Cyclobutadiene dianion derivatives – Planar 4c,6e or three-dimensional 6c,6e aromaticity?

The spatial magnetic properties (Through Space NMR Shieldings – TSNMRS) of two cyclobutadiene derivatives (2 and 5) and of a number of cyclobutadiene dianion derivatives (3, 4 and 6–8) have been calculated by the GIAO perturbation method employing the Nucleus-Independent Chemical Shift (NICS) concept of P. v. Ragué Schleyer, and visualized as Iso-Chemical-Shielding Surfaces (ICSS) of various size and direction. TSNMRS values can be successfully employed to quantify and visualize the (anti)aromaticity of the compounds studied and to discuss the influence of Li⁺ complexation to cyclobutadiene dianion (4a, 7 and 8) on planar 4c,6e or three-dimensional 6c,6e aromaticity.     

NOVEL pH-SENSITIVE DRUG DELIVERY SYSTEM BASED ON NATURAL POLYSACCHARIDE FOR DOXORUBICIN RELEASE

A novel pH-sensitive nanoparticle drug delivery system (DDS) derived fl'om natural polysaccharide pullulan for doxorubicin (DOX) release was prepared.Pullulan was functionalized by successive carboxymethylization and amidation to introduce hydrazide groups.DOX was then grafted onto pullulan backbone through the pH-sensitive hydrazone bond to form a pullulan/DOX conjugate.This conjugate self-assembled to form nano-sized particles in aqueous solution as a result of the hydrophobic interaction of the DOX.Tr...     

The study of the lipophilicity of alpha-(4-phenylpiperazin-1-yl)-gamma-phthalimidobutyramides using chromatographic and computational methods

The lipophilicity of the series of alpha-(4-phenylpiperazin-1-yl)-gamma-phthalimido-butyramides (1-8) has been investigated. Several methods, like reversed-phase thin-layer chromatography and high-performance liquid chromatography using reversed-phase RP18 and IAM.DD2 columns, were applied to determine RMO, log k0 and log k(0IAM) factors. The RP-TLC investigations were performed in mixtures of acetone-water and acetonitrile-water. For RP-HPLC method mixtures of acetonitrile, water and 0.01% TFA were used as the mobile phases while for IAM.DD2 investigations mixtures of acetonitrile and water were applied. The partition coefficients of compounds (1-8) were also calculated with the Pallas and CAChe programs. All the obtained data, both from experimental methods and computational calculations, were compared and a suitable conclusion was reached.     

Cyclopalladation of N-phenyl-4-ferrocenylmethylpyrazoles: Crystal structure of [Pd{κ-C,N-C6H4-1-[(3,5-Me2-C3N2)-CH2-(η-C5H4)Fe(η-C5H5)]}Cl(PPh3)] · CH2Cl2

The synthesis and characterization of pyrazole derivatives of general formula [C₆H₄-4-R-1-{(3,5-Me₂-C₃N₂)-CH₂-(η⁵-C₅H₄)Fe(η⁵-C₅H₅)}] [R = OMe (1a) or H (1b)] with a ferrocenylmethyl substituent are described.The study of the reactivity of compounds 1 with palladium(II) acetate has allowed the isolation of complexes (μ-AcO)₂[Pd{κ²-C,N-C₆H₃-4-R-1-[(3,5-Me₂-C₃N₂)-CH₂-(η⁵-C₅H₄)Fe(η⁵-C₅H₅)]}]₂ (2) [R = OMe (2a) or H (2b)] that contain a bidentate [C(sp², phenyl), N]⁻ ligand and a central “Pd(μ-AcO)₂Pd” unit.Furthermore, treatment of 2 with LiCl produced complexes (μ-Cl)₂[Pd{κ²-C,N-C₆H₃-4-R-1-[(3,5-Me₂-C₃N₂)-CH₂-(η⁵-C₅H₄)Fe(η⁵-C₅H₅)]}]₂ (3) [R = OMe (3a) or H (3b)] that arise from the replacement of the acetato ligands by the Cl⁻.Compounds 2 and 3 also react with PPh₃ giving the monomeric complexes [Pd{κ²-C,N-C₆H₃-4-R-1-[(3,5-Me₂-C₃N₂)-CH₂-(η⁵-C₅H₄)Fe(η⁵-C₅H₅)]}X(PPh₃)] {X⁻ = AcO⁻ and R = OMe (5a) or H (5b) or X⁻ = Cl⁻ and R = OMe (6a) or H (6b)}, where the phosphine is in a cis-arrangement to the metallated carbon atom. Treatment of 3 with thallium(I) acetylacetonate produced [Pd{κ²-C,N-C₆H₃-4-R-1-[(3,5-Me₂-C₃N₂)-CH₂-(η⁵-C₅H₄)Fe(η⁵-C₅H₅)]}(acac)] (7) [R = OMe (7a) or H (7b)]. Electrochemical studies of the free ligands and the cyclopalladated complexes are also reported. The dimeric complexes 3 also react with MeO₂C-CC-CO₂Me (in a 1:4 molar ratio) giving [Pd{(MeO₂C-CC-CO₂Me)₂C₆H₃-4-R-1-[(3,5-Me₂-C₃N₂)-CH₂-(η⁵-C₅H₄)Fe(η⁵-C₅H₅)]}Cl] (8) [R = OMe (8a) or H (8b)], which arise from the bis(insertion) of the alkyne into the σ{Pd-C(sp², phenyl)} bond of 3.     

