Domains in Melts of Comb-Coil Diblock Copolymers: Superstrong Segregation Regime

Conditions for the crossover from the strong to the superstrong segregation regime are analyzed for the case of comb-coil diblock copolymers. It is shown that the critical interaction energy between the components required to induce the crossover to the superstrong segregation regime is inversely proportional to mb = 1 + n/m, where n is the degree of polymerization of the side chain and m is the distance between successive grafting points. As a result, the superstrong segregation regime, being rather rare in the case of ordinary block copolymers, has a much better chance to be realized in the case of diblock copolymers with combs grafted to one of the blocks.

Interactions between lipid-free apolipoprotein-AI and a lipopeptide incorporating the RGDS cell adhesion motif

The interaction of a designed bioactive lipopeptide C16-GGGRGDS, comprising a hexadecyl lipid chain attached to a functional heptapeptide, with the lipid-free apoliprotein, Apo-AI, is examined. This apolipoprotein is a major component of high density lipoprotein and it is involved in lipid metabolism and may serve as a biomarker for cardiovascular disease and Alzheimers’ disease. We find via isothermal titration calorimetry that binding between the lipopeptide and Apo-AI occurs up to a saturation condition, just above equimolar for a 10.7 μM concentration of Apo-AI. A similar value is obtained from circular dichroism spectroscopy, which probes the reduction in α-helical secondary structure of Apo-AI upon addition of C16-GGGRGDS. Electron microscopy images show a persistence of fibrillar structures due to self-assembly of C16-GGGRGDS in mixtures with Apo-AI above the saturation binding condition. A small fraction of spheroidal or possibly “nanodisc” structures was observed. Small-angle X-ray scattering (SAXS) data for Apo-AI can be fitted using a published crystal structure of the Apo-AI dimer. The SAXS data for the lipopeptide/ Apo-AI mixtures above the saturation binding conditions can be fitted to the contribution from fibrillar structures coexisting with flat discs corresponding to Apo-AI/lipopeptide aggregates

Self-assembly of minimal peptoid sequences

Peptoids are biofunctional N-substituted glycine peptidomimics. Their self-assembly is of fundamental interest because they demonstrate alternatives to conventional peptide structures based on backbone chirality and beta-sheet hydrogen bonding. The search for self-assembling, water-soluble “minimal” sequences, be they peptide or peptidomimic, is a further challenge. Such sequences are highly desired for their compatibility with biomacromolecules and convenient synthesis for broader application. We report the self-assembly of a set of trimeric, water-soluble α-peptoids that exhibit a relatively low critical aggregation concentration (CAC ∼ 0.3 wt %). Cryo-EM and angle-resolved DLS show different sequence-dependent morphologies, namely uniform ca. 6 nm wide nanofibers, sheets, and clusters of globular assemblies. Absorbance and fluorescence spectroscopies indicate unique phenyl environments for π-interactions in the highly ordered nanofibers. Assembly of our peptoids takes place when the sequences are fully ionized, representing a departure from superficially similar amyloid-type hydrogen-bonded peptide nanostructures and expanding the horizons of assembly for sequence-specific bio- and biomimetic macromolecules

Geologically recent rearrangements in central Amazonian river network and their importance for the riverine barrier hypothesis

The riverine barrier hypothesis is a central concept in Amazonian biogeography. It states that large rivers limit species distributions and trigger vicariant speciation. Although the hypothesis has explanatory power, many recent biogeographical observations addressing it have produced conflicting results. We propose that the controversies arise because tributary arrangements in the Amazon river system have changed in geologically recent times, such that large tracts of forest that were on the same side of a river at one time got separated to different sides at another. Based on topographical data and sediment dating, we map about 20 major avulsion and river capture events that have rearranged the river network in central Amazonia during the late Pleistocene and Holocene. We identify areas where past riverine barrier effects might still linger in the absence of a major river, as well as areas where such effects may not yet have accumulated across an existing river. These results call for a reinterpretation of previous biogeographical studies and a reorientation of future works to take into account the idiosyncratic histories of individual rivers

