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Jan Reedijk

Publications and source records attributed to Jan Reedijk.

At least 55 records · Page 3Linked to original sources
PubMed2004

Coordination of 9-ethylguanine to the mixed-ligand compound alpha-[Ru(azpy)(bpy)Cl2] (azpy = 2-phenylazopyridine and bpy = 2,2'-bipyridine). An unprecedented ligand positional shift, correlated to the cytotoxicity of this type of [RuL2Cl2] (with L = azpy or bpy) complex.

The striking difference in cytotoxic activity between the inactive cis-[Ru(bpy)(2)Cl(2)] and the recently reported highly cytotoxic alpha-[Ru(azpy)(2)Cl(2)] (alpha indicating the isomer in which the coordinating Cl atoms, pyridine nitrogens, and azo nitrogens are in mutual cis, trans, cis orientation) encouraged the synthesis of the mixed-ligand compound cis-[Ru(azpy)(bpy)Cl(2)]. The synthesis and characterization of the only occurring isomer, i.e., alpha-[Ru(azpy)(bpy)Cl(2)], 1 (alpha denoting the isomer in which the Cl ligands are cis related to each other and the pyridine ring of azpy is trans to the pyridine ring of bpy), are described. The solid-state structure of 1 has been determined by X-ray structure analysis. The IC(50) values obtained for several human tumor cell lines have indicated that compound 1 shows mostly a low to moderate cytotoxicity. The binding of the DNA model base 9-ethylguanine (9-EtGua) to the hydrolyzed species of 1 has been studied and compared to DNA model base binding studies of cis-[Ru(bpy)(2)Cl(2)] and alpha-[Ru(azpy)(2)Cl(2)]. The completely hydrolyzed species of 1, i.e., alpha-[Ru(azpy)(bpy)(H(2)O)(2)](2+), has been reacted with 9-EtGua in water at room temperature for 24 h. This resulted in the monofunctional binding of only one 9-EtGua, coordinated via the N7 atom. The product has been isolated as alpha-[Ru(azpy)(bpy)(9-EtGua)(H(2)O)](PF(6))(2), 2, and characterized by 2D NOESY NMR spectroscopy. The NOE data show that the 9-EtGua coordinates (under these conditions) at the position trans to the azo nitrogen atom. Surprisingly, time-dependent (1)H NMR data of the 9-EtGua adduct 2 in acetone-d(6) show an unprecedented positional shift of the 9-EtGua from the position trans to the azo nitrogen to the position trans to the bpy nitrogen atom, resulting in the adduct alpha'-[Ru(azpy)(bpy)(9-EtGua)(H(2)O)](PF(6))(2) (alpha' indicating 9-EtGua is trans to the bpy nitrogen). This positional isomerization of 9-EtGua is correlated to the cytotoxicity of 1 in comparison to both the cytotoxicity and 9-EtGua coordination of cis-[Ru(bpy)(2)Cl(2)], alpha-[Ru(azpy)(2)Cl(2)], and beta-[Ru(azpy)(2)Cl(2)]. This positional isomerization process is unprecedented in model base metal chemistry and could be of considerable biological significance.

Crystallography, X-Ray↗
PubMed2004

Energy transfer pathways in dinuclear heteroleptic polypyridyl complexes: through-space vs through-bond interaction mechanisms.

A series of homo- and heteronuclear ruthenium and osmium polypyridyl complexes with the bridging ligands 1,3-bis(5-(2-pyridyl)-1H-1,2,4-triazol-3-yl)benzene (H(2)mL) and 1,4-bis(5-(2-pyridyl)-1H-1,2,4-triazol-3-yl)benzene (H(2)pL) are reported. The photophysical properties of these compounds are investigated, and particular attention is paid to the heteronuclear (RuOs) compounds, which exhibit dual emission. This is in contrast to phenyl-bridged polypyridine Ru-Os complexes with a similar metal-metal distance, in which the Ru emission is strongly quenched because the nature of the bridging ligand allows for an efficient through-bond coupling. The results obtained for the compounds reported here suggest that energy transfer is predominantly taking place via a dipole-dipole, Förster type, mechanism, that may dominate when through-bond coupling is weak. This is in stark contrast to ground state interaction, which is found to be critically dependent on the nature of the bridging unit employed.

