Title: Hydropersulfides (RSSH) and Nitric Oxide (NO) Signaling: Possible Effects on S-Nitrosothiols (RS-NO)
S-Nitrosothiol (RS-NO) formation in proteins and peptides have been implicated as factors in the etiology of many diseases and as possible regulators of thiol protein function. They have also been proposed as possible storage forms of nitric oxide (NO). However, despite their proposed functions/roles, there appears to be little consensus regarding the physiological mechanisms of RS-NO formation and degradation. Hydropersulfides (RSSH) have recently been discovered as endogenously generated species with unique reactivity. One important reaction of RSSH is with RS-NO, which leads to the degradation of RS-NO as well as the release of NO. Thus, it can be speculated that RSSH can be a factor in the regulation of steady-state RS-NO levels, and therefore may be important in RS-NO (patho)physiology. Moreover, RSSH-mediated NO release from RS-NO may be a possible mechanism allowing RS-NO to serve as a storage form of NO. more »« less
Khodade, Vinayak S.; Aggarwal, Sahil C.; Pharoah, Blaze M.; Paolocci, Nazareno; Toscano, John P.(
, Chemical Science)
null
(Ed.)
The recent discovery of the prevalence of hydropersulfides (RSSH) species in biological systems suggests their potential roles in cell regulatory processes. However, the reactive and transient nature of RSSH makes their study difficult, and dependent on the use of donor molecules. Herein, we report alkylsulfenyl thiocarbonates as a new class of RSSH precursors that efficiently release RSSH under physiologically relevant conditions. RSSH release kinetics from these precursors are tunable through electronic modification of the thiocarbonate carbonyl group's electrophilicity. In addition, these precursors also react with thiols to release RSSH with a minor amount of carbonyl sulfide (COS). Importantly, RSSH generation by these precursors protects against oxidative stress in H9c2 cardiac myoblasts. Furthermore, we demonstrate the ability of these precursors to increase intracellular RSSH levels.
Tolentino, Mark Q.; Hartmann, Alyssa K.; Loe, David T.; Rouge, Jesssica L.(
, Journal of Materials Chemistry B)
This work highlights a multifunctional nanoscale material which can effectively compartmentalize small molecules and biomolecules into a single, micellar structure with programmable degradation properties resulting in highly controllable release properties. The nanomaterial consists of a ZIF-8 metal organic framework (MOF) encapsulated within a DNA surfactant micelle assembly, referred to as a nucleic acid nanocapsule (NAN). NANs have been demonstrated to enter cells through endocytosis and result in intracellular cargo release upon enzyme-triggered degradation. By combining the favorable properties of MOFs (large storage capacity) with those of NANs (triggerable release), we show diverse molecular cargo can be integrated into a single, highly programmable nanomaterial with controllable release profiles. The hybrid MOF–NANs exhibit double-gated regulation capabilities as evidenced by kinetic studies of encapsulated enzymes that indicate individual layers of the particle influence the overall enzymatic rate of turnover. The degradation of MOF–NANs can be controlled under multiple combined stimuli ( i.e. varying pH, enzymes), enabling selective release profiles in solutions representative of more complex biological systems. Lastly, the enhanced control over the release of small molecules, proteins and plasmids, is evaluated through a combination of cell culture and in vitro fluorescence assays, indicating the potential of MOF–NANs for both therapeutic and diagnostic applications.
Non‐heme high‐spin (hs) {FeNO}8complexes have been proposed as important intermediates towards N2O formation in flavodiiron NO reductases (FNORs). Many hs‐{FeNO}8complexes disproportionate by forming dinitrosyl iron complexes (DNICs), but the mechanism of this reaction is not understood. While investigating this process, we isolated a new type of non‐heme iron nitrosyl complex that is stabilized by an unexpected spin‐state change. Upon reduction of the hs‐{FeNO}7complex, [Fe(TPA)(NO)(OTf)](OTf) (1), the N‐O stretching band vanishes, but no sign of DNIC or N2O formation is observed. Instead, the dimer, [Fe2(TPA)2(NO)2](OTf)2(2) could be isolated and structurally characterized. We propose that2is formed from dimerization of the hs‐{FeNO}8intermediate, followed by a spin state change of the iron centers to low‐spin (ls), and speculate that2models intermediates in hs‐{FeNO}8complexes that precede the disproportionation reaction.
