A Review of Chitin Solvents and Their Dissolution Mechanisms

Chitin is an abundant natural nitrogen-containing biopolymer with great application potential in materials, environment, energy, and health. However, the structure characteristics and processing technologies have required intense research in related applications. In particular, there have been great efforts to developing solvents for chitin, and the results so far are quite encouraging. This review summarizes the main solvent systems used for chitin, namely the aqueous solvent systems (mineral acids, inorganic salt aqueous solutions, alkali aqueous solutions) and non-aqueous ones (LiCl-dimethylacetamide solvents, CaCl2·2H2O saturated methanol, ionic liquids, deep eutectic solvents, and protic organic solvents). The solvent properties, dissolution methods, and solution properties are discussed in detail. Special attention is paid to the dissolution mechanism in each system. This review can provide a reference for understanding the dissolution behavior of chitin and finding suitable solvents for it.


INTRODUCTION
Chitin, which is composed of β-(1-4)-linked 2-acetamido-2deoxy-D-glucose, is the most abundant biopolymer after cellulose ( Fig. 1). [1] It can be found in crustaceans, mollusks, algae, fungi, and insects. [2,3] The annual production of crustaceans and mollusks around the world is about 7.86 million and 17.14 million tonnes, respectively, and most of it takes place in Asia (7.06 and 15.84 million tonnes). [4] The discovery of chitin dates from 1799, when Hatchett decalcified shells of crabs, lobsters, prawns, and crayfish with mineral acids. [5] In 1963, it was determined that crystalline chitin exists in three distinct forms, the α-, β-, and γ-form; [6] and the crystalline structures of α-and β-chitin were refined in 1980. [7] Recently, more accurate crystalline structures (1 Å resolution) of α-chitin [8] and β-chitin [9] and their hydrogen bonding network structures were determined (Fig. 2). [8,10] From the perspective of sustainable chemistry and marine economy, the exploitation of chitin as a high-value material has attracted growing interest [1,11−15] due to its good biological function, biocompatibility, and biodegradability. [5,16] In the area of advanced materials, chitin is typically used to fabricate chitin nanocrystals, chitin nanofibers, chitin derivatives, and other chitin-based materials (such as chitin films, hydrogels, aerogels, fibers, and microspheres). [3,14,17−20] For instance, by adopting a "top-down" strategy, chitin nanofibers and chitin nanocrystals can be prepared by ultrasonic, grinding, and homogenization techniques, aided by chemical pretreatments such as acid hydrolysis, [21] 2,2,6,6-tetramethyl-1piperidinyloxy (TEMPO)-mediated oxidation, [22,23] partial deacetylation, [24] and alkali deprotonation. [25] Chitin derivatives can be prepared by chemical modification, including deacetylation, acylation, tosylation, and alkylation under heterogeneous reaction conditions. [26] The most important area is the solution processing of chitin, where chitin nanofibers and chitin nanosheets may be prepared via a "bottom-up" approach, and homogeneous chemical modification could proceed with higher efficiency and uniformity. [27,28] Besides, solution processing is more suitable for the large-scale fabrication of products with desired shapes such as films, [29−32] fibers, [33,34] gels, [17,35,36] microspheres, [37−39] and sponges. [19,40] Unfortunately, the high crystallinity and abundant hydrogen bonding network of chitin make it insoluble in most common solvents, and thus great efforts have been made to discover suitable solvent systems. The typical solvents developed for chitin are listed in Fig. 3, and the solubilities of chitin in representative solvents are given in Table 1. These solvents can be divided into aqueous and non-aqueous types, and further classified into mineral acid, inorganic salt aqueous solvent, alkali aqueous solvent, salt/organic solvent, ionic liquids (ILs), deep eutectic solvent (DES), and protic organic solvent. The history of developing chitin solvents is inspiring, and many of these systems are ingenious. This review discusses representative solvent systems in detail, with a focus on the solution properties and dissolution mechanism of each system.