Journal Article↗
PubMed2004

Conformational and stereochemical flexibility in cadmium(II) complexes of aza-thioether macrocycles.

The synthesis and crystal structures of four CdII macrocyclic complexes containing mixed N-, O- and S-donors, [Cd(NO3)2([12]aneN2S2)] (1), [Cd(NO3)2([12]aneNS3)] (2), [Cd(NO3)2([15]aneNO2S2)] (3) and [Cd(NO3)([15]aneN2O2S)]NO3 (4), are presented. The metal ion is coordinated outside of the macrocyclic cavity in the complexes of the smaller macrocycles ([12]aneN2S2 and [12]aneNS3) while the flexibility of the larger macrocycles in and allows very different conformations to be adopted with a 'butterfly' geometry in and a flattened geometry in. No correlation between the number of sulfur donors and Cd-S bond distance in these types of complexes is observed, although the number and binding mode of the nitrato ligands is determined by the conformation and binding mode of the macrocycle. The position of the nitrato ligand also influences, through steric conflicts with the macrocyclic donor atoms, the bond distances in both ligand systems.

Journal Article↗
PubMed2004

Fast autoxidation of ethyl linoleate catalyzed by [Mn(acac)3] and bipyridine: a possible drying catalyst for alkyd paints.

It has been found that [Mn(acac)(3)], by functioning both as a radical initiator and a hydroperoxide decomposition catalyst, has a very high activity in the autoxidation of ethyl linoleate (EL), a model compound for the binder molecule in household alkyd paint. Adding 1 equiv of bipyridine (bpy) to a reaction mixture of EL and [Mn(acac)(3)] significantly enhances the autoxidation rate. The redox properties of [Mn(acac)(3)] and [Mn(acac)(2)(bpy)] have been compared with cyclic voltammetry; the observed peak potentials show that addition of bpy facilitates reduction of Mn(III) to Mn(II), which may explain the increase in autoxidation activity.

Journal Article↗
PubMed2004

Dinuclear platinum complexes with N, N'-bis(aminoalkyl)-1,4-diaminoanthraquinones as linking ligands. Part I. Synthesis, cytotoxicity, and cellular studies in A2780 human ovarian carcinoma cells.

A series of N, N'-bis(aminoalkyl)-1,4-diaminoanthraquinones (aminoalkyl=2-aminoethyl, 3-aminoprop-1-yl and 4-aminobut-1-yl) was functionalized with trans-platinum DNA-binding moieties. Cytotoxicity testing in A2780 human ovarian carcinoma cells revealed high anticancer activity of the formed cationic dinuclear platinum complexes. The cationic dinuclear platinum complexes with the shortest aminoalkyl chain were shown to be the most active, which agrees with the structure-activity relationship found for the corresponding free ligands without platinum. The N, N'-bis(aminoalkyl)-1,4-diaminoanthraquinones partly circumvent cisplatin resistance, whereas their dinuclear platinum complexes were found susceptible to the resistance mechanisms in A2780cisR. The platinum complexes have resistance factors comparable to the control dinuclear complex BBR3005 [(trans-PtCl(NH3)2)2)(micro-(NH2(CH2)6NH2))](NO3)2. The 1,4-diaminoanthraquinone moiety is fluorescent, and thus the cellular processing of the compounds could be monitored by time-lapse digital fluorescence microscopy. The intercalators without platinum were shown to enter the cells within minutes. The platinum complexes enter the cells more slowly. Most likely, the positive charges of the platinum complexes hamper the diffusion through the membrane. Interestingly, the platinum complexes are processed differently than the platinum-free compounds by the cells. After 24 hours the fluorescent platinum complexes are encapsulated in large vesicles in the cytosol. Co-localization of the anthraquinone fluorescence with Lysotracker Green DND-26 shows that these vesicles are acidic compartments, probably lysosomes.

Anthraquinones↗
PubMed2004

Dinuclear platinum complexes with N, N'-bis(aminoalkyl)-1,4-diaminoanthraquinones as linking ligands. Part II. Cellular processing in A2780 cisplatin-resistant human ovarian carcinoma cells: new insights into the mechanism of resistance.

