Synthesis and characterization of multidentate iminopyridine and polypyridine transition metal complexes

2013 Spring.Includes bibliographical references.The work described in this dissertation details the syntheses and characterization of transition metal complexes featuring polypyridyl and iminopyridine ligands. The primary focus has been the synthesis of 3d metal complexes of multidentate iminopyridine ligands bearing functionalizations relevant to spin crossover and photochemistry. These seemingly disparate areas of research are linked by the facts that subtle metal-ligand interactions play enormous roles in determining complex properties and that understanding these types of interactions is crucial for eventual property control. In Chapter 1, the underpinnings of spin crossover in transition metals with d4-d7 configurations are discussed along with progress toward linking spin-switching events with host-guest interactions in solution. My research on Fe(II) hexadentate iminopyridine complexes is placed into context with extending anion sensing to biologically and environmentally relevant media. Also in Chapter 1, my work on hexadentate iminopyridine and polypyridine Cr complexes is related to the current understanding of the excited state behavior of 3d iminopyridine complexes, specifically, and 3d aromatic diimines in general. Additionally, the redox non-innocence of iminopyridine and polypyridine ligands is discussed. In Chapter 2, the preparation and characterization of a series of divalent 3d transition metal complexes (Cr to Zn), featuring an ester functionalized multidentate, tripodal iminopyridine Schiff-base L5-OOMe is reported. X-ray structural studies reveal complex geometries ranging from local octahedral coordination to significant distortion towards trigonal prismatic geometry to heptacoordinate environments. Regardless of coordination mode, magnetic and spectroscopic studies show the ligand to provide moderately strong ligand fields: the Fe complex is low-spin, while the Co and Mn complexes are high-spin at all temperatures proved. Cyclic voltammograms exhibit multiple reversible ligand-based reductions, which are relatively consistent throughout the series; however, the electrochemical behavior of the Cr complex is fundamentally different from those of the other complexes. Time-dependent (TD) DFT and natural transition orbital (NTO) computational analyses for the ligand, its anion, and complexes were provided by Prof. Anthony Rappé: the computed spectra reproduce the major differential features of the observed visible absorption spectra, and NTOs provide viable interpretations for the observed features. The combined studies indicate that for Mn-Zn complexes, neutral ligands are bound to M(II) ions, but Cr is best described as a Cr(III) species bound to a radical anionic ligand. In Chapter 3, the syntheses and characterizations of Fe(II) complexes of hexadentate ligands poised for anion-triggered spin-state switching in polar solution media are reported. The tripodal iminopyridine ligands L5-OH, L6-OH and L5-ONHtBu, L6-ONHtBu contain methanolic or t-butylamide functional groups, respectively. Solid-state evidence for anion-cation hydrogen bonding interactions are observed for halide complexes of [Fe(L6-OH)]2+ and [Fe(L5-ONHtBu)]2+; [Fe(L5-ONHtBu)]2+ forms a preorganized pocket which strongly binds Cl-. Strong anion binding events in the 5-position complexes are also observed in solution via 1H NMR monitored chloride titrations in acetonitrile. And while no temperature dependence or anion dependence on spin-state is apparent for 6-position complexes in solution, a small but significant increase in magnetic susceptibility is observed for [Fe(L5-ONHtBu)]2+ as up to one equivalent of tetrabutylammonium chloride is added; suggesting that spin-state control by anion-cation interactions may be accessible for this class of compounds. In Chapter 4, the preparation and characterization of homo- and heteroleptic Cr(III) coordination complexes featuring the dimethyl 2,2'-bipyridine-4,4'-dicarboxylate (4-dmcbpy) ligand are discussed. Static and nanosecond time-resolved absorption and emission properties of these complexes dissolved in acidic aqueous (1 M HCl(aq)) solutions were investigated by Huan-Wei Tseng and Prof. Niels Damrauer. The photophysical data suggest that in these acidic aqueous environments these complexes store ~1.7 eV for multiple microseconds at room temperature. The electrochemical properties of these polypyridyl complexes were investigated by cyclic voltammetry. It is found that inclusion of 4-dmcbpy shifts the 'CrIII/II' E1/2 by +0.22 V compared to those of homoleptic parent complexes. The electrochemical and photophysical data allow for excited state potentials to be determined: for [Cr(4-dmcbpy)3]3+, CrIII*/II lies at +1.44 V versus Fc+/0 (~+2 V vs NHE), suggesting it would act as one of the most powerful photooxidants reported. In Chapter 5, the preparation, photophysical characterization, and computed excited state energies for Cr(III) complexes of a family of tripodal hexadentate and tris(bidentate) iminopyridine ligands are reported. Cyclic voltammograms reveal that the hexadentate and tris(bidentate) analogues have almost identical reduction potentials, and overall electrochemical behavior similar to the polypyridyl complexes described in Chapter 3. The absorption spectra of the hexadentate complexes show improved absorption of visible light compared to the tris(bidentate) analogues. Photophysical characterization provided by Huan-Wei Tesng and Prof. Niels Damrauer show a doublet excited state with 17 to 19 μs lifetime at room temperature for the ester functionalized tris(bidentate) complex, while no doublet states are observed for the ester functionalized hexadentate analogue under the same conditions. The electronic structure contributions to the differences in observed photophysical properties are compared by extensive computational analyses provided by Prof. Anthony Rappé. These studies indicate that the presence of non-ligated bridgehead nitrogen atoms in the complexes of tripodal hexadentate iminopyridines significantly reduce excited state doublet, quartet, and sextet energies and change the character of the low lying doublet states in compared to species that show population of doublet excited states. In Chapter 6 the syntheses and characterization of reduced forms of Cr complexes of 4-dmcbpy (described in Chapter 4), [Cr(4-dmcbpy)3]n+ (n = 2, 1), and tren(py)3 (L1, described in Chapter 5) [Cr(tren(py)3)]n+ (n = 2) are reported. Comparison of electrochemical data for the series (n = 3, 2, 1) and solid state structures of the divalent complexes are consistent with consecutive reducing equivalents added to Cr polypyridine or iminopyridine complexes not residing on the metal, and that these complexes are best described as Cr(III) ions ligated to anionic radical ligands. Final remarks about the work in Chapters 2-6 and suggested directions for future work are presented in Chapter 7

