Underwater Adhesives from Redox-Responsive Polyplexes of Thiolated Polyamide Polyelectrolytes.

We report the fabrication of optically clear underwater adhesives using polyplexes of oppositely charged partially-thiolated polyamide polyelectrolytes (TPEs). The thiol content of the constituent PEs was varied to assess its influence on the adhesive properties of the resulting glues. These catechol-free, redox-responsive TPE-adhesives were formulated in aquo and exhibited high optical transparency and strong adhesion even on submerged or moist surfaces of diverse polar substrates such as glass, aluminium, wood, and bone pieces. The adhesives could be cured under water through oxidative disulphide crosslinking of the constituent TPEs. The polyamide backbone provided multi-site H-bonding interactions with the substrates while the disulphide crosslinking provided the cohesive strength to the glue. Strong adhesion of mammalian bones (load bearing capacity upto 7 kg/cm2 ) was achieved using the adhesive containing 30 mol % thiol residues. Higher pH and use of oxidants such as povidone-iodine solution enhanced the curing rate of the adhesives, and so did the use of Tris buffer instead of Phosphate buffer. The porous architecture of the adhesive and its progressive degradation in aqueous medium over the course of three weeks bode well for diverse biomedical applications where temporary adhesion of tissues is required.

Modulating Helix-preference of an Axially-twisted Molecular Scaffold Through Diastereomeric Salt Formation with Tartaric Acid Stereoisomers.

Herein, we designed a chiral, axially-twisted molecular scaffold (ATMS) using pyridine-2,6-dicarboxamide (PDC) unit as pivot, chiral trans-cyclohexanediamine (CHDA) residues as linkers, and pyrene residues as fluorescent reporters. R,R-ATMS exclusively adopted M-helicity and produced differential response in UV-vis, fluorescence, and NMR upon addition of tartaric acid (TA) stereoisomers allowing naked-eye detection and enantiomeric excess determination. Circular dichroism (CD) profile of R,R-ATMS underwent unique changes during titration with TA stereoisomers - while loss of CD signal at 345 nm was observed with equimolar D-TA and meso-TA, inversion was seen with equimolar L-TA. Temperature increase weakened these interactions to partially recover the original CD signature of R,R-ATMS. 2D NMR studies also indicated the significant structural changes in R,R-ATMS in the solution state upon addition of L-TA. Single crystal X-ray diffraction (SCXRD) studies on the crystals of the R,R-ATMS⊃D-TA salt revealed the interacting partners stacked in arrays and ATMS molecules stabilized by π-π stacking between its PDC and pyrene residues. Contrastingly, tightly-packed supramolecular cages comprised of four molecules each of R,R-ATMS and L-TA were seen in R,R-ATMS⊃L-TA salt, and the ATMS molecules contorted to achieve CH-π interactions between its pyrene residues. These results may have implications in modulating the helicity of topologically-similar larger biomolecules.

Divergent self-assembly propensity of enantiomeric phenylalanine amphiphiles that undergo pH-induced nanofiber-to-nanoglobule conversion.

This study presents the pathway diversity in the self-assembly of enantiomeric single phenylalanine derived amphiphiles (single F-PDAs), viz.L-NapF-EDA and D-NapF-EDA, that form supramolecular hydrogels at varied concentrations (≥1 mg mL-1 and ≥3 mg mL-1, respectively). By fitting the variable temperature circular dichroism (VT-CD) data to the isodesmic model, various thermodynamic parameters associated with their self-assembly, such as association constant (K), changes in enthalpy (ΔH), entropy (ΔS), and Gibbs free energy (ΔG), were extracted. The self-assembly of these single F-PDAs was found to be enthalpy-driven but entropically-disfavored. Although self-assembly of the D-isomer was slow, it also exhibited greater free energy of association than the L-isomer. Consequently, thermally and mechanically more robust self-assemblies were formed by the D-isomer than the L-isomer. We term these results as the "butterfly effect in self-assembly" wherein the difference in the stereochemical orientation of the residues at a single chiral center present in these molecules resulted in strong differences in the self-assembly propensity as well as in their thermal and mechanical stability. These single F-PDAs form helical nanofibers of opposite chirality upon self-assembly at basic pH (≥8) that produce intense CD signals. However, upon decreasing the pH, a gradual nanofiber-to-nanoglobular transformation was noticed due to protonation-induced structural changes in the PDAs.

