Protometabolic Reduction of NAD+ with α-Keto Acids.

Deciphering the origins of the chemistry that supports life has frequently centered on determining prebiotically plausible paths that produce the molecules found in biology. What has been less investigated is how the energy released from the breakdown of foodstuff is coupled to the persistence of the protocell. To gain better insight into how such coupled chemistry could have emerged prebiotically, we probed the reactivity of the ribodinucleotide NAD+ with small organic molecules that were previously identified as potential constituents of protometabolism. We find that NAD+ is readily reduced nonenzymatically by α-keto acids, such as pyruvate and oxaloacetate, during oxidative decarboxylation. In the presence of FAD and a terminal electron acceptor, the consumption of α-keto acids by NAD+ initiates a plausible prebiotic electron transport chain. The observed reactivity suggests that components of the RNA world were capable of initiating the chemistry needed to capture the energy released from catabolism to drive anabolism.

AgI -Induced Switching of DNA Binding Modes via Formation of a Supramolecular Metallacycle.

The histidine derivative L1 of the DNA intercalator naphthalenediimide (NDI) forms a triangular AgI complex (C2). The interactions of L1 and of C2 with DNA were studied by circular dichroism (CD) and UV/Vis spectroscopy and by viscosity studies. Different binding modes were observed for L1 and for C2, as the AgI complex C2 is too large in size to act as an intercalator. If AgI is added to the NDI molecule that is already intercalated into a duplex, higher order complexes are formed within the DNA duplex and cause disruptions in the helical duplex structure, which leads to a significant decrease in the characteristic CD features of B-DNA. Thus, via addition of a metal we show how a classic and well-known organic intercalator unit can be turned into a partial metallo insertor. We also show how electrochemical impedance spectroscopy (EIS) can be used to probe DNA binding modes on DNA films that are immobilized on gold surfaces.

Luminescent Naphthalene Diimide-Based Peptide in Aqueous Medium and in Solid State: Rewritable Fluorescent Color Code.

This study convincingly demonstrates a unique example of the self-assembly of a naphthalene diimide (NDI)-appended peptide into a fluorescent J-aggregate in aqueous media. Moreover, this aggregated species shows a remarkable yellow fluorescence in solid state, an unusual phenomenon for NDI-based compounds. The aggregated species has been characterized using transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy, X-ray diffraction, time-correlated single proton counting (TCSPC), UV-vis, and photoluminescence studies. TEM images reveal cross-linked nanofibrillar morphology of this aggregated species in water (pH 7.4). TCSPC study clearly indicates that the aggregated species in water has a higher average lifetime compared to that of the non-aggregated species. Interestingly, this NDI-based peptide shows H+ ion concentration-dependent change in the emission property in water. The fluorescence output is erased completely in the presence of an alkali, and it reappears in the presence of an acid, indicating its erasing and rewritable property. This indicates its probable use in authentication tools for security purposes as a rewritable fluorescence color code. This NDI-appended peptide-based molecule can be used for encryption of information due to erasing and rewritable property of the molecule in the aggregated state in aqueous medium.

On the Role of Chirality in Guiding the Self-Assembly of Peptides.

Homochirality in peptides is crucial in sustaining "like-like" intermolecular interactions that allow the formation of assemblies and aggregates and is ultimately responsible for the resulting material properties. With the help of a series of stereoisomers of the tripeptide F-F-L, we demonstrate the critical role that peptide stereochemistry plays in the self-assembly of peptides, guided by molecular recognition, and for self-sorting. Homochiral self-assemblies are thermally and mechanically more robust compared to heterochiral self-assemblies. Morphological studies of the multicomponent peptide systems showed that aggregates formed from homochiral peptides possessed a uniform nano-fibrous structure, whereas heterochiral systems resulted in self-sorted systems with a heterogeneous morphology. In essence, homochiral peptides form the stronger aggregates, which may be one of reasons why homochirality is preferred in living systems.

