Metallosupramolecular chemistry of polydentate ligands and the solid state studies of diphenylcarbazide and dithizone

Described herein, is the synthesis and coordination chemistry of eight novel ligands L1-L8, and the solid state studies of diphenylcarbazide and dithizone. These ligands form metallosupramolecular assemblies upon coordination of transition metal ions resulting in a wide range of architectures. Described in chapter two is a series of ligands that contain both N-donor and N-oxide donor atoms, L1-L4. Reaction of L1 with Cu2+ results in the formation of a mononuclear complex [Cu(L1)(ClO4)2(sol)] (solvent = MeCN or H2O), whereas L2 forms the dinuclear double helicate [Ni2(L2)2]4+ with Ni2+. Reaction of L3 with Cu2+ results in the formation of a head-to-tail dinuclear double helicate [Cu2(L3)2]4+. The N-oxide units imparts flexibility in the ligand strand and where the unoxidised ligand strand forms a circular helicate, the incorporation of an N-oxide unit allows the formation of the dinuclear double helicate. Reaction of L4 with Co2+ results in the formation of a tetranuclear circular helicate [Co4(L4)4]8+. Analogous complexes that contain ligands with a 1,3-phenyl spacer unit give pentanuclear circular helicates, whereas with a 1,3-phenol spacer the lower tetranuclear species is observed. The difference in the nuclearity of the circular helicates is due to the steric bulk of the methyl group on the central phenol spacer. In the dinuclear double complex formed with L3 the N-oxide unit allows the ligand to flex, whereas the steric bulk of the –OH unit in L4 is sufficiently large that even with the added flexibility that the N-oxide units imparts a double helicate cannot be formed. Chapter three introduces a new class of polydentate ligands, L5-L7, these ligands consist of N-donor domains separated by a 1,3-phenol unit. The ligand L5 contains two identical tridentate N-donor domains, reaction of L5 with Zn2+ results in a tetranuclear circular helicate [Zn4(L5)4]8+. Within the structure all four Zn2+ ions are six-coordinate, arising from the coordination of two tridentate domains from two different ligand strands. Reaction of L6 with Ag+ results in the formation of the dinuclear double meso-helicate [Ag2(L6)2]2+. Reaction of L6 with Cd2+ produces a crystalline material that consists of both colourless and orange species. The colourless crystals correspond to the mononuclear complex [Cd(L6)2(MeCN)2]2+, whereas the orange crystals produce the dinuclear double meso-helicate [Cd2(L6)2]2+. This variation in self-assembly is a direct result of the –OH unit on the 1,3-phenol spacer; if the -OH unit is protonated the oxygen atom can only coordinate once and therefore the mononuclear complex forms, however deprotonation of one of the -OH unit results in the oxygen coordinating twice as a bridging donor to form the dinuclear complex. Both the [Cd(L6)2(MeCN)2]2+ and [Cd2(L6)2]2+ species are present in solution, under equilibrium conditions, varying the stoichiometry alters the predominant species. The ligand L7 is unsymmetrical, upon reaction with Co2+ the ligand partitions into two different binding sites; a tridentate N-donor domain and a tridentate domain consisting of the bidentate N-donor domain and the O-donor atom from the central 1,3-phenol spacer. The resulting dinuclear HH-[Co2(L7)2]3+ complex demonstrates that the two cobalt metal centres occupy different binding sites. Examining the solid state X-ray crystallographic data suggests that the two cobalt metal centres in the [Co2(L7)2]3+ complex occupy different oxidation states; Co2+ and Co3+ to give a mixed valence helicate. In an analogues fashion to L6, reaction of L7 with Zn2+ produces a crystalline material that consists of both colourless and orange species. The colourless crystals correspond to the mononuclear complex [Zn(L7)2]2+, whereas the orange crystals produce the dinuclear double helicate [Zn2(L6)2]3+. In the mononuclear [Zn(L7)2]2+ species the Zn2+ metal centre is coordinated by the tridentate N-donor domain of two different ligands. In the dinuclear [Zn2(L6)2]3+ species each Zn2+ metal centres is coordinated by the tridentate N-donor domain of one ligand and the tridentate domain, consisting of the bidentate N-donor and the O-donor from the central 1,3-phenol spacer, from another different