Electronic Supplementary Material

for Microchimica Acta

Surfactant assisted enrichment of nucleosides by using a sorbent consisting of magnetic polysulfone capsules and mesoporous silica nanoparticles modified with phenylboronic acid

Ting Cheng, † Yuan Zhang,‡Xiaoyan Liu, † Xiaoyu Zhang, ‡ Haixia Zhang†

State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of GansuProvince, and College of Chemistry and Chemical Engineering, LanzhouUniversity, Lanzhou 730000, China

‡Institute of Physiology, School of Basic Medical Sciences, LanzhouUniversity, Lanzhou 730000, China

Instrumentation and analytical conditions

Elemental analyses were carried out on a Elemental Analyses system (VarioEl element analyzer, Hanau, Germany). The content of the element B was measured by inductively coupled plasma optical emission spectroscopy (ICP-OES) (Varian VTSTA-MPX, USA). Fourier Transform Infrared (FT-IR) spectra were performed on a VEREEX 70V FT-IR (Bruker, US). Scanning electron microscopy (SEM) images were carried on a Hitachi S-3000N scanning electron microscope at an acceleration voltage of 5 kV. The magnetic property of the material was characterized by a vibrating sample magnetometer (VSM) (Lakeshore, USA). Nitrogen adsorption-desorption measurements were recorded on a Tristar 3020 Surface Area and Porosimetry analyzer (Micromeritics Instrument Corp., USA).

The chromatographic system consisted of a Varian 210 high performance liquid chromatography (CA, USA), a 325 UV–vis detector and Varian Star Chromatographic workstation. An analytical reversed-phase C18 column (5 μm, 4.6×250 mm, Dikma Technologies, Beijing, China) was used. The nucleosides were eluted from the column by gradient elution (A, acetonitrile; B, ammonium formate (25 mM)/acetonitrile=1/1); 0–2 min B=94 %; 8 min B=86%; 20 min B=30 %) at a flow rate of 0.8 mL min-1. The selectivity experiment was performed using an isocratic elution mode (acetonitrile / ammonium formate (25 mM)=6/94). Analysis of uridine was under the same isocratic elution as the selectivity experiment. UV detection was set at 259 nm. The injection volume was 10 μL.

Optimization of method

S-IPBA /PSF mass ratio screening

To estimate the influence of the S-IPBA content in the capsule on the nucleosides enrichment, different recipes with varied mass ratio of S-IPBA and PSF were researched. As shown in Fig. S2 (in ESM), by varying the amount of S-IPBA from 1 mg to 80 mg at a constant PSF mass of 120 mg, the enrichment efficiency of four nucleosides increased markedly and reached equilibrium with 10 mg S-IPBA. As a result, 10 mg IPBA functionalized SBA-15 and 120 mg PSF were used to prepare capsules.

Amount of surfactant in extraction

The amount of surfactant in the extraction system has a great influence on the enrichment ratio, a comparative study on the use of DTAB (Fig. S3a in ESM) and CTAB (Fig. S3b in ESM) as additives was presented. Fig. S3 (in ESM) depicts a similar adsorption tendency of the four nucleosides with increasing amount of CTAB or DTAB. In the absence of CTAB and DTAB, the enrichment ratio of four nucleosides is low. However, with the increasing amount of CTAB or DTAB, the enrichment ratio of uridine, inosine, guanosine and adenosine increased remarkably. And then kept equilibrium for DTAB and decreased gradually for CTAB. Maximum enrichment ratios are obtained when the added amounts are in the range of 10 to 15 mg for DTAB and 3 to 5 mg for CTAB, respectively. Compared Fig. S3a with Fig.S3b, we find CTAB-coated S-IPBA@mPSF exhibits better enrichment ratio than DTAB-coated S-IPBA@mPSF because it is easier for CTAB to be adsorbed on the PSF surface with longer hydrophobic chain. When the amount of CTAB is larger than its critical micell concentration (CMC, 0.91 mM), the extraction yield begins to decline due to the formation of micelles in the bulk aqueous solution, which causes the analytes redistribution into solution again. Therefore, 5 mg CTAB was added in the solution during extraction.