Mineral Acids
The dissolution of chitin in mineral acids was first reported in 1926, when Knecht and Hibbert mentioned that the chitin films could be prepared by precipitating chitin from a cold concentrated hydrochloric acid solution. [41] Clark and Smith found that chitin could be dissolved in hydrochloric acid when the molar concentration reached 8.5 mol/L, and a much higher molar concentration was needed for sulfuric acid. [42] The decreased chain length and enhanced degree of deacetylation in chitin dissolution were suggested to increase the solubility of chitin and hinder its precipitation. Meyer and Wehrli found that chitin can be dissolved in various mineral acids (hydrochloric, sulfuric, phosphoric, and nitric acids). [43] Hackman reported that chitin could be dissolved in concentrated mineral acids such as 10 mol/L hydrochloric acid, 10.5 mol/L sulfuric acid, and 85 wt% phosphoric acid (~15 mol/L) aqueous solutions. [44] Nagasawa and co-authors found that chitin can be readily dissolved in cold concentrated sulfuric acid through stirring at −5 °C, and subsequent storage of the solution for 2 h resulted in the depolymerization and sulfation of chitin. [45] It is worth noting that the hydrolysis rate of chitin in phosphoric acid is slower than in other mineral acids, making it a suitable solvent at that time. Vincendon found that concentrated phosphoric acid can readily dissolve chitin within 20 min at room temperature under vigorous stirring. [46] The 13 C-NMR spectra of 1 wt% chitin/85 wt% H 3 PO 4 aqueous solution are shown in Fig. 4(a), and the chemical shifts of chitin are listed in Table 2. The presence of N-acetyl signals indicates that after dissolution at room temperature for 12 h in phosphoric acid, no or few N-acetyl groups were cleaved. Notably, the viscosity of the solution started to decrease after dissolution, suggesting a continuous decrease in the molecular weight of chitin (Fig. 4b). If the solutions were kept at room temperature for less than 5 h, the main chemical modification was only a small increase in the phosphorus content from 0.08 wt% to 0.17 wt%, which mainly arises from the esterification of the anomeric end-chain (Fig. 4c). [46] Wu and co-authors found the optimal ratio to dissolve chitin is 3:50 water/85 wt% phosphoric acid (V/V), and the maximum chitin solubility is 4% (W/V). [47] The degree of N-acetylation decreased from 91% in native chitin to 77%-87% in regenerated chitin, suggesting slight deacetylation in the dissolution process. The storage temperature also has a significant effect on the morphology of regenerated chitin, transforming chitin nanofibers with a diameter around 25 nm to large aggregates consisting of short  Crystalline structure of α-chitin and β-chitin. Views perpendicular to the (a) ab-and (b) bc-planes of the α-chitin structure at 100 K (Reproduced with permission from Ref. [

Inorganic Salt Aqueous Solutions
The utilization of inorganic salt aqueous solutions to dissolve chitin can be traced to the 1927 work by Weimarn, [48] who had previously worked on the dissolution of cellulose in inorganic salt aqueous solutions. [49] Other polymers like chitin, fibroin, casein, fibrin, and keratin have also been proposed to dissolve or swell in the aqueous solutions of certain inorganic salts that are capable of strong hydration, [48] such as LiSCN, LiI, LiBr, LiCl, Ca(SCN) 2 , CaI 2 , CaBr 2 , CaCl 2 , and Ca(NO 3 ) 2 . The ability to dissolve or swell chitin is ranked in the order of LiSCN > Ca(SCN) 2 > CaI 2 >    CaBr 2 > CaCl 2 ; LiSCN > LiI > LiBr > LiCl; NaSCN > NaI. The salt concentration, solution temperature, and the preparation methods of chitin were also found to affect its dissolution behaviors, although details of the dissolution process and the chitin solubility have not been revealed. Clark and Smith reported the detailed dissolution process of chitin in LiSCN aqueous solution. [42] Typically, the saturated LiSCN solution at 60 °C was chosen as chitin solvent, which can readily dissolve chitin upon heating to 95 °C. LiI can also dissolve chitin, but the dissolution rate is lower than that of LiSCN. Vincendon and co-authors found that chitin could be dissolved in fresh saturated lithium thiocyanate (LiSCN) solutions to obtain a highly viscous chitin solution (3 wt%). [50] Chemical shifts in the 13 C-NMR spectra of the chitin/LiSCN aqueous solutions are listed in Table 2. The disappearance of amide carbon signals is probably owing to the strong ionic interaction between the Li + ion and the N-acetyl group. [50] The LiSCN aqueous solution is a non-derivative solvent of chitin.