Dong, Hai T.; Speelman, Amy L.; Kozemchak, Claire E.; Sil, Debangsu; Krebs, Carsten; Lehnert, Nicolai(
, Angewandte Chemie International Edition)
Abstract
Non‐heme high‐spin (hs) {FeNO}8complexes have been proposed as important intermediates towards N2O formation in flavodiiron NO reductases (FNORs). Many hs‐{FeNO}8complexes disproportionate by forming dinitrosyl iron complexes (DNICs), but the mechanism of this reaction is not understood. While investigating this process, we isolated a new type of non‐heme iron nitrosyl complex that is stabilized by an unexpected spin‐state change. Upon reduction of the hs‐{FeNO}7complex, [Fe(TPA)(NO)(OTf)](OTf) (1), the N‐O stretching band vanishes, but no sign of DNIC or N2O formation is observed. Instead, the dimer, [Fe2(TPA)2(NO)2](OTf)2(2) could be isolated and structurally characterized. We propose that2is formed from dimerization of the hs‐{FeNO}8intermediate, followed by a spin state change of the iron centers to low‐spin (ls), and speculate that2models intermediates in hs‐{FeNO}8complexes that precede the disproportionation reaction.
The traditional von Neumann architecture limits the increase in computing efficiency and results in massive power consumption in modern computers due to the separation of storage and processing units. The novel neuromorphic computation system, an in-memory computing architecture with low power consumption, is aimed to break the bottleneck and meet the needs of the next generation of artificial intelligence (AI) systems. Thus, it is urgent to find a memory technology to implement the neuromorphic computing nanosystem. Nowadays, the silicon-based flash memory dominates non-volatile memory market, however, it is facing challenging issues to achieve the requirements of future data storage device development due to the drawbacks, such as scaling issue, relatively slow operation speed, and high voltage for program/erase operations. The emerging resistive random-access memory (RRAM) has prompted extensive research as its simple two-terminal structure, including top electrode (TE) layer, bottom electrode (BE) layer, and an intermediate resistive switching (RS) layer. It can utilize a temporary and reversible dielectric breakdown to cause the RS phenomenon between the high resistance state (HRS) and the low resistance state (LRS). RRAM is expected to outperform conventional memory device with the advantages, notably its low-voltage operation, short programming time, great cyclic stability, and good scalability. Among the materials for RS layer, indium gallium zinc oxide (IGZO) has shown attractive prospects in abundance and high atomic diffusion property of oxygen atoms, transparency. Additionally, its electrical properties can be easily modulated by controlling the stoichiometric ratio of indium and gallium as well as oxygen potential in the sputter gas. Moreover, since the IGZO can be applied to both the thin-film transistor (TFT) channel and RS layer, it has a great potential for fully integrated transparent electronics application. In this work, we proposed amorphous transparent IGZO-based RRAMs and investigated switching behaviors of the memory cells prepared with different top electrodes. First, ITO was choosing to serve as both TE and BE to achieve high transmittance. A multi-target magnetron sputtering system was employed to deposit all three layers (TE, RS, BE layers) on glass substrate. I-V characteristics were evaluated by a semiconductor parameter analyzer, and the bipolar RS feature of our RRAM devices was demonstrated by typical butterfly curves. The optical transmission analysis was carried out via a UV-Vis spectrometer and the average transmittance was around 80% out of entire devices in the visible-light wavelength range, implying high transparency. We adjusted the oxygen partial pressure during the sputtering of IGZO to optimize the property because the oxygen vacancy concentration governs the RS performance. Electrode selection is crucial and can impact the performance of the whole device. Thus, Cu TE was chosen for our second type of device because the diffusion of Cu ions can be beneficial for the formation of the conductive filament (CF). A ~5 nm SiO 2 barrier layer was employed between TE and RS layers to confine the diffusion of Cu into the RS layer. At the same time, this SiO 2 inserting layer can provide an additional interfacial series resistance in the device to lower the off current, consequently, improve the on/off ratio and whole performance. Finally, an oxygen affinity metal Ti was selected as the TE for our third type of device because the concentration of the oxygen atoms can be shifted towards the Ti electrode, which provides an oxygengettering activity near the Ti metal. This process may in turn lead to the formation of a sub-stoichiometric region in the neighboring oxide that is believed to be the origin of better performance. In conclusion, the transparent amorphous IGZO-based RRAMs were established. To tune the property of RS layer, the sputtering conditions of RS were varied. To investigate the influence of TE selections on switching performance of RRAMs, we integrated a set of TE materials, and a barrier layer on IGZO-based RRAM and compared the switch characteristics. Our encouraging results clearly demonstrate that IGZO is a promising material in RRAM applications and breaking the bottleneck of current memory technologies.
