The role of intermolecular interactions in [Fe(X-salEen)2]ClO4 spin crossover complexes.

Two new spin crossover (SCO) Fe(III) compounds were prepared, their structures were analysed and their magnetic properties were investigated. An exhaustive analysis of the effects of halogen substitution and aromatic ring functionalisation on the magnetic properties of non-solvated Fe(III) perchlorate complexes has been performed. Through comparative analysis, different magnetic profiles were found for the compounds studied, namely F (1), Cl (2), H (3), Br (4a, 4b), and I (5). Using tools like Hirshfeld analysis, the study revealed patterns in octahedral distortions and deviations from the ideal octahedral geometry. The SCO phenomenon as the conducting wire in this study, emphasises the influence of intermolecular interactions on the low spin (LS) to high spin (HS) transitions in these halogen-substituted complexes. The prevalence of H⋯H contributions has been demonstrated, albeit being the weakest and an inverse strength relationship in H⋯X interactions ranging from F to I. The findings not only interpret the intricate balance between halogen substitution, functionalisation, and intermolecular interactions in modulating magnetic properties but also direct future works in designing similar molecular systems.

Development of Fluorescent Chemosensors for Calcium and Lead Detection.

In the present work, several coumarin-3-carboxamides with different azacrown ether moieties were designed and tested as potential luminescent sensors for metal ions. The derivative containing a 1-aza-15-crown-5 as a metal chelating group was found to yield the strongest response for Ca2+ and Pb2+, exhibiting an eight- and nine-fold emission increase, respectively, while other cations induced no changes in the optical properties of the chemosensor molecule. Job's plots revealed a 1:1 binding stoichiometry, with association constants of 4.8 × 104 and 8.7 × 104 M-1, and limits of detection of 1.21 and 8.04 µM, for Ca2+ and Pb2+, respectively. Computational studies suggest the existence of a PET quenching mechanism, which is inhibited after complexation with each of these two metals. Proton NMR experiments and X-ray crystallography suggest a contribution from the carbonyl groups in the coumarin-3-carboxamide fluorophore in the coordination sphere of the metal ion.

Antimicrobial Activity of Manganese(I) Tricarbonyl Complexes Bearing 1,2,3-Triazole Ligands.

BACKGROUND: Antimicrobial resistance is one of the most pressing health issues of our time. The increase in the number of antibiotic-resistant bacteria allied to the lack of new antibiotics has contributed to the current crisis. It has been predicted that if this situation is not dealt with, we will be facing 10 million deaths due to multidrug resistant infections per year by 2050, surpassing cancer-related deaths. This alarming scenario has refocused attention into researching alternative drugs to treat multidrug-resistant infections. AIMS: In this study, the antimicrobial activities of four manganese complexes containing 1,2,3,-triazole and clotrimazole ligands have been evaluated. It is known that azole antibiotics coordinated to manganese tricarbonyl complexes display interesting antimicrobial activities against several microbes. In this work, the effect of the introduction of 1,2,3,-triazole-derived ligands in the [Mn(CO)3(clotrimazole)] fragment has been investigated against one Gram-positive bacterium and five Gram-negative bacteria. METHODS: The initial antimicrobial activity of the above-mentioned complexes was assessed by determining the minimum inhibitory and bactericidal concentrations using the broth microdilution method. Growth curves in the presence and absence of the complexes were performed to determine the effects of these complexes on the growth of the selected bacteria. A possible impact on cellular viability was determined by conducting the MTS assay on human monocytes. RESULTS: Three of the Mn complexes investigated (4-6) had good antimicrobial activities against all the bacteria tested, with values ranging from 1.79 to 61.95 µM with minimal toxicity. CONCLUSIONS: Due to the increased problem of antibiotic resistance and a lack of new antibacterial drugs with no toxicity, these results are exciting and show that these types of complexes can be an avenue to pursue in the future.

Synthesis, Base Pairing Properties, and Biological Activity Studies of Platinum(II) Complexes Based on Uracil Nucleosides.

