Synthesis of Peptide Mimetics and Host-Guest Complex with β-Cyclodextrin: Functional Supramolecular Materials

Douzapau, M. (2016) Synthesis of Peptide Mimetics and Host-Guest Complex with β-Cyclodextrin: Functional Supramolecular Materials. PhD thesis, Indian Institute of Science Education and Research Kolkata.

Text (PhD thesis of M. Douzapau (21RS048)) 21RS048.pdf - Submitted Version Restricted to Repository staff only Download (7MB)

Abstract

This thesis, known as “Synthesis of Peptide Mimetics and Host–Guest Interactions with β-Cyclodextrins: Functional Supramolecular Materials,” was directed at the rational process of design, synthesis, characterization, and functional assessment of peptide mimetics. It investigates synthetic peptidomimetic systems incorporating proteinogenic and non-proteinogenic amino acids to understand their conformational behavior and self-assembly mechanisms. Particular emphasis is placed on understanding how these molecules organize into higher-order supramolecular architectures such as helices and sheets, and how these assemblies further evolve into advanced nanostructures including tubes, vesicles, fibers, and porous networks. The gelation properties of these materials were studied in detail and their potential applications across diverse fields of materials science and nanotechnology were reported. β-Cyclodextrin (β-CD) is a naturally derived cyclic oligosaccharide that can be readily modified through chemical synthesis. It possesses high structural stability and demonstrates pronounced chiral recognition through host–guest inclusion phenomena. Structurally, β-CD features a hydrophilic exterior and a relatively hydrophobic internal cavity. This nonpolar cavity creates a confined chiral environment that enables selective encapsulation of various guest molecules, including those that are otherwise achiral. Owing to these properties, β-CD exhibits notable stereoselectivity and has been widely utilized in asymmetric reduction processes. Molecular recognition and assembly of peptides stands for both biochemical mechanism of peptide/ protein targeting within the cells and a chemical process for creating, assembling, or isolating specific peptides. This is highly important for development of gels, targeted drug delivery, and responsive materials. Generally, the recognition and sensing have done by diverse non-covalent interactions such as hydrogen bonding, hydrophobic interactions, π–π stacking, host–guest complexation and metal coordination. These resultant materials have various morphologies such as ribbons, cubes, fibers, and rods. Eventually it can form supramolecular gel. The supramolecular gel derives from the controlled marriage of aromatic molecules and macrocycle-based host–guest interactions are unique in nature and highly important in a number of diverse fields like supramolecular chemistry, polymer science, materials science, information storage device and biomedical materials. The supramolecular gels have unique properties like responsiveness to external stimuli, tunability, self-healing resulting fascinating applications in drug delivery, tissue engineering, sensing, and smart materials. However, the analytical techniques involve often require expensive instruments and they are limited for practical application. This underscores the urgent quest to develop peptide mimetic and -CD host guest complex for advance functional materials Here, we present a stimuli-responsive supramolecular polymer gel developed by an amphiphile and β-cyclodextrin (β-CD) in DMSO/water (1:2). From X-ray single crystal diffraction, the amphiphile adopts a kink-like conformation. The amphiphile self- assembled to form a parallel sheet-like structure stabilized by multiple intermolecular hydrogen bonds. Moreover, the parallel sheet-like structure is also stabilized by edge-to- edge π–π stacking interactions. In higher-order packing, it forms a corrugated sheet-like structure stabilized by hydrophobic interactions. The amphiphile interacts with β-cyclodextrin and forms gel through supramolecular polymer formation in (DMSO)/water (1:2) by a simple heating-cooling cycle. The gel is temperature responsive and T gel is 70°C. The sol-to-gel transformation is accompanied by microstructure changes from nanofibers to micro-rods. The supramolecular polymer gel is responsive to stimuli such as picric acid and hydrochloric acid. The absorption and emission spectroscopic studies show that