Effect of CTAB concentration on the zeta-potential of S-IPBA

Zeta-potential isotherm can provide useful information on adsorption phenomena since changes in the zeta-potential reflect the adsorption on surface directly. Fig. S4 (in ESM) depicts the zeta-potential change of S-IPBA suspensions by adsorption of different amounts of CTAB. At the beginning, the suspension shows a negative zeta-potential value of –31.3 ± 0.6 mV due to the negative charge of boronate groups in basic media. Positively charged CTAB can adsorb on the S-IPBA via electrostatic and hydrophobic interaction. The zeta-potential of S-IPBA increases with the increase of CTAB concentration and remains constant when the amount of CTAB is above 5 mg. This result agrees well with the experimental data mentioned above.

Effect of extraction time and desorption time

The effect of time on the efficiency of extraction was accessed by changing the time from 1 to 30 min. Fig. S5a (in ESM) illustrates the rapid adsorption equilibrium within 15 min. The extraction equilibrium was much faster than that reported before [1, 2]. For later experiments, extraction was carried out within 15 min. Fig. S5b (in ESM) shows the desorption time profile with the time ranged from 1 to 10 min. We found that it was sufficient for 5 min to achieve complete desorption. The recoveries of four nucleosides are all above 85% with three times of elution (Fig. S5c).

Effect of pH

pH is another major factor to influence the adsorption behavior of CTAB-coatedS-IPBA@mPSF. The conventional boronate affinity chromatography columns require the binding pH above the pKa values of the boronic acid ligands. On the other hand, in more basic conditions, there existed more negative charges on the surface of S-IPBA@mPSF, benefiting the adsorption of surfactant. In the present study, the effect of pH was examined by varying the concentration of ammonia between 0 and 2 mM (pH between 9.7 and 10.5). As shown in Fig. S5d (in ESM), the extraction performance improved with increasing pH values and reached the maximum at 0.5 mM ammonia solution. Therefore, 0.5 mM ammonia solution was selected for further studies.

Effect of ionic strength

The effects of ionic strength were studied by varying the NaCl concentrations between 0 and 0.2 mol L-1 and outcomes are illustrated in Fig. S5e (in ESM). With increasing ionic strength, the extraction efficiency of four nucleosides decreases gradually. This phenomenon should be concluded that electrostatic interaction plays an important role in the adsorption process and the competition between sodium ions and CTAB absorbing on the surface of S-IPBA@mPSF is obvious. Therefore, no salt was added to the sample solution.

Sample preparation and treatment

Synthesis of gold nanoparticles (AuNPs)

Gold nanoparticles (AuNPs) were synthesized according to the procedure reported previously [3]. The AuNPs were measured by ICP-OES with a concentration of 1.27 mM.

HepG2 cells culture condition: HepG2 cells were cultured in DMEM medium contained 2 g L-1 NaHCO3 and 2.4 g L-1 HEPES supplemented with 10% fetal calf serum (FCS) at 37°C and 5% CO2/95% O2 atmosphere. About 1.0×105 HepG2 cells in growth medium (2 mL) were seeded in six-well plates and they were incubated with AuNPs at three different concentrations (0 μM, 5 μM, 100 μM) for 6 h, 24 h. After incubation, cells were washed twice with ice-cold PBS and counted under a microscope. The cells harvested were frozen at -20 °C until use.

Cell sample treatment

Due to the trace amount of nucleosides in cells, standard addition method was taken to assay nucleosides. The frozen cells were thawed at room temperature and 0.2 mL of nucleosides stock solution was added into each cells samples. The samples were lysed by ultrasonic cell disrupter. Next, 1.8 mL ammonia solution was added into samples to make the concentration range from 0.02 to 5.0 μg mL-1. The samples were centrifuged for 3 min at 14,797 g. The supernatant was collected, then 8 mg S-IPBA@mPSF and 1 mg CTAB were added into it for extraction. After the mixture was shaken for 15 min, the adsorbents were separated and washed twice with 0.5 mL of ammonia solution (0.5 mM). Then, they were eluted with 1.2 mL formic acid (20 mM, pH=2.7, 0.4 mL × 3) to release the targets. The collected eluates were dried under a nitrogen stream at 50 °C. Finally, the residue was dissolved in 100 μL ammonium formate/acetonitrile (v/v, 3:97) and 20 μL of this solution was injected into the HPLC system for analysis. The experiments were performed in triplicate.