The cellular processing of three fluorescent N, N'-bis(aminoalkyl)-1,4-diaminoanthraquinones (aminoalkyl=2-aminoethyl, 3-aminoprop-1-yl or 4-aminobut-1-yl) and their dinuclear platinum complexes in A2780 human ovarian carcinoma cells with acquired resistance to cisplatin has been monitored over time by time-lapse fluorescence microscopy. The results were compared with the previously reported observations in the parent A2780 cell line. The cellular distribution pattern for the free ligands is similar in sensitive and resistant cells, whereas significant differences in cellular distribution were observed in the case of the platinum complexes. In the cisplatin-resistant cell line the platinum complexes were found to be sequestrated in acidic vesicles in the cytosol from the very beginning of the incubation. This sequestration was not observed in the case of sensitive cells. Platinum accumulation in vesicles possibly presents a mechanism of resistance to platinum complexes. This mechanism appears to be unrelated to the mechanism of deactivation of platinum compounds by glutathione. Encapsulation of the dinuclear platinum complexes in lysosomal vesicles provides a plausible explanation for the decreased activity of these compounds in the resistant cell line, as compared to the sensitive cell line.

Anthraquinones↗
PubMed2004

Structure-dependent in vitro cytotoxicity of the isomeric complexes [Ru(L)2Cl2] (L= o-tolylazopyridine and 4-methyl-2-phenylazopyridine) in comparison to [Ru(azpy)2Cl2].

The dichlorobis(2-phenylazopyridine)ruthenium(II) complexes, [Ru(azpy)(2)Cl(2)], are under renewed investigation due to their potential anticancer activity. The three most common isomers alpha-, beta- and gamma-[RuL(2)Cl(2)] with L= o-tolylazopyridine (tazpy) and 4-methyl-2-phenylazopyridine (mazpy) (alpha indicating the coordinating Cl, N(pyridine) and Nazo atoms in mutual cis, trans, cis positions, beta indicating the coordinating Cl, N(pyridine) and Nazo atoms in mutual cis, cis, cis positions, and gamma indicating the coordinating Cl, N(pyridine) and Nazo atoms in mutual trans, cis, cis positions) are synthesized and characterized by NMR spectroscopy. The molecular structures of gamma-[Ru(tazpy)(2)Cl(2)] and alpha-[Ru(mazpy)(2)Cl(2)] are determined by X-ray diffraction analysis. The IC(50) values of the geometrically isomeric [Ru(tazpy)(2)Cl(2)] and [Ru(mazpy)(2)Cl(2)] complexes compared with those of the parent [Ru(azpy)(2)Cl(2)] complexes are determined in a series of human tumour cell lines (MCF-7, EVSA-T, WIDR, IGROV, M19, A498 and H266). These data unambiguously show for all complexes the following trend: the alpha isomer shows a very high cytotoxicity, whereas the beta isomer is a factor 10 less cytotoxic. The gamma isomers of [Ru(tazpy)(2)Cl(2)] and [Ru(mazpy)(2)Cl(2)] display a very high cytotoxicity comparable to that of the gamma isomer of the parent compound [Ru(azpy)(2)Cl(2)] and to that of the alpha isomer. These biological data are of the utmost importance for a better understanding of the structure-activity relationships for the isomeric [RuL(2)Cl(2)] complexes.

Antineoplastic Agents↗
PubMed2004

Bis[bis(pyrimidin-2-yl-kappaN)amine](dicyanamido-kappaN1)(trifluoromethanesulfonato-kappaO)copper(II) ethanol hemisolvate forms a hydrogen-bonded chain.

In the crystal structure of [Cu(CF(3)SO(3))(C(2)N(3))(C(8)H(7)N(5))(2)].0.5C(2)H(6)O, the Cu(II) atom adopts a distorted octahedral geometry, with the basal plane formed by two N atoms of one dipyrimidinylamine ligand, one N atom of the second pyrimidine ligand and a nitrile N atom of the dicyanamide anion [Cu-N = 1.972 (2)-2.021 (2) A]. The apical positions are occupied by an N atom of the second ligand [Cu-N = 2.208 (2) A], and an O atom of the trifluoromethanesulfonate anion [Cu-O = 2.747 (2) A] at a semi-coordination distance. Pairs of inversion-related N-H.N hydrogen bonds of the so-called Watson-Crick type, augmented by two C-H.N contacts, link adjacent complexes into an infinite one-dimensional chain running in the [101] direction.

