Synthesis, Structure, Spectroscopy, and Reactivity of Azapentadienyl-Ruthenium-Phosphine Complexes

This dissertation focuses on the systematic synthesis of ¬bis-azapentadienyl-ruthenium-phosphine complexes. The synthetic approach involves the treatment of Cl2Ru(PPh3)3 with potassium tert-butylazapentadienide reagent. The reactivity of this parent compound with other 2e- donor ligands is investigated. These resultant complexes\u27 reactivity with triflic acid is also studied. Treatment of Cl2Ru(PPh3)3 with potassium tert-butylazapentadienide produces [(1,2,3-η3)-5-tert-butylazapentadienyl]2Ru(PPh3)2 (1). Compound 1 undergoes single substitution of one of the triphenylphosphines when treated with PMe3, dmpe, P(OMe)3, CNCMe3, CO, and PEt3 at room temperature, resulting in [(1,2,3-η3)-5-tert-butylazapentadienyl]2Ru(PPh3)(L) (2, L = PMe3; 3, L= dmpe; 4, L = P(OMe)3; 5, L = CNCMe3; 6, L = CO; 7, L = PEt3). By increasing the reaction time of 1 with PEt3, double substitution of both triphenylphosphines occurs, resulting in [(1,2,3-η3)-5-tert-butylazapentadienyl]2Ru(PEt3)2 (8). Compounds 1 - 8 possess a pseudo-octahedral geometry where both ancillary ligands sit trans to the C3\u27s of the azapentadienyl ligands. Compounds 1 - 4, 7 and 8 exhibit a ligand orientation in which both ancillary ligands sit in the mouth of each azapentadienyl ligand, denoted as mC3/mC3. In contrast, 5 exhibits a ligand arrangement where the PPh3 sits in the mouth of one azapentadienyl ligand while CNCMe3 sits on the backbone of the other azapentadienyl ligand. Other double substitution reactions occur when 1 is treated with PMe3, P(OMe)3, and dmpe in THF at reflux, resulting in [(1,2,3-η3)-5-tert-butylazapentadienyl]2Ru(L)x (9, L = PMe3, x = 2; 10, L = P(OMe3), x = 2; 11, L = dmpe, x = 1). Compounds 9 and 10 exist in solution as an equilibrium mixture of two structural isomers. The two isomers in solution have either a mC3/mC3 or mC3/bC1 ligand orientation. Treatment of 8, 9 and 10 with triflic acid results in dicationic products, {[(1,2,3-η3)-(CH2CHCHCH=N(H)(CMe3)]2Ru(L)2}2+(-O3SCF3)2 (12, L = PEt3; 13, L = PMe3; 14, L = P(OMe)3), in which both azapentadienyl nitrogen atoms have been protonated. The protonated product, 12, shows a ligand conversion from mC3/mC3 (seen in 8) to mC3/bC3. Upon protonation, 9 and 10 each convert to a single isomer, 12 and 13, respectively. Like 12, compound 13 possesses a mC3/bC3 orientation while 14 has a ligand orientation in which the azapentadienyl ligands appear to be mC3/mC3. Treatment of 2, 4 and 5 with triflic acid results in multiple isomers of the diprotonated {[(1,2,3-η3)-CH2CHCHCH=N(H)(CMe3)]2Ru(PPh3)(L)}2+(-O3SCF3)2 (15, L = PMe3; 16, L = P(OMe)3; 17, L = CNCMe3). All of the compounds have been characterized, in part, by NMR spectroscopy, and the structures of 2, 4, 5, 7, 8, and 12 have been confirmed by single-crystal X-ray diffraction

Dicarbonyl­dichloridobis(trimethyl­phosphane)iron(II)–carbonyl­dichlorido­tris(trimethyl­phosphane)iron(II)–tetra­hydro­furan (1/1/2)

