Molecular Gels for Tissue Engineering - Soft Fibrillar Materials: Fabrication and Applications - page 144

interactions and form geometrically well-designed and organized structures like
helixes and lamellar motifs [76]. Non-covalent intermolecular interactions, for
instance hydrogen bonds, hydrophobic interaction, and aromatic stacking,

serve to bridge individual nucleobases subunits together and formspatially oriented
secondary structures, which could further interact and form increasingly intricate
tertiary structures, eventually producing extended interconnected networks capable
of trapping solvents and forming gels [10]. In this section, two major types of
nucleobase-containing gelators, namely nucleobases/nucleobase-containing hybrid
biomolecules, and nucleic acid chains, will be discussed. Nucleic acid chains are
grouped in a distinct category on their own, as they are structurally more complex
than simpler nucleobase monomers and their hybrid structures, and possess some
characteristics differing from those of conventional molecular gelators.

π - π

4.4.4.1 Nucleobases and Hybrid Biomolecules Containing Nucleobases
Nucleobases are substituted heteroaromatic purines or pyrimidines. Intermolecular
non-covalent interactions that can be formed between the nucleobases are pivotal for
the self-assembly of molecular structures. The presence of multiple hydrogen bond
acceptors and donors within the nucleobases enables them to form relatively strong
and directional hydrogen bonding via not only Watson-Crick or Hoogsteen type
base pairing, but also other hydrogen bonding patterns like reverse Watson-Crick,
reverse Hoogsteen, and Wobble base pairing [77]. stacking perpendicular to

the aromatic planes of nucleobases is also important in stabilizing self-assembled
structures. In general, the stacking ability between a purine and a purine is the
highest, followed by that between a purine and a pyrimidine and lastly between
two pyrimidines [78]. There are five main types of nucleobases, namely adenine,
guanine, thymine, cytosine, and uracil. Linking the nucleobases to either a ribose or
a deoxyribose sugar unit via a

π - π

-glycosidic bond yields the nucleosides, adenosine,
guanosine, thymidine, cytidine, and uridine, respectively.
Successful gelation attempts have been observed primarily with guanosine
derivatives. The formation of G-quartet cyclic tetrameric structures, templated by
alkali metal ions, produces homogenous gels. Cyclic tetramers involving guanine
moieties are stabilized by hydrogen bonding. These quartets further assemble
into columnar stacks, aided by both

β

aromatic stacking and alkali metal ions,
and eventually orient themselves in a hexagonal arrangement to form extended
molecular networks capable of entrapping solvents [79].
Nucleosides or nucleobases can be incorporated into various other biocompatible
and biostable LMWGs, such as peptides, lipids, and steroids, to generate novel
hybrid structures with improved gelation ability. Inclusion of nucleosides or
nucleobases often enhances intermolecular interactions between the gelating
agents by providing additional hydrogen bonding and/or

π - π

aromatic stacking.
Li et al . have successfully synthesized a multifunctional and biocompatible
molecular hydrogelator consisting of nucleobases, amino acids, and glycosides
[80]. This nucleobases-amino acids-glycosides hybrid is formed by attaching a
nucleobase, which can be adenine, thymine, guanine, or cytosine, to the N terminal
and a d -glucosamine residue to the C terminal of a phenylalanine residue. The

π - π