Chemistry of cyclopentadienylchromium complexes containing C-, N- and S- organic ligands

Master'sMASTER OF SCIENC

A common variant near TGFBR3 is associated with primary open angle glaucoma

Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10−33), we observed one SNP showing significant association to POAG (CDC7–TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10−8). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis

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Abstract Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array ), we observed one SNP showing significant association to POAG (CDC7-TGFBR3 rs1192415, OR G-allele = 1.13, P meta = 1.60 × 10 −8 ). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis

A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic.

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Synthesis of Cis,Syndiotactic ROMP Polymers Containing Alternating Enantiomers

Ring-opening metathesis polymerization (ROMP) of rac-endo,exo-5,6-dicarbomethoxynorbornene (inter alia) yields a cis,syndio,alt-polymer, one in which the sequential units in the cis,syndiotactic polymer consist of alternating enantiomers. Cis selectivity arises through addition of the monomer to produce an all-cis-metallacyclobutane intermediate, while syndioselectivity and alternating enantiomer structures arise as a consequence of inversion of configuration at the metal center with each metathesis step.United States. Army Research Office (Institute for Soldier Nanotechnologies, Contract No. DAAD-19-02-D-0002)United States. Dept. of Energy (DE-FG02- 86-ER13564)Singapore. Agency for Science, Technology and Research (A*STAR International Fellowship

Reactivity Studies of Oxo-Mo(IV) Complexes Containing Potential Hydrogen-Bond Acceptor/Donor Phenolate Ligands

Reactivity studies of oxo-Mo(IV) complexes, Tp iPr MoO{2-OC₆H4₄C(O)R-ᴋ²O,O'} (R = Me, Et, OMe, OEt, OPh, NHPh), containing chelated hydrogen-bond donor/acceptor phenolate ligands are reported

Stereoselective Ring-Opening Metathesis Polymerization (ROMP) of Methyl-N-(1-phenylethyl)-2-azabicyclo[2.2.1]hept-5-ene-3-carboxylate by Molybdenum and Tungsten Initiators

Ring-opening metathesis polymerization (ROMP) of methyl-N-(1-phenylethyl)-2-azabicyclo[2.2.1]hept-5-ene-3-carboxylate (PhEtNNBE; (S) and racemic) was investigated employing six molybdenum and tungsten imido alkylidene initiators and two tungsten oxo alkylidene initiators. Of the six initiators that we proposed should yield cis,syndiotactic-poly[(S)-PhEtNNBE], two molybdenum OHMT alkylidene initiators, Mo(NR)(CHMe2Ph)(pyr)(OHMT) (R = 1-adamantyl (Ad) or 2,6-Me[subscript 2]C[subscript 6]H[subscript 3] (Ar′); OHMT = O-2,6-mesityl[subscript 2]C[subscript 6]H[subscript 3]; pyr = pyrrolide), and two tungsten oxo alkylidene initiators, W(O)(CHMe[subscript 2]Ph)(2,5-dimethylpyrrolide)(PMe2Ph)(OR) (OR = OHMT or (R)-OBr[subscript 2]Bitet where (R)-Br[subscript 2]BitetOH = (R)-3,3′-dibromo-2′-(tert-butyldimethylsilyloxy)-5,5′,6,6′,7,7′,8,8′-octahydro-1,1′-binaphthyl-2-ol), produced essentially pure cis,syndiotactic-poly[(S)-PhEtNNBE]. Essentially pure cis,isotactic-poly[(S)-PhEtNNBE] was formed when (S)-PhEtNNBE was polymerized by Mo(NAr′)(CHCMe2Ph)(OBiphen[subscript CF3])(thf) or W(NAr′)(CHCMe[subscript 2]Ph)((S)-OBiphenMe) (OBiphenCF3 = 3,3′-di-tert-butyl-5,5′-bistrifluoromethyl-6,6′-dimethyl-1,1′-biphenyl-2,2′-diolate; (S)-OBiphen[subscript Me] = 3,3′-di-tert-butyl-5,5′,6,6′-tetramethyl-1,1′-biphenyl-2,2′-diolate). The best initiator for ROMP of rac-PhEtNNBE was Mo(NAd)(CHMe[subscript 2]Ph)(pyr)(OHMT) at 0 °C, which led to a polymer that is biased (∼80%) toward a cis,syndiotactic structure and that contains alternating enantiomers in the chain (cis,syndio,alt-poly[(rac)-PhEtNNBE]).United States. Department of Energy (grant DE-FG0286ER13564)Singapore. Agency for Science, Technology and Research (A*STAR International Fellowship)Alexander von Humboldt-Stiftung (Feodor Lynen Research Fellowship

