Supramolecular encapsulation of nanocrystalline Schiff bases into ß-cyclodextrin for multifold enrichment of bio-potency.

We report the solvent-free green synthesis of two Schiff bases, (E)-2-((2-hydroxy-3-methoxybenzylidene)amino)-4-methylphenol (SL1) and (E)-2-((2-hydroxybenzylidene) amino)-4-methylphenol (SL2), and their inclusion complexes with ß-cyclodextrin (ß-CD). The encapsulation phenomenon, structural characteristics and hydrolytic stabilities of the SL1, SL2 and their inclusion complexes are determined with a suite of spectroscopic, analytical and crystallographic analyses. Dose and time-dependent cytotoxicity study of SL1-ß-CD and SL2-ß-CD against two breast cancer cell lines, Michigan Cancer Foundation-7 (MCF-7) and metastatic mammary adenocarcinoma1 (MDA-MB-231), exhibit excellent inhibitory activity with significant non-cytotoxic concentrations and ensure a multifold elevation of bio-potency than the parent Schiff base compounds. The Annexin-V assay determines the efficacy of these inclusion complexes to trigger apoptosis, suggesting that SL2-ß-CD possesses better efficacy as an anti-cancer drug. To the best of our knowledge, we, for the first time, report the inclusion of nanocrystalline Schiff bases into ß-CD for multifold enrichment of bio-potency.

Development of a hydrolase mimicking peptide amphiphile and its immobilization on silica surface for stereoselective and enhanced catalysis.

Biocatalysis is an important area of modern research and is extensively explored by various industries to attain greener methods in various applications. Supramolecular interactions of short peptides have been under the scanner for developing artificial smart materials inspired from natural systems. Peptide-based artificial enzymes have been proved to show various enzyme-like activities. Therefore, immobilization of catalytic peptides on solid surfaces can be an extremely useful breakthrough for development of cost-effective catalytic formulations. In this work, a series of peptide amphiphiles (PAs) have been systematically analyzed to find the most effective catalyst with esterase like activity. The PA, containing a catalytic triad, 'Asp(Ser)His' in a branched manner, was further immobilized onto silica nanoparticles through covalent bonding method to obtain surface coated catalytic silica nanoparticles. The heterogenous catalytic formulation not only showed enhanced esterase activity than the self-assembled PA in homogenous phase, but also exceeded the activity of natural CV lipase. The catalytic formulation showed high stereoselectivity towards chiral esters. Moreover, the catalyst remained stable at higher temperature, in presence of various denaturant and retained its activity after several catalytic cycles. The ease of separation, robust nature, reusability and high stereoselectivity of the catalyst opens up the possibility of creating new generation heterogeneous catalysts for further industrial applications.

Unusual confinement properties of a water insoluble small peptide hydrogel.

Unlike polymeric hydrogels, in the case of supramolecular hydrogels, the cross-linked network formation is governed by non-covalent forces. Hence, in these cases, the gelator molecules inside the network retain their characteristic physicochemical properties as no covalent modification is involved. Supramolecular hydrogels thus get dissolved easily in aqueous medium as the dissolution leads to a gain in entropy. Thus, any supramolecular hydrogel, insoluble in bulk water, is beyond the present understanding and hitherto not reported as well. Herein, we present a peptide-based (PyKC) hydrogel which remained insoluble in water for more than a year. Moreover, in the gel state, any movement of solvent or solute to and from the hydrogel is highly restricted resulting in a high degree of compartmentalization. The hydrogel could be re-dissolved in the presence of some biomolecules which makes it a prospective material for in vivo applications. Experimental studies and all atom molecular dynamics simulations revealed that a cysteine containing gelator forms dimers through disulfide linkage which self-assemble into PyKC layers with a distinct PyKC-water interface. The hydrogel is stabilized by intra-molecular hydrogen bonds within the peptide-conjugates and the π-π stacking of the pyrene rings. The unique confinement ability of the hydrogel is attributed to the slow dynamics of water which remains confined in the core region of PyKC via hydrogen bonds. The hydrogen bonds present in the confined water need activation energies to move through the water depleted hydrophobic environment of pyrene rings which significantly reduces water transport across the hydrogel. The compartmentalizing ability is effectively used to protect enzymes for a long time from denaturing agents like urea, heat or methanol. Overall, the presented system shows unique insolubility and confinement properties that could be a milestone in the research of soft-materials.