Enzymatic Dimerization-Induced Self-Assembly of Alanine-Tyramine Conjugates into Versatile, Uniform, Enzyme-Loaded Organic Nanoparticles.

Herein, we report a novel enzymatic dimerization-induced self-assembly (e-DISA) procedure that converts alanine-tyramine conjugates into highly uniform enzyme-loaded nanoparticles (NPs) or nanocontainers by the action of horseradish peroxidase (HRP) in an aqueous medium under ambient conditions. The NP formation was possible with both enantiomers of alanine, and the average diameter could be varied from 150 nm to 250 nm (with a 5-12 % standard deviation of as-prepared samples) depending on the precursor concentration. About 60 % of the added HRP enzyme was entrapped within the NPs and was subsequently utilized for post-synthetic modification of the NPs with phenolic compounds such as tyramine or tannic acid. One-pot multi-enzyme entrapment of glucose oxidase (GOx) and peroxidase (HRP) within the NPs was also achieved. These GOx-HRP loaded NPs allowed multimodal detection of glucose, including that present in human saliva, with a limit of detection (LoD) of 740 nM through fluorimetry. The NPs exhibited good cytocompatibility and were stable to changes in pH (acidic to basic), temperature, ultrasonication, and even the presence of organic solvent (EtOH) to a certain extent, since they are stabilized by intermolecular hydrogen bonding, π-π, and CH-π interactions. The proposed e-DISA procedure can be widely expanded through the design of diverse enzyme-responsive precursors.

Design of Cationic Lipids with Acetal Linkers: Conformational Preferences, Hydrolytic Stability, and High Drug-Loading Abilities.

Lipids are key constituents of numerous biomedical drug delivery technologies. Here, we present the design, synthesis and biophysical characterizations of a library of cationic lipids containing an acetal residue in their linker region. These cationic acetal lipids (CALs) were conveniently prepared through a trans-acetalization protocol from commercially available precursors. NMR studies highlighted the conformational rigidity at the acetal residue and the high hydrolytic stability of these CALs. Fluorescence anisotropy studies revealed that the CAL with a pyridinium headgroup (CAL1) formed highly cohesive vesicular aggregates in water. These structural and self-assembly features of the CAL1 allowed up to 196 % w/w loading of curcumin (Cur) as a representative hydrophobic drug. A reconstitutable formulation of Cur was obtained as a result, which could deliver the drug inside mammalian cells with very high efficiency. The hemocompatibility and cytocompatibility of CAL1 was significantly enhanced by creating a coating of polydopamine (PDA) onto its vesicular assemblies to produce hybrid lipid-polymer nanocapsules. This work demonstrates rapid access to the useful synthetic lipid formulations with high potential in drug and gene delivery applications.

Bioinspired Design of an Uncharged Ambipolar Helical Scaffold To Achieve Efficient Solid-State Proton Conduction.

This work demonstrates highly efficient solid-state proton conduction in helical organic scaffolds inspired by the biomolecule gramicidin A. The scaffold, 1, derived from a pyridine-2,6-dicarboxamide (PDC) residue adopts a helical conformation that is stabilized by a network of strong bifurcated intramolecular H-bonds between the polar residues that align the inner (concave) face of the molecule, while the aromatic units in 1 are oriented outwards. As a result, the helix attains an ambipolar nature just like gramicidin A. Two different solid forms of 1 could be isolated: a yellow solid from high-polarity solvents and an orange solid from low-polarity solvents. Single-crystal X-ray diffraction (SCXRD) studies showed that in the former, molecules of 1 are stacked in a homochiral fashion, while in the latter heterochiral stacks of 1 were present. The yellow form exhibited an almost ∼300-fold higher conductivity (of up to 0.12 mS cm-1 at 95 °C and 95 % relative humidity) than the orange form as a result of closer intermolecular proximity and lower activation energy of 0.098 eV, thus indicating a Grotthus mechanism of proton transport. This study establishes the key role of bioinspired design and controlled stereo-organization of such discrete uncharged organic molecules in achieving efficient solid-state proton conduction.

