Growth of Merocyanine Dye J-Aggregate Nanosheets by Living Supramolecular Polymerization

J-aggregates are highly desired dye aggregates but so far there has been no general concept how to accomplish the required slip-stacked packing arrangement for dipolar merocyanine (MC) dyes whose aggregation commonly affords one-dimensional aggregates composed of antiparallel, co-facially stacked MCs with H-type coupling. Herein we describe a strategy for MC J-aggregates based on our results for an amphiphilic MC dye bearing alkyl and oligo(ethylene glycol) side chains. In an aqueous solvent mixture, we observe the formation of two supramolecular polymorphs for this MC dye, a metastable off-pathway nanoparticle showing H-type coupling and a thermodynamically favored nanosheet showing J-type coupling. Detailed studies concerning the self-assembly mechanism by UV-Vis spectroscopy and the packing structure by atomic force microscopy and wide-angle X-ray scattering show how the packing arrangement of such amphiphilic MC dyes can afford slip-stacked two-dimensional nanosheets whose macrodipole is compensated by the formation of a bilayer structure. As an additional feature we demonstrate how the size of the nanosheets can be controlled by seeded living supramolecular polymerization.     

Glycine Substitution Effects on the Supramolecular Morphology and Rigidity of Cell-Adhesive Amphiphilic Peptides

Self-assembling peptides that are capable of adopting β-sheet structures can generate nanofibers that lead to hydrogel formation. Herein, to tune the supramolecular morphologies, mechanical properties, and stimuli responses of the hydrogels, we investigated glycine substitution in a β-sheet-forming amphiphilic peptide. Glycine substitution generally enhances conformational flexibility. Indeed, glycine substitution in an amphiphilic peptide weakened the hydrogels or even inhibited the gelation. However, unexpectedly, glycine substitution at the center of the peptide molecule significantly enhanced the hydrogel stiffness. The central glycine substitution affected the molecular packing and led to twisted β-sheet structures and to nanofiber bundling, which likely led to the stiffened hydrogel. Importantly, the supramolecular structures were accurately predicted by molecular dynamics simulations, demonstrating the helpfulness of these techniques for the identification of self-assembling peptides. The hydrogel formed by the amphiphilic peptide with the central glycine substitution had cell adhesive function, and showed a reversible thermal gel-to-sol transition. Thus, glycine substitution is effective in modulating self-assembling structures, rheological properties, and dynamics of biofunctional self-assembling peptides.     

Conformational polymorphism and amphiphilic properties of resorcinarene octapodands

o-Nitroaniline functionalized resorcinarene octapodands 1-5 with pendant methyl, ethyl, pentyl, nonyl or 1-decenyl groups, respectively, were synthesized and their structural properties investigated using X-ray crystallography and NMR spectroscopy. The upper rim of each podand is identical containing flexible side arms, in which rotation around the -OCH(2)CH(2)N- linkers create excellent possibilities for polymorphism. Two conformational polymorphs of acetone solvate of 2 were identified containing different side arm orientation and crystal packing. Compound 1 crystallized from acetone and nitromethane yielding two pseudopolymorphs with different packing motifs. The longer alkyl chains of 3-5 lead to differences in solubility and induce amphiphilic properties, which were studied at the air-water interface using the Langmuir-film technique. Crystals of amphiphilic compound 5, which has hydrophobic alkyl tails at the lower rim and hydrophilic nitroaniline groups at the upper rim, showed an interesting packing motif with alternating aromatic and aliphatic layers. Versatile structures of the octapodands in solid state and in solution serve as an example of how conformational flexibility can be utilized in crystal engineering and creating self-assembling monolayer structures.     

A series of long-chain lamellar hydrated copper(II) alkylsulfonates with different chain molecular assemblies

Reaction of copper(II) salts with n-alkylsulfonate anions yields light blue lamellar Cu(C(n)H(2n + 1)SO3)2 x zH2O displaying distinct (mono/bi-layer) chain packing with increasing alkyl chain lengths. This may be attributed to the amphiphilic nature of the surfactants, i.e., the hydrophilic sulfonate head groups, mediating the coordination, and H-bonding interactions, and the hydrophobic alkyl chains.     

Fabrication of Chiral Materials via Self‐Assembly and Biomineralization of Peptides

With different scales of chirality, chiral materials have various particular properties and potential applications in many fields. Peptides are the fundamental building units of biological systems, and a variety of ordered functional nanostructures are produced through self‐assembly and biomineralization of peptides in nature. This Personal Account describes chiral silica materials fabricated by using amphiphilic peptides as building blocks. Three particular biomineralization approaches are described based on different kinds of geometry of amphiphilic peptides: the influence of the specific amino acid proline in the peptide sequence, the hydrophilicity of amphiphilic peptides, and different kinds of hydrophobic tails in amphiphilic peptides. These strategies are useful for designing peptides toward the bottom‐up synthesis of nanomaterials as well as improving the understanding of the mechanism of peptide self‐assembly.     

