Isomerization of various aldo-saccharides to the corresponding keto-saccharides under microwave heating using uncalcined scallop shell powder as a catalyst

Abstract

Fifty milliliters of 0.2 mol/L aqueous solutions containing two aldo-pentoses (ribose and xylose), two aldo-hexoses (glucose and galactose), and two aldo-disaccharides (cellobiose and lactose) were placed in a pressure-resistant vessel along with 0.5 g of uncalcined scallop shell powder and heated by a microwave oven at 700 W to isomerize the aldo-saccharides to the corresponding keto-saccharides (ribulose and xylulose, fructose and tagatose, and cellobiulose and lactulose). The yields of keto-saccharides were approximately 10 % for pentoses, 18 % for hexoses, and 25 % for disaccharides within 105 s. The selectivity from aldo-saccharide to the keto-saccharide followed the order of disaccharide > hexose > pentose. Measurements were taken for pH, calcium ion concentration, and absorbance at 280 nm and 420 nm. The acidic by-products formed during heating were neutralized by the shell powder, maintaining the pH of the reaction mixture above 7 to promote isomerization through Lobry de Bruyn–Alberda van Ekenstein transformation.

Introduction

Sugars that are scarce in nature are called rare sugars. Rare sugars have a sweet taste, are low in calories, and are known to have beneficial physiological functions, such as the suppression of body fat accumulation and blood glucose levels, as well as antioxidant effects (Sun et al., 2008; Bilal et al., 2018). Most of the rare sugars are keto-saccharides. The isomerization of aldo-saccharides, which are abundant in nature, to the corresponding keto-saccharides can be categorized into two methods. One is the biochemical method using microorganisms or enzymes isolated from microorganisms as catalysts (Granström et al., 2004; Zhang et al., 2017), and the other is the chemical method under alkaline conditions using sodium hydroxide, calcium hydroxide (Sowden and Schaffer, 1952; Zhao et al., 2023), or metal catalysts (Román-Leshkov et al., 2010). Biochemical methods have advantages such as high reaction selectivity and minimal by-product formation, but they require a great deal of effort to identify microorganisms and enzymes suitable as catalysts for each desired reaction. Moreover, the discovered biocatalysts are not always highly stable. Conversely, the chemical method is versatile because it can isomerize numerous saccharides, but the purification of desired keto-saccharides is expensive due to the formation of numerous by-products and, consequently, low selectivity.

Isomerization of saccharides under alkaline conditions proceeds through the well-known Lobry de Bruyn–Alberda van Ekenstein (LBAE) transformation (Sowden and Schaffer, 1952; Delidovich, 2023). We previously reported the isomerization of saccharides to their corresponding isomers in aqueous ethanol (Gao et al., 2015; Soisangwan et al., 2017) and phosphate buffer (Onishi et al., 2024; Hashimoto et al., 2024) under subcritical water conditions, which would be categorized as alkaline isomerization. In addition, we reported the isomerization of saccharides using arginine, a basic amino acid, as a catalyst (Milasing et al., 2023; Khuwijitjaru et al., 2023a) as well as the isomerization and epimerization of glucose in phosphate buffer and arginine under subcritical water conditions (Khuwijitjaru et al., 2023b). In these reaction systems, it took a long time to reach the desired reaction temperature because the substrate solution was heated through conduction heat transfer. In addition to the desired isomerization reaction, caramelization and Maillard reactions also occur during the heating process, resulting in the formation of colored substances and reducing the selectivity of the desired product.

Microwave heating is a rapid heating method that is particularly useful in aqueous systems because it is based on the motion of water molecules and charged ions induced by electromagnetic waves with frequencies in the range of 0.3 to 300 GHz (Meda et al., 2017). Microwave heating has been used to accelerate several types of chemical reactions and is recognized as a useful heating method in green chemistry (Bassyouni et al., 2012). Especially for reactions with short reaction times, microwave heating is more energy-efficient than conventional heating (Moseley and Woodman, 2009). For example, lactose was isomerized to lactulose in just 60 s in a solution adjusted to pH 9.0 with sodium hydroxide (Nooshkam and Madadlou, 2016). Conversely, Li et al. (2018) showed that microwave heating of glucose in an alkaline solution (pH 10.65) resulted in greater glucose degradation, a greater decrease in pH, and an increased absorbance at 420 nm compared to conventional heating methods.

