A series of [Ir(bpy)Cp*Cl]Cl (bpy: 2,2′-bipyridine; Cp*: pentamethylcyclopentadienyl) complexes with 4,4′- and 6,6′-substituents on the bipyridine ring were synthesized and used for water oxidation both electrochemically and with chemical oxidants. Under electrochemical water-oxidation reaction (WOR) conditions at pH = 1, blue films were observed to deposit on the electrode surfaces for all of the complexes, without the detection of oxygen. For chemically driven WORs, three oxidants with different overpotentials and electron-transfer kinetics led to very different behaviors. [Ru(bpy)3]3+ was shown to slowly oxidize the ligands without generating oxygen at pH = 3.7. With NaIO4 as the oxidant at neutral pH, oxygen generation was observed, but ligand oxidation was also seen for the complexes with electron-donating substituents such as –OMe or –OH groups. With Ce4+ as the oxidant at pH = 1, a competition between water oxidation and ligand decomposition existed; less ligand decomposition was observed for catalysts that are more active for WOR. These results indicate the intricate nature of molecule water-oxidation catalysts and their complex behaviors that are highly sensitive to water-oxidation conditions.

A variety of photoluminescent, and in some cases thermochromic, metal-organic networks of CuCN were self-assembled in aqueous reactions with amine ligands: (CuCN) 2(Pip) ( 1a), (CuCN) 20(Pip) 7 ( 1b), (CuCN) 7(MePip) 2 ( 2), (CuCN) 2(Me 2Pip) ( 3a), (CuCN) 4(Me 2Pip) ( 3b), (CuCN) 7(EtPip) 2 ( 4), (CuCN) 4(Et 2Pip) ( 5), (CuCN) 3(BzPip) 2 ( 6a), (CuCN) 5(BzPip) 2 ( 6b), (CuCN) 7(BzPip) 2 ( 6c), (CuCN) 4(BzPip) ( 6d), (CuCN) 2(Bz 2Pip) ( 7), (CuCN)(Ph 2CHPip) ( 8a), (CuCN) 2(Ph 2CHPip) ( 8b), (CuCN) 3(HMTA) 2 ( 9a), (CuCN) 5(HMTA) 2 ( 9b), and (CuCN) 5(HMTA) ( 9c) (Pip = piperazine, MePip = N-methylpiperazine, Me 2Pip = N, N'-dimethylpiperazine, EtPip = N-ethylpiperazine, Et 2Pip = N, N'-diethylpiperazine, BzPip = N-benzylpiperazine, Bz 2Pip = N, N'-dibenzylpiperazine, Ph 2CHPip = N-(diphenylmethyl)piperazine, and HMTA = hexamethylenetetramine). New X-ray structures are reported for 1b, 2, 3b, 4, 5, 6a, 6d, 7, 8b, 9b, and 9c. An important structural theme is the formation of (6,3) (CuCN) 2(piperazine) sheets with or without threading of independent CuCN chains. Strong luminescence at ambient temperature is observed for all but complexes 6 and 7. All luminescent compounds show a broad emission band in the blue region at about 450 nm attributable to metal-to-ligand charge transfer behavior based on the large Stokes shift between excitation and emission maxima. 3, 8, and 9 are thermochromic due to an additional lower energy emission band, which is absent at 77 K.

Nanoscale coordination polymers (NCPs) have been demonstrated as an interesting platform for drug delivery, as they possess many advantages over small-molecule chemotherapeutics such as high payloads, lower systemic toxicity, tunability, and enhanced tumor uptake. Existing formulations for the delivery of methotrexate (MTX), an antifolate cancer drug, have very low drug loadings. Herein, we report the incorporation of MTX as a building block in an NCP formulation with exceptionally high drug loadings (up to 79.1 wt%) and the selective delivery of the NCP to cancer cells. Encapsulation of the NCP in a functionalized lipid bilayer allows for targeted delivery and controlled release to cancer cells. A phosphor can be doped into the NCPs for monitoring particle uptake by optical imaging. The lipid-coated and anisamide-targeted NCPs have superior in vitro efficacy against acute lymphoblastic leukemia cells when compared to the free drug.

