Publications by authors named "Thomas J Meyer"

277 Publications

Small-Molecule Natural Product Physachenolide C Potentiates Immunotherapy Efficacy by Targeting BET Proteins.

Cancer Res 2021 Apr 9. Epub 2021 Apr 9.

Basic Science Program, Frederick National Laboratory for Cancer Research.

Screening for sensitizers of cancer cells to TRAIL-mediated apoptosis identified a natural product (NP) of the 17β-hydroxywithanolide (17-BHW) class, physachenolide C (PCC), as a promising hit. In this study, we show that PCC was also able to sensitize melanoma and renal carcinoma cells to apoptosis in response not only to TRAIL, but also to the synthetic polynucleotide poly I:C, a viral mimetic and immune activator, by reducing levels of anti-apoptotic proteins cFLIP and Livin. Both death receptor and TLR3 signaling elicited subsequent increased assembly of a pro-apoptotic ripoptosome signaling complex. Administration of a combination of PCC and poly I:C in human M14 melanoma xenograft and a syngeneic B16 melanoma model provided significant therapeutic benefit as compared to individual agents. Additionally, PCC enhanced melanoma cell death in response to activated human T cells in vitro and in vivo in a death ligand-dependent manner. Biochemical mechanism of action studies established bromo and extraterminal domain (BET) proteins as major cellular targets of PCC. Thus, by targeting of BET proteins to reduce anti-apoptotic proteins and enhance caspase 8-dependent apoptosis of cancer cells, PCC represents a unique agent that can potentially be used in combination with various immunotherapeutic approaches to promote tumor regression and improve outcome.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-2634DOI Listing
April 2021

A study of transposable element-associated structural variations (TASVs) using a de novo-assembled Korean genome.

Exp Mol Med 2021 Apr 8;53(4):615-630. Epub 2021 Apr 8.

Department of Biological Sciences, Pusan National University, Busan, 46283, Republic of Korea.

Advances in next-generation sequencing (NGS) technology have made personal genome sequencing possible, and indeed, many individual human genomes have now been sequenced. Comparisons of these individual genomes have revealed substantial genomic differences between human populations as well as between individuals from closely related ethnic groups. Transposable elements (TEs) are known to be one of the major sources of these variations and act through various mechanisms, including de novo insertion, insertion-mediated deletion, and TE-TE recombination-mediated deletion. In this study, we carried out de novo whole-genome sequencing of one Korean individual (KPGP9) via multiple insert-size libraries. The de novo whole-genome assembly resulted in 31,305 scaffolds with a scaffold N50 size of 13.23 Mb. Furthermore, through computational data analysis and experimental verification, we revealed that 182 TE-associated structural variation (TASV) insertions and 89 TASV deletions contributed 64,232 bp in sequence gain and 82,772 bp in sequence loss, respectively, in the KPGP9 genome relative to the hg19 reference genome. We also verified structural differences associated with TASVs by comparative analysis with TASVs in recent genomes (AK1 and TCGA genomes) and reported their details. Here, we constructed a new Korean de novo whole-genome assembly and provide the first study, to our knowledge, focused on the identification of TASVs in an individual Korean genome. Our findings again highlight the role of TEs as a major driver of structural variations in human individual genomes.
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http://dx.doi.org/10.1038/s12276-021-00586-yDOI Listing
April 2021

Dye-Sensitized Nonstoichiometric Strontium Titanate Core-Shell Photocathodes for Photoelectrosynthesis Applications.

ACS Appl Mater Interfaces 2021 Apr 21;13(13):15261-15269. Epub 2021 Mar 21.

Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.

A core-shell approach that utilizes a high-surface-area conducting core and an outer semiconductor shell is exploited here to prepare p-type dye-sensitized solar energy cells that operate with a minimal applied bias. Photocathodes were prepared by coating thin films of nanocrystalline indium tin oxide with a 0.8 nm AlO seeding layer, followed by the chemical growth of nonstoichiometric strontium titanate. Films were annealed and sensitized with either a porphyrin chromophore or a chromophore-catalyst molecular assembly consisting of the porphyrin covalently tethered to the ruthenium complex. The sensitized photoelectrodes produced cathodic photocurrents of up to -315 μA/cm under simulated sunlight (AM1.5G, 100 mW/cm) in aqueous media, pH 5. The photocurrent was increased by the addition of regenerative hole donors to the system, consistent with slow interfacial recombination kinetics, an important property of p-type dye-sensitized electrodes.
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http://dx.doi.org/10.1021/acsami.1c00933DOI Listing
April 2021

TCR-engineered T cells targeting E7 for patients with metastatic HPV-associated epithelial cancers.

Nat Med 2021 03 8;27(3):419-425. Epub 2021 Feb 8.

Genitourinary Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Genetically engineered T cell therapy can induce remarkable tumor responses in hematologic malignancies. However, it is not known if this type of therapy can be applied effectively to epithelial cancers, which account for 80-90% of human malignancies. We have conducted a first-in-human, phase 1 clinical trial of T cells engineered with a T cell receptor targeting HPV-16 E7 for the treatment of metastatic human papilloma virus-associated epithelial cancers (NCT02858310). The primary endpoint was maximum tolerated dose. Cell dose was not limited by toxicity with a maximum dose of 1 × 10 engineered T cells administered. Tumor responses following treatment were evaluated using RECIST (Response Evaluation Criteria in Solid Tumors) guidelines. Robust tumor regression was observed with objective clinical responses in 6 of 12 patients, including 4 of 8 patients with anti-PD-1 refractory disease. Responses included extensive regression of bulky tumors and complete regression of most tumors in some patients. Genomic studies, which included intra-patient tumors with dichotomous treatment responses, revealed resistance mechanisms from defects in critical components of the antigen presentation and interferon response pathways. These findings demonstrate that engineered T cells can mediate regression of common carcinomas, and they reveal immune editing as a constraint on the curative potential of cellular therapy and possibly other immunotherapies in advanced epithelial cancer.
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http://dx.doi.org/10.1038/s41591-020-01225-1DOI Listing
March 2021

Stabilization of a molecular water oxidation catalyst on a dye-sensitized photoanode by a pyridyl anchor.

