answer seems to be related to the supramolecular structure of the assembly that is
based on strong nonbonding interactions, including H-bonding. As a consequence,
the homochiral derived assembly resembles an isotactic polymer, the heterochiral a
syndiotactic polymer, and the racemic an atactic polymer. As a consequence, the
homochiral assemblies are crystalline, the heterochiral assemblies are semicrystalline, and the racemic assemblies are amorphous and in solution are micellar rather
than highly ordered structures [55, 58, 113, 114]. These series of results are
discussed in more detail in other publications and provide an answer to the question
of why biological systems are homochiral: “Most probably because homochirality
provides order for free!” Self-assembling dendrons forming porous structures
without the aid of dipeptides were also discovered [122]. The replacement of the
tapered self-assembling dendron (from the dendritic dipeptide) with a conical
dendron changes the mechanism of self-assembly such that the structure changes
from a porous protein mimic to a hollow globular container that is also chiral [123].
7 Self-Assembly of Amphiphilic Janus Dendrimers into
Monodisperse and Stable Dendrimersomes
Biological membranes are self-assembled from phospholipids containing cholesterol, transmembrane proteins, glycolipids, and glycoproteins. During the 1980s I
listen repeatedly to the lectures of Ringsdorf, who was demonstrating that biological phospholipids alone do not form stable synthetic liposomes [13]. He employed
a large arsenal of methodologies for the stabilization of vesicles and liposomes
[13]. Stable vesicles and liposomes are of great interest as containers for the
delivery of drugs, nucleic acids, and proteins, and as models of contemporary and
primitive biological membranes [124, 125]. Most successful and commercially
available for the delivery of cancer drugs are the stealth liposomes elaborated by
Teresa Allen (Fig. 12) [126]. They are obtained by the co-assembly of phospholipids with poly(ethyleneoxide)-conjugated lipids and are stabilized with 50%
cholesterol. As prepared, they are polydiserse and require extensive fractionation.
Polymersomes (Fig. 12), discovered by my Penn colleague Dan Hammer [127], are
vesicles assembled from amphiphilic block copolymers.
Polymersomes are stable in time but polydisperse and require fractionation. In
addition, they are generated from block copolymers that are not always biologically
compatible and nontoxic. One day, Dan Hammer challenged our library approach
as a potential tool to solve the problem of vesicles. We synthesized 11 libraries of
the simplest possible amphiphilic Janus dendrimers and, to our surprise, most of
them self-assembled, by simple injection in water of their ethanol or THF solutions,
into stable and monodisperse vesicles that were named dendrimersomes [128].
Figure 13 shows an example of an amphiphilic Janus dendrimer library
containing 13 molecules (Fig. 13a), the cryo-TEM of the self-assembled monodisperse dendrimersomes (Fig. 13b), and the confocal microscopy photo of a giant
190
V. Percec
based on strong nonbonding interactions, including H-bonding. As a consequence,
the homochiral derived assembly resembles an isotactic polymer, the heterochiral a
syndiotactic polymer, and the racemic an atactic polymer. As a consequence, the
homochiral assemblies are crystalline, the heterochiral assemblies are semicrystalline, and the racemic assemblies are amorphous and in solution are micellar rather
than highly ordered structures [55, 58, 113, 114]. These series of results are
discussed in more detail in other publications and provide an answer to the question
of why biological systems are homochiral: “Most probably because homochirality
provides order for free!” Self-assembling dendrons forming porous structures
without the aid of dipeptides were also discovered [122]. The replacement of the
tapered self-assembling dendron (from the dendritic dipeptide) with a conical
dendron changes the mechanism of self-assembly such that the structure changes
from a porous protein mimic to a hollow globular container that is also chiral [123].
7 Self-Assembly of Amphiphilic Janus Dendrimers into
Monodisperse and Stable Dendrimersomes
Biological membranes are self-assembled from phospholipids containing cholesterol, transmembrane proteins, glycolipids, and glycoproteins. During the 1980s I
listen repeatedly to the lectures of Ringsdorf, who was demonstrating that biological phospholipids alone do not form stable synthetic liposomes [13]. He employed
a large arsenal of methodologies for the stabilization of vesicles and liposomes
[13]. Stable vesicles and liposomes are of great interest as containers for the
delivery of drugs, nucleic acids, and proteins, and as models of contemporary and
primitive biological membranes [124, 125]. Most successful and commercially
available for the delivery of cancer drugs are the stealth liposomes elaborated by
Teresa Allen (Fig. 12) [126]. They are obtained by the co-assembly of phospholipids with poly(ethyleneoxide)-conjugated lipids and are stabilized with 50%
cholesterol. As prepared, they are polydiserse and require extensive fractionation.
Polymersomes (Fig. 12), discovered by my Penn colleague Dan Hammer [127], are
vesicles assembled from amphiphilic block copolymers.
Polymersomes are stable in time but polydisperse and require fractionation. In
addition, they are generated from block copolymers that are not always biologically
compatible and nontoxic. One day, Dan Hammer challenged our library approach
as a potential tool to solve the problem of vesicles. We synthesized 11 libraries of
the simplest possible amphiphilic Janus dendrimers and, to our surprise, most of
them self-assembled, by simple injection in water of their ethanol or THF solutions,
into stable and monodisperse vesicles that were named dendrimersomes [128].
Figure 13 shows an example of an amphiphilic Janus dendrimer library
containing 13 molecules (Fig. 13a), the cryo-TEM of the self-assembled monodisperse dendrimersomes (Fig. 13b), and the confocal microscopy photo of a giant
190
V. Percec