A series of new mesoporous silica (MS) sorbents were developed by functionalizing a large-pore 2-D hexagonal MS material, MSU-H, with amidoxime, imide dioxime, phosphonate, and carboxylate functional groups, and characterized by nitrogen adsorption, zeta-potential, infrared spectroscopy, and thermogravimetric analysis. These MS materials have a grafting density of 0.75 to 1.38 mmol/g, and exhibit BET surface areas of 186-526 m(2)/g and average pore sizes of 3.8-7.8 nm. The uranyl sorption by the functionalized MS sorbents was investigated in basic water and artificial seawater at pH = 8.3 +/- 0.1. The MS materials exhibited a high U sorption capacity in water (>40 mu g U/mg sorbent) with Langmuir isotherms suggesting a saturation U sorption capacity of 185.2 mu g U/mg sorbent for the phosphonic acid-modified MS material (MSPh-III). The U sorption capacity in artificial seawater was reduced to 12.1 mu g U/mg sorbent for MSPh-III. Langmuir isotherms indicated a saturation sorption capacity of 66.7 mu g U/mg sorbent for MSPh-III, which also had the greatest binding affinity for U of all sorbents tested, followed by the imide dioxime-functionalized material MSCA-I. Kinetics studies show rapid uranyl sorption and equilibration in less than 40 min. The U was quantitatively eluted from the MS sorbents by washing with strong acid (>0.1 M HCl). This work represents the first comprehensive study of organo-functionalized MS materials for U extraction, and shows that phosphonic acid- and imide dioxime-functionalized MS materials provide excellent platforms for developing novel sorbents for efficient U extraction from seawater. (C) 2013 Elsevier Inc. All rights reserved.

Nanoscale metal-organic frameworks (NMOFs) of the UiO-66 structure containing high Zr (37 wt%) and Hf (57 wt%) content were synthesized and characterized, and their potential as contrast agents for X-ray computed tomography (CT) imaging was evaluated. Hf-NMOFs of different sizes were coated with silica and poly(ethylene glycol) (PEG) to enhance biocompatibility, and were used for in vivo CT imaging of mice, showing increased attenuation in the liver and spleen.

Pt nanoparticles of 2-3 nm and 5-6 nm in diameter were loaded into stable, porous, and phosphorescent metal-organic frameworks (MOFs 1 and 2) built from [Ir(ppy)(2)(bpy)](+)-derived dicarboxylate ligands (L(1) and L(2)) and Zr(6)(μ(3)-O)(4)(μ(3)-OH)(4)(carboxylate)(12) secondary building units, via MOF-mediated photoreduction of K(2)PtCl(4). The resulting Pt@MOF assemblies serve as effective photocatalysts for hydrogen evolution by synergistic photoexcitation of the MOF frameworks and electron injection into the Pt nanoparticles. Pt@2 gave a turnover number of 7000, approximately five times the value afforded by the homogeneous control, and could be readily recycled and reused.

Nonporous, phosphorescent cross-linked polymers (Ru-CP and Ir-CP) were synthesized via Pd-catalyzed Sonogashira cross-coupling reactions between tetra(p-ethynylphenyl)methane and dibrominated Ru(bpy)32+ or Ir(ppy)2(bpy)+, respectively. The resultant particulate cross-linked polymer (CP) materials have very high catalyst loadings (76.3 wt % for Ru-CP and 71.6 wt % for Ir-CP), and are nonporous with negligibly small surface areas (2.9 m2/g for Ru-CP and 2.7 m2/g for Ir-CP). Despite their nonporous nature, the insoluble CP materials serve as highly active and recyclable heterogeneous photocatalysts for a range of organic transformations such as aza-Henry reaction, aerobic amine coupling, and dehalogenation of benzyl bromoacetate. An efficient light-harvesting mechanism, which involves collection of photons by exciting the 3MLCT states of the phosphors and migration of the excited states to the particle surface, is proposed to account for the very high catalytic activities of these nonporous CPs. Steady-state and time-resolved emission data, as well as the reduced catalytic activity of Os(bpy)32+-doped Ru-CPs supports efficient excited state migration for the CP frameworks. This work uncovers a new strategy in designing highly efficient photocatalysts based on light-harvesting cross-linked polymers.