Despite the aforementioned studies, the literature on chitin/inorganic salt aqueous solutions is very limited, and the detailed dissolution mechanism has not been reported.

Alkali Aqueous Solutions
Chitin viscose was prepared through the xanthation of alkali chitin in 1972 by applying a freezing procedure similar to that for cellulose viscose. [51,52] In 1975, the dissolution of chitin in alkali aqueous solutions was reported by Sannan, Kurita, and Iwakura. [53] Chitin could be dissolved in NaOH aqueous solutions, by first immersion in a concentrated NaOH solution and then mixing with ice. According to Vårum and co-authors, a typical dissolution process was as follows. Powdered chitin was suspended in 40 wt% NaOH and kept at 4 °C for 72 h, and then the mixture was diluted to 10 wt% NaOH using crushed ice. [54] They found that 2.77 mol/L NaOH was a good solvent for chitin, and the second virial coefficients were in the range of 1 × 10 −3 -2 × 10 −3 mL·mol/g 2 . The established Mark-Houwink equation of chitin in 10 wt% NaOH is [η] = 0.10M w 0.68 (mL/g), suggesting a random-coil chain conformation in the solution state.
The dissolution process can be divided into three steps: (1) formation of chitin/alkali complex in concentrated NaOH solution, (2) freezing, (3) diluting the NaOH to a low concentration with ice. The key in this multi-step method is to control the concentration of NaOH and the temperature in the dissolution process. Feng et al. studied the structural changes of chitin in 50 wt% NaOH aqueous solution after a freeze-thaw process through X-ray diffractometry (Fig. 5). [55] An increase in the crystalline interplanar spacing of αchitin was detected after the alkali-freezing process, and the (020) crystalline plane exhibited the most prominent expansion. While developing solvents for cellulose, Zhang and co-authors found that cellulose can be rapidly dissolved in NaOH/urea and LiOH/urea aqueous solutions without using the freeze-thaw cycle. [56−58] It was proposed that the fast dynamic self-assembly of small solvent molecules and cellulose at low temperature leads to the rapid dissolution of cellulose in NaOH/urea aqueous solutions. [59] In 2007, Du and co-authors reported that chitin could be dissolved in NaOH/urea aqueous solutions after a freeze-thaw procedure. [60] Using a 10 wt% NaOH/8 wt% urea solution as solvent, a maximum solubility of 91% was reached when dissolving 2 wt% chitin (M η = 1.88 × 10 6 g·mol −1 ) at −20 °C. Cai and co-authors found that the maximum dissolution of chitin could be achieved using 11 wt% NaOH/4 wt% urea solution, [61] whereas insufficient NaOH or urea would lead to incomplete dissolution of chitin, and excessive NaOH or urea would lead to quick gelation.
Besides NaOH, LiOH and KOH have also been tested for dissolving chitin (Fig. 6). [31,62,63] The chemical shifts of chitin carbon are listed in Table 2. Cai and co-authors found that KOH/urea aqueous solution dissolved chitin under low temperature after one freeze-thaw cycle, [36,64] whereas two and three repeated freeze-thaw cycles were needed to completely dissolve α-chitin in NaOH/urea and LiOH/urea aqueous solutions, respectively. This suggests the following order for the dissolution powers alkali hydroxide/urea aqueous solvents for α-chitin: aqueous KOH/urea > NaOH/urea > LiOH/urea. Moreover, the alkali/urea aqueous solutions were shown to be non-derivatizing solvents for α-chitin.
