegraded after acclimation for 5 and 23 days, respectively. Optical isomers of ethylenediamine-N,N′-disuccinic acid (EDDS) had different biodegradabilities: SS- and RS-isomers were susceptible to biodegradation, but the RR-isomer was resistant. SS-isomer was degraded even by activated sludge without acclimation.     

Effectiveness of N,N′-Bis(2-hydroxy-5-methylbenzyl) ethylenediamine-N,N′-diacetic acid (HJB) to supply iron to dicot plants

Iron chlorosis is commonly corrected by the application of EDDHA chelates, whose industrial synthesis produces o,oEDDHA together with a mixture of regioisomers and other unknown by-products. HJB, an o,oEDDHA analogous, is a new chelating agent with a purer synthesis pathway than EDDHA. The HJB/Fe³⁺ stability constant is intermediate between the racemic and meso o,oEDDHA/Fe³⁺ stereoisomers. This work studied the efficacy of HJB as a Fe source in plant nutrition. No significant differences between o,oEDDHA/Fe³⁺, HJB/Fe³⁺ and HBED/Fe³⁺ were observed when they are used as substrates of the iron-chelate reductase of mild chlorotic cucumber plants. Chelates prepared with the stable isotope ⁵⁷Fe were used in both soil and hydroponic experiments. In the hydroponic experiment, nutrient solutions with low doses of chelates were renewed weekly. Soybean plants treated with o,oEDDHA/⁵⁷Fe³⁺ recorded the highest results in biomass, SPAD index and Fe nutrition. In the soil experiment, chelates were added once at a rate of 2.5 mg Fe per kg of a calcareous soil. Soybean plants treated with HJB/⁵⁷Fe³⁺ recorded a higher biomass and SPAD index in young leaves than the plants treated with o,oEDDHA/⁵⁷Fe³⁺; however, ⁵⁷Fe and total Fe concentrations in leaves were lower. The results of both pot experiments are associated with a faster ability by o,oEDDHA to provide Fe to the plants and with a more continuous supply of Fe from HJB/Fe³⁺. HJB/⁵⁷Fe³⁺ effectively alleviated the Fe-deficiency chlorosis of soybean with a longer lasting effect than o,oEDDHA/⁵⁷Fe³⁺.     

Binuclear metal complexes. 59. Synthesis and magnetism of dicopper(II) and copper(II)-nickel(II) complexes with N,N′-ethylenedisalicylamidatocuprate(II)

The complexes [Cu(samen)Cu(L)] and [Cu(samen)Ni(L)₂] (Lbpy, phen) have been synthesized by the reaction of sodium N,N′-ethylenedisalicylamidatocuprate(II) pentahydrate (Na₂- [Cu(samen)]·5H₂O), a divalent metal ion, and 2,2′- dipyridyl or 1,10-phenanthroline. Cryomagnetic data for the CuCu complexes did not fit the Bleaney- Bowers equation; but the data did fit a modified Bleaney-Bowers equation

with a large negative J and a significant negative θ, suggesting that a considerable magnetic interaction operates between essentially planar [Cu(samen)Cu(L)] molecules. The magnetisms of the CuNi complexes were well interpreted in terms of the susceptibility equation based on the Heisenberg model. An antiferromagnetic spin-exchange interaction (J= −13∼−14 cm⁻¹) was suggested between the metal ions.     

Crystal structure and conformational analysis of s-cis-(acetylacetonato)(ethylenediamine-N,N′-diacetato)-chromium(III)

