Biomimicry: Synthetic Models of an Organometallic Nickel ......4 in aqueous solution, resulting in...
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Results We have synthesized key precursors to a series of related enzyme models. The reaction of Compound 1 with refluxing SOCl 2 was carried out at 65˚C under an atmosphere of nitrogen, producing Compound 2. [7] Compound 2 was oxidized by KMnO 4 in aqueous solution, resulting in the formation of Compound 3. [8] The products were isolated by vacuum filtration and characterized by nuclear magnetic resonance (NMR) spectroscopy. Biomimicry: Synthetic Models of an Organometallic Nickel Enzyme Satnam Singh , Johanna Parsnick, Adviser: Brandon K. Tate State University of New York College at Geneseo Conclusions We have demonstrated the synthesis of key precursors to synthetic models of the lactate racemase cofactor. These precursor compounds could serve as the basis for a whole library of enzyme models. Plans for future research include the investigation of the reactivity the enzyme models and their catalytic activity in hydride-transfer processes. These studies could include experiments to determine the effects of steric and electronic parameters on reaction rates as well as the optimization of catalytic conditions. We anticipate this project will shed light on the role of the unique organometallic cofactor of lactate racemase and may inform the design of biomimetic catalysts for related reactions, particularly reactions relevant to hydrogen storage and renewable fuels. References [1] NASA Scientific Data Visualization Studio https://svs.gsfc.nasa.gov/cgi- bin/details.cgi?aid=4626 [2] ChemLibre Texts General Chemistry. https://chem.libretexts.org/Bookshelves/General_Chemistry [3] Desguin, B.; Goffin, P.; Viaene, E.; Kleerebezem, M.; Martin-Diaconescu, V.; Maroney, M. J.; Declercq, J.-P.; Soumillion, P.; Hols, P. Lactate Racemase Is a Nickel-Dependent Enzyme Activated by a Widespread Maturation System. Nat. Commun. 2014, 5, 3615. [4] Desguin, B.; Zhang, T.; Soumillion, P.; Hols, P.; Hu, J.; Hausinger, R. P. A Tethered Niacin- Derived Pincer Complex with a Nickel-Carbon Bond in Lactate Racemase. Science 2015, 349 (6243), 66–69. [5] Xu, T., et al. “Nickel Pincer Model of the Active Site of Lactate Racemase Involves Ligand Participation in Hydride Transfer.” Proceedings of the National Academy of Sciences , vol. 114, no. 6, 2017, pp. 1242–1245., doi:10.1073/pnas.1616038114 [6] Rankin, J. A.; Mauban, R. C.; Fellner, M.; Desguin, B.; McCracken, J.; Hu, J.; Varganov, S. A.; Hausinger, R. P. The Lactate Racemase Nickel-Pincer Cofactor Operates by a Proton-Coupled Hydride Transfer Mechanism. Biochemistry 2018, 57, 3244–3251. doi:10.1021/acs.biochem.8b00100 [7] Höglund, Iisa P. J., et al. “Structure−Activity Relationship of Quinoline Derivatives as Potent and Selective α2C-Adrenoceptor Antagonists.” Journal of Medicinal Chemistry, vol. 49, no. 21, 2006, pp. 6351–6363., doi:10.1021/jm060262x [8] Zhang, X.-S.; Zhang, Y.-F.; Li, Z.-W.; Luo, F.-X.; Shi, Z.-J. Synthesis of Dibenzo[c,e]oxepin- 5(7H)-ones from Benzyl Thioethers and Carboxylic Acids: Rhodium-Catalyzed Double CH Activation Controlled by Different Directing Groups. Angew. Chem. Int. Ed. 2015, 54, 5478– 5482. doi: 10.1002/anie.201500486 Acknowledgements Funding provided by: The Geneseo Foundation SUNY Geneseo Student Association SUNY Geneseo Chemistry Department SUNY Geneseo Chemistry and Biochemistry Alumni Ronald E. McNair Postbaccalaureate Achievement Program SUNY Geneseo Biochemistry Program Synthetic Fuels Our society‘s reliance on carbon-based fossil fuels is not sustainable and has a substantial negative impact on our environment. Chemistry plays a vital role in the development of alternatives to fossil fuels. Clean energy sources such as solar power