Novel metal-based antimicrobial agents of copper(II) complexes: Synthesis,spectral characterization and DNA interaction study

Few novel mixed ligand copper(II) complexes of the type [Cu(L)(Cl)₂(H₂O)], [Cu(L)₂]Cl₂, [Cu(L)L¹] and [Cu(L)(phen)H₂O]Cl₂ (where L is the ligand obtained from the condensation of N-(2-aminoethyl)-1,3-propanediamine with m-nitrobenzaldehyde (L_a)/o-chlorobenzaldehyde (L_b)/benzaldehyde (L_c)/p-methoxybenzaldehyde (L_d)/p-hydroxybenzaldehyde (L_e)/furfuraldehyde (L_f)/pyrrole-2-carboxaldehyde (L_g); L¹ is another ligand obtained from the condensation of anthranilic acid with salicyaldehyde; phen = 1,10-phenanthroline) have been synthesized and characterized by the spectral and analytical techniques. From these data, it is found that the ligands adopt distorted octahedral geometry on metalation with Cu(II) ion. The XRD data indicate that the complexes are polycrystalline with nanosized grains. The SEM images of [Cu(L_a)phen(H₂O)]Cl₂ and [Cu(L_f)₂]Cl₂ complexes show that they have leaf and cauliflower like morphology. The in vitro biological screening effects of the investigated compounds have been tested against the bacteria such as Escherichia coli, Klebsiella pneumoniae, Salmonella typhi, Pseudomonas aeruginosa and Staphylococcus aureus and fungi such as Aspergillus niger, Rhizopus stolonifer, Aspergillus flavus, Rhizoctonia bataicola and Candida albicans by the well diffusion method. A comparative study of MIC values of the Schiff base ligands and their complexes indicates that the complexes exhibit higher antimicrobial activity than the free ligands. An electrochemical study of the copper complexes containing electron withdrawing substituted ligands reveals that they prefer to bind to DNA in Cu(II) rather than Cu(I) oxidation state.     

Investigation on the thermal decomposition some heterodinuclear NiII-MII complexes prepared from ONNO type reduced Schiff base compounds ( M II=ZnII, CdII)

N,N′-bis(salicylidene)-1,3-propanediamine (LH₂), N,N′-bis(salicylidene)-2,2′-dimethyl-1,3-propanediamine (LDMH₂), N,N′-bis(salicylidene)-2-hydroxy-1,3-propanediamine (LOH₃), N,N′-bis(2-hydroxyacetophenylidene)-1,3-propanediamine (LACH₂) and N,N′-bis(2-hydroxyacetophenone)-2,2′-dimethyl-1,3-propanediamine (LACDMH₂) were synthesized and reduced to their phenol-amine form in alcoholic media using NaBH₄ (L^HH₂, LDM^HH₂, LOH^HH₂, LAC^HH₂ and LACDM^HH₂). Heterodinuclear complexes were synthesized using Ni(II), Zn(II) and Cd(II) salts, according to the template method in DMF media. The complex structures were analyzed using elemental analysis, IR spectroscopy, and thermogravimetry. Suitable crystals of only one complex were obtained and its structure determined using X-ray diffraction, NiLAC^H·CdBr₂·DMF₂, space group orthorhombic, Pbca, a=20.249, b=14.881, c=20.565 ? and Z=8. The heterodinuclear complexes were seen to be of [Ni·ligand·MX₂·DMF₂] structure (ligand=L^H2−, LDM^H2−, LOH^H2−, LAC^H2−, LACDM^H2−, M=Zn^II, Cd^II, X=Br⁻, I⁻). Thermogravimetric analysis showed irreversible bond breakage of the coordinatively bonded DMF molecules followed by decomposition at this temperature.     

4-Substituted-3,4-dihydro-3-methyl-2H-1,3-benzoxazin-2-ones. III (2,3). Solvolytic-reductive transformation of 4-(2-keto)-benzoxazin-2-ones into oxazin-2-ones

A series of 4-(2-keto-substituted)-3,4-dihydro-3-methyl-2H-1,3-benzoxazin-2-ones 1 (Table I) was synthesized by condensation of 3-alkyl-3,4-dihydro-4-hydroxy-2H-1,3-benzoxazin-2-ones 4 with ketones 5 having active alpha hydrogens. In the presence of alcoholic potassium borohydride, compounds 1 underwent reductive transacylation to give 1,3-oxazin-2-one derivatives 3 (Table III, a,b,c). When the other side of the ketone possessed substituents other than hydrogen, there were always also normal reduction products, i.e., secondary alcohols 2 (Table II) in addition to 3.     

