Novel Thiophene Supported N,N\u27-Chelating Ligands and Their Main Group Compounds

Main group chemistry has advanced from studying fundamental curiosities, including low oxidation state, low-valent, p-block elements to tailoring these unique, reactive species for specific functional applications. This thesis examines the structure, bonding and reactivity of select group 13, 14 and 15 elements supported by N,N\u27-chelating ligands decorated with either thiophene, benzo[1,2-b:5,6-b\u27]dithiophene or bis(2,5-dimethylthienyl)ethene substituents and allowing for subsequent reactivity and photophysical properties to be determined. The synthesis of a new diamino ligand containing a thiophene ring in the backbone was used to support a 7-membered phosphenium cation. The 1:1 stoichiometric reaction between the amine:chlorophosphine was dependant on the substitution at nitrogen. A 1:1 stoichiometric reaction between PCl3 and diamine (R = 2,4,6-trimethyphenyl), yielded the acyclic bis(aminodichlorophosphine), while with diisopropylphenyl groups on nitrogen both the 1:1 cyclic aminochlorophosphine and 1:2 acyclic bis(aminodichlorophosphine) were observed in a 4:1 ratio. To amend the poor selectivity, a new diamine was designed with benzo[1,2-b:5,6-b\u27]dithiophene in the backbone as this ligand generates a rigid five-membered ring upon coordination to main group elements. The detailed synthesis of this ligand and its ability to support pnictenium cations (Pn = P, As and Sb) and their metal complexes were prepared, along with a discussion of spectroscopic properties. The synthesis of an N-heterocyclic carbene (NHC) with the benzo[1,2-b:5,6-b\u27]dithiophene in the backbone, silver(I) transfer reagent and the BPh3 adduct were also synthesized. The donor strength of the NHC was measured from the carbonyl IR stretching frequencies of the isolated NHC-Rh(CO)­2Cl complex along with the resulting photophysical properties. The synthesis of a versatile diimine ligand containing adjacent 2,5-dimethyl(thienyl) rings in the backbone and its coordination to main group atoms was also achieved. This diazabutadiene acts as a precursor to a novel photochromic ligand that has been used to coordinate to both boron and phosphorus elements, along with the synthesis of a phosphorane side chain functionalized polymer. A study of the resulting photochromic properties of these compounds was completed and the following was observed: (i) The UV-visible absorption spectra of the ring closed isomer was dependent of the element present in the N,N\u27-chelating pocket; and (ii) incorporating the dithienylethene into a side functionalized phosphorane polymer greatly increased the ring closed/open reversibility and decreased the formation of by-products

Synthesis and Characterization of Conjugated/Cross-Conjugated Benzene-Bridged Boron Difluoride Formazanate Dimers

One of the most common strategies for the production of molecular materials with optical properties in the far-red/near-IR regions of the electromagnetic spectrum is their incorporation into dimeric architectures. In this paper, we describe the synthesis and characterization (1H, 11B, 13C and 19F NMR spectroscopy, IR and UV-Vis absorption and emission spectroscopy, mass spectrometry and X-ray crystallography) of the first examples of boron difluoride (BF2) formazanate dimers. Specifically, the properties of meta- and para-substituted benzene-bridged dimers p-10 and m-10 were compared to closely related boron difluoride triphenyl formazanate complex 11 in order to assess the effect of electronic conjugation and cross conjugation on their light absorption/emission and electrochemical properties. While the properties of cross-conjugated dimer m-10 did not differ significantly from those of monomer 11, conjugated dimer p-10 exhibited red-shifted absorption and emission maxima and was easier to reduce electrochemically to its bis radical anion and bis dianion form compared to monomer 11. Both dimers are weakly emissive in the far-red/near-IR and exhibited large Stokes shifts (\u3e 110 nm, 3318 cm−1). Unlike a closely related para-substituted benzene-bridged boron dipyrromethene (BODIPY) dimer, the emission quantum yields measured for the BF2 formazanate dimers exceeded those observed for monomeric analogues

An Azide-Functionalized Nitronyl Nitroxide Radical: Synthesis, Characterization and Staudinger-Bertozzi Ligation Reactivity

An azide-functionalized nitronyl nitroxide was successfully synthesized and its reactivity towards the Staudinger-Bertozzi ligation was explored. While a model reaction in solution showed the conversion of the nitronyl nitroxide to an imino nitroxide radical, the same reaction at the interface of gold nanoparticles allowed for successful covalent incorporation of the nitronyl nitroxide radical onto the nanoparticles

