Method for producing zwitterionic sorbent with strong anion exchange and weak cation exchange properties
The method enhances silica gel-based zwitterionic sorbents by integrating strong anion and weak cation exchange, addressing the limitations of existing sorbents to achieve symmetric compound separation and optical isomer resolution.
Patent Information
- Authority / Receiving Office
- RU · RU
- Patent Type
- Patents
- Current Assignee / Owner
- FEDERALNOE GOSUDARSTVENNOE AVTONOMNOE OBRAZOVATELNOE UCHREZHDENIE VYSSHEGO OBRAZOVANIJA NATSIONALNYJ ISSLEDOVATELSKIJ TOMSKIJ GOSUDARSTVENNYJ UNIV TGU NI TGU
- Filing Date
- 2025-12-23
- Publication Date
- 2026-07-01
AI Technical Summary
Existing zwitterionic sorbents based on silica gel face challenges such as low dissociation constants of carboxyl groups, requiring specific mobile phases and limited charge separation capabilities, leading to asymmetric peaks and poor separation of charged compounds.
A method involving silica gel activation, attachment of 3-glycidoxypropyltrialkoxysilane, and modification with glutamic acid to create a sorbent with strong anion and weak cation exchange properties, enabling high symmetry in compound separation and optical isomer separation.
The developed sorbent achieves high symmetry in the separation of substituted and unsubstituted amino groups and optical isomers, with effective anion and cation exchange capabilities.
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Abstract
Description
[0001] This invention relates to analytical chemistry, specifically to a method for producing a zwitterionic sorbent based on silica gel. The invention consists of a method for modifying pure silica gel.
[0002] Zwitterionic sorbents are used to determine polar compounds of cationic, anionic and zwitterionic nature and have more flexible selectivity compared to single-modal ion-exchange sorbents.
[0003] The article [1] describes a method for producing a silica-based sorbent modified by the Ugi reaction. Ethyl isocyanate, obtained from ethyl N-formylglycine and sodium carbonate in the presence of triethylamine, dichloromethane, and phosphorus (V) oxychloride, is used as a modifier. The modifier is grafted to 3-aminopropyl silica gel in a methanol and ethanol medium, after which the residual unreacted amino groups are modified with glycolic acid. The structure of the described sorbent contains tertiary amino groups and carboxyl groups (pKa approximately 3.8) in a 1:1 ratio, which enables the implementation of strong anion and weak cation exchange. The disadvantage of this sorbent is the relatively low dissociation constant of the carboxyl group, since operation in the zwitterionic mode requires the use of a mobile phase with a pKa of less than 2.8, as well as a small distance between the cation and anion, which leads to mutual neutralization of charges.
[0004] The article [2] describes a method for producing a hyperbranched zwitterionic sorbent based on silica gel. Aminopropyl silica gel with a diameter of 5 μm is used as a matrix. In the first stage, 1,4-butanediol glycidyl ether is used as a linker to remove functional groups from the silica gel surface. Subsequently, amination with taurine is carried out to introduce strong cation-exchange sulfonic acid groups into the structure. 1,4-butanediol glycidyl ether is re-grafted, to which iminoacetic acid is attached as a second zwitterionic layer. This sorbent possesses both weak and strong cation-exchange groups, but, according to testing results, mainly exhibits anion-exchange properties and does not allow the separation of positively charged compounds.
[0005] Patent [3] describes a method for producing a zwitterionic sorbent by modifying silica gel with reaction products of sulfonic acid compounds and aminoalkylsilanes. The modifier structure contains a sulfonic acid group, which has strong cation-exchange properties, and an amino group, which has strong anion-exchange properties. This sorbent does not allow the determination of compounds with substituted and unsubstituted amino groups, as strong ionic interactions cause the peaks to broaden significantly and become asymmetric.
[0006] The prototype is the sorbent described in the article [4]. Chromatographic 3-glycidoxypropyl silica gel with a diameter of 5 μm is used as a matrix. The oxirane ring interacts with the amino group of glutamic acid, opening the ring via a nucleophilic substitution mechanism. The structure of the surface modifier is identical to that proposed in this patent, but the conditions for its preparation were not described.
[0007] The technical objective of the invention is to develop a method for producing a chromatographic sorbent based on silica gel, which has strong anion exchange and weak cation exchange properties.
[0008] Technical result: in the creation of a chromatographic sorbent based on silica gel, possessing strong anion-exchange and weak cation-exchange properties, which will allow the separation of mixtures of anions and cations, achieving high symmetry of compounds with substituted and unsubstituted amino groups, and also carrying out the separation of optical isomers due to the optical activity of the modifier.
[0009] The claimed method for producing a zwitterionic sorbent based on silica gel consists of the following steps:
[0010] 1. Silica gel activation
[0011] Activation of silica gel with a diameter of 3-5 μm involves the hydration of siloxane groups on the silica gel surface to form silanol groups capable of reacting with the linker (Fig. 1). Hydration is carried out with a 5-15% HCl solution for one hour using ultrasound, after which the silica gel is dried in an oven at a temperature of 80 °C to 150 °C for 12-24 hours.
[0012] 2. Attachment of linker (3-glycidoxypropyltrialkoxysilane) to the surface of regenerated silica gel (Fig. 2)
[0013] The addition of 3-glycidoxypropyltrialkoxysilane is carried out in a toluene medium at a temperature of 70-110 °C with constant stirring. To create an inert atmosphere, the synthesis is carried out under a constant flow of argon. The silanizing reagent is added dropwise into the flask. Gradual addition is necessary to minimize reagent attachment to the walls of the glass flask during the synthesis. The reagent is added to the silica gel suspension in a weight ratio of 1.0:10.8. Linker attachment occurs over 4-12 hours with constant stirring. After completion of the synthesis, the silica gel is filtered using a vacuum pump and washed with toluene. The reaction product is dried in a drying oven at a temperature of 80-150 °C for 12 hours.
