Synthesis and Assembly of Small Peptidomimetics

Gumtya, Milan (2024) Synthesis and Assembly of Small Peptidomimetics. PhD thesis, Indian Institute of Science Education and Research Kolkata.

Text (PhD thesis of Milan Gumtya (19RS109)) 19RS109.pdf - Submitted Version Restricted to Repository staff only Download (9MB)

Abstract

This thesis entitled as “Synthesis and Assembly of Small Peptidomimetics” is all about the design, synthesis, characterization, conformational analysis, self-assembly and application of peptimimetics. The main focus of this thesis is to develop synthetic Peptidomimetics composed of both genetically coded and non-coded amino acids for studying and understanding the molecular self-assembly processes of these peptides in supramolecular helices, sheets and to study their further aggregation behavior in forming gels or nanomaterials like tube, vesicle, fibre, porous structure and their versatile applications in several fields. Here, the self-assembly, organogelation, syneresis, and anti-adhesion properties of a peptidomimetic containing L-phenylalanine and 2,6-dimethylpyridine 3,5-dicarboxylic acid have been studied in detail. The peptidomimetic forms a transparent gel in aromatic solvents such as benzene, toluene, xylene and chlorobenzene. The hierarchical nature of the self-assembly process in the gel was characterized by a combination of POM and FE-SEM imaging, revealing an entangled fiber network. The rheology measurements then confirmed the formation of a thixotropic organogel. The storage modulus was about one order of magnitude higher than the loss modulus, which indicates the physical crosslinking in the organogel. The gel exhibits significant self-healing properties and allows diffusion of rhodamine 6G through the gel matrix. The peptidomimetic gel shows syneresis under an appropriate environment. The peptidomimetic organogel surfaces exhibit syneresis-induced anti-adhesion properties against ice and water. This peptidomimetic gelator molecule, being economically viable and easy to synthesize, has great prospects in materials chemistry. The thesis also represents structure and mechanical property of novel designer peptidomimetics containing L-phenylalanine, L-tryptophan and 2,6-dimethylpyridine 3,5-dicarboxylic acid have been reported. The peptidomimetic 1 containing L-phenylalanine crystals are sensitive to external stress and very brittle in nature but peptidomimetic 2 containing L- tryptophan exhibits moderate plastically deformed crystal under mechanical stress. From X-ray diffraction analysis, peptidomimetic 1 has kink-like conformation and formed spherical dimeric packing stabilized by multiple water mediated hydrogen bonding and π-π stacking interactions. However, the peptidomimetic 2 adopts an extended conformation where the indole groups from L-tryptophan side chains are in opposite direction. The peptidomimetic 2 molecules self-assemble by intermolecular N-H⋯O hydrogen bonds and form a supramolecular sheet-like structure which is further assembled to form a supramolecular tryptophan-zipper structure along the crystallographic a and c directions. The nanoindentation measurement of peptidomimetic 2 on the most prominent face (001) reveals the elastic modulus (E) was 10.33 ± 0.36 GPa and 10.41 ± 0.17 GPa at 3mN and 5mN loads respectively whereas, hardness (h) at both the loads were 553.21 ± 19.30 MPa and 526.91 ± 19.88 MPa. The value of the elasticity index I (0.053) is close to that of biological materials (0.05). B3LYP/6-31G(d,p) dispersion corrected DFT model was used to calculate the intermolecular interaction energies (kJ/mol) for the peptidomimetic 2. However, the interaction energy is small, the interdigitation of the indole groups in supramolecular tryptophan-zipper make scope of slippage and exhibits moderate plastically deformed crystal under external stress. The thesis includes the water electrolysis is critical for generating hydrogen and oxygen as alternative renewable fuels. The primary challenge lies in developing simple, economical, and eco-friendly catalysts with minimal overpotential. This study introduces a cobalt-based 1D Metal-Organic Framework (MOF) as a highly efficient catalyst for water oxidation under electrochemical conditions. Significantly, the ligand and water bridges between Co(II) centers play a crucial role in electrocatalysis. Through electrochemical, spectroscopic, and electron microscopy analyses, we demonstrate that the 1D MOF is an effective heterogeneous electrocatalyst for water oxidation, achieving a high Faradaic efficiency of 85% and an overpotential of just 390 mV. These findings offer a new direction in designing cost-effective and highly efficient transition-metal-based catalysts for water oxidation. The thesis also describes that two coordination complexes of Cu (II) with N-Phthaloyl-β-alanine and N-Phthaloyl-γ-aminobutyric acid have been achieved in this work. The crystallographic structural descriptions along with the anti-bacterial activity of these two coordination complexes have been explored. From X-ray crystallography, in complex 1, the Cu (II)-center shows a penta-coordinated geometry with oxygen donor sites from two N-Phthaloyl-β-alanine, two pyridines, along with one coordinated water molecule. In complex2, the Cu (II)-center shows a hexa-coordinated geometry with oxygen donor sites from two N-Phthaloyl- γ -aminobutyric acid and two pyridines. The complexes adopt a paddle-wheel conformation that eventually form a porous structure in higher order packing through multiple π-π stacking interactions. We have also investigated their inhibitory effects against both gram negative (Escherichia coli) and gram positive (Bacillus subtilis) bacteria. The Cu (II) complex with N-Phthaloyl-β-alanine showed the highest inhibitory effects. The thesis also demonstrates synthesis and self-assembly properties of imino m-Nifedipine luminophores and its Zn (II) Complexes has been reported. The m-Nifedipine was synthesized by reaction of 3-nitrobenzaldehyde, ethyl acetoacetate, and NH4OH in EtOH. The reduction of the m-Nifedipine with iron powder and glacial acetic acid provides corresponding amine, which on treatment with salicylaldehyde or m-diethylamino salicylaldehyde results the luminophores 1 and 2. The reaction of 1 or 2 with zinc acetate at 80 °C for 4 h result formation of green colour complex 3 or 4. The coordination compounds 3 and 4 show a broad absorption band with maxima at 355 and 395 nm, which can be ascribed to the MLCT transitions between Zinc (II) ion and the luminophores. The Zn complexes 3 shows green color (λex = 355 nm, λem = 450 nm) and Zn (II) complexes 4 shows bluish green color (λex = 395 nm, λem = 430 nm). From X-raycrystallography, in both the complexes 3 and 4, the Zn (II) center is tetrahedrally coordinated by two imine nitrogen atoms and phenolate oxygen atoms of the luminophores. Moreover, Zn (II)–oxygen–Zn (II) angles for 3 and 4 complexes were found to be 104.83Ǻ and 115.47Ǻ respectively. From FE-SEM, a supramolecular fiber-like network structure arises due to the self-assembly of Zn (II) complexes by non-covalent interactions such as hydrogen bonding, π–π interactions and hydrophobic effects.

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