Screening Libraries to Discover Molecular Design Principles for the Targeted Delivery of mRNA with One-Component Ionizable Amphiphilic Janus Dendrimers Derived from Plant Phenolic Acids.

Viral and synthetic vectors to deliver nucleic acids were key to the rapid development of extraordinarily efficient COVID-19 vaccines. The four-component lipid nanoparticles (LNPs), containing phospholipids, PEG-conjugated lipids, cholesterol, and ionizable lipids, co-assembled with mRNA via a microfluidic technology, are the leading nonviral delivery vector used by BioNTech/Pfizer and Moderna to access COVID-19 mRNA vaccines. LNPs exhibit a statistical distribution of their four components when delivering mRNA. Here, we report a methodology that involves screening libraries to discover the molecular design principles required to realize organ-targeted mRNA delivery and mediate activity with a one-component ionizable multifunctional amphiphilic Janus dendrimer (IAJD) derived from plant phenolic acids. IAJDs co-assemble with mRNA into monodisperse dendrimersome nanoparticles (DNPs) with predictable dimensions, via the simple injection of their ethanol solution in a buffer. The precise location of the functional groups in one-component IAJDs demonstrated that the targeted organs, including the liver, spleen, lymph nodes, and lung, are selected based on the hydrophilic region, while activity is associated with the hydrophobic domain of IAJDs. These principles, and a mechanistic hypothesis to explain activity, simplify the synthesis of IAJDs, the assembly of DNPs, handling, and storage of vaccines, and reduce price, despite employing renewable plant starting materials. Using simple molecular design principles will lead to increased accessibility to a large diversity of mRNA-based vaccines and nanotherapeutics.

An Accelerated Modular-Orthogonal Ni-Catalyzed Methodology to Symmetric and Nonsymmetric Constitutional Isomeric AB2 to AB9 Dendrons Exhibiting Unprecedented Self-Organizing Principles.

Five libraries of natural and synthetic phenolic acids containing five AB3, ten constitutional isomeric AB2, one AB4, and one AB5 were previously synthesized and reported by our laboratory in 5 to 11 steps. They were employed to construct seven libraries of self-assembling dendrons, by divergent generational, deconstruction, and combined approaches, enabling the discovery of a diversity of supramolecular assemblies including Frank-Kasper phases, soft quasicrystals, and complex helical organizations, some undergoing deracemization in the crystal state. However, higher substitution patterns within a single dendron were not accessible. Here we report three libraries consisting of 30 symmetric and nonsymmetric constitutional isomeric phenolic acids with unprecedented sequenced patterns, including two AB2, three AB3, eight AB4, five AB5, six AB6, three AB7, two AB8, and one AB9 synthesized by accelerated modular-orthogonal Ni-catalyzed borylation and cross-coupling. A single etherification step with 4-(n-dodecyloxy)benzyl chloride transformed all these phenolic acids, of interest also for other applications, into self-assembling dendrons. Despite this synthetic simplicity, they led to a diversity of unprecedented self-organizing principles: lamellar structures of interest for biological membrane mimics, helical columnar assemblies from rigid-solid angle dendrons forming Tobacco Mosaic Virus-like assemblies, columnar organizations from adaptable-solid angle dendrons forming disordered micellar-like nonhelical columns, columns from supramolecular spheres, five body-centered cubic phases displaying supramolecular orientational memory, rarely encountered in previous libraries forming predominantly Frank-Kasper phases, and two Frank-Kasper phases. Lessons from these self-organizing principles, discovered within a single generation of self-assembling dendrons, may help elaborate design principles for complex helical and nonhelical organizations of synthetic and biological matter.

Monodisperse Macromolecules by Self-Interrupted Living Polymerization.

