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).     

Stabilization of a hydrated ketone by metal complexation. The crystal and molecular structures of bis-2,2′,N,N′-bipyridyl ketone-hydrate nickel(II) sulfate,copper(II) chloride and copper(II) nitrate

The crystal structure of the complexes (I)Ni[C₁₁N₈N₂(OH)₂]₂SO₄, (II) Cu[C₁₁H₈N₂(OH)₂]₂Cl₂· 4H₂O and (III) Cu[C₁₁H₈N₂(OH)₂]₂(NO₃)₂·2H₂O have been determined by three-dimensional X-ray analysis methods. Crystal data are: (I), monoclinic, space group C2/c, Z = 4, a = 19.666(4), b = 7.994(2), c = 16.045(6) /rA, /gb = 111.231(9)°, (II), monoclinic, space group C2/c, Z = 4, a = 14.504(4), b = 12.333(8), c = 14.630(3) Å, /gb = 90.92°; and (IIl), monoclinic, space group P2₁/n, Z = 2, a = 7.601(5), b = 11.977(4), c = 14.463(6) Å, β = 93.10(8)°. These structural investigations clearly demonstrate that in each case hydration occurs across the ketone double bond in the ligand and that the resulting hydroxyl group coordinates to the metal. Two di-2-pyridyl ketone ligands are thus bonded to the metal atom in a tridentate fashion. In the nickel complex (I), all six coordination interactions appear to have approximately the same strength. However, in the copper complexes (II) and (III), the pyridyl nitrogens are strongly coordinating to the metal in the equatorial plane, while the hydroxyl groups are more weakly coordinating in the axial direction. The metal to ligand bond distances are: (I) d_Ni−O = 2.098(4), d_NiN = 2.062(4), 2.087(4) Å, (II) d_CuO = 2.465(5), d_CuN = 1.994(5), 2.006(5) Å, (III) d_CuO = 2.464(5), d_CuN = 1.990(5), 2.036(5) Å. The neutral diol that results from hydrolysis of di-2-pyridyl ketone is stabilized by coordination to the metal and such coordination is little affected by changes in the metal, the anion or the extent of hydration.     

Thermodynamics of metalligand bond formation XXXV. Lewis acidity of tin(IV) halides

Thermodynamic data have been obtained for the reactions in benzene solution at 30°C of tin tetrahalides with the following Lewis bases: triphenylarsine, tetrahydrothiophene, tetrahydrofuran, pyridine-N-oxide, dimethylsulphoxide, dimethylformamide and acetonitrile.Triphenylarsine forms a 1:1 adduct of low stability with tin tetrachloride and fails to react with the other halides. The other bases when they react form both 1:1 and 1:2 adducts, the reactivity decreasing in the order SnCl₄ > SnBr₄ > SnI₄. THT and THF do not react with SnI₄; CH₃CN does not react with SnBr₄ or SnI₄. When it is possible to determine data separately for formation of successive adducts it is found that K₁ > K₂ for SnCl₄ and SnBr₄ but K₁ < K₂ for SnI₄.     

Studies on the metal-amide bond. XX. A structural comparison of an unusual dimeric cobalt(III) complex,fac-[Co2(bpen)3]·12H2O,with the free ligand N,N′-Bis(2′-pyridinecarboxamide)-1,2-ethane,bpenH2

The crystal and molecular structures of the ligand bpenH₂ (N,N′-bis(2′-pyridinecarboxamide)-1,2-ethane) and its deprotonated dimeric cobalt(III) complex fac-[Co₂(bpen)₃]·12H₂O have been determined by single-crystal X-ray diffraction methods. Crystal data: (a) bpenH₂, C₁₄H₁₄N₄O₂, orthorhombic, space group Pccn, a=9.638(1), b= 15.288(1), c = 8.684(1) Å, Z=4; (b) Co₂(bpen)₃· 12H₂O, C₄₂H₆₀N₁₂O₁₈Co₂, triclinic, space group P$\text{1}$, a = 11.128(3), b = 14.316(5), c = 16.466(4) Å, α= 92.02(2)°, β = 95.21(2)°, γ = 99.30(2)°, Z = 2.The structures were refined to R 0.034 and 0.053 for 1064 and 7748 independent reflexions, respectively. The bpenH₂ molecule has a space group imposed centre of symmetry, with the amide group adopting a trans configuration in the closely planar picolinamide moiety. The cobalt complex is dimeric in which three bpen ligands, acting each as a bis(N₂-bidentate), bridge the two metal atoms. Each cobalt atom is octahedral with CoN_py 1.944(3) and Co N_am 1.933(3) Å. The Co··Co separation is 5.493(1) Å. The symmetry of the dimeric molecule is D₃ which is consistent with that indicated from solution NMR studies.     

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.     

