Stabilization of a Photoradiated Naphthalene Diimide-Based Organic Radical Anion Inside a Peptide-Based Gel Matrix with an Improvement of Optoelectronic Properties.

An amino acid-conjugated naphthalene diimide (NDI)-based highly red fluorescent radical anion has been found in a water medium under the photoradiated condition. This molecule has failed to form the radical anion in the monomeric state; however, the J aggregation in the aqueous medium has ensured the formation of radical anion in the ambient condition after the irradiation of both sunlight and UV light exposure. Electron paramagnetic resonance (EPR) studies clearly suggest the formation of radical anions. Herein, the stability of the radical anion in the aqueous medium is only a few minutes as a small amount of shaking is enough to quench the radical anion in the solution state. Furthermore, the incorporation of this molecule into a peptide-based hydrogel matrix and the consequent photoirradiation have not only helped to develop radical anion in the gel matrix but also increased the enormous stability of the radical anion inside the hydrogel matrix even for 30 days. It is envisaged that the formation of the radical anion within the gel matrix prevents the free movement of the NDI molecules and restricts the diffusion of molecular oxygen in the system, which leads to the stability of the radical anions in the gel. Moreover, the stability of the radical anion within the gel has helped to enhance the conductivity of the hybrid gel to a great extent. Interestingly, the radical anion-containing hybrid hydrogel has shown a potential photoswitching property.

Cationic and amphiphilic peptide-based hydrogels with dual activities as anticancer and antibacterial agents.

The emergence of peptide-based functional biomaterials is on the rise. To fulfil this purpose, a series of amphiphilic peptides, such as H2N-X-Met-Phe-C12H25, where X = L-lysine (CP1), X = L-histidine (CP2), and X = L-leucine (CP3), have been designed, synthesised, purified and fully characterised. Herein, we reported peptide-based supramolecular hydrogels with antibacterial and anticancer activities. An attempt has been made to investigate the antibacterial properties of these peptide-based hydrogels against Gram-positive (S. aureus and B. subtilis) and Gram-negative (E. coli and P. aeruginosa) bacteria. Investigations show that the L-lysine containing gelator, CP1, is active against both Gram-positive and Gram-negative bacteria and the L-histidine containing gelator, CP2, selectively inhibits the growth of Gram-negative bacteria. Interestingly, the L-leucine containing gelator, CP3, does not show any antibacterial properties. Moreover, the L-lysine containing gelator exhibits the best potency. Generation of reactive oxygen species (ROS) is a probable way to damage the bacterial membrane. To explore the cytotoxic properties and to determine the efficacy of the synthesized compounds in inhibiting cell viability, a comprehensive investigation was performed using three distinct cell lines: MDA-MB-231 (human triple-negative breast cancer), MDA-MB-468 (human triple-negative breast cancer) and HEK 293 (human embryonic kidney). Remarkably, the results of our study revealed a substantial cytotoxic impact of these peptide gelators on the MDA-MB-231 and MDA-MB-468 cell lines in comparison to the HEK 293 cells. Caspase 3/7 activity is the possible mechanistic path to determine the apoptotic rates of the cell lines. This finding emphasizes the promising potential of these peptide-based gelators in targeting and suppressing the growth of human triple negative breast cancer cells, while showing non-cytotoxicity towards non-cancerous HEK 293 cells. In a nutshell, these peptide-based materials are coming to light as next generation biomaterials.

Histidine-Containing Amphiphilic Peptide-Based Non-Cytotoxic Hydrogelator with Antibacterial Activity and Sustainable Drug Release.