Molecular clips with spatially proximal urea residues for efficient transmembrane co-transport of H+/Cl- ions.

We report the design of bis(urea) functionalized amphiphilic molecular clips viz. 1a-1e to achieve efficient transmembrane co-transport of H+/Cl- ions. The most promising molecule 1a demonstrated a low nanomolar EC50 value (6.96 nM) to co-transport H+/Cl- ions via a carrier-mediated pathway and showed selective toxicity against cancerous HeLa cells as a result.

Of Twists and Curves: Electronics, Photophysics, and Upcoming Applications of Non-Planar Conjugated Organic Molecules.

Non-planar conjugated organic molecules (NPCOMs) contain π-conjugation across their length and also exhibit asymmetry in their conformation. In other words, certain molecular fragments in NPCOMs are either twisted or curved out of planarity. This conformational asymmetry in NPCOMs leads to non-uniform charge-distribution across the molecule, with important photophysical and electronic consequences such as altered thermodynamic stability, chemical reactivity, as well as materials properties. Majorly, NPCOMs can be classified as having either Fused or Rotatable architectures. NPCOMs have been the focus of significant scientific attention in the recent past due to their exciting photophysical behavior that includes intramolecular charge-transfer (ICT), thermally activated delayed fluorescence (TADF) and long-lived charge-separated states. In addition, they also have many useful materials characteristics such as biradical character, semi-conductivity, dynamic conformations, and mechanochromism. As a result, rational design of NPCOMs and mapping their structure-property correlations has become imperative. Researchers have executed conformational changes in NPCOMs through a variety of external stimuli such as pH, temperature, anions-cations, solvent, electric potential, and mechanical force in order to tailor their photophysical, optoelectronic and magnetic properties. Converging to these points, this review highlights the lucrative electronic features, photophysical traits and upcoming applications of NPCOMs by a selective survey of the recent scientific literature.

Cholic Acid-Peptide Conjugates as Potent Antimicrobials against Interkingdom Polymicrobial Biofilms.

Interkingdom polymicrobial biofilms formed by Gram-positive Staphylococcus aureus and Candida albicans pose serious threats of chronic systemic infections due to the absence of any common therapeutic target for their elimination. Herein, we present the structure-activity relationship (SAR) of membrane-targeting cholic acid-peptide conjugates (CAPs) against Gram-positive bacterial and fungal strains. Structure-activity investigations validated by mechanistic studies revealed that valine-glycine dipeptide-derived CAP 3 was the most effective broad-spectrum antimicrobial against S. aureus and C. albicans CAP 3 was able to degrade the preformed single-species and polymicrobial biofilms formed by S. aureus and C. albicans, and CAP 3-coated materials prevented the formation of biofilms. Murine wound and catheter infection models further confirmed the equally potent bactericidal and fungicidal effect of CAP 3 against bacterial, fungal, and polymicrobial infections. Taken together, these results demonstrate that CAPs, as potential broad-spectrum antimicrobials, can effectively clear the frequently encountered polymicrobial infections and can be fine-tuned further for future applications.

An Electron-Rich Helical Host for the Exclusive Removal of a Planar Electron-Deficient Organic Compound.