The synthesis and base pairing properties of platinum complexes based on uridine and deoxyuridine nucleosides and preliminary studies of their antiproliferative activity are described. Platinum(II) uridine and deoxyuridine complexes were synthesized by C-I oxidative addition to Pt(0)(PPh3)4. First, the synthesis was performed with protected nucleosides to generate complexes 1 and 2, which were deprotected under basic conditions, affording complexes 3 and 4 in good yields. The synthesis with the unprotected nucleosides was also performed and provided complexes 3 and 4 effectively. Base pairing interactions were measured for complex 1, either for self-base pairing or for the Watson-Crick base pair. Complex 1 undergoes self-base pairing in CDCl3, and this aggregation was found not to be dependent on metalation. Contrastingly, for the Watson-Crick base pair with adenine, base pairing was also observed, but metalation was found to affect hydrogen bonding considerably. Complexes 3 and 4 and the corresponding ligand precursors were evaluated for their antiproliferative activity against human glioblastoma cell line U-251. The compounds showed IC50 values of 3.30 (3) and 1.84 (4) µM but are also toxic for nontumorous cell lines.

A Polymorph of Dipeptide Halide Glycyl-L-Alanine Hydroiodide Monohydrate: Crystal Structure, Optical Second Harmonic Generation, Piezoelectricity and Pyroelectricity.

A polymorph of glycyl-L-alanine HI.H2O is synthesized from chiral cyclo-glycyl-L-alanine dipeptide. The dipeptide is known to show molecular flexibility in different environments, which leads to polymorphism. The crystal structure of the glycyl-L-alanine HI.H2O polymorph is determined at room temperature and indicates that the space group is polar (P21), with two molecules per unit cell and unit cell parameters a = 7.747 Å, b = 6.435 Å, c = 10.941 Å, α = 90°, ß = 107.53(3)°, γ = 90° and V = 520.1(7) Å3. Crystallization in the polar point group 2, with one polar axis parallel to the b axis, allows pyroelectricity and optical second harmonic generation. Thermal melting of the glycyl-L-alanine HI.H2O polymorph starts at 533 K, close to the melting temperature reported for cyclo-glycyl-L-alanine (531 K) and 32 K lower than that reported for linear glycyl-L-alanine dipeptide (563 K), suggesting that although the dipeptide, when crystallized in the polymorphic form, is not anymore in its cyclic form, it keeps a memory of its initial closed chain and therefore shows a thermal memory effect. Here, we report a pyroelectric coefficient as high as 45 µC/m2K occurring at 345 K, one order of magnitude smaller than that of semi-organic ferroelectric triglycine sulphate (TGS) crystal. Moreover, the glycyl-L-alanine HI.H2O polymorph displays a nonlinear optical effective coefficient of 0.14 pm/V, around 14 times smaller than the value from a phase-matched inorganic barium borate (BBO) single crystal. The new polymorph displays an effective piezoelectric coefficient equal to deff=280 pCN-1, when embedded into electrospun polymer fibers, indicating its suitability as an active system for energy harvesting.

Antitumor Activity and Reductive Stress by Platinum(II) N-Heterocyclic Carbenes based on Guanosine.

Platinum(II) complexes bearing N-heterocyclic carbenes based guanosine and caffeine have been synthesized by unassisted C-H oxidative addition, leading to the corresponding trans-hydride complexes. Platinum guanosine derivatives bearing triflate as counterion or bromide instead of hydride as co-ligand were also synthesized to facilitate correlation between structure and activity. The hydride compounds show high antiproliferative activity against all cell lines (TC-71, MV-4-11, U-937 and A-172). Methyl Guanosine complex 3, bearing a hydride ligand, is up to 30 times more active than compound 4, with a bromide in the same position. Changing the counterion has no significant effect in antiproliferative activity. Increasing bulkiness at N7, with an isopropyl group (compound 6), allows to maintain the antiproliferative activity while decreasing toxicity for non-cancer cells. Compound 6 leads to an increase in endoplasmic reticulum and autophagy markers on TC71 and MV-4-11 cancer cells, induces reductive stress and increases glutathione levels in cancer cells but not in non-cancer cell line HEK-293.