The crystal structure of [Cr(edda)(acac)] (edda = ethylediamine-N,N′-diacetate; acac = acetylacetonato) has been determined by a single crystal X-ray diffraction study at 150 K. The chromium ion is in a distorted octahedral environment coordinated by two N and two O atoms of chelating edda and two O atoms of acac, resulting in s-cis configuration. The complex crystallizes in the space group P2₁/c of the monoclinic system in a cell of dimensions a = 10.2588(9), b = 15.801(3), c = 8.7015(11) ?, β =101.201(9)° and Z = 4. The mean Cr-N(edda), Cr-O(edda) and Cr-O(acac) bond distances are 2.0829(14), 1.9678(11) and 1.9477(11) ? while the angles O-Cr-O of edda and O-Cr-O of acac are 171.47(5) and 92.72(5)°, respectively. The crystal structure is stabilized by N–H⋯O hydrogen bonds linking [Cr(edda)(acac)] molecules in distinct linear strands. The visible electronic and IR spectroscopic properties are also discussed. An improved, physically more realistic force field, Vibrationally Optimized Force Field (VOFF), capable of reproducing structural and vibrational properties of [Cr(edda)(acac)] was developed and its transferability demonstrated on selected chromium(III) complexes with similar ligands.     

The molecular structure and magnetic properties of the dimeric N,N′-ethylenebis(salicylamine)Fe(II)-μ-methoxo-N,N′-ethylene(o-hydroxylphenylglycine)salicylamine Fe(III): A complex with a μ-monodentate acetato bridge

We have prepared and characterized a dimeric complex of the formula Fe₂L(OCH₃)L′·solvent where L = N,N′-ethylenebis(salicylamine) and L′ = N,N′-ethylene(o-hydroxylphenylglycine)salicylamine. Crystals of the methanol solvate were found to be orthorhombic, space group P2nb, with a = 13.748 (5), b = 22.426(9), c = 11.762(6) Å and d_calc = 1.41 g/cm³. Least squares refinement of 966 reflections gave a final R factor of 0.066. The structure shows that the two iron atoms are coordinated to two different ligands and are bridged by a methoxide ion and a μ-monodentate acetate oxygen from the pendant arm of L′. The magnetic susceptibility was measured over the range 2–300 K and gave a spin coupling constant J = −8.3 cm⁻¹. The significance of acetate bridges to the exchange coupling pathway is discussed.     

Chemical access to the mononuclear Mn(III) [(mL)Mn(OMe)]+ complex (mLH = N,N′-bis-(2-pyridylmethyl)-N-(2-hydroxybenzyl)-N′-methyl-ethane-1,2-diamine) and electrochemical oxidation to the Mn(IV) [(mL)Mn(OMe)]2+ species

Chemical oxidation in acetonitrile of the previously reported phenolato-bridged binuclear Mn(II) complex [(mL)MnMn(mL)]²⁺ (1), where mLH is pentadentate N,N′-bis-(2-pyridylmethyl)-N-(2-hydroxybenzyl)-N′-methyl-ethane-1,2-diamine ligand [C. Hureau, et al., Chem. Eur. J. 2004, 10, 1998–2010] using iodosylbenzene PhIO (dissolved in methanol) is described. The addition of one to four equivalents of PhIO per Mn ion leads to the transient formation of the mono-μ-oxo binuclear Mn₂(III,III) complex [(mL)Mn(μ-O)Mn(mL)]²⁺ (2), previously studied. After addition of five equivalents of PhIO per Mn ion, the mononuclear Mn(III) species [(mL)Mn(OMe)]⁺ (3) is quantitatively generated. The UV–Vis spectrum of 3 displays a broad band at 456 nm (ε = 1000 L mol⁻¹ cm⁻¹) attributed to phenolato to Mn(III) charge transfer transition. Complex 3 exhibits a reversible oxidation wave at E^1/2 = 0.68 V versus SCE, and the mononuclear Mn(IV) complex [(mL)Mn(OMe)]²⁺ (3^ox) can thus be generated by exhaustive electrolysis at 1.0 V versus SCE. The 9.4 GHz EPR spectrum of complex 3^ox shows a strong transition near g = 4 consistent with a rhombically distorted S = 3/2 system with a zero-field splitting dominating the Zeeman effect. UV–Vis spectrum displays a large phenolato to Mn(IV) charge transfer transition at 670 nm (ε = 2450 L mol⁻¹ cm⁻¹).