Search PubMed⌕ Search

Biomedical subjects

Kim R Dunbar

Publications and source records attributed to Kim R Dunbar.

At least 37 records · Page 2Linked to original sources
PubMed2005

Structural and magnetic properties of iron(II) complexes with 1,4,5,8,9,12-hexaazatriphenylene (HAT).

Reactions of Fe(II) salts with the ligand 1,4,5,8,9,12-hexaazatriphenylene (HAT) led to the isolation and characterization of four new compounds: [Fe3(HAT)(H2O)12](SO4)3.3.3H2O (1), [Fe2(HAT)(SO4)(H2O)5](SO4).2H2O.CH3OH (2), [Fe2(HAT)(SO4)(H2O)5](SO4).3H2O (3), and [Fe3Cl5(HAT)(CH3OH)4(H2O)]Cl (4). Compound 1 crystallizes as a trinuclear cluster in which HAT acts as a tris-chelating ligand. Compounds 2 and 3 are two polymorphs of an infinite one-dimensional structure in which the Fe atoms are coordinated to HAT and then connected into the chain through bridging sulfate anions. Compound 4 exhibits a similar chain structure, but with bridging chloride ligands. The magnetic behavior of the new compounds is indicative of weak antiferromagnetic coupling between the Fe(II) centers through the HAT ligand.

Journal Article↗
PubMed2005

Manganese(II) chemistry of a new N3O-donor chelate ligand: synthesis, X-ray structures, and magnetic properties of solvent- and oxalate-bound complexes.

The synthesis and characterization of a new N3O donor ligand N-benzyl-N-((6-pivaloylamido-2-pyridyl)methyl)-N-(2-pyridylmethyl)amine (bpppa) is reported. Treatment of bpppa with Mn(II)(ClO4)2.6H2O in acetonitrile solution yielded the mononuclear [(bpppa)Mn(CH3CN)(H2O)](ClO4)2 (1) which was characterized by X-ray crystallography, elemental analysis, IR spectroscopy, mass spectrometry, and a solution magnetic moment measurement. Admixture of equimolar equivalents of bpppa and Mn(II)(ClO4)2.6H2O in methanol solution, followed by addition of 0.5 or 1 equivalents of sodium oxalate, yielded the binuclear complex [{(bpppa)Mn}2([mu]-C2O4)](ClO4)2 (2), which was characterized by X-ray crystallography, elemental analysis, IR spectroscopy, mass spectrometry, and solid-state magnetic measurements. While 1 is mononuclear, the formation of the binuclear oxalate derivative indicates that use of the bpppa ligand does not enable isolation of a complex that is structurally relevant to a proposed 1:1 Mn(II)-oxalate adduct in the catalytic cycle of the oxalate degrading enzyme oxalate decarboxylase.

Benzyl Compounds↗
PubMed2005

Covalent binding and interstrand cross-linking of duplex DNA by dirhodium(II,II) carboxylate compounds.

The study of the interactions of double-stranded (ds) DNA with the dirhodium carboxylate compounds Rh(2)(O(2)CCH(3))(4)(H(2)O)(2) (Rh1), [Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6)](BF(4))(2) (Rh2), and Rh(2)(O(2)CCF(3))(4) (Rh3) supports the presence of covalently linked DNA adducts, including stable DNA interstrand cross-links. The present biochemical study refutes earlier claims that no reaction between dirhodium compounds and dsDNA occurs. The reversal behavior of these interstrand cross-links in 5 M urea at 95 degrees C (for different heating times) implies the presence of various coordination modes involving ax/ax, ax/eq, and eq/eq DNA interactions with the dirhodium core. The reaction rates of the dirhodium compounds with dsDNA were determined spectroscopically and are in the order Rh1 << Rh2 < Rh3. This difference in behavior of the three dirhodium compounds correlates with the lability of the leaving groups and corresponds to the extent of interstrand cross-link formation by these compounds on a 123 bp DNA fragment, as observed by denaturing polyacrylamide gel electrophoresis (dPAGE). Since all three dirhodium compounds form covalent Rh-DNA adducts, including interstrand cross-links, it is important that DNA be considered a potential target for biological activity of these dirhodium carboxylate compounds.

Carboxylic Acids↗
PubMed2005

catena-Poly[[diaquacobalt(II)]-mu-oxalato].

Single crystals of the title compound, [Co(C2O4)(H2O)2]n, have been prepared by hydrothermal methods and characterized by X-ray diffraction analysis. The crystal structure consists of infinite one-dimensional chains of diaquacobalt(II) units bridged by oxalate groups. These chains lie on twofold symmetry axes parallel to the b axis, and the [Co(C2O4)]n system is nearly planar within experimental error. The cobalt(II) coordination polyhedra are irregular octahedra, with oxalate O atoms at the equatorial positions and water molecules at the axial positions. The chains are linked by hydrogen bonds via the water molecules.

