Publications by authors named "Patricia Lara"

27 Publications

  • Page 1 of 1

Platinum nanoparticles stabilized by N-heterocyclic thiones. Synthesis and catalytic activity in mono- and di-hydroboration of alkynes.

Nanoscale 2020 Mar 17;12(12):6821-6831. Epub 2020 Mar 17.

Instituto de Investigaciones Químicas (IIQ), CSIC - Universidad de Sevilla, C/Américo Vespucio 49, 41092, Seville, Spain.

N-Heterocyclic Thiones (NHT) proved to be efficient ligands for the stabilization of small platinum nanoparticles (1.3-1.7 nm), synthesized by decomposition of [Pt(dba)], under a H atmosphere, in the presence of variable sub-stoichiometric amounts of the NHT. Full characterization by means of TEM, HR-TEM, NMR, ICP, TGA and XPS have been carried out, providing information about the nature of the metal nanoparticles and the interaction of the NHT ligands to the metal surface. Importantly, DFT calculations indicate that some NHT ligands interact with the metal through the C[double bond, length as m-dash]C double bond of the imidazole fragment in addition to the sulfur atom, thus providing additional stabilization to the nanoparticles. According to XPS, TGA and ICP techniques, the surface coverage by the ligand increases by decreasing the size of the substituents on the nitrogen atom. The platinum nanoparticles have been used as catalyst in the hydroboration of alkynes. The most active system is that with a less covered surface area lacking an interaction of the ligand by means of the C[double bond, length as m-dash]C double bond. This catalyst hydroborates alkynes with excellent selectivities towards the monoborylated anti-Markovnikov product (vinyl-boronate) when one equiv. of borane is used. Very interestingly, aliphatic alkynes undergo a second hydroborylation process leading to the corresponding 1,1- and 1,2-diboroylated species with good selectivities towards the former.
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http://dx.doi.org/10.1039/d0nr00251hDOI Listing
March 2020

Membrane integration and topology of RIFIN and STEVOR proteins of the Plasmodium falciparum parasite.

FEBS J 2020 Jul 26;287(13):2744-2762. Epub 2019 Dec 26.

Department of Biochemistry and Biophysics, Stockholm University, Sweden.

The malarial parasite Plasmodium exports its own proteins to the cell surfaces of red blood cells (RBCs) during infection. Examples of exported proteins include members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum. The presence of these parasite-derived proteins on surfaces of infected RBCs triggers the adhesion of infected cells to uninfected cells (rosetting) and to the vascular endothelium potentially obstructing blood flow. While there is a fair amount of information on the localization of these proteins on the cell surfaces of RBCs, less is known about how they can be exported to the membrane and the topologies they can adopt during the process. The first step of export is plausibly the cotranslational insertion of proteins into the endoplasmic reticulum (ER) of the parasite, and here, we investigate the insertion of three RIFIN and two STEVOR proteins into the ER membrane. We employ a well-established experimental system that uses N-linked glycosylation of sites within the protein as a measure to assess the extent of membrane insertion and the topology it assumes when inserted into the ER membrane. Our results indicate that for all the proteins tested, transmembranes (TMs) 1 and 3 integrate into the membrane, so that the protein assumes an overall topology of Ncyt-Ccyt. We also show that the segment predicted to be TM2 for each of the proteins likely does not reside in the membrane, but is translocated to the lumen.
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http://dx.doi.org/10.1111/febs.15171DOI Listing
July 2020

Murine astrotactins 1 and 2 have a similar membrane topology and mature via endoproteolytic cleavage catalyzed by a signal peptidase.

J Biol Chem 2019 03 29;294(12):4538-4545. Epub 2019 Jan 29.

From the Department of Biochemistry and Biophysics, Stockholm University 10691 Stockholm, Sweden and

Astrotactin 1 (Astn1) and Astn2 are membrane proteins that function in glial-guided migration, receptor trafficking, and synaptic plasticity in the brain as well as in planar polarity pathways in the skin. Here we used glycosylation mapping and protease protection approaches to map the topologies of mouse Astn1 and Astn2 in rough microsomal membranes and found that Astn2 has a cleaved N-terminal signal peptide, an N-terminal domain located in the lumen of the rough microsomal membranes (topologically equivalent to the extracellular surface in cells), two transmembrane helices, and a large C-terminal lumenal domain. We also found that Astn1 has the same topology as Astn2, but we did not observe any evidence of signal peptide cleavage in Astn1. Both Astn1 and Astn2 mature through endoproteolytic cleavage in the second transmembrane helix; importantly, we identified the endoprotease responsible for the maturation of Astn1 and Astn2 as the endoplasmic reticulum signal peptidase. Differences in the degree of Astn1 and Astn2 maturation possibly contribute to the higher levels of the C-terminal domain of Astn1 detected on neuronal membranes of the central nervous system. These differences may also explain the distinct cellular functions of Astn1 and Astn2, such as in membrane adhesion, receptor trafficking, and planar polarity signaling.
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http://dx.doi.org/10.1074/jbc.RA118.007093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433051PMC
March 2019