Biological macromolecules such as proteins and nucleic acids are monodisperse just as low-molar-mass organic compounds are. However, synthetic macromolecules contain mixtures of different chain lengths, the most uniform being generated by living polymerizations, which exhibit a maximum of 1-3% of chains with the desired length. Monodisperse natural and synthetic oligomers can be obtained in low quantities by tedious, multistep iterative methods. Here we report a methodology to synthesize monodisperse synthetic macromolecules by self-interrupted living polymerization. This methodology relies on a concept that combines supramolecular and macromolecular chemistry and differs from the conventional reactivity principles employed in the synthesis of polymers for over 100 years.

Supramolecular Spheres Self-Assembled from Conical Dendrons Are Chiral.

Frank-Kasper phases and liquid quasicrystals self-organize from supramolecular spheres of dendrimers, block copolymers, surfactants and other self-assembling molecules. These spheres are expected to be achiral due to their isotropic shape. Nevertheless, supramolecular spheres from short helical stacks of crown-like dendrimers self-organize a Pm3̅ n cubic (Frank-Kasper A15) phase which exhibits chirality on the macroscopic scale. However, the chirality of classic isotropic supramolecular micellar-like spheres, generated from conical dendrons, is unknown. Here we report a library of second and third generation biphenylpropyl dendrons with chiral groups at their apex that produces single-handed chiral supramolecular spheres. Up to 480 conical dendrons self-assemble to form micellar-like spheres, with a molar mass of up to 1.1 × 106 g/mol, that self-organize into a Pm3̅ n phase with chirality detectable on the macroscopic scale. This demonstration of chirality in micellar-like spheres of a Frank-Kasper phase raises the fundamental question whether micellar-like spheres forming 3D phases generated from other soft matter such as block copolymers, surfactants, and other molecules are chiral.

Dendronized Poly(2-oxazoline) Displays within only Five Monomer Repeat Units Liquid Quasicrystal, A15 and σ Frank-Kasper Phases.

Liquid quasicrystals (LQC) have been discovered in self-assembling benzyl ether, biphenylmethyl ether, phenylpropyl ether, biphenylpropyl ether and some of their hybrid dendrons and subsequently in block copolymers, surfactants and other assemblies. These quasiperiodic arrays, which lack long-range translational periodicity, are approximated by two Frank-Kasper periodic arrays, Pm3̅ n cubic (Frank-Kasper A15) and P42/ mnm tetragonal (Frank-Kasper σ), which have been discovered in complex soft matter in the same order and compounds. Poly(2-oxazoline)s dendronized with (3,4) nG1 minidendrons (where n denotes an alkyl chain, C nH2 n+1) self-organize into the Pm3̅ n cubic phase ( n = 14 and 15) and, as reported recently, the P42/ mnm tetragonal phase ( n = 16). However, no LQC of a poly(2-oxazoline) is yet known. Here we report the synthesis, structural and retrostructural analysis of a dendronized poly(2-oxazoline) with n = 17 which self-organizes not only into the LQC but also in the above two Frank-Kasper approximants. All three phases are observed from the same polymer within a very narrow range of degree of polymerization that corresponds to only five monomer repeat units (5 ≤ DP ≤ 10). The formation of the Pm3̅ n cubic, P42/ mnm tetragonal and LQC phases from a single polymer chain within such a narrow range of DP raises the questions of how and why each of these phases is self-organized. This system may provide a model for theoretical investigations into the self-organization of soft matter into Frank-Kasper and related periodic and quasiperiodic arrays.

Hierarchical Self-Organization of Chiral Columns from Chiral Supramolecular Spheres.