Fukuto, Jon M., Perez-Ternero, Cristina, Zarenkiewicz, Jessica, Lin, Joseph, Hobbs, Adrian J., and Toscano, John P. Hydropersulfides (RSSH) and Nitric Oxide (NO) Signaling: Possible Effects on S-Nitrosothiols (RS-NO). Retrieved from https://par.nsf.gov/biblio/10382960. Antioxidants 11.1 Web. doi:10.3390/antiox11010169.
Fukuto, Jon M., Perez-Ternero, Cristina, Zarenkiewicz, Jessica, Lin, Joseph, Hobbs, Adrian J., & Toscano, John P. Hydropersulfides (RSSH) and Nitric Oxide (NO) Signaling: Possible Effects on S-Nitrosothiols (RS-NO). Antioxidants, 11 (1). Retrieved from https://par.nsf.gov/biblio/10382960. https://doi.org/10.3390/antiox11010169
Fukuto, Jon M., Perez-Ternero, Cristina, Zarenkiewicz, Jessica, Lin, Joseph, Hobbs, Adrian J., and Toscano, John P.
"Hydropersulfides (RSSH) and Nitric Oxide (NO) Signaling: Possible Effects on S-Nitrosothiols (RS-NO)". Antioxidants 11 (1). Country unknown/Code not available. https://doi.org/10.3390/antiox11010169.https://par.nsf.gov/biblio/10382960.
@article{osti_10382960,
place = {Country unknown/Code not available},
title = {Hydropersulfides (RSSH) and Nitric Oxide (NO) Signaling: Possible Effects on S-Nitrosothiols (RS-NO)},
url = {https://par.nsf.gov/biblio/10382960},
DOI = {10.3390/antiox11010169},
abstractNote = {S-Nitrosothiol (RS-NO) formation in proteins and peptides have been implicated as factors in the etiology of many diseases and as possible regulators of thiol protein function. They have also been proposed as possible storage forms of nitric oxide (NO). However, despite their proposed functions/roles, there appears to be little consensus regarding the physiological mechanisms of RS-NO formation and degradation. Hydropersulfides (RSSH) have recently been discovered as endogenously generated species with unique reactivity. One important reaction of RSSH is with RS-NO, which leads to the degradation of RS-NO as well as the release of NO. Thus, it can be speculated that RSSH can be a factor in the regulation of steady-state RS-NO levels, and therefore may be important in RS-NO (patho)physiology. Moreover, RSSH-mediated NO release from RS-NO may be a possible mechanism allowing RS-NO to serve as a storage form of NO.},
journal = {Antioxidants},
volume = {11},
number = {1},
author = {Fukuto, Jon M. and Perez-Ternero, Cristina and Zarenkiewicz, Jessica and Lin, Joseph and Hobbs, Adrian J. and Toscano, John P.},
}
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