Notably, Cai and co-authors found that the precooling KOH/urea aqueous solution with a composition of 3.5 mol·L −1 KOH/0.67 mol·L −1 urea can dissolve α-and β-chitin in minutes without freezing (Fig. 7), [31,62,63,65] and this can dramatically reduce the dissolution time and energy consumption. The high efficiency and accessibility of the KOH/urea aqueous solution are promising for the large-scale utilization of chitin. In addition, the KOH aqueous system can dissolve chitosan, the main derivative of chitin, suggesting its potential as a universal solvent system for chitin and chitosan. [66] Zhang, Xu, and co-authors evaluated the properties of chitin NaOH/urea aqueous solutions. After storage at 5 °C, there were slight loss in viscosity (~5% after 25 h) and slight loss in the degree of acetylation (~5% after 45 h). [67] The solution also displayed wormlike chain structures with a structure-sensitive parameter (ρ) > 2.0 and a persistent length of 30 nm (Figs. 8a-8d). Compared with the random-coil structure in the NaOH aqueous solutions reported by Vårum et al., [54] it was suggested that chitin chains in NaOH solutions become more rigid after introducing urea to the alkali solvent system.
The dissolution mechanism of chitin in NaOH/urea aqueous solution has also attracted considerable attention. Du and coauthors proposed that when chitin was immersed in aqueous NaOH/urea solution at room temperature, water molecules could penetrate into chitin chains with the help of NaOH. The volume expansion of the solvent molecules at the freezing point broke the inter-and intra-molecular hydrogen bonds between the chitin chains and promoted the dissolution of chitin (Fig. 8e). [60] When the treatment temperature is lower than −30 °C, the freezing and expansion processes become shorter as the temperature decreases, leading to weaker expanding effects and lower solubility. Here, urea prevents the aggregation of chitin chains and increases their stability in the aqueous solution.
Huang found that the rapid dissolution of chitin in KOH/ urea aqueous solution relies on the disruption of intra-and intermolecular hydrogen bonding by (1) the strong ion-dipole interaction between hydrated K + ions and carbonyl oxygen, (2) the hydrogen bonding interaction between hydroxyl groups and hydrated OH − ions, and (3) the weakened hydrophobic interaction between chitin chains through preferential adsorption of urea to the pyran rings of chitin. [63] Zhang, Lu, Liu, and co-authors proposed that the strong interaction between cations (Na + and K + ) and carbonyl oxygen of chitin resulted in the stronger dissolution power of NaOH and KOH as compared to LiOH (Fig. 9). [68] Zhang, Xu, and coauthors proposed that the dissolution of chitin at low temperatures is a typical enthalpy-driven process. [67] Chitin is dissolved in NaOH/urea aqueous solutions by forming a hydrogen-bonded chitin/NaOH complex, which is surrounded by the urea hydrates. This sheath-like structure leads to good solubilization of chitin (Fig. 8f). Wang, Feng, and co-authors interpreted the role of urea in a different way. [69] They found that the NaOH/D 2 O mixture was almost completely frozen at −40 °C. After adding urea, the crystallization of NaOH hydrates was depressed, resulting in a low-temperature residual liquid phase. They proposed that the dissolution of chitin occurred in this low-temperature residual liquid phase, and that the reusidual liquid phase can be enhanced in turn by the appearance of chitin.
It is worth noting that most studies on the dissolution mechanism of chitin were performed in solutions by exploring the interaction between chitin (or its model compounds) and solvents. However, changes in the aggregated structure of chitin in the whole dissolution process have not been tracked so far. Therefore, current understanding on the dissolution mechanism of chitin in solvents remains incomplete.

LiCl/DMAc
The utilization of acidic solvents has been hampered due to the quick degradation of polymer chains in them. Searching for non-degradative solvents, Austin reported in 1977 for the first time that dimethylacetamide (DMAc) and N-methylpyrrolidone (NMP) mixed with LiCl can be used as a chitin solvent. [70] Compared with the corrosive acid solvents, the LiCl/DMAc solvent provides a stable chitin solution platform for material preparation and solution characterization at ambient temperature. [ (Figs. 10a and 10b). [27] LiCl/DMAc has proven to be a powerful complex solvent system for several insoluble polymers, such as polyamide, chitin, and cellulose. The interaction between the solvent components has attracted much attention. Germain and Vincendon found that LiCl is weakly dissociated in DMAc, suggesting ion pair formation in this solvent system. [72] The weakly dissociated LiCl interacts strongly with DMAc, leading to the formation of LiCl-DMAc complex.