A new metal-organic framework (MOF)-templated method has been developed for the synthesis of a metal oxide nanocomposite with interesting photophysical properties. Fe-containing nanoscale MOFs are coated with amorphous titania, then calcined to produce crystalline Fe(2)O(3)/TiO(2) composite nanoparticles. This material enables photocatalytic hydrogen production from water using visible light, which cannot be achieved by either Fe(2)O(3) or TiO(2) alone or a mixture of the two.

Phosphorescent cross-linked polymers 1 and 2 were synthesized via oxidative homo coupling reactions of tetra(ethynyl) derivatives of Ru(bpy)(3)(2+) (with the alkynyl groups located at 4,4'- or 5,5'- positions of two substituted bipyridines). These cross-linked polymer particles contain exceptionally high Ru(bpy)(3)(2+) loadings and serve as highly efficient and reusable heterogeneous photocatalysts for a range of organic transformations, presumably owing to the ability of the Ru(bpy)(3)(2+) moieties in the polymer network to transport triplet excited states to particle surfaces to initiate the organic reactions. This work illustrates the potential of developing photocatalytic cross-linked polymers from photoactive molecular building blocks for solar energy utilization.

Hydrogen production from water splitting provides a potential solution to storing harvested solar energy in chemical fuels, but this process requires active and robust catalysts that can oxidize water to provide a source of electrons for proton reduction. Here we report the direct, covalent grafting of molecular Ir complexes onto carbon electrodes, with up to a monolayer coverage. Carbon-grafted Ir complexes electrochemically oxidize water with a turnover frequency of up to 3.3 s(-1) and a turnover number of 644 during the first hour. Electrochemical water oxidation with grafted catalysts gave enhanced rates and stability compared to chemically driven water oxidation with the corresponding molecular catalysts. This strategy provides a way to systematically evaluate catalysts under tunable conditions, potentially providing new insights into electrochemical water oxidation processes and water oxidation catalyst design.

Porous cross-linked polymers (PCPs) with phosphorescent [Ru(bpy)(3)](2+) and [Ir(ppy)(2)(bpy)](+) building blocks were obtained via octacarbonyldicobalt (Co(2)(CO)(8))-catalyzed alkyne trimerization reactions. The resultant Ru- and Ir-PCPs exhibited high porosity with specific surface areas of 1348 and 1547 m(2)/g, respectively. They are thermally stable at up to 350 °C in air and do not dissolve or decompose in all solvents tested, including concentrated hydrochloric acid. The photoactive PCPs were shown to be highly effective, recyclable, and reusable heterogeneous photocatalysts for aza-Henry reactions, α-arylation of bromomalonate, and oxyamination of an aldehyde, with catalytic activities comparable to those of the homogeneous [Ru(bpy)(3)](2+) and [Ir(ppy)(2)(bpy)](+) photocatalysts. This work highlights the potential of developing photoactive PCPs as highly stable, molecularly tunable, and recyclable and reusable heterogeneous photocatalysts for a variety of important organic transformations.

