Periodic Reporting for period 1 - MFPFs (Metal-Foldamer Porous Frameworks)
Periodo di rendicontazione: 2021-09-01 al 2023-08-31
The design and precise construction of protein-inspired nanostructures through folding and metal-directed self-assembly is a challenging yet potentially rewarding endeavor for the development of new classes of functional materials. Peptides have been well established as flexible starting points for the construction of bioinspired architectures with a high level of sophistication and precise control over morphologies and functions. Concurrently, the power of metal coordination to drive assembly has been extensively explored to design functionally versatile metal-organic frameworks (MOFs). The functional versatility resulting from this level of control has led to MOFs applications in diverse areas such as catalysis, gas capture, sensing, energy technologies, organelle specific drug delivery, and also as detoxification agents. Yet, the synthesis of such coordination networks by a process that would combine folding, self-assembly and metal coordination in aqueous media is still partially unaccomplished. Foldamers - artificial synthetic folded oligomers - possess the advantages of structural robustness and high programmability which bodes well for their use in the construction of well-defined higher-order nanostructures. The project has moved a step forward towards the design, synthesis and structural characterization of metal-foldamer porous frameworks with a focus on foldamer sequence evolution and metal variation to influence the main features of the assembly (shape and catalytic property in particular).
This project successfully constructed metal-coordinated frameworks using foldamers as the organic ligand. The incorporation of metal centers enhanced mechanical properties and stability, setting these assemblies apart from previously reported foldamer assemblies. The resulting architectures exhibited diverse structures, offering unique functionalities. Preliminary results suggest that such metal-foldamer frameworks may exhibit catalytic ability in the hydrolysis of substrates, and their chemically modified versions were evaluated for on-demand functions. In particular, the frameworks were investigated for their capacity to bind guests, such as double-stranded DNA.
Results are currently being prepared for publication in high-impact, peer-reviewed journals. Remarkably, before project completion, the researcher secured an academic position at a leading university in India.
This project successfully constructed metal-coordinated frameworks using foldamers as the organic ligand. The incorporation of metal centers enhanced mechanical properties and stability, setting these assemblies apart from previously reported foldamer assemblies. The resulting architectures exhibited diverse structures, offering unique functionalities. Preliminary results suggest that such metal-foldamer frameworks may exhibit catalytic ability in the hydrolysis of substrates, and their chemically modified versions were evaluated for on-demand functions. In particular, the frameworks were investigated for their capacity to bind guests, such as double-stranded DNA.
Results are currently being prepared for publication in high-impact, peer-reviewed journals. Remarkably, before project completion, the researcher secured an academic position at a leading university in India.
By focusing on zinc coordination, we first evaluated the coordination properties of the foldamers as well as their folding and self-assembly upon adding increasing concentrations of the metal ion using spectroscopic methods (electronic circular dichroism (ECD) and UV/Vis spectroscopy) in aqueous solutions. Our research program also included substantial efforts to characterize the structure of the metal coordinated foldamer assemblies by X-ray crystallography. The newly synthesized sequences were systematically tested for single crystal growth first in the presence of Zn(II). We also explored other first row divalent metal ions like Co(II), Ni(II), Cu(II), as well as heavier metals such as Cd(II). This work thus involved growth of single crystals, their optimization and structural analyses. The researcher obtained the required training in macromolecular crystallography & validation of the use of crystallization robots. The stability of the metal-coordinated crystals in aqueous solutions, in the air and in different solvents, was systematically assessed through various analysis methods including transmission electron microscopy (TEM) and atomic force microscopy (AFM) and X-ray diffraction.
Despite these advancements, the growth of diffractable single crystals for metal-coordinated foldamers proved to be a challenging task, limiting our comprehensive understanding of the system. As a result, the design principles remain elusive, and further exploration is necessary to achieve a thorough understanding of these innovative systems. The Metal-foldamer frameworks demonstrated catalytic ability in the hydrolysis of substrates, and their chemically modified versions were evaluated for on-demand functions. The frameworks were also investigated for their capacity to bind guests, such as double-stranded DNA.
Metal-foldamer frameworks were tested for their ability to catalyse the hydrolysis of various substrates (e.g. chromogenic 4-nitrophenyl acetate). The required training in spectroscopic methods was obtained in the due course. Replacement during the synthesis of the residue pointing inside the cavity was evaluated to obtain on-demand functions. The ability of the chemically modified metal-coordinated frameworks as well as other cavities was investigated for binding guest such as double stranded DNA. Outreach activities, preparation of data management plan (DMP) and final report of MSCA were performed throughout the project tenure.
The project results have been presented at various stages during scientific events and are currently being prepared for publication in high-impact, peer-reviewed journals. This last part of the dissemination program was slowed down at the end of the project as the researcher obtained an academic position at a leading Indian university and had to shorten his time in the host laboratory.
Despite these advancements, the growth of diffractable single crystals for metal-coordinated foldamers proved to be a challenging task, limiting our comprehensive understanding of the system. As a result, the design principles remain elusive, and further exploration is necessary to achieve a thorough understanding of these innovative systems. The Metal-foldamer frameworks demonstrated catalytic ability in the hydrolysis of substrates, and their chemically modified versions were evaluated for on-demand functions. The frameworks were also investigated for their capacity to bind guests, such as double-stranded DNA.
Metal-foldamer frameworks were tested for their ability to catalyse the hydrolysis of various substrates (e.g. chromogenic 4-nitrophenyl acetate). The required training in spectroscopic methods was obtained in the due course. Replacement during the synthesis of the residue pointing inside the cavity was evaluated to obtain on-demand functions. The ability of the chemically modified metal-coordinated frameworks as well as other cavities was investigated for binding guest such as double stranded DNA. Outreach activities, preparation of data management plan (DMP) and final report of MSCA were performed throughout the project tenure.
The project results have been presented at various stages during scientific events and are currently being prepared for publication in high-impact, peer-reviewed journals. This last part of the dissemination program was slowed down at the end of the project as the researcher obtained an academic position at a leading Indian university and had to shorten his time in the host laboratory.
This project has facilitated a systematic exploration of metal coordination for controlling the folding and assembly of foldamers, leading to the formation of porous networks with functionalized channels. This main feature of these framework is the projection of a well-defined side chain into the interior of the pore. Structural studies conducted in this project have unveiled, for the first time, metal-coordinated assembly structures using foldamers as organic ligands. These studies also underscore our capability to modulate chemical functions within the pore. Foldamers, capable of mimicking natural biomolecules, offer a unique combination of small molecular size (synthetic accessibility) and the complex properties of proteins, including foldability. Our investigation has illuminated various intriguing aspects of these metal-coordinated assemblies. In the solid state, these metal-induced assemblies exhibit increased robustness compared to assemblies of foldamers stabilized solely by non-covalent interactions (hydrophobic effects, hydrogen bonding, and electrostatic interactions), allowing for crystal manipulation. Furthermore, these assemblies display modularity, where minor modifications of monomer units do not induce significant structural changes. This modularity provides an opportunity to meticulously design sequences for metal coordination and to fine-tune specific properties, such as the function of side chains within the pore. Overall, this approach enables precise adjustments in stability, solubility, crystallinity, and molecular recognition functions (such as the ability to bind small or macromolecules and catalyze reactions) without compromising structural attributes like folding, inter-helix interactions, and overall structure. This paves the way for the modular design of a novel class of metal-organic frameworks (MOFs)