Aerodynamics for the ADEPT SR-1 Flight Experiment

Adaptable, Deployable, Entry, and Placement Technology (ADEPT) is a combination of a heatshield and an aerodynamic decelerator for atmospheric entry applications. The ADEPT Sounding Rocket (SR)-1 mission was a suborbital flight experiment of an 0.7 m-diameter ADEPT to verify system-level performance and to characterize dynamic stability behavior. The aerodynamic database for ADEPT SR-1 was constructed from non-continuum and continuum flowfield computations, along with data from recent ADEPT ground testing and the IRVE-3 flight test vehicle. High-altitude (free-molecular and transitional regimes) data were generated using DSMC methods. Pre-flight predictions of continuum static aerodynamics coefficients were derived from Reynolds-Averaged Navier-Stokes solutions at conditions along a design trajectory, with comparisons to available ground test data of the nano-ADEPT geometry. Dynamic pitch damping characteristics were taken from functional forms developed for the IRVE-3 flight test vehicle through ballistic range testing. Comparison of pre-flight predictions to post-flight reconstruction of aerodynamic force and moment coefficients is presented

Daylighting Optimization Study: Rock Creek High School Commons Skylight Optimization

The aim of this study is to optimize the shape of the skylights in order to enhance daylighting. Rhino, Diva, Grasshopper, and Galapagos are the softwares utilized to test differing shapes on top and bottom of the shaft of the skylight, and the findings show preference to those with beneficial impacts on Spatial daylighting autonomy (sDA) of greater than 55% and Annual Solar Exposure (ASE) of less than 10%. Selecting metrics within the above parameters result in optimal skylight geometry with highest daylighting output. The initial purpose of the experiment was to optimize the design of the skylight shaft with the goal of providing the best distribution of daylight while minimizing potential for glare; however, it appears that this shaping may have negligible effects on how the skylight performs as long as the sDA is greater than 55%

Rock Creek Middle School Daylighting Analysis: Existing and Proposed Spaces

Bora is starting design work on a conversion of Rock Creek Middle School (completed by BORA in 2010) into a high school. This conversion was always envisioned and will soon become a reality. The project will double the size of the existing school, with additional structure being added lo most sides and even the roof of one wing. The will impact existing daylight access in various ways that we\u27d like to understand better. The goal of this research project is to help us understand existing daylight conditions in areas that will be impacted by proposed additions, leading to informed design decisions about how to mitigate negative effects and maintain optimal daylight in these spaces. BORA will identify a few key areas to study. Students will obtain field measurements to quantify existing daylight effectiveness, and conduct parallel Diva analysis lo establish a modeled baseline of the existing conditions. Then, our proposed additions will be added to the model to analyze resultant daylight performance. Impacts will be quantified and potential design studied as time allows.https://pdxscholar.library.pdx.edu/research_based_design/1087/thumbnail.jp

