Bolaform homodiamides of N-protected alanines as efficient and versatile sono- and thermo-gelators offering phase-selectivity, optical-transparency and enzyme-assisted release

Abstract

We report a series of bolaform homodiamides of N-protected alanines that exhibit efficient thermo-reversible gelation of a broad variety of solvents. Gelation of these solvents upon bath-sonication was also achieved. Overall superior gelation profiles were exhibited by gelators in which the aromatic moiety was bonded to the N-terminus of the alanine by amide bonds (rather than by carbamate bonds). Rigidification of aggressive, hydrogen-bonding solvents such as small-chain alcohols and alcohol–water mixtures was also achieved by these amide-gelators. AFM of chirally-pure samples showed the presence of nanofibers exhibiting helicity. The contributions of inter-molecular hydrogen bonding as well as π-stacking to the self-assembly of these gelators were assessed by variable-temperature NMR and UV-vis studies. FTIR data indicated the extensive propensity of these gelators to form β-sheet-like assemblies. Phase-selective gelation, even in the presence of salts in the aqueous layer, could be achieved – both by thermal processing as well as by bath-sonication at room temperature. The ability to achieve phase-selective gelation by sonication at ambient conditions opens new avenues for spill-control applications. Entrapment of tetracycline and its papain-assisted release was demonstrated to exemplify the potential utility of these gels in drug-delivery applications.