Complexation of tris(pentafluorophenyl)silanes with neutral Lewis bases

A detailed analysis of monodentate and bidentate complexation of tris(pentafluorophenyl)silyl (TPFS) derivatives with neutral Lewis bases was performed. The NMR spectroscopy and X-ray diffraction analysis (11 structures) were the key methods to characterize tetra- or pentacoordinate silicon compounds, whereas the peculiarities of crystal packing were analyzed by means of DFT calculations. The interaction of TPFS-X (X = F, Cl, OTf) with strong Lewis bases (HMPA, N-methylpyrrolidinone) may afford three different species: neutral pentacoordinate TPFS(X)-L, cationic tetracoordinate TPFS-L⁺ X⁻, and cationic pentacoordinate TPFS-(L)⁺₂X⁻, representatives of each type were characterized by X-ray diffraction. A variety of complexes with bidentate complexation, featuring the trigonal bipyramidal geometry with apical C₆F₅-group was prepared and structurally characterized. The extent of Si-C_apical bond elongation depends on the donating ability of the coordinating ligand, with the longest Si-C bond of 1.981(1) Å observed for six-membered complex of TPFS-ether of N-(2-hydroxybenzoyl)pyrrolidine.     

Synthesis, characterization and antitumor activity of 1,2-disubstituted ferrocenes and cyclodextrin inclusion complexes

Seven different ferrocene derivatives have been tested in vitro against Ehrlich ascites tumor cells. Neither ferrocene nor the monosubstituted derivative N,N-dimethylaminomethylferrocene showed cytotoxic activity (IC₅₀ > 1000 μM for 3 h treatments). Better results were obtained with 1,2-disubstituted derivatives. The IC₅₀ values ranged from 376.6 μM for 1,2-diformylferrocene to 71.2 μM for racemic 2-(N,N-dimethylaminomethyl)ferrocenecarboxamide. The latter derivative was also encapsulated in native β-cyclodextrin (CD), heptakis-2,3,6-tri-O-methyl-β-CD (TRIMEB) and 2-hydroxypropyl-β-CD (HPβCD) to give 1:1 (host:guest) inclusion compounds. The existence of true inclusion complexes in the solid state was confirmed by a combination of powder X-ray diffraction, thermogravimetric analysis, FTIR and ¹³C CP MAS NMR spectroscopy. The IC₅₀ value for the β-CD inclusion compound was identical to that obtained for the nonincluded ferrocene derivative. By contrast, the inclusion compounds comprising TRIMEB and HPβCD yielded IC₅₀ values of 25.2 and 20.0 μM, respectively. No obvious relationship could be established between the redox behavior of the compounds determined by cyclic voltammetry and the biochemical data.     