Journal Article↗
PubMed2005

Interactions of metal-metal-bonded antitumor active complexes with DNA fragments and DNA.

This Account summarizes the DNA binding properties of anticancer active dinuclear Rh, Re, and Ru compounds. The combined results of NMR spectroscopy, X-ray crystallography, and various biochemical tools provide incontrovertible evidence that dinuclear complexes are favorably poised to bind to purine nucleobases, DNA fragments, and double-stranded DNA. Moreover, direct DNA photocleavage in vitro is effected by dirhodium compounds in the presence of electron acceptors in solution or directly attached to the dirhodium core. This research has provided valuable insight in the interactions of dinuclear compounds with DNA, knowledge that is an excellent backdrop for rational design of promising dinuclear drugs.

Antineoplastic Agents↗
PubMed2004

Role of the orbitally degenerate Mn(III) ions in the single-molecule magnet behavior of the cyanide cluster ([MnII(tmphen)2]3[Mn(III)(CN)6]2) (tmphen = 3,4,7,8-tetramethyl-1,10-phenanthroline).

We report a new theoretical model that accounts for the unusual magnetic properties of the cyanide cluster ([MnII(tmphen)2]3[MnIII(CN)6]2) (tmphen = 3,4,7,8-tetramethyl-1,10-phenanthroline). The model takes into account (1) the spin-orbit interaction, (2) the trigonal component of the crystal field acting on the ground-state cubic (3)T(1) terms of the apical Mn(III) ions, and (3) the isotropic contribution to the exchange interaction between Mn(III) and Mn(II) ions. The ground state of the cluster was shown to be the state with the total angular momentum projection |M(J)| = 15/2; the energies of the low-lying levels obtained from this treatment increase with decreasing |M(J)| values, a situation that leads to a barrier for the reversal of magnetization (U(eff) approximately 30 cm(-1)). The new model explains the recently discovered single-molecule magnet behavior of the ([MnII(tmphen)2]3[MnIII(CN)6]2)in contrast to the traditional approach that takes into account only the ground-state spin (S) and a negative zero-field splitting parameter (D(S) < 0).

Journal Article↗
PubMed2004

DNA binding and photocleavage in vitro by new dirhodium(II) dppz complexes: correlation to cytotoxicity and photocytotoxicity.

Two new dirhodium(II) complexes possessing the intercalating dppz ligand (dppz = dipyrido[3,2-a:2',3'-c]phenazine), cis-[Rh(2)(mu-O(2)CCH(3))(2)(dppz)(eta(1)-O(2)CCH(3))(CH(3)OH)](+) (1) and cis-[Rh(2)(mu-O(2)CCH(3))(2)(dppz)(2)](2+) (2), were synthesized and characterized as potential agents for photochemotherapy. Various techniques show that 1 binds to DNA through intercalation, although some aggregation of the complex on the DNA surface is also present. In contrast, 2 does not intercalate between the DNA bases; however, strong hypochromic behavior is observed in the presence of DNA, which can be attributed to intermolecular pi-stacking of 2 enhanced by the polyanion. The apparent DNA binding constants determined using optical titrations are compared to those from dialysis experiments. Both complexes photocleave pUC18 plasmid in vitro under irradiation with visible light (lambda(irr) >or= 395 nm, 15 min), resulting in the nicked, circular form. Greater photocleavage is observed for 1 relative to 2, which may be due to the ability of 1 to intercalate between the DNA bases. The cytotoxicity toward human skin cells (Hs-27) measured as the concentration at which 50% cell death is recorded, LC(50), was found to be 135 +/- 8 microM for 2 in the dark (30 min), which is significantly lower than those of 1 (LC(50) = 27 +/- 2 microM) and Rh(2)(O(2)CCH(3))(4) (LC(50) = 15 +/- 2 microM). Irradiation of cell cultures containing 1 and Rh(2)(O(2)CCH(3))(4) with visible light (400-700 nm, 30 min) has little effect on their cytotoxicity, with LC(50) values of 21 +/- 3 and 13 +/- 2 microM, respectively. Interestingly, a 3.4-fold increase in the toxicity of 2 is observed when the cell cultures are irradiated (400-700 nm, 30 min), resulting in LC(50) = 39 +/- 1 microM. The greater toxicity of 1 compared to 2 in the dark may be related to the ability of the former compound to intercalate between the DNA bases. The lower cytotoxicity of 2, together with its significantly greater photocytotoxicity, makes this complex a potential agent for photodynamic therapy (PDT). These results suggest that intercalation or strong DNA binding may not be a desirable property of a potential PDT agent.

