Christopher J Chang

Publications of Christopher J Chang

• A selective reaction-based fluorescent probe for detecting cobalt in living cells.

  Authors: Ho Yu Au-Yeung, Elizabeth J New, Christopher J Chang

  Chemical communications (Cambridge, England). 04/2012;

  A reaction-based strategy exploiting cobalt-mediated oxidative C-O bond cleavage affords a selective turn-on fluorescent probe for paramagnetic Co(2+) in water and in living cells.

• Computational and experimental study of the mechanism of hydrogen generation from water by a molecular molybdenum-oxo electrocatalyst.

  Authors: Eric J Sundstrom, Xinzheng Yang, V Sara Thoi, Hemamala I Karunadasa, Christopher J Chang, Jeffrey R Long, Martin Head-Gordon

  Journal of the American Chemical Society. 03/2012; 134(11):5233-42.

  We investigate the mechanism for the electrocatalytic generation of hydrogen from water by the molecular molybdenum-oxo complex, [(PY5Me(2))MoO](2+) (PY5Me(2) =We investigate the mechanism for the electrocatalytic generation of hydrogen from water by the molecular molybdenum-oxo complex, [(PY5Me(2))MoO](2+) (PY5Me(2) = 2,6-bis(1,1-bis(2-pyridyl)ethyl)pyridine). Computational and experimental evidence suggests that the electrocatalysis consists of three distinct electrochemical reductions, which precede the onset of catalysis. Cyclic voltammetry studies indicate that the first two reductions are accompanied by protonations to afford the Mo-aqua complex, [(PY5Me(2))Mo(OH(2))](+). Calculations support hydrogen evolution from this complex upon the third reduction, via the oxidative addition of a proton from the bound water to the metal center and finally an α-H abstraction to release hydrogen. Calculations further suggest that introducing electron-withdrawing substituents such as fluorides in the para positions of the pyridine rings can reduce the potential associated with the reductive steps, without substantially affecting the kinetics. After the third reduction, there are kinetic bottlenecks to the formation of the Mo-hydride and subsequent hydrogen release. Computational evidence also suggests an alternative to direct α-H abstraction as a mechanism for H(2) release which exhibits a lower barrier. The new mechanism is one in which a water acts as an intramolecular proton relay between the protons of the hydroxide and the hydride ligands. The calculated kinetics are in reasonable agreement with experimental measurements. Additionally, we propose a mechanism for the stoichiometric reaction of [(PY5Me(2))Mo(CF(3)SO(3))](+) with water to yield hydrogen and [(PY(5)Me(2))MoO](2+) along with the implications for the viability of an alternate catalytic cycle involving just two reductions to generate the active catalyst.

• Inhibition of copper uptake in yeast reveals the copper transporter ctr1p as a potential molecular target of saxitoxin.

  Authors: Kathleen D Cusick, Steven C Minkin, Sheel C Dodani, Christopher J Chang, Steven W Wilhelm, Gary S Sayler

  Environmental science & technology. 03/2012; 46(5):2959-66.

  Saxitoxin is a secondary metabolite produced by several species of dinoflagellates and cyanobacteria which targets voltage-gated sodium and potassium channels in higher vertebrates. However, itsSaxitoxin is a secondary metabolite produced by several species of dinoflagellates and cyanobacteria which targets voltage-gated sodium and potassium channels in higher vertebrates. However, its molecular target in planktonic aquatic community members that co-occur with the toxin producers remains unknown. Previous microarray analysis with yeast identified copper and iron-homeostasis genes as being differentially regulated in response to saxitoxin. This study sought to identify the molecular target in microbial cells by comparing the transcriptional profiles of key copper and iron homeostasis genes (CTR1, FRE1, FET3, CUP1, CRS5) in cells exposed to saxitoxin, excess copper, excess iron, an extracellular Cu(I) chelator, or an intracellular Cu(I) chelator. Protein expression and localization of Ctr1p (copper transporter), Fet3p (multicopper oxidase involved in high-affinity iron uptake), and Aft1p (iron regulator) were also compared among treatments. Combined transcript and protein profiles suggested saxitoxin inhibited copper uptake. This hypothesis was confirmed by intracellular Cu(I) imaging with a selective fluorescent probe for labile copper. On the basis of the combined molecular and physiological results, a model is presented in which the copper transporter Ctr1p serves as a molecular target of saxitoxin and these observations are couched in the context of the eco-evolutionary role this toxin may serve for species that produce it.