The supramolecular column is an archetypal architecture in the field of periodic liquid crystalline and crystalline arrays. Columns are generated via self-assembly, coassembly, and polymerization of monomers containing molecules shaped as discs, tapered, twin- and Janus-tapered, crowns, hat-shaped crowns, and fragments thereof. These supramolecular columns can be helical and therefore exhibit chirality. In contrast, spheres represent a fundamentally distinct architecture, generated from conical and crown-like molecules, which self-organize into body-centered cubic, Pm3̅ n cubic (also known as Frank-Kasper A15), and tetragonal (also known as Frank-Kasper σ) phases. Supramolecular spherical aggregates are not known to further assemble into a columnar architecture, except as an intermediate state between a columnar periodic array and a cubic phase. In the present work, a chiral dendronized cyclotetraveratrylene (CTTV) derivative is demonstrated to self-organize into a supramolecular column unexpectedly constructed from supramolecular spheres, with no subsequent transition to a cubic phase. Structural and retrostructural analysis using a combination of differential scanning calorimetry, X-ray diffraction (XRD), molecular modeling, and simulation of XRD patterns reveals that this CTTV derivative, which is functionalized with eight chiral first-generation minidendrons, self-organizes via a column-from-spheres model. The transition from column to column-from-spheres was monitored by circular dichroism spectroscopy, which demonstrated that both the supramolecular column and supramolecular spheres are chiral. This column-from-spheres model, which unites two fundamentally distinct self-assembled architectures, provides a new mechanism to self-organize supramolecular columnar architectures.

Tetrahedral Arrangements of Perylene Bisimide Columns via Supramolecular Orientational Memory.

Chiral, shape, and liquid crystalline memory effects are well-known to produce commercial macroscopic materials with important applications as springs, sensors, displays, and memory devices. A supramolecular orientational memory effect that provides complex nanoscale arrangements was only recently reported. This supramolecular orientational memory was demonstrated to preserve the molecular orientation and packing within supramolecular units of a self-assembling cyclotriveratrylene crown at the nanoscale upon transition between its columnar hexagonal and Pm3̅n cubic periodic arrays. Here we report the discovery of supramolecular orientational memory in a dendronized perylene bisimide (G2-PBI) that self-assembles into tetrameric crowns and subsequently self-organizes into supramolecular columns and spheres. This supramolecular orientation memory upon transition between columnar hexagonal and body-centered cubic (BCC) mesophases preserves the 3-fold cubic [111] orientations rather than the 4-fold [100] axes, generating an unusual tetrahedral arrangement of supramolecular columns. These results indicate that the supramolecular orientational memory concept may be general for periodic arrays of self-assembling dendrons and dendrimers as well as for other periodic and quasiperiodic nanoscale organizations comprising supramolecular spheres, generated from other organized complex soft matter including block copolymers and surfactants.

Complex Arrangement of Orthogonal Nanoscale Columns via a Supramolecular Orientational Memory Effect.

Memory effects, including shape, chirality, and liquid-crystallinity, have enabled macroscopic materials with novel functions. However, the generation of complex supramolecular nanosystems via memory effects has not yet been investigated. Here, we report a cyclotriveratrylene-crown (CTV) compound that self-assembles into supramolecular columns and spheres forming, respectively, hexagonal and cubic mesophases. Upon transition from one phase to the other, an epitaxial relationship holds, via an unprecedented supramolecular orientational memory effect. Specifically, the molecular orientation and columnar character of supramolecular packing is preserved in the cubic phase, providing an otherwise inaccessible structure comprising orthogonally oriented domains of supramolecular columns. The continuous columnar character of tetrahedrally distorted supramolecular spheres self-organized from the CTV derivative in the faces of the Pm3̅n lattice is the basis of this supramolecular orientational memory, which holds throughout cycling in temperature between the two phases. This concept is expected to be general for other combinations of periodic and quasiperiodic arrays generated from supramolecular spheres upon transition to supramolecular columns.

Screening Libraries of Semifluorinated Arylene Bisimides to Discover and Predict Thermodynamically Controlled Helical Crystallization.