The molecular interaction between solvent and chitin has been characterized by nuclear magnetic resonance (NMR) techniques. Since the high viscosity of chitin LiCl/DMAc solution inevitably weakens the NMR signal, N-acetyl-D-glucosamine (GlcNAc, monomer) and methyl-β-D-chitobioside (dimer) were chosen as model compounds in place of chitin (Fig. 10c). By plotting the change of hydroxyl proton chemical shift with the LiCl concentration in DMAc, Vincendon found that there was a strong interaction between the GlcNAc labile protons and LiCl molecules at the molar ratio of 1:1. [73] Therefore, a "sandwich" structure was proposed for the interaction between GlcNAc and LiCl-DMAc (Fig. 10d). In the solution of dimer in LiCl/DMAc, the hydroxyl proton of O3H is distinguished from other labile protons by exhibiting a lower chemical shift that is also insensitive to temperature, suggesting that the O3H···O5ʹ hydrogen bonding is preserved in the solution state. [73] For the chitin/LiCl-DMAc solution, the influence of temperature on the shift of O3H labile protons shows a smaller Δδ/ΔT (1.8 × 10 −3 ppm/°C) than that of the dimer (1.25 × 10 −3 ppm/°C), suggesting stronger hydrogen bonding. Therefore, chitin dissolution was attributed to the strong in-teraction of LiCl molecule with the hydroxyl and acetamido groups in chitin, which destroys the NH···O＝C and O6H···O＝C intermolecular hydrogen bonds, allowing chitin to swell and then to dissolve in the solvent. However, the intramolecular O3H···O5ʹ hydrogen bond is unaffected by this dissolution mechanism and preserved in the solution state, leading to a stiff chain conformation. [73] Studying the viscosity behavior of chitin in LiCl/DMAc solutions, Fonseca and co-authors proposed that lithium-carbonyl complexation plays a very important role in the solubilization of chitin, similar to that for cellulose solutions in LiCl/DMAc (Fig. 10e). [74] The formation of these charged regions makes chitin behave like a polyelectrolyte. The high charge density of chitin in LiCl/DMAc solution results in a rigid, extended macromolecular chain conformation.
Notably, the LiCl/DMAc solvent system is sensitive to water, which would impair its dissolving ability. [75] Introduction of water into the organic medium could cause increased ionization, which is detrimental to the dissolution potential of the complex solvent. [72] Besides, the toxicity of Li + and DMAc limit their use in biological applications. [76,77]

Saturated CaCl 2 ·2H 2 O/Methanol
In 1995, Tokura and co-authors reported that saturated CaCl 2 ·2H 2 O methanol solution (calcium solvent) was a good chitin solvent. [78,79] In a typical dissolution process, α-chitin powder was suspended in the calcium solvent and refluxed for several hours with stirring to achieve dissolution. [80] The water content and calcium concentration are the two main factors affecting the dissolution of chitin. The optimum molar ratio between CaCl 2 and water is 1:2, the same as the composition of  that chelate formation between the calcium ions and the acetamide groups is the main driving force for the dissolution of chitin by destroying the rigid crystalline structure. The supporting experimental findings are: (1) a better solubility was observed for the reacetylated chitin than for native chitin, (2) similar solubility was also found for Nylon 6,6 and polyamide consisting of amide groups, and (3) chitin with a lower degree of acetylation showed decreased solubility. [79,80] The detailed mechanism for chitin dissolution in calcium solvent remains unknown. [81] Considering the structural similarities between Nylon 6,6 and chitin (both having amide groups and abundant intermolecular C＝O···HN hydrogen bonding), the dissolution mechanism of Nylon 6,6 in CaCl 2 / methanol solvent may be used for reference.
Sun proposed that in the CaCl 2 methanol solvent, the calcium cation and methanol form a CaCl 2 -CH 3 OH complex. [82] This complex is adsorbed on Nylon 6,6 through the hydrogen bonding of OH···O＝C. The calcium ion forms a stronger complex with the carbonyl group than with the hydroxyl group, leading to the formation of CaCl 2 -Nylon 6,6 complex and the release of methanol (Fig. 11). [82] In the dissolution process, methanol plays the role similar to a catalyst. The complexation of a Lewis acid with a Lewis base can disturb the intermolecular hydrogen bonding in polymers and promote their dissolution.