Insights into the anticancer activity of chiral alkylidene-ß-lactams and alkylidene-γ-lactams: Synthesis and biological investigation.

Chiral alkylidene-ß-lactams and alkylidene-γ-lactams were synthesized and screened for their in vitro activity against four human cancer cell lines (melanoma, esophageal, lung and fibrosarcoma carcinoma). Alkylidene-ß-lactams were synthesized via Wittig reaction of diverse phosphorus ylides with benzhydryl 6-oxopenicillanate, derived from 6-aminopenicillanic acid. Moreover, novel chiral alkylidene-γ-lactams were synthesized through a multistep strategy starting from a chiral substrate (d-penicillamine). The in vitro assays allowed the identification of four compounds with IC50 values < 10 µM for A375 cell line, and three compounds with IC50 values < 10 µM for OE19 cell line. The effect of the most promising compounds on cell death mechanism, reactive oxygen species generation as well as the evaluation of their ability to act as MMP-9 inhibitors were studied. The reported results unveil the potential of alkylidene-ß-lactams as anticancer agents.

Hypervalent Iodine(III) Reagents with Transferable Primary Amines: Structure and Reactivity on the Electrophilic α-Amination of Stabilized Enolates.

A new family of hypervalent iodine reagents containing transferable primary amine groups is described. Benziodoxolone-based reagents were synthesized on the gram-scale through operationally simple reactions in up to quantitative yields. These bench-stable solids were characterized by X-ray analysis and successfully employed in the α-amination of indanone-based ß-ketoesters in up to 83% yield. Mechanistic studies indicate a substitution mechanism involving an electrophilic amine.

Manganese(I) tricarbonyl complexes as potential anticancer agents.

The antiproliferative activity of [Mn(CO)3(N^N)Br] (N^N = phendione 1, bipy 3) and of the two newly synthesized Mn complexes [Mn(CO)3(acridine)(phendione)]OTf (2) and [Mn(CO)3(di-triazole)Br] (4) has been evaluated by MTS against three tumor cell lines A2780 (ovarian carcinoma), HCT116 (colorectal carcinoma), HCT116doxR (colorectal carcinoma resistant to doxorubicin), and in human dermal fibroblasts. The antiproliferative assay showed a dose-dependent effect higher in complex 1 and 2 with a selectivity toward ovarian carcinoma cell line 21 times higher than in human fibroblasts. Exposure of A2780 cells to IC50 concentrations of complex 1 and 2 led to an increase of reactive oxygen species that led to the activation of cell death mechanisms, namely via intrinsic apoptosis for 2 and autophagy and extrinsic apoptosis for 1. Both complexes do not target DNA or interfere with cell cycle progression but are able to potentiate cell migration and neovascularization (for 2) an indicative that their application might be directed for initial tumor stages to avoid tumor invasion and metastization and opening a new avenue for complex 2 application in regenerative medicine. Interestingly, both complexes do not show toxicity in both in vivo models (CAM and zebrafish).

Click-Derived Triazoles and Triazolylidenes of Manganese for Electrocatalytic Reduction of CO2.

A series of new fac-[Mn(L)(CO)3Br] complexes where L is a bidentate chelating ligand containing mixed mesoionic triazolylidene-pyridine (MIC^py, 1), triazolylidene-triazole (MIC^trz, 2), and triazole-pyridine (trz^py, 3) ligands have been prepared and fully characterized, including the single crystal X-ray diffraction studies of 1 and 2. The abilities of 1-3 and complex fac-[Mn(MIC^MIC)(CO)3Br] (4) to catalyze the electroreduction of CO2 has been assessed for the first time. It was found that all complexes displayed a current increase under CO2 atmosphere, being 3 and 4 the most active complexes. Complex 3, bearing a N^N-based ligand exhibited a good efficiency and an excellent selectivity for reducing CO2 to CO in the presence of 1.0 M of water, at low overpotential. Interestingly, complex 4 containing the strongly electron donating di-imidazolylidene ligand exhibited comparable activity to 3, when the experiments were performed in neat acetonitrile at slightly higher overpotential (-1.86 vs. -2.14 V).

