Multidrug-containing, salt-based, injectable supramolecular gels for self-delivery, cell imaging and other materials applications

Abstract

Both molecular and crystal-engineering approaches were exploited to synthesize a new class of multidrug-containing supramolecular gelators. A well-known nonsteroidal anti-inflammatory drug, namely, indomethacin, was conjugated with six different l-amino acids to generate the corresponding peptides having free carboxylic acid functionality, which reacted further with an antiviral drug, namely, amantadine, a primary amine, in 1:1 ratio to yield six primary ammonium monocarboxylate salts. Half of the synthesized salts showed gelation ability that included hydrogelation, organogelation and ambidextrous gelation. The gels were characterized by table-top and dynamic rheology and different microscopic techniques. Further insights into the gelation mechanism were obtained by temperature-dependent ¹H NMR spectroscopy, FTIR spectroscopy, photoluminescence and dynamic light scattering. Single-crystal X-ray diffraction studies on two gelator salts revealed the presence of 2D hydrogen-bonded networks. One such ambidextrous gelator (capable of gelling both pure water and methyl salicylate, which are important solvents for biological applications) was promising in both mechanical (rheoreversible and injectable) and biological (self-delivery) applications for future multidrug-containing injectable delivery vehicles.