MESOMORPHIC STATE OF POLY(VINYLPYRIDINE)-DODECYLBENZENESULFONIC ACID COMPLEXES IN BULK AND IN XYLENE SOLUTION

Theoretically, lyotropic behavior of flexible polymers can be induced by associating the polymers with a large amount of long-tail surfactants leading to bottle-brush type conformations in suitable solvents. To address this and related questions, complexes of poly(2-vinylpyridine) (P2VP) and poly(4-vinylpyridine) (P4VP) with p-dodecylbenzenesulfonic acid (DBSA), characterized by FT-IR, were investigated in the bulk and in xylene, i.e., a good solvent for the alkyl side chains. At a 1:1 molar ratio of vinylpyridine monomer and DBS, the polymers are shown by FT-IR to be almost completely protonated. In the bulk, the complexes form mesomorphic layer structures which have been characterized by polarized optical microscopy and by both wide- and small-angle X-ray scattering. In the xylene solutions, birefringence indicating liquid crystallinity is observed for concentrations of the fully protonated P4VP-(DBSA)(1.0) complex of ca. 50% (w/w) and higher. In contrast, for P2VP(DBSA)(1.0), this is only observed at complex concentrations of ca. 70% (w/w) and higher. The mesomorphic behavior of P4VP(DBSA)(1.0) in xylene was further demonstrated by SAXS

Surfactant induced mesomorphic behaviour of flexible polymers

Conditions for micro phase separated structures based on flexible polymers associated with surfactants have been investigated. Reasonably strong attractive interactions are required to oppose macro phase separation between polymer and surfactant. In order to obtain micro phase separation, additionally a sufficiently strong polar-nonpolar repulsion has to be present. Poly(4-vinyl pyridine), poly(2-vinyl pyridine) and polyamide 6 have been used as model polymers in this work. Associations based on protonation, metal coordination and hydrogen bonding are presented and shown to yield micro phase separation under suitable conditions. In the charged systems, the polar-nonpolar repulsion easily becomes large enough to render micro phase separated structures. In hydrogen bonded (i.e. noncharged) systems a more delicate balance can be achieved in which case an order-disorder transition takes place from a homogeneous state, exhibiting nonetheless a distinct SAXS peak due to characteristic block copolymer-like fluctuations, to a micro phase separated ordered state.</p

Chain-end modifications and sequence arrangements of antimicrobial peptoids for mediating activity and nano-assembly

Poly(N-substituted glycine) “peptoids” are an interesting class of peptidomimics that can resist proteolysis and mimic naturally found antimicrobial peptides (AMPs), which exhibit wide spectrum activity against bacteria. This work investigates the possibility of modifying peptoid AMP mimics (AMPMs) with aliphatic lipid “tails” to generate “lipopeptoids” that can assemble into micellar nanostructures, and evaluates their antimicrobial activities. Two families of AMPMs with different distributions of hydrophobic and cationic residues were employed—one with a uniform repeating amphiphilicity, the other with a surfactant-like head-to-tail amphiphilicity. To further evaluate the interplay between self-assembly and activity, the lipopeptoids were variously modified at the AMPM chain ends with a diethylene glycol (EG2) and/or a cationic group (Nlys-Nlys dipeptoid) to adjust amphiphilicity and chain flexibility. Self-assembly was investigated by critical aggregation concentration (CAC) fluorescence assays and dynamic light scattering (DLS). The structure of a key species was also verified by small-angle X-ray scattering (SAXS) and cryo-electron microscopy (cryo-EM). To screen for antibacterial properties, we measured the minimum inhibitory concentrations (MIC) against S. aureus, E. coli, and P. aeruginosa. We found that certain combinations of lipid tail and AMPM sequences exhibit increased antibacterial activity (i.e., decreased MICs). Perhaps counter-intuitively, we were particularly interested in increased MICs in combination with low CACs. Concealing antimicrobial interactions due to packing of AMPMs in nano-assemblies could pave the way to AMPMs that may be “inert” even if unintentionally released and prevent microbes from gaining resistance to the lipopeptoids. Overall, incorporation of EG2 significantly improved lipopeptoids packing while the hydrophobic tail length was found to have a major influence over the MIC. One particular sequence, which we named C15-EG2-(kss)4, exhibited a very low CAC of 34 μM (0.0075 wt.%) and a significantly increased MIC above values for the unmodified AMPM. With the sequence design trends uncovered from this study, future work will focus on discovering more species such as C15-EG2-(kss)4 and on investigating release mechanisms and the potency of the released lipopeptoids