Synthesis of 5H-chromeno[3,4-b]pyridines via DABCO-catalyzed [3 + 3] annulation of 3-nitro-2H-chromenes and allenoates.

The DABCO-catalyzed [3 + 3] annulation between 3-nitro-2H-chromenes and benzyl 2,3-butadienoate has been developed as a route to 5H-chromeno[3,4-b]pyridine derivatives. Under optimal reaction conditions, 5H-chromeno[3,4-b]pyridines incorporating two allenoate units were obtained in moderate to good yields (30-76%). The same type of transformation could be carried out using butynoates as allene surrogates. Mechanistic studies by mass spectrometry allowed the identification of the key intermediates involved in the reaction mechanism. The reported synthetic methodology represents an entirely new approach for the synthesis of the 5H-chromeno[3,4-b]pyridine core structure based on allene chemistry.

Synthesis of Platinum(II) N-Heterocyclic Carbenes Based on Adenosine.

Organometallic derivatization of nucleosides is a highly promising strategy for the improvement of the therapeutic profile of nucleosides. Herein, a methodology for the synthesis of metalated adenosine with a deprotected ribose moiety is described. Platinum(II) N-heterocyclic carbene complexes based on adenosine were synthesized, namely N-heterocyclic carbenes bearing a protected and unprotected ribose ring. Reaction of the 8-bromo-2',3',5'-tri-O-acetyladenosine with Pt(PPh3)4 by C8-Br oxidative addition yielded complex 1, with a PtII centre bonded to C-8 and an unprotonated N7. Complex 1 reacted at N7 with HBF4 or methyl iodide, yielding protic carbene 2 or methyl carbene 3, respectively. Deprotection of 1 to yield 4 was achieved with NH4OH. Deprotected compound 4 reacted at N7 with HCl solutions to yield protic NHC 5 or with methyl iodide yielding methyl carbene 6. Protic N-heterocyclic carbene 5 is not stable in DMSO solutions leading to the formation of compound 7, in which a bromide was replaced by chloride. The cis-influence of complexes 1-7 was examined by 31P{1H} and 195Pt NMR. Complexes 2, 3, 5, 6 and 7 induce a decrease of 1JPt,P of more than 300 Hz, as result of the higher cis-influence of the N-heterocyclic carbene when compared to the azolato ligand in 1 and 4.

Manganese complexes with chelating and bridging di-triazolylidene ligands: synthesis and reactivity.

New manganese complexes bearing di-triazolylidene (di-trz) ligands are described. Depending on the wingtip substituents of the triazolylidene ligand and the synthetic procedure, two different ligand coordination modes were observed, i.e, bridging and chelating. A series of Mn(i) complexes of the general type fac-[Mn(di-trzR)(CO)3Br] (R = Me, Et, Mes) with a chelating di-trz ligand were prepared via Ag-transmetalation. In contrast, the in situ deprotonation of the triazolium salts with KOBut yielded the bimetallic Mn(0) complexes [Mn2(CO)8(µ-di-trzR)] with a bridging di-trz ligand when short alkyl chains (Me, Et, i-Pr) are present as the N1 substituents of the triazolylidene ligand. The molecular structures of monometallic and bimetallic complexes were determined by X-ray diffraction studies. In addition, the cationic fac-[Mn(di-trzEt)(CO)2(PPh3)2]Br complex, a rare example of a dicarbonyl Mn(i) N-heterocyclic carbene, was obtained when fac-[Mn(di-trzEt)(CO)3Br] was irradiated with visible light in the presence of PPh3. The crystal structure revealed a slightly distorted octahedral geometry around the Mn(i) centre, with the chelating di-triazolylidene ligand situated in trans position to the two CO ligands in the equatorial plane, and the two phosphine ligands occupying the axial positions. Cyclic voltammetry studies show reversible redox processes for the monometallic Mn(i) complexes, and a quasi-reversible EC mechanism for the oxidation of the bimetallic complexes. Infrared spectroelectrochemical studies along with DFT calculations for fac-[Mn(di-trzEt)(CO)3Br] suggest that the observed two consecutive reductions both occur at the metal centre.

