Rapid Self-Healing and Thixotropic Organogelation of Amphiphilic Oleanolic Acid–Spermine Conjugates

Abstract

Natural and abundant plant triterpenoids are attractive starting materials for the synthesis of conformationally rigid and chiral building blocks for functional soft materials. Here, we report the rational design of three oleanolic acid–triazole–spermine conjugates, containing either one or two spermine units in the target molecules, using the Cu­(I)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction. The resulting amphiphile-like molecules 2 and 3, bearing just one spermine unit in the respective molecules, self-assemble into highly entangled fibrous networks leading to gelation at a concentration as low as 0.5% in alcoholic solvents. Using step-strain rheological measurements, we show rapid self-recovery (up to 96% of the initial storage modulus) and sol ⇔ gel transition under several cycles. Interestingly, rheological flow curves reveal the thixotropic behavior of the gels. To the best of our knowledge, this kind of behavior was not shown in the literature before, neither for a triterpenoid nor for its derivatives. Conjugate 4, having a bolaamphiphile-like structure, was found to be a nongelator. Our results indicate that the position and number of spermine units alter the gelation properties, gel strength, and their self-assembly behavior. Preliminary cytotoxicity studies of the target compounds 2–4 in four human cancer cell lines suggest that the position and number of spermine units affect the biological activity. Our results also encourage exploring other triterpenoids and their derivatives as sustainable, renewable, and biologically active building blocks for multifunctional soft organic nanomaterials.

Triterpenoid–PEG Ribbons Targeting Selectivity in Pharmacological Effects

“…The target compounds were tested to show their ability to form supramolecular gels. This investigation was made because we have found a relationship between cytotoxicity and the ability of compounds to form supramolecular aggregates capable of affecting cytotoxicity [43,47], and similar results have recently been published by other authors [48,49]. Among the studied series of compounds, the only 4c, 6c, and 6d produced a gel in glycerol; 8a produced a gel in ethylene glycol (Supplementary material, Figure S1).…”

“…Supplementary Material, Table S1). We had already observed such behavior in the investigation of cytotoxicity of another series of triterpenoid-based compounds [43,47]. The highest inhibition activity for S. aureus was observed when it is treated with 8a, which is a dimer-like molecular ribbon based on 1a.…”

“…Synthesis of propargyl ester of the starting triterpenoid (1c) was made by a substitution reaction of the carboxyl group of 1c with propargylic bromide in DMF in the presence of potassium carbonate [47]. Compound 2c was prepared using the procedure D (Scheme 2).…”

Novel Oleanolic Acid-Tryptamine and -Fluorotryptamine Amides: From Adaptogens to Agents Targeting In Vitro Cell Apoptosis

“…This basic investigation of supramolecular self-assembly was done because we had found a relationship between cytotoxicity and ability of compounds to form supramolecular aggregates capable of affecting cytotoxicity [ 10 , 35 ]. Similar results have recently been published by other authors [ 40 , 41 ].…”

“…Recently, several review papers have been published in pentacyclic triterpenoids and their structural modifications, including those resulting in the investigation of novel nitrogen-containing compounds [ 28 , 29 , 30 , 31 , 32 ]. However, neither of those review articles [ 28 , 29 , 30 , 31 , 32 ], nor any of the recent research papers [ 33 , 34 , 35 ] have dealt with tryptamine or fluorotryptamine derivatives of oleanolic acid that are the topic of this article as newly designed compounds.…”