elusive using conventional techniques. NCA polymerizations initiated by strong
bases are very fast. These polymerizations are poorly understood and well-defined
block copolymers cannot be prepared. Primary amine-initiated NCA polymerizations are also not free of side reactions. Even after fractionation of the crude
preparations, the resulting polypeptides are relatively ill-defined, which may
complicate unequivocal evaluation of their properties and potential applications.
Nevertheless, there are many reports on the preparation of block copolypeptides
using conventional primary amine initiators [66]. Examples include many
hydrophilic–hydrophobic and hydrophilic–hydrophobic–hydrophilic di- and triblock copolypeptides (where hydrophilic residues were glutamate and lysine,
and hydrophobic residues were leucine [67, 68], valine [69], isoleucine [16],
phenylalanine [15], and alanine [70]) prepared to study conformations of the
hydrophobic domain in aqueous solution. More recently, Cameron and coworkers
reported the synthesis of novel (α-helix)-b-(β-sheet) block copolypeptides using
amine initiation [71]. These polymers were reported to have polydispersities
ranging from 1.47 to 1.60.
The majority of amine-initiated block copolypeptides were often subjected
to only limited characterization (e.g., amino acid compositional analysis) and, as
such, their structures and the presence of homopolymer contaminants were not
conclusively determined. Some copolymers, which had been subjected to
chromatography, showed polymodal molecular weight distributions containing
substantial high and low molecular weight fractions [15]. The compositions
of these copolymers were found to be different from the initial monomer feed
compositions and varied widely for different molecular weight fractions. It appears
that most, if not all, block copolypeptides prepared using amine initiators under
conventional conditions have structures different to those than predicted by
monomer feed compositions and probably have considerable homopolymer
contamination due to the side reactions described above.
Block copolypeptides prepared via transition metal-mediated NCA polymerization are well defined, with the sequence and composition of block segments controlled by the order and quantity of monomer added to initiating species, respectively.
These block copolypeptides can be prepared with the same level of control found in
anionic and controlled radical polymerizations of vinyl monomers, which greatly
expands the potential of polypeptide materials. The unique chemistry of NCAs allows
these monomers to be polymerized in any order, which is a challenge in most vinyl
copolymerizations, and the robust chain ends allow the preparation of copolypeptides
with many block domains (e.g., >2). The robust nature of transition metal initiation
was shown by the linear, stepwise synthesis of triblock and pentablock
copolypeptides Eq. (17) [72, 73]. The N-TMS amine initiators and amine initiators
used under high vacuum and/or low temperature conditions have recently also been
used to prepare well-defined block copolypeptides [45, 63]. The self-assembly of
block copolypeptides has also been under extensive investigation in recent years,
typically in aqueous media to mimic biological conditions. In the following sections,
the assembly of block copolypeptides into different types of supramolecular assemblies is described.
Synthesis and Self-Assembly of Well-Defined Block Copolypeptides via. . .
17
bases are very fast. These polymerizations are poorly understood and well-defined
block copolymers cannot be prepared. Primary amine-initiated NCA polymerizations are also not free of side reactions. Even after fractionation of the crude
preparations, the resulting polypeptides are relatively ill-defined, which may
complicate unequivocal evaluation of their properties and potential applications.
Nevertheless, there are many reports on the preparation of block copolypeptides
using conventional primary amine initiators [66]. Examples include many
hydrophilic–hydrophobic and hydrophilic–hydrophobic–hydrophilic di- and triblock copolypeptides (where hydrophilic residues were glutamate and lysine,
and hydrophobic residues were leucine [67, 68], valine [69], isoleucine [16],
phenylalanine [15], and alanine [70]) prepared to study conformations of the
hydrophobic domain in aqueous solution. More recently, Cameron and coworkers
reported the synthesis of novel (α-helix)-b-(β-sheet) block copolypeptides using
amine initiation [71]. These polymers were reported to have polydispersities
ranging from 1.47 to 1.60.
The majority of amine-initiated block copolypeptides were often subjected
to only limited characterization (e.g., amino acid compositional analysis) and, as
such, their structures and the presence of homopolymer contaminants were not
conclusively determined. Some copolymers, which had been subjected to
chromatography, showed polymodal molecular weight distributions containing
substantial high and low molecular weight fractions [15]. The compositions
of these copolymers were found to be different from the initial monomer feed
compositions and varied widely for different molecular weight fractions. It appears
that most, if not all, block copolypeptides prepared using amine initiators under
conventional conditions have structures different to those than predicted by
monomer feed compositions and probably have considerable homopolymer
contamination due to the side reactions described above.
Block copolypeptides prepared via transition metal-mediated NCA polymerization are well defined, with the sequence and composition of block segments controlled by the order and quantity of monomer added to initiating species, respectively.
These block copolypeptides can be prepared with the same level of control found in
anionic and controlled radical polymerizations of vinyl monomers, which greatly
expands the potential of polypeptide materials. The unique chemistry of NCAs allows
these monomers to be polymerized in any order, which is a challenge in most vinyl
copolymerizations, and the robust chain ends allow the preparation of copolypeptides
with many block domains (e.g., >2). The robust nature of transition metal initiation
was shown by the linear, stepwise synthesis of triblock and pentablock
copolypeptides Eq. (17) [72, 73]. The N-TMS amine initiators and amine initiators
used under high vacuum and/or low temperature conditions have recently also been
used to prepare well-defined block copolypeptides [45, 63]. The self-assembly of
block copolypeptides has also been under extensive investigation in recent years,
typically in aqueous media to mimic biological conditions. In the following sections,
the assembly of block copolypeptides into different types of supramolecular assemblies is described.
Synthesis and Self-Assembly of Well-Defined Block Copolypeptides via. . .
17