Synthesis, crystal structures and in vitro antitumor activities of some arylantimony derivatives of analogues of demethylcantharimide

A series of novel arylantimony derivatives of analogues of demethylcantharimide with the formulae Ar_nSbL_(5−n) and Ar_nSbL^′_(5−n)(LH=N-hydroxy-demethyldehydrogencantharimide, L^′H=N-hydroxy-demethylcantharimide, n=3, 4; ArC₆H₅, 4-CH₃C₆H₄, 3-CH₃C₆H₄, 2-CH₃C₆H₄, 4-ClC₆H₄, 4-FC₆H₄) were synthesized and characterized by elemental analysis, IR, ¹H NMR and mass spectroscopy. The crystal structures of (C₆H₅)₄SbL, (4-CH₃C₆H₄)₃SbL₂ and (3-CH₃C₆H₄)₃SbL^′₂ were determined by X-ray diffraction. The in vitro antitumor activities of all compounds against six cancer cells are reported.     

Structural study of oxalamide compounds: H, C, and DFT calculations

The conformational properties of some N-alkyl, N,N′-dialky, and tetraalkyloxalamides have been investigated, in vacuo and in solvent using DFT methods at the B3LYP/6-31G^∗∗ computational level. Special emphasis has been given on oxalamides with substituents of the type -CH₂CH₂OH. In oxalamides with the N-H group (N-alkyl and N,N′-dialky), the most stable conformations are those in which the oxalamide moiety adopts a planar s-trans arrangement and the amide bonds are trans. A different situation appears in the case of tetraalkyloxalamides, in which the oxalamide moiety always adopts a skewed arrangement and there are conformations with similar energy. A careful study of ¹³C and ¹H NMR spectra together with theoretical calculations (GIAO method) allowed the assignment of the signals of these conformers. The presence of the -CH₂CH₂OH chain produces numerous rotamers. The most stable rotamers, in vacuo, are those with strong intramolecular hydrogen bonds, however in solvent, hydrogen bonds are not crucial to establish the most stable specie and depend on the solvent used.     

Cobalt complexes of a selenium diimide and a tellurium diimide dimer

[CoCl₂{N,N′-Te₂(N^tBu)₄}] (1) was obtained in good yields by the reaction of equimolar amounts of (^tBu)NTe(μ-N^tBu)₂TeN(^tBu) and CoCl₂ in toluene under an argon atmosphere. The crystal structure of 1·CH₂Cl₂ showed that the dimeric tellurium diimide ligand is N,N′-chelated to cobalt. The related reaction of Se(N^tBu)₂ and CoCl₂ affords a green product tentatively identified as a 1:1 adduct [CoCl₂{N,N′-Se(N^tBu)₂}] (CHN analysis). However, recrystallization from thf produces the ion-separated complex [Co₂(μ-Cl)₃{N,N′-Se(N^tBu)₂}₂(thf)₂][CoCl₃{NH₂(^tBu)}]·1½thf (2·1½thf), in which the monomeric selenium diimide ligand is N,N′-chelated to cobalt in the cation. A pathway for the formation of 2 from [CoCl₂{N,N′-Se(N^tBu)₂}] in thf is proposed.     

Synthesis, properties, and hepatic metabolism of strongly fluorescent fluorodipyrrinones

From non-fluorescent 8-H fluorophenyldipyrrinones, highly fluorescent (?_F 0.4-0.6) analogs have been synthesized by reaction with 1,1′-carbonyldiimidazole to bridge the dipyrrinone nitrogens and form an N,N′-carbonyldipyrrinone (3H,5H-dipyrrolo[1,2-c:2′,1′-f]pyrimidine-3,5-dione). Amphiphilic, water-soluble 8-sulfonic acid derivatives are then obtained by reaction with concd H₂SO₄. The resulting fluorinated and sulfonated N,N′-carbonyl-bridged dipyrrinones, isolated as their sodium salts, are potential cholephilic fluorescence and ¹⁹F MRI imaging agents for use in probing liver and biliary metabolism. After intravenous injection in the rat they were excreted rapidly and largely unchanged in bile. ¹⁹F NMR spectroscopy of a pentafluorophenyl-tosylpyrrolinone synthetic precursor exhibited rarely seen diastereotopicity.     