Antineoplastic Agents↗
PubMed2004

Molecular cube of Re(II) and Mn(II) that exhibits single-molecule magnetism.

A pseudocubic, paramagnetic cluster of ReII and MnII, [{MnCl}4{Re(triphos)(CN)3}4], has been prepared, and its magnetic properties have been investigated. Antiferromagnetic coupling is observed between the "S = 1/2" ReII and S = 5/2 MnII centers resulting in an effective S = 8 ground state. AC susceptibility studies reveal that the molecule is a single-molecule magnet with an effective barrier for magnetization reversal of Ueff = 8.8 cm-1.

Journal Article↗
PubMed2004

Binding of DNA purine sites to dirhodium compounds probed by mass spectrometry.

The adducts formed between the antitumor active compounds [Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6)](BF(4))(2), Rh(2)(O(2)CCH(3))(4), and Rh(2)(O(2)CCF(3))(4) with DNA oligonucleotides have been assessed by matrix-assisted laser desorption ionization (MALDI) and nanoelectrospray (nanoESI) coupled to time-of-flight mass spectrometry (TOF MS). A series of MALDI studies performed on dipurine (AA, AG, GA, and GG)-containing single-stranded oligonucleotides of different lengths (tetra- to dodecamers) led to the establishment of the relative reactivity cis-[Pt(NH(3))(2)(OH(2))(2)](2+) (activated cisplatin) approximately Rh(2)(O(2)CCF(3))(4) > cis-[Pt(NH(3))(2)Cl(2)] (cisplatin) >> [Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6)](BF(4))(2) > Rh(2)(O(2)CCH(3))(4) approximately Pt(C(6)H(6)O(4))(NH(3))(2) (carboplatin). The relative reactivity of the complexes is associated with the lability of the leaving groups. The general trend is that an increase in the length of the oligonucleotide leads to enhanced reactivity for Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6)](BF(4))(2) and Rh(2)(O(2)CCH(3))(4) (except for the case of [Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6)](2+), which reacts faster with the GG octamers than with the dodecamers), whereas the reactivity of Rh(2)(O(2)CCF(3))(4) is independent of the oligonucleotide length. When monitored by ESI, the dodecamers containing GG react faster than the respectiveAA oligonucleotides in reactions with Rh(2)(O(2)CCF(3))(4) and Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6)](BF(4))(2), whereas AA oligonucleotides react faster with Rh(2)(O(2)CCH(3))(4). The mixed (AG, GA) purine sequences exhibit comparable rates of reactivity with the homopurine (AA, GG) dodecamers in reactions with Rh(2)(O(2)CCH(3))(4). The observation of initial dirhodium-DNA adducts with weak axial (ax) interactions, followed by rearrangement to more stable equatorial (eq) adducts, was achieved by electrospray ionization; the Rh-Rh bond as well as coordinated acetate or acetonitrile ligands remain intact in these dirhodium-DNA adducts. MALDI in-source decay (ISD), collision-induced dissociation (CID) MS-MS, and enzymatic digestion studies followed by MALDI and ESI MS reveal that, in the dirhodium compounds studied, the purine sites of the DNA oligonucleotides interact with the dirhodium core. Ultimately, both MALDI and ESI MS proved to be complementary, valuable tools for probing the identity and stability of dinuclear metal-DNA adducts.

Binding Sites↗
PubMed2004

Electrochemical, spectroscopic, and structural evidence for the mild hydrolysis of tetracyanoethylene, TCNE, to form the 2,3,3-tricyanoacrylamidate ligand: isolation of an unexpected quadruply-bonded polymeric material [Mo2(O2CCMe3)3((NC)2CC(CN)CONH)]infinity.

Under strictly anhydrous conditions, no reaction occurs between Mo(2)(O(2)CCMe(3))(4) and tetracyanoethylene, TCNE, at room temperature, but after addition of 1 equiv of water, a reaction proceeds to form [Mo(2)(O(2)CCMe(3))(3)((NC)(2)CC(CN)CONH)], 1. The compound contains a quadruple-bonded Mo(2) unit and the 2,3,3-tricyanoacrylamidate anion as a ligand (TC3A), a very unusual hydrolyzed form of TCNE. Two different solid-state structures were obtained after crystallization of 1. Crystals obtained from CH(2)Cl(2) consist of a two-dimensional network, and crystals grown from a C(6)H(6) solution form a 1-D chain motif. In both cases, the TC3A ligand acts as a polydentate ligand involving a bidentate OCN bridging unit and two CN groups. The electrochemical and spectroscopic (IR, UV/vis/near-IR, NMR, EPR) properties of 1 support the formulation in solution as a discrete 1:1 complex of the TC3A donor ligand and a Mo(2) unit with no charge transfer. The coordinated TC3A ligand exhibits redox properties similar to those of free TCNE.