The meat of shellfish is edible, but most of the shells are considered waste. The primary component of shells is calcium carbonate, some of which is calcined and converted to calcium oxide (quicklime) (Ferraz et al., 2019) and used as a soil conditioner. An aqueous solution of calcium carbonate is slightly alkaline. The isomerization of sugars under alkaline conditions produces acidic substances as by-products, which lower the pH and prevent the isomerization reaction from proceeding (Onishi et al., 2022). Shells or their powder containing calcium carbonate are expected to neutralize the acidic substances formed during the isomerization of saccharides, thereby preventing a significant decrease in pH. In this study, we investigated the effect of the type of aldo-saccharide used as a substrate on the yield of the corresponding keto-saccharide, the decrease in pH, and coloration due to byproducts through microwave heating in the presence of uncalcined shell powder. In addition, we measured the concentration of calcium ions (Ca²⁺) leached from the shell powder. The saccharides tested included two pentoses (ribose and xylose), two hexoses (glucose and galactose), and two disaccharides (cellobiose and lactose), with their corresponding keto-saccharides being ribulose and xylulose, fructose and tagatose, and cellobiose and lactulose, respectively.

Materials and Methods

Materials Cellobiose (practical grade), lactose monohydrate (Wako special grade), glucose (> 98.0 %), d-galactose (Wako special grade), d-xylose (Wako special grade), d-ribose (Wako special grade), acetonitrile (HPLC grade), and distilled water (HPLC grade) were purchased from FUJIFILM Wako Chemical Corp. (Osaka, Japan). The prefix, d-, representing the steric structure of saccharides is omitted hereafter. Uncalcined scallop shell powder (Powder 12) is a product of Furusato Bussan (Aomori, Japan) and will hereinafter be referred to as shell powder.

Isomerization of aldo-saccharides to the corresponding keto-saccharide by microwave heating The initial concentration of all substrates (aldo-saccharides) was fixed to be 0.2 mol/L. In a pressure-resistant vessel (inner volume 120 mL, 0.7 MPa; Fluon Industries, Tokyo, Japan) made of perfluoroalkoxy alkane with a relief valve, 50 mL of the substrate solution and 0.5 g of shell powder were combined. The vessel was then placed in a domestic microwave oven (E-701S, Yuasa Primus, Osaka, Japan), and microwave heating was performed at a constant power of 700 W. The heating time was set from 30 s to 105 s at 15-s intervals. The maximum heating time of 105 s was determined as the longest duration during which the relief valve of the pressure-resistant vessel did not operate. Following the prescribed heating period, the vessel was removed from the oven and immediately cooled to room temperature in an ice water bath. Subsequently, the reaction mixture was filtered through a membrane filter (0.2 µm pore size, DISMIC-28CP, Toyo Roshi, Tokyo, Japan). Measurements were then taken for the concentrations of remaining aldo-saccharides and their corresponding keto-saccharides, pH, and Ca²⁺ in the clear reaction solution after removal of the shell powder. The absorbance at 280 nm and 420 nm (A₂₈₀ and A₄₂₀) was measured at room temperature as an indicator of the coloration of the reaction solution.

