Lucas Nguyen - Academia.edu (original) (raw)
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Papers by Lucas Nguyen
Systemic hypoxia, a major complication associated with reduced gestational time, affects more 60%... more Systemic hypoxia, a major complication associated with reduced gestational time, affects more 60% of preterm infants and is a known driver of hypoxia-induced Bcl-2-like 19kDa-interacting protein 3 (Bnip3) expression in the neonatal heart. At the level of the cardiomyocyte, Bnip3 activity plays a prominent role in the evolution of necrotic cell death, disrupting subcellular calcium homeostasis and initiating mitochondrial permeability transition (MPT). Emerging evidence suggests both a cardioprotective role for protein kinase A (PKA) through stimulatory prostaglandin (PG) E1 signalling during prolonged periods of hypoxia, and a cytoprotective role for Bnip3 phosphorylation, indicating that post-translational modifications of Bnip3 may be a point of convergence for these two protective pathways. Using a combination of in vivo and multiple cell models, including human iPSC-derived cardiomyocytes, we tested if the PGE1 analogue misoprostol is cardioprotective during neonatal hypoxic inj...
Lipotoxicity is a form of cellular stress caused by the accumulation of lipids resulting in mitoc... more Lipotoxicity is a form of cellular stress caused by the accumulation of lipids resulting in mitochondrial dysfunction and insulin resistance in muscle. Previously, we demonstrated that the mitophagy receptor Nix is responsive to lipotoxicity and accumulates in response to diacylglycerols induced by high-fat (HF) feeding. In addition, previous studies have implicated autophagy and mitophagy in muscle insulin sensitivity. To provide a better understanding of these observations, we undertook a gene expression array and shot-gun metabolomics studies in soleus muscle from rodents on an HF diet. Interestingly, we observed a modest reduction in several autophagy-related genes including Beclin-1, ATG3, and -5. Moreover, we observed alterations in the composition of cardiolipins and phosphatidic acids. Given the previously reported roles of these phospholipids and Nix in mitochondrial dynamics, we investigated aberrant mitochondrial fission and turn-over as a mechanism of myocyte insulin res...
Journal of the American Chemical Society, Jan 3, 2014
While olefin amination with aminium radical cations is a classical method for C-N bond formation,... more While olefin amination with aminium radical cations is a classical method for C-N bond formation, catalytic variants that utilize simple 2° amine precursors remain largely undeveloped. Herein we report a new visible-light photoredox protocol for the intramolecular anti-Markovnikov hydroamination of aryl olefins that proceeds through catalytically generated aminium radical intermediates. Mechanistic studies are consistent with a process involving amine oxidation via electron transfer, turnover-limiting C-N bond formation, and a second electron transfer step to reduce a carbon-centered radical, rendering the overall process redox-neutral. A range of structurally diverse N-aryl heterocycles can be prepared in good to excellent yields under conditions significantly milder than those required by conventional aminium-based protocols.
Molecular Physics, 2015
ABSTRACT Molar absorption coefficients were measured for select alkyl nitrates and β-hydroxyalkyl... more ABSTRACT Molar absorption coefficients were measured for select alkyl nitrates and β-hydroxyalkyl nitrates in methanol. The presence of the β-hydroxyl group has a relatively minor effect on the absorption spectrum in the vicinity of the weak n → π* transition, which is responsible for photolysis of organic nitrates in the atmosphere. For both alkyl nitrates and β-hydroxyalkyl nitrates, there is an enhancement in the absorption coefficients in solution compared to the gas-phase values. The effect of the β-hydroxyl group on the spectra was modelled with molecular dynamics simulations using an OM2/GUGA-CI Hamiltonian for ethyl nitrate and β-hydroxyethyl nitrate. The simulation provided a qualitatively correct shape of the low energy tail of the absorption spectrum, which is important for atmospheric photochemistry. The role of direct aqueous photolysis in removal of β-hydroxyalkyl nitrates in cloud and fog water was modelled using a relative rate approach, and shown to be insignificant relative to gas-phase photochemical processes and aqueous OH oxidation under typical atmospheric conditions.
Canadian Journal of Diabetes, 2014
The Journal of Organic Chemistry, 2012
A full account of the development of the base-mediated intramolecular Diels-Alder cycloadditions ... more A full account of the development of the base-mediated intramolecular Diels-Alder cycloadditions of tryptamine-derived Zincke aldehydes is described. This important complexity-generating transformation provides the tetracyclic core of many indole monoterpene alkaloids in only three steps from commercially available starting materials and played a key role in short syntheses of norfluorocurarine (five steps), dehydrodesacetylretuline (six steps), valparicine (seven steps), and strychnine (six steps). Reasonable mechanistic possibilities for this reaction, a surprisingly facile dimerization of the products, and an unexpected cycloreversion to regenerate Zincke aldehydes under specific conditions are also discussed.
