Jaromír Marek

Preparation, physicochemical properties and biological activity of copper(II) complexes with 6-(2-chlorobenzylamino)purine (HL1) or 6-(3-chlorobenzylamino)purine (HL2). The single-crystal X-ray structure of [Cu(H+L2)2Cl3]Cl·2H2O

Copper(II) complexes of 6-(2-chlorobenzylamino)purine (HL1) and 6-(3-chlorobenzylamino)purine (HL2), respectively, were prepared. Depending on the pH of the medium and the molar ratio of reactants the following mononuclear (trigonal-bipyramidal) and dinuclear (octahedral, trigonal-bipyramidal or tetrahedral) complexes were isolated: [Cu2(mu-HL1)2(mu-Cl2)2(HL1)2Cl2] (1a,b), [Cu2(mu-Cl)2(mu-L1)2(H2O)2] (2a), [Cu2(mu-Cl)2(mu-L2)2(H2O)2] (2b), [Cu(H+L2)2Cl3]Cl.H2O (3a,b), [Cu2(mu-Cl)2(HL1)2Cl2] (4a), and [Cu2(mu-Cl)2(HL2)2Cl2] (4b). The compounds were characterized by elemental analyses, electronic, infrared and mass (FAB+, ES+) spectral data, magnetic susceptibility temperature dependence measurements and molar conductivity data. An X-ray single-crystal structural analysis of [Cu(H+L2)2Cl3]Cl.2H2O (3b) showed that the Cu2+ ion is penta-coordinated by three chloride ions and by two H+L2 ligands. Thus, the Cu2+ ion adopts a distorted trigonal bipyramidal coordination geometry with the protonated H+L2 ligands coordinated in trans apical positions, while the three chloride ions are situated in an equatorial plane. The cytotoxic activity of the complexes was determined by a calcein AM assay. Mouse melanoma cell line B16-FO, human malignant melanoma cell line G361, human osteogenic sarcoma cell line HOS and human breast adenocarcinoma cell line MCF7 were used. IC50 values, the drug concentrations lethal to 50% of the tumor cells, were estimated. One of the important mechanisms responsible for the cytotoxicity of cytokinin-derived compounds, the inhibition of cyclin-dependent kinases by the studied complexes, was also determined.

A two-in-one dual channel chemosensor for Fe3+ and Cu2+ with nanomolar detection mimicking the IMPLICATION logic gate

A novel and easy-to-synthesize colorimetric and fluorescent chemosensor 1 was developed for the highly selective and sensitive recognition of Fe3+ and Cu2+. Receptor 1 showed a detectable color change from yellow to colorless with a blue-shift in the absorption spectra with Cu2+, while Fe3+ induced a color change from yellow to orange and a red-shift in the absorption spectra. In the emission study of 1, Fe3+ showed significant fluorescence enhancement with a slight red-shift while a selective fluorescence quenching was observed with Cu2+ over a wide range of tested metal ions. With Cu2+/Fe3+ as the chemical inputs, the ‘on–off’ emission profile of receptor 1 was developed as an IMPLICATION type logic gate at the molecular level.

Metal complexes as anticancer agents 2. Iron(III) and copper(II) bio-active complexes with N6-benzylaminopurine derivatives

Iron(III) complexes with 2-(3-hydroxypropylamino)-6-benzylaniino-9-isopropylpurine (Bohemin, HL1), in its protonized form, of the composition (H+HL1)(2)[FeCl5]. 2H(2)O (1), (H+HL1)(2)[FeCl5]. 3H(2)O (2) have been prepared by two different routes. A new way for synthesis of copper(II) complex with 6-(2-chlorobenzylamino)purine (HL2), [Cu-2(mu -Cl)(2)(mu -HL2)(2)(HL2)(2)Cl-2]. 2H(2)O (3), together with the preparation of copper(II) complex with 6-(3-chlorobenzylamino)purine (HL3), [Cu-2(mu -Cl)(2)(mu -HL3)(2)Cl-2] (4), is also reported. The characterization have been based on elemental analysis, electronic, infrared, ES + mass and Fe-57 Mossbauer spectra, conductivity data and magnetic susceptibility temperature measurements over the 4.5-300 K for 1-3, and 35-300 K for 4. temperature range, respectively. Molecular structure of an electroneutral form of the HL2 ligand, (HL2. 2H(2)O), and a protonized form of the HL3 ligand, (H+HL3-Cl), have been determined by a single-crystal X-ray analysis. A mononuclear trigonal-bipyramidal (for 1 and 2), binuclear octahedral (for 3) and binuclear trigonal-bipyramidal (for 4) structures of the complexes were proposed mainly on the basis of spectral and magnetic properties. An S = 3/2-5/2 spin-admixed state in 1 and 2 was found to be related to the presence of [FeCl5](2-) (S = 3/2) and [FeCl5(H2O)](2-) (S = 5/2) complex anions in I and 2, as found by Fe-57 Mossbauer spectroscopy. Cytotoxic activity of the complexes was determined by a calcein AM assay and IC50 values were also estimated. For testing, human malignant melanoma cell line G-361. human osteogenic sarcoma cell line HOS, human chronic myelogenous leukaemia K-562 and human breast adenocarcinoma cell line MCF7 were used. The inhibition of p34(cdc2) kinase by the complexes I and 2, which is known to be one of the important mechanisms responsible for cytotoxicity of cytokinin-derived compounds, was also studied.