and wind power are intermittent. We need efficient ways to store renewable energy in chemical fuels or fuel cells so that the energy can be released as needed. Hydrogen (H 2 ), produced renewably via the electrolysis of water, has the potential to replace fossil fuels. However, hydrogen has low energy density compared to liquid fuels such as petroleum. The goal of our research is to develop catalysts for the conversion of hydrogen to liquid or liquifiable fuels. We want to understand biological energy storage on a molecular level and use principles from biological catalysis to develop artificial catalysts for energy storage and the production of renewable fuels. Lactate Racemase Lactate racemase is an enzyme whose active site features the only known example of a biological pincer complex. The enzyme catalyzes the interconversion of the two optical isomers of lactic acid. [3] The cofactor of lactate racemase is an organometallic complex containing a nickel ion coordinated by a pincer ligand and a histidine residue. [4] The proposed mechanism for lactate racemization involves proton-coupled hydride transfer, an important step in proposed renewable fuel cycles. [5,6] We are developing synthetic models of the lactate racemase cofactor in order to study their reactivity and improve our understanding of the mechanism of lactate racemization. Our results could inform the development of catalysts for renewable fuel production. catalyst H 2 O sustainable electrolysis H 2 O 2 energy released CO 2 CH 4 , HC(O)OH, CH 3 OH, CH 3 CH 2 OH liquid/ liquifiable fuels O 2 CO 2 a b DMSO H 2 O c Source: [1] Source: [2] 16 92 7 39 S U N Y 32.07 238.03 14.01 88.91 32 30 34 8 Ge Ne Se O 72.59 20.18 78.92 16.00 This work is licensed under a Creative Commons Attribution-NonCommercial- ShareAlike 4.0 International License.
Transcript of Biomimicry: Synthetic Models of an Organometallic Nickel ......4 in aqueous solution, resulting in...
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ResultsWe have synthesized key precursors to a series of related enzyme models.
The reaction of Compound 1 with refluxing SOCl2 wascarried out at 65˚C under an atmosphere of nitrogen,producing Compound 2.[7]
Compound 2 was oxidized by KMnO4 in aqueous solution,resulting in the formation of Compound 3.[8]
The products were isolated by vacuum filtration andcharacterized by nuclear magnetic resonance (NMR)spectroscopy.
Biomimicry: Synthetic Models of an Organometallic Nickel EnzymeSatnam Singh, Johanna Parsnick,
Adviser: Brandon K. TateState University of New York College at Geneseo
ConclusionsWe have demonstrated the synthesis of key precursors tosynthetic models of the lactate racemase cofactor. Theseprecursor compounds could serve as the basis for a wholelibrary of enzyme models.
Plans for future research include the investigation of thereactivity the enzyme models and their catalytic activity inhydride-transfer processes. These studies could includeexperiments to determine the effects of steric and electronicparameters on reaction rates as well as the optimization ofcatalytic conditions.
We anticipate this project will shed light on the role of theunique organometallic cofactor of lactate racemase and mayinform the design of biomimetic catalysts for relatedreactions, particularly reactions relevant to hydrogen storageand renewable fuels.
References[1] NASA Scientific Data Visualization Studio https://svs.gsfc.nasa.gov/cgi-bin/details.cgi?aid=4626
[2] ChemLibre Texts General Chemistry. https://chem.libretexts.org/Bookshelves/General_Chemistry
[3] Desguin, B.; Goffin, P.; Viaene, E.; Kleerebezem, M.; Martin-Diaconescu, V.; Maroney, M. J.; Declercq, J.-P.; Soumillion, P.; Hols, P. Lactate Racemase Is a Nickel-Dependent Enzyme Activated by a Widespread Maturation System. Nat. Commun. 2014, 5, 3615.