Computational Chemistry for Homogeneous Redox Catalysis

Aquesta Tesis Doctoral s'ha centrat en l'estudi computacional mitjançant metodologia DFT (Teoria del funcional de la densitat) de reaccions redox catalitzades en fase homogènia. La primera part recau en l'estudi computacional de dos cicles catalítics d'acoblament oxidatiu. Aquest estudi ha aconseguit desxifrar una de les claus d'aquest tipus de reaccions, l'efecte de l'oxidant extern. Demostrem que en totes dues reaccions, diferents metalls de transició poden col•laborar per a donar una reacció més eficient i selectiva. A més a més, descobrim els factors claus per a la regioselectivitat de les dues reaccions estudiades. La segona reacció va ser estudiada en col•laboració amb el grup experimental del Prof. Frederic Patureau (University of Kaiserslautern). La segona part de la tesis es centra en canvi en l'estudi teòric de la reacció d'oxidació de l'aigua catalitzada per complexes de la primera serie de transició. S'ha desenvolupat una nova família de catalitzadors mononuclears de coure en col•laboració amb el grup del Prof. Antoni Llobet (ICIQ). S'ha descobert un nou mecanisme de formació de l'enllaç oxígen-oxígen que consisteix en l'atac nucleòfil de l'aigua mitjançant la transferència d'un electró (SET-WNA). Un cop descobert aquest mecanisme, es va veure que també operava sobre altres catalitzadors de coure i ruteni, redefinint així el context mecanístic d'aquesta reacció en catàlisis homogènia. Aquesta tesis, per tant, proporciona una profunda base mecanística sobre importants reaccions redox mitjançant la química computacional a través dels mètodes DFT.Esta Tesis Doctoral se ha centrado en el estudio computacional mediante metodología DFT (Teoría del funcional de la densidad) de reacciones redox catalizadas en fase homogénea. La primera parte versa sobre el estudio computacional de dos ciclos catalíticos de acoplamiento oxidativo. Este estudio dio con una de las claves en este tipo de reacciones, el efecto del oxidante externo. Demostramos en ambas reacciones como diferentes metales de transición podían colaborar para dar una reacción más eficiente y selectiva. Además descubrimos las claves para la regioselectividad en ambas reacciones. La segunda reacción fue estudiada en colaboración con el grupo experimental del profesor Frederic Patureau (University of Kaiserslautern). Por otro lado, la segunda parte de esta tesis se centra en el estudio teórico de la reacción de oxidación de agua catalizada por complejos de la primera serie de transición. Desarrollamos una nueva familia de catalizadores mononucleares de cobre con la colaboración experimental del grupo del profesor Antoni Llobet (ICIQ), descubriendo un nuevo mecanismo en la formación de enlace oxígeno-oxígeno, el ataque nucleófilo del agua mediante la transferencia de un electrón (SET-WNA). Tras esto extendimos este mecanismo a otros sistemas de cobre y de rutenio, redefiniendo el contexto mecanístico para esta reacción en catálisis homogénea. Esta tesis, por tanto, proporciona una profunda base mecanística sobre el estudio de importantes reacciones redox mediante química computacional a través de los métodos DFT.This Doctoral Thesis is focused on the computational study by DFT methodology (Density Functional Theory) of homogeneous redox catalized reactions. The first part describes successfully the mechanism of two different catalytic cycles of oxidative coupling reactions. This study found out the explanation about one of the challenging questions on the field, the key role of the external oxidant. We demonstrated the cooperation between different transition metals is essential to catalyze the reaction efficiently and with good selectivities. Additionally, we explained also the regioselectivity of both reactions, in very good agreement with the experimental results. The second reaction was studied in collaboration with the experimental group of professor Frederic Patureau (University of Kaiserslautern). On the other hand, the second part of the thesis is focused on the theoretical study of water oxidation reaction catalyzed by first-row transition metal complexes. Firstly, we developed a new family of mononuclear copper complexes in collaboration with the experimental group of professor Antoni Llobet (ICIQ), discovering a new mechanism for the oxygen-oxygen bond formation step, the water nucleophilic attack. single electron transfer (SET-WNA). From this point, we extended the new mechanism to other catalytic systems based on copper and ruthenium, redefining the mechanistic scenario for the homogeneous catalytic version of this reaction. Therefore, this thesis provides a deep theoretical knowledge abour the homogeneous redox catalysis mechanisms by DFT calculations