Converting 9-Methyldipyrrinones to 9-H and 9-CHO Dipyrrinones

Yellow 9-methyldipyrrinones can be converted readily and in high yields to symmetric linear tetrapyrroles, blue biliverdinoids, which are cleaved in half, smoothly at room temperature to afford yellow 9-H dipyrrinones, and 9-CHO dipyrrinones as their violet to orange colored adducts with the carbon acid used for the scission: thiobarbituric acid (TBA), N,N′-diethylthiobarbituric acid, barbituric acid, N,N′-dimethylbarbituric acid, and Meldrum's acid. The adducts, usually only of passing interest, are formally Knövenagel condensation products of a 9-CHO dipyrrinone with TBA and other carbon acids of this work, and a reverse Knövenagel reaction of such adducts leads to 9-CHO dipyrrinones. Under a set of improved reaction conditions the sequence thus efficiently converts 9-CH₃ dipyrrinones to 9-H and 9-CHO dipyrrinones.     

Synthesis of pyridine N-imine complexes of methylcobaloxime and reactions of bis(dimethylglyoximato)methyl(Pyridine N-imine)cobalt with acid anyhydrides and acetylenedicarboxylic acid dimethyl ester

Pyridine N-imine complexes of methylcobaloxime, CH₃Co(Hdmg)₂(R¹— C₅H_nN⁺N^?H) (n = 4; R¹ = H, 2-CH₃, 3-CH₃, 4-CH₃: n = 3; R¹ = 2,6-CH₃), have been synthesized by the reaction of CH₃Co(Hdmg)₂S(CH₃)₂ with a pyridine N-imine which is generated from a pyridine, hydroxylamine-O-sulfonic acid and K₂CO₃. The reactions of CH₃Co(Hdmg)₂(C₅H₅N⁺N^?H) with acid anhydrides form new methylcobaloxime complexes with N-substituted pyridine N-imines, CH₃Co(Hdmg)₂(C₅H₅N⁺N^?R²) R² = COPh, COMe, COEt). With maleic anhydride, (pyridine N-acryloylimine)carboxylic acid is formed. With acetylenedicarboxylic acid dimethyl ester, 1,3-dipolar cycloaddition of the ligand gives pyrazolo[1,5-a]pyridine-2,3-dicarboxylic acid dimethyl ester.     

Anionic alkyl diglycoldiamides with covalently bonded cobalt bis(dicarbollide)(1−) ions for lanthanide and actinide extractions

Ionic diamides composed of a N,N′-dialkyl diglycolyl complexing group and two cobalt bis(dicarbollide)(1−) anions were synthesized with the aim to develop efficient extraction agents for liquid-liquid extraction of polyvalent cations, i.e. lanthanides and actinides from high-level activity nuclear waste. Compounds of general formulation [{(N,N-(8-CH₂-CH₂O)₂-1,2-C₂B₉H₁₀)(1′,2′-C₂B₉H₁₁)-3,3′-Co)(N′,N′-R)NCOCH₂}₂O]Na₂, where R = n-C₄H₉, n-C₈H₁₇, n-C₁₂H₂₅ and 1-C₆H₄-4-CH₃ (1-4), were prepared and characterized by combination of ¹¹B ¹H, ¹³C NMR spectroscopy, ESI-MS, HPLC and other techniques. Effects of different nitrogen substitution in the structures of 1-4 on the extraction properties were tested. The study resulted in the observation that the compounds are significantly (2-3 orders in magnitude) more efficient extractants for Eu(III) and Am(III) than synergic mixtures of organic N,N′-tetra n-octyl diglycolic acid diamide (TODGA) and chlorinated cobalt bis(dicarbollide) at the same concentrations of both groups. Low polar mixtures of n-dodecane (D) and hexyl methyl ketone (HMK) can be applied as an auxiliary solvent for extraction, replacing thus the polar and less environmentally friendly nitro-, fluoro- and chloro- solvents used in the current dicarbollide liquid-liquid extraction process.     

Synthesis and properties of alkylruthenium complexes bearing primary and secondary amine ligands

A series of 18-electron alkylruthenium complexes, RuR[κ²(N,N′)-(S,S)-R′SO₂NCHPhCHPhNH₂](η⁶-arene) (Ph = C₆H₅, R′ = p-CH₃C₆H₄ and CH₃), bearing a N-sulfonylated diamine ligand was synthesized from the reaction of RuCl[κ²(N, N′)-(S,S)-R′SO₂NCHPhCHPhNH₂](η⁶-arene) with alkylzinc reagents, in which transmetalation proceeded smoothly to give the desired alkyl complexes in good yield and selectivity. Although the isolable amine Ru complexes bearing functionalized alkyl ligands were thermally stable, the simple methyl and ethyl Ru complexes underwent intramolecular deprotonation from NH protons to give the amido Ru complexes with release of the alkanes. The reactivity of the alkyl Ru complexes is highly affected by the structures of the arene ligands.     

