Synthesis Of Low-Molecular-Weight Gelators Based On Dipeptides And Cyclic Dipeptides And Investigation Into Their Gelation Properties

The low-molecular-weight gelators(LMWGs)rely on their own self-assembly into supramolecular network to capture a vast amount of solvent molecules to form fibrous 3D organo-and hydrogels via the inherent noncovalent interactions,such as van der Waals interactions,?-? stacking,hydrogen bonding,and electrostatic interactions.Significantly those physical intermolecular associations also endow the resulting gels with the fascinating stimuli-responsibility,such as p H value,thermal stimulus,enzyme,ultrasound and so on.Therefore,LMWGs have shown the great potential applications in the area such as nanofabrication,tissue engineering,sensing,and sewage treatments.Cyclic dipeptide(DKP)derivatives with outstanding structural variety,good biological compatibility and preferred intermolecular hydrogen bonding interaction become ideal LMWG candidates.To this end,research toward synthesis and characterization of cyclc dipeptides-based LMWGs was undertaken as follows.Firstly,a series of symmetrical peptidomimetics based on cysteine-modified cyclo(L-Lys-L-Lys)s were synthesized,and their gelation capability in organic solvents was dominated by Fmoc and the exchange of thiol-to-disulfide.The self-assembled fibrillar networks were distinctly evidenced in the organogels by TEM and SEM observations.FT-IR,fluorescence analyses and CD measurements revealed that the hydrogen bonding and ?-?stacking play as major driving forces for the self-assembly of these organogelators.Two organogelators could selectively gelate common chlorinated organic solvents from their mixture with water,and the xerogel could high efficiently adsorb tested dyes from aqueous solutions.Then,four L-Lys-L-Glu dipeptide derivatives were synthesized and they can not only give rise to thermo-reversible gels in a variety of organic solvents,but also create translucent gels under sonication.The gelation testing results suggested that Fmoc groups in the same molecule are indeed more advantageous over Boc group to boost the reorganization and self-assembly of LMWGs.Compared to the routine heating-cooling protocol,the ultrasound treatment substantially brought down the MGCs of the resulting organogels and affected the micromorphology.Moreover,the ultrasound-triggered organogels of the individual lysine protected with Fmoc exhibited the thixotropic property.Upon imposing a mechanical shear,its gels with the fibrous 3D network structure were unraveled into sols caused by the disruption of hydrogen bonds between the acyclic dimers of carboxylic acids and the intermolecular forces between the alkyl chains under the mechanical shearing.However,these sols returned to the gels after standing quiescently over time.Cyclo(L-Lys-L-Glu)s were obtained by one-pot deprotection and cyclization of L-Lys-L-Glu dipeptide.By altering either the hydrophilic functionalized groups or the hydrophobic protecting groups of the cyclic dipeptide gelators,the gelator bearing a Fmoc and carboxylic acid displayed a robust hydrogelation capability in PBS.The XRD studies showed the existence of interdigitated bilayers in the hydroxerogel,and cytotoxicity assay implied their aqueous solutions are biocompatible in the case of low concentration.Interestingly,a spontaneous chemical reaction proceeded in the organogel obtained from gelator with OtBu in acetone exhibiting visual color alteration due to the formation of Schiff base.To reveal the solvent effect on the gelation properties of gelators,Hansen solubility parameters were used and estimated by Stefanis? group contribution method toward 78 selected cyclic dipeptide derivatives obtained in our and other groups.The one-dimensional model,Teas plot model and Hansen space models were examined and discussed.These models could provide a guide for the development of new supramolecular gel systems of cyclic dipeptide and other dipeptide derivatives.