疏水相互作用引起Gemini表面活性剂柔性联接链的弯曲

为了理解gemini表面活性剂柔性烷基联接链在自组织过程中的特殊作用,我们合成了三种gemini表面活性剂烷基-a,w-二（二-十二烷基甲基溴化铵）（记为2C12-s-2C12×2Br (s=3, 6, 8)）。2C12-s-2C12×2Br在水表面构成铺展膜后,由于每个分子带有4根烷烃链,它们形成了稠密的烷烃尾链层。增强的烷烃尾链与联接链间的疏水相互作用促使联接链弯曲朝向空气一端,可发生弯曲的联接链长度要小于吸附在水溶液表面上的gemini表面活性剂C12-s-C12×2Br,后者每个分子只有2根烷烃链。由此可见,增强的烷烃尾链与联接链间的疏水相互作用可以有效地促进联接链的弯曲。     

Improved cooperativity of spin-labile iron(III) centers by self-assembly in solution

Supramolecular principles have been applied for improving the spin crossover activity of metal centers due to cooperative effects in solution. Thus, incorporation of alkyloxy tails at the phenyl group of Fe(sal2trien) 2a provides amphiphilic complexes Fe(sal-OR2trien) 2b-d (b, R = C6H13; c, R = C8H17; d, R = C18H37) comprising an apolar group for supramolecular organization and a polar headgroup with potential spin crossover activity due to the presence of a spin-labile iron(III) center. Self-assembly of these complexes in solution resulted in the formation of microsize and submicrosize particles when the alkyl chain was long enough (2d) but not with shorter chains (2a-c). Solutions of 2d showed enhanced spin crossover activity as compared to complexes 2a-c, both in terms of transition temperature and steepness of the transition. This observation has been correlated to an improved cooperativity of the metal centers in 2d due to self-assembly, thus facilitating a tandem spin transition.     

Solid-phase and solution-phase syntheses of oligomeric guanidines bearing peptide side chains

[reaction: see text] Synthetic strategies for preparing N,N'-bridged oligomeric guanidines bearing peptide side chains both on solid support and in solution are presented. Monomers are prepared from common alpha-amino acids and therefore contain conventionally protected peptide side chains. The side chains include alkyl, aromatic, hydroxyl, amino, carboxylic acid, and amide functional groups. Oligomer elongation utilizes acid-sensitive sulfonyl activated thiourea through the formation of carbodiimide intermediate. With proper preparation of monomers, synthesis of oligomer can be performed in two directions (equivalent to N to C terminal or C to N terminal in a peptide sequence) with excellent efficiency.     

Resorcinarene bis-crown silver complexes and their application as antibacterial Langmuir-Blodgett films

Silver complexes of a cation binding supramolecular host, resorcinarene bis-crown (CNBC5) with propyl, nonyl, decyl and undecyl alkyl chains were investigated by NMR titration, picrate extraction and single crystal X-ray diffraction. Binding studies showed that both 1 : 1 and 1 : 2 (host-Ag(+)) complexes are present in solution with only a slight effect of the lower rim alkyl chain length on the binding constants (log K 4.0-4.2 for 1 : 2 complexes). Solid state complexes of the resorcinarene bis-crowns bearing either C(3) or C(11) chains were obtained. Single crystal X-ray analyses showed that both derivatives bind silver ions by metal-arene and Ag···O coordination from the crown ether bridges and from the solvent, and pack in layered or bilayered fashion. Furthermore, the amphiphilic nature of C11BC5 was demonstrated using the Langmuir balance technique. Langmuir-Blodgett films of the amphiphilic C11BC5-Ag complex were transferred onto a substrate and shown to possess antibacterial activity against E. coli.     