• Near-infrared fluorescent sensor for in vivo copper imaging in a murine Wilson disease model.

  Authors: Tasuku Hirayama, Genevieve C Van de Bittner, Lawrence W Gray, Svetlana Lutsenko, Christopher J Chang

  Proceedings of the National Academy of Sciences of the United States of America. 02/2012; 109(7):2228-33.

  Copper is an essential metal nutrient that is tightly regulated in the body because loss of its homeostasis is connected to severe diseases such as Menkes and Wilson diseases, Alzheimer's disease,Copper is an essential metal nutrient that is tightly regulated in the body because loss of its homeostasis is connected to severe diseases such as Menkes and Wilson diseases, Alzheimer's disease, prion disorders, and amyotrophic lateral sclerosis. The complex relationships between copper status and various stages of health and disease remain challenging to elucidate, in part due to a lack of methods for monitoring dynamic changes in copper pools in whole living organisms. Here we present the synthesis, spectroscopy, and in vivo imaging applications of Coppersensor 790, a first-generation fluorescent sensor for visualizing labile copper pools in living animals. Coppersensor 790 combines a near-infrared emitting cyanine dye with a sulfur-rich receptor to provide a selective and sensitive turn-on response to copper. This probe is capable of monitoring fluctuations in exchangeable copper stores in living cells and mice under basal conditions, as well as in situations of copper overload or deficiency. Moreover, we demonstrate the utility of this unique chemical tool to detect aberrant increases in labile copper levels in a murine model of Wilson disease, a genetic disorder that is characterized by accumulation of excess copper. The ability to monitor real-time copper fluxes in living animals offers potentially rich opportunities to examine copper physiology in health and disease.

• A molecular MoS₂ edge site mimic for catalytic hydrogen generation.

  Authors: Hemamala I Karunadasa, Elizabeth Montalvo, Yujie Sun, Marcin Majda, Jeffrey R Long, Christopher J Chang

  Science (New York, N.Y.). 02/2012; 335(6069):698-702.

  Inorganic solids are an important class of catalysts that often derive their activity from sparse active sites that are structurally distinct from the inactive bulk. Rationally optimizing activity isInorganic solids are an important class of catalysts that often derive their activity from sparse active sites that are structurally distinct from the inactive bulk. Rationally optimizing activity is therefore beholden to the challenges in studying these active sites in molecular detail. Here, we report a molecule that mimics the structure of the proposed triangular active edge site fragments of molybdenum disulfide (MoS(2)), a widely used industrial catalyst that has shown promise as a low-cost alternative to platinum for electrocatalytic hydrogen production. By leveraging the robust coordination environment of a pentapyridyl ligand, we synthesized and structurally characterized a well-defined Mo(IV)-disulfide complex that, upon electrochemical reduction, can catalytically generate hydrogen from acidic organic media as well as from acidic water.

• Slow magnetic relaxation in a pseudotetrahedral cobalt(ii) complex with easy-plane anisotropy.

  Authors: Joseph M Zadrozny, Junjie Liu, Nicholas A Piro, Christopher J Chang, Stephen Hill, Jeffrey R Long

  Chemical communications (Cambridge, England). 01/2012;

  A pseudotetrahedral cobalt(ii) complex with a positive axial zero-field splitting parameter of D = 12.7 cm(-1), as determined by high-field EPR spectroscopy, is shown to exhibit slow magneticA pseudotetrahedral cobalt(ii) complex with a positive axial zero-field splitting parameter of D = 12.7 cm(-1), as determined by high-field EPR spectroscopy, is shown to exhibit slow magnetic relaxation under an applied dc field.

• A high-spin iron(IV)-oxo complex supported by a trigonal nonheme pyrrolide platform.

  Authors: Julian P Bigi, W Hill Harman, Benedikt Lassalle-Kaiser, Damon M Robles, Troy A Stich, Junko Yano, R David Britt, Christopher J Chang

  Journal of the American Chemical Society. 01/2012; 134(3):1536-42.