Effect of N,N′-bis (alkyldimethyl)-α,ω-alkanediammonium dibromides on bacteria of the genusclostridium

Antibacterial effect of 17 ammonium compounds of the type of N,N′-bis(alkyldimethyl)-α,ω-alkanediammonium dibromides was tested on anaerobically sporulating bacteria of the genusClostridium. A sizable antibacterial activity was displayed by five N,N′-bis(alkyldimethyl)-1,6-hexanediammonium dibromides and by four N,N′-bis(decyldimethyl)-α,ω-alkanediammonium dibromides. These compounds exhibited activity higher than, or comparable with, that of the reference standards Ajatin and Septonex. The maximum antibacterial activity was found in compounds whose alkyl chain contained 9–12 carbon atoms. Compounds with a lower number of carbon atoms in the chain (less than 8) exhibited a low activity.     

Synthesis and characterization of 5,5,7,12,12,14-hexamethyl- 1,4,8,11-tetraazacyclotetradecane-N′,N‴-diacetic acid and its transition metal complexes; crystal structure of the nickel(II) monohydrogen bromide monohydrate complex of this macrocycle

The synthesis and characterization of a new 14- membered tetraazamacrocylic ligand 5,5,7,12,12,14- hexamethyl-1,4,8,11-tetraazacyclotetradecane-N′,N‴- diacetic acid (H₂L²) are reported. Cobalt(III),nickel(II) and copper(II) complexes with this ligand were prepared and their IR and visible spectra studied.The molecular structure of the complex NiL²· HBr·H₂O was proved by single-crystal X-ray analysis. The compound crystallizes in the space group P2₁/n, with cell parameters a = 16.7109(13), b = 9.0539(9), c = 17.0277(13) Å, β = 107.46(6)° and Z = 4. The structure was solved by direct and Fourier methods and refined by full matrix least square calculation to R = 0.042 for 4355 observed reflections (I > 3σ(I)). The complex shows a cis-octahedral geometry with the macrocycle coordinated in a folded configuration to four sites around the central nickel atom. The two carboxylate groups of the side chain are on the same side of the approximate plane of the macrocycle.     

The thermal decomposition of group IIB metal(II) halide complexes. Part III. Low frequency infrared spectra and thermal behaviour of N,N,N′-trimethylethylenediamine complexes

The group IIb metal dihalide-N,N,N′-trimethylethylenediamine complexes are described. Low frequency infrared spectroscopic studies and conductance data have provided evidence for the formulation and structure of the complexes. The thermal behaviour of these complexes has been examined by thermogravimetry and differential scanning calorimetry. For cadmium and mercury complexes complete loss of ligand occurred followed eventually by sublimation of the metal halide, whereas the zinc complexes sublimed unchanged.     

Conformations of septanosides. The crystal and molecular structure of 5-O-(chloroacetyl)-1,2:3,4-di-O-isopropylidene-α-D-glucoseptanose

The crystal structure of 5-O-(chloroacetyl)-1,2:3,4-di-O-isopropylidene-α-D-glucoseptanose, a seven-membered ring sugar, has been determined by using 1234 reflections measured on a diffractometer. The crystals belong to the orthorhombic space group P2₁2₁2₁, having cell dimensions a  27.750, b  10.714, and c  5.702 Å. The measured and calculated densities are 1.25 g.cm⁻³ and 1.32 g.cm⁻³, respectively; the latter value assumed four molecules in the unit cell. The structure was determined by a combination of the heavy-atom technique and the tangent method. Full-matrix least-squares refinement with anisotropic temperature factors for the nonhydrogen atoms and isotropic temperature factors for the hydrogen atoms lowered the conventional R value to 0.066. The seven-membered ring adopts a ^5.6C₂(D) twist-chair conformation. Both of the dioxolane rings have the envelope shape, the puckered atoms being C-2 and C-4 of the seven-membered ring. The molecular packing is dominated by Van der Waals forces. The conformations of three known 7-membered ring sugars are compared. It is found that the pseudorotation of the septanose ring and the dioxolane rings are correlated to the position of attachment of the latter rings to the central septanose ring.     

Calcium-loaded 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid blocks cell-to-cell diffusion of carboxyfluorescein in staminal hairs of Setcreasea purpurea

The effect of microinjected calcium-loaded 1,2-bis(2-aminophenoxy) ethane-N,N,N,N-tetraacetic acid (CaBAPTA) on cell-to-cell diffusion of carboxyfluorescein (CF) was examined in staminal hairs of S. purpurea Boom. The CaBAPTA was microinjected into the cytoplasm of the staminal hairs either with CF or prior to a subsequent microinjection of CF. The cell-to-cell diffusion of CF along the hair was monitored using enhanced-fluorescence video microscopy. Cytoplasmic streaming stopped in cells treated with CaBAPTA, indicating that intracellular Ca²⁺ had increased. Cell-to-cell diffusion of CF was blocked in cells treated with Ca-BAPTA. An inhibition of cytoplasmic streaming and cell-to-cell diffusion was observed in the cells adjoining the CaBAPTA-microinjected cell, indicating that the Ca-BAPTA appeared to pass through plasmodesmata. While cytoplasmic streaming resumed 5–10 min after CaBAPTA treatment, cell-to-cell diffusion did not resume until 30–120 min later. These data support an involvement of calcium in the regulation of cell-to-cell communication in plants.Abbreviations BAPTA 1,2-bis(2-aminophenoxy)ethane-N,N,N, N-tetraacetic acid - CF carboxyfluorescein This work was supported by Professional Staff Congress-City University (PSC-CUNY) of New York grant No. 667180 and U.S. Department of Agriculture grant No. 87-CRCR-1-244.     

