Synthesis and photobiological evaluation of Ru(II) complexes with expanded chelate polypyridyl ligands.

Photoreactive Ru(II) complexes capable of ejecting ligands have been used extensively for photocaging applications and for the creation of "photocisplatin" reagents. The incorporation of distortion into the structure of the coordination complex lowers the energy of dissociative excited states, increasing the yield of the photosubstitution reaction. While steric clash between ligands induced by adding substituents at the coordinating face of the ligand has been extensively utilized, a lesser known, more subtle approach is to distort the coordination sphere by altering the chelate ring size. Here a systematic study was performed to alter metal-ligand bond lengths, angles, and to cause intraligand distortion by introducing a "linker" atom or group between two pyridine rings. The synthesis, photochemistry, and photobiology of five Ru(II) complexes containing CH2, NH, O, and S-linked dipyridine ligands was investigated. All systems where stable in the dark, and three of the five were photochemically active in buffer. While a clear periodic trend was not observed, this study lays the foundation for the creation of photoactive systems utilizing an alternative type of distortion to facilitate photosubstitution reactions.

Chemical State of Potassium on the Surface of Iron Oxides: Effects of Potassium Precursor Concentration and Calcination Temperature.

Potassium is used extensively as a promoter with iron catalysts in Fisher-Tropsch synthesis, water-gas shift reactions, steam reforming, and alcohol synthesis. In this paper, the identification of potassium chemical states on the surface of iron catalysts is studied to improve our understanding of the catalytic system. Herein, potassium-doped iron oxide (α-Fe2O3) nanomaterials are synthesized under variable calcination temperatures (400-800 °C) using an incipient wetness impregnation method. The synthesis also varies the content of potassium nitrate deposited on superfine iron oxide with a diameter of 3 nm (Nanocat®) to reach atomic ratios of 100 Fe:x K (x = 0-5). The structure, composition, and properties of the synthesized materials are investigated by X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, Fourier-transform infrared, Raman spectroscopy, inductively coupled plasma-atomic emission spectroscopy, and X-ray photoelectron spectroscopy, as well as transmission electron microscopy, with energy-dispersive X-ray spectroscopy and selected area electron diffraction. The hematite phase of iron oxide retains its structure up to 700 °C without forming any new mixed phase. For compositions as high as 100 Fe:5 K, potassium nitrate remains stable up to 400 °C, but at 500 °C, it starts to decompose into nitrites and, at only 800 °C, it completely decomposes to potassium oxide (K2O) and a mixed phase, K2Fe22O34. The doping of potassium nitrate on the surface of α-Fe2O3 provides a new material with potential applications in Fisher-Tropsch catalysis, photocatalysis, and photoelectrochemical processes.

Biological Investigations of Ru(II) Complexes With Diverse ß-diketone Ligands.

The ß-diketone scaffold is a commonly used synthetic intermediate, and is a functional group found in natural products such as curcuminoids. This core structure can also act as a chelating ligand for a variety of metals. In order to assess the potential of this scaffold for medicinal inorganic chemistry, seven different κ2-O,O'-chelating ligands were used to construct Ru(II) complexes with polypyridyl co-ligands, and their biological activity was evaluated. The complexes demonstrated promising structure-dependent cytotoxicity. Three complexes maintained high activity in a tumor spheroid model, and all complexes demonstrated low in vivo toxicity in a zebrafish model. From this series, the best compound exhibited a ~ 30-fold window between cytotoxicity in a 3-D tumor spheroid model and potential in vivo toxicity. These results suggest that κ2-O,O'-ligands can be incorporated into Ru(II)-polypyridyl complexes to create favorable candidates for future drug development.

Avobenzone incorporation in a diverse range of Ru(II) scaffolds produces potent potential antineoplastic agents.

Four structurally distinct classes of polypyridyl ruthenium complexes containing avobenzone exhibited low micromolar and submicromolar potencies in cancer cells, and were up to 273-fold more active than the parent ligand. Visible light irradiation enhanced the cytotoxicity of some complexes, making them promising candidates for combined chemo-photodynamic therapy.

Bis-tridentate N-Heterocyclic Carbene Ru(II) Complexes are Promising New Agents for Photodynamic Therapy.