Analysis An HPLC system, comprising a pump (LC-10AD_VP, Shimadzu Corp., Kyoto, Japan), COSMOSIL Sugar-D column (4.6 mm i.d. × 250 mm, Nacalai Tesque, Kyoto, Japan), differential refractometer (Shodex RI-101, Resonac Corp., Tokyo, Japan), and recorder (Chromatopac C-R8A, Shimadzu Corp., Kyoto, Japan), was used to measure the concentrations of saccharides in the reaction mixture. A microsyringe (701N, Hamilton, Reno, NV, USA) was used to load 5 µL of the reaction solution onto the column and eluted at a flow rate of 1.0 mL/min. The eluent was a mixture of acetonitrile and water, with volumetric contents of acetonitrile of 80 % (v/v) for lactose, glucose, and galactose as substrates, 75 % for cellobiose, 85 % for xylose, and 88 % for ribose. The pH and Ca²⁺ concentration in the reaction solution were measured using a LAQUAtwin pH meter and a LAQUAtwin calcium ion meter (Horiba Corp., Kyoto, Japan), respectively. The absorbance of the reaction solution at 280 nm and 420 nm was measured using a UV-visible spectrophotometer (UV-1280, Shimadzu Corp., Kyoto, Japan) as an indicator of the coloration of the reaction solution. All analyses were performed at room temperature.

Results and Discussion

Isomerization of aldo-saccharides to the corresponding keto-saccharides Figure 1 shows the changes over time in the fraction of remaining substrates (C_S/C_S0), the yield of the corresponding keto-saccharides (major product) (C_P/C_S0), pH, Ca²⁺ concentration, A₄₂₀, and A₂₈₀ during the isomerization of various saccharides by microwave heating using shell powder as a catalyst. The temperature change of the reaction solution during microwave heating, which was estimated by our proposed method (Khuwijitjaru et al., 2024), is shown by the thick solid curve in Fig. 1(a). The temperature of the reaction solution at a heating time of 105 s was estimated to reach 159 °C. In addition to the keto-saccharides, the major product corresponding to the substrate, other peaks were observed in the HPLC chromatogram, which were presumed to be isomers or enantiomers of the substrate or major product. However, these peaks were extremely small and could not be discussed quantitatively based on analytical precision. Therefore, we focused only on the yield of the major product.

Fig. 1

Changes over time of (a) the fraction of remaining substrate C_S/C_S0 (open symbols) and the yield of the major product C_P/C_S0 (filled symbols), (b) pH (open symbols) and calcium ion (Ca²⁺) concentration (filled symbols), and (c) absorbance at 420 nm (A₄₂₀, open symbols) and 280 nm (A₂₈₀, filled symbols) when 50 mL of 0.2 mol/L aqueous aldo-saccharide (substrate) solution and 0.5-g shell powder were placed in a pressure-resistant vessel and microwaved at 700 W. Substrates: (△, ▲) ribose, (▽, ▼) xylose, (□, ■) glucose, (○, ●) galactose, (⟡, ♦) cellobiose, and (, ) lactose. The thick solid curve in (a) shows the temperature of the reaction solution estimated by our proposed method (Khuwijitjaru et al., 2024). The dashed, solid, and dotted curves were empirically connected the plots for pentoses, hexoses and disaccharides.

With microwave heating, the temperature of the reaction solution increased over time, accelerating the decrease in the fraction of remaining substrate. Correspondingly, the yield of the product increased rapidly in the latter half of the reaction. The pressure-resistant vessel had a relief valve that operated when the internal pressure exceeded 0.7 MPa, causing the contents to spew out. This prevented measurements beyond 105 s. The decrease in the fraction of remaining substrate and increase in the yield of the product followed the order of disaccharides > hexoses > pentoses, with yields of about 25 %, 18 %, and 10 %, respectively, for keto-disaccharides, keto-hexoses, and keto-pentoses.

The pH remained constant at about 9 in the first half of the reaction but gradually decreased as the reaction progressed, approaching pH 7 in the latter half. The decrease in pH was milder and smaller than that for the isomerization of saccharides in subcritical phosphate buffer (Onishi et al., 2022). This would be due to the neutralization of acidic byproducts formed during the isomerization process by calcium carbonate, the major component of shell powder. In contrast, the calcium ion concentration increased rapidly in the latter half of the reaction. The higher the yield of keto-saccharides, the higher the Ca²⁺ concentration. This may be partly because keto-saccharides tend to form complexes with calcium ion through a ligand exchange reaction (Angyal, 1989).