Syntheses of Variations of Stereogenic-at-Metal Imido Alkylidene Complexes of Molybdenum

In this paper we describe the syntheses of several new stereogenic-at-metal imido alkylidene complexes of molybdenum, Mo(NR)(CHR′)(X)(Y), many of which had to be prepared through selective nucleophilic displacement reactions in imido alkylidene complexes. The reported compounds include Mo(NAd)(CHCMe[subscript 2]Ph)(MesPyr)[subscript 2] (1a; MesPyr = 2-mesitylpyrrolide, Ad = 1-adamantyl), Mo(NAd)(CHCMe[subscript 2]Ph)(2-CNPyr)[subscript 2] (1b; 2-CNPyr = 2-cyanopyrrolide), Mo(NAd)(CHCMe[subscript 2]Ph)(MesPyr)(OTPP) (2a; OTPP = 2,3,5,6-tetraphenylphenoxide), Mo(NAd)(CHCMe[subscript 2]Ph)(MesPyr)(OBr[subscript 2]Bitet) (2b; OBr[subscript 2]Bitet = (R)-3,3′-dibromo-2′-(tert-butyldimethylsilyloxy)-5,5′,6,6′,7,7′,8,8′-octahydro-1,1′-binaphthyl-2-olate), Mo(NAd)(CHCMe[subscript 2]Ph)(OHIPT)(2-Mespyr) (2c; HIPT = 2,6-(2,4,6-iPr[subscript 3]C[subscript 6]H[subscript 2])[subscript 2]C[subscript 6]H[subscript 3]), Mo(NAd)(CHCMe[subscript 2]Ph)(OTf)(OHIPT) (3), Mo(NAd)(CHCMe[subscript 2]Ph)(OTf)(OHIPT)(PMe[subscript 3]) (3(PMe[subscript 3])), Mo(NAd)(CHCMe[subscript 2]Ph)(2-CNPyr)(OHIPT) (4), Mo(NAd)(CHCMe[subscript 2]Ph)(OHIPT)(OCMe[subscript 3]) (5), Mo(NR)(CHCMe[subscript 2]Ph)(OR[subscript F6])(OHMT) (OR[subscript F6] = OCMe(CF[subscript 3])[subscript 2]; HMT = 2,6-Mes[subscript 2]C[subscript 6]H[subscript 3]; R = 2,6-iPr[subscript 2]C[subscript 6]H[subscript 3] (Ar, 6a), 2,6-Me[subscript 2]C[subscript 6]H[subscript 3] (Ar′, 6b), 2-iPrC[subscript 6]H[subscript 4] (Ar[sueprscript iPr], 6c), Ad (6d)), Mo(NR)(CHCMe[subscript 2]Ph)(OR[subscript F6])[N(H)HMT] (7a (R = Ar′) and 7b (R = Ar[superscript iPr])), and Mo(NAd)(CHCMe[subscript 2]Ph)(OR[subscript F6])(HMT) (8). X-ray structural studies were carried out on 1b, 2a–c, 3(PMe[subscript 3]), 4, 5, 6d, 7b, and 8. Compound 1b is an octamer in which two η[superscript 1]-pyrrolides are trans to one another at each metal center and cyano groups bind from neighboring Mo centers trans to the alkylidene and imido ligands.National Science Foundation (U.S.) (CHE-0841187)National Science Foundation (U.S.) (CHE-0946721)National Science Foundation (U.S.) (CHE-111133)National Science Foundation (U.S.) (CHE-9808061