In this study, a series of electron-rich helical hosts, viz. Pyr-HAC, Anth-HAC and Ben-HAC, containing pyrene, anthracene and benzene residues, respectively, at their periphery, were screened for their interaction with different planar electron-deficient organic guests (PEDOGs). A strong and highly selective charge-transfer interactions (CTI) was observed between the host Pyr-HAC and the guest 1,2,4,5-tetracyano-benzene (TCNB), leading to a yellow-to-bright-red color change in both the solubilized and the solid state. The interaction between Pyr-HAC and TCNB also induced profound structural and morphological changes. Pyr-HAC self-assembled into belt-like morphology created by homochiral stacking of the host molecules, but in the Pyr-HAC⊃TCNB complex, square bipyramids containing intertwined heterochiral C2 -double helices of Pyr-HAC were observed. Other PEDOGs did not induce any of the above changes in Pyr-HAC. Detailed UV/Vis absorption and fluorescence spectroscopy, NMR, and X-ray diffraction studies confirmed this selectivity, which arises due to CTI assisted by complementary, directional intermolecular hydrogen bonding (DIHB) between Pyr-HAC and TCNB. This allowed for the exclusive extraction of TCNB from a solution enriched in other PEDOGs. Thus, this study provides a ground work for designing responsive helical hosts towards CTI-driven selective "catch-and-release" of guests.

Chirally Twisted Ultrathin Polydopamine Nanoribbons: Synthesis and Spontaneous Assembly of Silver Nanoparticles on Them.

Polydopamine (PDA) is a synthetic polymeric material with immense potential in biomedical and surface functionalization applications. Herein, we have screened self-assemblies formed by Phenylalanine-based amphiphiles (Phe-AMPs) as soft templates for preparing chiral PDA nanostructures. Our study revealed that the amphiphile 2 endowed with a primary amine residue afforded chirally-twisted ultrathin nanoribbons of PDA under optimized conditions. The chirality at the Phe residue of 2 modulated the twist-chirality of the PDA nanoribbons; the l-2 resulted in nanoribbons with right-handed twist, whereas the d-2 induced a left-handed twist to the ribbons. The racemic mixture of these two amphiphiles produced flat, achiral tapes. The PDA ribbon thickness was ≈5.86±0.40 nm, whereas its width and length were ≈133.5±3.2 nm and >5000 nm, respectively. Upon dialysis, hollow PDA nanotubes were obtained due to curling of the PDA nanoribbons. These PDA-nanoarchitectures were employed to spontaneously form and assemble Ag-nanoparticles along the edges of the PDA nanoribbons. In this work we are reporting chirality controlled synthesis of PDA nanostructures for the first time.

Dietary-phytochemical mediated reversion of cancer-specific splicing inhibits Warburg effect in head and neck cancer.

BACKGROUND: The deregulated alternative splicing of key glycolytic enzyme, Pyruvate Kinase muscle isoenzyme (PKM) is implicated in metabolic adaptation of cancer cells. The splicing switch from normal PKM1 to cancer-specific PKM2 isoform allows the cancer cells to meet their energy and biosynthetic demands, thereby facilitating the cancer cells growth. We have investigated the largely unexplored epigenetic mechanism of PKM splicing switch in head and neck cancer (HNC) cells. Considering the reversible nature of epigenetic marks, we have also examined the utility of dietary-phytochemical in reverting the splicing switch from PKM2 to PKM1 isoform and thereby inhibition of HNC tumorigenesis. METHODS: We present HNC-patients samples, showing the splicing-switch from PKM1-isoform to PKM2-isoform analyzed via immunoblotting and qRT-PCR. We performed methylated-DNA-immunoprecipitation to examine the DNA methylation level and chromatin-immunoprecipitation to assess the BORIS (Brother of Regulator of Imprinted Sites) recruitment and polII enrichment. The effect of dietary-phytochemical on the activity of denovo-DNA-methyltransferase-3b (DNMT3B) was detected by DNA-methyltransferase-activity assay. We also analyzed the Warburg effect and growth inhibition using lactate, glucose uptake assay, invasion assay, cell proliferation, and apoptosis assay. The global change in transcriptome upon dietary-phytochemical treatment was assayed using Human Transcriptome Array 2.0 (HTA2.0). RESULTS: Here, we report the role of DNA-methylation mediated recruitment of the BORIS at exon-10 of PKM-gene regulating the alternative-splicing to generate the PKM2-splice-isoform in HNC. Notably, the reversal of Warburg effect was achieved by employing a dietary-phytochemical, which inhibits the DNMT3B, resulting in the reduced DNA-methylation at exon-10 and hence, PKM-splicing switch from cancer-specific PKM2 to normal PKM1. Global-transcriptome-analysis of dietary-phytochemical-treated cells revealed its effect on alternative splicing of various genes involved in HNC. CONCLUSION: This study identifies the epigenetic mechanism of PKM-splicing switch in HNC and reports the role of dietary-phytochemical in reverting the splicing switch from cancer-specific PKM2 to normal PKM1-isoform and hence the reduced Warburg effect and growth inhibition of HNC. We envisage that this approach can provide an effective way to modulate cancer-specific-splicing and thereby aid in the treatment of HNC.