The asymmetric unit of the title crystal, [FeCl2(C3H9P)3(CO)]·[FeCl2(C3H9P)2(CO)2]·2C4H8O, contains half mol­ecules of the two closely related FeII complexes lying on mirror planes and a tetra­hydro­furan solvent mol­ecule, one C atom of which is disordered over two sets of sites with site occupancy factors 0.633 (9) and 0.367 (9). In both FeII complex mol­ecules, a distorted octa­hedral coordination geometry has been observed around the Fe atoms. Weak intermolecular C—H⋯O inter­actions are observed in the crystal structure

Expression quantitative trait locus fine mapping of the 17q12–21 asthma locus in African American children: a genetic association and gene expression study

Background: African ancestry is associated with a higher prevalence and greater severity of asthma than European ancestries, yet genetic studies of the most common locus associated with childhood-onset asthma, 17q12–21, in African Americans have been inconclusive. The aim of this study was to leverage both the phenotyping of the Children's Respiratory and Environmental Workgroup (CREW) birth cohort consortium, and the reduced linkage disequilibrium in African Americans, to fine map the 17q12–21 locus. Methods: We first did a genetic association study and meta-analysis using 17q12–21 tag single-nucleotide polymorphisms (SNPs) for childhood-onset asthma in 1613 European American and 870 African American children from the CREW consortium. Nine tag SNPs were selected based on linkage disequilibrium patterns at 17q12–21 and their association with asthma, considering the effect allele under an additive model (0, 1, or 2 effect alleles). Results were meta-analysed with publicly available summary data from the EVE consortium (on 4303 European American and 3034 African American individuals) for seven of the nine SNPs of interest. Subsequently, we tested for expression quantitative trait loci (eQTLs) among the SNPs associated with childhood-onset asthma and the expression of 17q12–21 genes in resting peripheral blood mononuclear cells (PBMCs) from 85 African American CREW children and in upper airway epithelial cells from 246 African American CREW children; and in lower airway epithelial cells from 44 European American and 72 African American adults from a case-control study of asthma genetic risk in Chicago (IL, USA). Findings: 17q12–21 SNPs were broadly associated with asthma in European Americans. Only two SNPs (rs2305480 in gasdermin-B [GSDMB] and rs8076131 in ORMDL sphingolipid biosynthesis regulator 3 [ORMDL3]) were associated with asthma in African Americans, at a Bonferroni-corrected threshold of p<0·0055 (for rs2305480_G, odds ratio [OR] 1·36 [95% CI 1·12–1·65], p=0·0014; and for rs8076131_A, OR 1·37 [1·13–1·67], p=0·0010). In upper airway epithelial cells from African American children, genotype at rs2305480 was the most significant eQTL for GSDMB (eQTL effect size [β] 1·35 [95% CI 1·25–1·46], p<0·0001), and to a lesser extent showed an eQTL effect for post-GPI attachment to proteins phospholipase 3 (β 1·15 [1·08–1·22], p<0·0001). No SNPs were eQTLs for ORMDL3. By contrast, in PBMCs, the five core SNPs were associated only with expression of GSDMB and ORMDL3. Genotype at rs12936231 (in zona pellucida binding protein 2) showed the strongest associations across both genes (for GSDMB, eQTLβ 1·24 [1·15–1·32], p<0·0001; and for ORMDL3 (β 1·19 [1·12–1·24], p<0·0001). The eQTL effects of rs2305480 on GSDMB expression were replicated in lower airway cells from African American adults (β 1·29 [1·15–1·44], p<0·0001). Interpretation: Our study suggests that SNPs regulating GSDMB expression in airway epithelial cells have a major role in childhood-onset asthma, whereas SNPs regulating the expression levels of 17q12–21 genes in resting blood cells are not central to asthma risk. Our genetic and gene expression data in African Americans and European Americans indicated GSDMB to be the leading candidate gene at this important asthma locus.6 month embargo; published: 01 May 2020This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]