Displacement of triphenylphosphine from Cu(PPh3)2NO3 and Co(PPh3)2Cl2 by a diselenoimidodiphosphinato ligand. X-ray crystal structure of (PPh3)Cu[Ph2P(Se)NP(Se)Ph2] and Co[Ph2P(Se)NP(Se)Ph2]2 containing the novel CuSe2P2N and CoSe2P2N inorganic metallocycles

The reaction of Cu(PPh3)2NO3 with K[Ph2P(Se)-N-P(Se)Ph2] produced a tricoordinate copper(I) complex, Cu(PPh3)[Ph2P(Se)-N-P(Se)Ph2], containing the novel inorganic (carbon-free) CuSe2P2N metallocycle. The same diselenium reagent gave with Co(PPh3)2Cl2 a spirobicyclic compound Co[Ph2P(Se)-N-P(Se)Ph2]2, containing the novel inorganic CoSe2P2N metallocycle. The crystal structure of the two compounds was investigated by X-Ray diffraction. In both compounds the inorganic metallocycles are nonplanar and display strongly distorted twisted boat conformations.

A new coordination mode for the tartrato ligand. Synthesis of vanadium(V) oxo peroxo tartrato complexes and the X-ray crystal structure of K2[{VO(O2)(L-tartH2)}2(μ-H2O]5H2O

Abstract Vanadium(V) oxo peroxo tartrato complexes M2[{VO(O2)(L-tartH2}2(μ-H2O)]. 5H2O (M = K+, NH4+; tart4− = C4O6H24− have been prepared from aqueous-ethanolic medium and characterized by elemental analysis and IR spectroscopy. The X-ray crystal structure of K2[{VO(O2) (L-tartH2)}2(μ-H2O)]. 5H2O, as the first crystal structure of a vanadium(V) tartrato complex has been determined. The dinuclear anion exhibits two pentagonal bipyramidal polyhedra about vanadium atoms which are joined to each other by sharing two oxygen atoms of hydroxyl groups and oxygen atom from water molecule. The tartrate group is bonded to the vanadium atom in a bidentate way via oxygen atoms of neighbouring carboxylic and hydroxyl groups. The coordinated hydroxyl oxygen atom is bonded also to the second vanadium atom, but in a monodentate way. This type of bonding of tartrate group was not observed so far.

Mixed ligand complexes of platinum(II) and palladium(II) with cytokinin-derived compounds Bohemine and Olomoucine: X-ray structure of [Pt(BohH+-N7)Cl3]·9/5H2O {Boh=6-(benzylamino)-2-[(3-(hydroxypropyl)-amino]-9-isopropylpurine, Bohemine}

The new square-planar Pt(II) and Pd(II) complexes with cytokinin-derived compounds Bohemine and Olomoucine, having the formulae [Pt(BohH(+))Cl(3)].H(2)O (1), [Pt(Boh)(2)Cl(2)].3H(2)O (2), [Pt(Boh-H)Cl(H(2)O)(2)].H(2)O (3), [Pt(OloH(+))Cl(3)].H(2)O (4), [Pd(BohH(+))Cl(3)].H(2)O (5), [Pd(Boh)Cl(2)(H(2)O)] (6), [Pd(Boh-H)Cl(H(2)O)].EtOH (7) and [Pd(OloH(+))Cl(3)].H(2)O (8), where Boh=6-(benzylamino)-2-[(3-(hydroxypropyl)amino]-9-isopropylpurine and Olo=6-(benzylamino)-2-[(2-(hydroxyethyl)amino]-9-methylpurine, have been synthesized. The complexes have been characterized by elemental analyses, IR, FAB+ mass, 1H, 13C and 195Pt NMR spectra, and conductivity data. The molecular structure of the complex [Pt(BohH(+)-N7)Cl(3)].9/5H(2)O has been determined by an X-ray diffraction study. Results from physical studies show that both Bohemine and Olomoucine are coordinated to transition metals through the N(7) atom of purine ring in all the complexes. The prepared compounds have been tested in vitro for their possible cytotoxic activity against G-361 (human malignant melanoma), HOS (human osteogenic sarcoma), K-562 (human chronic myelogenous leukemia) and MCF-7 (human breast adenocarcinoma) cell lines and IC(50) values have been also determined for all the complexes. IC(50) values estimated for the Pt(II)-Bohemine complexes (2.1-16 microM) allow us to conclude that they could find utilization in antineoplastic therapy. Thus, from a pharmacological point of view, Pt(II) complexes of Bohemine may represent compounds for a new class of antitumor drugs.