Bone healing in an aged murine fracture model is characterized by sustained callus inflammation and decreased cell proliferation

Geriatric fractures take longer to heal and heal with more complications than those of younger patients; however, the mechanistic basis for this difference in healing is not well understood. To improve this understanding, we investigated cell and molecular differences in fracture healing between 5‐month‐old (young adult) and 25‐month‐old (geriatric) mice healing utilizing high‐throughput analysis of gene expression. Mice underwent bilateral tibial fractures and fracture calluses were harvested at 5, 10, and 20 days post‐fracture (DPF) for analysis. Global gene expression analysis was performed using Affymetrix MoGene 1.0 ST microarrays. After normalization, data were compared using ANOVA and evaluated using Principal Component Analysis (PCA), CTen, heatmap, and Incromaps analysis. PCA and cross‐sectional heatmap analysis demonstrated that DPF followed by age had pronounced effects on changes in gene expression. Both un‐fractured and 20 DPF aged mice showed increased expression of immune‐associated genes (CXCL8, CCL8, and CCL5) and at 10 DPF, aged mice showed increased expression of matrix‐associated genes, (Matn1, Ucma, Scube1, Col9a1, and Col9a3). Cten analysis suggested an enrichment of CD8+ cells and macrophages in old mice relative to young adult mice and, conversely, a greater prevalence of mast cells in young adult mice relative to old. Finally, consistent with the PCA data, the classic bone healing pathways of BMP, Indian Hedgehog, Notch and Wnt clustered according to the time post‐fracture first and age second. Clinical Significance: Greater understanding of age‐dependent molecular changes with healing will help form a mechanistic basis for therapies to improve patient outcomes. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:149–158, 2018.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142531/1/jor23652.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142531/2/jor23652_am.pd

Exploring structural and electronic effects in three isomers of tris{bis(trifluoromethyl)phenyl}borane: Towards the combined electrochemical-frustrated Lewis pair activation of H2

Three structural isomers of tris{bis(trifluoromethyl)phenyl}borane have been studied as the acidic com- ponent of frustrated Lewis pairs. While the 3,5-substituted isomer is already known to heterolytically cleave H2 to generate a bridging-hydride; ortho-substituents in the 2,4- and 2,5-isomers quench such reactivity through electron donation into the vacant boron pz orbital and steric blocking of the boron centre; as shown by electrochemical, structural and computational studies. Electrochemical studies of the corresponding borohydrides identify that the two-electron oxidation of terminal-hydrides occurs at more positive potentials than observed for [HB(C6F5)3]−, while the bridging-hydride oxidizes at a higher poten- tial still, comparable to that of free H2

K

Article discussing K-shell ionization by low-velocity ions. K-shell x-ray-production measurements are reported for protons, deuterons, and alpha particles incident on thin foils of copper, niobium, silver, and antimony

Implementation of the CALM intervention for anxiety disorders: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Investigators recently tested the effectiveness of a collaborative-care intervention for anxiety disorders: Coordinated Anxiety Learning and Management(CALM) []) in 17 primary care clinics around the United States. Investigators also conducted a qualitative process evaluation. Key research questions were as follows: (1) What were the facilitators/barriers to implementing CALM? (2) What were the facilitators/barriers to sustaining CALM after the study was completed?</p> <p>Methods</p> <p>Key informant interviews were conducted with 47 clinic staff members (18 primary care providers, 13 nurses, 8 clinic administrators, and 8 clinic staff) and 14 study-trained anxiety clinical specialists (ACSs) who coordinated the collaborative care and provided cognitive behavioral therapy. The interviews were semistructured and conducted by phone. Data were content analyzed with line-by-line analyses leading to the development and refinement of themes.</p> <p>Results</p> <p>Similar themes emerged across stakeholders. Important facilitators to implementation included the perception of "low burden" to implement, provider satisfaction with the intervention, and frequent provider interaction with ACSs. Barriers to implementation included variable provider interest in mental health, high rates of part-time providers in clinics, and high social stressors of lower socioeconomic-status patients interfering with adherence. Key sustainability facilitators were if a clinic had already incorporated collaborative care for another disorder and presence of onsite mental health staff. The main barrier to sustainability was funding for the ACS.</p> <p>Conclusions</p> <p>The CALM intervention was relatively easy to incorporate during the effectiveness trial, and satisfaction was generally high. Numerous implementation and sustainability barriers could limit the reach and impact of widespread adoption. Findings should be interpreted with the knowledge that the ACSs in this study were provided and trained by the study. Future research should explore uptake of CALM and similar interventions without the aid of an effectiveness trial.</p

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival