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.

Freeze the dynamicity: charge transfer complexation assisted control over the reaction pathway.

Charge transfer (CT) complexes between electron donor and acceptor molecules provide unique alternate D-A arrangements. However, these arrangements cannot be fully translated into chemo-selective organic transformations as the dynamicity of CT complexes in solution results in the co-existence of D-A assemblies and free monomers during the reaction time-scale. A conceptually new strategy to exploit CT complexes toward chemo-selective products by means of seizing the dynamicity of CT complexes is reported here. Aqueous CT complexes of donor and acceptor molecules bearing reactive thiol groups were frozen instantly and cryo-desiccated to get the alternate D-A assemblies intact in the solid state. Oxidation of reactive thiols in an oxygen rich solvent in the solid state resulted in the formation of the hetero-dimer exclusively. CT complexation and appropriate molecular arrangements are the key factors behind successful execution of this novel methodology. The strategy also paves the way to prepare unsymmetrical disulfide molecules from two dissimilar thiols.

Unorthodox Combination of Cation-π and Charge-Transfer Interactions within a Donor-Acceptor Pair.

Cation-π and charge-transfer (CT) interactions are ubiquitous in nature and involved in several biological processes. Although the origin of both the interactions in isolated pairs has extensively been studied, CT interactions are more prominent in supramolecular chemistry. Involvement of cation-π interactions in the preparation of advanced functional soft materials is uncommon. Moreover, a combination of these two interactions within a pair of electron donor (D) and acceptor (A) is uncharted. Here, we present a rational design to incorporate a combination of these two interactions within a D-A pair. A pyrene-peptide conjugate exhibits a combination of cation-π and CT interactions with a cationic naphthalenediimide (NDI) molecule in water. Nuclear Overhauser effect spectroscopy NMR along with other techniques and density functional theory calculations reveal the involvement of these interactions. The π-planes of pyrene and NDI adopt an angle of 56° to satisfy both the interactions, whereas ß-sheet formation by the peptide sequence facilitates self-assembly. Notably, the binary system forms a self-supporting hydrogel at a higher concentration. The hydrogel shows efficient self-healing and injectable property. The hydrogel retains its thixotropic nature even at an elevated temperature. Broadly, we demonstrate a pathway that should prove pertinent to various areas, ranging from understanding biological assembly to peptide-based functional soft materials.

Multiple Cross-Linking of a Small Peptide to Form a Size Tunable Biopolymer with Efficient Cell Adhesion and Proliferation Property.

Development of biocompatible polymeric systems capable of cell adhesion and proliferation is a challenging task. Proper cross-linking of small cell adhesive peptide sequences is useful in this respect as it provides the inherent nontoxic environment as well as the cross-linked polymeric network to the cells for adhesion and proliferation. A multiple cross-linking strategy is applied to create a peptide-based cross-linked polymer. Covalent linkage through disulfide bond formation, supramolecular linkage using homoternary complexation by CB[8], and enzymatic cross-linking by HRP-mediated dimerization of tyrosine are used to prepare the cross-linked, peptide-based polymer decorated with cell-adhesive RGDS sequence. The supramolecular cross-linking via CB[8] provided stability as well as brings the RGDS sequences at the surface of the polymer particles. The order of cross-linking allowed to fine-tune the particle size of the polymer and polymer particles of wide range (200-1000 nm) can be prepared by varying the order. The cross-linked polymer particles (P1 and P2) were found to be stable at wide range of temperature and pH. Moreover, as intended, the polymer was noncytotoxic in nature and showed efficient cell adhesion and proliferation property, which can be used for further biological applications.

Hydrogelation of a Naphthalene Diimide Appended Peptide Amphiphile and Its Application in Cell Imaging and Intracellular pH Sensing.

This study reports the self-assembly and application of a naphthalene diimide (NDI)-appended peptide amphiphile (PA). H-bonding among the peptide moiety in conjunction with π-stacking between NDI and hydrophobic interactions within the alkyl chain are the major driving forces behind the stepwise aggregation of the PA to form hydrogels. The PA produced efficient self-assemblies in water, forming a nanofibrous network that further formed a self-supportive hydrogel. The molecule followed a three-step self-assembly mechanism. At a lower concentration (50 µM), it forms extremely small aggregates with a very low population of the molecules. With an increase in concentration, spherical aggregates are formed above 450 µM concentration. Importantly, this water-soluble conjugate was found to be nontoxic, cell permeable, and usable for cell imaging. Moreover, the aggregation process and consequently the emission behavior are highly responsive to the pH of the medium. Thus, the pH responsive aggregation and emission behavior has an extended biological application for assessing intracellular pH. The biocompatibility and intracellular pH determining capability suggest it is a promising candidate for use as a supramolecular material in biomedical applications.

Solvent Assisted Tuning of Morphology of a Peptide-Perylenediimide Conjugate: Helical Fibers to Nano-Rings and their Differential Semiconductivity.

Understanding the regulatory factors of self-assembly processes is a necessity in order to modulate the nano-structures and their properties. Here, the self-assembly mechanism of a peptide-perylenediimide (P-1) conjugate in mixed solvent systems of THF/water is studied and the semiconducting properties are correlated with the morphology. In THF, right handed helical fibers are formed while in 10% THF-water, the morphology changes to nano-rings along with a switch in the helicity to left-handed orientation. Experimental results combined with DFT calculations reveal the critical role of thermodynamic and kinetic factors to control these differential self-assembly processes. In THF, P-1 forms right handed helical fibers in a kinetically controlled fashion. In case of 10% THF-water, the initial nucleation of the aggregate is controlled kinetically. Due to differential solubility of the molecule in these two solvents, elongation of the nuclei into fibers is restricted after a critical length leading to the formation of nano-rings which is governed by the thermodynamics. The helical fibers show superior semi-conducting property to the nano-rings as confirmed by conducting-AFM and conventional I-V characteristics.

A Viologen-Perylenediimide Conjugate as an Efficient Base Sensor with Solvatochromic Property.

A viologen-perylenediimide conjugate, denoted PDEV, is prepared for efficient base sensing. The conjugate shows solvatochromic behavior as well. The base sensitivity of viologen is purposefully coupled with the emission property of perylenediimide (PDI) to lower the detection limit. PDEV shows base-sensing ability at the ppb level, which is at least three orders of magnitude lower than those of previously reported sensors. The probe is sensitive toward solvent polarity and generates different shades of colors according to the polarity of the medium (solvent). The photophysical properties show a linear correlation with the solvent polarity, and this makes it an efficient solvatochromic agent. On the other hand, the generation of viologen radical cations by bases affects the aggregation and consequently the absorption and emission behavior of the PDI core. The effect of bases can also be visualized, because the probe generates different colors in the presence of bases, both under normal and under UV light. Organic amines can be detected even in the crystalline state, since the dark red color of the PDEV crystals changes to purple in a reversible fashion on exposure to amine vapors. An easy and practical paper-based tool created by using the probe can efficiently be used to detect solvent polarity and presence of bases optically.