Catalytically competent Ir, Re, and Ru complexes H(2)L(1)-H(2)L(6) with dicarboxylic acid functionalities were incorporated into a highly stable and porous Zr(6)O(4)(OH)(4)(bpdc)(6) (UiO-67, bpdc = para-biphenyldicarboxylic acid) framework using a mix-and-match synthetic strategy. The matching ligand lengths between bpdc and L(1)-L(6) ligands allowed the construction of highly crystalline UiO-67 frameworks (metal-organic frameworks (MOFs) 1-6) that were doped with L(1)-L(6) ligands. MOFs 1-6 were isostructural to the parent UiO-67 framework as shown by powder X-ray diffraction (PXRD) and exhibited high surface areas ranging from 1092 to 1497 m(2)/g. MOFs 1-6 were stable in air up to 400 °C and active catalysts in a range of reactions that are relevant to solar energy utilization. MOFs 1-3 containing [Cp*Ir(III)(dcppy)Cl] (H(2)L(1)), [Cp*Ir(III)(dcbpy)Cl]Cl (H(2)L(2)), and [Ir(III)(dcppy)(2)(H(2)O)(2)]OTf (H(2)L(3)) (where Cp* is pentamethylcyclopentadienyl, dcppy is 2-phenylpyridine-5,4'-dicarboxylic acid, and dcbpy is 2,2'-bipyridine-5,5'-dicarboxylic acid) were effective water oxidation catalysts (WOCs), with turnover frequencies (TOFs) of up to 4.8 h(-1). The [Re(I)(CO)(3)(dcbpy)Cl] (H(2)L(4)) derivatized MOF 4 served as an active catalyst for photocatalytic CO(2) reduction with a total turnover number (TON) of 10.9, three times higher than that of the homogeneous complex H(2)L(4). MOFs 5 and 6 contained phosphorescent [Ir(III)(ppy)(2)(dcbpy)]Cl (H(2)L(5)) and [Ru(II)(bpy)(2)(dcbpy)]Cl(2) (H(2)L(6)) (where ppy is 2-phenylpyridine and bpy is 2,2'-bipyridine) and were used in three photocatalytic organic transformations (aza-Henry reaction, aerobic amine coupling, and aerobic oxidation of thioanisole) with very high activities. The inactivity of the parent UiO-67 framework and the reaction supernatants in catalytic water oxidation, CO(2) reduction, and organic transformations indicate both the molecular origin and heterogeneous nature of these catalytic processes. The stability of the doped UiO-67 catalysts under catalytic conditions was also demonstrated by comparing PXRD patterns before and after catalysis. This work illustrates the potential of combining molecular catalysts and MOF structures in developing highly active heterogeneous catalysts for solar energy utilization.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Abstract The major DNA adducts formed by Debio 0507 in HCT116 human colon carcinoma cells were determined by a combination of inductively coupled mass spectrometry (ICP-MS) and ultraperformance liquid chromatography mass spectrometry (UPLC-MS/MS). Debio 0507 is a micellular copolymer of trans-RR-diaminocyclohexane-platinum(II) (DACH-Pt) with polyethylene-glycol (PEG)-polyglutamate (pGlu). Debio 0507 is long lasting compared to oxaliplatin (platinum is detectable in plasma and tumor for up to 14 days) and has shown anti-tumor activity and low toxicity in several tumor models. Debio 0507 has been shown to accumulate in tumors, but the intracellular activation mechanism and type of DNA adducts formed were not previously known. We have previously reported an UPLC-MS/MS method for the identification and quantification of the intrastrand GG DNA adducts formed by cisplatin (Baskerville-Abraham et al, Chem. Res. Toxicol., 22: 905-912, 2009). The limit of quantification of this assay was 3 fmol or 3.7 adducts per 108 nucleotides. This assay was modified slightly to identify the major DNA adducts formed by Debio 0507 and to compare them to the major DNA adducts formed by oxaliplatin. HCT116 cells were incubated with equitoxic doses of Debio 0507 (0.014 ug Pt/ml) and oxaliplatin (0.0006 ug Pt/ml) for 3 days. DNA was isolated from the cells and digested as described previously for cisplatin-treated DNA. ICP-MS was used to quantify Pt adducts in the DNA digests. The Pt adducts were 7.4/104 deoxynucleosides for Debio 0507-treated cells and 5.5/104 deoxynucleosides for oxaliplatin-treated cells following the DNA digestion step. DACH-Pt-d(GpG) and DACH-Pt-d(ApG) adducts were then separated from deoxynucleosides by HPLC. Following HPLC purification, the total Pt DNA adducts recovered were 63 pmoles (29% recovery) for Debio 0507 and 58 pmoles (38% recovery) for oxalipltin by ICP-MS, with approximately equal amounts of DACH-Pt-d(GpG) and DACH-Pt-d(ApG) adducts recovered at this stage (The DACH-Pt-d(GpG) peak overlapped with the deoxythymidine peak, which diminished the recovery of DACH-Pt-d(GpG)). Finally, UPLC-MS/MS in the positive ion mode was used to confirm the identity of the DACH-Pt-d(GpG) (904.2 m/z→459 m/z and 904.2 m/z→610 m/z) and DACH-Pt-d(ApG) (888.2 m/z→459 m/z and 888.2 m/z→594 m/z). These data show that the major DNA adducts formed by Debio 0507 are the DACH-Pt-GG and DACH-Pt-AG adducts and at equitoxic doses Debio 0507 and oxaliplatin form similar levels of DACH-Pt-GG and DACH-Pt-AG adducts which makes it unlikely that Debio 0507 forms significant amounts of other DNA adducts of equal or greater cytotoxicity. (Supported by Research Contract Debio 0507-069 with Debiopharm SA and P30-ES10126) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3504.

