Facile one-pot multicomponent synthesis of peptoid based gelators as novel scaffolds for drug incorporation and pH-sensitive release.

Infections caused by bacteria are the primary cause of illness and death globally, and antibiotics are the most commonly used medications to treat them. However, there are certain inherent problems in administering these drugs without any changes to their effectiveness. In order to sustain the targeted dosage over time, the use of a biocompatible local drug delivery system using low molecular mass gelators is preferred as a potential approach to reduce its side effects. Low molecular weight organic gelators (LMWOGs) have drawn a lot of attention due to their numerous and varied applications in multiple fields. But nowadays its quite a challenging task to synthesize new types of LMWOGs that can fill the significant gap towards potential applications. In this work, we have explored a multicomponent pathway for the synthesis of a small repertoire of peptoids from simple building blocks by a one-pot Ugi reaction. A variety of novel effective low molecular weight organic gelators have been synthesized, leading to the formation of stable self-assembled aggregates in various solvents such as DMSO, aqueous DMSO, and methanol. Consequently, these aggregates give rise to the creation of organogels and organo/hydrogels. The gels have a minimum gelation concentration (MGC) of 1-2% w/v with high thermal stability. Furthermore, successful encapsulation and release of metronidazole (MZ) were achieved within the gel matrix under physiological pH conditions at 37 °C, ensuring the preservation of its structural and functional properties. The results demonstrated that the release rate of MZ from the organo/hydrogels is contingent on pH, exhibiting a gradual and regulated release in mild alkaline environments. Moreover, the devised system displayed noteworthy antimicrobial efficacy against , underscoring the potential of these novel low molecular weight organic gels (LMWOGs) as effective drug delivery systems in the pharmaceutical industry. The gel formulations exhibit biocompatibility and negligible cytotoxicity, as evidenced by cell viability studies conducted using the MTT assay.