Benign Synthesis of Black Microspheres of Anatase TiO2 with Paramagnetic Oxygen Vacancies through NH3 Treatment.

Coloured TiO2 is coveted for its ability to extract energy from the visible region of electromagnetic spectrum. Here a facile synthesis of black anatase titania microspheres (B-TiO2 ) through a two-step process is reported. In the first step, amorphous white TiO2 microspheres (W-TiO2 ) are obtained by hydrolysing titanium tetraisopropoxide by ammonia vapours in ethanol. In the second step, the W-TiO2 is thermally annealed at 500 °C to obtain B-TiO2 . The diffuse reflectance analysis showed that B-TiO2 absorbs across visible spectrum with absorption extending well into NIR region. Raman scattering together with EPR analysis showed compelling evidence of the existence of oxygen deficiency within the crystal in B-TiO2 that induces black colouration in the sample. The defects present in the black anatase sample were confirmed to be single-electron-trapped (or paramagnetic) oxygen vacancies (Vo ⋅) by XPS and EPR studies. The magnetic susceptibility studies showed existence of antiferromagnetic interactions between these unpaired electron spins.

Heli(aza)cene: A Helical Molecular Tweezer with Tunable Intra- and Intermolecular Charge Transfer.

Non-planar fluorophores offer unique avenues of intra- and intermolecular energy transfer not available in their planar counterparts. We have rationally designed a molecular tweezer based on the pyridine-2,6-dicarboxamide framework having two structurally similar arms with extended π-surface. We termed this molecular tweezer as Heli(aza)cene (HAC) due to its spontaneous adoption of helical conformation stabilized by the amide and imine moieties present in it. In the helical conformation, the two arms of HAC are twisted unequally. This asymmetry confers dissimilar electronic character to the two arms and results in intramolecular charge transfer interactions in HAC. Homochiral stacking of the P- and the M- helices in crystal, and profound redshifting of the emission at higher concentrations of HAC was attributed to intermolecular charge-transfer interactions in aggregated/crystal state. Exposure of HAC, in solution as well as in the solid state, to Lewis/Brønsted acids results in rapid and vibrant color changes. This is the first example of a π-layered helical molecule exhibiting tunable intra-/intermolecular charge-transfer characteristics.

Nano "Koosh Balls" of Mesoporous MnO2 : Improved Supercapacitor Performance through Superior Ion Transport.

Manganese dioxide nanomaterials with "Koosh-ball"-like morphology (MnO2 -KBs) as well as worm-like nanotubes (MnO2 -NWs) are obtained by employing Tween 20 as the reducing and structure-directing agent, and KMnO4 as a MnO2 precursor. Whereas the MnO2 -KBs are interconnected through tubular extensions, the MnO2 -NWs are largely disconnected. Both MnO2 -KBs and MnO2 -NWs have large BET surface areas (>200 m2 g-1 ), and are thermally robust up to 300 °C. Electrochemical studies reveal that the highest specific capacitance (Csp ) obtained for MnO2 -KBs (272 F g-1 ) is significantly higher than that of MnO2 -NWs (129 F g-1 ). The Csp values correlate well with the electroactive surface areas of the materials: MnO2 -KBs have a significantly higher electrolyte-accessible surface area. Electrochemical impedance spectroscopy (EIS) reveals a higher electron-transfer rate at the electrode/electrolyte interface for MnO2 -KBs than for MnO2 -NWs. The multiple tubular interconnections between individual MnO2 -KBs allow improved ion penetration and act as conduits for their propagation, shortening the diffusion distances of the ions from external electrolytes to the interior of the MnO2 framework. Thus, this work exemplifies the importance of interconnections for enhancing the electrochemical performance of nanomaterials employed for energy storage.

