Periodic Reporting for period 4 - CaTs n DOCs (Chemically and Thermally Stable Nano-sized Discrete Organic Cage Compounds)
Reporting period: 2021-10-01 to 2022-03-31
In organic chemistry reactions can be either kinetically or thermodynamically controlled to adress different products from the same starting materials. This can be widely exploited for smaller compounds and single reactions. As soon as the synthetic objected product is a larger or more complex molecule it needs either be synthesized in multiple concecutive steps when kinetically controlled reactions are performed or can be build up in just one step from readily accessible molecular building blocks, if bond formations are chosen, that are reversible under the reaction conditions. Thus these reactions are thermodynamically driven, giving the products very often in high to excellent yields. This topic of chemistry is termed dynamic covalent chemistry (DCC). Both approaches have their advantages and disadvantages: Using kinetically controlled reactions are irreversible in nature thus forming more robust chemical bonds, which is important e.g. in the field of materials chemistry. The disadvantage is that the bond formation is irreversible, therefore larger molecules have to be synthesized in multiple steps, and "wrong" or unwanted connections cannot be corrected, reducing the isolated yields of a given product dramatically. On the other hand DCC products can be made in just one synthetic step from readily accessible precursors giving the product (e.g. a shape-persistent cage) in very high to excellent yields. This is because the system can self-correct until it reaches a thermodynamic minimum due to reversible bond formation. Unfortunately it is exactly the advantage of reversibility making these compounds chemically labile.
In recent years, shape-persistent organic cage compounds found multiple applications as new type of porous materials, e.g. for separation of compounds, selective recognition or sensing applications. The advantage in comparison to 'common' porous materials is their molecular nature and thus their solubility, making it easier to process them or get crystalline materials. However, the vast majority of cages is made by DCC reactions and thus these are less stable as well as the materials, based on these.
The objective of the ERC project is to combine both advantages of reversible and irreversible bond formations to make chemically and thermally stable nanosized discrete organic cage compounds to provide the next generation of porous or functional organic molecules.
In recent years, shape-persistent organic cage compounds found multiple applications as new type of porous materials, e.g. for separation of compounds, selective recognition or sensing applications. The advantage in comparison to 'common' porous materials is their molecular nature and thus their solubility, making it easier to process them or get crystalline materials. However, the vast majority of cages is made by DCC reactions and thus these are less stable as well as the materials, based on these.
The objective of the ERC project is to combine both advantages of reversible and irreversible bond formations to make chemically and thermally stable nanosized discrete organic cage compounds to provide the next generation of porous or functional organic molecules.
The objectives of the project was to make chemically ad thermally robust organic cages by first applying dynamic covalent chemistry (imine bond formation, disulfide formation) and then transform these to more robust, still shape-persistnet organic cages.
One main achievement is the the transformation of shape-persistent imine cages to amide cages (Angew. Chem. Int. Ed. 2019, 58, 8819-8823; Chem. Eur. J. 2022, e202201527) by Pinnick-oxidation. These are very stable and the smaller ones, we have generated by this method are exceptionally good nitrate receptors, which may lead to new materials to remove nitrate from drinking water. Another succesful approch was the conversion to quinoline cages by Povarov reactions (Angew. Chem. Int. Ed. 2020, 59, 19675-19679). These are to the best of our knowledge the most stable cages, reported so far in a wide pH-range. The quinoline cages show a pronounced acidochromy, which can be used for sensing applications. We also were able to demonstrate that imine cages can be stabilized by hosting charged species inside (ChemistryOpen 2020, 9, 183-190.). This is known from nature, e.g. for the tobacco mosaic viru. A real highlight was the transformation of imine cages to pure hydrocarbon cages by the Overberger-Lombardino reaction (Angew. Chem. Int. Ed. 2019, 58, 1768-1773). With this reaction, the fundament is formed to open new synthetic routes to larger fullerenes. It is wort to be mentioned that all the conversion these reactions occurred with good to sometimes even excellent overall yields. During the action, the formation of new cage geometries were developed (Chem. Eur. J. 2018, 24, 1816-1820; Angew. Chem. Int. Ed. 2021, 60, 8896-890; Org. Chem. Front. 2021, 8, 3668-3674) as well as an unforeseen catenation based on weak dispersion interactions (Nat. Chem.; accepted). Very important are also cage formation studies as well as studies toward their reversibility and stability (J. Org. Chem. 2020, 85, 13757-13771;Chem. Eur. J. 2021, 27, 9383-9390). Besides transforming imines, we also developed a new reaction to transfom disulfides to thioethers with N-heterocyclic carbenes (patent filed: WO2021214243A1;EP3901135A4). We applied this to materials chemistry but also to peptide chemistry; here to model compounds found in lantibiotics.
One main achievement is the the transformation of shape-persistent imine cages to amide cages (Angew. Chem. Int. Ed. 2019, 58, 8819-8823; Chem. Eur. J. 2022, e202201527) by Pinnick-oxidation. These are very stable and the smaller ones, we have generated by this method are exceptionally good nitrate receptors, which may lead to new materials to remove nitrate from drinking water. Another succesful approch was the conversion to quinoline cages by Povarov reactions (Angew. Chem. Int. Ed. 2020, 59, 19675-19679). These are to the best of our knowledge the most stable cages, reported so far in a wide pH-range. The quinoline cages show a pronounced acidochromy, which can be used for sensing applications. We also were able to demonstrate that imine cages can be stabilized by hosting charged species inside (ChemistryOpen 2020, 9, 183-190.). This is known from nature, e.g. for the tobacco mosaic viru. A real highlight was the transformation of imine cages to pure hydrocarbon cages by the Overberger-Lombardino reaction (Angew. Chem. Int. Ed. 2019, 58, 1768-1773). With this reaction, the fundament is formed to open new synthetic routes to larger fullerenes. It is wort to be mentioned that all the conversion these reactions occurred with good to sometimes even excellent overall yields. During the action, the formation of new cage geometries were developed (Chem. Eur. J. 2018, 24, 1816-1820; Angew. Chem. Int. Ed. 2021, 60, 8896-890; Org. Chem. Front. 2021, 8, 3668-3674) as well as an unforeseen catenation based on weak dispersion interactions (Nat. Chem.; accepted). Very important are also cage formation studies as well as studies toward their reversibility and stability (J. Org. Chem. 2020, 85, 13757-13771;Chem. Eur. J. 2021, 27, 9383-9390). Besides transforming imines, we also developed a new reaction to transfom disulfides to thioethers with N-heterocyclic carbenes (patent filed: WO2021214243A1;EP3901135A4). We applied this to materials chemistry but also to peptide chemistry; here to model compounds found in lantibiotics.
The found formation of catenated structures was unforseen and is unprecedented and will open a new approach toward complex and interwined structures. The transformation of imine cages to amide cages (see figure) is very attractive in the field of creating new hsots for specific recognition events, including anions. This method was adopted already by other groups in the field. The new approch to make three-dimensional hydrocarbon cages are paving the way to new fullerene derivatives. However, this is just the "seed that is planted". Now this method needs to be adopted by others. The developed sulfur extrusion reaction with N-heterocyclic carbenes is offering a method, that goes beyond the interest in materials chemsitry and may find its use in medicinal or phramaceutical chemistry.