Development and Preliminary Assessment of Interprofessional Education Focused on Vulnerable Populations.

J Allied Health 2018 ;47(3):e75-e81

DPT Program, University of Texas at El Paso, 500 West University Ave., El Paso, TX 79968, USA. Tel 915-747-7289, fax 915-747-8211.

With the current state of the U.S. healthcare system, interprofessional collaborative practice (IPCP) has never been more important. Health professions educators are increasingly incorporating interprofessional education (IPE) in their curricula in order to prepare students for IPCP. The Health- Focused IPE Community of Practice (representing nursing, occupational therapy, pharmacy, physical therapy, rehabilitation counseling, social work, and speech-language pathology) at the University of Texas at El Paso has created a unique IPE model centered on vulnerable populations. The purposes of this paper are to describe the early development of this innovative IPE model and present findings from an evaluation of an IPE learning experience focused on a case involving a transgender individual. The evaluation of the first IPE activity demonstrated that the students' knowledge and attitudes related to interprofessional collaboration improved for all participating professions. Additionally, the post-training evaluation revealed that students were more comfortable providing services to transgender individuals than interacting with them. This IPE model has leveraged the strengths of community-engaged faculty in order to infuse content related to vulnerable populations across multiple curricula. This holistic approach models to the students that complex problems require multifaceted solutions generated by IPCP.
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January 2019

Developing Trans-Affirming Health Services in an Underserved Area: An Intersectional Approach.

Transgend Health 2018 1;3(1):127-135. Epub 2018 Jul 1.

Department of Pediatrics, Texas Tech University Health Sciences Center, El Paso, El Paso, Texas.

Gender-nonconforming patients are at higher risk for medical problems that require prompt medical and mental health intervention. Barriers to healthcare for transgender individuals have been well characterized in the literature, but not in low resource settings. The purpose of this paper is to present the barriers encountered when bringing healthcare to transgender children, adolescents, and adults in a medically underserved, predominantly Hispanic area of the United States. In this medically underserved area on the U.S.-Mexico border, there is a severe shortage of medical expertise for transgender individuals at both the primary- and specialty-care levels. Further, given the mainly Hispanic population, there is an additional culturally based barrier to obtaining medical care for transgender patients. It is important for academic centers in these regions to collaborate to overcome these barriers through a multidisciplinary approach that includes providing education for medical students and physicians in training and identifying medical providers who are able and willing to provide transgender-competent care adapted to local culture and gender norms. In this manuscript, we will describe the efforts of various groups to address the needs of the transgender community in the region.
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http://dx.doi.org/10.1089/trgh.2018.0011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6049340PMC
July 2018

Stabilisation of gold nanoparticles by N-heterocyclic thiones.

Dalton Trans 2017 Jul;46(26):8367-8371

Instituto de Investigaciones Químicas (IIQ), CSIC and Universidad de Sevilla, Avda. Américo Vespucio 49, 41092 Sevilla, Spain.

Gold nanoparticles (Au-NPs) have been prepared using N-heterocyclic thiones (NHTs) as ligand stabilisers. These Au-NPs have been shown to be very stable, even in air, and have been characterized by a combination of several techniques (TEM, HR-TEM, STEM-HAADF, EDX, DLS, elemental analysis and H NMR). These nanoparticles are active in the catalytic reduction of nitroarenes to anilines.
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http://dx.doi.org/10.1039/c7dt01856hDOI Listing
July 2017

Refined topology model of the STT3/Stt3 protein subunit of the oligosaccharyltransferase complex.

J Biol Chem 2017 07 16;292(27):11349-11360. Epub 2017 May 16.

