Anna C G Hotze

Leiden University, Leyden, South Holland, Netherlands

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Publications (32)131.89 Total impact

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    [Show abstract] [Hide abstract] ABSTRACT: The electron capture dissociation (ECD) of metallo-supramolecular dinuclear triple-stranded helicate Fe2L 34+ ions was determined by Fourier transform ion cyclotron resonance mass spectrometry. Initial electron capture by the di-iron(II) triple helicate ions produces dinuclear double-stranded complexes analogous to those seen in solution with the monocationic metal centers CuI or AgI. The gas-phase fragmentation behavior [ECD, collision-induced dissociation (CID), and infrared multiphoton dissociation (IRMPD)] of the di-iron double-stranded complexes, (i.e., MS3 of the ECD product) was compared with the ECD, CID, and IRMPD of the CuI and AgI complexes generated from solution. The results suggest that iron-bound dimers may be of the form Fe 2IL 22+ and that ECD by metallo-complexes allows access, in the gas phase, to oxidation states and coordination chemistry that cannot be accessed in solution.
    Preview · Article · Nov 2009 · Journal of the American Society for Mass Spectrometry
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    [Show abstract] [Hide abstract] ABSTRACT: Various interaction modes between a group of six ruthenium polypyridyl complexes and DNA have been studied using a number of spectroscopic techniques. Five mononuclear species were selected with formula [Ru(tpy)L1L2](2−n)+, and one closely related dinuclear cation of formula [{Ru(apy)(tpy)}2{μ-H2N(CH2)6NH2}]4+. The ligand tpy is 2,2′:6′,2″-terpyridine and the ligand L1 is a bidentate ligand, namely, apy (2,2′-azobispyridine), 2-phenylazopyridine, or 2-phenylpyridinylmethylene amine. The ligand L2 is a labile monodentate ligand, being Cl−, H2O, or CH3CN. All six species containing a labile L2 were found to be able to coordinate to the DNA model base 9-ethylguanine by 1H NMR and mass spectrometry. The dinuclear cationic species, which has no positions available for coordination to a DNA base, was studied for comparison purposes. The interactions between a selection of four representative complexes and calf-thymus DNA were studied by circular and linear dichroism. To explore a possible relation between DNA-binding ability and toxicity, all compounds were screened for anticancer activity in a variety of cancer cell lines, showing in some cases an activity which is comparable to that of cisplatin. Comparison of the details of the compound structures, their DNA binding, and their toxicity allows the exploration of structure–activity relationships that might be used to guide optimization of the activity of agents of this class of compounds. Electronic supplementary material The online version of this article (doi:10.1007/s00775-008-0460-x) contains supplementary material, which is available to authorized users.
    Full-text · Article · Mar 2009 · European Journal of Biochemistry
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    [Show abstract] [Hide abstract] ABSTRACT: The supramolecular iron cylinder, [Fe(2)L(3)]Cl(4) (L = C(25)H(20)N(4)), shows unprecedented DNA binding in vitro, inducing intramolecular DNA coiling and also targeting Y-shaped DNA junctions. We investigated its effects on proliferation and survival in both tumor and normal cell lines. Iron cylinder reduced mitochondrial activity of cultures with potency similar to cisplatin, inhibited the cell cycle, and increased cell death by apoptosis. Associated with this, we observed a lowering of the association of propidium iodide with cellular DNA consistent with an observed competitive displacement of PI from naked DNA by cylinders. Importantly, and in contrast to existing anticancer drugs such as cisplatin, the iron cylinder [Fe(2)L(3)](4+) was not genotoxic. In summary, the design of metal complexes such as [Fe(2)L(3)](4+) with potential anticancer properties in the absence of genotoxicity may represent a significant step toward therapeutic advancement.