Triazole-Based Half-Sandwich Ruthenium(II) Compounds: From In Vitro Antiproliferative Potential to In Vivo Toxicity Evaluation.

A new series of half-sandwich ruthenium(II) compounds [(η6-arene)Ru(L)Cl][CF3SO3] bearing 1,2,3-triazole ligands (arene = p-cymene, L = L1 (1); arene = p-cymene, L = L2 (2); arene = benzene, L = L1 (3); arene = benzene, L2 (4); L1 = 2-[1-(p-tolyl)-1H-1,2,3-triazol-4-yl]pyridine and L2 = 1,1'-di-p-tolyl-1H,1'H-4,4'-bi(1,2,3-triazole) have been synthesized and fully characterized by 1H and 13C NMR and IR spectroscopy, mass spectrometry, and elemental analysis. The molecular structures of 1, 2, and 4 have been determined by single-crystal X-ray diffraction. The cytotoxic activity of 1-4 was evaluated using the MTS assay against human tumor cells, namely ovarian carcinoma (A2780), colorectal carcinoma (HCT116), and colorectal carcinoma resistant to doxorubicin (HCT116dox), and against normal primary fibroblasts. Whereas compounds 2 and 4 showed no cytotoxic activity toward tumor cell lines, compounds 1 and 3 were active in A2780, while showing no antiproliferative effect in human normal dermal fibroblasts at the IC50 concentrations of the A2780 cell line. Exposure of ovarian carcinoma cells to IC50 concentrations of compound 1 or 3 led to an accumulation of reactive oxygen species and an increase of apoptotic and autophagic cells. While compound 3 displayed low levels of angiogenesis induction, compound 1 showed an ability to induce cell cycle delay and to interfere with cell migration. When the in vivo toxicity studies using zebrafish and chicken embryos are considered, compounds 1 and 3, which were not lethal, are promising candidates as anticancer agents against ovarian cancer due to their good cytotoxic activity in tumor cells and their low toxicity both in vitro and in vivo.

Mechanochemistry in Portugal-A Step towards Sustainable Chemical Synthesis.

In Portugal, publications with mechanochemical methods date back to 2009, with the report on mechanochemical strategies for the synthesis of metallopharmaceuticals. Since then, mechanochemical applications have grown in Portugal, spanning several fields, mainly crystal engineering and supramolecular chemistry, catalysis, and organic and inorganic chemistry. The area with the most increased development is the synthesis of multicomponent crystal forms, with several groups synthesizing solvates, salts, and cocrystals in which the main objective was to improve physical properties of the active pharmaceutical ingredients. Recently, non-crystalline materials, such as ionic liquids and amorphous solid dispersions, have also been studied using mechanochemical methods. An area that is in expansion is the use of mechanochemical synthesis of bioinspired metal-organic frameworks with an emphasis in antibiotic coordination frameworks. The use of mechanochemistry for catalysis and organic and inorganic synthesis has also grown due to the synthetic advantages, ease of synthesis, scalability, sustainability, and, in the majority of cases, the superior properties of the synthesized materials. It can be easily concluded that mechanochemistry is expanding in Portugal in diverse research areas.

Antimicrobial and antitumor activity of S-methyl dithiocarbazate Schiff base zinc(II) complexes.

