ABSTRACT
With growing threats from counterfeiting-based security breaches, multi-level and specific stimuli-responsive anti-counterfeiting devices and message encryption methods have attracted immense research interest. Fluorescence-based encryption from aggregation-induced emission (AIE)-based materials solves the problems to a considerable extent. However, the development of smarter patterns with hierarchical security levels alongside dynamic display is still challenging. To screen out this complication, we bring forward a pH-switchable fluorescent assembly of an AIEgen and an aliphatic acid. We later temporally direct the molecular assembly with the aid of a chemical trigger-regulated pH clock, generating a transitory multicolor emission, including transient white light generation. The pH-dependent emissions were further implemented in constructing smart multi-input fluorescent chemical AND gates. Subsequently, we integrate the time-gated emissive system to develop an advanced multi-dimensionally secure data encryption strategy. This novel approach enhances anti-counterfeiting measures by introducing an additional layer of security based on temporal characteristics.
ABSTRACT
An intricate synergism between multiple biochemical processes and physical conditions determines the formation and function of various biological self-assemblies. Thus, a complex set of variables dictate the far-from-equilibrium nature of these biological assemblies. Mimicking such systems synthetically is a challenging task. We report multi-stimuli responsive transient coacervation of an aldehyde-appended polymer and a short peptide. The coacervates are formed by the disulphide linkages between the peptide molecules and the imine bond between the polymer and the peptide. Imines are susceptible to pH changes and the disulphide bonds can be tuned by oxidation/reduction processes. Thus, the coacervation is operational only under the combined effect of appropriate pH and oxidative conditions. Taking advantage of these facts, the coacervates are transiently formed under a pH cycle (urea-urease/gluconolactone) and a non-equilibrium redox cycle (TCEP/H2 O2 ). Importantly, the system showed high adaptability toward environmental changes. The transient existence of the coacervates can be generated without any apparent change in size and shape within the same system through the sequential application of the above-mentioned nonequilibrium reaction cycles. Additionally, the coacervation allows for efficient encapsulation/stabilisation of proteins. Thus, the system has the potential to be used for protein/drug delivery purposes in the future.
ABSTRACT
Supramolecular assembly of short peptides is a crucial process and has shown numerous potential applications as biomaterials. In the present work, the hydrogelation process of short peptides containing C-terminal "Lys-Cys" (KC) residues have been studied in detail. The N-terminal capping is found to be essential for effective gelation. Out of 12 peptides we studied, two of them could form hydrogels efficiently: Ac-VVKC-NH2 and Ac-FFKC-NH2. In both cases, the monomer-to-dimer formation through disulfide linkages by Cys residues controls the aggregation process. Interestingly, the presence of H2O2 facilitated the dimerization and thereby reduced the gelation time but could not impart much effect on the mechanical properties of the gels. Detailed rheological study revealed that both hydrogels are thixotropic in nature. Moreover, they are responsive to glutathione (GSH) due to the presence of disulfide linkages. However, the hydrogel of Ac-FFKC-NH2 is found to be stronger and more effective for biological applications. The thixotropic nature as well as a model drug release study in response to varying GSH concentration indicates the possible use of the hydrogel as an injectable local drug delivery vehicle. The hydrogel of Ac-FFKC-NH2 is noncytotoxic in nature. Three-dimensional cell proliferation has been found to be more effective than 2D, as it mimics the in vivo situation more closely if not exactly. In the present study, we have shown that both differentiated RAW macrophages and undifferentiated THP-1 monocytes could proliferate significantly within the 3D matrix of the hydrogel, without depicting any apparent cytotoxicity. Thus, the hydrogel of Ac-FFKC-NH2 has potential for application in localized drug administration and as a supporting biomaterial to study basic phenomena involving cell behavior.