Structure and binding specificity of the receiver domain of sensor histidine kinase CKI1 from Arabidopsis thaliana.

Multistep phosphorelay (MSP) signaling mediates responses to a variety of important stimuli in plants. In Arabidopsis MSP, the signal is transferred from sensor histidine kinase (HK) via histidine phosphotransfer proteins (AHP1-AHP5) to nuclear response regulators. In contrast to ancestral two-component signaling in bacteria, protein interactions in plant MSP are supposed to be rather nonspecific. Here, we show that the C-terminal receiver domain of HK CKI1 (CKI1(RD) ) is responsible for the recognition of CKI1 downstream signaling partners, and specifically interacts with AHP2, AHP3 and AHP5 with different affinities. We studied the effects of Mg²⁺, the co-factor necessary for signal transduction via MSP, and phosphorylation-mimicking BeF₃⁻ on CKI1(RD) in solution, and determined the crystal structure of free CKI1(RD) and CKI1(RD) in a complex with Mg²⁺. We found that the structure of CKI1(RD) shares similarities with the only known structure of plant HK, ETR1(RD) , with the main differences being in loop L3. Magnesium binding induces the rearrangement of some residues around the active site of CKI1(RD) , as was determined by both X-ray crystallography and NMR spectroscopy. Collectively, these results provide initial insights into the nature of molecular mechanisms determining the specificity of MSP signaling and MSP catalysis in plants.

Stereospecific formation of α-hydroxycarboxylato oxo peroxo complexes of vanadium(V). Crystal structure of (NBu4)2[V2O2(O2)2(l-lact)2]·2H2O and (NBu4)2[V2O2(O2)2(d-lact)(l-lact)]·2H2O

An overview of structurally characterized α-hydroxycarboxylatodioxo- and α-hydroxycarboxylatooxoperoxovanadates(V) is presented and the geometric parameters of the V2O2 bridging core are discussed. The first case of a stereospecific formation of oxoperoxovanadates(V) is reported: The crystal structures of the isomeric compounds (NBu4)2[V2O2(O2)2(l-lact)2]·2H2O and (NBu4)2[V2O2(O2)2(d-lact)(l-lact)]·2H2O (lact=C3H4O32−, the anion of the lactic acid) differ mainly in the arrangement of the V2O2 core and in mutual orientation of the VO bonds. The complexes with achiral ligands adopt the same structural type as the complexes formed from a racemic mixture of a chiral ligand, while the structure obtained using an enantiopure l,l-hydroxycarboxylate is different.

Synthesis of spiropyrrolidines and spiropyrrolizidines by 1,3-dipolar cycloadditions of azomethine ylides to substituted α-methylene-γ-lactones

Abstract 1,3-Dipolar cycloadditions of (E)- and (Z)-substituted α-methylene-γ-lactones with azomethine ylides derived from N-methyl glycine and l -proline gave the corresponding spiropyrrolidine and spiropyrrolizidine cycloadducts in good to moderate yields with various extent of stereoselectivity and regioselectivity. Cycloadditions of the azomethine ylide derived from l -proline exhibited endo selectivity especially in the case of (Z)-isomers of starting methylene lactones. Reactivity and regioselectivity were rationalized by a comparison with quantum chemical calculations (AM1). Structures of derivatives prepared were determined by NMR spectroscopy and by X-ray.

Coordination compounds of nickel with trithiocyanuric acid: Part III. Crystal and molecular structure of [Ni(bapen)(ttcH)]·2H2O (bapen=N,N′-bis(3-aminopropyl)ethylenediamine, ttcH3=trithiocyanuric acid)

Abstract Coordination compounds of compositions [Ni(bapen)(ttcH)]·2H2O (1), [Ni(bappn)(ttcH)] (2), [Ni(mdpta)(ttcH)(H2O)] (3), [Ni(nphen)2(ttcH)]·H2O (4), [Ni(nphen)3](ttcH)·2H2O (5), [Ni(ampy)2(ttcH)]·H2O (6) and [Ni(aepy)2(ttcH)]·2H2O (7), where bapen=N,N′-bis(3-aminopropyl)ethylenediamine, bappn=N,N′-bis(3-aminopropyl)-1,3-propanediamine, mdpta=3,3′-diamino-N-methyldipropylamine, nphen=5-nitro-1,10-phenanthroline, ampy=2-aminomethylpyridine, aepy=2-aminoethylpyridine and ttcH3=trithiocyanuric acid, have been prepared. The crystal and molecular structure of (1) was determined by X-ray analysis. Nickel atom is six-coordinated by four N atoms of amine and S and N donor atoms of trithiocyanuric dianion, whereas two water molecules are situated outside the coordination sphere. Cyclic voltammetry showed that the complexes undergo an oxidation attributable to Ni2+→Ni3+ in the range 550–950 mV. The magnetic behaviour of (6) and (7) has been studied in the 291–94 K temperature range. Magnetic susceptibility follows the Curie-Weiss law.