Schiff bases (SB) obtained from S-methyl dithiocarbazate and aromatic aldehydes: salicylaldehyde (H2L1), o-vanillin (H2L2), pyridoxal (H2L3) and 2,6-diformyl-4-methylphenol (H3L4), and their corresponding Zn(II)-complexes (1-4), are synthesized. All compounds are characterized by elemental analyses, infrared, UV-Vis, nuclear magnetic resonance spectroscopy and mass spectrometry. The structures of H2L2 and [Zn2(L1)2(H2O)(DMF)] (1a) (DMF = dimethylformamide) are solved by single crystal X-ray diffraction. The SB coordinates the metal center through the Ophenolate, Nimine and Sthiolate atoms. The radical scavenging activity is tested using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, with all ligand precursors showing IC50 values ~40 µM. Cytotoxicity studies with several tumor cell lines (PC-3, MCF-7 and Caco-2) as well as a non-tumoral cell line (NHDF) are reported. Interestingly, 1 has relevant and selective antiproliferative effect against Caco-2 cells (IC50 = 9.1 µM). Their antimicrobial activity is evaluated in five bacterial strains (Klebsiella pneumoniae, Acinetobacter baumannii, Listeria monocytogenes, Pseudomonas aeruginosa and Staphylococcus aureus) and two yeast strains (Candida albicans and Candida tropicalis) with some compounds showing bacteriostatic and fungicidal activity. The minimal inhibitory concentration (MIC90) of HnL against Mycobacterium tuberculosis is also reported, with H2L2 and H3L4 showing very high activity (MIC90 < 0.6 µg/mL). The ability of the compounds to bind bovine serum albumin (BSA) and DNA is evaluated for H3L4 and [Zn2(L4)(CH3COO)] (4), both showing high binding constants to BSA (ca. 106 M-1) and ability to bind DNA. Overall, the reported compounds show relevant antitumor and antimicrobial properties, our data indicating they may be promising compounds in several fields of medicinal chemistry.

Luminescent halogen-substituted 2-(N-arylimino)pyrrolyl boron complexes: the internal heavy-atom effect.

A group of new boron complexes [BPh2{κ2N,N'-NC4H3-2-C(H)[double bond, length as m-dash]N-C6H4X}] (X = 4-Cl 4c, 4-Br 4d, 4-I 4e, 3-Br 4f, 2-Br 4g, 2-I 4h) containing different halogens as substituents in the N-aryl ring have been synthesized and characterized in terms of their molecular properties. Their photophysical characteristics have been thoroughly studied in order to understand whether these complexes exhibit an internal heavy-atom effect. Phosphorescence emission was found for some of the synthesized halogen-substituted boron molecules, particularly for 4g and 4h. DFT and TDDFT calculations showed that the lower energy absorption band resulted from the HOMO to LUMO (π-π*) transition, except for 2-I 4h, where the HOMO-1 to LUMO transition was also involved. The strong participation of iodine orbitals in HOMO-1 is reflected in the calculated absorption spectra of the iodine derivatives, especially 2-I 4h, when spin-orbit coupling (SOC) was included. Organic light-emitting diodes (OLEDs) based on these complexes, in the neat form or dispersed in a matrix, were also fabricated and tested. The devices based on films prepared by thermal vacuum deposition showed the best performance. When neat complexes were used, a maximum luminance (Lmax) of 1812 cd m-2 was obtained, with a maximum external quantum efficiency (EQEmax) of 0.15%. An EQEmax of ca. 1% along with a maximum luminance of 494 cd m-2 were obtained for a device fabricated by co-deposition of the boron complex and a host compound (1,3-bis(N-carbazolyl)benzene, mCP).

Boron complexes of aromatic 5-substituted iminopyrrolyl ligands: synthesis, structure, and luminescence properties.