[4] Desguin, B.; Zhang, T.; Soumillion, P.; Hols, P.; Hu, J.; Hausinger, R. P. A Tethered Niacin-Derived Pincer Complex with a Nickel-Carbon Bond in Lactate Racemase. Science 2015, 349(6243), 66–69.
[5] Xu, T., et al. “Nickel Pincer Model of the Active Site of Lactate Racemase Involves Ligand Participation in Hydride Transfer.” Proceedings of the National Academy of Sciences, vol. 114, no. 6, 2017, pp. 1242–1245., doi:10.1073/pnas.1616038114
[6] Rankin, J. A.; Mauban, R. C.; Fellner, M.; Desguin, B.; McCracken, J.; Hu, J.; Varganov, S. A.; Hausinger, R. P. The Lactate Racemase Nickel-Pincer Cofactor Operates by a Proton-Coupled Hydride Transfer Mechanism. Biochemistry 2018, 57, 3244–3251. doi:10.1021/acs.biochem.8b00100
[7] Höglund, Iisa P. J., et al. “Structure−Activity Relationship of Quinoline Derivatives as Potent and Selective α2C-Adrenoceptor Antagonists.” Journal of Medicinal Chemistry, vol. 49, no. 21, 2006, pp. 6351–6363., doi:10.1021/jm060262x
[8] Zhang, X.-S.; Zhang, Y.-F.; Li, Z.-W.; Luo, F.-X.; Shi, Z.-J. Synthesis of Dibenzo[c,e]oxepin-5(7H)-ones from Benzyl Thioethers and Carboxylic Acids: Rhodium-Catalyzed Double CH Activation Controlled by Different Directing Groups. Angew. Chem. Int. Ed. 2015, 54, 5478–5482. doi: 10.1002/anie.201500486
AcknowledgementsFunding provided by:The Geneseo FoundationSUNY Geneseo Student AssociationSUNY Geneseo Chemistry DepartmentSUNY Geneseo Chemistry and Biochemistry AlumniRonald E. McNair Postbaccalaureate Achievement ProgramSUNY Geneseo Biochemistry Program
Synthetic FuelsOur society‘s reliance on carbon-based fossil fuels is notsustainable and has a substantial negative impact on ourenvironment. Chemistry plays a vital role in the developmentof alternatives to fossil fuels.
Clean energy sources such as solar power and wind powerare intermittent. We need efficient ways to store renewableenergy in chemical fuels or fuel cells so that the energy canbe released as needed.
Hydrogen (H2), produced renewably via the electrolysis ofwater, has the potential to replace fossil fuels. However,hydrogen has low energy density compared to liquid fuelssuch as petroleum. The goal of our research is to developcatalysts for the conversion of hydrogen to liquid orliquifiable fuels.
We want to understand biological energy storage on amolecular level and use principles from biological catalysisto develop artificial catalysts for energy storage and theproduction of renewable fuels.
Lactate RacemaseLactate racemase is an enzyme whose active site features theonly known example of a biological pincer complex. Theenzyme catalyzes the interconversion of the two opticalisomers of lactic acid.[3]
The cofactor of lactate racemase is an organometalliccomplex containing a nickel ion coordinated by a pincerligand and a histidine residue.[4]
The proposed mechanism for lactate racemization involvesproton-coupled hydride transfer, an important step inproposed renewable fuel cycles.[5,6]
We are developing synthetic models of the lactate racemasecofactor in order to study their reactivity and improve ourunderstanding of the mechanism of lactate racemization.Our results could inform the development of catalysts forrenewable fuel production.
catalyst
H2O
sustainableelectrolysis
H2
O2
energy released
CO2
CH4, HC(O)OH,CH3OH, CH3CH2OH
liquid/liquifiable fuels
O2
CO2
a
b
DMSO
H2O
c
Source: [1]
Source: [2]
16 92 7 39
S U N Y32.07 238.03 14.01 88.91
32 30 34 8
Ge Ne Se O72.59 20.18 78.92 16.00
This work is licensed under a Creative Commons Attribution-NonCommercial-
ShareAlike 4.0 International License.
