Poly[l-2-aminopyrazine-j2 N1 :N4 - l-cyanido-copper(I)]: A Three-dimensional Network From Laboratory Powder Diffraction Data

In the title compound, [Cu(CN)(C4H5N3)]n or [Cu(-CN)(-PyzNH2)]n (PyzNH2 is 2-amino­pyrazine), the CuI center is tetra­hedrally coordinated by two cyanide and two PyzNH2 ligands. The CuI-cyano links give rise to [Cu-CN] chains running along the c axis, which are bridged by bidentate PyzNH2 ligands. The three-dimensional framework can be described as being formed by two inter­penetrated three-dimensional honeycomb-like networks, both made of 26-membered rings of composition [Cu6(-CN)2(-PyzNH2)4]

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

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

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

Debio 0507 primarily forms diaminocyclohexane-Pt-d(GpG) and -d(ApG) DNA adducts in HCT116 cells

To characterize the cellular action mechanism of Debio 0507, we compared the major DNA adducts formed by Debio 0507- and oxaliplatin-treated HCT116 human colon carcinoma cells by a combination of inductively coupled plasma mass spectrometry (ICP-MS) and ultra-performance liquid chromatography mass spectrometry (UPLC-MS/MS)

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

Amino acids as highly efficient modulators for single crystals of zirconium and hafnium metal–organic frameworks

The synthesis of zirconium and hafnium metal–organic frameworks (MOFs) often relies on coordination modulation – the addition of competing monotopic modulators to reaction mixtures – to reproducibly generate highly crystalline material. Typically, large excesses of monocarboxylic acids such as formic, acetic and benzoic acid are applied, but access to diffraction quality single crystals, particularly of UiO-66 topology MOFs, remains troublesome. Herein, we show that amino acids, in particular L-proline, are highly efficient modulators of Zr and Hf MOFs of the UiO-66 series, with as little as four equivalents affording access to large, diffraction quality single crystals that are free of defects. Five crystal structures are reported, including MOFs which previously could not be characterised in this manner, with molecular dynamics simulations utilised to understand dynamic disorder. Additionally, a series of MOFs are characterised in depth, allowing a comparison of the thermal stabilities and porosities for Zr and Hf analogues. We also show that the protocol can be extended to microwave synthesis, and that modulating ability varies dramatically across a series of amino acids. Access to single crystals has facilitated our own in depth study of the mechanical properties of these MOFs, and we expect that our protocols will enable the discovery of new Zr and Hf MOFs as well as offer new insights into their materials properties

Phosphorescent Nanoscale Coordination Polymers as Contrast Agents for Optical Imaging

Optical imaging, which uses neither ionizing radiation (as in X-ray computed tomography) nor radioactive materials (as in positron emission tomography or single photon emission computed tomography),[1] has emerged as a powerful imaging modality during the last two decades.[2] Optical imaging has been widely employed for oncological and other applications due to its ability to noninvasively differentiate between diseased (e.g., tumor) and healthy tissues based on differential dye accumulations.[3] The need for relatively high (up to ~µM) concentrations of dyes in optical imaging, however, limits its application in many areas, such as detecting low concentrations of biological targets. For example, many biomarkers are overexpressed in the nM concentrations in diseased tissues,[4] and cannot be readily visualized by optical imaging. Dye-loaded nanoparticles represent a logical solution to lowering the detection limit due to their ability to carry a large payload of dye molecules as well as to target certain cell types by conjugation to affinity molecules. Luminescent quantum dots have indeed been extensively explored as bright and stable contrast agents for optical imaging.[5] The non-degradable nature of and the use of toxic elements in many quantum dot formulations however limit their applications in many areas. Most of fluorescent dye molecules, on the other hand, have small Stokes shifts and tend to have a significant overlap between absorption and fluorescent emission spectra. As a result, these fluorescence dyes will suffer from severe self-quenching if they are brought into close proximity with each other, as in nanoparticles with high dye loadings