A group of new mononuclear boron chelate compounds [BPh2{κ2N,N'-5-R-NC4H2-2-C(H)[double bond, length as m-dash]N-Ar}] (R = Ar = C6H57; R = C6H5, Ar = 2,6-iPr2C6H38; R = Anthracen-9-yl (Anthr), Ar = C6H59; R = Anthr, Ar = 2,6-iPr2C6H310) were synthesized via the reaction of B(C6H5)3 with the corresponding 5-substituted 2-(N-arylformimino)pyrrole ligand precursors 3-6. These complexes were prepared in order to evaluate the luminescence potential derived from the substitution of the position 5 of the pyrrolyl ring with an aromatic group. Compounds 7-10 were photophysically characterized in solution and in the solid state. The 5-phenyl-2-iminopyrrolyl-BPh2 complexes 7 and 8 are blue emitters and have enhanced photoluminescence quantum yields in the solid state (ΦPL) up to 0.95, whereas the 5-anthracenyl derivatives 9 and 10 have green-bluish fluorescence and a ΦPL of 0.49 and 0.24, respectively. DFT and TDDFT studies were performed, considering the effect of solvent and dispersion, in order to show how the geometries of compounds 7-10 changed from the ground to the excited state, to assign electronic transitions, and to rationalize the observed luminescence. These materials were applied in organic light-emitting diodes (OLEDs), with various device structures, the best showing an external quantum efficiency of 2.75% together with a high luminance of 23 530 cd m-2.

Tetrahydropyrazolo[1,5-a]pyridine-fused steroids and their in vitro biological evaluation in prostate cancer.

The androgen receptor (AR) is a steroid hormone receptor and its high expression and disruption of its regulation are strongly implicated in prostate cancer (PCa) development. One of the current therapies includes application of steroidal antiandrogens leading to blockade of the AR action by the abrogation of AR-mediated signaling. We introduced here novel 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused steroidal compounds, described their synthesis based on [8π+2π] cycloaddition reactions of diazafulvenium methides with different steroidal scaffolds and showed their biological evaluation in different prostate cancer cell lines in vitro. Our results showed the ability of novel compounds to suppress the expression of known androgen receptor targets, Nkx3.1 and PSA in two prostate cell lines, 22Rv1 and VCaP. Candidate compound diminished the transcription of AR-regulated genes in the reporter cell line in a concentration-dependent manner. Antiproliferative activity of the most promising steroid was studied by clonogenic assay and induction of apoptosis in treated cells was documented by immunoblot detection of cleaved PARP.

New phenyl-nickel complexes of bulky 2-iminopyrrolyl chelates: synthesis, characterisation and application as aluminium-free catalysts for the production of hyperbranched polyethylene.

A family of mono(2-iminopyrrolyl) complexes with the general formula [Ni{κ2N,N'-5-(aryl)-NC4H2-2-C(H)[double bond, length as m-dash]N-2,6-(aryl)}(C6H5)(PPh3)] were obtained from the reaction of the sodium salts of the newly synthesised 5-aryl-2-(N-arylformimino)pyrroles with the square planar complex trans-[Ni(C6H5)(PPh3)2Cl]. These new iminopyrrole ligand precursors, designed with increasing bulkiness and different electronic properties, and their corresponding nickel(ii) complexes were characterised by NMR spectroscopy and elemental analysis, and their structural features were analysed by single crystal X-ray diffraction. The nickel complexes were tested as aluminium-free catalysts for the polymerisation of ethylene, at low to moderate pressures and different temperatures and in the absence or presence of the phosphine scavenger [Ni(COD)2], giving rise to catalytic activities in the range of 3.61-73.12 kgPE molNi-1 h-1 bar-1. The polyethylene products formed in these catalytic reactions were characterised by GPC/SEC and NMR spectroscopy. Generally, low molecular weight (Mn 510-1300 g mol-1) low viscosity oils were obtained, presenting high branching degrees (80-125 branches per 1000 C atoms), which are characteristic of hyperbranched polyethylene products. In particular, polymerisation reactions using catalyst 7 led to higher viscosity oils with molecular weights between 11 000 and 20 000 g mol-1, and branching degrees of 100-120 branches per 1000 C atoms.