The first synthesis of N,O-protected β-isoserines bearing two adjacent quaternary stereogenic centers and their corresponding β-lactams

The reaction of chiral (2S)-enolates of dioxolan-4-ones, derived from lactic and mandelic acids, with (S_R)-tert-butyl sulfinyl ketimines, derived from butan-2-one, pentan-2-one, and decan-2-one, afforded conformationally restrained β^2,2,3,3-isoserines bearing two adjacent quaternary stereogenic centers in the form of N-sulfinyl protected 1′-amino-dioxolan-4-ones. The selective acid-induced removal of the sulfinyl protecting group provided the corresponding 1′-aminodioxolanones, whose base-induced cyclization afforded the corresponding chiral tetra-substituted 3-hydroxy-β-lactams. The synthesis of a dipeptide by reaction coupling between the 1′-aminodioxolanone (2S,5R,1′R)-19 and N,N-dimethylglycine was successfully achieved.     

rac-Lactide polymerization using aluminum complexes bearing tetradentate phenoxy-amine ligands

A family of aluminum-methyl complexes supported by tetradentate phenoxy-amine ligands has been prepared and employed in the ring-opening polymerization of rac-lactide; the ligands include N,N-bis(3,5-dimethyl-2-hydroxybenyl)-N′,N′-dimethyl-1,2-diaminoethane (L¹), N,N-bis(3,5-diisopropyl-2-hydroxybenyl)-N′,N′-dimethyl-1,2-diaminoethane (L²) and N,N-bis(3,5-dichloro-2-hydroxybenyl)-N′,N′-dimethyl-1,2-diaminoethane (L³). Polymerizations of rac-lactide were carried out by treatment of the aluminum-methyl complexes with PhCH₂OH and rac-lactide at 70 °C, affording well-controlled formation of polylactide (PLA) and a moderate isotactic bias for initiators bearing L¹ and L²; the chloro-substituted ligand L³ afforded largely atactic PLA.     

Heavier alkali metal complexes of the bulky alkyl ligand 2-(bis(trimethylsilyl)methyl)-6-methylpyridine: Crystal structures of [{6-Me(2 Pyr)}(Me3Si)2CNa(pmdta)] and [{6-Me(2-Pyr)}(Me3Si)2CK]∞

Reaction of the bulky pyridyl based ligand 6-Me(2-Pyr)(Me₃Si)₂CH with ⁿBuM (M = Na, K) in the presence of the N donors pmdta (N,N′,N′,N″,N″ pentamethyldiethylenetriamine) and tmeda (N,N,N′,N′ tetramethylethylenediamine) resulted in the formation and crystallisation of the heavy alkali metal complexes, [{6-Me(2-Pyr)}(Me₃Si)₂CNa(pmdta)], 1, and [{6-Me(2-Pyr)}(Me₃Si)₂CK]_∞, 2. Single crystal X-ray diffraction studies show the sodium complex, 1, to be monomeric with a six coordinate metal centre, while the unsolvated potassium complex, 2, is polymeric, involving repeating η³ 1-aza-allyl and allylic interactions of the pyridyl moiety with the potassium cation.     

Synthesis and structural characterization of three copper coordination polymers with pyridine derivatives from hydro(solvo)thermal in situ decarboxylation reactions of 2,5-dicarboxylpyridine