Subject(s)
Disulfides , Hydrogels , Cell Proliferation , Hydrogen Peroxide , PeptidesABSTRACT
Peptide amphiphiles (PAs) are extremely attractive as molecular building blocks, especially in the bottom-up fabrication of supramolecular soft materials, and have potential in many important applications across various fields of science and technology. In recent years, we have designed and synthesized a large group of peptide amphiphiles. This library of PAs has the ability to self-assemble into a variety of aggregates such as fibers, nanosphere, vesicles, nanosheet, nanocups, nanorings, hydrogels, and so on. The mechanism behind the formation of such a wide range of structures is intriguing. Each system has its individual method of aggregation and results in assemblies with important applications in areas including chemistry, biology, and materials science. The aim of this feature article is to bring together our recent achievements with designer PAs with respect to their self-assembly processes and applications. Emphasis is placed on rational design, mechanistic aspects of the self-assembly processes, and the applications of these PAs. We hope that this article will provide a conceptual demonstration of the different approaches taken toward the construction of these task-specific PAs.
Subject(s)
Hydrogels/chemistry , Nanostructures/chemistry , Peptides/chemistry , Female , Humans , Male , Portraits as TopicABSTRACT
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.
ABSTRACT
Molecular organization of electron-deficient aromatic systems like perylenediimides (PDI) is extremely appealing, as they are potential candidates for organic electronics. The performance of these molecules in such applications primarily depends on the self-organization of the molecules. However, any correlation between the morphology of these self-assembled semiconducting molecules and their electrical performances has not yet been formulated. Herein, for the first time, we have made an effort to find such a correlation by studying the self-assembly, morphology, and their conducting properties for a peptide-PDI conjugate. The PDI conjugate formed fiber-like morphology in relatively nonpolar solvents (THF and CHCl3) while in more polar solvents (HFIP, MeOH, ACN, and acetone), spherical morphology could be found. Interestingly, the self-assembly and the morphologies showed a clear dependence on the solvent polarity. In polar solvents, the conjugate aggregates more efficiently than in the nonpolar solvents, and with decrease in solvent polarity, the dimension of the nanostructures increased. However, in all the tested solvents, irrespective of their polarity, the PDI-peptide conjugate adopts a right-handed helicity. To find a correlation between the morphologies with the conducting property, detailed electrical characterization of these nanostructures was carried out. While no significant change could be observed for the dc conductivities of these nanostructures, the ac conductivities show prominent difference at the low-frequency region. A dispersion of conductivity was observed for the nanospheres due to the polarization effect. A critical correlation between the nanostructures and the activation energy was observed as with decrease in radii of curvature of the aggregates the activation energy increases with an exception in the case of MeOH. The observed results suggest that the long-range transport of charge carriers is less favorable when the aggregates are small and closely packed.
Subject(s)
Imides/chemistry , Nanostructures/chemistry , Peptides/chemistry , Perylene/analogs & derivatives , Solvents/chemistry , Perylene/chemistryABSTRACT
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.
Subject(s)
Biopolymers/chemistry , Cell Adhesion , Cell Proliferation , Cross-Linking Reagents/chemistry , Macrophages/physiology , Oligopeptides/chemistry , Animals , Biopolymers/pharmacology , Cells, Cultured , Horseradish Peroxidase/metabolism , Macrophages/cytology , Mice , Oligopeptides/pharmacology , Tyrosine/metabolismABSTRACT
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.
ABSTRACT
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.
Subject(s)
Cell Tracking/methods , Hydrogels/chemistry , Imides/chemistry , Naphthalenes/chemistry , Peptides/chemistry , Biosensing Techniques , Cytoplasm/chemistry , Humans , Hydrogen Bonding , Hydrogen-Ion Concentration , Hydrophobic and Hydrophilic Interactions , Peptides/chemical synthesis , Water/chemistryABSTRACT
An efficient, direct C6-arylation of 2-pyridones has been successfully accomplished with quinone diazides under Rh(III)-catalyzed redox-neutral conditions. The optimized method is simple, mild, and highly regioselective with a broad substrate scope. The strict regioselectivity is guided by the pyridyl substituent attached to the nitrogen of the pyridone ring. As the directing 2-pyridyl group can easily be removed at any suitable stage after functionalization, the method provides a facile access to complex heteroarylated phenol moieties by wide-ranging heterocyclic scaffolds.