  We report the generation and characterization of a new high-spin iron(IV)-oxo complex supported by a trigonal nonheme pyrrolide platform. Oxygen-atom transfer to [(tpa(Mes))Fe(II)](-) (tpa(Ar) =We report the generation and characterization of a new high-spin iron(IV)-oxo complex supported by a trigonal nonheme pyrrolide platform. Oxygen-atom transfer to [(tpa(Mes))Fe(II)](-) (tpa(Ar) = tris(5-arylpyrrol-2-ylmethyl)amine) in acetonitrile solution affords the Fe(III)-alkoxide product [(tpa(Mes2MesO))Fe(III)](-) resulting from intramolecular C-H oxidation with no observable ferryl intermediates. In contrast, treatment of the phenyl derivative [(tpa(Ph))Fe(II)](-) with trimethylamine N-oxide in acetonitrile solution produces the iron(IV)-oxo complex [(tpa(Ph))Fe(IV)(O)](-) that has been characterized by a suite of techniques, including mass spectrometry as well as UV-vis, FTIR, Mössbauer, XAS, and parallel-mode EPR spectroscopies. Mass spectral, FTIR, and optical absorption studies provide signatures for the iron-oxo chromophore, and Mössbauer and XAS measurements establish the presence of an Fe(IV) center. Moreover, the Fe(IV)-oxo species gives parallel-mode EPR features indicative of a high-spin, S = 2 system. Preliminary reactivity studies show that the high-spin ferryl tpa(Ph) complex is capable of mediating intermolecular C-H oxidation as well as oxygen-atom transfer chemistry.

• Increase of sodium delivery stimulates the mitochondrial respiratory chain H2O2 production in rat renal medullary thick ascending limb.

  Authors: Yusuke Ohsaki, Paul O'Connor, Takefumi Mori, Robert P Ryan, Bryan C Dickinson, Christopher J Chang, Yi Lu, Sadayoshi Ito, Allen W Cowley

  American journal of physiology. Renal physiology. 01/2012; 302(1):F95-F102.

  The mitochondria-rich epithelial cells of the renal medullary thick ascending limb (mTAL) reabsorb nearly 25% of filtered sodium (Na(+)) and are a major source of cellular reactive oxygen species.The mitochondria-rich epithelial cells of the renal medullary thick ascending limb (mTAL) reabsorb nearly 25% of filtered sodium (Na(+)) and are a major source of cellular reactive oxygen species. Although we have shown that delivery of Na(+) to the mTAL of rats increases superoxide (O(2)(·-)) production in mTAL, little is known about H(2)O(2) production, given the lack of robust and selective fluorescent indicators for determining changes within the whole cell, specifically in the mitochondria. The present study determined the effect of increased tubular flow and Na(+) delivery to mTAL on the production of mitochondrial H(2)O(2) in mTAL. H(2)O(2) responses were determined in isolated, perfused mTAL of Sprague-Dawley rats using a novel mitochondrial selective fluorescent H(2)O(2) indicator, mitochondria peroxy yellow 1, and a novel, highly sensitive and stable cytosolic-localized H(2)O(2) indicator, peroxyfluor-6 acetoxymethyl ester. The results showed that mitochondrial H(2)O(2) and cellular fluorescent signals increased progressively over a period of 30 min following increased tubular perfusion (5-20 nl/min), reaching levels of statistical significance at ∼10-12 min. Responses were inhibited with rotenone or antimycin A (inhibitors of the electron-transport chain), polyethylene glycol-catalase and by reducing Na(+) transport with furosemide or ouabain. Inhibition of membrane NADPH-oxidase with apocynin had no effect on mitochondrial H(2)O(2) production. Cytoplasmic H(2)O(2) (peroxyfluor-6 acetoxymethyl ester) increased in parallel with mitochondrial H(2)O(2) (mitochondria peroxy yellow 1) and was partially attenuated (∼65%) by rotenone and completely inhibited by apocynin. The present data provide clear evidence that H(2)O(2) is produced in the mitochondria in response to increased flow and delivery of Na(+) to the mTAL, and that whole cell H(2)O(2) levels are triggered by the mitochondrial reactive oxygen species production. The mitochondrial production of H(2)O(2) may represent an important target for development of more effective antioxidant therapies.

• A two-photon fluorescent probe for ratiometric imaging of hydrogen peroxide in live tissue.

  Authors: Chul Chung, Duangkhae Srikun, Chang Su Lim, Christopher J Chang, Bong Rae Cho

  Chemical communications (Cambridge, England). 09/2011; 47(34):9618-20.

