Low-Molecular-Weight Organo- and Hydrogelators Based on Cyclo(l-Lys-l-Glu)

Abstract

Four cyclo(l-Lys-l-Glu) derivatives (3-6) were synthesized from the coupling reaction of protecting l-lysine with l-glutamic acid followed by the cyclization, deprotection, and protection reactions. They can efficiently gelate a wide variety of organic solvents or water. Interestingly, a spontaneous chemical reaction proceeded in the organogel obtained from 3 in acetone exhibiting not only visual color alteration but also increasing mechanical strength with the progress of time due to the formation of Schiff base. Moreover, 6 bearing a carboxylic acid and Fmoc group displayed a robust hydrogelation capability in PBS solution. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) revealed the characteristic gelation morphologies of 3D fibrous network structures in the resulting organo- and hydrogels. FT-IR and fluorescence analyses indicated that the hydrogen bonding and π-π stacking play as major driving forces for the self-assembly of these cyclic dipeptides as low-molecular-weight gelators. X-ray diffraction (XRD) measurements and computer modeling provided information on the molecular packing model in the hydrogelation state of 6. A spontaneous chemical reaction proceeded in the organogel obtained from 3 in acetone exhibiting visual color alteration and increasing mechanical strength. 6 bearing an optimized balance of hydrophilicity to lipophilicity gave rise to a hydrogel in PBS with MGC at 1 mg/mL.

Spontaneous Aminolytic Cyclization and Self‐Assembly of Dipeptide Methyl Esters in Water

“…Govindaraju's group has extensively investigated their assembly, highlighting interesting properties of these systems, including the increased stability towards proteolysis. [37][38][39] Both supramolecular organogels [40] and hydrogels [41] have been reported based on these structures. Gazit and Reches demonstrated the spontaneous formation and self-assembly of surface-bound arrays of cyclic diphenylalanine peptide nanotubes using chemical vapor deposition.…”

Simple Tyrosine Derivatives Act as Low Molecular Weight Organogelators

“…The entanglement of these secondary structures eventually results in the immobilization of the solvent, which can be referred to as a gel 7 . Amino acids are versatile compounds for self-assembled structures and, therefore, have found various applications as LMWO 8–14 . However, amino acids usually suffer a lack of wide range solvent applicability or require several steps to synthesize.…”

Molecular Self‐Assembly of Cyclic Dipeptide Derivatives and Their Applications

“…Feng and co‐workers have investigated a series of bifunctional cyclo ( l ‐Lys– l ‐Glu) derivatives ( 64 – 67 , Scheme ) with various tert ‐butyl and Fmoc modifications of Glu and Lys side chains, respectively, to understand the structure–gelation relationship of CDPs . CDPs 64 , 66 and 67 exhibited good gelation propensity with a variety of alcohols and organic solvents through molecular self‐assembly.…”