Nanoscale coordination polymers for biomedical applications and hybrid materials for solar fuel catalysis

This dissertation describes the design, synthesis, and characterization of hybrid materials and their evaluation for use in several biomedical and solar fuel applications. Most of the materials are nanoparticles based on coordination polymers (CPs), a class of highly tunable hybrid materials composed of organic bridging ligands linked together by metal ions. Nanoscale CPs (NCPs) have been developed for biomedical imaging contrast enhancement and for drug delivery. They have been designed to carry high payloads of diagnostic or therapeutic agents, and to overcome the disadvantages of conventional small-molecule agents by improved pharmacokinetics and biodistribution. NCPs containing elements with high X-ray attenuation have been developed for use as contrast agents for computed tomography (CT) imaging. NCPs based on an iodinated ligand or on Zr or Hf ions were synthesized, and their potential for CT contrast enhancement was demonstrated in phantom studies. The robust Hf-based NCPs were coated and functionalized to increase biocompatibility and performance, and were used for in vivo CT imaging. NCPs for drug delivery have been designed based on methotrexate, a molecular anticancer drug that is a first-line treatment for leukemia. The NCP approach to drug formulations offers a potential way to target and deliver high payloads of methotrexate to cancer cells. Photocatalytic and electrocatalytic materials have been developed toward the goal of storing harvested solar energy in chemical fuels by water splitting. A new CP-templated method has been developed for the synthesis of a metal oxide nanocomposite with interesting photophysical properties. Fe-containing NCPs were coated with amorphous titania, then calcined to produce crystalline Fe2O3/TiO2 composite nanoparticles. This material enables photocatalytic hydrogen production from water using visible light, which cannot be achieved by either Fe2O3 or TiO2 alone or a mixture of the two. Molecular Ir and Ru complexes were directly and covalently grafted onto carbon electrodes, for electrocatalytic water oxidation. The catalysts had enhanced rates and stability when grafted and driven electrochemically compared to being chemically-driven in solution. 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

Threaded Structure and Blue Luminescence of (CuCN)20(Piperazine)7

The structurally unique and highly luminescent 20 : 7 complex of CuCN with piperazine (Pip) was formed under aqueous conditions; its structure reveals two interpenetrated 2D sub-networks in 6 : 1 ratio: (CuCN)2(Pip) and (CuCN)8(Pip), the latter consisting of Cu18(CN)16(Pip)2 macrocycles

Lipid-coated nanoscale coordination polymers for targeted delivery of antifolates to cancer cells

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 free drug

Zr- and Hf-based nanoscale metal–organic frameworks as contrast agents for computed tomography

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

Development of an ultra performance LC/MS method to quantify cisplatin 1,2 intrastrand guanine-guanine adducts

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 15N10 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 [15N10] CP-d(GpG)). Recovery of standards was >90% and quantification was unaffected by increasing concentrations of calf thymus DNA. This method utilizes 25 μg of DNA per injection. The limit of quantification was 3 fmol or 3.7 adducts per 108 nucleotides, which approaches the sensitivity of the 32P 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

Pt Nanoparticles@Photoactive Metal–Organic Frameworks: Efficient Hydrogen Evolution via Synergistic Photoexcitation and Electron Injection

Pt nanoparticles of 2–3 nm and 5–6 nm in diameter were loaded into stable, porous, and phosphorescent metal–organic frameworks (MOFs <b>1</b> and <b>2</b>) built from [Ir­(ppy)₂(bpy)]⁺-derived dicarboxylate ligands (<b>L</b>_<b>1</b> and <b>L</b>_<b>2</b>) and Zr₆(μ₃-O)₄(μ₃-OH)₄(carboxylate)₁₂ secondary building units, via MOF-mediated photoreduction of K₂PtCl₄. 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@<b>2</b> gave a turnover number of 7000, approximately five times the value afforded by the homogeneous control, and could be readily recycled and reused

Light-Harvesting Cross-Linked Polymers for Efficient Heterogeneous Photocatalysis

Nonporous, phosphorescent cross-linked polymers (<b>Ru-CP</b> and <b>Ir-CP</b>) were synthesized via Pd-catalyzed Sonogashira cross-coupling reactions between tetra­(<i>p</i>-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 <b>Ru-CP</b> and 71.6 wt % for <b>Ir-CP</b>), and are nonporous with negligibly small surface areas (2.9 m²/g for <b>Ru-CP</b> and 2.7 m²/g for <b>Ir-CP</b>). 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 <b>Ru-CP</b>s 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

Cross-linked Polymers with Exceptionally High Ru(bipy)₃²⁺ Loadings for Efficient Heterogeneous Photocatalysis

Phosphorescent cross-linked polymers <b>1</b> and <b>2</b> were synthesized via oxidative homocoupling reactions of tetra­(ethynyl) derivatives of Ru­(bpy)₃²⁺ (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)₃²⁺ 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)₃²⁺ 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

Electrochemical Water Oxidation with Carbon-Grafted Iridium Complexes

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