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Omar K Farha - One of the best experts on this subject based on the ideXlab platform.
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product inhibition and the catalytic destruction of a Nerve Agent simulant by zirconium based metal organic frameworks
ACS Applied Materials & Interfaces, 2021Co-Authors: Yijun Liao, Omar K Farha, Thomas R Sheridan, Jian Liu, Joseph T. HuppAbstract:Rapid degradation/destruction of chemical warfare Agents, especially ones containing a phosphorous-fluorine bond, is of notable interest due to their extreme toxicity and typically rapid rate of human incapacitation. Recent studies of the hydrolytic destruction of a key Nerve Agent simulant, dimethyl 4-nitrophenylphosphate (DMNP), catalyzed by Zr6-based metal-organic frameworks (MOFs), have suggested deactivation of the active sites due to inhibition by the products as the reaction progresses. In this study, the interactions of two MOFs, NU-1000 and MOF-808, and two hydrolysis products, dimethyl phosphate (DMP) and ethyl methyl phosphonate (EMP), from the hydrolysis of the simulant (DMNP) and Nerve Agent ethyl methylphosphonofluoridate (EMPF), resembling the hydrolysis degradation product of the G-series Nerve Agent, Sarin (GB), have been investigated to deconvolute the effect of product inhibition from other effects on catalytic activity. Kinetic studies via in situ nuclear magnetic resonance spectroscopy indicated substantial product inhibition upon catalyst activity after several tens to several thousand turnovers, depending on specific conditions. Apparent product binding constants were obtained by fitting initial reaction rates at pH 7.0 and pH 10.5 to a Langmuir-Freundlich binding/adsorption model. For the fits, varying amounts/concentrations of candidate inhibitors were introduced before the start of catalytic hydrolysis. The derived binding constants proved suitable for quantitatively describing product inhibition effects upon reaction rates over the extended time course of simulant hydrolysis by aqua-ligand-bearing hexa-zirconium(IV) nodes.
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rapid biomimetic degradation of a Nerve Agent simulant by incorporating imidazole bases into a metal organic framework
ACS Catalysis, 2021Co-Authors: Hongbin Luo, Omar K Farha, Anthony J Castro, Megan C Wasson, Willmer I Flores, Yangyang LiuAbstract:Metal-organic frameworks (MOFs) are excellent catalytic materials for the hydrolytic degradation of Nerve Agents and their simulants. However, most of the MOF-based hydrolysis catalysts to date are reliant on liquid water media buffered by a volatile liquid base. To overcome this practical limitation, we developed a simple and feasible strategy to synthesize MOF composites that structurally mimic phosphotriesterase's active site as well as its ligated histidine residues. By incorporating imidazole and its derivative into the pores of MOF-808, the obtained MOF composites achieved rapid degradation of a Nerve Agent simulant (dimethyl-4-nitrophenyl phosphate, DMNP) in pure water as well as in a humid environment without liquid base. Remarkably, one of the composites Im@MOF-808 displayed the highest catalytic activity for DMNP hydrolysis in unbuffered aqueous solutions among all reported MOF-based catalysts. Furthermore, solid-phase catalysis showed that Im@MOF-808 can also rapidly hydrolyze DMNP under high-humidity conditions without bulk water or external bases. This work provides a viable solution toward the implementation of MOF materials into protective equipment for practical Nerve Agent detoxification.
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nanosizing a metal organic framework enzyme carrier for accelerating Nerve Agent hydrolysis
ACS Nano, 2016Co-Authors: Peng Li, Su-young Moon, Joseph T. Hupp, Mark A Guelta, Diego A Gomezgualdron, Randall Q Snurr, Steven P Harvey, Omar K FarhaAbstract:We report the synthesis and characterization of a water-stable zirconium metal–organic framework (MOF), NU-1003, featuring the largest mesoporous aperture known for a zirconium MOF. This material has been used to immobilize the Nerve Agent hydrolyzing enzyme, organophosphorus acid anhydrolase (OPAA). The catalytic efficiency of immobilized OPAA in nanosized NU-1003 is significantly increased compared to that of OPAA immobilized in microsized NU-1003 and even exceeds that of the free OPAA enzyme. This paper highlights a method for rapid and highly efficient hydrolysis of Nerve Agents using nanosized enzyme carriers.