The hydro(solvo)thermal self-assembles of CuI, KI and 2,5-dicarboxylpyridine [2,5-(COOH)₂py] in different molar ratios in H₂O/alcohol solutions produced three Cu coordination polymers as 2-D [N-C₂H₅py][Cu₃I₄] 1, 1-D [N-CH₃py][Cu₂I₃] 2 as well as 1-D [Cu(2-COOpy)₂]H₂O 3 (N-C₂H₅py=N-ethylpyridine, N-CH₃py=N-methylpyridine, 2-COOpy=2-carboxylpyridine). N-C₂H₅py in 1 and N-CH₃py in 2 derived from the solvothermal in situ simultaneous decarboxylation and N-alkylation reactions of 2,5-(COOH)₂py. The semi-decarboxylation reaction of 2,5-(COOH)₂py into 2-COOpy occurred in the preparation of 3. X-ray single-crystal analysis revealed that CuI is transformed into a 2-D [Cu₃I₄]⁻ layer in compound 1 and a 1-D chain in compound 2, templated by [N-C₂H₅py]⁺ and [N-CH₃py]⁺, respectively. Compound 3 is a divalent Cu compound. The Cu(II) centers with a 4+2 geometry are coordinated by μ₃-mode 2-COOpy ligands. All of the title compounds were characterized by CHN analysis, IR spectrum analysis and TG analysis. Compounds 1 and 2 exhibit fluorescence properties with the maximum emissions at 581 nm for 1 and 537 nm for 2.     

Synthesis and characterization of monomeric siloxo palladium(II) complexes: crystal structure of [Pd(tmeda)(C6F5)(OSiPh3)]

Mononuclear palladium-hydroxo complexes of the type [Pd(N-N)(C₆F₅)(OH)] [(N-N)=2,2^′-bipyridine (bipy), 4,4^′-dimethyl-2,2^′-bipyridine (Me₂bipy), or N,N,N^′,N^′-tetramethylethylenediamine (tmeda)] react with silanols HOSiR₃ in toluene giving the corresponding siloxo complexes [Pd(N-N)(C₆F₅)(OSiR₃)]. The X-ray crystal structure of [Pd(tmeda)(C₆F₅)(OSiPh₃)] has been determined. In one of the two molecules in the asymmetric unit there is an intramolecular interaction by phenyl-pentafluorophenyl π-stacking.     

An iodide/anion exchange route to benzimidazolylidene silver complexes from benzimidazolium iodide: Crystal structures of N,N′-dibutylbenzimidazolylidene silver chloride, bromide, cyanide and nitrate

Syntheses of N,N′-dibutylbenzimidazolylidene silver complexes having chloride, nitrate or cyanide as an anion part through an iodide/anion exchange from N,N′-dibutylbenzimidazolium iodide are described, representing a practical route to benzimidazolylidene silver complexes from readily accessible benzimidazolium iodide. The crystal structures of N,N′-dibutylbenzimidazolylidene silver chloride, bromide, cyanide and nitrate have been determined, showing a close ligand-unsupported Ag-Ag interaction in [(NHC)₂]Ag⁺[AgX₂]⁻ and a “T” shape geometry about the silver(I) cation in complexes of chloride, bromide and cyanide, but a nearly linear shape in the bis(N,N′-dibutylbenzimidazolylidene) silver complex [ with non-coordinating nitrate anion.     

Reaction of ferrocenecarboxylic acid with N,N-disubstituted carbodiimides: synthesis, spectroscopic and X-ray crystallographic analysis of N,N-disubstituted N-ferrocenoylureas and identification of a one-pot coupling reagent for the formation of ferrocenecarboxamides in a non-aqueous solvent

N,N^′-dicyclohexyl-N-ferrocenoylurea 2, N,N^′-diisopropyl-N-ferrocenoylurea 3, N,N^′-di-p-tolyl-N-ferrocenoylurea 4 and N,N^′-di-tert-butyl-N-ferrocenoylurea 5 were obtained by reaction of ferrocenecarboxylic acid 1 with N,N^′-dicyclohexylcarbodiimide (DCC), N,N^′-diisopropylcarbodiimide (DIC), N,N^′-di-p-tolylcarbodiimide 10 and N,N^′-di-tert-butylcarbodiimide 11, respectively. Both N-tert-butyl-N^′-ethyl-N-ferrocenoylurea 6 and N^′-tert-butyl-N-ethyl-N-ferrocenoylurea 7 were obtained by reaction of 1 with N-tert-butyl-N^′-ethylcarbodiimide 12. In all cases a small amount of ferrocenecarboxylic anhydride 8 was formed as a by-product. All compounds were characterized by ¹H NMR, ¹³C NMR, IR and MS. Single crystal X-ray structural analyses were made of 2, 3 and 4. From the consistent results, the reaction products of 1 with carbodiimides appear different from those proposed by some earlier workers. With N-(3-dimethylaminopropyl)-N^′-ethylcarbodiimidehydrochloride 9 ferrocenoylurea was not isolated, but the main product was rather 8. The suitability of 8 as acylation reagent was applied by using 9 to obtain N-(3-triethoxysilyl)-propylferrocenecarboxamide in a one-pot reaction from 1 and 3-(triethoxysilyl)-propylamine.     