Studies on the Synthesis of N′-Acetyl AZA-Analogues of Ganciclovir—Unexpected Liability of N′-(2-Hydroxyethyl)-Azanucleosides Under Basic Conditions

The O′-pivaloyl diesters of N′-acetyl-azanucleosides were obtained from N-[1,3-di(pivaloyloxy)prop-2-yl]-N-(pivaloyloxymethyl)acetamide and a silylated nucleobase under Vorbrüggen's conditions. Unexpectedly, de-pivaloylation of the diesters under basic conditions afforded the corresponding nucleobase and N-acetylserinol. Mechanistic investigations showed that these products result from the following cascade of spontaneous transformations initiated by the mono de-pivaloylation of the starting diesters. N′-Deacetylation of the resultant mono-esters via the intramolecular N-O acetyl migration is the key step of the cascade; the corresponding NH-azanucleosides in the form of O-acetyl-O′-pivaloyl diesters are formed. Fragmentation of these diester intermediates gives the nucleobase and O-acetyl-O′-pivaloylserinol. Conversion of the latter to N-acetylserinol involves the selective O-N acetyl migration followed by de-pivaloylation of the resulting N-acetyl-O-pivaloylserinol.     

Heteropolymetallic complexes of 1,1′-bis(diphenylphosphino)ferrocene (dppf). IV. Solvolytic behavior and cytostatic properties towards the KB cell-line of dppf and 1,2-bis(diphenylphosphino)ethane cis-complexes of Pt(II) and Pd(II)

The novel cis-platinum(II) complexes [(dppe)Pt(μ-OH)]₂(BF₄)₂ and [(dppe)Pt(DMF)₂](BF₄)₂ have been prepared and characterized by ³¹P NMR, together with cis-[(dppe)Pt(μ-Cl)]₂(BF₄)₂, both in poorly and strongly coordinating solvents (dppe = 1,2-bis(diphenylphosphino)ethane). All these complexes and their dppf analogs (dppf = 1,1′-bis(diphenylphosphino)ferrocene) as well as (dppf)PtCl₂, (dppe)PtCl₂, (dppf)PdCl₂, [(dppf)Pd(μ-Cl)]₂(BF₄)₂ and [(dppf)Pd(μ-OH)]₂(BF₄)₂ have been tested as antiproliferating agents towards Eagle's KB cell-line. Their activity is compared with that of free diphosphine ligands. For Pt(II) complexes, the ID₅₀ figures are found to be higher than those observed for free dppf and dppe. On the contrary, the activity of the palladium dppf complexes is substantially identical to that of free diphosphine.     

He(I) and He(II) photoelectron spectra of Hyprrole-2-CHN′t-Bu and the biscarbonyl Rh(I) and Ir(I) complexes of its anion

The He(I) and He(II) photoelectron spectra of a series of [(LL)M(CO)₂] (LL = pyrrole-2-CHN′ R; R = t-Bu; M = Rh, Ir) complexes are reported. Assignments are proposed based on He(I)/He(II) intensity differences, on molecular orbital calculations of related complexes and of free ligands, and by comparison with the spectra of the free ligands Hpyrrole-2-CHN′t-Bu, Hpyrrole-2-carbaldehyde and Hpyrrole.The electronic structure of the complexes is discussed and conclusions are drawn about the metal-ligand interaction.     

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.     

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.     

Nucleosides. 145. Synthesis of 2,5′-Anhydro-2-Thiouridine and its Conversion to 3′-O-Acetyl-2,2′-Anhydro-5′-Chloro-5′-Deoxy-2-Thiouridine. Studies Directed Toward the Synthesis of 2′-Deoxy-2′-Substituted arabino Nucleosides (7)

Abstract

In an attempt to introduce a substituent at C-2′ in the “up” arabino configuration directly by nucleophilic displacement reaction of a preformed pyrimidine ribonucleoside, we synthesized 2,5′-anhydro-5′-deoxy-2-thiouridine (6) in three steps from uridine. Compound 6 was converted into the 3′-O-acetyl derivative 7. Upon treatment of 7 with triflyl chloride in methylene chloride in the presence of triethylamine and p-dimethylaminopyridine, 2,2′-anhydro-1-(3-O-acetyl-5-chloro-2,5-dideoxy-β-D-arabinofuranosyl)-2-thiouracil (9) was obtained as the only isolable product. Obviously, the intermediate 3′-O-acetyl-2,5′-anhydro-2′-O-triflyl-2-thiouridine (8) was attacked by the chloride nucleophile at C-5′ first giving the 2′-O-triflyl-2-thiouridine intermediate from which 9 was formed by intramolecular nucleopilic reaction.