Development of Supramolecular Organo-Gel Based on Tripeptide Skeletons

Abstract

Low molecular weight (supramolecular) gels have attracted attention in the fields of supramolecular chemistry and material chemistry over the past two decades. [1][2][3][4][5][6] The gel phase is a wettable viscoelastic physical state that shares some properties of both liquid and solid phases. Gelation occurs when self-organizing gelators produce an entangled three-dimensional network of fibers that constrains the mobility of the embedded solvent molecules. Low molecular weight gelators based on amino acids, 7-10) ureas, [11][12][13] amides, [14][15][16] and saccharides [17][18][19] have been developed, and the responses of these gels to photo irradiation, 20,21) ultrasonic frequencies, 22,23) and biologically active agents 10,24,25) have been described. However, organic reactions (covalent bond forming reactions) in the gel phase have received relatively little attention. 26,27) We are trying to develop novel organic reactions in a supramolecular gel phase using a dualfunctional molecule that is capable of catalyzing reaction as well as forming gel. In this paper, we describe the synthesis and gelation properties of several tripeptide derivatives, which form the backbone of the dual-functional molecule.N-t-Butoxycarbonyl (Boc) and O-benzyl protected tripeptide gelators, composed of Gly, Ala, and Val, were designed because this combination was previously and accidentally shown to yield interesting gelation properties.28) Twentyseven tripeptides, 1-27, based on various combinations of Gly, Ala, and Val, were synthesized by repeated condensation and deprotection in the liquid phase (Chart 1). [29][30][31] Each amino acid benzyl ester (third fragment) was reacted with a Boc-protected amino acid (second fragment) under 1-hydroxybenzotriazole hydrate (HOBt · H 2 O)/1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDAC · HCl)/triethylamine conditions in 27% to quantitative yields. The dipeptide was subsequently deprotected by removal of the Boc group in HCl/dioxane to give an O-benzyl dipeptide. A Boc-protected amino acid (first fragment) was then introduced to the dipeptide under similar conditions to afford the desired tripeptides 1-27 in yields of 15-99%.The gelation abilities of the 27 tripeptide derivatives in each of ten organic solvents (hexane, EtOAc, CHCl 3 , CH 2 Cl 2 , acetone, acetonitrile, EtOH, MeOH, toluene, and chlorobenzene) were surveyed as follows. Each tripeptide/ solvent combination was mixed in a microtube and (as appropriate) irradiated with ultrasound for 30 min at temperatures ranging from room temperature to 60°C to afford a homogeneous solution. The solutions were stored in an incubator at 20°C for 24 h. When the tube was inverted and tapped, the absence of a fluid phase was defined as a gel (transparent or opaque gel), and a crumpled jelly object was defined as a partial gel. Table 1 shows the results of the first screening and the minimum gelation concentration for those tripeptide/solvent combinations that yielded a gel.The results shown in Table 1 indicate that toluene and ...