ligand. The variation in the self-assembly is a direct result of the stoichiometry of the reaction; the formation of these two complexes is under the same equilibrium conditions of the previous L6 structures. Described in chapter four is the potentially pentadentate N-donor ligand L8, which comprises of a bidentate and tridentate binding domains separated by a 1,3-pyrene spacer. Reaction of L8 with Cu2+ results in the formation of a tetranuclear circular helicate [Cu4(L8)4]8+. Each of the Cu2+ ions adopts a 5-coordinate geometry formed by the coordination of the bidentate domain of one ligand strand and the tridentate domain of a different ligand strand, resulting in a head-to-tail tetranuclear circular helicate. The formation of this head-to-tail circular helicate is a result of the 1,3-pyrene spacer preventing the formation of the linear double stranded assemblies and secondly the stereoelectronic preference of Cu2+. Chapter five reports the solid state studies of diphenylcarbazide and dithizone, which are both useful reagents for the colorimetric determination of a variety of different metal ions. Examination of the scientific literature over the past 100 years shows that the coordination chemistry of DPC and DPTC is inconsistent, with literature sources proposing contradictory and non-definitive explanations, this chapter aims to extend the knowledge surrounding these reagents by isolating crystals. DPC reacts with Cd2+ to form the mononuclear species [Cd(DPC)2]2+ the two ligands are coordinating through both the N-donor and O-donor domains. The discrepancies surrounding the DPC reaction is whether the redox reactions between the metal and ligand occur, upon reaction of DPC and Cd2+ the metal does not oxidise the ligand. Reaction of DPC and Cu2+ is more complex than the previous Cd2+ reaction, the resulting [Cu3OH(OH2)3(DPTO)6]5+ structure comprises of six ligands and three metal ions. DPC undergoes oxidative intramolecular cyclisation to form the nitrogen containing heterocycle 2,3-diphenyltetrazolium-5-olate (DPTO) and coordinates the Cu2+ metal centre in two different modes: via both the oxygen and amide nitrogen atoms or by the bridging carbonyl unit. The [Cu3OH(OH2)3(DPTO)6]5+ structure is also generated when reacting DPCO with Cu2+. Unfortunately a crystal of a chromium or vanadium complex with DPC was not achieved; however the cyclised ligand was isolated, highlighting that the oxidation and cyclisation of DPC is important in the coordination chemistry of these ions. Reaction of the sulphur derivative DPTC with various metal ions results in the deprotonation of the ligand to form the monoanionic species, which coordinates the metal ions via the S-donor and azo N-donor atoms. Reaction of DPTC with Hg2+ to form the mononuclear complex [Hg(DPTC)2]. The simple mononuclear complex involves two DPTC ligands coordinating the four-coordinate Hg2+ ion as a bidentate donor via the N-donor and S-donor atoms. The reaction of DPTC with both Hg2+ and Ag+ results in an interesting structure containing two Ag+, two Hg2+ and four DPTC ligands. The DPTC appears to first react with Hg2+ to form the previous [Hg(DPTC)2] complex, this then acts as a bidentate ligand, coordinating via the S-donor atom and the Hg2+ itself to form the [Hg2Ag2(DPTC)4(acetone)2(ClO4)2] complex. The reaction of DPTC with Cu2+, whether the anion is perchlorate or tetrafluoroborate, results in a very interesting structure, which comprises of eight DPTC ligands and eight Cu+ metal ions. The reaction of Cu2+ with DPTC results in the metal ion reducing to Cu+ and simultaneously the DPTC deprotonates to form the monoanionic form. The counter-anion acts as a template and the formation of the “Cu8” is a result of the presence of the anion. Reaction of copper (II) acetate with DPTC results in the [Cu2(DPTC)2(DPTCO)] complex. The structure contains three ligands and two reduced distorted tetrahedral Cu+ ions. Each Cu+ ion has four-coordinate geometry arising from the coordination of two different forms of the DPTC ligands. Two of the ligands present are the monoanionic DPTC, coordinating via the S-donor and terminal N-donor azo atoms. Whereas the third ligand has completely oxidised to form DPTCO, coordinating via both the terminal N-donor azo N-donor atoms, the sulphur atom bridges both of the metal ions

