Synthesis and Study of Molecular Assemblies Formed by 4,6-O-(2-Phenylethylidene)-Functionalized d-Glucosamine Derivatives

Abstract

Low-molecular-weight gelators are interesting small molecules with potential applications as advanced materials. Carbohydrate-based small molecular gelators are especially useful because they are derived from renewable resources and are more likely to be biocompatible and biodegradable. Various 4,6-benzylidene acetal protected α-methyl 2-d-glucosamine derivatives have been found to be effective low-molecular-weight gelators. To understand the influence of the 4,6-benzylidene acetal functional group toward molecular self-assembly and to obtain effective molecular gelators, we synthesized and analyzed a new series of d-glucosamine derivatives in which the phenyl group of the acetal is replaced by a benzyl group. The homologation of the acetal protection from aromatic to aliphatic functional groups allows us to probe the effect of increasing structural flexibility on molecular self-assembly and gelation. In this study, nine representative amides and nine urea analogs were synthesized, and their gelation properties were analyzed in a series of organic solvents and aqueous solutions. The resulting amide and urea derivatives are versatile organogelators forming gels in toluene, ethanol, isopropanol, ethylene glycol, and aqueous mixtures of organic solvents. More interestingly, the amide analogs are also effective gelators for pump oil and engine oil. NMR spectroscopy at variable temperatures was used to analyze the molecular assemblies and intermolecular forces. The selected gelators with several drug and dye molecules in DMSO and water were studied for their effectiveness of encapsulation and release of these agents.

Carbohydrate Derived Organogelators and the Corresponding Functional Gels Developed in Recent Time

“…d -glucosamine has also been used as a natural resource by Chen et al [70] for preparation of several 4,6- O -benzylidene- and alkylidene-protected amides, and their corresponding urea analogs ( 8 and 9 , Figure 7). These could gelate toluene, EtOH, iPrOH, ethylene glycol, and aqua-organic solvents.…”

“…Of the 4,6- O -benzylidene/alkylidene protected glucosamine derivatives ( 8 and 9 , Figure 7), Chen et al tested one gel in DMSO/H 2 O, formed by the 4,6- O -alkylidene protected amide containing cyclohexoyl group on the nitrogen atom ( 8 with R = C 6 H 13 ), for drug encapsulation and sustained release of chloramphenicol; the gelator concentration and gel strength have a large effect on the sustained release of the drug [70].…”

Configuration‐Controlled Crystal and/or Gel Formation of Protected d‐Glucosamines Supported by Promiscuous Interaction Surfaces and a Conformationally Heterogeneous Solution State

“…Several free -OH containing or partially protected monoand oligosaccharides as well as the fully unprotected N-Fmoca,b-d-glucosamine have been shownt of orm hydrogels. [2,[17][18][19][20][21] An ovel class of supramolecular hydrogelsw as thus established, wheret he self-association of hydrophobic( aromatic) and hydrophilic (free -OH) molecularf ragments make up the amphiphilic system in which CH-p interactions were proposed to take over the role of more conventional p-p stacking and hydrogen-bond driven associations. [17] High-resolution NMR and X-ray crystallographic data wouldhave been needed, however,t oe laborate this promisingc oncept further.…”

In situ formation of low molecular weight organogelators for slick solidification

“…Low molecular weight organogelators (LMWOs or LMOGs) are small molecules designed to form supramolecular networks on addition to oil, turning the oil into a solid gel. [1][2][3][4][5] Once gelled, the oil can then be more easily removed. This makes LMWOs of great interest in the clean-up of marine oil and fuel spills, especially close to the shoreline or on bodies of inland water.…”

“…These urea-based LMWOs have been widely characterised and explored. [1][2][3][4] The choice of nucleophilic "tail" (amine) is critical in order to impart solubility to the LMWO whilst still allowing the self-assembled structure to form. Previously, we have demonstrated a selection of p, m and o-tolyl isocyanates forming stable oil binding gels in sea water.…”