Nat Commun 2020 Sep 14;11(1):4610. Epub 2020 Sep 14.

Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.

Understanding and controlling the properties of water-splitting assemblies in dye-sensitized photoelectrosynthesis cells is a key to the exploitation of their properties. We demonstrate here that, following surface loading of a [Ru(bpy)] (bpy = 2,2'-bipyridine) chromophore on nanoparticle electrodes, addition of the molecular catalysts, Ru(bda)(L) (bda  =  2,2'-bipyridine-6,6'-dicarboxylate) with phosphonate or pyridyl sites for water oxidation, gives surfaces with a 5:1 chromophore to catalyst ratio. Addition of the surface-bound phosphonate derivatives with L = 4-pyridyl phosphonic acid or diethyl 3-(pyridin-4-yloxy)decyl-phosphonic acid, leads to well-defined surfaces but, following oxidation to Ru(III), they undergo facile, on-surface dimerization to give surface-bound, oxo-bridged dimers. The dimers have a diminished reactivity toward water oxidation compared to related monomers in solution. By contrast, immobilization of the Ru-bda catalyst on TiO with the 4,4'-dipyridyl anchoring ligand can maintain the monomeric structure of catalyst and gives relatively stable photoanodes with photocurrents that reach to 1.7 mA cm with an optimized, applied bias photon-to-current efficiency of 1.5%.
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http://dx.doi.org/10.1038/s41467-020-18417-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490713PMC
September 2020

Glycolytic metabolism of pathogenic T cells enables early detection of GVHD by 13C-MRI.

Blood 2021 01;137(1):126-137

Experimental Transplantation and Immunotherapy Branch and.

Graft-versus-host disease (GVHD) is a prominent barrier to allogeneic hematopoietic stem cell transplantation (AHSCT). Definitive diagnosis of GVHD is invasive, and biopsies of involved tissues pose a high risk of bleeding and infection. T cells are central to GVHD pathogenesis, and our previous studies in a chronic GVHD mouse model showed that alloreactive CD4+ T cells traffic to the target organs ahead of overt symptoms. Because increased glycolysis is an early feature of T-cell activation, we hypothesized that in vivo metabolic imaging of glycolysis would allow noninvasive detection of liver GVHD as activated CD4+ T cells traffic into the organ. Indeed, hyperpolarized 13C-pyruvate magnetic resonance imaging detected high rates of conversion of pyruvate to lactate in the liver ahead of animals becoming symptomatic, but not during subsequent overt chronic GVHD. Concomitantly, CD4+ T effector memory cells, the predominant pathogenic CD4+ T-cell subset, were confirmed to be highly glycolytic by transcriptomic, protein, metabolite, and ex vivo metabolic activity analyses. Preliminary data from single-cell sequencing of circulating T cells in patients undergoing AHSCT also suggested that increased glycolysis may be a feature of incipient acute GVHD. Metabolic imaging is being increasingly used in the clinic and may be useful in the post-AHSCT setting for noninvasive early detection of GVHD.
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http://dx.doi.org/10.1182/blood.2020005770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808015PMC
January 2021

Induction of phenotypic changes in HER2-postive breast cancer cells and .

Oncotarget 2020 Jul 28;11(30):2919-2929. Epub 2020 Jul 28.

Department of Bioengineering, Clemson University, Clemson, SC, USA.

The influence of breast cancer cells on normal cells of the microenvironment, such as fibroblasts and macrophages, has been heavily studied but the influence of normal epithelial cells on breast cancer cells has not. Here using and models we demonstrate the impact epithelial cells and the mammary microenvironment can exert on breast cancer cells. Under specific conditions, signals that originate in epithelial cells can induce phenotypic and genotypic changes in cancer cells. We have termed this phenomenon "cancer cell redirection." Once breast cancer cells are redirected, either or , they lose their tumor forming capacity and undergo a genetic expression profile shift away from one that supports a cancer profile towards one that supports a non-tumorigenic epithelial profile. These findings indicate that epithelial cells and the normal microenvironment influence breast cancer cells and that under certain circumstances restrict proliferation of tumorigenic cells.
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http://dx.doi.org/10.18632/oncotarget.27679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392627PMC
July 2020

A Novel Bactericidal Drug Effective Against Gram-Positive and Gram-Negative Pathogenic Bacteria: Easy as AB569.

DNA Cell Biol 2020 Sep 27;39(9):1473-1477. Epub 2020 Jul 27.

Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

Global antibiotic resistance, driven by intensive antibiotic exposure/abuse, constitutes a serious challenge to all health care, particularly in an era when new antimicrobial development has slowed to a trickle. Recently, we published work demonstrating the discovery and partial mechanism of action of a novel bactericidal agent that is effective against both gram-positive and gram-negative multidrug-resistant bacteria. This drug, called AB569, consists of acidified nitrite (A-NO) and EDTA, of which there is no mechanism of resistance. Using both chemistry-, genetic-, and bioinformatics-based techniques, we first discovered that AB569 was able to generate bactericidal levels of nitric oxide (NO), while the EDTA component stabilized -nitrosyl thiols, thereby furthering NO and downstream reactive nitrogen species production. This elegant chemistry triggered a paralytic downregulation of vital genes using RNA-seq involved in the synthesis of DNA, RNA, ATP, and protein in the representative ESKAPE pathogen, .
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http://dx.doi.org/10.1089/dna.2020.5824DOI Listing
September 2020

Chemical approaches to artificial photosynthesis: A molecular, dye-sensitized photoanode for O production prepared by layer-by-layer self-assembly.

J Chem Phys 2020 Jun;152(24):244706

Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3290, USA.

We describe here the preparation of a family of photoanodes for water oxidation that incorporate an electron acceptor-chromophore-catalyst in single molecular assemblies on nano-indium tin oxide (nanoITO) electrodes on fluorine-doped tin oxide (FTO). The assemblies were prepared by using a layer-by-layer, Atomic Layer Deposition (ALD), self-assembly approach. In the procedure, addition of an electron acceptor viologen derivative followed by a Ru(bpy) chromophore and a pyridyl derivative of the water oxidation catalyst [Ru(bda) (L)] (bda = 2,2'-bipyridine-6,6'-dicarboxylate), were linked by ALD by addition of the bridge precursors TiO, ZrO, and AlO as the bridging groups giving the assemblies, FTO|nanoITO|-MV-ALD MO-RuP-ALD M'O-WOC. In a series of devices, the most efficient gave water oxidation with an incident photon to current efficiency of 2.2% at 440 nm. Transient nanosecond absorption measurements on the assemblies demonstrated that the slow step in the intra-assembly electron transfer is the electron transfer from the chromophore through the viologen bridge to the nanoITO electrode.
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http://dx.doi.org/10.1063/5.0007383DOI Listing
June 2020

Ultrafast Relaxations in Ruthenium Polypyridyl Chromophores Determined by Stochastic Kinetics Simulations.

J Phys Chem B 2020 07 1;124(28):5971-5985. Epub 2020 Jul 1.

Chemical Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States.

Maximizing the efficiency of solar energy conversion using dye assemblies rests on understanding where the energy goes following absorption. Transient spectroscopies in solution are useful for this purpose, and the time-resolved data are usually analyzed with a sum of exponentials. This treatment assumes that dynamic events are well separated in time, and that the resulting exponential prefactors and phenomenological lifetimes are related directly to primary physical values. Such assumptions break down for coincident absorption, emission, and excited state relaxation that occur in transient absorption and photoluminescence of tris(2,2'-bipyridine)ruthenium(2+) derivatives, confounding the physical meaning of the reported lifetimes. In this work, we use inductive modeling and stochastic chemical kinetics to develop a detailed description of the primary ultrafast photophysics in transient spectroscopies of a series of Ru dyes, as an alternative to sums of exponential analysis. Commonly invoked three-level schemes involving absorption, intersystem crossing (ISC), and slow nonradiative relaxation and incoherent emission to the ground state cannot reproduce the experimentally measured spectra. The kinetics simulations reveal that ultrafast decay from the singlet excited state manifold to the ground state competes with ISC to the triplet excited state, whose efficiency was determined to be less than unity. The populations predicted by the simulations are used to estimate the magnitudes of transition dipoles for excited state excitations and evaluate the influence of specific ligands. The mechanistic framework and methodology presented here are entirely general, applicable to other dye classes, and can be extended to include charge injection by molecules bound to semiconductor surfaces.
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http://dx.doi.org/10.1021/acs.jpcb.0c03110DOI Listing
July 2020

A molecular tandem cell for efficient solar water splitting.

Proc Natl Acad Sci U S A 2020 06 1;117(24):13256-13260. Epub 2020 Jun 1.

Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;

Artificial photosynthesis provides a way to store solar energy in chemical bonds. Achieving water splitting without an applied external potential bias provides the key to artificial photosynthetic devices. We describe here a tandem photoelectrochemical cell design that combines a dye-sensitized photoelectrosynthesis cell (DSPEC) and an organic solar cell (OSC) in a photoanode for water oxidation. When combined with a Pt electrode for H evolution, the electrode becomes part of a combined electrochemical cell for water splitting, 2HO → O + 2H, by increasing the voltage of the photoanode sufficiently to drive bias-free reduction of H to H The combined electrode gave a 1.5% solar conversion efficiency for water splitting with no external applied bias, providing a mimic for the tandem cell configuration of PSII in natural photosynthesis. The electrode provided sustained water splitting in the molecular photoelectrode with sustained photocurrent densities of 1.24 mA/cm for 1 h under 1-sun illumination with no applied bias.
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http://dx.doi.org/10.1073/pnas.2001753117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306789PMC
June 2020

AB569, a nontoxic chemical tandem that kills major human pathogenic bacteria.

Proc Natl Acad Sci U S A 2020 03 18;117(9):4921-4930. Epub 2020 Feb 18.

Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267;

Antibiotic-resistant superbug bacteria represent a global health problem with no imminent solutions. Here we demonstrate that the combination (termed AB569) of acidified nitrite (A-NO) and Na-EDTA (disodium ethylenediaminetetraacetic acid) inhibited all Gram-negative and Gram-positive bacteria tested. AB569 was also efficacious at killing the model organism in biofilms and in a murine chronic lung infection model. AB569 was not toxic to human cell lines at bactericidal concentrations using a basic viability assay. RNA-Seq analyses upon treatment of with AB569 revealed a catastrophic loss of the ability to support core pathways encompassing DNA, RNA, protein, ATP biosynthesis, and iron metabolism. Electrochemical analyses elucidated that AB569 produced more stable SNO proteins, potentially explaining one mechanism of bacterial killing. Our data implicate that AB569 is a safe and effective means to kill pathogenic bacteria, suggesting that simple strategies could be applied with highly advantageous therapeutic/toxicity index ratios to pathogens associated with a myriad of periepithelial infections and related disease scenarios.
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http://dx.doi.org/10.1073/pnas.1911927117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060718PMC
March 2020

Electron-Withdrawing Boron Dipyrromethene Dyes As Visible Light Absorber/Sensitizers on Semiconductor Oxide Surfaces.

ACS Appl Mater Interfaces 2020 Feb 29;12(6):7768-7776. Epub 2020 Jan 29.

Department of Chemistry , University of North Carolina at Chapel Hill , CB3290 , Chapel Hill , North Carolina 27599 , United States.

The synthesis, characterization, and electrochemical and photophysical properties of the phosphonate-derivatized carbazole () and boron dipyrromethene () chromophores in the dyes, BODIPY(CBZ)POH () and BODIPY(Tol)POH (), are described. The oxide-bound dyes have been explored as light absorbers in dye-sensitized photoelectrosynthesis cell (DSPEC) applications. The BODIPY-CBZ phosphonate ester () features a broad, intense UV-visible absorption spectrum with absorptions at 297 and 650 nm that arise from mixed transitions at the CBZ and BODIPY units. Electrochemical measurements on BODIPY(CBZ)Br () in 0.1 M [nBuN][PF] in dichloromethane, vs normal hydrogen electrode (NHE), reveal reversible oxidations at 1.19 and 1.41 V and a reversible reduction at -0.59 V. On indium tin oxide (ITO) and TiO, a reversible one-electron oxidation appears for at 0.86 and 0.90 V vs NHE in dichloromethane, respectively, which demonstrates the redox stability on metal oxide surfaces. The results of nanosecond transient absorption measurements on SnO/TiO electrodes provide direct evidence for excited-state electron injection into the conduction band of TiO following 590 nm excitation. A longer lifetime for compared to is consistent with extensive intramolecular charge separation between the CBZ and BODIPY units on the surface. Photoelectrochemical studies on on a SnO/TiO photoanode resulted in sustained photocurrents with current maxima of ∼200 μA/cm with hydroquinone added as a reductant under 1 sun (AM1.5 100 mW·cm) illumination at pH 4.5 in 0.1 M acetate buffer and 0.4 M LiClO. On mixed SnO/TiO electrode surfaces, with the added catalyst [Ru(Mebimpy)((4,4'-(OH)PO-CH)bpy)(OH)] and chromophores and , addition of 0.1 M benzyl alcohol resulted in sustained photocurrents of 12 and 35 μA/cm, consistent with oxidation to benzaldehyde.
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http://dx.doi.org/10.1021/acsami.9b20167DOI Listing
February 2020

CO Reduction: From Homogeneous to Heterogeneous Electrocatalysis.

Acc Chem Res 2020 Jan 8;53(1):255-264. Epub 2020 Jan 8.

Department of Chemistry , University of North Carolina at Chapel Hill , Chapel Hill , North Carolina 27599 , United States.

Due to increasing worldwide fossil fuel consumption, carbon dioxide levels have increased in the atmosphere with increasingly important impacts on the environment. Renewable and clean sources of energy have been proposed, including wind and solar, but they are intermittent and require efficient and scalable energy storage technologies. Electrochemical CO reduction reaction (CORR) provides a valuable approach in this area. It combines solar- or wind-generated electrical production with energy storage in the chemical bonds of carbon-based fuels. It can provide ways to integrate carbon capture, utilization, and storage in energy cycles while maintaining controlled levels of atmospheric CO. Electrochemistry allows for the utilization of an electrical input to drive chemical reactions. Because CO is kinetically inert, highly active catalysts are required to decrease reaction barriers sufficiently so that reaction rates can be achieved that are sufficient for electrochemical CO reduction. Given the reaction barriers associated with multiple electron-proton reduction of CO to CO, formaldehyde (HC(O)H), formic acid, or formate (HC(O)OH, HC(O)O), or more highly reduced forms of carbon, there is also a demand for high selectivity in catalysis. Catalysts that have been explored include homogeneous catalysts in solution, catalysts immobilized on surfaces, and heterogeneous catalysts. In homogeneous catalysis, reduction occurs following diffusion of the catalyst to an electrode where multiple proton coupled electron transfer reduction occurs. Useful catalysts in this area are typically transition-metal complexes with organic ligands and electron transfer properties that utilize combinations of metal and ligand redox levels. As a way to limit the amount of catalyst, in device-like configurations, catalysts are added to the surfaces of conductive substrates by surface binding, in polymeric films, or on carbon electrode surfaces with molecular structures and electronic configurations related to catalysts in solution. Immobilized, homogeneous catalysts can suffer from performance losses and even decomposition during long-term CO reduction cycles, but they are amenable to detailed mechanistic investigations. In parallel efforts, heterogeneous nanocatalysts have been explored in detail with the development of facile synthetic procedures that can offer highly active catalytic surface areas. Their high activity and stability have attracted a significant level of investigation, including possible exploitation for large-scale applications. However, translation of catalytic reactivity to the surface creates a new reactivity environment and complicates the elucidation of mechanistic details and identification of the active site in exploring reaction pathways. Here, the results of previous studies based on transition-metal complex catalysts for CO electroreduction are summarized. Early studies showed that transition-metal complexes of Ru, Ir, Rh, and Os, with well-defined structures, are all capable of catalyzing CO reduction to CO or formate. Derivatives of the complexes were surface attached to conducting electrodes by chemical bonding, noncovalent bonding, or polymerization. The concept of surface binding has also been extended to the preparation of surface area electrodes by the chemically controlled deposition of nanostructured catalysts such as nano tin, nano copper, and nano carbon, all of which have been shown to have high selectivities and activities toward CO reduction. In our presentation, we end this Account with recent advances and a perspective about the application of electrocatalysis in carbon dioxide reduction.
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http://dx.doi.org/10.1021/acs.accounts.9b00496DOI Listing
January 2020

