Recently Developed Carbohydrate Based Gelators and Their Applications

Abstract

Carbohydrate based low molecular weight gelators have been an intense subject of study over the past decade. The self-assembling systems built from natural products have high significance as biocompatible materials and renewable resources. The versatile structures available from naturally existing monosaccharides have enriched the molecular libraries that can be used for the construction of gelators. The bottom-up strategy in designing low molecular weight gelators (LMWGs) for a variety of applications has been adopted by many researchers. Rational design, along with some serendipitous discoveries, has resulted in multiple classes of molecular gelators. This review covers the literature from 2017-2020 on monosaccharide based gelators, including common hexoses, pentoses, along with some disaccharides and their derivatives. The structure-based design and structure to gelation property relationships are reviewed first, followed by stimuli-responsive gelators. The last section focuses on the applications of the sugar based gelators, including their utilization in environmental remediation, ion sensing, catalysis, drug delivery and 3D-printing. We will also review the available LMWGs and their structure correlations to the desired properties for different applications. This review aims at elucidating the design principles and structural features that are pertinent to various applications and hope to provide certain guidelines for researchers that are working at the interface of chemistry, biochemistry, and materials science.

Keywords: carbohydrates; drug delivery; hydrogelators; hydrogels; metallogels; monosaccharides; organogelators; stimuli-responsive; supramolecular gels.

Figure 1

Structures of the sugar starting materials used often for designing low molecular weight gelators (LMWGs).

Figure 2

General structures of several classes of glucose ester derivatives as LMWGs [31,32], n represents the number of repeating CH₂.

Figure 3

Oxygen linked carbamate derivatives of methyl-a-D-glucopyranoside [34].

Figure 4

Structures for sugar based glycolipid derivative 10a–h [43].

Figure 5

Structures of phenyl boronic ester protected alkyl glucoside derivatives [44].

Figure 6

Sophorolipid-based gelators [46].

Figure 7

Gelators from methyl alpha-D-glucopyranoside [47].

Figure 8

Structure of glucosamine derivative 15 and dipeptoids [37].

Figure 9

Structures of carbamate derivatives of 4,6-O-benzylidene-methyl-a-D-glucosamine [34].

Figure 10

Sugar-based gelators containing amide and urea functions [33], n (in the formula) represents the number of repeating CH₂.

Figure 11

Structures of amide derivatives as organogelators and hydrogelators [42].

Figure 12

Structures of hybrid ester derivatives from N-acetyl-D-glucosamine [52].

Figure 13

Atomic force microscopy (AFM) phase images of the gels formed by: (a) compound 20c in water at 2.9 mg/mL; (b) compound 20j in DMSO/H₂O (v/v 1:2) at 1.4 mg/mL; (c) compound 20l in DMSO/H₂O (v/v 1:8) at 2.25 mg/mL with toluidine blue dye (0.031 mg/mL) entrapped. Reprinted with permission from [52]. Copyright 2020 American Chemical Society.

Figure 14

Structures of C-3 ester derivatives of the NAG headgroup [53].

Figure 15

Structures of C-3 carbamates [54], n stands for the number of repeating CH₂.

Figure 16

Scanning electron micrographs showing the morphology of two gels: (a and b) compound 22i in EtOH:H₂O (v/v 1: 1) at 2.5 mg mL⁻¹, (c and d) compound 22j in EtOH:H₂O (v/v 1: 1) at 4.0 mg mL⁻¹. Reprinted with permission from [54]. Copyright 2020 The Royal Society of Chemistry under the creative commons license.

Figure 17

Triamcinolone acetonide-based gelators with a sugar moiety [55].

Figure 18

Structures of carbohydrate amphiphiles and a peptide amphiphilic molecule [59,60].

Figure 19

Structures of D-mannose derivative 26 and several arabinose derivatives 27 [61,62].

Figure 20

Structures of novel glycosyl squaramide supramolecular gelators [63].

Figure 21

Structure of poly aryl ether glucose cored dendron-based LMWGs [64].

Figure 22

Galactonamide based gelators [65,66,67].

Figure 23

Gluconamide-based gelators [68].

Figure 24

_D-gluconic acetal-based gelators 33 and their response to different stimuli. Adapted with permission from [69]. Copyright 2016 The Royal Society of Chemistry.