Synthesis and evaluation of thermal, photophysical and magnetic properties of novel starlike fullerene–organosilane macromolecules

Thermal, photophysical and magnetic properties of some novel fullerenol–silane adducts are described. Excellent improvement of thermal stability and high char yield due to the presence of silicon is the key feature of these adducts. Highest luminescence quenching due to maximum π–π electronic interactions between phenyl ring and fullerene are observed in the aromatic-silane adducts and the quenching ability of the aromatic ring reduces with further delocalization of the π-electrons as in naphthyl silane. The alkyl vinyl silane, on the other hand, records better fluorescence intensity owing to increase population of the electron density (+I effect) and non-effective charge transfer complex formation between isolated vinylic double bond and fullerene. Emission peak positions of these adducts are comparable to fullerenol because of control derivatization of fullerene ring causing less perturbation of the symmetric π-electronic system. These adducts are paramagnetic in nature with peaks around 3515 G and higher g-values (2.005–2.009) compared to fullerenol (1.985). The fullerenol–silane adducts are synthesized using fullerenol as substrate and different chloro and alkoxy silanes as silylating agents adopting simple nucleophilic displacement and transesterification reactions. All the fullerenol–silane adducts are characterized spectroscopically.     

Synthesis of 5-{[(1Hbenzo[d]imidazol-2-yl)sulfonyl]methyl}-3-phenyl-4,5-dihydroisoxazole derivatives,invitro antibacterial and antioxidant studies along with their insilico analyses

Synthesis of a series of novel sulfone derivatives 6(a-u) possessing benzimidazoles and isoxazoline rings tailored in a single molecule 5(a-u) was done by reactions using 5-(bromomethyl)-3-phenyl-4,5-dihydroisoxazoles 3(a-u) and 5-{[(1H-benzo[d]imidazol-2-yl)thio]methyl}-3-phenyl-4,5-dihydroisoxazoles 4(a-u) molecules. The chemical structures of all the newly synthesized compounds were established by IR, ¹HNMR, ¹³CNMR and LCMS spectral data. The biological characteristics of the novel sulfone compounds, such as their antioxidant and antibacterial activity, were evaluated. Among the synthesized sulfones derivatives, compounds 6 g, 6b, and 6e demonstrated outstanding antibacterial activity while compounds 6b, 6c, 6i, 6j, and 6 k demonstrated higher antioxidant activity. Further insilico absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies of synthesized sulfones were studied which exhibited excellent intestinal absorption which is more than 80 %, and relatively moderate toxicity. Molecular docking studies confirmed the antibacterial and antioxidant potential which is comparable with the standard.     

Design,synthesis, characterization,and antimicrobial evaluation of some new pyridine and chromene derivatives containing Lidocaine analogue

In an attempt to find a new class of antimicrobial agents, a series 2-pyridinone and 2-iminochromene derivatives containing Lidocaine analogue were designed and synthesized. The 2-pyridinone derivatives (3), (4), and (6) were obtained through the cyclocondensation of 2-cyano-N-(2,6-dimethylphenyl)-acetamide (2) with 1,3-dicarbonyl compounds and/or ternary condensation of (2), aromatic aldehyde, and malononitrile. Also, a series of 2-iminochromene derivatives (7–9) were synthesized through the condensation reaction of cyanoacetamide derivative (2) with salicylaldehyde derivatives. The structure of the new compounds were confirmed based on elemental analysis and spectral data. These compounds were screened for their antibacterial and antifungal activity The minimal inhibitory concentration (MIC) (µg/mL) of the most active (4), (5b), and (8) derivatives were determined. The MIC values between 7.81 and 31.26 µg/mL against bacterial species for (8) derivative, and upon comparison to tetracycline exhibited a positive control MIC (31.26–62.6 µg/mL). Besides, the activity against C. albicans (ATCC 1023) showed a MIC value of 15.63 µg/mL, which is similar to that of Amphotericin B.     

Syntheses of novel series benzo [1,5] oxazepin-4-one-based compounds from 1,5-difluoro-2,4-dinitrobenzene

A novel benzo [ 1,5] oxazepin-4-one skeleton compound and its four derivatives were synthesized effectively from 1,5-difluoro- 2,4-dinitrobenzene （DFDNB） under mild conditions. In the process, four intermediates were synthesized by substitutions of the two fluorine atoms and reductions of the meta-dinitro groups in DFDNB respectively. The results showed that the key for synthesizing the intermediates was the substitution of one of the two fluorine atoms in DFDNB by 3-hydroxy butyric acid ethyl ester first, then the other fluorine atom by morpholine, and then the reduction of the meta-dinitro groups in the substitute by HCOONH4 with Pd/C. The products were purified with silica gel column chromatography, and confirmed by HPLC, LC-MS and 1H NMR. They should contribute to construct the molecular libraries for therapeutic applications.