Kamide and co-authors reported that at low CaCl 2 concentrations (below 4.7 wt%), the dissociated Ca 2+ and Cl − ions strongly interact with methanol. At high CaCl 2 concentrations (40 wt%), these ions could form a [Ca(CH 3 OH) 4 ] 2+ (Cl − ) 2 complex (Fig. 12). [83] It was found that the carbonyl oxygen of Nylon 6,6 interacts with the hydroxyl protons of methanol in this complex, while the amide NH protons interact with Cl − or CH 3 OH···Cl − , suggesting strong hydrogen bonding interactions between the amide groups and the solvent complex. [83] Despite the ability to dissolve chitin, calcium solvent is not a suitable platform for homogeneous chemical modification, because a high calcium concentration would affect the functional groups of chitin. [80] Besides, the high viscosity, flammability, and volatility of the calcium solvent make it unfavourable in industrial production.

Ionic Liquids
Ionic liquids (ILs) are salts of organic cations and organic or inorganic anions that are liquid at low temperatures (< 100 °C). [84] Only certain ILs can dissolve chitin, and the representative ones are listed in Table 3. Rogers and co-authors reported the successful dissolution of cellulose in the IL 1-butyl-3-methylimidazolium chloride ([Bmim]Cl) in 2002. [85] At the same time, it was also shown that [Bmim]Cl [86,87] and 1-butyl-3-methylimidazolium acetate ([Bmim]OAc) [88] can be used for solubilization and derivatization of chitin, although the details were not given in the literature. [89] Later, Zhang and co-authors reported in 2006 that chitin could be dissolved in [Bmim]Cl at 110 °C under an inert atmosphere. [90] Wu and co-authors found that [Bmim]-OAc has better dissolving potential than [Bmim]Cl, and attributed it to the stronger hydrogen-bond accepting properties of acetate ions, which disrupts the hydrogen bonding networks in the chitin chains by depriving the proton of the amino (-NH) or hydroxyl groups. [91] Kadokawa and co-authors reported that [Bmim]Br and 1-methyl-3-propylimidazolium bromide showed no ability to dissolve chitin, whereas 1-allyl-3-methylimidazolium bromide ([Amim]Br) possessed great dissolving ability. [92] Their report suggested that the cations of ILs also have a significant effect on chitin dissolution.
Rogers and co-authors reported that 1-ethyl-3-methylimidazolium acetate ([Emim]OAc or [C 2 mim]OAc) can directly dissolve chitin with no need for deproteinization and demineralization. [93] It can be used to extract chitin directly from crustacean shells while maintaining the high molecular weight of natural chitin that is beneficial to spinning fibers  Fig. 11 Schematics of the formation of CaCl 2 -Nylon 6,6 complex (Reproduced with permission from Ref. [82]; Copyright (1994) Chinese Chemical Society, Institute of Chemistry (CAS) and Springer-Verlag GmbH Germany, a part of Springer Nature). with high strength. In addition, microwave heating (3 s pulses at full power for 2 min, with vigorous stirring between pulses) can improve the dissolution efficiency significantly, reducing the time from hours in oven heating to 2 min of microwave heating. Besides, they found that a "statistical mixture" of different ILs can demonstrate a better dissolving power than any individual ILs. [94] For example, in a "statistical mixture" of Unlike the common dissolution temperatures when using other ILs (above 100 °C), a lower temperature of 45 °C was required for [Amim]Cl to dissolve chitin. They proposed that Cl − is a weaker hydrogen bond acceptor than OAc − . A lower temperature can strengthen its hydrogen bonding accepting ability, which would improve the dissolution ability.
Kamlet and Taft et al. used the solvatochromic comparison method to probe particular solvent properties, and established a set of parameters such as α, β, and π * to describe the hydrogen-bond donor acidity, hydrogen-bond acceptor basicity, and polarity-polarizability effects, respectively. [96][97][98][99] It was shown that the Kamlet-Taft parameters α and β of ILs mainly depend on the cations and anions, respectively. [100] Ohno and co-authors found that the tris(2-hydroxyethyl) methylammonium (THEMA) type ILs with β values in the range of 0.09-0.41 were unable to dissolve chitin, while those with β = 0.52-0.67 could partially dissolve it (0.1 wt% chitin for solubility test). [101] After adding ethylenediamine (EDA), which increased the β values of the tested THEMA type ILs, complete dissolution was observed for only certain ILs ([THEMA]OAc and [THEMA]MeOSO 3 ), suggesting that the β value is an important but not the only factor governing the chitin dissolution. In addition, chitin is less soluble in ILs with higher α values, which show relatively high viscosity.