ABSTRACT
A rhodium catalyzed direct regioselective oxidative annulation by double C-H activation is described to synthesize highly substituted quinolones from pyridones. The reaction proceeds at mild conditions with broad scope and wide functional group tolerance. These novel quinolones were explored to recognize nitroaromatic compounds.
ABSTRACT
A Rh(III)-catalyzed highly efficient C6-alkylation of 2-pyridones has been achieved successfully with α-diazo carbonyl compounds. The developed method is simple, mild, and highly regioselective with a broad range of substrate scope. The regioselectivity is guided by the pyridyl substituent attached to the nitrogen center of the pyridone ring. The directing group can be easily removed, and the only formed byproduct is nitrogen. Furthermore, other similar heterocyclic scaffolds can also be functionalized regioselectively under the developed conditions.
ABSTRACT
A systematic study of the ternary complex formation process for aromatic amino acids using ucurbit[8]uril (CB[8]) and a viologen amphiphile shows that the affinity of the amino acid needs to be higher or in a comparable range to that of CB[8] for the amphiphile in order to form the ternary complex. Based on these observations, a supramolecular peptide amphiphile and its corresponding vesicle are prepared using a peptide containing an azobenzene moiety. The azobenzene group at the N-terminus of the peptide served as the second guest for CB[8]. The vesicles obtained from this peptide amphiphile show response to a number of external triggers. The trans-cis isomerization of the azobenzene group upon irradiation with UV-light of 365 nm leads to the breakdown of the ternary complex and eventually to the disruption of the vesicle. The deformation-reformation of the vesicle can be controlled by illuminating the disrupted solution with light of 420 nm as it facilitates the cis-trans isomerization. Thus, the vesicle showed a controlled and reversible response to UV-light with the ability for manipulation of the formation-deformation of the vesicle by the choice of an appropriate wavelength. The vesicle showed response to a stronger guest (1-adamantylamine) for CB[8], which displaces both the guests from the CB[8] cavity and consequently ruptures the vesicle structure. 2,6-Dihydroxynaphthalene acts as a competitive guest and thereby behaves as another external trigger for replacing the peptide from the CB[8] cavity by self-inclusion to form the ternary complex. Henceforth, it allows retaining the vesicle structure and results in the release of the peptide from the vesicle.
Subject(s)
Liposomes/chemistry , Peptides/chemistry , Surface-Active Agents/chemistry , Azo Compounds/chemistry , Bridged-Ring Compounds/chemistry , Imidazoles/chemistry , Liposomes/radiation effects , Naphthols/chemistry , Ultraviolet Rays , Viologens/chemistryABSTRACT
A systematic study on the cucurbit[8]uril (CB[8]) assisted transformation of a mixed micellar system of CTAB and a viologen surfactant to vesicles is depicted. The micelle to vesicle transformation is assisted by a charge transfer complex mediated ternary complexation between the viologen group of the surfactant, CB[8], and 2,6-dihydroxynaphthalene. In the presence of CB[8], both the surfactants formed U-shaped binary inclusion complexes inside the CB[8] cavity, and no selective binding is observed. Upon addition of DHN, CB[8] showed two different self-sorting mechanisms. The U-shaped binary complex with CTAB breaks down, and CB[8] moves toward the viologen headgroup of the other surfactant to form a stable ternary complex. In the case of the viologen surfactant, CB[8] moved toward the headgroup leaving the hydrophobic tail free in order to form the ternary complex. The mechanistic detail of this micelle to vesicle transformation is revealed through methodical studies using (1)H and DOSY NMR, ESI-MS, ITC, and other instrumental techniques.
