Naphthalene Exchange in [Re(η6-napht)2]+ with Pharmaceuticals Leads to Highly Functionalized Sandwich Complexes [M(η6-pharm)2]+ (M=Re/99mTc)

Bis-arene sandwich complexes are generally prepared by the Fischer-Hafner reaction, which conditions are incompatible with most O- and N- functional groups. We report a new way for the synthesis of sandwich type complexes [Re(η⁶-arene)₂]⁺ and [Re(η⁶-arene)(η⁶-benzene)]⁺ from [Re(η⁶-napht)₂]⁺ and [Re(η⁶-napht)(η⁶-benzene)]⁺, with functionalized arenes and pharmaceuticals. N-methylpyrrolidine (NMP) facilitates the substitution of naphthalene with the incoming arene. A series of fully characterized rhenium sandwich complexes with simple arenes, such as aniline, as well as with active compounds like lidocaine and melatonin are presented. With these rhenium compounds in hand, the radioactive sandwich complexes [^99mTc(η⁶-pharm)₂]⁺ (pharm=pharmaceutical) can be unambiguously confirmed. The direct labelling of pharmaceuticals with ^99mTc through η⁶-coordination to phenyl rings and the confirmation of the structures with the rhenium homologues opens a path into molecular theranostics.     

Controlled copper-mediated chlorination of phenol rings under mild conditions

The very unusual case of copper-mediated chlorination of phenol rings under mild conditions at room temperature is reported. Reaction of the ligand 1,7-bis(2-hydroxyphenyl)-2,6-diaza-4-hydroxylheptane (H3L1) with CuCl2 in acetonitrile leads to either the formation of a tetranuclear copper(II) complex [Cu4(HL3)2(mu-Cl)2Cl2](CH3CN) (1) or a linear trinuclear complex [Cu3(HL1)2Cl2(CH3CN)2](CH3CN)2 (2), depending on the reaction conditions. Both compounds have been fully characterized, including the determination of their 3D structures by X-ray diffraction. The unprecedented tetranuclear compound 1 is constituted of a dichlorido-bridged dimer of di-mu-phenoxido-dinuclear species, whereas the trinuclear complex 2 presents a linear array of copper(II) ions, held together through di-mu-phenoxido bridges of the central and external ions. The magnetic susceptibility of the two compounds was investigated, revealing either very strong (J<-500 cm-1) or strong (J value around -370(1) cm-1) antiferromagnetic dominant interactions among the CuII ions for 1 and 2, respectively. The tetranuclear complex 1 is obtained, under dry conditions, through the in situ formation of ligand HL3 (H3L3=1,7-bis(2-hydroxy-5-chlorophenyl)-2,6-diaza-4-hydroxylheptane) by oxidative chlorination of (HL1)2-. In the presence of traces of water, 1 is partially hydroxylated at the ortho position of one of the phenyl rings. The use of trimethylorthoformate as the dehydrating agent prevents the formation of hydroxylated ligands. Several partly chlorinated/hydroxylated products (identified as H3L2) have also been obtained through slight variations of the synthetic procedures (presence or absence of water and/or triethylamine in the reaction mixtures). These partially chlorinated and/or hydroxylated coordination species are mutually isomorphous to either 1 or 2. Several "modified" ligands have been isolated and characterized by 1H NMR and MS, after reaction with sodium sulfide of the complexes formed.     

1-Methoxycarbonyl-substituiertes 2,3-Dihydropyridin-4(1H)-on (= Methyl-1,2,3,4-tetrahydro-4-oxopyridin-1-carboxylat) als Chromophor für die photochemische [2 + 2]-Cycloaddition

1-Methoxycarbonyl-Substituted 2,3-Dihydropyridin-4(1H)-one(= Methyl 1,2,3,4-Tetrahydro-4-oxopyridine-1-carboxylate) as Chromophore for Photochemical [2 + 2]-Cycloadditions With olefins having an electron-acceptor as well as with olefins having an electron-donor substituent, 1-methoxycarbonyl-substituted dihydropyridinone 12 undergoes [2 + 2] cycloaddition in good preparative yields. The photochemical cycloaddition is highly regioselective. For preparative purposes, the ring junction can be equilibrated to the thermodynamically more stable cis-junction. Only the ‘endo’/‘exo’ selectivity at the C-atom bearing the olefin substituent cannot be controlled. The photodimerization of 12 is the only side reaction. Using a slight excess of the olefin, the photodimerization can be suppressed. The protecting group at the N-atom of the dihydropyridinone can be varied in order to introduce an internal sensitizer, as shown with 1-acyl-substituted compound 29 , which underwent the cycloaddition process even with sunlight.     

Liposomal structure: A comparative study on light scattering and chromatography techniques

Liposomes play an important role in medical and pharmaceutical science as, nanoscale drug carriers. One of the most important features is their size and size distribution, influencing both their bio-distribution and their targeting efficiency to tumors and also therapeutic activity of liposomal antitumor drugs. In this study, the effect of preparation method and molecular interaction on size and shape of liposome was studied. The size and shape characterization of liposomes was performed by asymmetrical flow field-flow fractionation coupled online with multi-angle light scattering (AF4-MALS). The size distributions obtained by AF4-MALS were compared to mean particle sizes and size distribution measured with other standard method such as Photon Correlation Spectroscopy (PCS). Furthermore, the effect of molecular interaction (hydrophilic and hydrophobic model drugs) on liposomal structure was assessed.     

The synthesis of phosphine derivatives of [Fe4N(CO)12]: Crystal structures of [Fe4N(CO)9(NO)(PPh3)2], [HFe4N (CO)11)PPh3)] and [(PPh3)2N][Fe4N(CO)11(PMe2Ph)]

Phosphines react with butterfly tetranuelear nitrido-iron clusters, [Fe₄N(CO)₁₂]⁻ and [Fe₄N(CO)₁₁(NO)], to give mono- and di-substituted complexes. X-Ray analyses of the title compounds showed that the phosphine ligands are bound to the wing-tip atoms.     

In Vitro Antiplasmodial and Cytotoxic Activities of Compounds from the Roots of Eriosema montanum Baker f. (Fabaceae)

Malaria remains one of the leading causes of death in sub-Saharan Africa, ranked in the top three infectious diseases in the world. Plants of the Eriosema genus have been reported to be used for the treatment of this disease, but scientific evidence is still missing for some of them. In the present study, the in vitro antiplasmodial activity of the crude extract and compounds from Eriosema montanum Baker f. roots were tested against the 3D7 strain of Plasmodium falciparum and revealed using the SYBR Green, a DNA intercalating compound. The cytotoxicity effect of the compounds on a human cancer cell line (THP-1) was assessed to determine their selectivity index. It was found that the crude extract of the plant displayed a significant antiplasmodial activity with an IC₅₀ (µg/mL) = 17.68 ± 4.030 and a cytotoxic activity with a CC₅₀ (µg/mL) = 101.5 ± 12.6, corresponding to a selective antiplasmodial activity of 5.7. Bioactivity-guided isolation of the major compounds of the roots’ crude extract afforded seven compounds, including genistein, genistin and eucomic acid. Under our experimental conditions, using Artemisinin as a positive control, eucomic acid showed the best inhibitory activity against the P. falciparum 3D7, a well-known chloroquine-sensitive strain. The present results provide a referential basis to support the traditional use of Eriosema species in the treatment of malaria.