Sulfonamide as amide isostere for fine-tuning the gelation properties of physical gels

• Published in: RSC advances Vol. 1; no. 19; pp. 11481 - 11492
• Main Authors: Alegre-Requena, Juan V, Grijalvo, Santiago, Sampedro, Diego, Mayr, Judith, Saldías, César, Marrero-Tellado, José Juan, Eritja, Ramón, Herrera, Raquel P, Díaz, David Díaz
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 20-03-2020; The Royal Society of Chemistry
• Subjects: Antibiotics; Chemistry; Gelation; Gels; Mechanical properties; Morphology; NMR; Nuclear magnetic resonance; Sol-gel processes; Solvents; Substitutes; Sulfonamides; Supramolecular compounds; Tables (data); Transition temperature; Vancomycin
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/d0ra00943a

(
S
)-2-Stearamidopentanedioic acid (
C
18
-Glu
) is a known LMW gelator that forms supramolecular gels in a variety of solvents. In this work, we have carried out the isosteric substitution of the amide group by a sulfonamide moiety yielding the new isosteric gelator (
S
)-2-(octadecylsulfonamido)pentanedioic acid (
Sulfo-Glu
). The gelation ability and the key properties of the corresponding gels were compared in terms of gelation concentration, gel-to-sol transition temperature, mechanical properties, morphology, and gelation kinetics in several organic solvents and water. This comparison was also extended to (
S
)-2-(4-hexadecyl-1
H
-1,2,3-triazol-4-yl)pentanedioic acid (
Click-Glu
), which also constitutes an isostere of
C
18
-Glu
. The stabilizing interactions were explored through computational calculations. In general,
Sulfo-Glu
enabled the formation of non-toxic gels at lower concentrations, faster, and with higher thermal-mechanical stabilities than those obtained with the other isosteres in most solvents. Furthermore, the amide-sulfonamide isosteric substitution also influenced the morphology of the gel networks as well as the release rate of an embedded antibiotic (vancomycin) leading to antibacterial activity
in vitro
against
Staphylococcus aureus
.
Amide-sulfonamide isosteric substitution in a low-molecular-weight gelator enables fine-tuning of its gelation ability and the properties of the corresponding supramolecular gels.