Thermal decompositions of dinitropyridyl and dinitrothienyl dithiocarbamates and t-butyl trithiocarbonates

The title compounds on heating cyclized to yield 7-nitro-1,3-dithiolo[4,5-c]pyridin-2-one (III), 6-nitro-1,3-dithiolo[2,3-c]pyridin-2-one (VIIa), 6-nitrothieno[2,3-d]-1,3-dithiol-2-one (XIVa) and 6-nitrothteno[2,3-d]-1,3-dithiole-2-thione (XIVb).     

Thermal decomposition of some linear trinuclear schiff base complexes with acetate bridges

Ni(II)–M(II)–Ni(II) nuclear structured complexes were prepared from N,N’-bis(salicylidene)-1,3-propanediamine (LH2) and its derivatives N,N’-bis(salicylidene)-2,2’-dimethyl-1,3-propanediamine (LDMH₂) and N,N’-bis(salicylidene)-2-hydroxy-1,3-propanediamine (LOH3), where M represents one of the following metal ions; Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II). Two different μ-bridges are found between the metal nucleus of the complexes. The phenolic oxygens and acetate ions tend to form μ-bridges between the terminal Ni(II) ions and central metal(II) ion. The coordinatively bonded DMF molecules, in the complexes, were observed to abandon the structure between 160–180°C. Further heating resulted primarily in the thermal decomposition of the complexes above 310°C, whereas metal oxide residue mixtures were observed above 650°C.     

In vitro antifungal and antibacterial properties of thiodiamine transition metal complexes

Synthesis, characterization and biological studies of some thiodiamine metal complexes are described. Cobalt(II) and copper(II) complexes of type [Cu(L)₂Cl₂] and [Co(L)₂SO₄], where L = (cyclohexyl-N-thio)-1,2-ethylenediamine (L¹) and (cyclohexyl-N-thio)-1,3-propanediamine (L²), were synthesized. The synthesized copper and cobalt thiodiamine complexes were characterized by elemental analysis, IR, mass, UV-VIS and ¹H NMR spectroscopic studies. Thiodiamines coordinate as a bidentate N-S ligand. The binding sites are azomethine nitrogen and thioamide sulfur. Molar conductance values in dimethylsulfoxide indicate non-electrolyte nature of the complexes. In vitro-antimicrobial screening shows promising results against both bacterial and fungal strains.     

An efficient synthesis of 1,3-diaryl-pyrrolo[1,2-<Emphasis Type="Italic">a</Emphasis>]quinoxalines from 2-(1h-pyrrol-1-yl)phenylamines

The condensation of 1,3-diaryl-4-bromo-2-buten-1-ones with o-phenylenediamine leads to 2-[2,4-diaryl-1H-pyrrol-1-yl]phenylamines. Heating solutions of these compounds in formic acid leads to formylation and intramolecular condensation to give 1,3-diarylpyrrolo[1,2-a]quinoxalines. The acylation of 2-[2,4-diphenyl-1H-pyrrol-1-yl]phenylamine with acetic anhydride in acetic acid leads to an acetamide, which readily cyclizes to give 4-methyl-1,3-diphenylpyrrolo[1,2-a]quinoxaline upon heating with POCl₃.     

Synthesis of 1,2,3,4-tetrahydroquinazoline derivatives as potential alpha-adrenergic blocking agents

The synthesis of N,N′-bis[6-(1,2,3,4-tetrahydro-3-quinazolidyl)hexyl]cystamine (I) and 3-(6-aminohexyl)-1,2,3,4-tetrahydroquinazoline (II) are described. Compound I is obtained by condensation of o-nitrobenzoyl chloride with 3-(6-aminohexyl)-1,3-thiazolidine (III) followed by dimerization, reduction and formation of tetrahydroquinazoline ring. A similar method was used for preparation of compound II. These compounds and some synthesis intermediates are potential alpha-adrenergic blockers.     