From the Department of Biochemistry and Biophysics, Stockholm University, SE-10691 Stockholm, Sweden and

The oligosaccharyltransferase complex, localized in the endoplasmic reticulum (ER) of eukaryotic cells, is responsible for the -linked glycosylation of numerous protein substrates. The membrane protein STT3 is a highly conserved part of the oligosaccharyltransferase and likely contains the active site of the complex. However, understanding the catalytic determinants of this system has been challenging, in part because of a discrepancy in the structural topology of the bacterial eukaryotic proteins and incomplete information about the mechanism of membrane integration. Here, we use a glycosylation mapping approach to investigate these questions. We measured the membrane integration efficiency of the mouse STT3-A and yeast Stt3p transmembrane domains (TMDs) and report a refined topology of the N-terminal half of the mouse STT3-A. Our results show that most of the STT3 TMDs are well inserted into the ER membrane on their own or in the presence of the natural flanking residues. However, for the mouse STT3-A hydrophobic domains 4 and 6 and yeast Stt3p domains 2, 3a, 3c, and 6 we measured reduced insertion efficiency into the ER membrane. Furthermore, we mapped the first half of the STT3-A protein, finding two extra hydrophobic domains between the third and the fourth TMD. This result indicates that the eukaryotic STT3 has 13 transmembrane domains, consistent with the structure of the bacterial homolog of STT3 and setting the stage for future combined efforts to interrogate this fascinating system.
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http://dx.doi.org/10.1074/jbc.M117.779421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5500801PMC
July 2017

Gene Duplication Leads to Altered Membrane Topology of a Cytochrome P450 Enzyme in Seed Plants.

Mol Biol Evol 2017 08;34(8):2041-2056

Centre National de la Recherche Scientifique, Institute of Plant Molecular Biology, University of Strasbourg, Strasbourg, France.

Evolution of the phenolic metabolism was critical for the transition of plants from water to land. A cytochrome P450, CYP73, with cinnamate 4-hydroxylase (C4H) activity, catalyzes the first plant-specific and rate-limiting step in this pathway. The CYP73 gene is absent from green algae, and first detected in bryophytes. A CYP73 duplication occurred in the ancestor of seed plants and was retained in Taxaceae and most angiosperms. In spite of a clear divergence in primary sequence, both paralogs can fulfill comparable cinnamate hydroxylase roles both in vitro and in vivo. One of them seems dedicated to the biosynthesis of lignin precursors. Its N-terminus forms a single membrane spanning helix and its properties and length are highly constrained. The second is characterized by an elongated and variable N-terminus, reminiscent of ancestral CYP73s. Using as proxies the Brachypodium distachyon proteins, we show that the elongation of the N-terminus does not result in an altered subcellular localization, but in a distinct membrane topology. Insertion in the membrane of endoplasmic reticulum via a double-spanning open hairpin structure allows reorientation to the lumen of the catalytic domain of the protein. In agreement with participation to a different functional unit and supramolecular organization, the protein displays modified heme proximal surface. These data suggest the evolution of divergent C4H enzymes feeding different branches of the phenolic network in seed plants. It shows that specialization required for retention of gene duplicates may result from altered protein topology rather than change in enzyme activity.
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http://dx.doi.org/10.1093/molbev/msx160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850782PMC
August 2017

Energetics of side-chain snorkeling in transmembrane helices probed by nonproteinogenic amino acids.

Proc Natl Acad Sci U S A 2016 09 6;113(38):10559-64. Epub 2016 Sep 6.

Department of Biochemistry and Biophysics, Center for Biomembrane Research, Stockholm University, SE-106 91 Stockholm, Sweden; Science for Life Laboratory, Stockholm University, SE-171 21 Solna, Sweden

Cotranslational translocon-mediated insertion of membrane proteins into the endoplasmic reticulum is a key process in membrane protein biogenesis. Although the mechanism is understood in outline, quantitative data on the energetics of the process is scarce. Here, we have measured the effect on membrane integration efficiency of nonproteinogenic analogs of the positively charged amino acids arginine and lysine incorporated into model transmembrane segments. We provide estimates of the influence on the apparent free energy of membrane integration (ΔGapp) of "snorkeling" of charged amino acids toward the lipid-water interface, and of charge neutralization. We further determine the effect of fluorine atoms and backbone hydrogen bonds (H-bonds) on ΔGapp These results help establish a quantitative basis for our understanding of membrane protein assembly in eukaryotic cells.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5035864PMC
http://dx.doi.org/10.1073/pnas.1606776113DOI Listing
September 2016

Membrane insertion and topology of the amino-terminal domain TMD0 of multidrug-resistance associated protein 6 (MRP6).