Journal Article↗
PubMed2004

Dichlorobis(2-phenylazopyridine)ruthenium(II) complexes: characterisation, spectroscopic and structural properties of four isomers.

The didentate ligand 2-phenylazopyridine (azpy) can--in theory--give rise to five different isomeric complexes of the type [Ru(azpy)2Cl2], of which three have been known since 1980. The molecular structures of the cis-dichlorobis(2-phenylazopyridine) ruthenium(II) complexes alpha-[Ru(azpy)2Cl2] and beta-[Ru(azpy)2Cl2](in which the coordinating pyridine nitrogen atoms are in mutually trans and cis positions, respectively, whilst the azo nitrogen atoms are in mutually cis positions) were unambiguously determined in the early 1980s. The third isomer, gamma-[Ru(azpy)2Cl2], has for two decades, erroneously, been assumed to be the all-trans isomer. In a recent communication we have proven that for this gamma isomer the chloride ions are indeed in a trans geometry, but the pyridine nitrogen and azo nitrogen atoms of the two azpy ligands are in mutually cis geometries. In this paper the isolation of a fourth isomer is presented, the hitherto unknown delta-[Ru(azpy)2Cl2]. The isomeric structure of delta-[Ru(azpy)2Cl2] has been determined by 1H-NMR spectroscopy and single-crystal X-ray diffraction analysis, and is the all-trans isomer. The bis(azpy)-ruthenium(II) isomers are of interest because of the pronounced cytotoxicity they exhibit against tumour cell lines and could be very useful in the search for structure-activity relationships of antitumour-active ruthenium complexes, as among the isomers there is a significant difference in activity. It is of paramount importance to have a good understanding of the structural and spectroscopic properties of these complexes, which in this paper are compared and discussed, with a particular emphasis on 1D and 2D 1H NMR spectroscopies.

Chlorine↗
PubMed2004

The hydrolysis of the anti-cancer ruthenium complex NAMI-A affects its DNA binding and antimetastatic activity: an NMR evaluation.

The coordination of the antimetastatic agent NAMI-A, [H(2)im][trans-RuCl(4)(dmso-S)(Him)], (Him=imidazole; dmso=dimethyl sulfoxide), to the DNA model base 9-methyladenine (9-MeAde) was investigated in water. NMR spectroscopy was first applied for the study of the molecular stability and hydrolysis of NAMI-A in aqueous solution over a range of pH (3.0-7.4) and chloride ion concentrations (0-1 M) at 37.0 degrees C. In physiological conditions (phosphate buffer, pH 7.4) NAMI-A disappears from the solution in 15 min due to chloride and dmso hydrolysis, leading to uncharacterised poly-oxo Ru species. Conversely, at lower pH (3.0-6.0) and in water (pH approximately 5.5), only a partial dmso hydrolysis occurs, slowly forming the [trans-RuCl(4)(H(2)O)(Him)](-) complex. This latter species coordinates to 9-MeAde (via the N7 of 9-MeAde), forming the [trans-RuCl(4)(9-MeAde)(Him)](-) complex. NAMI-A and [trans-RuCl(4)(H(2)O)(Him)](-) give comparable intracellular ruthenium concentrations and accumulate in KB cells (human mouth carcinoma) and accumulate these at the G(2)/M phase, while poly-oxo Ru species do not, and their cell uptake is reduced to 50%. On the contrary, G(2)/M arrest and protein content in the murine metastatic cell line metGM, are not influenced by NAMI-A hydrolysis. Hydrolysed NAMI-A species apparently are easier taken up by the metGM cells, showing intracellular ruthenium concentrations one order of magnitude greater than those of intact NAMI-A. Therefore, it is proposed that the selective antimetastatic activity of NAMI-A during in vivo experiments can be attributed to its hydrolysed species.

Antineoplastic Agents↗
PubMed2004

Water-soluble platinum(II) complexes of diamine chelating ligands bearing amino-acid type substituents: the effect of the linked amino acid and the diamine chelate ring size on antitumor activity, and interactions with 5'-GMP and DNA.