    Full-text · Article · Jan 2009 · Chemistry & biology
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    Preview · Dataset · Dec 2008
  • [Show abstract] [Hide abstract] ABSTRACT: Two novel copper(ii) terpyridine complexes, [Cu(atpy)(NO(3))(H(2)O)](NO(3)).3H(2)O () and [Cu(ttpy)(NO(3))(2)] () (atpy = 4'-p-N9-adeninylmethylphenyl-2,2':6,2''-terpyridine; ttpy = 4'-p-tolyl-2,2':6,2''-terpyridine) have been prepared and structurally characterized by X-ray crystallography. Both complexes show a CuN(3)O(2) coordination in a square pyramidal (4 + 1) geometry with terpyridine acting as an equatorial ligand. For complex , intermolecular AA base pairing interaction is observed between N(6) and N(1) of adjacent adenines with N(6)N(1) of 3.027(7) A. A molecular dynamics simulation of the DNA binding of two complexes showed that the adenine moiety plays an important role in the intercalation of into DNA. This is verified by UV, fluorescence, circular dichroism and flow linear dichroism studies. The promotional effect from the adenine moiety to the intracellular DNA binding of complex is also confirmed by the inductively coupled plasma mass (ICP-MS) spectrometry data which showed a significant higher copper content in DNA isolated from complex treated MCF-7 and HeLa cells.
    No preview · Article · Jun 2008 · Dalton Transactions
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    [Show abstract] [Hide abstract] ABSTRACT: Enantiopure dinuclear ruthenium polypyridyl complexes of the form [Ru(2)(LL)(4)L(1)](PF(6))(4) (LL = 2,2'-bipyridine (bpy) or 1,10-phenanthroline (phen); L(1)= C(25)H(20)N(4) a bis(pyridylimine) ligand containing a diphenylmethane spacer) have been synthesized using the chiral building blocks cis-[Ru(bpy)(2)(py)(2)](2+) and cis-[Ru(phen)(2)(py)(2)](2+). These dinuclear ruthenium complexes have been characterised using NMR, mass spectrometry, UV-visible absorbance, circular dichroism and linear dichroism. The compounds exhibit good photo and thermal stability. The extinction coefficient for the bpy complex at 478 nm is epsilon(478) = 15,700 mol(-1) cm(-1) dm(3) and for the phen complex is epsilon(478) = 24,900 mol(-1) cm(-1) dm(3). Both complexes have their longest wavelength (metal to ligand charge transfer) transition predominantly x/y (short axis)-polarised while the transitions at shorter wavelength are a mixture of x/y and z-polarisations, similar to both the copper helicate and iron triple helicate studied previously. Cytotoxicity studies reveal that the compounds are dramatically less active against cancer cell lines than the recently reported supramolecular cylinders prepared from the same bis(pyridylimine) ligand.
    Full-text · Article · Mar 2008 · Dalton Transactions
  • [Show abstract] [Hide abstract] ABSTRACT: The binding capability of three ruthenium polypyridyl compounds of structural formula [Ru(apy)(tpy)Ln-](ClO4)(2-n) [1a-c; apy = 2,2'-azobis(pyridine), tpy = 2,2':6',2''-terpyridine, L = Cl, H2O, CH3CN] to a fragment of DNA was studied. The interaction between each of these complexes and the DNA model base 9-ethylguanine (9-EtGua) was followed by means of 1H NMR studies. Density functional theory calculations were carried out to explore the preferential ways of coordination between the ruthenium complexes and guanine. The ruthenium-9-EtGua adduct formed was isolated and fully characterized using different techniques. A variable-temperature 1H NMR experiment was carried out that showed that while the 9-EtGua fragment was rotating fast at high temperature, a loss of symmetry was suffered by the model base adduct as the temperature was lowered, indicating restricted rotation of the guanine residue.
    No preview · Article · Sep 2007 · Inorganic Chemistry
  • [Show abstract] [Hide abstract] ABSTRACT: (Figure presented) A fluorescent supramolecular cylinder binds noncovalently to DNA and shows anticancer activity in cell lines.