A profile in FIRE: resolving the radial distributions of satellite galaxies in the Local Group with simulations

While many tensions between Local Group (LG) satellite galaxies and LCDM cosmology have been alleviated through recent cosmological simulations, the spatial distribution of satellites remains an important test of physical models and physical versus numerical disruption in simulations. Using the FIRE-2 cosmological zoom-in baryonic simulations, we examine the radial distributions of satellites with Mstar > 10^5 Msun around 8 isolated Milky Way- (MW) mass host galaxies and 4 hosts in LG-like pairs. We demonstrate that these simulations resolve the survival and physical destruction of satellites with Mstar >~ 10^5 Msun. The simulations broadly agree with LG observations, spanning the radial profiles around the MW and M31. This agreement does not depend strongly on satellite mass, even at distances <~ 100 kpc. Host-to-host variation dominates the scatter in satellite counts within 300 kpc of the hosts, while time variation dominates scatter within 50 kpc. More massive host galaxies within our sample have fewer satellites at small distances, likely because of enhanced tidal destruction of satellites via the baryonic disks of host galaxies. Furthermore, we quantify and provide fits to the tidal depletion of subhalos in baryonic relative to dark matter-only simulations as a function of distance. Our simulated profiles imply observational incompleteness in the LG even at Mstar >~ 10^5 Msun: we predict 2-10 such satellites to be discovered around the MW and possibly 6-9 around M31. To provide cosmological context, we compare our results with the radial profiles of satellites around MW analogs in the SAGA survey, finding that our simulations are broadly consistent with most SAGA systems.Comment: 18 pages, 10 figures, plus appendices. Main results in figures 2, 3, and 4. Accepted versio

The Resolved Stellar Halo of NGC 253

We have obtained Magellan/IMACS and HST/ACS imaging data that resolve red giant branch stars in the stellar halo of the starburst galaxy NGC 253. The HST data cover a small area, and allow us to accurately interpret the ground-based data, which cover 30% of the halo to a distance of 30 kpc, allowing us to make detailed quantitative measurements of the global properties and structure of a stellar halo outside of the Local Group. The geometry of the halo is significantly flattened in the same sense as the disk, with a projected axis ratio of b/a ~ 0.35 +/- 0.1. The total stellar mass of the halo is estimated to be M_halo ~ 2.5 +/- 1.5 x 10^9 M_sun, or 6% of the total stellar mass of the galaxy, and has a projected radial dependence that follows a power law of index -2.8 +/- 0.6, corresponding to a three-dimensional power law index of ~ -4. The total luminosity and profile shape that we measure for NGC 253 are somewhat larger and steeper than the equivalent values for the Milky Way and M31, but are well within the scatter of model predictions for the properties of stellar halos built up in a cosmological context. Structure within the halo is seen at a variety of scales: there is small kpc-scale density variation and a large shelf-like feature near the middle of the field. The techniques that have been developed will be essential for quantitatively comparing our upcoming larger sample of observed stellar halos to models of halo formation.Comment: ApJ, in press. Version with full resolution figures available at http://www.astro.lsa.umich.edu/~jbailin/papers/bailin_n253halo.pd

Anticancer, Biophysical and Computational Investigations of Half-Sandwich Ruthenium(II) Thiosemicarbazone Complexes: The Effect of Arene \u3ci\u3eVersus\u3c/i\u3e Thiacrown Face-Cap

A series of half-sandwich ruthenium complexes, two containing an arene face-cap and the other a thiacrown ether face-cap were synthesized to investigate the necessity of the arene for anticancer activity in this class of compounds. The complexes are formulated as [(h6-p-cymene)Ru(dmabTSC)Cl]PF6, [(h6-benzene)Ru(dmabTSC)Cl]PF6 (arene complexes), and [([9]aneS3(dmabTSC)Cl]PF6 (dmabTSC = dimethylaminobenzaldehye thiosemicarbazone). It was observed that none of the complexes showed good anticancer activity in vitro against HCT-116 and Caco-2 (colon adenocarcinoma) cells. All three complexes can bind strongly to calf-thymus DNA with binding constants on the order of 105 M-1. In addition they all bind strongly to human serum albumin with binding constants between 105 and 106 M-1. There appears to be a single binding site on the protein for these complexes. A computational investigation of these complexes and their hydrolysis products was carried out by molecular docking with DNA and topoisomerase II. From this analysis it is noted that the type of face-capping ligand had different effects on the two macromolecules. It is therefore noted that the knowledge gained from this study will be useful in identifying the type of complexes in this class that show useful metallodrug potential