Ruthenium(II) complexes developed for photodynamic therapy (PDT) are almost exclusively tris-bidentate systems with C2 or D3 symmetry. This is due to the fact that this structural framework commonly produces long-lived excited states, which, in turn, allow for the generation of large amounts of singlet oxygen (1O2) and other reactive oxygen species. Complexes containing tridentate ligands would be advantageous for biological applications as they are generally achiral (D2d or C2v symmetry), which eliminates the possibility of multiple isomers which could exhibit potentially different interactions with chiral biological entities. However, Ru(II) complexes containing tridentate ligands are rarely studied as candidates for photobiological applications, such as PDT, since they almost exclusively exhibit low quantum yields and very short excited-state lifetimes and, thus, are not capable of generating sufficient 1O2 or engaging in electron transfer reactions. Here, we report a proof-of-concept approach to make bis-tridentate Ru(II) complexes useful for PDT applications by altering their photophysical properties through the inclusion of N-heterocyclic carbene (NHC) ligands. Three NHC and two terpyridine ligands were studied to evaluate the effects of structural and photophysical modulations of bis-substituted Ru(II) complexes. The NHC complexes were found to have superior excited-state lifetimes, 1O2 production, and photocytotoxicity. To the best of our knowledge, these complexes are the most potent light-activated bis-tridentate complexes reported.

More examples of the 15-crown-5...H2O-M-OH2...15-crown-5 motif, M = Al3+, Cr3+ and Pd2+.

Five structures of co-crystals grown from aqueous solutions equimolar in 15-crown-5 (or 15C5) and [M(H(2)O)(6)](NO(3))(n), M = Al(3+), Cr(3+) and Pd(2+), are reported. The hydrogen-bonding patterns in all are similar: metal complexes including the fragment trans-H(2)O-M-OH(2) alternate with 15C5 molecules, to which they are hydrogen bonded, to form stacks. A literature survey shows that this hydrogen-bonding pattern is very common. In each of the two polymorphs of the compound [Al(H(2)O)(6)](NO(3))(3).15C5.4H(2)O there are two independent cations; one forms hydrogen bonds directly to the 15C5 molecules adjacent in the stack, while the other cation is hydrogen-bonded to two water molecules that act as spacers in the stack. These stacks are then crosslinked by hydrogen bonds formed by the three nitrate counterions and the three lattice water molecules. The hydrogen-bonded stacks in [Cr(H(2)O)(5)(NO(3))](NO(3))(2).1.5(15C5).H(2)O are discrete rather than infinite; each unit contains two Cr(3+) complex cations and three 15C5 molecules. These units are again crosslinked by the uncoordinated nitrate ions and a lattice water molecule. In [Pd(H(2)O)(2)(NO(3))(2)].15C5 the infinite stacks are electrically neutral and are not crosslinked. In [Pd(H(2)O)(2)(NO(3))(2)].2(15C5).2H(2)O.2HNO(3) a discrete, uncharged unit containing one Pd complex and two 15C5 molecules is ;capped off' at either end by a lattice water molecule and an included nitric acid molecule. In all five structures the infinite stacks or discrete units form an array that is at least approximately hexagonal.

Linear and spiral forms of longitudinal cuts in graphitized N-doped multiwalled carbon nanotubes (g-N-MWCNTs).

Nitrogen-containing multiwalled nanotubes (N-MWCNTs), formed by CVD from a nitrogen-containing feedstock have a 'bamboo' structure in which the axes of the graphene planes are not parallel to the axis of the nanotube and the core is periodically bridged. We find that thermal and chemical treatment of these materials can produce nanotubes that have been cut longitudinally in either a linear or in a spiral manner. In addition, these longitudinally cut nanotubes can be partially or fully unrolled by sonication in an aqueous surfactant, producing graphite platelets as well as narrow structures that could be thin graphite ribbons or very narrow, intact N-MWCNTs. These different morphologies of graphite, available from one source, suggest that there are multiple structures of N-MWCNTs present, few as simple as stacked cups or nested scrolls.

The elusive [Ni(H2O)2(15-crown-5)]2+ cation and related co-crystals of nickel(II) hydrates and 15-crown-5.