Kadokawa and co-authors used molecular dynamics (MD) simulation to evaluate the dissolution behavior of α-chitin crystal in imidazolium-based ILs. [102] The results show that the dissolution process in [Amim]Br can be described by a peeling model, namely "peeling" of chitin chains from the crystal surface via cleaving the hydrogen bonds of chitin (Fig. 13). Specifically, the Br − ions disrupt the hydrogen bonding network in chitin crystal through forming amide NH···Br -···HO hydrogen bonding to induce twisting and peeling in the chitin chains. Meanwhile, [Amim] + prevents the peeled chitin chains from going back to the crystalline phase by entering the gaps between the chains. In contrast, in ILs that are poor solvents for chitin, the peeled chains occasionally return to the crystalline phase since the cations could not occupy the gaps between chitin chains quickly enough. They found that Cl − prefers to interact with hydroxyl groups rather than amide groups, whereas Br − and OAc − are the opposite. Another important factor is the self-diffusion coefficient, which shows an inverse correlation with the viscosity. It turned out that most good solvents have a high self-diffusion coefficient, suggesting the dissolution of chitin in ILs is determined by the synergy between kinetic and thermodynamic effects. [102] Cleavage of hydrogen bonds  The toxicity and environmental impacts of ILs have generated some concern. [103] Also, the hydrolysis and flammability of ILs need to be evaluated. [104,105] It was found that the toxic effect of imidazolium ILs increases with the length of the side chain. The most promising ILs, namely [Emim]OAc with ethyl and methyl side chains, are relatively safe choices among current ILs for scale-up industrial utilization owing to their short side chains. [89,106] The strong dissolving power and ability to extract chitin directly from shrimp shells make [Emim]OAc an excellent platform for chitin isolation and processing.

Deep Eutectic Solvents
Deep eutectic solvents (DESs) are mixed liquids containing two or more compounds, with a significantly lowered melting temperature than each of the individual components. A series of DESs can be prepared by mixing quaternary ammonium salts (hydrogen bond acceptors, HBAs) with hydrogen bonding donors (HBD) such as amides, amines, alcohols, and acids. [107−109] The most investigated DES is choline chloride-urea (CCU), which is prepared by mixing choline chloride (Fig. 14a) and urea (Fig. 14b) in 1:2 molar ratio as reported by Abbott and  (Fig. 14c). [107,108,110] This complex anion is associated with the [Choline] + cation and migrates in the solution, showing a certain conductivity at room temperature similar to ILs. [107] Hunt and co-authors reported that the hydrogen-bonded urea[Choline] + complex cation (Fig.  14d)  Prasad and co-authors reported that DESs such as CCU, choline bromide-urea, chlorocholine chloride-urea, betaine hydrochloride-urea, and choline chloride-thiourea (CCT) could be used to dissolve chitin. [112,113] Typically, chitin was mixed with DES and heated under an inert atmosphere to realize dissolution. CCU and CCT are good solvents for dissolving chitin (M w = 5.22 × 10 5 g/mol) at 100 °C, with a maximum concentration of 6 wt% and 9 wt%, respectively. It was proposed that the stronger interaction between the amide groups with thiourea is responsible for the higher dissolving ability of CCT than CCU. The insolubility of chitosan in both CCT and CCU also confirms the indispensable role played by the acetamido groups of chitin. In addition, other DESs com-prised of choline chloride-ethylene glycol and choline chloride-glycerol were found ineffective for dissolving both chitin and cellulose. They attributed this to the inability of these HBD molecules to break the hydrogen bonds in chitin.