the aromatic hydrophobic side chain forms an inclusion complex with β-CD. The stimuli-responsive designer supramolecular gel has the potential to be an eco-friendly advanced functional material. In this thesis we studied the aggregation induced emission of tetrahydropyridine containing -amino acid ethyl ester 1 and its tuning by host-guest complex formation with -cyclodextrin. The NMR, FT-IR and single-crystal X-ray analysis data collectively demonstrate that the molecule adopts a folded robust conformation stabilized by (i) one intra-molecular N-H….O hydrogen bond, and (ii) π-π stacking interactions. The aggregation induced emission property of the -amino acid ethyl ester 1 has studied by solvent-titration, absorption and emission spectroscopy and fluorescence microscopy. Importantly, this locked architecture persists even in highly polar solvents (DMF) and exhibits emission at 360 and 487 nm. However, on addition of -cyclodextrin the emission at 360 nm enhance and 487 nm disappear. The β-amino acid ethyl ester 1 and -cyclodextrin host-guest complex formation was studied by dynamic light scattering as well as FE-SEM experiments. Traditionally, the closed conformation of β-amino acid ethyl ester 1 is non-responsive to reactions like hydrolysis, addition or substitution. But the host-guest complex has enabled the hydrolysis of ester by NaOH. The host-guest complex also promotes reaction engineering such as bromination resulting 2,4,6-tribromo phenol. This thesis also demonstrates the Metal-organic gels, a type of supramolecular complex that have become highly intriguing due to their synergistic combination of organic and organometallic moieties. We report the synthesis and characterization of two new ferrocene appended peptides containing L-Phe and L-DOPA. From solid and solution studies, the peptide containing L-Phe form anti perallel sheet-like structure and the peptide containing L-DOPA form anti perallel sheet-like structure. We investigated their gelling abilities and found that only L-Phe containing peptide was capable of forming gel exclusively with β-CD in DMSO-water(1:1) by heating at 54°C as a result of host–guest complex formation. The supramolecular gel responded temperature reversably. Additionally, this gelation was found to be reversible under redox stimuli; changing of the redox state of ferrocene induced a reversible gel–sol phase transition. This thesis depicts the supramolecular polymer formation by host-guest complex formation of a ferrocene-appended bisamide with β-cyclodextrin. The FT-IR and single-crystal X-ray diffraction analysis collectively demonstrate that the ferrocene-appended bisamide 2 adopts an extended conformation. In solid state, one molecule of ferrocene-appended bisamide 2 interact with four neighboring molecules through intermolecular N-H....O hydrogen bonds. In higher order packing, it forms a sheet-like structure. The ferrocene-appended bisamide 2 exhibits absorption bands at 286, 350 and 450 nm. With increasing concentration of ferrocene-appended bisamide 2, the absorption bands increases and the band at 286 nm shifted to 295 nm, indicating persistent of the stacked architecture even in highly polar solvents like DMF. However, on addition of -cyclodextrin the absorption bands reduced gradually. The supramolecular polymer formation was studied by absorption, emission, FT-IR spectroscopy, dynamic light scattering, fluorescence microscopy and FE-SEM. Moreover, the supramolecular polymer is redox responsive. This thesis also describes the sorting of tryptophan containing peptide by tuning AIE with -Cyclodextrin through host-guest complex formation. The FT-IR and NMR spectra demonstrate that the peptides 1 and 2 adopt similar helical conformations. The L-Tyr containing tripeptide 1 exhibits emission band at 310 nm. With increasing concentration of tripeptide 1, the emission band decreases. However, the L-Trp containing tripeptide 2 exhibits emission band at 340 nm and with increasing concentration of tripeptide 2, the emission band increases due to AIE effect and the band at 340 nm shifted to 360 nm, indicating persistent of the J-type aggregate. Moreover, on addition of -cyclodextrin capped magnetic nanoparticle the emission band of tripeptide 2 reduced gradually due to host-guest complex formation. The study could provide an effective method for the recognition and sorting of Trp containing peptides.

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