Blanckaert, Pauline

Gerbaux, Pascal

ORBi UMONS

Pauline BlanckaertSupervised by Prof. Pascal Gerbaux17th october 2024     Design and synthesis of an artificial catalyst inspired by carbonic anhydraseCarbon Capture, Utilization and Storage - CCUS1Introduction – Objectives – Results and discussion – Conclusions and outlook Global warming : • A global temperature rise prevision of 1.5 °C between 2021 and 2040• Excessive anthropogenic greenhouse gases (GHG) • CO2 contributes to 72% of GHG• Urgent need to reduce atmospheric CO2 rateCCUS : Capture & Utilization (new chemicals including fuels) or storage (underground & offshore) Gas Science and Engineering. 2024, 123, 205237Biocatalysts – enzymes – to reduce energy consumption Carbonic anhydrase as a promising candidate Chemical absorptionCurr Opin Biotechnol. 2022, 74, 230–240CO2  dissolution and hydration2HCO3-CO2(aqueous)--------------------------------------------GasAqueousk 1= 10 10 s -1k 1= 10 10 s -1kwithout CA= 3,58 .10 -2 s -1kwith CA= 10 6 s -1Carbonic anhydraseUncatalyzedIntroduction – Objectives – Results and discussion – Conclusions and outlook HCO3-CO2(aqueous)GasAqueousk 1= 10 10 s -1k 1= 10 10 s -1kwithout CA= 3,58 .10 -2 s -1kwith CA= 10 6 s -1Carbonic anhydraseUncatalyzed𝐶𝑂2 + 𝐻2𝑂 ⇌ 𝐻𝐶𝑂3− + 𝐻+Curr Opin Biotechnol. 2022, 74, 230–240 UCSF Chimera de pdb 1CA2 2Introduction – Objectives – Results and discussion – Conclusions and outlook --------------------------------------------HCA II (pdb)MW = 29.3 kDa260 amino acidCO2  dissolution and hydration➢ Metalloenzyme➢ Discovered in red blood cells in 1933➢ Distributed in the cytoplasm ofvertebrates, green plants, algae, andbacteria➢ pH regulation, breathing …Active site environment of CA3pKa~7active site1st sphereTetrahedral geometry 2nd sphere 2+Inorg Chem. 2012, 51 (12), 6803–6812Introduction – Objectives – Results and discussion – Conclusions and outlook Catalytic mechanism41) Deprotonation𝑍𝑛2+ − 𝐻2𝑂 ⇄ 𝑍𝑛2+ − 𝑂𝐻− + 𝐻+2) Nucleophilic addition𝑍𝑛2+ − 𝑂𝐻− + 𝐶𝑂2  ⇄ 𝑍𝑛2+ − 𝐻𝐶𝑂3−3) Substitution𝑍𝑛2+ − 𝐻𝐶𝑂3− + 𝐻2𝑂 ⇄ 𝑍𝑛2+ − 𝐻2𝑂 +  𝐻𝐶𝑂3−Inorganica Chimica Acta. 2019, 484, 167-173123Introduction – Objectives – Results and discussion – Conclusions and outlook Context :Carbonic anhydrase for CO2 capture in industrial researchDrawback : thermal stability → loss of enzyme activity ➔ New cost-effective materials with simple preparation conditions, high substrate affinity …Tailor-made sequence-defined macromolecules as peptidomimeticsContext and objective5Introduction – Objectives – Results and discussion – Conclusions and outlook Peptoid PeptideObjective :  Design and synthesis of a peptoid-based artificial catalyst inspired by carbonic anhydraseGas Science and Engineering. 