Phosphorescent cyclometalated iridium tris(2-phenylpyridine) derivatives were designed and incorporated into coordination polymers as tricarboxylate bridging ligands. Three different crystalline coordination polymers were synthesized using a solvothermal technique and were characterized using a variety of methods, including, single-crystal X-ray diffiraction, PXRD, TGA, IR spectroscopy, gas adsorption measurements, and luminescence measurements. The coordination polymer built from 1r-[3-(2-pyridyl)benzoate](3), 1, was found to be highly porous with a nitrogen BET surface area of 764 m(2)/g, whereas the coordination polymers built from Ir-[4-(2-pyridyl)benzoate](3), 2 and were nonporous. The (MLCT)-M-3 phosphorescence of each of the three coordination polymers was quenched in the presence of O-2. However, only 1 showed quick and reversible luminescence quenching by oxygen, whereas 2 and 3 exhibited gradual and irreversible luminescence quenching by oxygen. The high permanent porosity of 1 allows for rapid diffusion of oxygen through the open channels, leading to efficient and reversible quenching of the (MLCT)-M-3 phosphorescence. This work highlights the opportunity of designing highly porous and luminescent coordination polymers for sensing other important analytes.

Platinum chemotherapeutic agents have been widely used in the treatment of cancer. Cisplatin was the first of the platinum based chemotherapeutic agents and therefore has been extensively studied as an anti-tumor agent since the late 1960s. Because this agent forms several DNA adducts, a highly sensitive and specific quantitative assay is needed to correlate the molecular dose of individual adducts with the effects of treatment. An ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay for quantification of 1,2 guanine-guanine intrastrand cisplatin adducts [CP-d(GpG)], using 15 N 10 CP-d(GpG) as an internal standard, was developed. The internal standard was characterized by MS/MS and its concentration was validated by ICP-MS. Samples containing CP-d(GpG) in DNA were purified by enzyme hydrolysis , centrifugal filtration and HPLC with fraction collection prior to quantification by UPLC-MS/MS in the selective reaction monitoring (SRM) mode (m/z 412.5 → 248.1 for CP-d(GpG); m/z 417.5 → 253.1 for [ 15 N 10 ] CP-d(GpG)). Recovery of standards was >90% and quantification was unaffected by increasing concentrations of calf thymus DNA. This method utilizes 25 μ g of DNA per injection. The limit of quantification was 3 fmol or 3.7 adducts per 10 8 nucleotides, which approaches the sensitivity of the 32 P postlabeling method for this adduct. These data suggested that this method is suitable for in vitro and in vivo assessment of CP-d(GpG) adducts formed by cisplatin and carboplatin. Subsequently the method was applied to studies using ovarian carcinoma cell lines and C57/BL6 mice to illustrate that this method is capable of quantifying CP-d(GpG) adducts using biologically relevant systems and doses. The development of biomarkers to determine tissue-specific molecular dosimetry during treatment will lead to a more complete understanding of both therapeutic and adverse effects of cisplatin and carboplatin. This will support the refinement of therapeutic regimes and appropriate individualized treatment protocols.