A histidine-based amphiphilic peptide (P) has been found to form an injectable transparent hydrogel in phosphate buffer solution over a pH range from 7.0 to 8.5 with an inherent antibacterial property. It also formed a hydrogel in water at pH = 6.7. The peptide self-assembles into a nanofibrillar network structure which is characterized by high-resolution transmission electron microscopy, field-emission scanning electron microscopy, atomic force microscopy, small-angle X-ray scattering, Fourier-transform infrared spectroscopy, and wide-angle powder X-ray diffraction. The hydrogel exhibits efficient antibacterial activity against both Gram-positive bacteria Staphylococcus aureus (S. aureus) and Gram-negative bacteria Escherichia coli (E. coli). The minimum inhibitory concentration of the hydrogel ranges from 20 to 100 µg/mL. The hydrogel is capable of encapsulation of the drugs naproxen (a non-steroidal anti-inflammatory drug), amoxicillin (an antibiotic), and doxorubicin, (an anticancer drug), but, selectively and sustainably, the gel releases naproxen, 84% being released in 84 h and amoxicillin was released more or less in same manner with that of the naproxen. The hydrogel is biocompatible with HEK 293T cells as well as NIH (mouse fibroblast cell line) cells and thus has potential as a potent antibacterial and drug releasing agent. Another remarkable feature of this hydrogel is its magnification property like a convex lens.

Effect of molar ratio and concentration on the rheological properties of two-component supramolecular hydrogels: tuning of the morphological and drug releasing behaviour.

Self-assembled supramolecular hydrogels offer great potential as biomaterials and drug delivery systems. Specifically, peptide-based multicomponent hydrogels are promising materials due to their advantage that their mechanical and physical properties can be tuned to enhance their functionalities and broaden their applications. Herein, we report two-component assembly and formation of hydrogels containing inexpensive complementary anionic, BUVV-OH (A), and cationic, KFFC12 (B), peptide amphiphiles. Individually, neither of these components formed a hydrogel, while mixtures with compositions 1 : 1, 1 : 2, and 2 : 1 (molar ratio) as A : B show hydrogel formation (Milli-Q water, at pH = 6.79). These hydrogels displayed a good shear-thinning behaviour with different mechanical stabilities and nano-fibrous network structures. The 1 : 1 hydrogel shows good cell viability for human embryonic kidney (HEK-293) cells and CHO cells indicating its non-cytotoxicity. The biocompatible, thixotropic 1 : 1 hydrogel with a nanofiber network structure shows the highest mechanical strength with a storage modulus of 3.4 × 103 Pa. The hydrogel is able to encapsulate drugs including antibiotics amoxicillin and rifampicin, and anticancer drug doxorubicin, and it exhibits sustainable release of 76%, 70%, and 81% respectively in vitro after 3 days. The other two mixtures (composition 1 : 2 and 2 : 1) are unable to form a hydrogel when they are loaded with these drugs. Interestingly, it is noticed that with an increase in concentration, the mechanical strength of a 1 : 1 hydrogel is significantly enhanced, showing potential that may act as a scaffold for tissue engineering. The two-component gel offers tunable mechanical properties, thixotropy, injectability, and biocompatibility and has great potential as a scaffold for sustained drug release and tissue engineering.

Metal ion-induced assembly of dipeptide-attached perylenediimide for fluorometric "turn on" detection of biologically important small molecule.

A dipeptide-appended perylenediimide (PDI-CFF) fluorescent molecule was designed, synthesized, and characterized. Though the molecule does not dissolve in any individual solvent, it dissolves well in an organic/water mixed solvent system such as tetrahydrofuran/water. This new fluorescent molecule was self-assembled in a tetrahydrofuran/water mixture to form both nanofibrous network structures and a nano ring structure. It has shown nanofibril morphology by the interactions with ferric ions (PDI-CFF/Fe3+ system) with diminishing fluorescent property. Interestingly, L-ascorbic acid (LAA) interacts with the PDI-CFF/Fe3+ system, showing turn-on fluorescence. Another interesting feature is that the minimum detection limits for Fe3+ ions and LAA are at the submicromolar levels of 6.2 × 10-8 and 3 × 10-8  M, respectively. Moreover, the fluorescent (10 µM) signals can be monitored by the naked eye under handheld UV lamp irradiation at 365 nm, and this is very convenient for the real application. In this study, the molecule offers the opportunity for processing these sequential fluorescence responses in order to fabricate a implication logic gate that includes NOT, AND, and OR simple logic gates using chemical stimuli (ferric ions and LAA) as inputs and fluorescence emission at 536 nm as output. The detailed mechanism of interactions of Fe3+ with PDI-CFF and LAA with the PDI-CFF/Fe3+ system is vividly studied by using Fourier transform infrared (FT-IR) analysis and fluorescence. Moreover, this new molecule was reusable for several times without significant loss of its activity. The construction of logic gates using biologically important molecules/ions holds future promise for the design and development of new bio-logic gates.