A₄₂₀ and A₂₈₀ also increased rapidly in the latter half of the reaction along with the increase in temperature of the reaction solution and the Ca²⁺ concentration. However, the increases in A₄₂₀ and A₂₈₀ did not correspond to the formation of keto-saccharides or the increase in Ca²⁺ but increased rapidly after the yield of keto-saccharide reached near its maximum value. This suggests that after the yield of keto-saccharide reaches its maximum value, the by-product is converted to substances with higher absorbance. Therefore, stopping the reaction as soon as the yield reaches near the maximum value would allow a keto-saccharide solution with low coloration to be obtained at a high yield.

Selectivity in the isomerization of aldo-saccharide to the corresponding keto-saccharide Figure 2 shows the relationship between the conversion of each aldo-saccharide, 1 - C_S/C_S0, and the yield of the corresponding keto-saccharide, C_P/C_S0. The plots for each saccharide are represented by straight lines passing through the origin, and the selectivities calculated from the slopes were 0.55 for ribulose, 0.42 for xylulose, 0.74 for fructose, 0.63 for tagatose, 0.79 for cellobiulose, and 0.84 for lactulose. The selectivity follows the order of disaccharide > hexose > pentose. This trend is consistent with that previously observed for isomerization in subcritical aqueous ethanol (Gao et al., 2015). Among the tested saccharides, the selectivity of xylose was significantly low, likely because it is easily colored through the formation of many by-products at high temperatures (del Pilar Buera, 1987). The high selectivity of disaccharides may be attributed to the higher stability of 1,2-enediol, an intermediate in LBAE transformation, than that of monosaccharides, making the pathway for the formation of organic acids, etc. less likely to proceed.

Fig. 2

Selectivity in the isomerization of various aldo-saccharides to their corresponding keto-saccharides. Symbols are the same as in Fig. 1. The dashed, solid, and dotted lines represent for pentoses, hexoses and disaccharides, respectively.

Relationship between the absorbance at 280 nm and that at 420 nm Figure 3 shows the relationship between A₂₈₀ and A₄₂₀, measured as an indicator of coloration of the reaction solution. The relationship for the monosaccharides pentoses and hexoses was represented by a single curve. Conversely, the relationship for the disaccharides cellobiose and lactose was represented by a separate curve. In the coloration of saccharides, substances with absorption in the ultraviolet region are initially formed, which are further converted to a substance with absorption in the visible region, giving a brown color (Onishi et al., 2022). The fact that the relationship between A₂₈₀ and A₄₂₀ for monosaccharides was represented by a single curve suggests that monosaccharides produce colored substances through a similar reaction pathway. However, disaccharides had high absorbance at 280 nm but low absorbance at 420 nm. The observed phenomenon may be attributed to various factors. One possible explanation is that the conversion pathway from substances with absorption at 280 nm to those with absorption at 420 nm differs from that of monosaccharides. Alternatively, the absorption coefficient of the produced substances with absorbance at 420 nm could be smaller than that of monosaccharides. However, the details are presently unknown.

Fig. 3

Relationship between absorbance at 280 nm and 420 nm (A₂₈₀ and A₄₂₀) of reaction solutions during the isomerization of various aldo-saccharides. Symbols are the same as in Fig. 1. The plots for pentoses and hexoses are located almost on a single curve, so they are connected by a single solid curve. The dotted curve was drawn for disaccharides.

Relationship between the fraction of by-products and coloration Figure 4 shows the relationship between the fraction of by-products (1 - C_S/C_S0 - C_P/C_S0) and A₄₂₀ during the isomerization process. The fraction of by-products was small for disaccharides due to a high selectivity for isomerization to the target products. A₄₂₀ increased sharply at the fraction of by-products of around 0.04. This suggests that, even after disaccharide isomerization reached apparent equilibrium, the by-products may be converted to substances with different absorption coefficients. Xylose, which had a low selectivity in isomerization to xylulose, had a high fraction of by-products and a large A₄₂₀. This is because xylose is easily colored at high temperatures (as mentioned by del Pilar Buera, 1987).