FEBS Lett 2015 Dec 3;589(24 Pt B):3921-8. Epub 2015 Nov 3.

Department of Sciences, University of Basilicata, 85100 Potenza, Italy. Electronic address:

The function of the ATP-binding cassette transporter MRP6 is unknown but mutations in its gene cause pseudoxanthoma elasticum. We have investigated the membrane topology of the N-terminal transmembrane domain TMD0 of MRP6 and the membrane integration and orientation propensities of its transmembrane segments (TMs) by glycosylation mapping. Results demonstrate that TMD0 has five TMs, an Nout-Cin topology and that the less hydrophobic TMs have strong preference for their orientation in the membrane that affects the neighboring TMs. Two disease-causing mutations changing the number of positive charges in the loops of TMD0 did not affect the membrane insertion efficiencies of the adjacent TMs.
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http://dx.doi.org/10.1016/j.febslet.2015.10.030DOI Listing
December 2015

New Route to Stabilize Ruthenium Nanoparticles with Non-Isolable Chiral N-Heterocyclic Carbenes.

Chemistry 2015 Nov 20;21(48):17495-502. Epub 2015 Oct 20.

Laboratoire de Physique et Chimie des Nano-Objets, UMR5215 INSA-CNRS-UPS, Institut des Sciences appliquées, 135, Avenue de Rangueil, 31077 Toulouse (France).

Ru nanoparticles (RuNPs) stabilized by non-isolable chiral N-heterocyclic carbenes (NHCs), namely SIDPhNp ((4S,5S)-1,3-di(naphthalen-1-yl)-4,5-diphenylimidazolidine) and SIPhOH ((S)-3-((1S,2R)-2-hydroxy-1,2-diphenylethyl)-1-((R)-2-hydroxy-1,2-diphenylethyl)-4,5-dihydro-3H-imidazoline), have been synthesized through a new procedure that does not require isolation of the free carbenes. The obtained RuNPs have been characterized by state-of-the-art techniques and their surface chemistry has been investigated by FTIR and solid-state MAS NMR upon the coordination of CO, which indicated the presence of free and reactive Ru sites. Their catalytic activity has been tested in various hydrogenation reactions involving competition between different sites, whereby interesting differences in selectivity were observed, but no enantioselectivity.
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http://dx.doi.org/10.1002/chem.201502601DOI Listing
November 2015

Folding and Intramembraneous BRICHOS Binding of the Prosurfactant Protein C Transmembrane Segment.

J Biol Chem 2015 Jul 3;290(28):17628-41. Epub 2015 Jun 3.

From the Department of Biochemistry and Molecular Biology I, Complutense University of Madrid, 28040 Madrid, Spain, the Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain,

Surfactant protein C (SP-C) is a novel amyloid protein found in the lung tissue of patients suffering from interstitial lung disease (ILD) due to mutations in the gene of the precursor protein pro-SP-C. SP-C is a small α-helical hydrophobic protein with an unusually high content of valine residues. SP-C is prone to convert into β-sheet aggregates, forming amyloid fibrils. Nature's way of solving this folding problem is to include a BRICHOS domain in pro-SP-C, which functions as a chaperone for SP-C during biosynthesis. Mutations in the pro-SP-C BRICHOS domain or linker region lead to amyloid formation of the SP-C protein and ILD. In this study, we used an in vitro transcription/translation system to study translocon-mediated folding of the WT pro-SP-C poly-Val and a designed poly-Leu transmembrane (TM) segment in the endoplasmic reticulum (ER) membrane. Furthermore, to understand how the pro-SP-C BRICHOS domain present in the ER lumen can interact with the TM segment of pro-SP-C, we studied the membrane insertion properties of the recombinant form of the pro-SP-C BRICHOS domain and two ILD-associated mutants. The results show that the co-translational folding of the WT pro-SP-C TM segment is inefficient, that the BRICHOS domain inserts into superficial parts of fluid membranes, and that BRICHOS membrane insertion is promoted by poly-Val peptides present in the membrane. In contrast, one BRICHOS and one non-BRICHOS ILD-associated mutant could not insert into membranes. These findings support a chaperone function of the BRICHOS domain, possibly together with the linker region, during pro-SP-C biosynthesis in the ER.
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http://dx.doi.org/10.1074/jbc.M114.630343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4498095PMC
July 2015

Ruthenium(II) Complexes Containing Lutidine-Derived Pincer CNC Ligands: Synthesis, Structure, and Catalytic Hydrogenation of C-N bonds.