Amino acid containing amphiphilic hydrogelators with antibacterial and antiparasitic activities.

Nanoscale self-assembly of peptide constructs represents a promising means to present bioactive motifs to develop new functional materials. Here, we present a series of peptide amphiphiles which form hydrogels based on ß-sheet nanofibril networks, several of which have very promising anti-microbial and anti-parasitic activities, in particular against multiple strains of Leishmania including drug-resistant ones. Aromatic amino acid based amphiphilic supramolecular gelators C14-Phe-CONH-(CH2)n-NH2 (n = 6 for P1 and n = 2 for P3) and C14-Trp-CONH-(CH2)n-NH2 (n = 6 for P2 and n = 2 for P4) have been synthesized and characterized, and their self-assembly and gelation behaviour have been investigated in the presence of ultrapure water (P1, P2, and P4) or 2% DMSO(v/v) in ultrapure water (P3). The rheological, morphological and structural properties of the gels have been comprehensively examined. The amphiphilic gelators (P1 and P3) were found to be active against both Gram-positive bacteria B. subtilis and Gram-negative bacteria E. coli and P. aeruginosa. Interestingly, amphiphiles P1 and P3 containing an L-phenylalanine residue show both antibacterial and antiparasitic activities. Herein, we report that synthetic amphiphiles with an amino acid residue exhibit a potent anti-protozoan activity and are cytotoxic towards a wide array of protozoal parasites, which includes Indian varieties of Leishmania donovani and also kill resistant parasitic strains including BHU-575, MILR and CPTR cells. These gelators are highly cytotoxic to promastigotes of Leishmania and trigger apoptotic-like events inside the parasite. The mechanism of killing the parasite is shown and these gelators are non-cytotoxic to host macrophage cells indicating the potential use of these gels as therapeutic agents against multiple forms of leishmaniasis in the near future.

Peptide-Based Gel in Environmental Remediation: Removal of Toxic Organic Dyes and Hazardous Pb2+ and Cd2+ Ions from Wastewater and Oil Spill Recovery.

A dipeptide-based synthetic amphiphile bearing a myristyl chain has been found to form hydrogels in the pH range 6.9-8.5 and organogels in various organic solvents including petroleum ether, diesel, kerosene, and petrol. These organogels and hydrogels have been thoroughly studied and characterized by different techniques including high-resolution transmission electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, and rheology. It has been found that the xerogel obtained from the peptide gelator can trap various toxic organic dyes from wastewater efficiently. Moreover, the hydrogel has been used to remove toxic heavy metal ions Pb2+ and Cd2+ from wastewater. Dye adsorption kinetics has been studied, and it has been fitted by using the Freundlich isotherm equation. Interestingly, the gelator amphiphilic peptide gels fuel oil, kerosene, diesel, and petrol in a biphasic mixture of salt water and oil within a few seconds. This indicates that these gels not only may find application in oil spill recovery but also can be used to remove toxic organic dyes and hazardous toxic metal ions from wastewater. Moreover, the gelator can be recycled several times without significant loss of activity, suggesting the sustainability of this new gelator. This holds future promise for environmental remediation by using peptide-based gelators.