ABSTRACT
A systematic study of the self-assembly process of a viologen-containing surfactant in aqueous medium is reported. Dodecyl-ethyl-viologendibromide (DDEV) is mixed in different proportions with dodecyltrimethylammonium bromide (DTAB), and the physicochemical properties of micellization are evaluated in order to find a suitable combination which does not interfere with the micellar properties of DTAB but introduces the characteristic properties of viologen. In this process, 1% doping of DDEV with DTAB was found to be the most appropriate, as negligible changes were observed in the physicochemical behavior of this system with respect to that of pure DTAB. The 1% DDEV-doped DTAB mixed micellar system showed the characteristic two-step reduction process for the viologen units at the interface as revealed by CV experiments. 1% mixing of DDEV with DTAB also allowed us to prepare stable w/o microemulsions containing viologen units at the interface which is otherwise unattainable with pure viologen surfactants. The charge-transfer capability of the viologen unit to the electron-rich 2,6-dihydroxynaphthalene (DHN) moiety inside the macrocyclic host, cucurbit[8]uril (CB[8]) is also evaluated for this system, and surprisingly even at this very low concentration, the ternary complex of DDEV-DHN@CB[8] transformed the micellar assembly to uniform vesicles. All of these properties have been further extended to other tetraalkylammonium surfactants, and similar effects were observed.
ABSTRACT
A new conductive and transparent organohydrogel is developed with high stretchability, excellent mechanical, self-healing, antifreezing, and adhesive properties. A simple one-pot polymerization method is used to create polyacrylamide cross-linked through N,N'-methylenebis(acrylamide) (MBAA) and divinylbenzene (DVB). The dual chemical cross-linked gel network is complemented by several physical cross-links via hydrogen bonding and π-π interaction. Multiple chemical and physical cross-links are used to construct the gel network that allows toughness (171 kPa), low modulus (≈45 kPa), excellent stretchability (>1100%), and self-healing ability. The use of appropriate proportions of the water/glycerol binary solvent system ensures efficient environment tolerance (-20 to 40 °C). Phytic acid is used as a conductive filler that provides excellent conductivity and contributes to the physical cross-linking. Dopamine is incorporated in the gel matrix, which endows excellent adhesive property of the gel. The organohydrogel-based strain sensors are developed with state-independent properties, highly linear dependence, and excellent antifatigue performance (>100 cycles). Moreover, during the practical wearable sensing tests, human motions can be detected, including speaking, smiling, and joint movement. Additionally, the sensor is biocompatible, indicating the potential applications for the next generation of epidermal sensors.
Subject(s)
Acrylamide , Dopamine , Humans , Electric Conductivity , Epidermis , Excipients , HydrogelsABSTRACT
A lysine based peptide amphiphile (PA) is designed and synthesized for efficient water immobilization. The PA with a minimum gelation concentration (MGC) of 1% w/v in water shows prolonged stability and can also efficiently immobilize aqueous mixtures of some other organic solvents. The presence of a free amine induced pH dependency of the gelation as the PA could form hydrogel at a pH range of 1-8 but failed to do so above that pH. Various spectroscopic and microscopic experiments such as steady state fluorescence, NMR, IR, CD, and FESEM reveal the presence of hydrophobic interaction, hydrogen bond, and π-π stacking interaction in the self-assembly process. The self-aggregation has been correlated with the design of the molecule to show the involvement of supramolecular forces and the hierarchical pathway. While the L analogue formed left-handed helical nanofibers, the other enantiomer showed opposite helicity. Interestingly the equimolar mixture of the isomers failed to form any fibrous aggregate. Although fibers formed at a subgel concentration, no helical nature was observed at this stage. The length and thickness of the fibers increased with increase in the gelator concentration. The nanofibers formed by the gelator are used as a template to prepare mesoporous single wall silica nanotubes (SWSNTs) in situ in plain water without the requirement of any organic solvent as well as any external hydrolyzing agent. The SWSNTs formed are open at both ends, are few micrometers in length, and have an average diameter of ~10 nm. The BET isotherm showed a type IV hysteresis loop suggesting mesoporous nature of the nanotubes.