Steering CO electroreduction toward ethanol production by a surface-bound Ru polypyridyl carbene catalyst on N-doped porous carbon.

Proc Natl Acad Sci U S A 2019 Dec 10. Epub 2019 Dec 10.

Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;

Electrochemical reduction of CO to multicarbon products is a significant challenge, especially for molecular complexes. We report here CO reduction to multicarbon products based on a Ru(II) polypyridyl carbene complex that is immobilized on an N-doped porous carbon (RuPC/NPC) electrode. The catalyst utilizes the synergistic effects of the Ru(II) polypyridyl carbene complex and the NPC interface to steer CO reduction toward C2 production at low overpotentials. In 0.5 M KHCO/CO aqueous solutions, Faradaic efficiencies of 31.0 to 38.4% have been obtained for C2 production at -0.87 to -1.07 V (vs. normal hydrogen electrode) with 21.0 to 27.5% for ethanol and 7.1 to 12.5% for acetate. Syngas is also produced with adjustable H/CO mole ratios of 2.0 to 2.9. The RuPC/NPC electrocatalyst maintains its activity during 3-h CO-reduction periods.
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http://dx.doi.org/10.1073/pnas.1907740116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6936396PMC
December 2019

A stable dye-sensitized photoelectrosynthesis cell mediated by a NiO overlayer for water oxidation.

Proc Natl Acad Sci U S A 2020 06 5;117(23):12564-12571. Epub 2019 Sep 5.

Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;

In the development of photoelectrochemical cells for water splitting or CO reduction, a major challenge is O evolution at photoelectrodes that, in behavior, mimic photosystem II. At an appropriate semiconductor electrode, a water oxidation catalyst must be integrated with a visible light absorber in a stable half-cell configuration. Here, we describe an electrode consisting of a light absorber, an intermediate electron donor layer, and a water oxidation catalyst for sustained light driven water oxidation catalysis. In assembling the electrode on nanoparticle SnO/TiO electrodes, a Ru(II) polypyridyl complex was used as the light absorber, NiO was deposited as an overlayer, and a Ru(II) 2,2'-bipyridine-6,6'-dicarboxylate complex as the water oxidation catalyst. In the final electrode, addition of the NiO overlayer enhanced performance toward water oxidation with the final electrode operating with a 1.1 mA/cm photocurrent density for 2 h without decomposition under one sun illumination in a pH 4.65 solution. We attribute the enhanced performance to the role of NiO as an electron transfer mediator between the light absorber and the catalyst.
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http://dx.doi.org/10.1073/pnas.1821687116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293597PMC
June 2020

Excitation energy-dependent photocurrent switching in a single-molecule photodiode.

Proc Natl Acad Sci U S A 2019 08 31;116(33):16198-16203. Epub 2019 Jul 31.

Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;

The direction of electron flow in molecular optoelectronic devices is dictated by charge transfer between a molecular excited state and an underlying conductor or semiconductor. For those devices, controlling the direction and reversibility of electron flow is a major challenge. We describe here a single-molecule photodiode. It is based on an internally conjugated, bichromophoric dyad with chemically linked (porphyrinato)zinc(II) and bis(terpyridyl)ruthenium(II) groups. On nanocrystalline, degenerately doped indium tin oxide electrodes, the dyad exhibits distinct frequency-dependent, charge-transfer characters. Variations in the light source between red-light (∼1.9 eV) and blue-light (∼2.7 eV) excitation for the integrated photodiode result in switching of photocurrents between cathodic and anodic. The origin of the excitation frequency-dependent photocurrents lies in the electronic structure of the chromophore excited states, as shown by the results of theoretical calculations, laser flash photolysis, and steady-state spectrophotometric measurements.
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http://dx.doi.org/10.1073/pnas.1907118116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697812PMC
August 2019

Papillomavirus can be transmitted through the blood and produce infections in blood recipients: Evidence from two animal models.

Emerg Microbes Infect 2019 ;8(1):1108-1121

a The Jake Gittlen Laboratories for Cancer Research, Pennsylvania State University College of Medicine , Hershey , PA , USA.