Chemistry 2015 May 27;21(20):7540-55. Epub 2015 Mar 27.

Centro de Investigaciones Químicas, Universidad Autónoma del Estado de Hidalgo, Carretera Pachuca-Tulacingo Km 4.5, 42184 Mineral de la Reforma, Hidalgo (Mexico).

A series of Ru complexes containing lutidine-derived pincer CNC ligands have been prepared by transmetalation with the corresponding silver-carbene derivatives. Characterization of these derivatives shows both mer and fac coordination of the CNC ligands depending on the wingtips of the N-heterocyclic carbene fragments. In the presence of tBuOK, the Ru-CNC complexes are active in the hydrogenation of a series of imines. In addition, these complexes catalyze the reversible hydrogenation of phenantridine. Detailed NMR spectroscopic studies have shown the capability of the CNC ligand to be deprotonated and get involved in ligand-assisted activation of dihydrogen. More interestingly, upon deprotonation, the Ru-CNC complex 5 e(BF4 ) is able to add aldimines to the metal-ligand framework to yield an amido complex. Finally, investigation of the mechanism of the hydrogenation of imines has been carried out by means of DFT calculations. The calculated mechanism involves outer-sphere stepwise hydrogen transfer to the C-N bond assisted either by the pincer ligand or a second coordinated H2 molecule.
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http://dx.doi.org/10.1002/chem.201406040DOI Listing
May 2015

RIFINs are adhesins implicated in severe Plasmodium falciparum malaria.

Nat Med 2015 Apr 9;21(4):314-7. Epub 2015 Mar 9.

Center for Infectious Disease Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.

Rosetting is a virulent Plasmodium falciparum phenomenon associated with severe malaria. Here we demonstrate that P. falciparum-encoded repetitive interspersed families of polypeptides (RIFINs) are expressed on the surface of infected red blood cells (iRBCs), where they bind to RBCs--preferentially of blood group A--to form large rosettes and mediate microvascular binding of iRBCs. We suggest that RIFINs have a fundamental role in the development of severe malaria and thereby contribute to the varying global distribution of ABO blood groups in the human population.
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http://dx.doi.org/10.1038/nm.3812DOI Listing
April 2015

Live-cell topology assessment of URG7, MRP6₁₀₂ and SP-C using glycosylatable green fluorescent protein in mammalian cells.

Biochem Biophys Res Commun 2014 Aug 15;450(4):1587-92. Epub 2014 Jul 15.

School of Biological Sciences, Seoul National University, Seoul 151-747, South Korea. Electronic address:

Experimental tools to determine membrane topology of a protein are rather limited in higher eukaryotic organisms. Here, we report the use of glycosylatable GFP (gGFP) as a sensitive and versatile membrane topology reporter in mammalian cells. gGFP selectively loses its fluorescence upon N-linked glycosylation in the ER lumen. Thus, positive fluorescence signal assigns location of gGFP to the cytosol whereas no fluorescence signal and a glycosylated status of gGFP map the location of gGFP to the ER lumen. By using mammalian gGFP, the membrane topology of disease-associated membrane proteins, URG7, MRP6102, SP-C(Val) and SP-C(Leu) was confirmed. URG7 is partially targeted to the ER, and inserted in Cin form. MRP6102 and SP-C(Leu/Val) are inserted into the membrane in Cout form. A minor population of untargeted SP-C is removed by proteasome dependent quality control system.
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http://dx.doi.org/10.1016/j.bbrc.2014.07.046DOI Listing
August 2014

The code for directing proteins for translocation across ER membrane: SRP cotranslationally recognizes specific features of a signal sequence.

J Mol Biol 2015 Mar 28;427(6 Pt A):1191-201. Epub 2014 Jun 28.

Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75235, USA. Electronic address:

The signal recognition particle (SRP) cotranslationally recognizes signal sequences of secretory proteins and targets ribosome-nascent chain complexes to the SRP receptor in the endoplasmic reticulum membrane, initiating translocation of the nascent chain through the Sec61 translocon. Although signal sequences do not have homology, they have similar structural regions: a positively charged N-terminus, a hydrophobic core and a more polar C-terminal region that contains the cleavage site for the signal peptidase. Here, we have used site-specific photocrosslinking to study SRP-signal sequence interactions. A photoreactive probe was incorporated into the middle of wild-type or mutated signal sequences of the secretory protein preprolactin by in vitro translation of mRNAs containing an amber-stop codon in the signal peptide in the presence of the N(ε)-(5-azido-2 nitrobenzoyl)-Lys-tRNA(amb) amber suppressor. A homogeneous population of SRP-ribosome-nascent chain complexes was obtained by the use of truncated mRNAs in translations performed in the presence of purified canine SRP. Quantitative analysis of the photoadducts revealed that charged residues at the N-terminus of the signal sequence or in the early part of the mature protein have only a mild effect on the SRP-signal sequence association. However, deletions of amino acid residues in the hydrophobic portion of the signal sequence severely affect SRP binding. The photocrosslinking data correlate with targeting efficiency and translocation across the membrane. Thus, the hydrophobic core of the signal sequence is primarily responsible for its recognition and binding by SRP, while positive charges fine-tune the SRP-signal sequence affinity and targeting to the translocon.
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http://dx.doi.org/10.1016/j.jmb.2014.06.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4277940PMC
March 2015

Changed membrane integration and catalytic site conformation are two mechanisms behind the increased Aβ42/Aβ40 ratio by presenilin 1 familial Alzheimer-linked mutations.

FEBS Open Bio 2014 24;4:393-406. Epub 2014 Apr 24.

Department of NVS, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden.

The enzyme complex γ-secretase generates amyloid β-peptide (Aβ), a 37-43-residue peptide associated with Alzheimer disease (AD). Mutations in presenilin 1 (PS1), the catalytical subunit of γ-secretase, result in familial AD (FAD). A unifying theme among FAD mutations is an alteration in the ratio Aβ species produced (the Aβ42/Aβ40 ratio), but the molecular mechanisms responsible remain elusive. In this report we have studied the impact of several different PS1 FAD mutations on the integration of selected PS1 transmembrane domains and on PS1 active site conformation, and whether any effects translate to a particular amyloid precursor protein (APP) processing phenotype. Most mutations studied caused an increase in the Aβ42/Aβ40 ratio, but via different mechanisms. The mutations that caused a particular large increase in the Aβ42/Aβ40 ratio did also display an impaired APP intracellular domain (AICD) formation and a lower total Aβ production. Interestingly, seven mutations close to the catalytic site caused a severely impaired integration of proximal transmembrane/hydrophobic sequences into the membrane. This structural defect did not correlate to a particular APP processing phenotype. Six selected FAD mutations, all of which exhibited different APP processing profiles and impact on PS1 transmembrane domain integration, were found to display an altered active site conformation. Combined, our data suggest that FAD mutations affect the PS1 structure and active site differently, resulting in several complex APP processing phenotypes, where the most aggressive mutations in terms of increased Aβ42/Aβ40 ratio are associated with a decrease in total γ-secretase activity.
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http://dx.doi.org/10.1016/j.fob.2014.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4050182PMC
June 2014

Probing the surface of platinum nanoparticles with 13CO by solid-state NMR and IR spectroscopies.

Nanoscale 2014 Jan 15;6(1):539-46. Epub 2013 Nov 15.

CNRS, LCC (Laboratoire de Chimie de Coordination du CNRS), BP 44099, 205 Route de Narbonne, F-31077 Toulouse Cedex 4, France.

The synthesis and full characterization of platinum nanoparticles (Pt NPs) prepared by decomposition of the Pt(dba)2 complex in the presence of CO and H2 and stabilized either sterically by a polymer, polyvinylpyrrolidone or chemically by a ligand, diphenylphosphinobutane, are reported. In these studies, (13)CO was used as a probe molecule to investigate the surface of the particles, using IR and solid-state NMR spectroscopies with magic angle spinning (MAS-NMR). Three nanosystems with different sizes are described: Pt/PVP/(13)CO (monomodal: 1.2 nm), Pt/dppb/(13)CO (bimodal: 1.2 nm and 2.0 nm) and Pt/dppb/H2 (monomodal: 2.0 nm) NPs. Spectroscopic data suggest a modification of the electronic state of the nanoparticles between 1.2 nm and 2.0 nm which can be related to the presence of Knight shift.
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http://dx.doi.org/10.1039/c3nr03948jDOI Listing
January 2014

On the influence of diphosphine ligands on the chemical order in small RuPt nanoparticles: combined structural and surface reactivity studies.

Dalton Trans 2013 Jan 15;42(2):372-82. Epub 2012 Oct 15.

CNRS, LCC (Laboratoire de Chimie de Coordination), 205, Route de Narbonne, F-31077 Toulouse, France.

