*Article* **Neutron Total Scattering Investigation of the Dissolution Mechanism of Trehalose in Alkali/Urea Aqueous Solution**

**Changli Ma 1,2, Taisen Zuo 1,2 , Zehua Han 1,2 , Yuqing Li 1,2,3, Sabrina Gärtner 4, Huaican Chen 1,2, Wen Yin 1,2, Charles C. Han <sup>5</sup> and He Cheng 1,2,\***


**Abstract:** The atomic picture of cellulose dissolution in alkali/urea aqueous solution is still not clear. To reveal it, we use trehalose as the model molecule and total scattering as the main tool. Three kinds of alkali solution, i.e., LiOH, NaOH and KOH are compared. The most probable all-atom structures of the solution are thus obtained. The hydration shell of trehalose has a layered structure. The smaller alkali ions can penetrate into the glucose rings around oxygen atoms to form the first hydration layer. The larger urea molecules interact with hydroxide groups to form complexations. Then, the electronegative complexation can form the second hydration layer around alkali ions via electrostatic interaction. Therefore, the solubility of alkali aqueous solution for cellulose decreases with the alkali cation radius, i.e., LiOH > NaOH > KOH. Our findings are helpful for designing better green solvents for cellulose.

**Keywords:** neutron total scattering; cellulose; dissolution mechanism; layered structure; complexation

### **1. Introduction**

Cellulose is the world's most produced natural polymer, and it is a potential candidate to replace petroleum-based materials. To achieve high performance, cellulose has to be dissolved first [1].

Cellulose is difficult to dissolve. Strong inter- and intra-chain interactions prevent its structure from being deconstructed. In industry, the widely used viscose method produces a large amount of alkaline and acidic waste, carbon disulfide and hydrogen sulfide gases. It pollutes the environment. N-methylmorpholine noxide (NMMO) and ionic liquids (ILS) are environment friendly, but they have high costs [1].

Around 2000, Prof. Zhang proposed the use of precooled NaOH/LiOH urea aqueous solution to dissolve cellulose [1,2]. This solvent has the advantages of fast dissolution, low cost and low pollution and, thus, has good application prospects. Unfortunately, the solubility of cellulose in green solvent is still too low to reach the requirements of industrial production. We need to know the dissolution mechanism first to increase its solubility. Lots of methods, such as NMR, FTIR, DSC, TEM, et al., have been used. These studies qualitatively showed that cationic hydrates are more easily adsorbed around cellulose molecules to form a new, stable hydrogen bond network at low temperatures, and hydrates of urea molecules form a sheath-like inclusion complex (IC) around their periphery [3–5]. Bjorn et al. summarized the dissolution mechanism of cellulose and proposed that cellulose is amphiphilic and that hydrophobic interactions are important for its solubility [6–9]. Wolfgang et al. agreed that hydrophobic interactions are the

**Citation:** Ma, C.; Zuo, T.; Han, Z.; Li, Y.; Gärtner, S.; Chen, H.; Yin, W.; Han, C.C.; Cheng, H. Neutron Total Scattering Investigation of the Dissolution Mechanism of Trehalose in Alkali/Urea Aqueous Solution. *Molecules* **2022**, *27*, 3395. https:// doi.org/10.3390/molecules27113395

Academic Editors: Reza Haghbakhsh, Sona Raeissi and Rita Craveiro

Received: 28 April 2022 Accepted: 23 May 2022 Published: 25 May 2022

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**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

driving forces in an amorphous system, but all types of cellulose are highly crystalline so hydrogen bonds must be broken before hydrophobic interactions can be effective, and this requires a strong alkaline medium [10]. To reveal the dissolution mechanism of cellulose in alkaline/urea aqueous solution, a detailed atomic picture needs to be presented.

The combination of neutron total scattering and empirical potential structure refinement (EPSR) can observe in situ the most probable all-atom structure of the liquids [11,12]. In a previous study, we used the combined methods to study the atomic structure of trehalose in NaOH/urea aqueous solution [13]. We used trehalose as the model molecule for cellulose, because it has similar glucose rings and is one of the disaccharide molecules that has no reducibility (other binary sugars, such as cellobiose, glucose, maltose and lactose, are oxidized in the alkaline solution during neutron total scattering experiments). We found that NaOH, urea and water work cooperatively to dissolve trehalose. Na+ accumulates around electronegative oxygen atoms in the hydration shell, while urea molecules only participate in the dissolution process via Na<sup>+</sup> bridging. Additionally, we predicted that alkali with smaller ions, such as LiOH, have better solubility for cellulose.

To prove this, we further observed the microscopic dissolution pictures in two different alkali/urea aqueous solutions, i.e., LiOH and KOH. Then, we compared them with previous results in NaOH/urea aqueous solution. The hydration shell of trehalose has a layered structure; cations directly interact with the glucose rings to form the first hydration layer. It destroys their intra- and intermolecular hydrogen bonds. Thus, the smaller the radius of the cation, the easier it approaches the inside of the glucose ring. From K+ to Na<sup>+</sup> to Li+, its ability to dissolve cellulose gradually increases. Urea does not directly interact with glucose rings, and it forms strong complexations with hydroxide groups. The urea hydration complexation forms the second hydration layer via electric interaction. It prevents it from re-aggregating. Temperature effect was also investigated. The atomic structure of the solution did not change when it was cooled down to −10 ◦C (or −5 ◦C). Taking into account the fact that cellulose only dissolves in green solvent at lower temperatures, the dissolution had to be a dynamic process.