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tailoring the pore size and functionality of uio type metal organic frameworks for optimal Nerve Agent destruction
Inorganic Chemistry, 2015Co-Authors: Gregory W Peterson, Su-young Moon, Joseph T. Hupp, Jared B Decoste, George W Wagner, Morgan G Hall, Omar K FarhaAbstract:Evaluation of UiO-66 and UiO-67 metal–organic framework derivatives as catalysts for the degradation of soman, a chemical warfare Agent, showed the importance of both the linker size and functionality. The best catalysts yielded half-lives of less than 1 min. Further testing with a Nerve Agent simulant established that different rate-assessment techniques yield similar values for degradation half-lives.
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Instantaneous hydrolysis of Nerve-Agent simulants with a six-connected zirconium-based metal-organic framework
Angewandte Chemie - International Edition, 2015Co-Authors: Su-young Moon, Yangyang Liu, Joseph T. Hupp, Omar K FarhaAbstract:A Nerve-Agent simulant based on a phosphate ester is hydrolyzed using a MOF-based catalyst. Suspensions of MOF-808 (6-connected), a material featuring 6-connected zirconium nodes, display the highest hydrolysis rates among all MOFs that have been reported to date. A plug-flow reactor was also prepared with MOF-808 (6-connected) as the active layer. Deployed in a simple filtration scheme, the reactor displayed high hydrolysis efficiency and reusability.
Joseph T. Hupp - One of the best experts on this subject based on the ideXlab platform.
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product inhibition and the catalytic destruction of a Nerve Agent simulant by zirconium based metal organic frameworks
ACS Applied Materials & Interfaces, 2021Co-Authors: Yijun Liao, Omar K Farha, Thomas R Sheridan, Jian Liu, Joseph T. HuppAbstract:Rapid degradation/destruction of chemical warfare Agents, especially ones containing a phosphorous-fluorine bond, is of notable interest due to their extreme toxicity and typically rapid rate of human incapacitation. Recent studies of the hydrolytic destruction of a key Nerve Agent simulant, dimethyl 4-nitrophenylphosphate (DMNP), catalyzed by Zr6-based metal-organic frameworks (MOFs), have suggested deactivation of the active sites due to inhibition by the products as the reaction progresses. In this study, the interactions of two MOFs, NU-1000 and MOF-808, and two hydrolysis products, dimethyl phosphate (DMP) and ethyl methyl phosphonate (EMP), from the hydrolysis of the simulant (DMNP) and Nerve Agent ethyl methylphosphonofluoridate (EMPF), resembling the hydrolysis degradation product of the G-series Nerve Agent, Sarin (GB), have been investigated to deconvolute the effect of product inhibition from other effects on catalytic activity. Kinetic studies via in situ nuclear magnetic resonance spectroscopy indicated substantial product inhibition upon catalyst activity after several tens to several thousand turnovers, depending on specific conditions. Apparent product binding constants were obtained by fitting initial reaction rates at pH 7.0 and pH 10.5 to a Langmuir-Freundlich binding/adsorption model. For the fits, varying amounts/concentrations of candidate inhibitors were introduced before the start of catalytic hydrolysis. The derived binding constants proved suitable for quantitatively describing product inhibition effects upon reaction rates over the extended time course of simulant hydrolysis by aqua-ligand-bearing hexa-zirconium(IV) nodes.
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nanosizing a metal organic framework enzyme carrier for accelerating Nerve Agent hydrolysis
ACS Nano, 2016Co-Authors: Peng Li, Su-young Moon, Joseph T. Hupp, Mark A Guelta, Diego A Gomezgualdron, Randall Q Snurr, Steven P Harvey, Omar K FarhaAbstract:We report the synthesis and characterization of a water-stable zirconium metal–organic framework (MOF), NU-1003, featuring the largest mesoporous aperture known for a zirconium MOF. This material has been used to immobilize the Nerve Agent hydrolyzing enzyme, organophosphorus acid anhydrolase (OPAA). The catalytic efficiency of immobilized OPAA in nanosized NU-1003 is significantly increased compared to that of OPAA immobilized in microsized NU-1003 and even exceeds that of the free OPAA enzyme. This paper highlights a method for rapid and highly efficient hydrolysis of Nerve Agents using nanosized enzyme carriers.