Control of metallo-supramolecular assemblies via steric, hydrogen bonding and argentophilic interactions; formation of a 3-dimensional polymer of circular helicates

This work shows how multiple non-covalent interactions are employed to control metallosupramolecular architectures and we demonstrate that a ligand, which contains two bidentate domains separated by a ArOH spacer, forms a mesocate when complexed with Ag(I). However, changing this to an ArOCH2CH2Ph spacer unit results in a 1-dimensional helical polymer upon reaction with the same cation. Reaction of Ag(I) with the ArOMe derivative gives a hexanuclear circular helicate which forms inter-assembly Ag⋯Ag interactions resulting in a 3-dimensional honeycomb-like polymer of hexanuclear circular helicates

The Equity Impact Vaccines May Have On Averting Deaths And Medical Impoverishment In Developing Countries.

With social policies increasingly directed toward enhancing equity through health programs, it is important that methods for estimating the health and economic benefits of these programs by subpopulation be developed, to assess both equity concerns and the programs' total impact. We estimated the differential health impact (measured as the number of deaths averted) and household economic impact (measured as the number of cases of medical impoverishment averted) of ten antigens and their corresponding vaccines across income quintiles for forty-one low- and middle-income countries. Our analysis indicated that benefits across these vaccines would accrue predominantly in the lowest income quintiles. Policy makers should be informed about the large health and economic distributional impact that vaccines could have, and they should view vaccination policies as potentially important channels for improving health equity. Our results provide insight into the distribution of vaccine-preventable diseases and the health benefits associated with their prevention

Incorporating FRAX into a nurse-delivered integrated care review: a multi-method qualitative study.

Background People with inflammatory rheumatological conditions (IRCs) are at increased risk of common comorbidities including osteoporosis. Aim To explore the barriers to, and facilitators of, implementing nurse-delivered fracture risk assessments in primary care, in the context of multi-morbidity reviews for people with IRCs. Design and Setting A multi-method qualitative study in primary care. Methods As part of a process evaluation in a pilot trial, semi-structured interviews were conducted with 20 patients, 2 nurses and 3 General Practitioners (GPs) and 24 consultations were audio-recorded and transcribed. A framework analysis was conducted using the Theoretical Domains Framework (TDF). Results Nurses reported positive views about the value of FRAX® assessments and confidence in delivering them. Barriers to implementation, as identified by TDF, particularly related to the domains of knowledge, skills, professional roles and environmental context. GPs reported difficulty keeping up to date with osteoporosis guidelines and voiced differing opinions about whether fracture risk assessment was the role of primary or secondary care. Lack of integration of FRAX® into IT systems was a barrier to use. GPs and nurses had differing views about the nurse role in communicating risk and acting on FRAX® findings: explanations of the FRAX® result and action needed were limited. Patients reported limited understanding of FRAX® outcomes. Conclusion The findings suggest that, with appropriate training including risk communication, practice nurses are likely to be confident to play a key role in conducting fracture risk assessments, but further work is needed to address the barriers identified

Procalcitonin Is Not a Reliable Biomarker of Bacterial Coinfection in People With Coronavirus Disease 2019 Undergoing Microbiological Investigation at the Time of Hospital Admission

Abstract Admission procalcitonin measurements and microbiology results were available for 1040 hospitalized adults with coronavirus disease 2019 (from 48 902 included in the International Severe Acute Respiratory and Emerging Infections Consortium World Health Organization Clinical Characterisation Protocol UK study). Although procalcitonin was higher in bacterial coinfection, this was neither clinically significant (median [IQR], 0.33 [0.11–1.70] ng/mL vs 0.24 [0.10–0.90] ng/mL) nor diagnostically useful (area under the receiver operating characteristic curve, 0.56 [95% confidence interval, .51–.60]).</jats:p