Spider-web amphiphiles as artificial lipid clusters: design, synthesis, and accommodation of lipid components at the air-water interface

As a novel category of two-dimensional lipid clusters, dendrimers having an amphiphilic structure in every unit were synthesized and labeled "spider-web amphiphiles". Amphiphilic units based on a Lys-Lys-Glu tripeptide with hydrophobic tails at the C-terminal and a polar head at the N-terminal are dendrically connected through stepwise peptide coupling. This structural design allowed us to separately introduce the polar head and hydrophobic tails. Accordingly, we demonstrated the synthesis of the spider-web amphiphile series in three combinations: acetyl head/C16 chain, acetyl head/C18 chain, and ammonium head/C16 chain. All the spider-web amphiphiles were synthesized in satisfactory yields, and characterized by 1H NMR, MALDI-TOFMS, GPC, and elemental analyses. Surface pressure (pi)-molecular area (A) isotherms showed the formation of expanded monolayers except for the C18-chain amphiphile at 10 degrees C, for which the molecular area in the condensed phase is consistent with the cross-sectional area assigned for all the alkyl chains. In all the spider-web amphiphiles, the molecular areas at a given pressure in the expanded phase increased in proportion to the number of units, indicating that alkyl chains freely fill the inner space of the dendritic core. The mixing of octadecanoic acid with the spider-web amphiphiles at the air-water interface induced condensation of the molecular area. From the molecular area analysis, the inclusion of the octadecanoic acid bears a stoichiometric characteristic; i.e., the number of captured octadecanoic acids in the spider-web amphiphile roughly agrees with the number of branching points in the spider-web amphiphile.     

Peptoads, a group of amphiphilic long-chain triamides

Eleven triamides bearing long alkyl chains have been synthesized to produce a new class of amphiphilic compounds (dubbed "peptoad"). The properties of these molecules have been investigated by X-ray analysis, solubility studies, light and electron microscopy, surface tensiometry, light scattering, drug dissolution, and molecular dynamics. In the solid state, the peptoads assemble in layers with both intra- and interlayer hydrogen bonding coupled to side-by-side proximity of the hydrocarbon chains. Peptoads with a terminal primary amide and a total of three amide NH sites are water-insoluble owing presumably to attractive forces in the solid state. However, peptoads with terminal -CONMe(2) groups and two internal amide NH sites are water-soluble at room temperature. This solubility is critically dependent upon the chain length. For example, a C(7)-chained peptoad is 1600 times more soluble than its C(9) analogue. High concentrations (6-8 M) of C(7) peptoads in water are clear and do not gel. Light microscopy shows long fibers floating in an isotropic liquid. Water-soluble peptoads are highly surface-active, lowering water's surface tension as effectively as a soap with a much longer chain. Surface tension plots show a "critical aggregation concentration", but it is believed from light scattering and molecular dynamics that the aggregates grow continuously as more peptoad is added to the water. In answer to the inevitable (but valid) question, "What possible good are they?", it can be pointed out that a peptoad solubilizes a water-insoluble drug, paclitaxel (Taxol), as efficiently as does Cremophor EL, a commercial excipient widely used with paclitaxel and other nonpolar drugs. Peptoads, being small molecules and consisting of hydrolyzable amide groups, are likely biodegradable and less prone to the hypersensitivity and neurotoxicity found with Cremophor EL.     

Linear and branched alkyl substituted octakis(dimethylsiloxy)octasilsesquioxanes: WAXS and thermal properties

A series of octakis(dimethylsiloxy)octasilsesquioxanes bearing linear and branched alkyl substituents has been prepared in high yield by Pt-catalyzed hydrosilylation of alkenes with octakis(hydrodimethylsiloxy)octasilsesquioxane, chain length varying between C3 and C8 for the straight-chain derivatives and between C5 and C7 for the branched-chain derivatives. On the basis of a WAXS study, we showed that the linear derivatives are amorphous and that the interdigitation of alkyl chains between neighboring POSS molecules increases as the alkyl chain length increases from propyl to octyl. The thermal behavior of these compounds was studied by DSC, polarized optical microscopy and TGA in nitrogen and air atmosphere. The derivatives with shorter n-alkyl chains from C3 to C6 crystallize below 0 °C whereas the derivatives with longer n-alkyl chains (C7 and C8) can be regarded as amorphous glasses with a T_g around –100 °C. The morphology and thermal properties change considerably with branching of the alkyl chain. Melting points above ambient temperature were found for the iso-hexyl and iso-heptyl POSS derivatives whereas the iso-pentyl POSS derivative is liquid at 25 °C. From the values of the heat of fusion as well as entropy of fusion, it was concluded that packing of the side groups in the crystal structure increases as the size of the branched alkyl group increases. TGA evidenced a negative effect of the branching of the alkyl chain on the thermal stability in air.     