  We report a two-photon fluorescent probe (PN1) that can be excited by 750 nm femto-second pulses, shows high photostability and negligible toxicity, and can visualize H(2)O(2) distribution in liveWe report a two-photon fluorescent probe (PN1) that can be excited by 750 nm femto-second pulses, shows high photostability and negligible toxicity, and can visualize H(2)O(2) distribution in live cells and tissue by two-photon microscopy.

• A nuclear-localized fluorescent hydrogen peroxide probe for monitoring sirtuin-mediated oxidative stress responses in vivo.

  Authors: Bryan C Dickinson, Yan Tang, Zengyi Chang, Christopher J Chang

  Chemistry & biology. 08/2011; 18(8):943-8.

  Hydrogen peroxide (H(2)O(2)) can serve as a beneficial signaling agent or toxin depending on its concentration and location within a cell or organism. Methods to measure the localized accumulation ofHydrogen peroxide (H(2)O(2)) can serve as a beneficial signaling agent or toxin depending on its concentration and location within a cell or organism. Methods to measure the localized accumulation of H(2)O(2) in living specimens remain limited. Motivated to meet this need, we have developed a nuclear-localized fluorescent probe for H(2)O(2), Nuclear Peroxy Emerald 1 (NucPE1), to selectively interrogate ROS fluxes within this sensitive organelle. NucPE1 selectively accumulates in the nuclei of a variety of mammalian cell lines as well as in whole model organisms like Caenorhabditis elegans, where it can respond to subcellular changes in H(2)O(2) fluxes. Moreover, in vivo NucPE1 imaging reveals a reduction in nuclear H(2)O(2) levels in worms overexpressing sir-2.1 compared with wild-type congeners, supporting a link between this longevity-promoting sirtuin protein and enhanced regulation of nuclear ROS pools.

• Boronate oxidation as a bioorthogonal reaction approach for studying the chemistry of hydrogen peroxide in living systems.

  Authors: Alexander R Lippert, Genevieve C Van de Bittner, Christopher J Chang

  Accounts of chemical research. 08/2011; 44(9):793-804.

  Reactive oxygen species (ROS), such as hydrogen peroxide, are important products of oxygen metabolism that, when misregulated, can accumulate and cause oxidative stress inside cells. Accordingly,Reactive oxygen species (ROS), such as hydrogen peroxide, are important products of oxygen metabolism that, when misregulated, can accumulate and cause oxidative stress inside cells. Accordingly, organisms have evolved molecular systems, including antioxidant metalloenzymes (such as superoxide dismutase and catalase) and an array of thiol-based redox couples, to neutralize this threat to the cell when it occurs. On the other hand, emerging evidence shows that the controlled generation of ROS, particularly H(2)O(2), is necessary to maintain cellular fitness. The identification of NADPH oxidase enzymes, which generate specific ROS and reside in virtually all cell types throughout the body, is a prime example. Indeed, a growing body of work shows that H(2)O(2) and other ROS have essential functions in healthy physiological signaling pathways. The signal-stress dichotomy of H(2)O(2) serves as a source of motivation for disentangling its beneficial from its detrimental effects on living systems. Molecular imaging of this oxygen metabolite with reaction-based probes is a powerful approach for real-time, noninvasive monitoring of H(2)O(2) chemistry in biological specimens, but two key challenges to studying H(2)O(2) in this way are chemoselectivity and bioorthogonality of probe molecules. Chemoselectivity is problematic because traditional methods for ROS detection suffer from nonspecific reactivity with other ROS. Moreover, some methods require enzymatic additives not compatible with live-cell or live-animal specimens. Additionally, bioorthogonality requires that the reactions must not compete with or disturb intrinsic cellular chemistry; this requirement is particularly critical with thiol- or metal-based couples mediating the major redox events within the cell. Chemoselective bioorthogonal reactions, such as alkyne-azide cycloadditions and related click reactions, the Staudinger-Bertozzi ligation, and the transformations used in various reaction-based molecular probes, have found widespread application in the modification, labeling, and detection of biological molecules and processes. In this Account, we summarize H(2)O(2) studies from our laboratory using the H(2)O(2)-mediated oxidation of aryl boronates to phenols as a bioorthogonal approach to detect fluxes of this important ROS in living systems. We have installed this versatile switch onto organic and inorganic scaffolds to serve as "turn-on" probes for visible and near-infrared (NIR) fluorescence, ratiometric fluorescence, time-gated lanthanide luminescence, and in vivo bioluminescence detection of H(2)O(2) in living cells and animals. Further chemical and genetic manipulations target these probes to specific organelles and other subcellular locales and can also allow them to be trapped intracellularly, enhancing their sensitivity. These novel chemical tools have revealed fundamental new biological insights into the production, localization, trafficking, and in vivo roles of H(2)O(2) in a wide variety of living systems, including immune, cancer, stem, and neural cell models.