2024, 123, 205237Peptoid designPeptoid APeptoid B9 units12 units6Introduction – Objectives – Results and discussion – Conclusions and outlook UCSF Chimera de pdb 1CA2Solid phase synthesisJ. Am. Chem. SOC. 1992, 10646–10647.R-NH2 = →Chloroacetylation→Nucleophilic substitutionPeptoids A and B characterized by MS and MS/MSIntroduction – Objectives – Results and discussion – Conclusions and outlook 7Targeted sequence and lengthFlash chromatography purification (C18)Complexation in solutionInteraction between  Zn2+ and peptoidPeptoid A Peptoid A – Zn(ClO4)220 °C ; H2O mQ ; 100 𝜇𝑀 Wavelength (nm)Circular dichroism (mdeg)Introduction – Objectives – Results and discussion – Conclusions and outlook                   Peptoid A Peptoid A – Zn(ClO4)21H NMR 500 MHzD2O න = 6න = 10Circular dichroism 1H NMR8Specific interaction to imidazole groups9Several characterization techniques needed to understand how the metal complexes formCD & NMRSpecific interaction between imidazoles and Zn2+m/zSynapt G2-SiESI(+)-MSH2O[M+H]+1189.7[M+2H]2+595.3[M+3H]3+      397.7MW = 1188.7 g/molStoichiometry determination by ESI-MS101200600 1000800400Introduction – Objectives – Results and discussion – Conclusions and outlook [M+Zn]2+626.3[M+Zn+H+Cl]2+644.3MW = 1188.7 g/molAfter addition ZnCl2m/zSynapt G2-SiESI(+)-MSH2O11600 1000800400Introduction – Objectives – Results and discussion – Conclusions and outlook [M-Npro+Zn]2+576.8Stoichiometry determination by ESI-MSUCSF Chimera de pdb 1CA212CD & NMRSpecific interaction between imidazoles and Zn2+12CD & NMRSpecific interaction between imidazoles and Zn2+Catalytic activityCO2 Hydration4-Nitrophenyl acetate (4-NPA)13Introduction – Objectives – Results and discussion – Conclusions and outlook Ester HydrolysisvsJ. Biol. Chem. 1967, 242 (18) 4221-4229. Deprotonation Nucleophilic additionEliminationSubstitutionH2O                                     2+Time (h)AbsorbanceControl ▼Control Zn2+● Peptoid A/Zn2+▲Peptoid B/Zn2+Hydrolysis of 4-NPA𝐴𝑏𝑠348 𝑛𝑚Reaction conditions :• Substrate = 4-NPA (10-3 M) • Peptoid/Zn(ClO4)2 (10-4 M)• 35 °C ; H2O (2 % acetone) ; pH = 414Introduction – Objectives – Results and discussion – Conclusions and outlook J. Biol. Chem. 1967, 242 (18) 4221-4229.15       CD & NMRSpecific interaction between imidazoles and Zn2+15CD & NMRSpecific interaction between imidazoles and Zn2+Conclusions and outlookKey results :• Formation of 1:1 complexes (peptoid/Zn²⁺)• Specific complexation between Zn²⁺ and imidazole groups• The hydrolysis of 4-NPA is faster in the presence of complexesHow to improve? • Hydrolysis of 4-NPA under different conditions (pH, counter anion, temperature,…)• Evaluation of different metal ions (Cu2+, Ni2+, Co2+)• Elaboration of a protocol for CO₂ hydration16Introduction – Objectives – Results and discussion – Conclusions and outlook Thank youProf. Pascal GerbauxDr. Julien De WinterDr. Quentin Duez Dr. Benjamin TassignonDr. Antoine NiteletLouis GroignetEmma Piplart Thomas Robert Gwendal HenrardAri Serez Sarajit NaskarPaul GuebenStella Kamga Kamguem Amandine Portier Roshan HayatProf. Mathieu Surin David DellemmeProf. Sophie Laurent Dr. Céline Henoumont Design and synthesis of an artificial catalyst inspired by carbonic anhydrasePauline BlanckaertThank you for your attention18

Design and synthesis of an artificial catalyst inspired by carbonic anhydrase

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Design and synthesis of an artificial catalyst inspired by carbonic anhydrase

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