Clathrin-Independent Killing of Intracellular Mycobacteria and Biofilm Disruptions Using Synthetic Antimicrobial Polymers.

Current membrane targeting antimicrobials fail to target mycobacteria due to their hydrophobic membrane structure, ability to form drug-resistant biofilms, and their natural intracellular habitat within the confines of macrophages. In this work, we describe engineering of synthetic antimicrobial polymers (SAMPs) derived from biocompatible polyamides that can target drug-sensitive and drug-resistant mycobacteria with high selectivity. Structure-activity relationship studies revealed that reduced hydrophobicity of cationic pendants induces enhanced and selective permeabilization of mycobacterial membranes. The least hydrophobic SAMP (TAC1) was found to be the most active with maximum specificity toward mycobacteria over E. coli, S. aureus, and mammalian cells. Membrane perturbation studies, scanning electron microscopy, and colony PCR confirmed the ability of TAC1 to induce membrane lysis and to bind to the genomic material of mycobacteria, thereby inducing mycobacterial cell death. TAC1 was most effective in perfusing and disrupting the mycobacterial biofilms and was also able to kill the intracellular mycobacteria effectively without inducing any toxicity to mammalian cells. Cellular uptake studies revealed clathrin independent uptake of TAC1, thereby allowing it to escape hydrolytic lysosomal degradation and effectively kill the intracellular bacteria. Therefore, this manuscript presents the design and selective antimycobacterial nature of polyamide polymers with charged hydrophobic pendants that have ability to disrupt the biofilms and kill intracellular mycobacteria.

Anion Binding-Induced White Light Emission using a Water-Tolerant Fluorescent Molecular Tweezer.

A novel fluorescent molecular tweezer (FMT), built on the pyridine-2,6-bis-carboxamide framework, has been developed that, in presence of a red emitter, gives rise to white light emission in response to the addition of H2 PO4- anions. The FMT incorporates two pyrene moieties as fluorescent reporter units and a strategically placed amine residue that imparts pH sensitivity to the fluorescence and offers additional electrostatic/hydrogen-bonding interactions to the anions. As a result, this FMT selectively binds monoanionic tetrahedral oxyanions such as H2 PO4- and HSO4- that contain hydrogen bond donors and acceptors, and can sense their presence in aqueous acetonitrile through changes in fluorescence. Anion binding results in excimer formation by the pyrenes and a bluish-green emission from the FMT. Both amide and amine residues of the FMT interact with these anions. The binding stoichiometry with H2 PO4- and HSO4- was found to be 1:1 and affinity of the FMT for these anions is of the order of 104 m-1 . The limit of detection for H2 PO4- was found to be 13 nm. Addition of a perylene monoimide-based red emitter gives rise to panchromatic emission perceived as white light.

Cell Permeating Nano-Complexes of Amphiphilic Polyelectrolytes Enhance Solubility, Stability, and Anti-Cancer Efficacy of Curcumin.