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tailoring the pore size and functionality of uio type metal organic frameworks for optimal Nerve Agent destruction
Inorganic Chemistry, 2015Co-Authors: Gregory W Peterson, Su-young Moon, Joseph T. Hupp, Jared B Decoste, George W Wagner, Morgan G Hall, Omar K FarhaAbstract:Evaluation of UiO-66 and UiO-67 metal–organic framework derivatives as catalysts for the degradation of soman, a chemical warfare Agent, showed the importance of both the linker size and functionality. The best catalysts yielded half-lives of less than 1 min. Further testing with a Nerve Agent simulant established that different rate-assessment techniques yield similar values for degradation half-lives.
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Instantaneous hydrolysis of Nerve-Agent simulants with a six-connected zirconium-based metal-organic framework
Angewandte Chemie - International Edition, 2015Co-Authors: Su-young Moon, Yangyang Liu, Joseph T. Hupp, Omar K FarhaAbstract:A Nerve-Agent simulant based on a phosphate ester is hydrolyzed using a MOF-based catalyst. Suspensions of MOF-808 (6-connected), a material featuring 6-connected zirconium nodes, display the highest hydrolysis rates among all MOFs that have been reported to date. A plug-flow reactor was also prepared with MOF-808 (6-connected) as the active layer. Deployed in a simple filtration scheme, the reactor displayed high hydrolysis efficiency and reusability.
Diego Troya - One of the best experts on this subject based on the ideXlab platform.
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Correlated Multimodal Approach Reveals Key Details of Nerve-Agent Decomposition by Single-Site Zr-Based Polyoxometalates.
The Journal of Physical Chemistry Letters, 2019Co-Authors: Yiyao Tian, Anna M. Plonka, Amani M. Ebrahim, Robert M. Palomino, Sanjaya D. Senanayake, Alex Balboa, Wesley O. Gordon, Diego Troya, Djamaladdin G. Musaev, John R. MorrisAbstract:Development of technologies for protection against chemical warfare Agents (CWAs) is critically important. Recently, polyoxometalates have attracted attention as potential catalysts for Nerve-Agent decomposition. Improvement of their effectiveness in real operating conditions requires an atomic-level understanding of CWA decomposition at the gas–solid interface. We investigated decomposition of the Nerve Agent Sarin and its simulant, dimethyl chlorophosphate (DMCP), by zirconium polytungstate. Using a multimodal approach, we showed that upon DMCP and Sarin exposure the dimeric tungstate undergoes monomerization, making coordinatively unsaturated Zr(IV) centers available, which activate nucleophilic hydrolysis. Further, DMCP is shown to be a good model system of reduced toxicity for studies of CWA deactivation at the gas–solid interface.
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Correlated Multimodal Approach Reveals Key Details of Nerve-Agent Decomposition by Single-Site Zr-Based Polyoxometalates
2019Co-Authors: Yiyao Tian, Anna M. Plonka, Amani M. Ebrahim, Robert M. Palomino, Sanjaya D. Senanayake, Alex Balboa, Wesley O. Gordon, Diego Troya, Djamaladdin G. Musaev, John R. MorrisAbstract:Development of technologies for protection against chemical warfare Agents (CWAs) is critically important. Recently, polyoxometalates have attracted attention as potential catalysts for Nerve-Agent decomposition. Improvement of their effectiveness in real operating conditions requires an atomic-level understanding of CWA decomposition at the gas–solid interface. We investigated decomposition of the Nerve Agent Sarin and its simulant, dimethyl chlorophosphate (DMCP), by zirconium polytungstate. Using a multimodal approach, we showed that upon DMCP and Sarin exposure the dimeric tungstate undergoes monomerization, making coordinatively unsaturated Zr(IV) centers available, which activate nucleophilic hydrolysis. Further, DMCP is shown to be a good model system of reduced toxicity for studies of CWA deactivation at the gas–solid interface
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reaction mechanism of Nerve Agent decomposition with zr based metal organic frameworks
Journal of Physical Chemistry C, 2016Co-Authors: Diego TroyaAbstract:We present a detailed study of the decomposition of Sarin on the Zr-based UiO-66 and MOF-808 metal organic frameworks (MOFs) using electronic structure calculations. The central step of the mechanism involves nucleophilic addition of OH to the Nerve Agent coordinated to a Zr atom of the MOF. This addition process generates a phosphorus pentacoordinated intermediate from which phosphonic acid products are formed through an elimination step, which also produces HF or isopropanol. Two major mechanisms have been probed. In the lowest-energy mechanism, a hydroxide ligand coordinated to a MOF Zr atom acts as the nucleophile in the addition step. In the second mechanism, which exhibits a slightly larger barrier, this Zr–OH group acts as a base to deprotonate a water molecule and generate a hydroxide moiety that concertedly adds to the Nerve Agent. In both mechanisms, the phosphonic acid products of the Nerve-Agent decomposition are strongly bound to the MOFs, suggesting that regeneration of the catalyst at the g...