Self-assembly, nematic phase formation and organocatalytic behaviour of a proline-functionalized lipopeptide

The self-assembly of the amphiphilic lipopeptide PAEPKI-C16 (P = proline, A = alanine, E = glutamic acid, K = lysine, I = isoleucine, C16 = hexadecyl) was investigated using a combination of spectroscopic, microscopic and scattering methods and compared to C16-IKPEAP with the same (reversed) peptide sequence and the alkyl chain positioned N-terminally and which lacks a free N-terminal proline residue. The catalytic activity of these peptides were then compared using a model aldol reaction system. For PAEPKI-C16, Cryo-TEM images showed the formation of micrometer length fibers, which by Small-angle X-ray scattering (SAXS) were found to have a radius of 2.5 - 2.6 nm. Spectroscopic analysis shows these fibers are built from -sheets. This behaviour is in complete contrast to that of C16-IKPEAP which forms spherical micelles with peptides in a disordered conformation [Hutchinson, J. A. et al. J. Phys. Chem. B 2019, 123, 613]. For PAEPKI-C16, the spontaneous alignment of fibers was observed upon increasing pH, which was accompanied by observed birefringence and anisotropy of SAXS patterns. This shows the formation of a nematic liquids and unprecedented nematic hydrogel formation was also observed these lipopeptides at sufficiently high concentrations. SAXS shows retention of an ultrafine (1.7 nm core radius) fibrillar network within the hydrogel. PAEPKI-C16 with free N-terminal proline shows enhanced anti:syn diastereoselectivity and better conversion compared to C16-IKPEAP. The cytotoxicity of PAEPKI-C16 was also lower than C16-IKPEAP for both fibroblast and cancer cell lines. These results highlight the sensitivity of lipopeptide properties to the presence of a free proline residue. The spontaneous nematic phase formation by PAEPKI-C16 points to the highly anisotropy of its ultrafine fibrillar structure and the formation of such a phase at low concentration in aqueous solution may be valuable for future applications

Self-Assembly of Supramolecular Triblock Copolymer Complexes

Four different poly(tert-butoxystyrene)-b-polystyrene-b-poly(4-vinylpyridine) (PtBOS-b-PS-b-P4VP) linear triblock copolymers, with the P4VP weight fraction varying from 0.08 to 0.39, were synthesized via sequential anionic polymerization. The values of the unknown interaction parameters between styrene and tert-butoxystyrene and between tert-butoxystyrene and 4-vinylpyridine were determined from random copolymer blend miscibility studies and found to satisfy 0.031<χS,tBOS<0.034 and 0.39<χ4VP,tBOS<0.43, the latter being slightly larger than the known 0.30<χS,4VP≤0.35 value range. All triblock copolymers synthesized adopted a P4VP/PS core/shell cylindrical self-assembled morphology. From these four triblock copolymers supramolecular complexes were prepared by hydrogen bonding a stoichiometric amount of pentadecylphenol (PDP) to the P4VP blocks. Three of these complexes formed a triple lamellar ordered state with additional short length scale ordering inside the P4VP(PDP) layers. The self-assembled state of the supramolecular complex based on the triblock copolymer with the largest fraction of P4VP consisted of alternating layers of PtBOS and P4VP(PDP) layers with PS cylinders inside the latter layers. The difference in morphology between the triblock copolymers and the supramolecular complexes is due to two effects: (i) a change in effective composition and, (ii) a reduction in interfacial tension between the PS and P4VP containing domains. The small angle X-ray scattering patterns of the supramolecules systems are very temperature sensitive. A striking feature is the disappearance of the first order scattering peak of the triple lamellar state in certain temperature intervals, while the higher order peaks (including the third order) remain. This is argued to be due to the thermal sensitivity of the hydrogen bonding and thus directly related to the very nature of these systems.