Diphenylphosphinobutane (dppb) stabilized bimetallic RuPt nanoparticles were prepared by co-decomposition of [Ru(COD)(COT)] [(1,5-cyclooctadiene)(1,3,5-cyclooctatriene)ruthenium] and [Pt(CH(3))(2)(COD)] [dimethyl(1,5-cyclooctadiene) platinum(II)] organometallic precursors under mild conditions (room temperature, 3 bar of dihydrogen) and in the presence of dppb. The determination of the nanoparticles' chemical composition was made possible thanks to a combination of several characterization techniques (HREM, STEM-HAADF, WAXS, EXAFS, IR, NMR) associated with surface reactivity studies based on simple catalytic reactions. The obtained nanoparticles display a ruthenium rich core and a disordered shell containing both ruthenium and platinum. The results were compared with those obtained on nanoparticles of similar size and composition but not containing ligands. The complexity observed in the present structure of these nanoparticles arises from the high chemical affinity of the diphosphine ligand used as a stabilizer for both metals.
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http://dx.doi.org/10.1039/c2dt31646cDOI Listing
January 2013

Carbon-supported palladium and ruthenium nanoparticles: application as catalysts in alcohol oxidation, cross-coupling and hydrogenation reactions.

Recent Pat Nanotechnol 2013 Nov;7(3):247-64

CNRS; LCC (Laboratoire de Chimie de Coordination); 205, Route de Narbonne, F-31077 Toulouse, France; Université de Toulouse; UPS, INPT; LCC; F-317077 Toulouse, France.

In the last fifteen-years, the application of metal nanoparticles as catalysts in organic synthesis has received a renewed interest. Therefore, much attention is currently being paid to the synthesis of metal nanoparticles in order to achieve the control of their characteristics in terms of size, shape and surface chemistry. Besides this, the recyclability as well as the recovery from the reaction medium still remain the major drawbacks to widespread the use of nanoparticles in catalysis. To overcome these problems, the immobilization of metal nanoparticles on solid supports appears as a promising alternative. In that context, carbon materials offer several advantages as solid supports such as availability, relatively low cost, high mechanical strength, chemical stability, and a pore structure along with an attractive surface chemistry which allows easy modifications, such as its functionalization, to suit the nanoparticles immobilization needs. Among the transition metals Palladium and Ruthenium are widely employed as efficient catalysts in many reactions. Herein, the most recent advances, from recent papers and patents, in relation to the preparation of carbon-supported Pd or Ru nanoparticles systems as well as their application as catalysts in alcohol oxidation, cross-coupling or hydrogenation reactions, are reviewed.
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http://dx.doi.org/10.2174/187221050703131127110716DOI Listing
November 2013

Ruthenium nanoparticles stabilized by N-heterocyclic carbenes: ligand location and influence on reactivity.

Angew Chem Int Ed Engl 2011 Dec 28;50(50):12080-4. Epub 2011 Oct 28.

CNRS, Laboratoire de Chimie de Coordination, 205, Route de Narbonne, 31077 Toulouse, France.

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http://dx.doi.org/10.1002/anie.201106348DOI Listing
December 2011

Synthetic, mechanistic, and theoretical studies on the generation of iridium hydride alkylidene and iridium hydride alkene isomers.

Chemistry 2009 Sep;15(36):9046-57

Instituto de Investigaciones Químicas and Departamento de Química Inorgánica, Consejo Superior de Investigaciones Científicas and Universidad de Sevilla, Av. Américo Vespucio 49, Isla de la Cartuja, 41092 Sevilla, Spain.