• Mfc1 is a novel forespore membrane copper transporter in meiotic and sporulating cells.

  Authors: Jude Beaudoin, Raphaël Ioannoni, Luis López-Maury, Jürg Bähler, Samia Ait-Mohand, Brigitte Guérin, Sheel C Dodani, Christopher J Chang, Simon Labbé

  The Journal of biological chemistry. 08/2011; 286(39):34356-72.

  To gain insight in the molecular basis of copper homeostasis during meiosis, we have used DNA microarrays to analyze meiotic gene expression in the model yeast Schizosaccharomyces pombe. ProfilingTo gain insight in the molecular basis of copper homeostasis during meiosis, we have used DNA microarrays to analyze meiotic gene expression in the model yeast Schizosaccharomyces pombe. Profiling data identified a novel meiosis-specific gene, termed mfc1(+), that encodes a putative major facilitator superfamily-type transporter. Although Mfc1 does not exhibit any significant sequence homology with the copper permease Ctr4, it contains four putative copper-binding motifs that are typically found in members of the copper transporter family of copper transporters. Similarly to the ctr4(+) gene, the transcription of mfc1(+) was induced by low concentrations of copper. However, its temporal expression profile during meiosis was distinct to ctr4(+). Whereas Ctr4 was observed at the plasma membrane shortly after induction of meiosis, Mfc1 appeared later in precursor vesicles and, subsequently, at the forespore membrane of ascospores. Using the fluorescent copper-binding tracker Coppersensor-1 (CS1), labile cellular copper was primarily detected in the forespores in an mfc1(+)/mfc1(+) strain, whereas an mfc1Δ/mfc1Δ mutant exhibited an intracellular dispersed punctate distribution of labile copper ions. In addition, the copper amine oxidase Cao1, which localized primarily in the forespores of asci, was fully active in mfc1(+)/mfc1(+) cells, but its activity was drastically reduced in an mfc1Δ/mfc1Δ strain. Furthermore, our data showed that meiotic cells that express the mfc1(+) gene have a distinct developmental advantage over mfc1Δ/mfc1Δ mutant cells when copper is limiting. Taken together, the data reveal that Mfc1 serves to transport copper for accurate and timely meiotic differentiation under copper-limiting conditions.

• Molecular cobalt pentapyridine catalysts for generating hydrogen from water.

  Authors: Yujie Sun, Julian P Bigi, Nicholas A Piro, Ming Lee Tang, Jeffrey R Long, Christopher J Chang

  Journal of the American Chemical Society. 06/2011; 133(24):9212-5.

  A set of robust molecular cobalt catalysts for the generation of hydrogen from water is reported. The cobalt complex supported by the parent pentadentate polypyridyl ligand PY5Me(2) features highA set of robust molecular cobalt catalysts for the generation of hydrogen from water is reported. The cobalt complex supported by the parent pentadentate polypyridyl ligand PY5Me(2) features high stability and activity and 100% Faradaic efficiency for the electrocatalytic production of hydrogen from neutral water, with a turnover number reaching 5.5 × 10(4) mol of H(2) per mole of catalyst with no loss in activity over 60 h. Control experiments establish that simple Co(II) salts, the free PY5Me(2) ligand, and an isostructural PY5Me(2) complex containing redox-inactive Zn(II) are all ineffective for this reaction. Further experiments demonstrate that the overpotential for H(2) evolution can be tuned by systematic substitutions on the ancillary PY5Me(2) scaffold, presaging opportunities to further optimize this first-generation platform by molecular design.

• Nickel N-heterocyclic carbene-pyridine complexes that exhibit selectivity for electrocatalytic reduction of carbon dioxide over water.

  Authors: V Sara Thoi, Christopher J Chang

  Chemical communications (Cambridge, England). 06/2011; 47(23):6578-80.

