Emad Aqad

Self-Assembly of Janus Dendrimers into Uniform Dendrimersomes and Other Complex Architectures

Janus Drug Delivery Vehicle Efficient drug delivery vehicles need to be produced in a limited size range and with uniform size distribution. The self-assembly of traditional small-molecule and polymeric amphiphiles has led to the production of micelles, liposomes, polymeric micelles, and polymersomes for use in drug delivery applications. Now, Percec et al. (p. 1009) describe the self-assembly of Janus-type (i.e., two-headed) dendrimers to produce monodisperse supramolecular constructs, termed “dendrimersomes,” and other complex architectures. The structures, which showed long-term stability as well as very narrow size distributions, were easily produced by the injection of an ethanolic solution of the dendrimer into water. The dendrimersomes could be loaded with the anticancer drug doxorubicin and exhibited controlled drug release with changing pH. Amphiphilic, spherically shaped polymers self-assemble into larger hollow complexes that could be used for drug delivery. Self-assembled nanostructures obtained from natural and synthetic amphiphiles serve as mimics of biological membranes and enable the delivery of drugs, proteins, genes, and imaging agents. Yet the precise molecular arrangements demanded by these functions are difficult to achieve. Libraries of amphiphilic Janus dendrimers, prepared by facile coupling of tailored hydrophilic and hydrophobic branched segments, have been screened by cryogenic transmission electron microscopy, revealing a rich palette of morphologies in water, including vesicles, denoted dendrimersomes, cubosomes, disks, tubular vesicles, and helical ribbons. Dendrimersomes marry the stability and mechanical strength obtainable from polymersomes with the biological function of stabilized phospholipid liposomes, plus superior uniformity of size, ease of formation, and chemical functionalization. This modular synthesis strategy provides access to systematic tuning of molecular structure and of self-assembled architecture.

Self-Assembly of Dendronized Perylene Bisimides into Complex Helical Columns

The synthesis of perylene 3,4:9,10-tetracarboxylic acid bisimides (PBIs) dendronized with first-generation dendrons containing 0 to 4 methylenic units (m) between the imide group and the dendron, (3,4,5)12G1-m-PBI, is reported. Structural analysis of their self-organized arrays by DSC, X-ray diffraction, molecular modeling, and solid-state (1)H NMR was carried out on oriented samples with heating and cooling rates of 20 to 0.2 °C/min. At high temperature, (3,4,5)12G1-m-PBI self-assemble into 2D-hexagonal columnar phases with intracolumnar order. At low temperature, they form orthorhombic (m = 0, 2, 3, 4) and monoclinic (m = 1) columnar arrays with 3D periodicity. The orthorhombic phase has symmetry close to hexagonal. For m = 0, 2, 3, 4 ,they consist of tetramers as basic units. The tetramers contain a pair of two molecules arranged side by side and another pair in the next stratum of the column, turned upside-down and rotated around the column axis at different angles for different m. In contrast, for m = 1, there is only one molecule in each stratum, with a four-strata 2(1) helical repeat. All molecules face up in one column, and down in the second column, of the monoclinic cell. This allows close and extended π-stacking, unlike in the disruptive up-down alteration from the case of m = 0, 2, 3, 4. Most of the 3D structures were observed only by cooling at rates of 1 °C/min or less. This complex helical self-assembly is representative for other classes of dendronized PBIs investigated for organic electronics and solar cells.

Self-Repairing Complex Helical Columns Generated via Kinetically Controlled Self-Assembly of Dendronized Perylene Bisimides

The dendronized perylene 3,4:9,10-tetracarboxylic acid bisimide (PBI), (3,4,5)12G1-3-PBI, was recently reported to self-assemble in complex helical columns containing tetramers of PBI as basic repeat unit. These tetramers contain a pair of two molecules arranged side-by-side and another pair in the next stratum of the column turned upside-down and rotated around the column axis. Intra- and intertetramer rotation angles and stacking distances are different. At high temperature, (3,4,5)12G1-3-PBI self-assembles via a thermodynamically controlled process in a 2D hexagonal columnar phase while at low temperature in a 3D orthorhombic columnar array via a kinetically controlled process. Here, we report the synthesis and structural analysis, by a combination of differential scanning calorimetry, X-ray and electron diffraction, and solid-state NMR performed at different temperatures, on the supramolecular structures generated by a library of (3,4,5)nG1-3-PBI with n = 14-4. For n = 11-8, the kinetically controlled self-assembly from low temperature changes in a thermodynamically controlled process, while the orthorhombic columnar array for n = 9 and 8 transforms from the thermodynamic product into the kinetic product. The new thermodynamic product at low temperature for n = 9, 8 is a self-repaired helical column with an intra- and intertetramer distance of 3.5 Å forming a 3D monoclinic periodic array via a kinetically controlled self-assembly process. The complex dynamic process leading to this reorganization was elucidated by solid-state NMR and X-ray diffraction. This discovery is important for the field of self-assembly and for the molecular design of supramolecular electronics and solar cell.

Long-range electron transport in a self-organizing n-type organic material

Nondispersive time-of-flight electron transport has been observed in a self-organizing perylene diimide derivative, (3,4,5Pr)12G1-3-perylenetetracarboxyldiimide, yielding long-range transport mechanisms that correlate with molecular packing in several structural phases. The consistency of temperature and electric field dependences of electron mobility in the isotropic and columnar Φh1 phases with static rather than dynamic disorder formalisms provides a link between molecular packing, energetic and positional disorders, and magnitudes of mobility.

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.

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.

Losing supramolecular orientational memory via self-organization of a misfolded secondary structure

Supramolecular orientational memory (SOM) provides a route to otherwise inaccessible nanoscale architectures for certain molecules. In these privileged cases, columnar domains organized from self-assembling dendrons undergo reorientation during heating to, and subsequent cooling from, a 3D phase composed of “spheres”, such as a body-centered cubic phase or a Pmn cubic phase, known also as Frank-Kasper A15. The directions of the reoriented columns preserve key interactions from the preceding cubic phase. However, SOM was observed so far in a very limited number of assemblies. The molecular determinants enabling SOM, and its generality, remain poorly understood. Here we report the synthesis and structural and retrostructural analysis of a perylene bisimide (PBI) with two self-assembling benzyl ether dendrons, 3,5-G2-PBI, and compare its assemblies with those of a previously reported PBI, 3,4,5-G2-PBI, which exhibits SOM and has an additional minidendritic building block in its dendrons. The removal of this minidendron in 3,5-G2-PBI eliminates its ability to self-assemble into supramolecular spheres and organize into a cubic phase, thereby precluding 3,5-G2-PBI from exhibiting SOM. This finding demonstrates hierarchical transfer of structural information from primary structure to material function, analogous to the misfolding of proteins into toxic structures such as those implicated in Alzheimers and Prion diseases. The concepts exemplified here provide new insights into the hierarchical basis for SOM and will aid in the translation of the SOM concept to a broader diversity of soft matter such as block copolymers and surfactants.