A tripeptide-based self-shrinking hydrogel for waste-water treatment: removal of toxic organic dyes and lead (Pb2+) ions.

A triphenylalanine-based superhydrogel shows automatic syneresis (self-compressing properties) with time and this self-shrinking behavior has been successfully utilized to remove toxic lead ions and organic dyes from waste-water efficiently with the ability to re-use for a few times.

Metal coordination of ferrocene-histidine conjugates.

This study presents a few bis(histidine) ligands working to build a small peptidic model system of zinc structural sites. Ferrocene-peptide conjugates Fc[CO-His(Trt)-His(Trt)-OMe]2 (3), Fc[CO-His(Trt)-Asp(OMe)-OMe]2 (4), and Fc[CO-His(Trt)-Glu(OMe)-OMe]2 (5) were synthesized and characterized spectroscopically. 1H-NMR and IR spectroscopic studies reveal hydrogen bonding interactions and while more detailed circular dichroism studies show a 1,2'-P helical "Herrick conformation" for Fc-conjugates 4 and 5, we discovered M-helical chirality in Fc-peptide 3. The half-wave potentials (E1/2) of ferrocene-peptides follow the sequence 3 < 5 < 4 which is rationalized by the capability of the peptide side chains to stabilize the oxidized ferrocene-peptide form. The diffusion coefficient (D) and electron transfer rate constant (ksh) values for all Fc-conjugates were determined by their resultant cyclic voltammetry data. The interactions for all Fc-conjugates were probed with metal ions Zn2+, Cd2+, Ni2+, Cu2+, Mn2+, and Mg2+ which were detected to interact at 1 : 1 ratio between the ligand and metal ion verified by 1H-NMR and UV titration studies, electrochemical investigations, and ESI-MS experiments. Electrochemical studies for all Fc-conjugates exhibit anodic potential shifts upon the addition of metal ions, which follow the order Cu2+ > Zn2+ > Ni2+ > Cd2+ > Mn2+ > Mg2+. NMR spectroscopic experiments show that the two nitrogen atoms present on each imidazole ring of His residues are the site of metal coordination. There is a strong indication that peptide conjugates 4 and 5 in the presence of Zn2+ enforce a coordination number of four as the CD spectra of Fc-conjugates 4 and 5 exhibited a red shift which corresponds to the third and fourth coordination sites occupied by neutral carbonyl oxygen donor atoms, in addition, carbonyl amide appears downward shifted in wavenumber upon metal addition.

A Ferrocene-Tryptophan Conjugate: The Role of the Indolic Nitrogen in Supramolecular Assembly.

Bio-organometallic ferrocene-containing amino acids and peptides have been reported to form gels and are interesting to study due to their structural properties and applications for biological purposes. In this study, a ferrocene-dicarboxylic acid derivative of the dipeptide tryptophan-tryptophan was investigated. The indolic nitrogen in the amino acid tryptophan is important for biological functions due to its role in hydrogen bonding. Here, intermolecular interactions with the indolic nitrogen allow this conjugate to self-assemble into a fibrous supramolecular structure that forms a stable gel. Rheological analysis demonstrates the self-healing nature of this gel. Interestingly, X-ray analysis of this ferrocene-peptide conjugate reveals close contacts involving tryptophan, in particular the indole NH group in interactions with an adjacent neighboring molecule.

Two-Component Fluorescent-Semiconducting Hydrogel from Naphthalene Diimide-Appended Peptide with Long-Chain Amines: Variation in Thermal and Mechanical Strengths of Gels.