Andrew C. Hemmert - One of the best experts on this subject based on the ideXlab platform.
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Nerve Agent hydrolysis activity designed into a human drug metabolism enzyme.
PloS one, 2011Co-Authors: Andrew C. Hemmert, Tamara C. Otto, Monika Wierdl, Carol C. Edwards, Roberto A. Chica, Jonathan Edwards, Steven L. Lewis, Lyudmila Tsurkan, C. Linn Cadieux, Shane A. KastenAbstract:Organophosphorus (OP) Nerve Agents are potent suicide inhibitors of the essential neurotransmitter-regulating enzyme acetylcholinesterase. Due to their acute toxicity, there is significant interest in developing effective countermeasures to OP poisoning. Here we impart Nerve Agent hydrolysis activity into the human drug metabolism enzyme carboxylesterase 1. Using crystal structures of the target enzyme in complex with Nerve Agent as a guide, a pair of histidine and glutamic acid residues were designed proximal to the enzyme's native catalytic triad. The resultant variant protein demonstrated significantly increased rates of reactivation following exposure to sarin, soman, and cyclosarin. Importantly, the addition of these residues did not alter the high affinity binding of Nerve Agents to this protein. Thus, using two amino acid substitutions, a novel enzyme was created that efficiently converted a group of hemisubstrates, compounds that can start but not complete a reaction cycle, into bona fide substrates. Such approaches may lead to novel countermeasures for Nerve Agent poisoning.
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human carboxylesterase 1 stereoselectively binds the Nerve Agent cyclosarin and spontaneously hydrolyzes the Nerve Agent sarin
Molecular Pharmacology, 2010Co-Authors: Andrew C. Hemmert, Tamara C. Otto, Monika Wierdl, Carol C. Edwards, Christopher D Fleming, Mary Macdonald, Philip M Potter, Douglas M Cerasoli, Matthew R RedinboAbstract:Organophosphorus (OP) Nerve Agents are potent toxins that inhibit cholinesterases and produce a rapid and lethal cholinergic crisis. Development of protein-based therapeutics is being pursued with the goal of preventing Nerve Agent toxicity and protecting against the long-term side effects of these Agents. The drug-metabolizing enzyme human carboxylesterase 1 (hCE1) is a candidate protein-based therapeutic because of its similarity in structure and function to the cholinesterase targets of Nerve Agent poisoning. However, the ability of wild-type hCE1 to process the G-type Nerve Agents sarin and cyclosarin has not been determined. We report the crystal structure of hCE1 in complex with the Nerve Agent cyclosarin. We further use stereoselective Nerve Agent analogs to establish that hCE1 exhibits a 1700- and 2900-fold preference for the P R enantiomers of analogs of soman and cyclosarin, respectively, and a 5-fold preference for the P S isomer of a sarin analog. Finally, we show that for enzyme inhibited by racemic mixtures of bona fide Nerve Agents, hCE1 spontaneously reactivates in the presence of sarin but not soman or cyclosarin. The addition of the neutral oxime 2,3-butanedione monoxime increases the rate of reactivation of hCE1 from sarin inhibition by more than 60-fold but has no effect on reactivation with the other Agents examined. Taken together, these data demonstrate that hCE1 is only reactivated after inhibition with the more toxic P S isomer of sarin. These results provide important insights toward the long-term goal of designing novel forms of hCE1 to act as protein-based therapeutics for Nerve Agent detoxification.