Experimental and theoretical studies on equilibria between iridium hydride alkylidene structures, [(Tp(Me2))Ir(H){=C(CH(2)R)ArO}] (Tp(Me2) = hydrotris(3,5-dimethylpyrazolyl)borate; R = H, Me; Ar = substituted C(6)H(4) group), and their corresponding hydride olefin isomers, [(Tp(Me2))Ir(H){R(H)C=C(H)OAr}], have been carried out. Compounds of these types are obtained either by reaction of the unsaturated fragment [(Tp(Me2))Ir(C(6)H(5))(2)] with o-C(6)H(4)(OH)CH(2)R, or with the substituted anisoles 2,6-Me(2)C(6)H(3)OMe, 2,4,6-Me(3)C(6)H(2)OMe, and 4-Br-2,6-Me(2)C(6)H(2)OMe. The reactions with the substituted anisoles require not only multiple C-H bond activation but also cleavage of the Me-OAr bond and the reversible formation of a C-C bond (as revealed by (13)C labeling studies). Equilibria between the two tautomeric structures of these complexes were achieved by prolonged heating at temperatures between 100 and 140 degrees C, with interconversion of isomeric complexes requiring inversion of the metal configuration, as well as the expected migratory insertion and hydrogen-elimination reactions. This proposal is supported by a detailed computational exploration of the mechanism at the quantum mechanics (QM) level in the real system. For all compounds investigated, the equilibria favor the alkylidene structure over the olefinic isomer by a factor of between approximately 1 and 25. Calculations demonstrate that the main reason for this preference is the strong Ir-carbene interactions in the carbene isomers, rather than steric destabilization of the olefinic tautomers.
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http://dx.doi.org/10.1002/chem.200900654DOI Listing
September 2009

Experimental and computational studies on the iridium activation of aliphatic and aromatic C-H bonds of alkyl aryl ethers and related molecules.

Chemistry 2009 Sep;15(36):9034-45

Instituto de Investigaciones Químicas and Departamento de Química Inorgánica, Consejo Superior de Investigaciones Científicas and Universidad de Sevilla, Av. Américo Vespucio 49, Isla de la Cartuja, 41092 Sevilla, Spain.

Reaction of the Ir(III) complex [(Tp(Me2))Ir(C(6)H(5))(2)(N(2))] (1N(2)) with ortho-cresol (2-methylphenol) occurs with cleavage of the O-H and two C(sp(3))-H bonds of the phenol and formation of the electrophilic hydride alkylidene derivative [(Tp(Me2))Ir(H){=C(H)C(6)H(4)-o-O}] (2). The analogous reaction of 2-ethylphenol gives a related product 3. Both 2 and 3 have been shown to be identical to the minor, unidentified products of the already reported reactions of 1 with anisole and phenetole, respectively. Thus, in addition to the route that leads to the known heteroatom-stabilized hydride carbene [(Tp(Me2))Ir(H){=C(H)OC(6)H(4)-o-}] (B), anisole can react with 1 with cleavage of the O-CH(3) bond and formation of a new carbon-carbon bond. In contrast, only C-H bond-activation products with structures akin to B result from 1N(2) and 3,5-dimethylanisole (complex 8) or 4-fluoroanisole (9). Using anisole as a model, a computational study of the triple C-H bond activation (two aliphatic C-H bonds plus an ortho-metalation reaction) that is responsible for the formation of these heteroatom-stabilized hydride carbenes has been undertaken.
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http://dx.doi.org/10.1002/chem.200900646DOI Listing
September 2009

Monodentate, N-heterocyclic carbene-type coordination of 2,2'-bipyridine and 1,10-phenanthroline to iridium.

Angew Chem Int Ed Engl 2008 ;47(23):4380-3

Instituto de Investigaciones Químicas, Departamento de Química Inorgánica, Consejo Superior de Investigaciones Científicas, Universidad de Sevilla, Avda. Américo Vespucio 49, Isla de la Cartuja, 41092 Sevilla, Spain.

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http://dx.doi.org/10.1002/anie.200800705DOI Listing
July 2008

Rearrangement of pyridine to its 2-carbene tautomer mediated by iridium.

J Am Chem Soc 2007 Nov 31;129(46):14130-1. Epub 2007 Oct 31.

Instituto de Investigaciones Químicas, Departamento de Química InorgAnica, CSIC, Universidad de Sevilla, Avda. Américo Vespucio 49, 41092 Sevilla, Spain.

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http://dx.doi.org/10.1021/ja075685iDOI Listing
November 2007

Formation and cleavage of C-H, C-C, and C-O bonds of ortho-methyl-substituted anisoles by late transition metals.

J Am Chem Soc 2006 Mar;128(11):3512-3

Instituto de Investigaciones Químicas, Departamento de Química Inorganica, CSIC, Universidad de Sevilla, Avda. Américo Vespucio no 49, 41092 Sevilla, Spain.

2,6-Dimethyl-substituted anisoles can be converted into the corresponding 2-ethyl-6-methylphenols in a several-step reaction mediated by a TpMe2Ir(III) complex; use of the 13C-enriched anisoles, ArO13CH3, shows that the 13C label distributes across the two ethyl sites with a preference for the terminal position.
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http://dx.doi.org/10.1021/ja0586790DOI Listing
March 2006