Journal Article↗
PubMed2004

A charge-transfer-induced spin transition in the discrete cyanide-bridged complex [[Co(tmphen)2]3[Fe(CN)6]2].

A charge-transfer-induced spin transition (CTIST) is observed in the discrete cyanide-bridged complex, {[Co(tmphen)2]3[Fe(CN)6]2}. Single-crystal X-ray diffraction, 57Fe Mössbauer spectroscopy, and magnetic susceptibility were used collectively to describe the oxidation states of the Co and Fe ions in this cluster as a function of temperature. This pentanuclear complex represents the first example of a CTIST at the discrete molecular level.

Journal Article↗
PubMed2004

Direct DNA photocleavage by a new intercalating dirhodium(II/II) complex: comparison to Rh2(mu-O2CCH3)4.

Transition metal complexes possessing the intercalating dppz ligand (dppz = dipyrido[3,2-a:2',3'-c]phenazine) typically bind ds-DNA through intercalation (K(b) approximately 10(5)-10(6) M(-1)), and DNA photocleavage by these complexes with visible light proceeds through the generation of a reactive oxygen species. The DNA binding and photocleavage by [Rh(2)(mu-O(2)CCH(3))(2)(eta(1)-O(2)CCH(3))(CH(3)OH)(dppz)](+) (2) is reported and compared to that of Rh(2)(mu-O(2)CCH(3))(4) (1). Spectral changes and an increase in viscosity provide evidence for the intercalation of 2 to double stranded DNA with K(b) = 1.8 x 10(5) M(-1). DNA photocleavage by 2 is observed upon irradiation with lambda(irr) > 395 nm both in air and deoxygenated solution. DNA photocleavage is not observed for 1 or free dppz ligand under these irradiation conditions. The coupling of a single dppz ligand to a dirhodium(II/II) bimetallic core in 2 provides a means to access oxygen-independent DNA photocleavage with visible light.

Antineoplastic Agents↗
PubMed2004

Structural characterization, magnetic properties, and electrospray mass spectrometry of two Jahn-Teller isomers of the single-molecule magnet [Mn12O12(CF3COO)16(H2O)4].

The syntheses and characterization of two new, highly soluble, single-molecule magnets [Mn12O12(CF3COO16(H2O)4].2CF3COOH.4H2O (1) and Mn12O12(CF3COO16(H2O)4].CF3COOH.7H2O (2) are reported. Compound 1 was isolated from the reaction of Mn12O12(CF3COO16(H2O)4] with trifluoroacetic acid in CH2Cl2. Compound 1 crystallizes in the tetragonal space group Ifourmacr; (No. 82) with unit cell parameters a = b = 18.128(3) A, c = 13.048(3) A, V = 4287.9(19) A3, Z = 2 and is isostructural to [Mn12O12(CH3COO)16(H2O)4]. Compound 2 was prepared from the reaction of Mn12O12(CF3COO16(H2O)4] with neat trifluoroacetic acid, and crystallizes in the monoclinic space group P2(1)/n (No. 14) with unit cell parameters a = 15.221(8) A, b = 21.870(12) A, c = 27.217(15) A, beta = 90.53(1) degrees, V = 9060(9) A3, and Z = 4. The dc magnetic susceptibility measurements in the 2-300 K temperature range support a high-spin ground state. The magnetization data collected in the 1-7 T field range from 1.8 to 4.0 K were best fit to the parameters S = 10, g = 2.15, D = -0.65 cm(-1), and E = 0 cm(-1) for 1 and S = 10, g = 1.87, D = -0.34 cm(-1), and E = -0.10 cm(-1) for 2. The ac susceptibility data for compound 1 reveal out-of-phase (chi(m)") signals in the 4-7 K temperature range, whereas the chi(m)" signals for compound 2 appear below temperatures of 4 K. This variation in blocking temperatures is a consequence of the two different crystallographic forms of compounds 1 and 2. Compound 1 exhibits the same structural geometry and distortions found in [Mn12O12(CH3COO)16(H2O)4], while compound 2 is of lower molecular symmetry with two Jahn-Teller axes of distortion being oriented along oxide ligands. This different structural arrangement facilitates a different tunneling pathway that leads to a lower effective barrier for magnetization reorientation for compound 2. The substitution of the acetate ligands by trifluoroacetic acid was monitored by mass spectrometry, which is a convenient tool for judging completion of the substitution process.

Journal Article↗