Human papillomaviruses (HPV) contribute to most cervical cancers and are considered to be sexually transmitted. However, papillomaviruses are often found in cancers of internal organs, including the stomach, raising the question as to how the viruses gain access to these sites. A possible connection between blood transfusion and HPV-associated disease has not received much attention. Here we show, in rabbit and mouse models, that blood infected with papillomavirus yields infections at permissive sites with detectable viral DNA, RNA transcripts, and protein products. The rabbit skin tumours induced via blood infection displayed decreased expression of SLN, TAC1, MYH8, PGAM2, and APOBEC2 and increased expression of SDRC7, KRT16, S100A9, IL36G, and FABP9, as seen in tumours induced by local infections. Furthermore, we demonstrate that blood from infected mice can transmit the infection to uninfected animals. Finally, we demonstrate the presence of papillomavirus infections and virus-induced hyperplasia in the stomach tissues of animals infected via the blood. These results indicate that blood transmission could be another route for papillomavirus infection, implying that the human blood supply, which is not screened for papillomaviruses, could be a potential source of HPV infection as well as subsequent cancers in tissues not normally associated with the viruses.
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http://dx.doi.org/10.1080/22221751.2019.1637072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6713970PMC
November 2019

A Silicon-Based Heterojunction Integrated with a Molecular Excited State in a Water-Splitting Tandem Cell.

J Am Chem Soc 2019 Jul 24;141(26):10390-10398. Epub 2019 Jun 24.

Department of Chemistry , University of North Carolina at Chapel Hill , Chapel Hill , North Carolina 27599 , United States.

Semiconductor-based photocathodes with high light-absorption capability are of interest in the production of solar fuels, but many of them are limited by low efficiencies due to rapid interfacial back electron transfer. We demonstrate here that a nanowire-structured p-type Si (p-Si) electrode, surface-modified with a perylene-diimide derivative (PDI'), can undergo photoreduction of a surface-bound, water reduction catalyst toward efficient H evolution under a low applied bias. At the electrode interface, the PDI' layer converts green light into high-energy holes at its excited state for extraction of photogenerated electrons at the photoexcited p-Si. The photogenerated electrons at the reduced PDI' are subsequently transferred to the molecular H-evolution catalyst. Involvement of the photoexcited PDI' enables effective redox separation between the electrons at the reduced catalyst and the holes at the valence band of p-Si. The heterojunction photocathode was used in a tandem cell by coupling with a dye-sensitized photoanode for solar-driven water splitting into H and O.
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http://dx.doi.org/10.1021/jacs.9b04238DOI Listing
July 2019

A strategy for stabilizing the catalyst CoO in a metal-organic framework.

Proc Natl Acad Sci U S A 2019 07 20;116(28):13719-13720. Epub 2019 Jun 20.

Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599

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http://dx.doi.org/10.1073/pnas.1909543116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628654PMC
July 2019

Crossing the bridge from molecular catalysis to a heterogenous electrode in electrocatalytic water oxidation.

Proc Natl Acad Sci U S A 2019 06 16;116(23):11153-11158. Epub 2019 May 16.

Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599

Significant progress has been made in designing single-site molecular Ru(II)-polypyridyl-aqua catalysts for homogenous catalytic water oxidation. Surface binding and transfer of the catalytic reactivity onto conductive substrates provides a basis for heterogeneous applications in electrolytic cells and dye-sensitized photoelectrosynthesis cells (DSPECs). Earlier efforts have focused on phosphonic acid (-POH) or carboxylic acid (-COH) bindings on oxide surfaces. However, issues remain with limited surface stabilities, especially in aqueous solutions at higher pH under conditions that favor water oxidation by reducing the thermodynamic barrier and accelerating the catalytic rate using atom-proton transfer (APT) pathways. Here, we address the problem by combining silane surface functionalization and surface reductive electropolymerization on mesoporous, nanofilms of indium tin oxide (ITO) on fluorine-doped tin oxide (FTO) substrates (FTO|ITO). FTO|ITO electrodes were functionalized with vinyltrimethoxysilane (VTMS) to introduce vinyl groups on the electrode surfaces by silane attachment, followed by surface electropolymerization of the vinyl-derivatized complex, [Ru(Mebimpy)(dvbpy)(OH)] (1; Mebimpy: 2,6-bis(1-methyl-1-benzo[]imidazol-2-yl)pyridine; dvbpy: 5,5'-divinyl-2,2'-bipyridine), in a mechanism dominated by a grafting-through method. The surface coverage of catalyst 1 was controlled by the number of electropolymerization cycles. The combined silane attachment/cross-linked polymer network stabilized 1 on the electrode surface under a variety of conditions especially at pH > ∼6. Surface-grafted poly1 was stable toward redox cycling at pH ∼ 7.5 over an ∼4-h period. Sustained heterogeneous electrocatalytic water oxidation by the electrode gave steady-state currents for at least ∼6 h with a Faradaic efficiency of ∼68% for O production.
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http://dx.doi.org/10.1073/pnas.1902455116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561241PMC
June 2019

Electrocatalytic CO Reduction with a Ruthenium Catalyst in Solution and on Nanocrystalline TiO.

ChemSusChem 2019 Jun 15;12(11):2402-2408. Epub 2019 May 15.

Department of Chemistry, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, USA.

A Ru complex [Ru(PO Et -ph-tpy)(6-mbpy)(NCCH )] [PO Et -ph-tpy=diethyl(4-[(2,2':6',2''-terpyridin)-4'-yl]phenyl)phosphonate; 6-mbpy=6-methyl-2,2'-bipyridine] is explored as a molecular catalyst for electrocatalytic CO reduction in both a homogeneous solution and, as a phosphonated derivative, on nanocrystalline-TiO surfaces. In CH CN, the complex acts as a selective electrocatalyst for reduction of CO to CO at a low overpotential of 340 mV but with a limited turnover number (TON). An enhancement in reactivity was observed by immobilizing the phosphonated derivative of the catalyst on a nanocrystalline-TiO electrode surface, with the catalyst surface protected by a thin overlayer of NiO. The surface-functionalized electrode was characterized by X-ray photoelectron and diffuse reflectance spectroscopies (XPS and DRS). Electrocatalytic reduction of CO to CO occurred at -1.65 V versus Fc with a TON of 237 per catalyst site during 4 h of electrocatalysis. Post-catalysis XPS measurements reveal that the molecular structure of the catalyst is retained on TiO after the long-term electrocatalysis.
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http://dx.doi.org/10.1002/cssc.201900730DOI Listing
June 2019

A donor-chromophore-catalyst assembly for solar CO reduction.