Self-assembly of organic-inorganic hybrid amphiphilic surfactants with large polyoxometalates as polar head groups

Mn-Anderson-C6 and Mn-Anderson-C16, A type of inorganic-organic hybrid molecules containing a large anionic polyoxometalate (POM) cluster and two C6 and C16 alkyl chains, respectively, demonstrate amphiphilic surfactant behavior in the mixed solvents of acetonitrile and water. The amphiphilic hybrid molecules can slowly assemble into membrane-like vesicles by using the POM clusters as polar head groups, as studied by laser light scattering and TEM techniques. The hollow vesicles have a typical bilayer structure with the hydrophilic Mn-Anderson cluster facing outside and long hydrophobic alkyl chains staying inside to form the solvent-phobic layer. Due to the rigidity of the POM polar heads, the two alkyl tails have to bend significantly for the vesicle formation, which makes the vesicle formation more difficult compared to some conventional surfactants. This is the first example of using hydrophilic POM macroions as polar head groups for a surfactant system.     

Organic hydrogen-bonded assembly of asymmetric phenol amide molecules

The significant involvement of weak intermolecular interactions and steric and/or symmetry-related packing features was assessed with supramolecular arrays of 4-hydroxyphenyl amides in the crystal structure. The one-dimensional chain is observed in the aryl substituted 4-hydroxyphenyl amides, while alkyl analogs generate 2D or 3D arrays. A comparison of supramolecular assemblies in the similar 4-hydroxyphenyl amide compounds in the Cambridge Structural Database has been presented. It is correlated with the different steric constraints of aryl and alkyl groups to create chains, 2D sheets and 3D-interpenetrated networks in the asymmetric 4-hydroxyphenyl amides. A comprehensive analysis of crystal packing and energy features of the selected 4-hydroxyphenyl amide derivatives is reported.     

Oxidation of peptides by methyl(trifluoromethyl)dioxirane: the protecting group matters

Representative Boc-protected and acetyl-protected peptide methyl esters bearing alkyl side chains undergo effective oxidation using methyl(trifluoromethyl)dioxirane (1b) under mild conditions. We observe a protecting group dependency in the chemoselectivity displayed by the dioxirane 1b. N-Hydroxylation occurs in the case of the Boc-protected peptides, and side chain hydroxylation takes place in the case of acetyl-protected peptides. Both are attractive transformations since they yield derivatized peptides that serve as valuable synthons.     

Amphiphilic laminin peptides at air/water interface--effect of single amino acid mutations on surface properties

Amphiphilic derivative of the laminin peptide YIGSR and three other mutated peptides with mutation at Y with V (valine), I (isoleucine), and L (leucine) have been synthesized. The monolayer formation and the stability of these peptide analogues at air/water interface and the interaction with phospholipid monolayers have been studied using surface pressure-molecular area (pi-A) and surface potential-molecular area (DeltaV-A) isotherms. The single amino acid mutation in the native sequence leads to appreciable changes in surface activity, orientation and insertion into lipid monolayers with LIGSR showing most hydrophobic character while YIGSR showed most polar nature. The morphology of spread monolayers in the most close packed state was carried out using Brewster angle microscopy (BAM). LB films of these amphiphilic peptide derivatives transferred to hydrophilic quartz surfaces and hydrophobically modified surfaces showed significant changes in the work of adhesion as well as spreading behavior of water with the L substituted sequence showing maximum work of adhesion and the native sequence YIGSR, the least work of adhesion. From theoretical estimates, the long-range effects of the different amino acid residues in position 1 on the alkyl chains have been studied from charge on the carbon and hydrogen atoms of the alkyl tails. The present study demonstrates that amphiphilic derivatives of the laminin peptide YIGSR show enhanced activity compared to the original sequence. This work shows that the amino acid substituents on the head group clearly influence the distal methylene groups of the tail. Thus, any mutation of even single amino acid in a peptide sequence influences and plays an important role in determining macroscopic properties such as surface energy and adhesion both at air/solution and solid/solution interfaces.     

Enzymatic Hydrolysis-Responsive Supramolecular Hydrogels Composed of Maltose-Coupled Amphiphilic Ureas

Maltose is a ubiquitous disaccharide produced by the hydrolysis of starch. Amphiphilic ureas bearing hydrophilic maltose moiety were synthesized via the following three steps: I) construction of urea derivatives by the condensation of 4-nitrophenyl isocyanate and alkylamines, II) reduction of the nitro group by hydrogenation, and III) an aminoglycosylation reaction of the amino group and the unprotected maltose. These amphiphilic ureas functioned as low molecular weight hydrogelators, and the mixtures of the amphipathic ureas and water formed supramolecular hydrogels. The gelation ability largely depended on the chain length of the alkyl group of the amphiphilic urea; amphipathic urea having a decyl group had the highest gelation ability (minimum gelation concentration=0.4 mM). The physical properties of the supramolecular hydrogels were evaluated by measuring their thermal stability and dynamic viscoelasticity. These supramolecular hydrogels underwent gel-to-sol phase transition upon the addition of α-glucosidase as a result of the α-glucosidase-catalyzed hydrolysis of the maltose moiety of the amphipathic urea.     