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Nerve Agent Hydrolysis Activity Designed into a Human Drug Metabolism Enzyme
2010Co-Authors: Andrew C. Hemmert, Tamara C. Otto, Monika Wierdl, Carol C. Edwards, Roberto A. Chica, Steven L. Lewis, Lyudmila Tsurkan, Jonathan S. Edwards, Linn C. Cadieux, Shane A. KastenAbstract:Organophosphorus (OP) Nerve Agents are potent suicide inhibitors of the essential neurotransmitter-regulating enzyme acetylcholinesterase. Due to their acute toxicity, there is significant interest in developing effective countermeasures to OP poisoning. Here we impart Nerve Agent hydrolysis activity into the human drug metabolism enzyme carboxylesterase 1. Using crystal structures of the target enzyme in complex with Nerve Agent as a guide, a pair of histidine and glutamic acid residues were designed proximal to the enzyme’s native catalytic triad. The resultant variant protein demonstrated significantly increased rates of reactivation following exposure to sarin, soman, and cyclosarin. Importantly, the addition of these residues did not alter the high affinity binding of Nerve Agents to this protein. Thus, using two amino acid substitutions, a novel enzyme was created that efficiently converted a group of hemisubstrates, compounds that can start but not complete a reaction cycle, into bona fide substrates. Such approaches may lead to novel countermeasures for nerv
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Human Carboxylesterase 1 Stereoselectively Binds the Nerve Agent Cyclosarin and Spontaneously Hydrolyzes the Nerve Agent Sarin
2009Co-Authors: Andrew C. Hemmert, Tamara C. Otto, Monika Wierdl, Carol C. Edwards, Christopher D Fleming, Mary Macdonald, Philip M Potter, Douglas M Cerasoli, Matthew R RedinboAbstract:Organophosphorus (OP) Nerve Agents are potent toxins that inhibit cholinesterases and produce a rapid and lethal cholin-ergic crisis. Development of protein-based therapeutics is be-ing pursued with the goal of preventing Nerve Agent toxicity and protecting against the long-term side effects of these Agents. The drug-metabolizing enzyme human carboxylesterase 1 (hCE1) is a candidate protein-based therapeutic because of its similarity in structure and function to the cholinesterase targets of Nerve Agent poisoning. However, the ability of wild-type hCE1 to process the G-type Nerve Agents sarin and cyclosarin has not been determined. We report the crystal structure of hCE1 in complex with the Nerve Agent cyclosarin. We further use ste-reoselective Nerve Agent analogs to establish that hCE1 exhib-its a 1700- and 2900-fold preference for the PR enantiomers o
Su-young Moon - One of the best experts on this subject based on the ideXlab platform.
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nanosizing a metal organic framework enzyme carrier for accelerating Nerve Agent hydrolysis
ACS Nano, 2016Co-Authors: Peng Li, Su-young Moon, Joseph T. Hupp, Mark A Guelta, Diego A Gomezgualdron, Randall Q Snurr, Steven P Harvey, Omar K FarhaAbstract:We report the synthesis and characterization of a water-stable zirconium metal–organic framework (MOF), NU-1003, featuring the largest mesoporous aperture known for a zirconium MOF. This material has been used to immobilize the Nerve Agent hydrolyzing enzyme, organophosphorus acid anhydrolase (OPAA). The catalytic efficiency of immobilized OPAA in nanosized NU-1003 is significantly increased compared to that of OPAA immobilized in microsized NU-1003 and even exceeds that of the free OPAA enzyme. This paper highlights a method for rapid and highly efficient hydrolysis of Nerve Agents using nanosized enzyme carriers.
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tailoring the pore size and functionality of uio type metal organic frameworks for optimal Nerve Agent destruction
Inorganic Chemistry, 2015Co-Authors: Gregory W Peterson, Su-young Moon, Joseph T. Hupp, Jared B Decoste, George W Wagner, Morgan G Hall, Omar K FarhaAbstract:Evaluation of UiO-66 and UiO-67 metal–organic framework derivatives as catalysts for the degradation of soman, a chemical warfare Agent, showed the importance of both the linker size and functionality. The best catalysts yielded half-lives of less than 1 min. Further testing with a Nerve Agent simulant established that different rate-assessment techniques yield similar values for degradation half-lives.
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Instantaneous hydrolysis of Nerve-Agent simulants with a six-connected zirconium-based metal-organic framework
Angewandte Chemie - International Edition, 2015Co-Authors: Su-young Moon, Yangyang Liu, Joseph T. Hupp, Omar K FarhaAbstract:A Nerve-Agent simulant based on a phosphate ester is hydrolyzed using a MOF-based catalyst. Suspensions of MOF-808 (6-connected), a material featuring 6-connected zirconium nodes, display the highest hydrolysis rates among all MOFs that have been reported to date. A plug-flow reactor was also prepared with MOF-808 (6-connected) as the active layer. Deployed in a simple filtration scheme, the reactor displayed high hydrolysis efficiency and reusability.
