Designing a Transparent and Fluorine Containing Hydrogel

Abstract

Physical hydrogels are supramolecular materials obtained by self-assembly of small molecules called gelators. Aromatic amino acids and small peptides containing aromatic rings are good candidates as gelators due to their ability to form weak bonds as π-π interactions and hydrogen bonds between NH and CO of the peptide chain. In this paper we show our results in the preparation of a transparent hydrogel that was obtained by self-assembly of a fluorine-containing dipeptide that relies on the additional formation of halogen bonds due to the fluorine atoms contained in the dipeptide. We used Boc-D-F2Phe-L-Oxd-OH (F2Phe = 3,4-difluorophenylalainine; Oxd = 4-methyl-5-carboxy-oxazolidin-2-one) that formed a strong and transparent hydrogel in 0.5% w/w concentration at pH = 4.2. The formation of a hydrogel made of unnatural fluorinated amino acids may be of great interest in the evaluation of patients with parkinsonian syndromes and may be used for controlled release.

Fluorine Effect in the Gelation Ability of Low Molecular Weight Gelators

“…The heterocycle D-Oxd was prepared starting from D-threonine, according to the procedure reported by Falb [41], followed by esterification with benzyl bromide. Then three molecules F0, [42] F1 and F2 [27] were prepared in multigram scale by peptide coupling between the commercially available Boc-L-F n Phe-OH (n = 0, 1, 2) with D-Oxd-OBn. Finally, to obtain the free carboxy groups, the benzyl esters were removed by hydrogenolysis (Scheme S1, for the details see Supporting Information).…”

“…It is interesting to notice that several gels (mainly in Then, the gelation ability of F0, F1 and F2 in PB (phosphate buffer) solution was tested, using as a trigger both the pH change method [39] and the addition of calcium chloride [43] (Table 2). The use of PB solution as a solvent in 0.03 or 0.06 M concentration, according to the gelator concentration, was required to avoid a high pH that favors the hydrolysis of gelators F1 and F2, as we reported in our previous paper (for details see Table S2) [27]. In both cases, the samples were dissolved in phosphate buffer solution at pH 7.4 (see section Materials and Methods for more details), as in pure water the molecules are not soluble.…”

“…To carry out the analysis of the fluorine effect, we prepared the three gelators F0 , 42 F1 and F2 27 all sharing the Boc-L-Phe-D-Oxd-OH scaffold and differing for the number of fluorine atoms on the aromatic ring.…”

“…We recently reported the gelation ability of protected and derivatized 3,4-difluorophenylalanine (F2-Phe) [ 27 ]. We compared the gelation ability of Boc-D-F 2 -Phe-OH (Boc = tert -butoxycarbonyl) with that of dipeptides where it was coupled with L-Oxd or D-Oxd (Oxd = 4-methyl-5-carboxy-oxazolidin-2-one) and we found out that Boc-D-F 2 Phe-L-Oxd-OH has the best performance among them.…”

“…To carry on this study, we compared the gelation ability of three gelators: Boc-D-Phe-L-Oxd-OH, [ 37 ] Boc-D-F 1 Phe-L-Oxd-OH and Boc-D-F 2 Phe-L-Oxd-OH [ 27 ] (Phe= phenylalanine; F 1 Phe = 4-fluorophenylalanine; F 2 Phe = 3,4-difluorophenylalanine) ( Figure 1 ). We report the preparation of gels starting from these three compounds and using several methodologies and triggers: solvent switch (from either ethanol or 2-propanol to water), pH change and calcium ions addition [ 38 , 39 , 40 ].…”