New syntheses of pyrido[3,2-d]pyrimidines

New synthetic routes to pyrido[3,2-d]pyrimidines starting with 5-amino-1,3,6-trimethyluracil (I) or 1,3,6-trimethyl-5-nitrouracil (X) are described. Thus, condensation of I with arylaldehydes gave 5-arylideneamino-1,3,6-trimethyluracils (IIa-h), which upon heating with dimethylformamide dimethylacetal afforded 6-aryl-1,3-dimethylpyrido[3,2-d]pyrimidine-2,4(1H,3H)-diones (Va-h) via 5-arylideneamino-1,3-dimethyl-6-(2-dimethylaminovinyl)uracils (IIIa-h). On the other hand, reaction of X with phenylacetaldehyde in the presence of base yielded Va and its 5-oxide (XI).     

Thermally induced isomeric transformations ofbis-(diamine) complexes of nickel(II) nitrate in the solid phase

Summary Thermal reactions of [Ni(diamine)₂(H₂O)₂](NO₃)₂ and [Ni(diamine)₂(NO₃)₂] (where diamine=1,2-ethanediamine,N-methyl-1,2-ethanediamine,N-ethyl-1,2-ethanediamine, 1,3-propanediamine andN-methyl-1,3-propanediamine) have been investigated in the solid phase. The 1,2-ethanediamine andN-methyl-1,2-ethanediamine complexes undergo thermally induced endothermic irreversible isomeric transformations. In the 1,2-ethanediamine complex the transformation is thermochromic, whereas it is not for theN-methyl-1,2-ethanediamine complex. The transformations are explained in terms of the axial interaction of NO₃ ions with nickel as well as to ligand field weakening resulting from conformational changes of the individual diamine chelate rings.Supplememtary data available: X-ray powder diffraction data (Table3).     

4-Substituted-3-alkyl-3,4-dihydro-2H-1,3-benzoxazin-2-ones. IV (2-4). Keto-Enol tautomerism of β-keto ester derivatives. Reaction of β-dicarbonyl compounds with diamines

A series of α-[3-alkyl-3,4-dihydro-2-oxo-2H-1,3-benzoxazin-4-yl]-β-keto ester derivatives 1 (Table I) were synthesized by the condensation of 3-alkyl-3,4-dihydro-4-hydroxy-2H-1,3-benzoxazine-2-ones 3 (2) with β-keto esters 4 in the presence of traces of mineral acids under azeotropic conditions. Condensation of 1 with hydrazines 5 gave pyrazolone derivatives 2 (Table II). Condensation of β-diketone derivatives 6 with hydrazines 5 and with 1,2-benzenediamine ( 8 ) resulted in the formation of pyrazoles ( 7a-c ) and diazepine derivatives 12 (Table III) and 13 , respectively.     

Synthesis of Benzo[a]phenanthridine Derivatives by Condensation of N-Arylmethylene-2-naphthylamines with 5-Phenyl- and 5-(p-Methoxyphenyl)-1,3-cyclohexanediones

Condensation of N-arylmethylene-2-naphthylamines with 5-phenyl- and 5-(p-methoxyphenyl)-1,3-cyclohexanediones in various solvents gave new hexahydrobenzo[a]phenanthridin-4-one derivatives. Three-component condensation of 2-naphthylamine, appropriate aldehyde, and 5-(p-methoxyphenyl)-1,3-cyclohexanedione was also studied.     

Preparation and structural characterization of hetero-dinuclear Schiff base copper(II)-zinc(II) complexes and their inhibition studies on Helicobacter pylori urease

A series of hetero-dinuclear Cu^II-Zn^II complexes, [CuZnCl₂L¹] (1), [CuZnCl₂L²] (2), [CuZnBr₂L³] (3), [CuZnBr₂L⁴(DMF)] (4), [CuZnCl₂L⁴] (5), [CuZnCl₂L⁵] (6), [CuZnCl₂L³] (7) and [CuZnBr₂L¹] (8), where L¹, L², L³, L⁴ and L⁵ are the deprotonated forms of N,N′-bis(3-ethoxysalicylidene)-1,3-propanediamine (H₂L¹), N,N′-bis(2-hydroxynaphthylmethylidene)-1,3-propanediamine (H₂L²), N,N′-bis(3-methoxysalicylidene)-1,3-propanediamine (H₂L³), N,N′-bis(salicylidene)-1,3-propanediamine (H₂L⁴) and N,N′-bis(salicylidene)-1,4-butanediamine (H₂L⁵), respectively, have been synthesized and characterized by physico-chemical methods and single-crystal X-ray diffraction. The complexes were tested for their urease inhibitory activity. Complexes 1 and 8 show effective urease inhibitory activity with IC₅₀ values of 2.2 and 10.7 μM. The molecular docking study of the complexes with the Helicobacter pylori urease was performed.     