    No preview · Article · Jun 2007 · Angewandte Chemie International Edition
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    [Show abstract] [Hide abstract] ABSTRACT: A new metallo-organic gelator formed from an admixture of a substituted nicotinic acid and its sodium salt is described. The nicotinic acid is substituted in the 6-position by an acetal functionality. The crystal structure of the 1:1 mixture revealed that the sodium atoms are aligned in infinite chains with the two organic units hydrogen bonded together to create potentially trinucleating ligands that encase the metal core, which leads to tube-like structures. These one-dimensional crystals were found to spontaneously gelify dichloromethane and provide pyridine gels with high thermal resistance. Gel formation was investigated by several analytical techniques, which included differential scanning calorimetry, TEM, freeze fracture electron microscopy (FFEM), IR spectroscopy and X-ray diffraction, and was found to be induced by the swelling of the one-dimensional material. FFEM and powder X-ray diffraction have revealed that the sodium chains are associated in a highly compacted state into a layered structure inside the gel. Doping these robust gels with dyes by diffusion, such as xylene cyanol, methyl yellow and bromo thymol blue, is feasible without destruction of the gels.
    Full-text · Article · Feb 2007 · Chemistry
  • D. Bardelang · F. Camerel · A. C. G. Hotze · B. Kariuki · B. Paik · M. Schmutz · R. Ziessel · M. J. Hannon
    No preview · Article · Jan 2007
  • Anna C G Hotze · Benson M Kariuki · Michael J Hannon
    [Show abstract] [Hide abstract] ABSTRACT: Brücken schlagen: Metallosupramolekulare Krebstherapeutika wurden entwickelt, die hoch aktiv gegen menschliche Brustkrebszelllinien sind. Die drei vorgestellten Isomere – ein nichthelicales Metallocyclophan, ein nichtgesättigtes Doppelhelicat und eine neue Art von Doppelhelicat – bilden eine Brücke zwischen den Gebieten der metallosupramolekularen Architektur und des Designs von Krebstherapeutika (Bild: doppelhelicales trans/cis-Isomer; rot Ru, grün Cl).
    No preview · Article · Jul 2006 · Angewandte Chemie International Edition
  • [Show abstract] [Hide abstract] ABSTRACT: Ruthenium(II) pyridylimine complexes are explored for their potential as units that might be incorporated into electronic or photonic arrays. The complexes [Ru(bipy)2(L)][PF6]2 (1) and [Ru(tpy)(L)Cl][BF4] (2) with L = phenylpyridin-2-ylmethylene-amine are synthesized and fully characterised using X-ray diffraction analysis and (2D) NMR spectroscopy. 1 displays emission in the far-red area of the spectrum at room temperature. The emission is significantly shifted to longer wavelength with respect to [Ru(bpy)3]2+ indicating that the lowest MLCT state is localised on the pyridylimine ligand. 2 is non-emissive at room temperature and at 77 K.
    No preview · Article · Jul 2006 · Dalton Transactions
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    [Show abstract] [Hide abstract] ABSTRACT: Three ruthenium polypyridyl compounds of structural formula [Ru(apy)(tpy)Ln−](ClO4)(2−n) (apy=2,2′-azobispyridine; tpy=2,2′:6′,2″-terpyridine; L=Cl, H2O, CH3CN) (1a–c) were synthesized and crystallized. These complexes were fully characterized by means of 1D and 2D 1H NMR spectroscopy, as well as mass spectrometry and elemental analysis. Although in theory two isomers are possible, i.e. the one in which the central N atom in tpy is trans to the azo N in apy and the one in which the former is trans to the pyridine N in apy, in all cases only the latter was observed. The molecular structures of the compounds were elucidated by single-crystal X-ray diffraction.