Chem Sci 2019 Apr 14;10(16):4436-4444. Epub 2019 Mar 14.

Department of Chemistry , University of North Carolina Chapel Hill , Chapel Hill , North Carolina 27599 , USA . Email:

We describe here the preparation and characterization of a photocathode assembly for CO reduction to CO in 0.1 M LiClO acetonitrile. The assembly was formed on 1.0 μm thick mesoporous films of NiO using a layer-by-layer procedure based on Zr(iv)-phosphonate bridging units. The structure of the Zr(iv) bridged assembly, abbreviated as NiO|-DA-RuCP-Re(i), where DA is the dianiline-based electron donor (,,','-((CH)POH)-4,4'-dianiline), RuCP is the light absorber [Ru((4,4'-(POHCH)-2,2'-bipyridine)(2,2'-bipyridine))], and Re(i) is the CO reduction catalyst, Re((4,4'-POHCH)-2,2'-bipyridine)(CO)Cl. Visible light excitation of the assembly in CO saturated solution resulted in CO reduction to CO. A steady-state photocurrent density of 65 μA cm was achieved under one sun illumination and an IPCE value of 1.9% was obtained with 450 nm illumination. The importance of the DA aniline donor in the assembly as an initial site for reduction of the RuCP excited state was demonstrated by an 8 times higher photocurrent generated with DA present in the surface film compared to a control without DA. Nanosecond transient absorption measurements showed that the expected reduced one-electron intermediate, RuCP, was formed on a sub-nanosecond time scale with back electron transfer to the electrode on the microsecond timescale which competes with forward electron transfer to the Re(i) catalyst at = 2.6 μs ( = 2.7 × 10 s).
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http://dx.doi.org/10.1039/c8sc03316aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6482438PMC
April 2019

Molecular Photoelectrode for Water Oxidation Inspired by Photosystem II.

J Am Chem Soc 2019 05 3;141(19):7926-7933. Epub 2019 May 3.

Department of Chemistry , University of North Carolina at Chapel Hill , Chapel Hill , North Carolina 27599-3290 , United States.

In artificial photosynthesis, the sun drives water splitting into H and O or converts CO into a useful form of carbon. In most schemes, water oxidation is typically the limiting half-reaction. Here, we introduce a molecular approach to the design of a photoanode that incorporates an electron acceptor, a sensitizer, an electron donor, and a water oxidation catalyst in a single molecular assembly. The strategy mimics the key elements in Photosystem II by initiating light-driven water oxidation with integration of a light absorber, an electron acceptor, an electron donor, and a catalyst in a controlled molecular environment on the surface of a conducting oxide electrode. Visible excitation of the assembly results in the appearance of reductive equivalents at the electrode and oxidative equivalents at a catalyst that persist for seconds in aqueous solutions. Steady-state illumination of the assembly with 440 nm light with an applied bias results in photoelectrochemical water oxidation with a per-photon absorbed efficiency of 2.3%. The results are notable in demonstrating that light-driven water oxidation can be carried out at a conductive electrode in a structure with the functional elements of Photosystem II including charge separation and water oxidation.
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http://dx.doi.org/10.1021/jacs.9b02548DOI Listing
May 2019

Stabilization of Ruthenium(II) Polypyridyl Chromophores on Mesoporous TiO Electrodes: Surface Reductive Electropolymerization and Silane Chemistry.

ACS Cent Sci 2019 Mar 15;5(3):506-514. Epub 2019 Feb 15.

Department of Chemistry, University of North Carolina at Chapel Hill, CB#3290, Chapel Hill, North Carolina 27599-3290, United States.

Stabilization is a critical issue in the long term operation of dye-sensitized photoelectrosynthesis cells (DSPECs) for water splitting or CO reduction. The cells require a stable binding of the robust molecular chromophores, catalysts, and chromophore/catalyst assemblies on metal oxide semiconductor electrodes under the corresponding (photoelectro)chemical conditions. Here, an efficient stabilization strategy is presented based on functionalization of FTOTiO (mesoporous, nanostructured TiO deposited on fluorine-doped tin oxide (FTO) glass) electrodes with a vinylsilane followed by surface reductive electropolymerization of a vinyl-derivatized Ru(II) polypyridyl chromophore. The surface electropolymerization was dominated by a grafting-through mechanism, and rapidly completed within minutes. Chromophore surface coverages were controlled up to three equivalent monolayers by the number of electropolymerization cycles. The silane immobilization and cross-linked polymer network produced highly (photo)stabilized chromophore-grafted FTOTiO electrodes. The electrodes showed significant improvements over structures based on atomic layer deposition and polymer dip-coating stabilization methods in a wide pH range from pH ≈ 1 to pH ≈ 12.5 under both dark and light conditions. Under illumination, with hydroquinone added as a sacrificial electron transfer donor, a photoresponse for sustained electron transfer mediation occurred for at least ∼20 h in a pH ≈ 7.5 phosphate buffer (0.1 M NaHPO/NaHPO, with 0.5 M NaClO). The overall procedure provides an efficient way to fabricate highly stabilized molecular assemblies on electrode surfaces with potential applications for DSPECs in solar fuels.
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http://dx.doi.org/10.1021/acscentsci.8b00914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439529PMC
March 2019

Homogeneous catalysis for the nitrogen fuel cycle.