Six new Pt(II) complexes are described having the general formula PtCl(2)(LL), in which LL is a chelating diamine ligand bearing an amino acid as substituent. The amino acids chosen are l-alanine and its methyl ester, and l-phenylalanine. The compounds have been characterized using analytical and spectroscopic methods. The influence on the biological properties of the size of the chelate ring and the structure of the amino acid substituent has been studied. The effect of the presence of a carboxylic or carboxylate group on the amino acid C-terminus has also been determined. It is demonstrated by circular dichroism (CD) that the effect on the secondary structure of DNA induced by the six complexes differ from each other. In all cases, the interaction takes place at the N7 position of the purine bases, as shown by NMR monitoring. The general behavior of these platinum complexes, with one exception, is to uncoil the DNA from the B form to the C form. The interactions with 5'-GMP and DNA have been compared with their expected antitumour activity. The complexes with l-alanine and l-phenylalanine exhibit cytotoxic activity in HeLa and HL-60 cell lines, in a dose- and time-dependent manner. No cytotoxic activity of the methyl ester derivatives have been determined because of their low solubility in aqueous solution.

Amino Acids↗
PubMed2003

Platinum complexes of diaminocarboxylic acids and their ethyl ester derivatives: the effect of the chelate ring size on antitumor activity and interactions with GMP and DNA.

A number of new Pt(II) complexes is described having the general formula PtCl(2)(LL), where LL is a chelating diamine ligand. Ligands LL were chosen as D,L-2,3-diaminopropionic acid and its ethyl ester, and D,L-2,4-diaminobutyric acid and its ethyl ester. The compounds were characterized using analytical and spectroscopic methods. The influence of the size of the chelate ring and its functionalization on the biological properties was studied. It was demonstrated by circular dichroism (CD) that the effects on the secondary structure of DNA induced by the four complexes are different. The interaction takes place at the N7 position of the purine bases, as shown by NMR studies. The platinum complexes of 2,3-diaminopropionic acid and 2,4-diaminobutyric acid are able to form intrastrand adducts with DNA and to distort the double helix by changing the base stacking. The ethyl ester derivatives uncoil the DNA from the B form to the C form. The interactions with 5'-GMP and DNA were compared with their antitumor activity. The platinum complexes of diaminocarboxylic acids exhibit cytotoxic activity in the A431, HeLa, and HL-60 cell lines in a dose- and time-dependent manner.

Antineoplastic Agents↗
PubMed2003

Kinetic study of azole-bridged dinuclear platinum(II) complexes reacting with a hairpin-stabilized double-stranded oligonucleotide.

The cytotoxic dinuclear platinum(II) complexes [[cis-Pt(NH(3))(2)](2)(mu-OH)(mu-pz)](NO(3))(2) (pz=pyrazolate) (1) and [[cis-Pt(NH(3))(2)](2)(mu-OH)(mu-1,2,3-ta-N1,N2)](NO(3))(2) (1,2,3-ta=1,2,3-triazolate) (2), were allowed to react with the hairpin-stabilized double-stranded oligonucleotide d(TATGGCATT(4)ATGCCATA), to determine the amounts of intrastrand and interstrand DNA adducts. The reaction kinetics was investigated by reversed-phase HPLC, and the resulting products were analyzed using mass spectroscopy combined with enzymatic digestion, and Maxam-Gilbert sequencing. The reaction of 1 results in the formation of the 1,2-intrastrand d(GG) adduct as the major final product. The two most abundant products of 2 were identified as isomeric 1,2-intrastrand d(GG) adducts differing probably in platinum coordination to the triazole ring. No GG-interstrand crosslinks were detected with either compound. d(GGC)-d(GCC) sequences of DNA do thus not appear to represent significant targets for forming interstrand crosslinks with either 1 or 2.

Azoles↗
PubMed2003

The interaction of peptide-tethered platinum(II) complexes with DNA.