Two-component fluorescent hydrogels have been discovered, containing the mixtures of naphthalene diimide (NDI)-conjugated peptide-functionalized bola-amphiphile and primary amines with long alkyl chains at physiological pH 7.46. The aggregation-induced enhanced emission associated with an NDI-appended peptide in aqueous medium is rare, as water is known to be a good quencher of fluorescence. In this study, an NDI-containing gelator peptide forms a highly fluorescent aggregate in aqueous medium. Absorption and emission spectroscopic techniques reveal the formation of J-aggregates among the chromophoric moieties in their aggregated state in aqueous medium. However, this NDI-containing peptide does not form any gel in aqueous medium. In the presence of the primary amines with long alkyl chains in the buffer solution, it forms two-component fluorescent hydrogels exhibiting bright yellow fluorescence under a UV lamp (365 nm). Probably, the acid-amine interaction between the amines and the bola-amphiphile triggers the gel formation, as evident from Fourier transform infrared data, indicating the presence of a carboxylate group (-COO-) and an ammonium species (NH3+) in the coassembled two-component gel system. Low- and wide-angle powder X-ray diffraction and small-angle X-ray scattering further support the fact that the coassembled state in the gel form is produced by the supramolecular interaction between the NDI-based bola-amphiphile and the long-chain amines. Field-emission scanning electron microscopy and high-resolution transmission electron microscopy images reveal that the π-conjugated coassembled hydrogels exhibit nanofibrillar network morphologies. Interestingly, the coassembled hydrogels exhibit an enhanced fluorescence emission, excited-state lifetime, and quantum yield when compared with those of the NDI-containing amphiphile alone in its self-assembled state in aqueous medium. Moreover, the thermal stability and mechanical strength of these gels have been successfully tuned by varying the alkyl chain length of the corresponding amine. Moreover, these NDI-peptide-conjugated soft materials exhibit semiconducting behavior in their respective coassembled states. This holds future promise to use these peptide-appended NDI-based coassembled soft materials for applications in optoelectronic and other devices.

Peptide based hydrogels for cancer drug release: modulation of stiffness, drug release and proteolytic stability of hydrogels by incorporating d-amino acid residue(s).

Synthetic tripeptide based noncytotoxic hydrogelators have been discovered for releasing an anticancer drug at physiological pH and temparature. Interestingly, gel stiffness, drug release capacity and proteolytic stability of these hydrogels have been successfully modulated by incorporating d-amino acid residues, indicating their potential use for drug delivery in the future.

Fluorescence from an H-aggregated naphthalenediimide based peptide: photophysical and computational investigation of this rare phenomenon.

Fluorescence associated with J-aggregated naphthalenediimides (NDIs) is common. However, in this study an NDI based synthetic peptide molecule is found to form a fluorescent H-aggregate in a chloroform (CHCl3)-methylcyclohexane (MCH) mixture. An attempt has been made to explain the unusual fluorescence property of this H-aggregated NDI derivative. Time correlated single photon counting (TCSPC) shows that the average lifetime of the NDI based molecule is on the order of a few nanoseconds. It is revealed from the computational study that the transition from the second exited state (S2) to the ground energy state (S0) is responsible for the fluorescence as S1 is a dark state. Such rare violation of Kasha's rule accounts for the unusual fluorescence properties of this type of NDI molecule in the H-aggregated state.

Time-dependent gel to gel transformation of a peptide based supramolecular gelator.

A dipeptide with a long fatty acid chain at its N-terminus gives hydrogels in phosphate buffer in the pH range 7.0-8.5. The hydrogel with a gelator concentration of 0.45% (w/v) at pH 7.46 (physiological pH) provides a very good platform to study dynamic changes within a supramolecular framework as it exhibits remarkable change in its appearance with time. Interestingly, the first formed transparent hydrogel gradually transforms into a turbid gel within 2 days. These two forms of the hydrogel have been thoroughly investigated by using small angle X-ray scattering (SAXS), powder X-ray diffraction (PXRD), field emission scanning electron microscopic (FE-SEM) and high-resolution transmission electron microscopic (HR-TEM) imaging, FT-IR and rheometric analyses. The SAXS and low angle PXRD studies substantiate different packing arrangements for the gelator molecules for these two different gel states (the freshly prepared and the aged hydrogel). Moreover, rheological studies of these two gels reveal that the aged gel is stiffer than the freshly prepared gel.