    Full-text · Article · Feb 2006 · Inorganica Chimica Acta
  • [Show abstract] [Hide abstract] ABSTRACT: Manganese complexes of the ligand HphoxCOOR (R=H or Me) have been synthesized and characterized by X-ray analysis, ESI-MS, ligand-field spectroscopy, electrochemistry, and paramagnetic 1H NMR. The ligands, chirally pure or racemic, influence the structures of the complexes formed. Manganese(III) complexes of the ligand HphoxCOOMe are square-pyramidal or octahedral with two ligands bound in a trans fashion in the solid state. The racemic ligand (RS-HphoxCOOMe) as well as the enantiopure ligand (R-HphoxCOOMe) forms manganese complexes with similar solid-state structures. Ligand-exchange reactions occur in solution giving rise to meso complexes as confirmed by ESI-MS and deuteration studies. The manganese(III) complex of R-HphoxCOOH is octahedral, with two dianionic ligands bound in a fac-cct fashion in a tridentate manner. The manganese(III) complex of RS-HphoxCOOH is also octahedral with two dianionic ligands now bound in a trans fashion in a didentate manner and with two water molecules occupying axial sites. The paramagnetic 1H NMR spectra of the complexes have been interpreted on the basis of the relaxation times with the help of the inversion-recovery pulse technique. The binding of imidazole with the metal center depends on the chirality of the ligands in the metal complexes of HphoxCOOMe. Imidazole coordination was found to occur with the metal complex that contains two ligands with the same chirality (R and R) (R-1), while no imidazole coordination was found upon reaction with the metal complex that contains two ligands with opposite chirality (R and S) (RS-1). Epoxidation reactions of various alkenes with H2O2 as the oxidant reveal that the complexes give turnover numbers in the range of 10-35, the epoxide being the major product. The catalytic activity depends on the additives used, and a clear base effect is observed. The turnover numbers have been found to be higher in the complexes where no binding of N-Meim is observed. The latter fact unambiguously shows that imidazole binding is not a prerequisite for higher turnover numbers, in contrast to the Mn-Schiff base catalysts.
    No preview · Article · Jan 2006 · Inorganic Chemistry
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    [Show abstract] [Hide abstract] ABSTRACT: Tris(ligand) complexes [RuL3](PF6)2 (L = 2-phenylazopyridine or o-tolylazopyridine) and mixed ligand [RuL′ 2L″](PF6)2 (L′ and L″ are 2-phenylazopyridine or 2,2′-bipyridine) have been synthesized, structurally characterized and investigated for cytotoxic activity. These complexes are important to study the hypothesis that the compound α-[Ru(azpy)2Cl2] (azpy = 2-phenylazopyridine) exhibits a high cytotoxicity due to its two cis chloride ligands, which might be exchanged for biological targets as DNA. Molecular structures of mer[Ru(azpy)3](PF6)2 (1) and mer-[Ru(tazpy)3](PF6)2 (5) (tazpy = o-tolylazopyridine) have been determined by X-ray diffraction. Series of complexes [RuL3] (PF6)2 and [RuL′2L″] (PF6)2 show interesting NMR spectroscopic data; e.g. the spectrum of mer-[Ru(azpy)3](PF 6)2 (1) shows extremely broadened resonances at room temp, but sharpened resonances at low temperature. In the 1H NMR spectra of compounds [Ru(azpy)2-(bpy)]2+ and [Ru(bpy) 2(azpy)]2+ (bpy = 2,2-bipyridine), respectively, less broadened (room temp.) or completely sharp resonances (room temp.) occur in comparison to 1 (under same conditions). By selecting the right temperature and/or concentration, NMR spectra of these series of compounds have been resolved using 2D COSY and NOESY NMR spectroscopy. Remarkably, the cytotoxicity data against a series of human tumor cell lines (A498, EVSA-T, H226, IGROV, M19, MCF-7 and WIDR) show a moderate cytotoxicity for these series of tris(ligand) complexes. So, even though no chloride ligands are present in these tris(ligand) complexes, a considerable cytotoxic activity is observed. This would imply that the 2-phenylazopyridine ruthenium(II) complexes act by a completely different mechanism than the well-known cisplatin. This finding is important, because an anticancer compound acting via a different mechanism is a prerequisite in designing new anticancer drugs. © Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005.