Many hydrophobic drugs encounter severe bioavailability issues owing to their low aqueous solubility and limited cellular uptake. We have designed a series of amphiphilic polyaspartamide polyelectrolytes (PEs) that solubilize such hydrophobic drugs in aqueous medium and enhance their cellular uptake. These PEs were synthesized through controlled (∼20 mol %) derivatization of polysuccinimide (PSI) precursor polymer with hydrophobic amines (of varying alkyl chain lengths, viz. hexyl, octyl, dodecyl, and oleyl), while the remaining succinimide residues of PSI were opened using a protonable and hydrophilic amine, 2-(2-amino-ethyl amino) ethanol (AE). Curcumin (Cur) was employed as a representative hydrophobic drug to explore the drug-delivery potential of the resulting PEs. Unprecedented enhancement in the aqueous solubility of Cur was achieved by employing these PEs through a rather simple protocol. In the case of PEs containing oleyl/dodecyl residues, up to >65000× increment in the solubility of Cur in aqueous medium could be achieved without requiring any organic solvent at all. The resulting suspensions were physically and chemically stable for at least 2 weeks. Stable nanosized polyelectrolyte complexes (PECs) with average hydrodynamic diameters (DH) of 150-170 nm (without Cur) and 220-270 nm (after Cur loading) were obtained by using submolar sodium polyaspartate (SPA) counter polyelectrolyte. The zeta potential of these PECs ranged from +36 to +43 mV. The PEC-formation significantly improved the cytocompatibility of the PEs while affording reconstitutable nanoformulations having up to 40 wt % drug-loading. The Cur-loaded PECs were readily internalized by mammalian cells (HEK-293T, MDA-MB-231, and U2OS), majorly through clathrin-mediated endocytosis (CME). Cellular uptake of Cur was directly correlated with the length of the alkyl chain present in the PECs. Further, the PECs significantly improved nuclear transport of Cur in cancer cells, resulting in their death by apoptosis. Noncancerous cells were completely unaffected under this treatment.

Cell penetrating synthetic antimicrobial peptides (SAMPs) exhibiting potent and selective killing of mycobacterium by targeting its DNA.

Naturally occurring antimicrobial peptides (AMPs) are powerful defence tools to tackle pathogenic microbes. However, limited natural production and high synthetic costs in addition to poor selectivity limit large-scale use of AMPs in clinical settings. Here, we present a series of synthetic AMPs (SAMPs) that exhibit highly selective and potent killing of Mycobacterium (minimum inhibitory concentration <20 µg mL(-1)) over E. coli or mammalian cells. These SAMPs are active against rapidly multiplying as well as growth saturated Mycobacterium cultures. These SAMPs are not membrane-lytic in nature, and are readily internalized by Mycobacterium and mammalian cells; whereas in E. coli, the lipopolysaccharide layer inhibits their cellular uptake, and hence, their antibacterial action. Upon internalization, these SAMPs interact with the unprotected genomic DNA of mycobacteria, and impede DNA-dependent processes, leading to bacterial cell death.

Mechano-responsive gelation of water by a short alanine-derivative.

We report the design of a structurally concise alanine derivative (Ala-hyd) that has a rotationally flexible aromatic N-protecting group for alanine and a hydrazide functionality at its carboxylic end. Ala-hyd requires mechanical agitation (physically stirring, vortexing or sonicating) to form supramolecular hydrogels at medium concentrations (0.4-0.8 wt%). At higher concentrations (>0.8 wt%), it spontaneously gelates water on undisturbed cooling of the hot solution, while at lower concentrations (<0.4 wt%), only turbid suspensions were formed upon agitation. In the <0.8 wt% regime, hydrogelation by Ala-hyd is modulated by its concentration as well as by the extent of applied mechanical agitation. Turbidimetry and fluorescence spectroscopy indicate enhanced self-assembly of Ala-hyd upon agitation, and FTIR studies point towards stronger hydrogen bonds in the resulting assemblies. Since Ala-hyd requires mechanical agitation to undergo self-assembly, its aqueous sols exhibited mild shear-thickening behaviour in buffered as well as salt-free conditions. During shearing, the formation of an entangled mesh of long, helical nanofibers coincided with the maximum in the bulk shear viscosity. pH-dependent rheological investigations indicate that protonation of the amine unit (pKa = 8.9) of hydrazide diminishes the self-assembly propensity of this compound. The self-assembly of Ala-hyd can thus be modulated through mechanical as well as chemical cues.