Lattice-QCD-based equations of state at finite temperature and density

The equation of state (EoS) of QCD is a crucial input for the modeling of heavy-ion-collision (HIC) and neutron-star-merger systems. Calculations of the fundamental theory of QCD, which could yield the true EoS, are hindered by the infamous Fermi sign problem which only allows direct simulations at zero or imaginary baryonic chemical potential. As a direct consequence, the current coverage of the QCD phase diagram by lattice simulations is limited. In these proceedings, two different equations of state based on first-principle lattice QCD (LQCD) calculations are discussed. The first is solely informed by the fundamental theory by utilizing all available diagonal and non-diagonal susceptibilities up to $\mathcal{O}(\mu_B^4)$ in order to reconstruct a full EoS at finite baryon number, electric charge and strangeness chemical potentials. For the second, we go beyond information from the lattice in order to explore the conjectured phase structure, not yet determined by LQCD methods, to assist the experimental HIC community in their search for the critical point. We incorporate critical behavior into this EoS by relying on the principle of universality classes, of which QCD belongs to the 3D Ising Model. This allows one to study the effects of a singularity on the thermodynamical quantities that make up the equation of state used for hydrodynamical simulations of HICs. Additionally, we ensure that these EoSs are valid for applications to HICs by enforcing conditions of strangeness neutrality and fixed charge-to-baryon-number ratio.Comment: Contribution to the 37th Winter Workshop on Nuclear Dynamics. arXiv admin note: text overlap with arXiv:2103.0814

Evaluating a Modular Approach to Therapy for Children With Anxiety, Depression, Trauma, or Conduct Problems (MATCH) in School-Based Mental Health Care: Study Protocol for a Randomized Controlled Trial

Introduction: Schools have become a primary setting for providing mental health care to youths in the U.S. School-based interventions have proliferated, but their effects on mental health and academic outcomes remain understudied. In this study we will implement and evaluate the effects of a flexible multidiagnostic treatment called Modular Approach to Therapy for Children with Anxiety, Depression, Trauma, or Conduct Problems (MATCH) on students' mental health and academic outcomes. Methods and Analysis: This is an assessor-blind randomized controlled effectiveness trial conducted across five school districts. School clinicians are randomized to either MATCH or usual care (UC) treatment conditions. The target sample includes 168 youths (ages 7-14) referred for mental health services and presenting with elevated symptoms of anxiety, depression, trauma, and/or conduct problems. Clinicians randomly assigned to MATCH or UC treat the youths who are assigned to them through normal school referral procedures. The project will evaluate the effectiveness of MATCH compared to UC on youths' mental health and school related outcomes and assess whether changes in school outcomes are mediated by changes in youth mental health. Ethics and Dissemination: This study was approved by the Harvard University Institutional Review Board (IRB14-3365). We plan to publish the findings in peer-reviewed journals and present them at academic conferences. Clinical Trial Registration: ClinicalTrials.gov ID: NCT02877875. Registered on August 24, 2016

Disrupting LIN28 in atypical teratoid rhabdoid tumors reveals the importance of the mitogen activated protein kinase pathway as a therapeutic target

Atypical teratoid rhabdoid tumor (AT/RT) is among the most fatal of all pediatric brain tumors. Aside from loss of function mutations in the SMARCB1 (BAF47/INI1/SNF5) chromatin remodeling gene, little is known of other molecular drivers of AT/RT. LIN28A and LIN28B are stem cell factors that regulate thousands of RNAs and are expressed in aggressive cancers. We identified high-levels of LIN28A and LIN28B in AT/RT primary tumors and cell lines, with corresponding low levels of the LIN28-regulated microRNAs of the let-7 family. Knockdown of LIN28A by lentiviral shRNA in the AT/RT cell lines CHLA-06-ATRT and BT37 inhibited growth, cell proliferation and colony formation and induced apoptosis. Suppression of LIN28A in orthotopic xenograft models led to a more than doubling of median survival compared to empty vector controls (48 vs 115 days). LIN28A knockdown led to increased expression of let-7b and let-7g microRNAs and a down-regulation of KRAS mRNA. AT/RT primary tumors expressed increased mitogen activated protein (MAP) kinase pathway activity, and the MEK inhibitor selumetinib (AZD6244) decreased AT/RT growth and increased apoptosis. These data implicate LIN28/RAS/MAP kinase as key drivers of AT/RT tumorigenesis and indicate that targeting this pathway may be a therapeutic option in this aggressive pediatric malignancy