Synthesis, structural, and retrostructural analysis of a library containing 16 self-assembling perylene (PBI), 1,6,7,12-tetrachloroperylene (Cl4PBI), naphthalene (NBI), and pyromellitic (PMBI) bisimides functionalized with environmentally friendly AB3 chiral racemic semifluorinated minidendrons at their imide groups via m = 0, 1, 2, and 3 methylene units is reported. These semifluorinated compounds melt at lower temperatures than homologous hydrogenated compounds, permitting screening of all their thermotropic phases via structural analysis to discover thermodynamically controlled helical crystallization from propeller-like, cogwheel, and tilted molecules as well as lamellar-like structures. Thermodynamically controlled helical crystallization was discovered for propeller-like PBI, Cl4PBI and NBI with m = 0. Unexpectedly, assemblies of twisted Cl4PBIs exhibit higher order than those of planar PBIs. PBI with m = 1, 2, and 3 form a thermodynamically controlled columnar hexagonal 2D lattice of tilted helical columns with intracolumnar order. PBI and Cl4PBI with m = 1 crystallize via a recently discovered helical cogwheel mechanism, while NBI and PMBI with m = 1 form tilted helical columns. PBI, NBI and PMBI with m = 2 generate lamellar-like structures. 3D and 2D assemblies of PBI with m = 1, 2, and 3, NBI with m = 1 and PMBI with m = 2 exhibit 3.4 Å π-π stacking. The library approach applied here and in previous work enabled the discovery of six assemblies which self-organize via thermodynamic control into 3D and 2D periodic arrays, and provides molecular principles to predict the supramolecular structure of electronically active components.

Hierarchical Self-Organization of Perylene Bisimides into Supramolecular Spheres and Periodic Arrays Thereof.

Perylene bisimide derivatives (PBIs) are known to form only columnar or lamellar assemblies. There is no known example of a PBI self-assembling into a supramolecular sphere. Therefore, periodic and quasiperiodic arrays generated from spherical assemblies produced from PBIs are also not known. Here, a PBI functionalized at its imide groups with a second generation self-assembling dendron is reported to self-assemble into supramolecular spheres. These spheres self-organize in a body-centered cubic (BCC) periodic array, rarely encountered for self-assembling dendrons but often encountered in block copolymers. These supramolecular spheres also assemble into a columnar hexagonal array in which the supramolecular columns are unexpectedly and unprecedentedly made from spheres. At lower temperature, two additional columnar hexagonal phases consisting of symmetric and asymmetric tetrameric crowns of PBI are observed. Structural and retrostructural analysis via X-ray diffraction (XRD), molecular modeling, molecular simulation, and solid state NMR suggests that inversion of the symmetric tetrameric crowns at high temperature mediates their transformation into supramolecular spheres. The tetrameric crowns of PBIs are able to form an isotropic sphere in the cubic phase due to rapid molecular motion at high temperature, unobservable by XRD but demonstrated by solid state NMR studies. This mechanism of hierarchical self-organization of PBI into supramolecular spheres is most probably general and can be applied to other related planar molecules to generate new functions.

Onion-like glycodendrimersomes from sequence-defined Janus glycodendrimers and influence of architecture on reactivity to a lectin.

A library of eight amphiphilic Janus glycodendrimers (GDs) with d-mannose (Man) headgroups, a known routing signal for lectin-mediated transport processes, was constructed via an iterative modular methodology. Sequence-defined variations of the Janus GD modulate the surface density and sequence of Man after self-assembly into multilamellar glycodendrimersomes (GDSs). The spatial mode of Man presentation is decisive for formation of either unilamellar or onion-like GDS vesicles. Man presentation and Janus GD concentration determine GDS size and number of bilayers. Beyond vesicle architecture, Man topological display affects kinetics and plateau level of GDS aggregation by a tetravalent model lectin: the leguminous agglutinin Con A, which is structurally related to endogenous cargo transporters. The agglutination process was rapid, efficient, and readily reversible for onion-like GDSs, demonstrating their value as versatile tools to explore the nature of physiologically relevant glycan/lectin pairing.

Why Do Membranes of Some Unhealthy Cells Adopt a Cubic Architecture?