Initial attempts to make [Ni(H2O)2(15-crown-5)](NO3)2, i.e. to insert the Ni2+ ion into the 15-crown-5 macrocycle, gave the mono- (two polymorphs) and dihydrate of a co-crystal of[Ni(H2O)6](NO3)2 and 15-crown-5 (1,4,7,10,13-pentaoxacyclopentadecane=15C5). Synthetic routes designed to restrict the water available to the Ni2+ cation gave three additional compounds, [Ni(H2O)6](NO3)2-trans-[Ni(H2O)4(MeOH)2]-(NO3)2x2(15C5), cis-[Ni(H2O)4(NO3)2]-trans-[Ni(H2O)4-(NO3)2]x2(15C5) and [Ni(H2O)2(MeCN)(NO3)2]x15C5x-MeCN. All five compounds contain Ni2+ ions with two trans aqua ligands. In all six structures these aqua ligands make hydrogen bonds to the 15C5 molecules to form stacks in which the Ni complexes and 15C5 molecules alternate. The structures are surprisingly complicated: all are co-crystals,some are also solvates, and most have Z0 > 1. The target compound was finally prepared by heating pale green crystals of [Ni(H2O)6](NO3)2x15C5x2H2O to over 350 K and then cooling the resulting mixture of yellow crystals and solution to room temperature. Formation of the target compound seems to be favored at higher temperatures by a positive Delta(rxn)S(o) and an increased rate of ligand exchange.

Molecular characterization of the cytotoxic mechanism of multiwall carbon nanotubes and nano-onions on human skin fibroblast.

The increasing use of nanotechnology in consumer products and medical applications underlies the importance of understanding its potential toxic effects to people and the environment. Although both fullerene and carbon nanotubes have been demonstrated to accumulate to cytotoxic levels within organs of various animal models and cell types and carbon nanomaterials have been exploited for cancer therapies, the molecular and cellular mechanisms for cytotoxicity of this class of nanomaterial are not yet fully apparent. To address this question, we have performed whole genome expression array analysis and high content image analysis based phenotypic measurements on human skin fibroblast cell populations exposed to multiwall carbon nano-onions (MWCNOs) and multiwall carbon nanotubes (MWCNTs). Here we demonstrate that exposing cells to MWCNOs and MWCNTs at cytotoxic doses induces cell cycle arrest and increases apoptosis/necrosis. Expression array analysis indicates that multiple cellular pathways are perturbed after exposure to these nanomaterials at these doses, with material-specific toxigenomic profiles observed. Moreover, there are also distinct qualitative and quantitative differences in gene expression profiles, with each material at different dosage levels (6 and 0.6 microg/mL for MWCNO and 0.6 and 0.06 microg/mL for MWCNT). MWCNO and MWCNT exposure activates genes involved in cellular transport, metabolism, cell cycle regulation, and stress response. MWCNTs induce genes indicative of a strong immune and inflammatory response within skin fibroblasts, while MWCNO changes are concentrated in genes induced in response to external stimuli. Promoter analysis of the microarray results demonstrate that interferon and p38/ERK-MAPK cascades are critical pathway components in the induced signal transduction contributing to the more adverse effects observed upon exposure to MWCNTs as compared to MWCNOs.

Synthesis, characterization, and structure of cyclopenta[c]thiophenes and their manganese complexes.

1,3-Diaryl-4H-cyclopenta[c]thiophenes are efficiently prepared from 1,2-diaroylcyclopentadienes by use of Lawesson's reagent. eta5-Cyclopenta[c]thienyl complexes, [Mn(eta5-SC7H3-1,3-R2)(CO)3] (R = Me, Ph), are prepared in high yield by ligand substitution reactions of [MnBr(CO)5] with [SnMe3(SC7H3-1,3-R2)]. Alternatively, thiation with P4S10/NaHCO3 converts [Mn{eta5-1,2-C5H3(COR)2)(CO)3] to [Mn(eta5-SC7H3-1,3-R2)(CO)3] (R = Ph, 4-tolyl, 4-MeOC6H4, benzo[2,3-b]thienyl). The molecular structures of complexes with R = Me, Ph show planar eta5-cyclopenta[c]thienyl ligands, with the manganese atom slightly displaced away from the ring-fusion bond.

Monitoring the growth of polyoxomolybdate nanoparticles in suspension by flow field-flow fractionation.