Figure 25

Structures of _D-gluconic acetal-based gelators [71].

Figure 26

Chemical structures of other reported D-gluconic acetal based gelators [72].

Figure 27

Structures of sorbitol diacetals 37 and monoacetals 38 [74].

Figure 28

Structures of isosorbide derivative 39 and D-mannitol derivatives 40a–b [75].

Figure 29

Xylitol based organogelators [76].

Figure 30

Structures of glucosyl triazole-based gelators [39].

Figure 31

D-glucosamine triazole derivatives synthesized by the copper (I) catalyzed azide alkyne cycloaddition reaction [36], n represents the number of CH₂ unit.

Figure 32

Structures of the benzylidene acetal protected β-triazolyl glucosides as gelators [79].

Figure 33

Structures of 4,6-O-benzylidene–galactopyranoside gelators [80].

Figure 34

Structures of a series of triazolylarabinoside derivatives [81].

Figure 35

Other gelators with a triazole backbone [40], n stands for the number of repeating CH₂.

Figure 36

Triazole linked N-acetylglucosamine-based gelators [82].

Figure 37

Uracile based glycosyl-nucleoside-lipids amphiphiles and bolaamphiphiles [83].

Figure 38

Structures of amide and urea containing bolaamphiphiles [84,85].

Figure 39

Structures of peracetylated lactosyl and maltosyl triazole derivatives [41].

Figure 40

Structures of thiolactose-based amphiphilic gelators [86], n is the number of repeating unit.

Figure 41

AFM images of a 10 mg/mL hydrogel from 62 (left, height image; right, phase image) [87].

Figure 42

Structures of several glycoclusters that are effective LMWGs [87,88].

Figure 43

(a) Structure of the trimer glycocluster 66; (b) AFM image of the gel formed by 66 in 1:2 ethanol/water (v/v); (c) A copper metallogel column formed by 66 in 1:2 ethanol/water (v/v) was transferred to a syringe, which was used as a reaction vessel. This figure is adapted from [88] with modifications.

Figure 44

Cytosine and cytosine-based gelators [91,92].

Figure 45

Nucleoside derivatives based on guanosine analogs [93].

Figure 46

Cytidine- and guanosine-based nucleotide–lipids [94].

Figure 47

Structures of thymidine-based gelators [95].

Scheme 1

The synthesis and self-assembly of a nucleoside-based gelator with potassium ion [96].

Figure 48

Guanosine monophosphate and the self-assembled G-quadruplex with Ca²⁺ [97].

Figure 49

The self-assembled G-quadruplex with Fe³⁺ [97].

Figure 50

Adenosine nucleolipid derivatives 83a-d and uridine nucleolipid derivatives 84a–e [98].

Figure 51

Conjugated cytidine and ribothymidine derivatives [99].

Figure 52

5-Benzofuran and 5-benzothiophene based nucleolipid gelators derived from uracil [100].

Figure 53

Nucleosides functionalized with carbazole [101].

Figure 54

Synthetic route for the adenosine monophosphate-based gelator [102].

Figure 55

Photographs of respective gels in acidic conditions. (a) A gel formed by compound 94 in DMSO/H₂O (1:2) at 5 mg/mL. (b) A gel formed by compound 95 in DMSO/H₂O (1:2) at 5 mg/mL. Reprinted with permission from [35]. Copyright 2014 Beilstein-Institute.

Figure 56

Structures of N-alkyl-2-anilino-3-chloromaleimide (AAC) containing bola-amphiphilic glycolipids with peripheral sugar units [111].

Figure 57

Structures of sugar azobenzene-derived LMWGs [112].

Figure 58

The cis-trans isomerization of the macrocyclic compound [113].

Figure 59

Structures of light-sensitive glycosylated nucleoside-based bolaamphiphiles (GNBAs) 99–100 [114].

Figure 60

Structures of diacetylene containing glycolipids from D-glucose [30,31], n is the number of repeating CH₂.

Figure 61

The gel formed by compound 105f in ethanol at below10 mg/mL. (a) a clear solution of the heated gelator, (b) a stable gel after cooling to room temperature, (c) the gel turned blue after irradiation of UV lamp from the top of the glass vial, (d) the gel was transferred to a quartz tube and irradiated for 1 min, (e) the same gel turned dark blue after UV treatment for 3 min, (f) the red gel was obtained by heating the gel in (e). Reprinted with permission from [31]. Copyright 2011 Beilstein-Institut.

