Gelators may be divided into chemical gels and physical gels: the internal structure of chemical gels is made of chemical bonds, while physical gels are characterized by dynamic cross-links that are constantly created and broken. The gelator present in physical gels may be an inorganic or an organic compound, the latter having a molecular weight of ≤500 amu. These compounds are generally called "low molecular weight gelators" (LMWGs). In this tutorial review we want to focus our attention on short peptides or peptidomimetics that behave as LMWGs. Peptidomimetics are small protein-like molecules designed to mimic natural peptides. To efficiently design a peptidomimetic, local constraints must be introduced into the skeleton, to induce the formation of preferred secondary structures.
Some compounds containing the L‐Phe‐D‐Oxd [L‐Phe = L‐phenylalanine; D‐Oxd = (4R,5S)‐4‐carboxy‐5‐methyl oxazolidin‐2‐one] moiety have been prepared and their properties as supramolecular material have been determined. Some derivatives of the dipeptide L‐Phe‐L‐Phe (which usually forms nanotubes) and some long‐chain derivatives that behave as low‐molecular‐weight gelators have been prepared. We have also replaced the D‐Oxd moiety with a D‐Pro (D‐Pro = D‐proline) moiety to check if the presence of the Oxd moiety was essential for the existence of those materials. In contrast to the D‐Oxd‐containing compounds, no material was ever formed with any of the D‐Pro‐containing molecules. This outcome suggests that the L‐Phe‐D‐Oxd moiety may be defined as a “privileged scaffold” for the formation of supramolecular materials and it can be introduced into more complex structures to induce some selected properties in the solid state.
We have prepared a small library of 13 peptidomimetics containing the L‐Phe‐D‐Oxd unit (or the isosteric L‐Phe‐D‐pGlu unit), which is a privileged scaffold for the preparation of supramolecular materials. These compounds were prepared in solution in excellent yields and tested as organogelators and/or hydrogelators at 10 mM concentration with a plethora of solvents and solvent mixtures. Two molecules were very efficient gelators: one is a organogelator and the other is a hydrogelator. As these compounds have quite different skeletons, a rationale to explain the different behaviour of these molecules as gelators takes into consideration their hydrophobicity, expressed as log P. Finally, Fmoc‐L‐Phe‐D‐pGlu‐OH (6b) efficiently gelated phosphate‐buffered saline (PBS 1X) at 1.5 % w/w concentration and is an excellent candidate for the preparation of novel materials for applications in, for example, drug release, biological assays, and tissue engineering.
A small library of stereoisomeric pseudopeptides able to make gels in different solvents has been prepared and their attitude to make gels in the presence of several metal ions was evaluated. Four benzyl esters and four carboxylic acids, all containing a moiety of azelaic acid (a long chain dicarboxylic acid) coupled with four different pseudopeptide moieties sharing the same skeleton (a phenyl group one atom apart from the oxazolidin-2-one carboxylic group), were synthesized in solution, by standard coupling reaction. The tendency of these pseudopeptides to form gels was evaluated using the inversion test of 10 mM solutions of pure compounds and of stoichiometric mixtures of pseudopeptides and metal ions. To obtain additional information on the molecular association, the gel samples were left dry in the air to form xerogels that were further analyzed using SEM and XRD. The formation of gel containing Zn(II) or Cu(II) ions gave good results in term of incorporation of the metal ions, while the presence of Cu(I), Al(III) and Mg(II) gave less satisfactory results. This outcome is a first insight in the formation of stable LMWGs formed by stoichiometric mixtures of pseudopeptides and metal ions. Further studies will be carried out to develop similar compounds of pharmacological interest.
Foldamers are artificial molecules capable of organization into well defined secondary structures such as helixes, β sheets and turns. The essential requirement for an oligomer to qualify for inclusion in the foldamer family is to possess a well defined, repetitive secondary structure, imparted by conformational restrictions imposed by the monomeric unit. These compounds may be composed of subunits of any kind, but most of them contain unusual amino acids and/or aromatic units. We describe the synthesis, the conformation analysis and the physical properties (in the solid state) of pseudopeptide foldamers containing imido‐type functions, obtained by coupling the nitrogen of a 4‐carboxy oxazolidin‐2‐one unit with the carboxylic acid moiety of the next unit, which may be another 4‐carboxy oxazolidin‐2‐one or an amino acid. Such an imido‐type function is characterized by a nitrogen atom connected both to an endocyclic and to an exocyclic carbonyl group, and tends always to adopt the trans conformation. As a consequence of this remarkable property, which causes local constraint, these imido‐type oligomers are forced to fold in ordered conformations. In combination with interactions of other kinds (H bond, apolar interactions, etc.), these lead to the formation of supramolecular materials. The synthetic approach is highly tuneable with endless variations, so materials with required properties may be prepared “on demand”, simply by changing the design and the synthesis.
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