Nonlamellar lipid arrangements, including cubosomes, appear in unhealthy cells, e.g., when they are subject to stress, starvation, or viral infection. The bioactivity of cubosomes-nanoscale particles exhibiting bicontinuous cubic structures-versus more common vesicles is an unexplored area due to lack of suitable model systems. Here, glycodendrimercubosomes (GDCs)-sugar-presenting cubosomes assembled from Janus glycodendrimers by simple injection into buffer-are proposed as mimics of biological cubic membranes. The bicontinuous cubic GDC architecture has been demonstrated by electron tomography. The stability of these GDCs in buffer enabled studies on lectin-dependent agglutination, revealing significant differences compared with the vesicular glycodendrimersome (GDS) counterpart. In particular, GDCs showed an increased activity toward concanavalin A, as well as an increased sensitivity and selectivity toward two variants of banana lectins, a wild-type and a genetically modified variant, which is not exhibited by GDSs. These results suggest that cells may adapt under unhealthy conditions by undergoing a transformation from lamellar to cubic membranes as a method of defense.

A supramolecular helix that disregards chirality.

The functions of complex crystalline systems derived from supramolecular biological and non-biological assemblies typically emerge from homochiral programmed primary structures via first principles involving secondary, tertiary and quaternary structures. In contrast, heterochiral and racemic compounds yield disordered crystals, amorphous solids or liquids. Here, we report the self-assembly of perylene bisimide derivatives in a supramolecular helix that in turn self-organizes in columnar hexagonal crystalline domains regardless of the enantiomeric purity of the perylene bisimide. We show that both homochiral and racemic perylene bisimide compounds, including a mixture of 21 diastereomers that cannot be deracemized at the molecular level, self-organize to form single-handed helical assemblies with identical single-crystal-like order. We propose that this high crystalline order is generated via a cogwheel mechanism that disregards the chirality of the self-assembling building blocks. We anticipate that this mechanism will facilitate access to previously inaccessible complex crystalline systems from racemic and homochiral building blocks.

Increasing 3D Supramolecular Order by Decreasing Molecular Order. A Comparative Study of Helical Assemblies of Dendronized Nonchlorinated and Tetrachlorinated Perylene Bisimides.

A nonplanar, twisted, and flexible tetrachlorinated perylene bisimide (Cl4PBI) was functionalized with two AB3 minidendrons containing hydrogenated or semifluorinated dodecyl groups. The hydrogenated dendron was attached to the imide groups of Cl4PBI via m = 0, 1, and 2 methylenic units, whereas the dendron containing semifluorinated groups was attached via m = 3 or a di(ethylene oxide) linker (m = 2EO). The supramolecular structures of these compounds, determined by a combination of differential scanning calorimetry, X-ray diffraction, and solid-state NMR, were compared with those of nonchlorinated planar and rigid PBI reported previously, which demonstrated the thermodynamically controlled formation of 2D periodic arrays at high temperatures and 3D arrays at low temperatures. The molecularly less ordered Cl4PBI containing hydrogenated dendrons self-organize into exclusively 3D crystalline periodic arrays under thermodynamic control for m = 0 and 2, while the more highly molecularly ordered PBI produced less stable and ordered 3D crystals and also 2D assemblies. This induction of a higher degree of 3D order in supramolecular assemblies of the less well-ordered molecular building blocks was unanticipated. The semifluorinated dendronized Cl4PBI with m = 3 formed a 2D columnar hexagonal array under kinetic control, whereas the compound with m = 2EO formed an unusual 2D honeycomb-like hexagonal phase under thermodynamic control. These Cl4PBI compounds provide a new route to stable crystalline assemblies via thermodynamic control at lower temperatures than previously obtained with PBI, thus generating 3D order in an accessible range of temperature of interest for structural analysis and for technological applications.

Complex columnar hexagonal polymorphism in supramolecular assemblies of a semifluorinated electron-accepting naphthalene bisimide.