Analytical Chemistry, 2010
Systemic hypoxia, a major complication associated with reduced gestational time, affects more 60%... more Systemic hypoxia, a major complication associated with reduced gestational time, affects more 60% of preterm infants and is a known driver of hypoxia-induced Bcl-2-like 19kDa-interacting protein 3 (Bnip3) expression in the neonatal heart. At the level of the cardiomyocyte, Bnip3 activity plays a prominent role in the evolution of necrotic cell death, disrupting subcellular calcium homeostasis and initiating mitochondrial permeability transition (MPT). Emerging evidence suggests both a cardioprotective role for protein kinase A (PKA) through stimulatory prostaglandin (PG) E1 signalling during prolonged periods of hypoxia, and a cytoprotective role for Bnip3 phosphorylation, indicating that post-translational modifications of Bnip3 may be a point of convergence for these two protective pathways. Using a combination of in vivo and multiple cell models, including human iPSC-derived cardiomyocytes, we tested if the PGE1 analogue misoprostol is cardioprotective during neonatal hypoxic inj...
Lipotoxicity is a form of cellular stress caused by the accumulation of lipids resulting in mitoc... more Lipotoxicity is a form of cellular stress caused by the accumulation of lipids resulting in mitochondrial dysfunction and insulin resistance in muscle. Previously, we demonstrated that the mitophagy receptor Nix is responsive to lipotoxicity and accumulates in response to diacylglycerols induced by high-fat (HF) feeding. In addition, previous studies have implicated autophagy and mitophagy in muscle insulin sensitivity. To provide a better understanding of these observations, we undertook a gene expression array and shot-gun metabolomics studies in soleus muscle from rodents on an HF diet. Interestingly, we observed a modest reduction in several autophagy-related genes including Beclin-1, ATG3, and -5. Moreover, we observed alterations in the composition of cardiolipins and phosphatidic acids. Given the previously reported roles of these phospholipids and Nix in mitochondrial dynamics, we investigated aberrant mitochondrial fission and turn-over as a mechanism of myocyte insulin res...
Journal of the American Chemical Society, Jan 3, 2014
While olefin amination with aminium radical cations is a classical method for C-N bond formation,... more While olefin amination with aminium radical cations is a classical method for C-N bond formation, catalytic variants that utilize simple 2° amine precursors remain largely undeveloped. Herein we report a new visible-light photoredox protocol for the intramolecular anti-Markovnikov hydroamination of aryl olefins that proceeds through catalytically generated aminium radical intermediates. Mechanistic studies are consistent with a process involving amine oxidation via electron transfer, turnover-limiting C-N bond formation, and a second electron transfer step to reduce a carbon-centered radical, rendering the overall process redox-neutral. A range of structurally diverse N-aryl heterocycles can be prepared in good to excellent yields under conditions significantly milder than those required by conventional aminium-based protocols.
Molecular Physics, 2015
ABSTRACT Molar absorption coefficients were measured for select alkyl nitrates and β-hydroxyalkyl... more ABSTRACT Molar absorption coefficients were measured for select alkyl nitrates and β-hydroxyalkyl nitrates in methanol. The presence of the β-hydroxyl group has a relatively minor effect on the absorption spectrum in the vicinity of the weak n → π* transition, which is responsible for photolysis of organic nitrates in the atmosphere. For both alkyl nitrates and β-hydroxyalkyl nitrates, there is an enhancement in the absorption coefficients in solution compared to the gas-phase values. The effect of the β-hydroxyl group on the spectra was modelled with molecular dynamics simulations using an OM2/GUGA-CI Hamiltonian for ethyl nitrate and β-hydroxyethyl nitrate. The simulation provided a qualitatively correct shape of the low energy tail of the absorption spectrum, which is important for atmospheric photochemistry. The role of direct aqueous photolysis in removal of β-hydroxyalkyl nitrates in cloud and fog water was modelled using a relative rate approach, and shown to be insignificant relative to gas-phase photochemical processes and aqueous OH oxidation under typical atmospheric conditions.
Canadian Journal of Diabetes, 2014
The Journal of Organic Chemistry, 2012
A full account of the development of the base-mediated intramolecular Diels-Alder cycloadditions ... more A full account of the development of the base-mediated intramolecular Diels-Alder cycloadditions of tryptamine-derived Zincke aldehydes is described. This important complexity-generating transformation provides the tetracyclic core of many indole monoterpene alkaloids in only three steps from commercially available starting materials and played a key role in short syntheses of norfluorocurarine (five steps), dehydrodesacetylretuline (six steps), valparicine (seven steps), and strychnine (six steps). Reasonable mechanistic possibilities for this reaction, a surprisingly facile dimerization of the products, and an unexpected cycloreversion to regenerate Zincke aldehydes under specific conditions are also discussed.
Analytical Chemistry, 2010