Fig. 4

Relationship between the fraction of byproducts (1 - C_S/C_S0 - C_P/C_S0) and the absorbance at 420 nm of the reaction solution (A₄₂₀) during the isomerization of various aldo-saccharides. Symbols are the same as in Fig. 1. Dashed, solid, and dotted lines represent xylose, ribose and hexose, and disaccharides, respectively. Curves were drawn empirically.

Figure 5 shows the relationship between the decrease in pH and A₂₈₀ and A₄₂₀ during the isomerization process for all saccharides. As the isomerization proceeded, the pH decreased from approximately 9 to about 7.3, during which the coloration increased slightly. Around pH 7.3, the yield of each keto-saccharide almost reached its maximum value (Fig. 1). In contrast, the coloration tended to increase in the latter half of the reaction, and the acidic byproducts reacted further, changing into substances with high absorbance. However, the pH hardly decreased due to the neutralizing effect of the calcium carbonate contained in the shell powder described above. Therefore, stopping the reaction when the product yield is nearly at its maximum would result in a keto-saccharide solution with low coloration.

Fig. 5

Relationship between pH and absorbance at 420 nm (A₄₂₀, open symbols) and 280 nm (A₂₈₀, filled symbols) during the isomerization of various saccharides. Symbols are the same as in Fig. 1. All plots show almost the same trend, so they are empirically connected by a single curve.

Relationship between the yield of keto-saccharide and calcium concentration Figure 6 shows the relationship between the yield of keto-saccharides (C_P/C_S0) and Ca²⁺ concentration. pentoses showed high Ca²⁺ concentrations despite their low yields. The fraction of by-products formed during the isomerization process of pentoses was high because most of the by-products are acidic substances, and the solubilized shell powder was used to neutralize them, resulting in an increased Ca²⁺ concentration. In contrast, the relationship between the yield of keto-saccharides and Ca²⁺ concentration for hexoses and disaccharides was comparable, but the disaccharides with higher yields had higher Ca²⁺ concentrations. For both substrates, Ca²⁺ concentrations increased in the region where the increase in product yield decelerated. Given that coloration increased in this region, the reaction time should be determined by considering three factors: product yield, desired Ca²⁺ concentration, and coloration.

Fig. 6

Relationship between the yield of the major product (keto-saccharide) (C_P/C_S0) and the Ca²⁺ concentration in the reaction solution during the isomerization of various aldo-saccharides. Symbols are the same as in Fig. 1. Dashed, solid, and dotted curves represent pentoses, hexoses, and disaccharides, respectively. Curves were drawn empirically.

Conclusion

The dispersion of scallop shell powder, primarily composed of calcium carbonate, in water exhibits weak alkalinity. Therefore, we focused on microwave heating, which can rapidly raise the temperature of aqueous solutions, and attempted to isomerize various aldo-saccharides to the corresponding keto-saccharides using uncalcined scallop shell powder. The concentration and volume of each substrate were 0.2 mol/L and 50 mL, respectively, and the amount of shell powder was 0.5 g. The maximum reaction time was 105 s due to the pressure limitation of the reaction vessel. The yields of the corresponding keto-saccharides followed the order of disaccharides > hexoses > pentoses. The selectivity in isomerization was also in the same order. Although acidic substances were formed as by-products during the isomerization process of these saccharides, the calcium carbonate in the shell powder effectively neutralized these acidic substances. This maintained the pH of the reaction solution above 7, the level at which isomerization by LBAE transformation proceeds. In addition, Ca²⁺ dissolved from the shell powder as the keto-saccharides were formed, resulting in a reaction solution with a high Ca²⁺ concentration. Most keto-saccharides are rare sugars. Therefore, the isomerization method proposed in this study is promising to produce rare sugar solutions with a high Ca²⁺ concentration in a short reaction time.

Acknowledgements We express our gratitude to Mr. F. Gotoh for his technical assistance.

Conflict of interest There are no conflicts of interest to declare.

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