Complexes derived from the general copper(II)/maleamic acid/N,N′,N′′-chelate reaction systems: Synthetic,reactivity, structural and spectroscopic studies

The synthetic investigation of the Cu^II/maleamate(−1) ion (HL⁻)/N,N′,N′′-chelate general reaction system has allowed access to compounds [Cu₂(HL)₂(bppy)₂](ClO₄)₂·H₂O (1·H₂O), [Cu(HL)(bppy)(ClO₄)] (2) and [Cu(HL)(terpy)(H₂O)](ClO₄) (4) (bppy = 2,6-bis(pyrazol-1-yl)pyridine, terpy = 2,2′;6′,2′′-terpyridine). In the absence of externally added hydroxides, compound [Cu₂(L′)₂(bppy)₂](ClO₄)₂ (3) was obtained from MeOH solutions; L′⁻ is the monomethyl maleate(−1) ligand which is formed in situ via the Cu^II-assisted HL⁻ → L′⁻ transformation. In the case of tptz-containing (tptz = 2,4,6-tris(2-pyridyl)-1,3,5-triazine) reaction systems, the Cu^II-assisted hydrolysis of tptz to pyridine-2-carboxamide (L1) afforded complex [Cu(L1)₂(NO₃)₂] (5). The crystal structures of 1–5 are stabilized by intermolecular hydrogen bonding and π–π stacking interactions. Characteristic IR bands of the complexes are discussed in terms of the known structures and the coordination modes of the ligands.     

A study on the reaction between N-substituted p-phenylenediamines and ozone: experimental results and theoretical aspects in relation to their antiozonant activity

The following p-phenylenediamines (PPD): N,N,N^′,N^′-tetramethyl-p-phenylenediamine (TMPPD), N,N^′-dimethylbutyl-p-phenylenediamine (6PPD), N,N^′-diaryl-p-phenylenediamine (DPPD), tris-(N-dimethylpentyl-p-phenylenediamine)-N^′,N^′,N^′-1,3,5-triazine (6PPDTZ), have been oxidized under the action of O₃ in diluted solutions. In all cases the radical cation or semiquinone radical was the first derivative formed by monoelectronic oxidation of the substrate. The radical cation has been studied by electronic spectroscopy and the electronic spectral changes of all mentioned PPD has been followed as function of the ozonation time. The results have been discussed in the frame of the antiozonant properties of these PPD which are used as antiozonant agents in diene rubber protection. It is shown that the antiozonant activity of each PPD considered correlates with the free enthalpy of formation of the respective radical cation. The lowest is the free energy of formation of a PPD radical cation and the highest is the antiozonant activity in a diene rubber compound.     

Design, synthesis, and evaluation of a novel bridged nucleic acid, 2′,5′-BNA, with S-type sugar conformation fixed by N-O linkage

We designed a novel 2′-O,5′-N bridged nucleic acid, 2′,5′-BNA^ON, whose sugar puckering was fixed to S-type conformation by an N-O linkage. A dimer unit formed from 2′,5′-BNA^ON-U and thymidine was synthesized via a coupling reaction between a protected 2′,5′-BNA^ON-U monomer and a thymidine derivative. Introduction of 2′,5′-BNA^ON-U into DNA was carried out using conventional phosphoramidite chemistry with a DNA synthesizer. The hybridization abilities of 2′,5′-BNA^ON-U-modified oligonucleotides against DNA or RNA complement were evaluated.     

Sulfide oxygenation by tert-butyl hydroperoxide with mononuclear (Me3TACN)Mn catalysts

Mononuclear (Me₃TACN)MnX₃ compounds, where X is Cl⁻, Br⁻, or N₃⁻, and Me₃TACN is 1,4,7-N,N′,N″-trimethyl-1,4,7-triazacyclononane, have been tested for catalyzing both sulfide oxygenation and styrene epoxidation by tert-butyl hydroperoxide (TBHP) and display turnover frequencies (TOF) up to 200 h⁻¹ at room temperature. Sulfoxides or sulfones may be produced selectively by varying reaction conditions. Product distribution from the oxygenation reactions of ethyl phenyl sulfide, 2-chloroethyl phenyl sulfide, and styrene is consistent with a mechanism involving an early single-electron transfer (SET) step.