Kadokawa and co-authors prepared DES by mixing imidazolium ILs with thiourea in order to improve the chitin dissolving ability. [114]  Cl showed no improvement. It was suggested that both substituents on the imidazolium rings and the counter anions of the ILs could influence dissolution ability of the prepared DES.
The representative DES solvents of chitin are shown in Table 4. So far, their underlying dissolution mechanism has not been clarified. The hydrogen bond interaction and Lewis acid-base interaction between the DES components make this solvent system rather complicated compared to the ILs.

HFIP
Hexafluoroisopropanol (HFIP) is a fluorine-containing compound with a low boiling point, a high polarity, and strong dissolving ability for various polymers. [115] Because of the strong negative inductive effect of fluorine, the acidity (pK a = 9.3) of the hydroxyl hydrogen is strengthened significantly. Thus, HFIP is also a strong hydrogen bonding donator. Compared with other protic organic solvents of chitin such as formic acid, [50] dichloroacetic acid, trichloroacetic acid, and methanesulfonic acid, [116,117] HFIP is less degradative and corrosive. Buffington and Stevens reported the far-ultraviolet circular dichroism spectra of chitin/HFIP solution and chitin gels. [118] In the chitin HFIP solutions, the amide groups are solvated by HFIP. Removal of the HFIP-amide interaction would increase the solute-solute interaction, forming hydrogen bonding between amide groups and leading to the gelation of chitin. It was found that only the trans amide conformation would permit the amide groups to participate in two types of hydrogen bonds as both donors and acceptors, crosslinking the chitin chains and forming chitin gels.
Park and co-authors reported that α-chitin can be dissolved in HFIP for electrospinning. [119] In a typical dissolution process, chitin powder was first depolymerized to M w = 9.1 × 10 4 and then dissolved in HFIP for 3 days. The solubility of chitin is related to the molecular weight, and its maximum concentration is approximately 0.65 wt% for M w ≈ 9.1 × 10 5 and 6 wt% for M w = 9.1 × 10 4 . Rolandi and co-authors reported that β-chitin dissolved in HFIP can self-assemble to form chitin nanofibers through evaporation of the solvent. [27] Considering this fast self-assembly process, they hypothesized that HFIP had dissolved chitin through hydrogen bond disruption without itself forming any bonds with chitin, leading to the quick evaporation of solvent and the formation of chitin nanofibers through intermolecular hydrogen bonding.
HFIP has an advantage over other solvent systems in the regeneration process, in that no regeneration bath is needed when fabricating chitin nanopapers and films. [27,119] The low boiling point (58.6 °C) and thermal stability of HFIP facilitate its removal from the chitin solution. [115] The detailed dissolution mechanism of chitin in HFIP has not been reported so far, however.

CONCLUSIONS AND OUTLOOK
In this review article, we discussed past research endeavors on chitin solvents and their possible dissolution mechanisms. We can find common ground and gain insight from these solvent systems. The proposed dissolution mechanisms of chitin have focused on disrupting hydrogen bonding interactions among the amide groups and hydroxyl groups of chitin through strong hydrogen bonding and Lewis acid-base interactions between the chitin chains and solvents. Besides, additives such as urea and thiourea can help improve the dissolving power of some specific solvent systems including alkali aqueous solvents, ILs, and DESs. Results from other polymers such as polyamide and cellulose have also contributed to the development of chitin solvents. Differences in the chemical structure and the aggregated structure of these macromolecules may lead to completely different rules of dissolution, which will bring us new perspectives on the dissolution mechanism of polymers.
The mentioned solvent systems allow facile and efficient chitin processing and preparation of chitin-based functional materials. Notably, the alkali solvents are a much safer choice for chitin-based materials including fibers, films, hydrogels, aerogels, microspheres, and chitin derivatives. [14,31,36,39,61,65] The alkali can play the role of a catalyst when crosslinking chitin chains and fabricating chitin derivatives in etherification, deacetylation, and alkylation reactions. [26,36,65] The appealing bioactivity, biocompatibility, biodegradability, and mechanical property would make chitin-based materials promising in food additives, wound dressings, packaging materials, electrochemical energy materials, and flexible electronics. We believe that new techniques and theories developed in the future regarding chitin processing would deepen our comprehensive understanding on the structure and properties of biomacromolecules in general.