Simple synthetic methods for a strongly electron-accepting naphthalene bisimide (NBI) derivative functionalized with a new environmentally friendly chiral racemic semifluorinated alkyl group and with AB3 minidendrons containing the same semifluorinated group are reported. The semifluorinated dendron was attached to the imide groups of the NBI via one, two, and three (m = 1, 2, 3) methylenic units. The NBI-containing semifluorinated groups and the dendronized NBI with m = 1 and 2 self-organize into lamellar crystals. The dendronized NBI with m = 3 self-assembles into an unprecedentedly complex and ordered column that self-organizes in a columnar hexagonal periodic array. This array undergoes a continuous transition to a columnar hexagonal superlattice that does not display a first-order phase transition during analysis by differential scanning calorimetry at heating and cooling rates of 10 and 1 °C/min. These complex columnar hexagonal periodic arrays with intramolecular order could be elucidated only by a combination of powder and fiber X-ray diffraction studies and solid-state NMR experiments. The lamellar crystals self-organized from m = 1 and the two highly ordered columnar hexagonal periodic arrays of m = 3 are assembled via thermodynamically controlled processes. Since strongly electron-accepting derivatives are of great interest to replace fullerene acceptors in organic photovoltaics and for other supramolecular electronic materials, the multitechnique structural analysis methodology elaborated here must be taken into consideration in all related studies.

Self-organisation of dodeca-dendronized fullerene into supramolecular discs and helical columns containing a nanowire-like core.

Twelve chiral and achiral self-assembling dendrons have been grafted onto a [60]fullerene hexa-adduct core by copper-catalyzed alkyne azide "click" cycloaddition. The structure adopted by these compounds was determined by the self-assembling peripheral dendrons. These twelve dendrons mediate the self-organisation of the dendronized [60]fullerene into a disc-shaped structure containing the [60]fullerene in the centre. The fullerene-containing discs self-organise into helical supramolecular columns with a fullerene nanowire-like core, forming a 2D columnar hexagonal periodic array. These unprecedented supramolecular structures and their assemblies are expected to provide new developments in chiral complex molecular systems and their application to organic electronics and solar cells.

Modular synthesis of amphiphilic Janus glycodendrimers and their self-assembly into glycodendrimersomes and other complex architectures with bioactivity to biomedically relevant lectins.

The modular synthesis of 7 libraries containing 51 self-assembling amphiphilic Janus dendrimers with the monosaccharides D-mannose and D-galactose and the disaccharide D-lactose in their hydrophilic part is reported. These unprecedented sugar-containing dendrimers are named amphiphilic Janus glycodendrimers. Their self-assembly by simple injection of THF or ethanol solution into water or buffer and by hydration was analyzed by a combination of methods including dynamic light scattering, confocal microscopy, cryogenic transmission electron microscopy, Fourier transform analysis, and micropipet-aspiration experiments to assess mechanical properties. These libraries revealed a diversity of hard and soft assemblies, including unilamellar spherical, polygonal, and tubular vesicles denoted glycodendrimersomes, aggregates of Janus glycodendrimers and rodlike micelles named glycodendrimer aggregates and glycodendrimermicelles, cubosomes denoted glycodendrimercubosomes, and solid lamellae. These assemblies are stable over time in water and in buffer, exhibit narrow molecular-weight distribution, and display dimensions that are programmable by the concentration of the solution from which they are injected. This study elaborated the molecular principles leading to single-type soft glycodendrimersomes assembled from amphiphilic Janus glycodendrimers. The multivalency of glycodendrimersomes with different sizes and their ligand bioactivity were demonstrated by selective agglutination with a diversity of sugar-binding protein receptors such as the plant lectins concanavalin A and the highly toxic mistletoe Viscum album L. agglutinin, the bacterial lectin PA-IL from Pseudomonas aeruginosa, and, of special biomedical relevance, human adhesion/growth-regulatory galectin-3 and galectin-4. These results demonstrated the candidacy of glycodendrimersomes as new mimics of biological membranes with programmable glycan ligand presentations, as supramolecular lectin blockers, vaccines, and targeted delivery devices.

Transformation from kinetically into thermodynamically controlled self-organization of complex helical columns with 3D periodicity assembled from dendronized perylene bisimides.