The sequence specificity and intensity of DNA damage induced by six peptide-tethered platinum complexes was compared to cisplatin and Pt(en)Cl(2). DNA damage was investigated in pUC19 plasmid and in intact HeLa cells, and quantitatively analyzed using a Taq DNA polymerase/linear amplification assay. The DNA sequence specificity of the peptide-platinum compounds was found to be very similar to cisplatin and Pt(en)Cl(2), with runs of consecutive guanines being the most intensely damaged sites. The observed reactivity of the peptide-platinum complexes towards plasmid DNA was lower compared to cisplatin and Pt(en)Cl(2), with the glycine-tethered complex 3 and the phenylalanine-tethered complex 4 producing the highest relative damage intensity, followed by (in decreasing order) lysine-tethered (5), arginine-tethered (6), serine-tethered (7) and glutamate-tethered (8). The reactivity of the peptide-platinum complexes towards cellular DNA was also lower compared to cisplatin and Pt(en)Cl(2). For most investigated complexes, the relative damage intensities were found to be similar in cells compared to plasmid DNA, but were greatly reduced for 3 and 4. The lysine-tethered 5 complex produced the highest DNA damage intensity in cells followed by (in decreasing order) 6, 7, 3, 4 and 8.

Antineoplastic Agents↗
PubMed2003

New cytotoxic and water-soluble bis(2-phenylazopyridine)ruthenium(II) complexes.

New water-soluble bis(2-phenylazopyridine)ruthenium(II) complexes, all derivatives of the highly cytotoxic alpha-[Ru(azpy)(2)Cl(2)] (alpha denoting the coordinating pairs Cl, N(py), and N(azo) as cis, trans, cis, respectively) have been developed. The compounds 1,1-cyclobutanedicarboxylatobis(2-phenylazopyridine)ruthenium(II), alpha-[Ru(azpy)(2)(cbdca-O,O')] (1), oxalatobis(2-phenylazopyridine)ruthenium(II), alpha-[Ru(azpy)(2)(ox)] (2), and malonatobis(2-phenylazopyridine)ruthenium(II), alpha-[Ru(azpy)(2)(mal)] (3), have been synthesized and fully characterized. X-ray analyses of 1 and 2 are reported, and compound 1 is the first example in which the cbdca ligand is coordinated to a ruthenium center. The cytotoxicity of this series of water-soluble bis(2-phenylazopyridine) complexes has been determined in A2780 human ovarian carcinoma and A2780cisR, the corresponding cisplatin-resistant cell line. For comparison reasons, the cytotoxicity of the complexes alpha-[Ru(azpy)(2)Cl(2)], alpha-[Ru(azpy)(2)(NO(3))(2)], beta-[Ru(azpy)(2)Cl(2)] (beta indicating the coordinating pairs Cl, N(py), and N(azo) as cis, cis, cis, respectively), and beta-[Ru(azpy)(2)(NO(3))(2)] have been determined in this cell line. All the bis(2-phenylazopyridine)ruthenium(II) compounds display a promising cytotoxicity in the A2780 cell line (IC(50) = 0.9-10 microM), with an activity comparable to that of cisplatin and even higher than the activity of carboplatin. Interestingly, the IC(50) values of this series of ruthenium compounds (except the beta isomeric compounds) are similar in the cisplatin-resistant A2780cisR cell line compared to the normal cell line A2780, suggesting that the activity of these compounds might not be influenced by the multifactorial resistance mechanism that affect platinum anticancer agents.

Antineoplastic Agents↗
PubMed2003

A versatile approach towards regioselective platinated DNA sequences.

Undesired N(7) platination of 2'-deoxyguanosine residues at predetermined sites in an oligodeoxynucleotide (ODN) sequence is prevented by applying the sterically demanding diphenylcarbamoyl (DPC) as an O(6)-protecting group. The presence of a base-labile oxalyl linker between the immobilized 3'-nucleotide and controlled pore glass (CPG) allows cleavage of the protected ODN from the support and leaves DPC protection unaffected. This method provides an ODN with specifically blocked guanine-N(7) sites for platination. In the hexanucleotides prepared in this study, 5'-GGBGGT-3'(for B=T, C and A), a platinum GG adduct is introduced at G4,G5. These site-specific platinated hexamers were isolated in a yield of 65 %, and were fully characterized by using reversed-phase HPLC (high performance liquid chromotography), LCMS (liquid chromatography-mass spectrometry), MALDI-TOF MS (matrix-assisted laser desorption/ionization time-of-flight mass spectrometry), PAGE (polyacrylamide gel electrophoresis) and Maxam-Gilbert sequencing analysis.

Base Sequence↗