We follow the evolution of polyoxomolybdate nanoparticles in suspensions derived from the keplerate (NH4)42[MoVI72MoV60O372(CH3CO2)30(H2O)72].ca..300H2O.ca..10CH3CO2NH4 ({Mo132}) by flow field-flow fractionation (FlFFF) to monitor the particle-size distribution in situ, atomic force and high-resolution transmission electron microscopy (AFM, SEM, and HRTEM) to confirm particle sizes, inductively coupled plasma-optical emission spectrometry (ICP-OES) to determine the Mo content of the FlFFF-separated fractions, and UV/visible spectroscopy to confirm the identity of the species in suspension. We observe the formation of 3-75-nm polyoxomolybdate particles in suspension and the dynamic growth of {Mo132} crystals.

C,O-dialkylation of Meldrum's acid: synthesis and reactivity of 1,3,7,7-tetramethyl-4H,10H-6,8,9-trioxa-2-thiabenz[f]azulen-5-one.

Reaction of Meldrum's acid with 3,4-bis(chloromethyl)-2,5-dimethylthiophene (1) or 3,4-bis(bromomethyl)-2,5-dimethylthiophene (2) produces the kinetically favored C,O-dialkylation product, 1,3,7,7-tetramethyl-4H,10H-6,8,9-trioxa-2-thiabenz[f]azulen-5-one (4). Recrystallization of 4 from refluxing methanol results in the methanolysis product 5-(4-methoxymethyl-2,5-dimethylthiophen-3-ylmethyl)-2,2-dimethyl[1,3]dioxane-4,6-dione (5). Attempts to isomerize 4 to the thermodynamically favored C,C-dialkylation product, 1,3-dimethyl-5,6-dihydro-4H-cyclopenta[c]thiophene(2-spiro-5)2,2-dimethyl-4,6-dione (8), result in the formation of 1,3-dimethyl-7,8-dihydro-4H-thieno[3,4-c]oxepin-6-one (6). The transformation occurs via a retro-Diels-Alder elimination of acetone followed by hydrolysis and decarboxylation of the resulting ketene. The ketene is trapped by tert-butyl alcohol, furnishing 1,3-dimethyl-6-oxo-7,8-dihydro-4H,6H-thieno[3,4-c]oxepine-7-carboxylic acid tert-butyl ester (7). All compounds are characterized spectroscopically as well as by X-ray crystallography of products 4-7.

Dichloro[1,1'-(5,9-dithia-2,12-diazoniatrideca-1,12-diene-1,13-diyl)dinaphthalen-2-olato-kappa2O,O']dimethyltin(IV) acetonitrile solvate.

Reaction of the potentially hexadentate ligand 1,9-bis(2-hydroxy-1-naphthalenemethylimino)-3,7-dithianonane with dimethyltin chloride gave the title 1:1 adduct, in which the long ligand wraps around the SnCl(2)Me(2) unit and in which the stereochemistry is fully trans. This compound crystallizes from acetonitrile as the 1:1 solvate [Sn(CH(3))(2)(C(29)H(30)N(2)O(2)S(2))Cl(2)].C(2)H(3)N. During the reaction, the hydroxyl protons move to the N atoms. Most of the chemically equivalent bond lengths agree to within experimental uncertainty, but the Sn-Cl bond that is inside the ligand pocket is substantially longer than the Sn-Cl bond that points away from the long ligand [2.668 (1) versus 2.528 (1) A]. The O-Sn-O angle is 166.0 (1) degrees. Comparison of the Sn-O, C-O and aryl C-C bond lengths with those of related compounds shows that the most important resonance forms for the Schiff base aryloxide ligand are double zwitterions, but that the uncharged resonance forms having carbonyl groups also contribute significantly.

Separation and characterization of single-walled and multiwalled carbon nanotubes by using flow field-flow fractionation.

Oxidatively shortened single-walled and multiwalled carbon nanotubes were characterized by using flow field-flow fractionation (FIFFF) under normal and steric modes, respectively. Narrow size fractions were collected from FlFFF separations. The carbon nanotubes in each fraction were further characterized by using scanning and transmission electron microscopy. FlFFF separates carbon nanotubes principally on the basis of length, leading to fractions with relatively uniform lengths. The relationship between nanotube length and FlFFF elution volume is discussed.

High resolution capillary electrophoresis of carbon nanotubes.

Purification of single-walled carbon nanotubes by capillary electrophoresis (CE) is demonstrated. Real-time Raman spectroscopy of the separation process and single-wavelength UV/vis detection show the ability of CE to provide high-resolution separations of nanotube fractions with baseline separation. AFM images of collected fractions demonstrate that separations are based on tube length. The separation method is suggested to be based on alignment of the nanotubes along the separation field.