[0014] 3. Addition of a modifier to the functional epoxy groups of 3-glycidoxypropyltrialkoxysilane (Fig. 3)
[0015] The synthesis is carried out with heating, constant stirring, and an inert argon atmosphere for 3-12 hours. An aqueous solution with a pH >7 is used as a solvent. The molar ratio between glutamic acid and 3-glycidoxypropyltrialkoxysilane groups is 2:1. After completion of the synthesis, the modified silica gel is filtered using a vacuum pump and washed with water. The reaction product is dried in an oven at 90-100°C for 12 hours.
[0016] Below are examples of implementing the invention.
[0017] Example 1
[0018] This example uses a previously used chemically pure sorbent with a diameter of 5 μm and an grafted octadecyl fragment. This fragment was removed by calcination in a muffle furnace for 12 hours at 600°C. Surface activation was performed with a 10% HCl solution for 1 hour while being treated in an ultrasonic bath. The silica gel was then dried in an oven at 100°C for 12 hours.
[0019] 3 grams of silica gel and 100 ml of toluene were added to a three-necked flask, and the air inside the flask was replaced with argon. The flask contents were heated to 80°C with constant stirring, after which 1.17 mmol of 3-glycidoxypropyltrialkoxysilane was added dropwise over 30 minutes. Linker attachment was carried out for 6 hours with constant stirring. After completion of the synthesis, the silica gel was filtered using a vacuum pump and washed with 100 ml of toluene. The reaction product was dried in an oven at 90-100°C for 12 hours.
[0020] The addition of glutamic acid was carried out in a round-bottomed, three-necked flask, heated to 50°C, with constant stirring, and under an inert argon atmosphere. The molar ratio between glutamic acid and oxirane groups was 2:1, and a twofold excess of the acid was used. The pH of the solution was adjusted to 10. The synthesis time was 5 hours. After completion of the synthesis, the silica gel was filtered using a vacuum pump and washed with 100 ml of water. The reaction product was dried in an oven at 90-100°C for 12 hours.
[0021] The carbon content of the resulting sorbent was determined using synchronous thermogravimetric analysis (Fig. 4). The mass loss during drying due to the combustion of organic matter was 6.19%, indicating the presence of a modifier on the silica gel surface.
[0022] To study the selectivity, the column body with a length of 150 mm and an internal diameter of 4.6 mm was filled with a modified sorbent using the suspension method.
[0023] The study of selectivity in the reversed-phase mode was carried out using toluene, naphthalene and anthracene as model substances (Fig. 5). Acetonitrile was used as a stronger solvent, and water as a weaker one. With an increase in the proportion of acetonitrile from 0 to 70%, a decrease in the retention time (RT) is observed, and from 70 to 100%, it increases. The bell-shaped dependence indicates the implementation of both reversed-phase and normal-phase modes [5].
[0024] A selectivity study in hydrophilic mode was conducted using thiourea. A formate buffer was used as the stronger solvent, while acetonitrile was used as the weaker solvent. With increasing acetonitrile content in the mobile phase, a decrease in retention time was observed up to 50% acetonitrile, followed by an exponential increase, indicating a transition from reversed-phase to hydrophilic interactions (Figure 6).
[0025] A selectivity study in anion-exchange mode was conducted using iodide ion as a model component. Phosphate buffer at concentrations of 10, 25, and 50 mM with pH 6.5 was used as a stronger solvent, while acetonitrile served as a weaker solvent. The solvent ratios in the mobile phase and the buffer molarity were varied. The obtained dependences (Fig. 7) indicate the implementation of an anion-exchange mode in conjunction with cation-exchange.
[0026] A selectivity study in anion-exchange mode was conducted using novocaine as a model component. Phosphate buffer at concentrations of 10, 25, and 50 mM with pH 6.5 was used as a stronger solvent, while acetonitrile served as a weaker solvent. The solvent ratios in the mobile phase and the buffer molarity were varied. The obtained dependences (Fig. 8) indicate the predominantly cation-exchange mode.
[0027] Example 2
[0028] Differs from Example 1 in that silica gel with a diameter of 3 μm was used. The characteristics of the resulting silica gel are similar to those given in Example 1.
[0029] List of references
[0030] 1. Chikurova N. Yu., Shemyakina I. V., Litkovskaya N. Yu. / New sorbent for hydrophilic chromatography based on silica gel modified by the Ugi reaction / / Journal of Analytical Chemistry. - 2021. - Vol. 76, No. 9. - P. 832-843.
[0031] 2. Shemyakina O., Uzhel A., Chernobrovkina A. / Study of chromatographic properties of the developed hyperbranched zwitterionic sorbent based on silica gel in the hydrophilic chromatography mode / / Sorption and chromatographic processes. - 2024. - Vol. 24, No. 3. - P. 304-320.
[0032] 3. Patent No. EP 2210662 A2. Method for producing adsorbent materials for liquid chromatography using zwitterionic silanes. Publ. 07 / 28 / 2010.
[0033] 4. Ion-exchange properties of glutamic acid-bonded silica / AI Elefterov, MG Kolpachnikova, PN Nesterenko, OA Shpigun / / Journal of Chromatography A. - 1997. - T. 769, No. 2. - pp. 179-188.
[0034] 5. Acclaim Mixed-Mode HILIC-1 columns: product specifications. - US: Thermo Fisher Scientific Inc., 2020. - 6 pp. - URL: https: / / assets.thermofisher.com / TFS-Assets / CMD / Specification-Sheets / 61824DS_Acclaim_Mixed_Mode_HILIC_1_29Aug07_LPN1963.pdf