    Full-text · Article · Jun 2005 · Berichte der deutschen chemischen Gesellschaft
  • Aldrik H Velders · Anna C G Hotze · Jan Reedijk
    [Show abstract] [Hide abstract] ABSTRACT: 1H NMR data of α-[Ru(azpy)2(MeBim) 2](PF6)2 (azpy = 2-phenylazopyridine, MeBim = 1-methylbenzimidazole), 2, revealed the presence of a total of seven atropisomers at -95 °C: three head-to-tail, HT, isomers (A, C, and D), and four head-to-head, HH, isomers which, due to the presence of an intrinsic C 2 axis in the α-[Ru(azpy)2] moiety, are two sets of identical pairs (B/B and E/E). The NMR data of 2 represent a unique example of a coordination compound that shows a variable temperature (VT) behavior with more, well-defined steps of slow-to-fast exchange of its atropisomers. At 65 °C, all atropisomers are in fast exchange; on lowering the temperature the sharp signals first broaden (at room temperature) and consecutively split up into two sets of relatively sharp signals, in slow exchange, at about 0 °C (D, 40%, and the coalesced signals of ABBCEE, 60%). Upon further cooling, the set of peaks belonging to D remain sharp until the lowest recording temperatures. The signals of the other set of resonances, on the other hand, first broaden again and then separate into two sets of broad peaks (C/E/E and A) and one set of sharp peaks (B and B in fast exchange); on lowering the temperature even more, these signals broaden once again and finally, at -95 °C, are split up into a total of four sets of signal (A, B/B, C, and E/E). At low temperatures, ROESY experiments revealed that atropisomerization occurs through the synchronous rotation of both MeBim ligands in the interconversion of the two "identical" HH atropisomers B and B, as well as in the interconversion between C and E/E. The HH rotamers B/B furthermore exhibit a slow-to-fast exchange atropisomerization behavior that is observed independently from the other dynamic processes in this compound. The versatile cis bifunctional binding of the DNA model bases (MeBim ligands) in 2 parallels the observation of α-[Ru(azpy)2Cl2] which shows extraordinarly high cytotoxicity against tumor cell lines.
    No preview · Article · Feb 2005 · Chemistry
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    [Show abstract] [Hide abstract] ABSTRACT: 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.
    Preview · Article · Sep 2004 · Inorganic Chemistry
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    [Show abstract] [Hide abstract] ABSTRACT: Isomers of dichlorobis(2-phenylazopyridine)ruthenium(II) [Ru(azpy)2Cl2], especially the so-called α isomer, display remarkably high cytotoxicities against human tumor cell lines. Unfortunately, the parent [Ru(azpy)2Cl2] compounds are poorly water-soluble. In this paper the synthesis and characterization of the new water-soluble ligand 2-phenylazopyridine-5-sulfonic acid (Hsazpy) is described. Use of this ligand in reaction with RuCl3 gave two isomers, which were isolated as α- and β-[NEt4]2[Ru(sazpy)2Cl2]. The compounds have been fully characterized by (2D) NMR spectroscopy. The molecular structure of the α isomer of [NEt4]2[Ru(sazpy)2Cl2]·2H2O has been determined by single-crystal structure analysis. The packing in the crystal structure of α-[NEt4]2[Ru(sazpy)2Cl2]·2H2O shows an interesting hydrogen-bonding pattern in which two water molecules are involved. One water molecule bridges between a Cl ligand and a SO3− group within one ruthenium moiety, the other water molecule forms a bridge between two SO3− groups from two different ruthenium centers, resulting in a chain-like structure. Preliminary evaluation of the cytotoxicity by means of the IC50 value in A2780 cell line classifies α-[NEt4]2[Ru(sazpy)2Cl2] as non-toxic, but this does not rule out other anticancer activities.
    Full-text · Article · May 2004 · New Journal of Chemistry
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    [Show abstract] [Hide abstract] ABSTRACT: 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.
    Full-text · Article · May 2004 · JBIC Journal of Biological Inorganic Chemistry
  • [Show abstract] [Hide abstract] ABSTRACT: A new tris(dimine)ruthenium(II) complex containing a free flexible tail on one ligand, available for the coordination of a second metal, has been synthesised.
    No preview · Article · Mar 2004 · Tetrahedron Letters