Table S1 Element analysis results of SBA-15 series materials

Materials / N% (wt.%) / C% (wt.%) / H% (wt.%)
SBA-15 / 0.00 / 0.97 / 0.75
S-Cl / 0.00 / 9.84 / 1.50
S-IPBA / 1.60 / 13.27 / 1.63
S-IPBA@mPSF / 0.42 / 57.14 / 4.05

Table S2Physicochemical properties of the mPSF, SBA-15 and S-IPBA@mPSF

Sample / SBET / SBJH(m2/g)b / VBJH(cm3/g)c / DBJH d (nm)
(m2/g)a / Adsorption / Desorption / Adsorption / Desorption / Adsorption / Desorption
mPSF / 1.72 / 0.33 / 0.57 / 0.0036 / 0.0040 / 43.50 / 28.04
SBA-15 / 486.09 / 456.24 / 522.51 / 0.8714 / 0.9089 / 7.64 / 6.96
S-IPBA@mPSF / 24.07 / 25.79 / 33.52 / 0.0442 / 0.0484 / 6.85 / 5.78

a BET surface area.
bBJH adsorption and desorption cumulative surface area of pores.
c BJH adsorption and desorption cumulative volume of pores.
d BJH adsorption and desorption average pore sizes (4V/A).

Table S3 Survival rate of 1.0×105 HepG2 cells upon exposure to different concentrations of AuNPs for 6 h and 24 h (n = 3).

0 μM / 5 μM / 100 μM
6 h / 99 ± 0.13% / 99 ± 0.17% / 95 ± 0.28%
24 h / 99 ± 0.21% / 90 ± 0.34% / 85 ± 0.59%

Fig. S1(a) FT-IR spectra of(i)SBA-15, (ii)S-Cl, (iii)S-IPBA, (b) magnetization curves of S-IPBA@mPSF (insert: a photo of magnetic separation).

Fig. S2 Effect of weight of S-IPBA on enrichment ratio of nucleosides at a constant PSF mass of 120 mg. Conditions: adsorption time: 15 min; desorption time: 5 min; sample volume: 10 mL (0.5 μg mL-1); desorption solution: 20 mM formic acid (1.2 mL, 0.4 mL/times). Data are means ±SD (n = 3).

Fig. S3 Effects of the amount of DTAB (a) and CTAB (b) on the adsorption of nucleosides. Conditions: adsorption time: 15 min; desorption time: 5 min; 40 mg adsorbent with 10 mL nucleosides (0.5 μg mL-1) mixture solution (uridine, inosine, guanosine and adenosine) were dissolved in 0.5 mM ammonia solution, desorpted in 20 mM formic acid (1.2 mL, 0.4 mL/times). Data are means ±SD (n = 3).

Fig. S4 The zeta-potential of S-IPBA as a function of CTAB concentration at pH of 10.3. Data are means ±SD (n = 3)

Fig. S5 Effect of extraction time (a); desorption time (b); elution times (c); concentration of ammonia (d); ionic strength (e) on the extraction efficiency. Data are means ±SD (n = 3)

Fig. S6 Chromatograms of 0.5 μg mL-1 uridine analyzed directly (a), and after enrichment with non-coated S-Cl@mPSF (b); CTAB-coated S-Cl@mPSF (c); non-coated S-IPBA@mPSF (d); CTAB-coated S-IPBA@mPSF (e). CTAB-coated S-IPBA (f). Chromatographic conditions: mobile phase was 25 mM HCOONH4/ACN (94/6, v/v), flow rate was 0.8 mL min-1. The wavelength was 259 nm.

Fig. S7 Recycling experiments of S-IPBA@mPSF for enrichment of uridine. Data are means ±SD (n = 3).

References

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Corresponding author: Tel.: +86 931 8912058; Fax: +86 931 8912582. E-mail address: (Haixia Zhang)