The dendronized perylene 3,4:9,10-tetracarboxylic acid bisimide (PBI), (3,4,5)12G1-1-PBI, was reported by our laboratory to self-assemble into complex helical columns containing dimers of dendronized PBI with one molecule in each stratum, with different intra- and interdimer rotation angles but identical intra- and interdimer distance of 3.5 Å, exhibiting a four-strata 2(1) helical repeat. A thermodynamically controlled 2D columnar hexagonal phase with short-range intracolumnar order represents the thermodynamic product at high temperature, while a kinetically controlled monoclinic columnar array with 3D periodicity is the thermodynamic product at low temperature. With heating and cooling rates higher than 10 °C/min to 1 °C/min, at low temperature the 2D columnar periodic array is the kinetic product for this dendronized PBI. Here the synthesis and structural analysis of a library of (3,4,5)nG1-m-PBI with n = 12 to 6 and m = 1 are reported. A combination of differential scanning calorimetry, X-ray diffraction on powder and orientated fibers, including pattern simulation and electron density map reconstruction, and solid-state NMR, all as a function of temperature and heating and cooling rate, was employed for their structural analysis. It was discovered that at low temperature the as-prepared n = 12 to 10 exhibit a 3D layered array that transforms irreversibly into columnar periodicities during heating and cooling. Also the kinetically controlled 3D columnar phase of n = 12 becomes thermodynamically controlled for n = 10, 9, 8, 7, and 6. This unprecedented transformation is expected to facilitate the design of functions from dendronized PBI and other self-assembling building blocks.

Self-organizable vesicular columns assembled from polymers dendronized with semifluorinated Janus dendrimers act as reverse thermal actuators.

The synthesis and structural analysis of polymers dendronized with self-assembling Janus dendrimers containing one fluorinated and one hydrogenated dendrons are reported. Janus dendrimers were attached to the polymer backbone both from the hydrogenated and from the fluorinated parts of the Janus dendrimer. Structural analysis of these dendronized polymers and of their precursors by a combination of differential scanning calorimetry, X-ray diffraction experiments on powder and oriented fibers, and electron density maps have demonstrated that in both cases the dendronized polymer consists of a vesicular columnar structure containing fluorinated alkyl groups on its periphery. This vesicular columnar structure is generated by a mechanism that involves the intramolecular assembly of the Janus dendrimers into tapered dendrons followed by the intramolecular self-assembly of the resulting dendronized polymer in a vesicular column. By contrast with conventional polymers dendronized with self-assembling tapered dendrons this new class of dendronized polymers acts as thermal actuators that decrease the length of the supramolecular column when the temperature is increased and therefore, are called reverse thermal actuators. A mechanism for this reversed process was proposed.

Predicting the size and properties of dendrimersomes from the lamellar structure of their amphiphilic Janus dendrimers.

Dendrimersomes are stable, monodisperse unilamellar vesicles self-assembled in water from amphiphilic Janus dendrimers. Their size, stability, and membrane structure are determined by the chemical structure of Janus dendrimer and the method of self-assembly. Comparative analysis of the periodic arrays in bulk and dendrimersomes assembled by ethanol injection in water of 11 libraries containing 108 Janus dendrimers is reported. Analysis in bulk and in water was performed by differential scanning calorimetry, X-ray diffraction, dynamic light scattering, and cryo-TEM. An inverse proportionality between size, stability, mechanical properties of dendrimersomes, and thickness of their membrane was discovered. This dependence was explained by the tendency of alkyl chains forming the hydrophobic part of the dendrimersome to produce the same local packing density regardless of the branching pattern from the hydrophobic part of the dendrimer. For the same hydrophobic alkyl chain length, the largest, toughest, and most stable dendrimersomes are those with the thinnest membrane that results from the interdigitation of the alkyl groups of the Janus dendrimer. A simplified spherical-shell model of the dendrimersome was used to demonstrate the direct correlation between the concentration of Janus dendrimer in water, c, and the size of self-assembled dendrimersome. This concentration-size dependence demonstrates that the mass of the vesicle membrane is proportional with c. A methodology to predict the size of the dendrimersome based on this correlation was developed. This methodology explains the inverse proportionality between the size of dendrimersome and its membrane thickness, and provides a good agreement between the experimental and predicted size of dendrimersome.