Effect of hydrogen-bonded supramolecular assembling on liquid crystal properties of imidazole-containing azomethines and their chelates with copper(II)

A series of imidazole-containing rod-like Schiff's bases and their ionic copper(II) chelates with various lengths of the terminal alkyl chain containing 6, 8, 10, 12, 14 and 16 carbon atoms have been synthesised. The synthesised compounds were characterised by elemental analyses, ¹H NMR, IR and UV–vis and mass spectroscopies. Thermotropic smectic C mesophases in the ligands and smectic A mesophases in the copper(II) complexes were identified using POM, DSC and small-angle XRD scattering methods. X-ray diffraction patterns of the prepared imidazole imines indicate to supramolecular self-assembled structures in the liquid crystal state, which are formed by means of intermolecular hydrogen bonds. It was established that both liquid crystal arrangement and supramolecular assemblies in ligands disappeared near 190°C, mainly regardless of the lengths of the terminal alkyl chains. Contrary, assembling of the copper(II) complexes into supramolecular bilayers occurs near 200°C, which causes their transition to a smectic A mesophase.     

Self‐Assembly of Imidazolium‐Based Rodlike Ionic Liquid Crystals: Transition from Lamellar to Micellar Organization

By using aryl‐amination chemistry, a series of rodlike 1‐phenyl‐1H‐imidazole‐based liquid crystals (LCs) and related imidazolium‐based ionic liquid crystals (ILCs) has been prepared. The number and length of the C‐terminal chains (at the noncharged end of the rodlike core) and the length of the N‐terminal chain (on the imidazolium unit in the ILCs) were modified and the influence of these structural parameters on the mode of self‐assembly in LC phases was investigated by polarizing microscopy, differential scanning calorimetry, and X‐ray diffraction. For the single‐chain imidazole derivatives nematic phases (N) and bilayer SmA₂ phases were found, but upon increasing the number of alkyl chains the LC phases were lost. For the related imidazolium salts LC phases were preserved upon increasing the number and length of the C‐terminal chains and in this series it leads to the phase sequence SmA–columnar (Col)–micellar cubic (Cub_I/Pm3n). Elongation of the N‐terminal chain gives the reversed sequence. Short N‐terminal chains prefer an end‐to‐end packing of the mesogens in which these chains are separated from the C‐terminal chains. Elongation of the N‐terminal chain leads to a mixing of N‐ and C‐terminal chains, which is accompanied by complete intercalation of the aromatic cores. In the smectic phases this gives rise to a transition from bilayer (SmA₂) to monolayer smectic (SmA) phases. For the columnar and cubic phases the segregated end‐to‐end packing leads to core–shell aggregates. In this case, elongation of the N‐terminal chains distorts core–shell formation and removes Cub_I and Col phases in favor of single‐layer SmA phases. Hence, by tailoring the length of the N‐terminal chain, a crossover from taper‐shaped to polycatenar LC tectons was achieved, which provides a powerful tool for control of self‐assembly in ILCs.     

Virus-sized DNA nanoparticles for gene delivery based on micelles of cationic calixarenes

Macrocyclic amphiphilic molecules based on calix[4]arenes are highly attractive for controlled supramolecular assembly of DNA into small nanoparticles, since they present a unique conical architecture and can bear multiple charged groups. In the present work, we synthesized new amphiphilic calixarenes bearing cationic groups at the upper rim and alkyl chains at the lower rim. Their self-assembly in aqueous solution was characterized by fluorescent probes, fluorescence correlation spectroscopy, dynamic light scattering, gel electrophoresis and atomic force microscopy. We found that calixarenes bearing long alkyl chains (octyl) self-assemble into micelles of 6 nm diameter at low critical micellar concentration and present the unique ability to condense DNA into small nanoparticles of about 50 nm diameter. In contrast, the short-chain (propyl) analogues that cannot form micelles at low concentrations failed to condense DNA, giving large polydisperse DNA complexes. Thus, formation of small DNA nanoparticles is hierarchical, requiring assembly of calixarenes into micellar building blocks that further co-assemble with DNA into small virus-sized particles. The latter showed much better gene transfection efficiency in cell cultures relative to the large DNA complexes with the short-chain analogues, which indicates that gene delivery of calixarene/DNA complexes depends strongly on their structure. Moreover, all cationic calixarenes studied showed low cytotoxicity. Thus, this work presents a two-step hierarchical assembly of small DNA nanoparticles for gene delivery based on amphiphilic cone-shaped cationic calixarenes.