Synthesis,characterization, and catalytic oxidation of ethylbenzene over host (zeolite-Y)/guest (copper(II) complexes of tetraaza macrocyclic ligands) nanocomposite materials

Cu(II) complexes of 14- and 16-membered tetraaza macrocyclic ligands have been encapsulated in nanopores of zeolite-Y by a two-step process in the liquid phase: (1) adsorption of [bis(diamine)copper(II)] (diamine = 1,2-diaminoethane, 1,3-diaminopropane, 1,2-diaminobenzene, and 1,3-diaminobenzene); [Cu(N–N)₂]²⁺–NaY; in the nanopores of the zeolite-Y and (2) in situ condensation of the copper(II) precursor complex with ethylcinnamate. The new host–guest nanocomposite materials were characterized by chemical analysis and spectroscopic methods. The “neat” and encapsulated complexes exhibit good catalytic activity in the oxidation of ethylbenzene at 333 K, using tert-butyl hydroperoxide as the oxidant. Acetophenone was the major product though small amounts of o- and p-hydroxyacetophenones were also formed revealing that C–H bond activation takes place both at benzylic and aromatic ring carbon atoms.     

A 2D coordination polymer with canted ferromagnetism constructed from ferromagnetic [Ni(II)Co(II)] nodes

A bimetallic coordination polymer, infinity (2)[{LNi (II)Co (II)}(dca) 2], has been constructed from heterobinuclear [Ni (II)Co (II)] nodes and dicyanamido spacers [L (2-) is the dianion of the Schiff base resulting from the 2:1 condensation of 3-methoxysalicyladehyde with 1,3-propanediamine; L (2-) = N, N'-propylenebis(3-methoxysalycilideneiminato)]. The intranode Co (II)-Ni (II) interaction was found to be ferromagnetic because of the orthogonality of the magnetic orbitals. Below 12 K, the onset of the canted ferromagnetic ordering is observed.     

1,4-Cycloaddition reactions. II. Preparation of p-dioxino[2,3-g]furo[3,2-c] quinolines,p-dioxino[2,3-f] furo[3,2-c] quinolines,and [1,3] dioxolo[4,5-g] furo[3,2-c] quinolines from 2,3-dihydro-5-methylfuran and schiff bases

The boron trifluoride catalyzed 1,4-addition of 2,3-dihydro-5-methylfuran to N-(p-methoxy-benzylidene)-1,4-benzodioxan-6-amine (II) gave 2 pairs of epimers, 2,3,3a,4,5,8,9,11b-octahydro-4-(p-methoxyphenyl)-11b-methyl-p-dioxino[2,3-g]furo[3,2-c]quinoline (IIIa and b) and 2,3,7,8,8a,9.10,1la-octahydro-8-(p-methoxyphenyl)-11a-methyl-p-dioxino[2,3-f]furo[3,2-c]quinoline (IVa and b). When N-(p-methoxybenzylidene)-3,4-methylenedioxyaniline (V) was condensed with 2,3-dihydro-5-methylfuran in an analogous manner, a mixture of 2 epimers of 2,3,3a,4,5,10b-hexahydro-4-(p-methoxyphenyl)-10b-methyl[1,3]dioxolo[4,5-g]furo[3,2-c]quinoline (VIa and b) was isolated. Treatment of this mixture with sulfur afforded 6-(p-methoxyphenyl)-8-methyl-1,3-dioxolo[4,5-g]quinoline-7-ethanol (VIII). Structural assignments for all of the products were made from NMR spectra. None of the compounds possessed appreciable biological activity.     