Tailor-made design of J- or H-aggregated naphthalenediimide-based gels and remarkable fluorescence turn on/off behaviour depending on solvents.

A naphthalenediimide (NDI)-based new gelator molecule has been discovered, the molecule forms interesting J/H-aggregated species depending on solvents (aliphatic/aromatic) and remarkably, the fluorescence of the gel phase materials is nicely tuned according to the electron donating capacity of the aromatic solvent.

Selective binding of hydrogen chloride and its trapping through supramolecular gelation.

A pyridine containing amino acid based gelator forms gel in aqueous media in the presence of hydrochloric acid and the chloride ion is found to be very selective for gelation. The gelator is successfully applied for the detection and trapping of hydrogen chloride gas and this indicates its probable application for removing hazardous HCl gas from the environment.

Charge-transfer complex formation in gelation: the role of solvent molecules with different electron-donating capacities.

A naphthalenediimide (NDI)-based synthetic peptide molecule forms gels in a particular solvent mixture (chloroform/aromatic hydrocarbon, 4:1) through charge-transfer (CT) complex formation; this is evident from the corresponding absorbance and fluorescence spectra at room temperature. Various aromatic hydrocarbon based solvents, including benzene, toluene, xylene (ortho, meta and para) and mesitylene, have been used for the formation of the CT complex. The role of different solvent molecules with varying electron-donation capacities in the formation of CT complexes has been established through spectroscopic and computational studies.

Multi-stimuli responsive self-healing metallo-hydrogels: tuning of the gel recovery property.

A series of amphiphilic tyrosine based self-healable, multi-stimuli responsive metallo-hydrogels have been discovered. Formation of these hydrogels is highly selective to Ni(2+) ions. The self-healing property and the stiffness of these metallo-hydrogels can be tuned by varying the chain length of the corresponding gelator amphiphile.

Assembly of naphthalenediimide conjugated peptides: aggregation induced changes in fluorescence.

Naphthalenediimide appended peptide based self-assembly was studied. Interestingly, an aggregation induced drastic change in the fluorescence property and gel formation were observed depending on the solvent composition (chloroform : methylcyclohexane) at a fixed concentration of 1.6 mM at room temperature.

Formation of hybrid hydrogels consisting of tripeptide and different silver nanoparticle-capped ligands: modulation of the mechanical strength of gel phase materials.

An N-terminally Boc (tert-butyloxycarbonyl) group-protected synthetic tripeptide (Boc-Phe-Phe-Ala-OH) has been found to form a translucent hydrogel in basic aqueous medium. This hydrogel material has been characterized using field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), Fourier transformed infrared spectroscopy, differential scanning calorimetric, X-ray diffraction (XRD), and rheological studies. FE-SEM and TEM studies have revealed the formation of a nanofibrillar network structure upon gelation. Thiol (-SH) containing ligands (amino acid/peptide) have been used to stabilize small silver nanoparticles (AgNPs), and these thiol-capped silver nanoparticles have been incorporated into this hydrogel to prepare hybrid hydrogels. Morphological study of silver nanoparticles containing a hybrid hydrogel (using TEM experiments) has indicated the nice fabrication of AgNPs along the gel nanofibers. Fabrication of nanoparticles upon the gel nanofibers is due to noncovalent interactions between the capping ligands of the nanoparticles and the peptide-based hydrogel nanofibers. Rheological investigations of these hybrid hydrogels have shown the weakening of the mechanical strength of the hydrogel after incorporation of AgNPs within the native hydrogel system. Our studies have vividly shown the dependence of the elastic modulus (G') and yield stress (σ(y)) on three factors: (a) the nature of the stabilizing ligands used for AgNPs, (b) the size of the AgNPs, and (c) the amount of AgNPs used for the preparation of hybrid hydrogel systems. Modulation of the mechanical strength of the hybrid hydrogel can be successfully achieved by varying these above-mentioned factors. This modulation of the mechanical properties keeps a future promise to make tunable soft materials with interesting properties.