Proc Natl Acad Sci U S A 2019 02 8;116(8):2794-2795. Epub 2019 Feb 8.

Department of Chemistry, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;

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http://dx.doi.org/10.1073/pnas.1822090116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386706PMC
February 2019

Light-driven water oxidation by a dye-sensitized photoanode with a chromophore/catalyst assembly on a mesoporous double-shell electrode.

J Chem Phys 2019 Jan;150(4):041727

Department of Chemistry, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.

A mesoporous atomic layer deposition (ALD) double-shell electrode, AlO (insulating core)//ALD ZnO|ALD TiO, on a fluorine-doped tin oxide (FTO) conducting substrate was explored for a photoanode assembly, FTO//AlO (insulating core)//ALD ZnO|ALD TiO|-chromophore-catalyst, for light-driven water oxidation. Photocurrent densities at photoanodes based on mesoporous ALD double-shell (ALD ZnO|ALD TiO|) and ALD single-shell (ALD ZnO|, ALD TiO|) electrodes were investigated for O evaluation by a generator-collector dual working electrode configuration. The high photocurrent densities obtained based on the mesoporous ALD ZnO|ALD TiO photoanode for O evolution arise from a significant barrier to back electron transfer (BET) by the optimized tunneling barrier in the structure with the built-in electric field at the ALD ZnO|ALD TiO interface. The charge recombination is thus largely decreased. In the films, BET following injection has been investigated through kinetic nanosecond transient absorption spectra, and the results of energy band analysis are used to derive insight into the internal electronic structure of the electrodes.
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http://dx.doi.org/10.1063/1.5048780DOI Listing
January 2019

HMGN1 and R848 Synergistically Activate Dendritic Cells Using Multiple Signaling Pathways.

Front Immunol 2018 18;9:2982. Epub 2018 Dec 18.

Cancer and Inflammation Program, Frederick National Laboratory for Cancer Research, Center for Cancer Research, National Cancer Institute, Frederick, MD, United States.

High mobility group nucleosome-binding protein 1 (HMGN1 or N1) is a Th1-polarizing alarmin, but alone is insufficient to induce antitumor immunity. We previously showed that combination of N1 and R848, a synthetic TLR7/8 agonist, synergistically activates dendritic cells (DCs) and induces therapeutic antitumor immunity, however, it remained unclear how N1 and R848 synergistically activate DCs. Here, we show that co-stimulation with N1 and R848 of human monocyte-derived DCs (MoDCs) markedly upregulated DC's surface expression of CD80, CD83, CD86, and HLA-DR, as well as synergistic production of pro-inflammatory cytokines including IL-12p70, IL-1β, and TNF-α. This combination also synergistically activated NF-κB and multiple MAPKs that are involved in DC maturation. Moreover, N1 and R848 synergistically increased nuclear translocation of interferon (IFN) regulatory transcription factors (e.g., IRF3 and IRF7) and promoted the expression of type 1 IFNs such as IFN-α2, IFN-α4, and IFN-β1. Similar signaling pathways were also induced in mouse bone marrow-derived DCs (BMDCs). RNA-seq analysis in human MoDCs revealed that N1 plus R848 synergistically upregulated the expression of genes predominantly involved in DC maturation pathway, particularly genes critical for the polarization of Th1 immune responses (e.g., , and , etc.). Overall, our findings show that (1) N1 synergizes with R848 in activating human and mouse DCs and (2) the synergistic effect based on various intracellular signaling events culminated in the activation of multiple transcriptional factors. These findings have important implications for future clinical trials since N1 and R848 synergistically promoted optimal Th1 lineage immune responses resulting in tumor rejection in mice.
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http://dx.doi.org/10.3389/fimmu.2018.02982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305469PMC
November 2019

Stable Molecular Surface Modification of Nanostructured, Mesoporous Metal Oxide Photoanodes by Silane and Click Chemistry.

ACS Appl Mater Interfaces 2019 Jan 16;11(4):4560-4567. Epub 2019 Jan 16.

Department of Chemistry , University of North Carolina at Chapel Hill , Chapel Hill , North Carolina 27599 , United States.

Binding functional molecules to nanostructured mesoporous metal oxide surfaces provides a way to derivatize metal oxide semiconductors for applications in dye-sensitized photoelectrosynthesis cells (DSPECs). The commonly used anchoring groups, phosphonates and carboxylates, are unstable as surface links to oxide surfaces at neutral and high pH, leading to rapid desorption of appended molecules. A synthetically versatile molecular attachment strategy based on initial surface modification with a silyl azide followed by click chemistry is described here. It has been used for the stable installation of surface-bound metal complexes. The resulting surfaces are highly stabilized toward complex loss with excellent thermal, photochemical, and electrochemical stabilities. The procedure involves binding 3-azidopropyltrimethoxysilane (APTMS) to nanostructured mesoporous TiO or tin-doped indium oxide (ITO) electrodes by silane attachment followed by azide-terminated, Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions with an alkyne-derivatized ruthenium(II) polypyridyl complex. The chromophore-modified electrodes display enhanced photochemical and electrochemical stabilities compared to phosphonate surface binding with extended photoelectrochemical oxidation of hydroquinone for more than ∼6 h with no significant decay.
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http://dx.doi.org/10.1021/acsami.8b17824DOI Listing
January 2019