Subject(s)
Hydrophobic and Hydrophilic Interactions , Nanofibers/chemistry , Nanotubes/chemistry , Peptides/chemistry , Silicon Dioxide/chemistry , Hydrogels/chemistry , Hydrogen Bonding , Hydrogen-Ion Concentration , Lysine/chemistry , Models, Molecular , Protein Structure, SecondaryABSTRACT
Post-translational isoprenylation of proteins is carried out by three related enzymes: farnesyltransferase, geranylgeranyl transferase-I, and Rab geranylgeranyl transferase (RabGGTase). Despite the fact that the last one is responsible for the largest number of individual protein prenylation events in the cell, no structural information is available on its interaction with substrates and products. Here, we present structural and biophysical analyses of RabGGTase in complex with phosphoisoprenoids as well as with the prenylated peptides that mimic the C terminus of Rab7 GTPase. The data demonstrate that, unlike other protein prenyl transferases, both RabGGTase and its substrate RabGTPases completely 'outsource' their specificity for each other to an accessory subunit, the Rab escort protein (REP). REP mediates the placement of the C terminus of RabGTPase into the active site of RabGGTase through a series protein-protein interactions of decreasing strength and selectivity. This arrangement enables RabGGTase to prenylate any cysteine-containing sequence. On the basis of our structural and thermodynamic data, we propose that RabGGTase has evolved from a GGTase-I-like molecule that 'learned' to interact with a recycling factor (GDI) that, in turn, eventually gave rise to REP.
Subject(s)
Alkyl and Aryl Transferases/chemistry , Alkyl and Aryl Transferases/physiology , Alkyl and Aryl Transferases/metabolism , Amino Acid Sequence , Animals , Cysteine/chemistry , Models, Biological , Models, Molecular , Molecular Sequence Data , Prenylation , Protein Binding , Protein Conformation , Protein Interaction Mapping , Protein Processing, Post-Translational , Protein Structure, Tertiary , Rats , ThermodynamicsABSTRACT
Protein modification with isoprenoid lipids affects hundreds of signaling proteins in eukaryotic cells. Modification of isoprenoids with reporter groups is the main approach for the creation of probes for the analysis of protein prenylation in vitro and in vivo. Here, we describe a new strategy for the synthesis of functionalized phosphoisoprenoids that uses an aminederivatized isoprenoid scaffold as a starting point for the synthesis of functionalized phosphoisoprenoid libraries. This overcomes a long-standing problem in the field, where multistep synthesis had to be carried out for each individual isoprenoid analogue. The described approach enabled us to synthesize a range of new compounds, including two novel fluorescent isoprenoids that previously could not be generated by conventional means. The fluorescent probes that were developed using the described approach possess significant spectroscopic advantages to all previously generated fluorescent isoprenoid analogue. Using these analogues for flow cytometry and cell imaging, we analyzed the uptake of isoprenoids by mammalian cells and zebrafish embryos. Furthermore, we demonstrate that derivatization of the scaffold can be coupled in a one-pot reaction to enzymatic incorporation of the resulting isoprenoid group into proteins. This enables rapid evaluation of functional groups for compatibility with individual prenyltransferases and identification of the prenyltransferase specific substrates.
Subject(s)
Dimethylallyltranstransferase/metabolism , Fluorescent Dyes/chemical synthesis , Fluorescent Dyes/metabolism , Polyisoprenyl Phosphates/chemical synthesis , Polyisoprenyl Phosphates/metabolism , Animals , Cell Line , Cricetinae , Flow Cytometry , Fluorescent Dyes/chemistry , Kinetics , Molecular Structure , Polyisoprenyl Phosphates/chemistry , Prenylation , Spodoptera , Stereoisomerism , ZebrafishABSTRACT
Nature has evolved a unique mechanism of self-regulatory feedback loops that help in maintaining an internal cellular environment conducive to growth, healing and metabolism. In biology, enzymes display feedback controlled switchable behaviour to upregulate/downregulate the generation of metabolites as per the need of the cells. To mimic the self-inhibitory nature of certain biological enzymes under laboratory settings, herein, we present a cucurbit[8]uril based pH responsive supramolecular peptide amphiphile (SPA) that assembles into hydrolase mimetic vesicular nanozymes upon addition of alkaline TRIS buffer (activator) but disintegrates gradually owing to the catalytic generation of acidic byproducts (deactivator). The lifetime of these nanozymes could be manipulated in multiple ways, either by varying the amount of catalytic groups on the surface of the vesicles, by changing the acid generating substrate, or by changing the ratio between the activator and the substrate. The self-inhibitory nanozymes displayed highly tunable lifetimes ranging from minutes to hours, controlled and in situ generation of deactivating agents and efficient reproducibility across multiple pH cycles.