  We report a homologous series of nickel(II) complexes supported by N-heterocyclic carbene-pyridine ((R)bimpy, R = Me, Et, Pr) ligands that exhibit high selectivity for reducing carbon dioxide overWe report a homologous series of nickel(II) complexes supported by N-heterocyclic carbene-pyridine ((R)bimpy, R = Me, Et, Pr) ligands that exhibit high selectivity for reducing carbon dioxide over water under electrocatalytic conditions.

• Reaction-based fluorescent probes for selective imaging of hydrogen sulfide in living cells.

  Authors: Alexander R Lippert, Elizabeth J New, Christopher J Chang

  Journal of the American Chemical Society. 06/2011; 133(26):10078-80.

  Hydrogen sulfide (H(2)S) is emerging as an important mediator of human physiology and pathology but remains difficult to study, in large part because of the lack of methods for selective monitoringHydrogen sulfide (H(2)S) is emerging as an important mediator of human physiology and pathology but remains difficult to study, in large part because of the lack of methods for selective monitoring of this small signaling molecule in live biological specimens. We now report a pair of new reaction-based fluorescent probes for selective imaging of H(2)S in living cells that exploit the H(2)S-mediated reduction of azides to fluorescent amines. Sulfidefluor-1 (SF1) and Sulfidefluor-2 (SF2) respond to H(2)S by a turn-on fluorescence signal enhancement and display high selectivity for H(2)S over other biologically relevant reactive sulfur, oxygen, and nitrogen species. In addition, SF1 and SF2 can be used to detect H(2)S in both water and live cells, providing a potentially powerful approach for probing H(2)S chemistry in biological systems.

• A targetable fluorescent sensor reveals that copper-deficient SCO1 and SCO2 patient cells prioritize mitochondrial copper homeostasis.

  Authors: Sheel C Dodani, Scot C Leary, Paul A Cobine, Dennis R Winge, Christopher J Chang

  Journal of the American Chemical Society. 06/2011; 133(22):8606-16.

  We present the design, synthesis, spectroscopy, and biological applications of Mitochondrial Coppersensor-1 (Mito-CS1), a new type of targetable fluorescent sensor for imaging exchangeableWe present the design, synthesis, spectroscopy, and biological applications of Mitochondrial Coppersensor-1 (Mito-CS1), a new type of targetable fluorescent sensor for imaging exchangeable mitochondrial copper pools in living cells. Mito-CS1 is a bifunctional reporter that combines a Cu(+)-responsive fluorescent platform with a mitochondrial-targeting triphenylphosphonium moiety for localizing the probe to this organelle. Molecular imaging with Mito-CS1 establishes that this new chemical tool can detect changes in labile mitochondrial Cu(+) in a model HEK 293T cell line as well as in human fibroblasts. Moreover, we utilized Mito-CS1 in a combined imaging and biochemical study in fibroblasts derived from patients with mutations in the two synthesis of cytochrome c oxidase 1 and 2 proteins (SCO1 and SCO2), each of which is required for assembly and metalation of functionally active cytochrome c oxidase (COX). Interestingly, we observe that although defects in these mitochondrial metallochaperones lead to a global copper deficiency at the whole cell level, total copper and exchangeable mitochondrial Cu(+) pools in SCO1 and SCO2 patient fibroblasts are largely unaltered relative to wild-type controls. Our findings reveal that the cell maintains copper homeostasis in mitochondria even in situations of copper deficiency and mitochondrial metallochaperone malfunction, illustrating the importance of regulating copper stores in this energy-producing organelle.

• A hydrogen peroxide-responsive hyperpolarized 13C MRI contrast agent.

  Authors: Alexander R Lippert, Kayvan R Keshari, John Kurhanewicz, Christopher J Chang

  Journal of the American Chemical Society. 03/2011; 133(11):3776-9.