Figure 62

Optical micrographs of the ethanol gel in Figure 61 by compound 105f under bright field (a,b) and scanning electron micrograph (c). These gels were prepared by transferring the ethanol gel after UV treatment for 3 min. Reprinted with permission from [31]. Copyright 2011 Beilstein-Institut.

Figure 63

Structures of diacetylene containing amide and urea derivatives [38], n and m represent the number of repeating CH₂ unit.

Figure 64

Diacetylene and glyco-polymer-based gelators [115], n represents the number of repeating units.

Figure 65

Structures of glyconucleo-bolaamphiphiles [118].

Figure 66

Gelator precursor for β-galactosidase [119].

Figure 67

Structure of glycoconjugates 114 and 115.

Figure 68

Structures of eight glycolipids containing aliphatic tails with increasing degree of unsaturation [123].

Figure 69

Enzyme instructed self-assembly and antibacterial properties of a galactose-based gelator. Reprinted with permission from [124]. Copyright 2020 Royal Society of Chemistry under the creative commons license.

Figure 70

Enzyme instructed self-assembly of a hydrogelator and its applications. (a) Enzyme instructed self-assembly of the glycopeptide gelator forming a fibrous network within the hydrogel; (b) Impact of the hydrogel on the growth of fibroblast cells and E. coli; (c) Prospective usage of the hydrogel for wound healing applications in a mouse model. Reprinted with permission from [125]. Copyright 2019 Jon Wiley and Sons, Inc.

Figure 71

Process of solidifying and removing toluene from an oil-water mixture: (a) Aqueous biphasic mixture of toluene, dyed with Disperse Red 152; (b) Addition of the powdered gelator; (c) Instantaneous gelation of the toluene layer; (d) Removal of the solidified toluene layer; (e) Toluene gel after removal; (f) Graduated cylinder containing the recovered toluene and recovered gelator (separated by vacuum distillation). Reprinted with permission from [72]. Copyright (2020) Elsevier.

Figure 72

Structure of D-glucose acetal-based gelators 118 and 119 [129,130].

Figure 73

Sorbitol based supramolecular gelator [131].

Figure 74

Carbohydrate salt-based derivatives [132].

Figure 75

(a) Phase selective gelation (toluene/water) followed by absorption of dye from the aqueous layer; (b) UV-vis spectra of dye absorption over time; (c) Aqueous methyl violate solution (0.02 mM) (left) and the solution after the addition of a xerogel made in toluene (right); (d) Phase selective gelation of a diesel-water mixture. Reprinted with permission from [61]. Copyright 2017 John Wiley & Sons, Inc. (Hoboken, NJ, USA).

Scheme 2

Synthesis of a thiolated hyaluronic acid copolymer for drug delivery, EDCI: 1-ethyl-3-(3-dimethyllaminopropyl)carbodiimide hydrochloride, NHS: N-hydroxysuccinimide [137], n represents the number of repeating units.

Figure 76

G-Quadruplex formation of a cytidine-based gelator and its features. Reprinted with permission from [138]. Copyright 2020 American Chemical Society.

Figure 77

Gelators for antibacterial and wound healing applications [139,140,141].

Figure 78

Schematic illustration of the glycopeptide self-assembly and its utilization as a cell growth medium. Reprinted with permission from [152]. Copyright 2020 American Chemical Society.

Figure 79

(a) Apparatus setup for wet spinning gel. (b) Magnification of the coiled gel filament after extrusion, gelator solution: 4 wt % 31b solution in DMSO (50 μL min⁻¹, 20 G needle, ID 600 μm. (c) Schematic explanation of the wet spinning method. (d) Image of the DMSO jet after escaping the needle at a speed of 30 μL min⁻¹. Reprinted with permission from [66]. Copyright 2019 Royal Society of Chemistry under the creative commons license.

Figure 80

Mesitylene gels at 0.3% w/v. (a) Pieces of doped and undoped gel in alternating order; (b) Compressing the pieces to promote self-healing; (c) Rod of gel after self-healing; (d) Handheld gel rod; (e) Image showing the diffusion of the azo dye into the undoped segments of the gel rod. Reprinted with permission from [61]. Copyright 2017 John Wiley & Sons, Inc.