HEИндивидуална стипендия2023–2025

Cu-CATARMs · Asymmtric Copper(I) Catalysis in Artificial Metalloenzymes

„Хоризонт Европа“ — Действия „Мария Склодовска-Кюри“

Период: 2023-04-01 → 2025-03-31
Финансиране от ЕС: 203 464 €
Участници: 1
Схема: HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

Изкуствени металоензими с меден център се разработват за провеждането на специфични химични реакции, като например създаването на циклопропанови структури. Тези процеси помагат за откриването на нови начини за синтезиране на органични молекули и материали.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Asymmtric Copper(I) Catalysis in Artificial Metalloenzymes

The Cu-CATARMs project (Asymmetric Copper(I) Catalysis in Artificial Metalloenzymes) aims to design and develop a highly efficient artificial metalloenzyme featuring a low oxidation state copper center, Cu(I), which facilitates a range of enantioselective, new-to-nature transformations in a protein environment. The Roelfes group has been engaged in creating LmrR-based artificial metalloenzymes (ARMs) for copper-catalyzed asymmetric unnatural reactions. They have developed reliable methods for efficiently incorporating copper (II) catalytic center into the artificial protein pocket, either by introducing metal-binding unnatural amino acids through in vivo stop codon suppression or via supramolecular assembling the metal complex, utilizing π–π stacking interactions between tryptophan residues. Our approach to creating Cu(I)-dependent artificial metalloenzymes (Cu(I)-ArMs)involves the in situ reduction of the established copper(II) center to a copper(I) center using mild and efficient reductants (Objective 1). The created Cu(I)-ArM will be utilized to achieve the following objectives: Objective 2, asymmetric conjugate addition of alkynes; Objective 3, asymmetric intramolecular cyclopropanation; and Objective 4, the detailed mechanisms underlying these reactions will be investigated, aiming to provide theoretical insights for future related research. In perspective, the successful development of the Cu-CATARMs project will offer a powerful strategy for utilizing low oxidation state transition metals in enzyme catalysis. The project’s outcomes will inspire the development of C–C and C–N bond formation reactions through copper(I) catalysis in ARMs, providing new strategies for the organic chemistry and materials science communities in designing synthetic routes for specific targets.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

The proposal that Cu-CATARMs (Asymmetric Copper(I) Catalysis in Artificial Metalloenzymes) aims to design and develop a proficient artificial metalloenzyme which contains a low oxidation state copper (Cu(I)) center, enabling a series of enantioselective new-to-nature transformations in a protein environment.The Roelfes group has been engaged in creation of LmrR based ARMs for the asymmetric copper-catalyzed new-to-nature reactions. Reliable approaches have been developed by the Roelfes group to efficiently recruited the copper(II) species to the LmrR pore, either introducing metal binding unnatural amino acids through in vivo stop codon suppression or supramolecular assembly via the stacking interaction between tryptophan moieties and metal complex. Our approach is enabled by reducing the copper(II) center which is chelated by anchoring moiety of LmrR to copper(I) center with mild and efficient reductants in situ (objective 1). This design of copper(I) catalysis in LmrR based artificial metalloenzyme will be exploited to develop the following objectives: Objective 2. Asymmetric conjugate addition of alkynes; Objective 3. Asymmetric intramolecular cyclopropanation; Objective 4. Apart from developing the novel methodologies, we will also devote ourselves to reveal the detailed mechanism, aiming to provide theoretical guidance for future works. Overall, the successful development of Cu-CATARMs project will represent a proficient strategy to apply low oxidation state transition metals in enzyme catalysis. The results of the project will inspire the development of C-C/C-N bond formation reactions through copper(I) catalysis in ARMs and offer new strategy for the organic chemistry and material communities when planning a synthetic route for a specific target.

Оригинален текст от CORDIS (на английски).

Участници

RIJKSUNIVERSITEIT GRONINGEN · GroningenКоординаторНидерландия