  We report a new reaction-based approach for the detection of hydrogen peroxide (H(2)O(2)) using hyperpolarized (13)C magnetic resonance imaging ((13)C MRI) and the H(2)O(2)-mediated oxidation ofWe report a new reaction-based approach for the detection of hydrogen peroxide (H(2)O(2)) using hyperpolarized (13)C magnetic resonance imaging ((13)C MRI) and the H(2)O(2)-mediated oxidation of α-ketoacids to carboxylic acids. (13)C-Benzoylformic acid reacts selectively with H(2)O(2) over other reactive oxygen species to generate (13)C-benzoic acid and can be hyperpolarized using dynamic nuclear polarization, providing a method for dual-frequency detection of H(2)O(2). Phantom images collected using frequency-specific imaging sequences demonstrate the efficacy of this responsive contrast agent to monitor H(2)O(2) at pre-clinical field strengths. The combination of reaction-based detection chemistry and hyperpolarized (13)C MRI provides a potentially powerful new methodology for non-invasive multi-analyte imaging in living systems.

• Calcium-dependent copper redistributions in neuronal cells revealed by a fluorescent copper sensor and X-ray fluorescence microscopy.

  Authors: Sheel C Dodani, Dylan W Domaille, Christine I Nam, Evan W Miller, Lydia A Finney, Stefan Vogt, Christopher J Chang

  Proceedings of the National Academy of Sciences of the United States of America. 03/2011; 108(15):5980-5.

  Dynamic fluxes of s-block metals like potassium, sodium, and calcium are of broad importance in cell signaling. In contrast, the concept of mobile transition metals triggered by cell activationDynamic fluxes of s-block metals like potassium, sodium, and calcium are of broad importance in cell signaling. In contrast, the concept of mobile transition metals triggered by cell activation remains insufficiently explored, in large part because metals like copper and iron are typically studied as static cellular nutrients and there are a lack of direct, selective methods for monitoring their distributions in living cells. To help meet this need, we now report Coppersensor-3 (CS3), a bright small-molecule fluorescent probe that offers the unique capability to image labile copper pools in living cells at endogenous, basal levels. We use this chemical tool in conjunction with synchotron-based microprobe X-ray fluorescence microscopy (XRFM) to discover that neuronal cells move significant pools of copper from their cell bodies to peripheral processes upon their activation. Moreover, further CS3 and XRFM imaging experiments show that these dynamic copper redistributions are dependent on calcium release, establishing a link between mobile copper and major cell signaling pathways. By providing a small-molecule fluorophore that is selective and sensitive enough to image labile copper pools in living cells under basal conditions, CS3 opens opportunities for discovering and elucidating functions of copper in living systems.

• A structurally characterized nitrous oxide complex of vanadium.

  Authors: Nicholas A Piro, Michael F Lichterman, W Hill Harman, Christopher J Chang

  Journal of the American Chemical Society. 02/2011; 133(7):2108-11.

  Nitrous oxide (N(2)O), a widespread greenhouse gas, is a thermodynamically potent and environmentally green oxidant that is an attractive target for activation by metal centers. However, N(2)ONitrous oxide (N(2)O), a widespread greenhouse gas, is a thermodynamically potent and environmentally green oxidant that is an attractive target for activation by metal centers. However, N(2)O remains underutilized owing to its high kinetic stability, and the poor ligand properties of this molecule have made well-characterized metal-N(2)O complexes a rarity. We now report a vanadium-pyrrolide system that reversibly binds N(2)O at room temperature and provide the first single-crystal X-ray structure of such a complex. Further characterization by vibrational spectroscopy and DFT calculations strongly favor assignment as a linear, N-bound metal-N(2)O complex.

• Bacterial killing by dry metallic copper surfaces.

  Authors: Christophe Espírito Santo, Ee Wen Lam, Christian G Elowsky, Davide Quaranta, Dylan W Domaille, Christopher J Chang, Gregor Grass

  Applied and environmental microbiology. 02/2011; 77(3):794-802.

  Metallic copper surfaces rapidly and efficiently kill bacteria. Cells exposed to copper surfaces accumulated large amounts of copper ions, and this copper uptake was faster from dry copper than fromMetallic copper surfaces rapidly and efficiently kill bacteria. Cells exposed to copper surfaces accumulated large amounts of copper ions, and this copper uptake was faster from dry copper than from moist copper. Cells suffered extensive membrane damage within minutes of exposure to dry copper. Further, cells removed from copper showed loss of cell integrity. Acute contact with metallic copper surfaces did not result in increased mutation rates or DNA lesions. These findings are important first steps for revealing the molecular sensitive targets in cells lethally challenged by exposure to copper surfaces and provide a scientific explanation for the use of copper surfaces as antimicrobial agents for supporting public hygiene.

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