Synthese des (R)-trans-11-Hydroxy-8-dodecensäure-lactons (Recieifeiolid)

Synthesis of Recifeiolide The synthesis of the mould metabolite recifeiolide (VIII), a 12-membered ring lactone, is described. 1,3-Butandiol was resolved with (?)-camphanic acid via (R)-1-iodo-3-butanol (II) into (R)-3-hydroxybutyl triphenyl phosphonium iodide (III). Wittig condensation of the phosphorane derived from III with methyl 8-oxo-octanoate (V) led to the methyl trans-11-hydroxy-8-dodecenoate (VI). The corresponding hydroxy acid VII was transformed into the S-(2-pyridyl) carbothioate which cyclizes under the influence of silver ion to the lactone VIII. With (?)-(R)-1,3-butandiol (I) as starting material the naturally occurring (+)-(R)-recifeiolide (VIII) is produced in 70% yield from VII.     

Platinum(IV) and palladium(II) thiosemicarbazide and thiodiamine complexes: A spectral and antibacterial study

Platinum(IV) and palladium(II) complexes [Pt(L)₂Cl₂] and [Pd(L)Cl₂], [where, L?=?1,1-diphenyl-2-thiosemicarbazide (L¹) and (1,1-diphenyl-2-thio)-1,3-propanediamine (L²) have been synthesized. The thiosemicarbazides and thiodiamines exist as the thione-thiol tautomer and coordinate as a bidentate N-S ligand. The ligands are monobasic bidentate. The complexes have been characterized by elemental analysis, IR, mass, electronic and 1H NMR spectroscopic studies. In vitro antibacterial studies have also been carried out for some complexes.     

Synthèse et propriétés photochromiques de 1, 3-dihydrospiro[2H-indole-2,3′-[3H]pyrimido[5,4-f][1,4]benzoxazines] et de 1,3-dihydrospiro[2H-indole-2,7′-[7H]thiazolo[5,4-f][1,4]benzoxazines]

Synthesis and Photochrmic Characteristics of 1,3-Dihydrospiro[2H-indole-2,3′-[3H-]pyrimido[5,4-f][1,4]benzoxazines] and 1,3-Dihydrospiro[2H-indole-2,7′[7H]thiazolo[5,4-f][1,4]benzoxazines] Two new series of 1,3-dihydrospiro[2H-indole-ozazine] derivatives were synthesized, the 1,3-dihydrospiro[2H-indole-2,3′-[3H]pyrimido[5,4]pyrimido[5,4-f][1,4]benzoxaines] 4-10 and the 1,3-dihydrospiro[2H-indole2,7′-[7H]thiazolo-[5,4-f][1,4]benzoxaines] 11–17 . These series extend the available range of photochromic properties (rate constant of thermal bleaching, UV/VIS spectrum of the opened coloured form, and photocoloration yield), an interesting feature of variable-transmission materials. The synthesis of these compounds (Scheme 1) required the preliminary synthesis of intermediate β-hydroxy-α-nitrosotherocycles 18 and 19 (Scheme 2). Important amounts of a coloured, non-photochromic, stable secondary product (See 20 ) were found in the condensation in the spiro[indole-thiazolobenzoxazine] series. The photochromic characteristics of the new derivatives were determined using a flash-photolysis apparatus coupled to a fast-scanning spectrometer. The role of the heteroatoms in the oxazine moiety and the role of substitutents in the indole moiety were investigated quantitatively through the study of the photochromic properties and the solvent effects. The presence of an S-atom gives rise to interesting properties which open up new prospects for synthesis and application.     

Synthesis of new benzo[<Emphasis Type="Italic">c</Emphasis>]phenanthridine derivatives

Three-component condensation of naphthalen-1-amine with triethyl orthoformate and dimedone or cyclopentane-1,3-dione, as well as the reaction of naphthalen-1-amine with 2-acetyl-5,5-dimethylcyclohexane-1,3-dione, gave the corresponding 2-[1-(α-naphthylamino)alkylidene]cycloalkane-1,3-diones which underwent intramolecular cyclization to 7,8,9,10-tetrahydrobenzo[c]phenanthridin-7-one derivatives on heating in polyphosphoric acid. 9,9-Dimethyl-7,8,9,10-tetrahydrobenzo[c]phenanthridin-7-one was reduced to 9,9-dimethyl-7,8,9,10-tetrahydrobenzo[c]phenanthridin-7-ol with sodium tetrahydridoborate.