Decorated single-enantiomer phosphoramide-based silica/magnetic nanocomposites for direct enantioseparation

Abstract

The nano-composites Fe₃O₄@SiO₂@(–O₃Si[(CH₂)₃NH])P(=O)(NH-R(+)CH(CH₃)(C₆H₅))₂ (Fe₃O₄@SiO₂@PTA(+)) and Fe₃O₄@SiO₂@(–O₃Si[(CH₂)₃NH])P(=O)(NH-S(−)CH(CH₃)(C₆H₅))₂ (Fe₃O₄@SiO₂@PTA(−)) were prepared and used for the chiral separation of five racemic mixtures (PTA = phosphoric triamide). The separation results show chiral recognition ability of these materials with respect to racemates belonging to different families of compounds (amine, acid, and amino-acid), which show their feasibility to be potential adsorbents in chiral separation. The nano-composites were characterized by FTIR, TEM, SEM, EDX, XRD, and VSM. The VSM curves of nano-composites indicate their superparamagnetic property, which is stable after their use in the separation process. Fe₃O₄, Fe₃O₄@SiO₂, Fe₃O₄@SiO₂@PTA(+) and Fe₃O₄@SiO₂@PTA(−) are regularly spherical with uniform shape and the average sizes of 17–20, 18–23, 36–47 and 43–52 nm, respectively.

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Introduction

Chirality is a major concern in modern pharmaceuticals,^1,2 pesticides,³ flavorings,⁴ food additives,⁵ non-linear optical materials^5,6 and asymmetric catalysis.^7–10 Chiral recognition/resolution is of great interest and ever-increasing importance, thus large efforts have been made towards techniques suitable for this aim such as chromatography,^11–14 enzyme resolution,¹⁵ membrane separation,^16–18 and chemical recognition.¹⁹ In this regard, the applications of chiral materials/chiral selectors in the enantioseparations based on the formation of different diastereomeric adducts, were studied,^20–24 and the interactions such as hydrogen bonding, hydrophobic/hydrophilic, π–π, dipole–dipole, and ionic were reported in the adduct formation.^25–28

Since their discovery, silica-based materials have emerged as a source of immense potential for applications like for example in selective adsorption, separation, catalysis, and preparation of novel functional materials.^29–36 Chemically modifiable surfaces and superparamagnetic property of magnetic modified silica nanoparticles have attracted much attention.^31,37–41 The usefulness of magnetic adsorbents is due to their easily and rapidly separation under an external magnetic field, and in such purposes Fe₂O₃ nanorods, Fe₃O₄ and Fe–Pt alloy nanoparticles, and Fe₃O₄–polymer composites were studied.^41–49 Recently, with regard to chiral discrimination, some magnetic nano-structured materials decorated with appropriate chiral molecules have been inspected.^50–56 Typical examples are Fe₃O₄@SiO₂@PNCD and Fe₃O₄@SiO₂@CBDMPC, where the chiral selectors PNCD and CBDMPC are substituted β-cyclodextrin and cellulose, respectively, and their most important functional groups are OH and ether oxygen. Direct separation of enantiomers via such decorated magnetic nanomaterials would show great advantages compared with traditional methods of chiral separation.^29,57 One example is the application of R(+)-α-methylbenzylamine-modified magnetic chiral sorbent in enantioseparation of mandelic acid.⁵⁸

From our previous studies on phosphorus–oxygen, phosphorus–nitrogen and phosphorus–sulfur compounds,^59–64 the P=O group was found as the best hydrogen-bond acceptor with respect to the other possible acceptor groups which usually exist in the molecules, typically C=O, S=O, N–O, P=S, ester and ether oxygen atoms, nitrogen, and π-system, examined with X-ray diffraction study, statistical analysis based on the data deposited in the Cambridge Structural Database (CSD)^65,66 and quantum chemical calculations in some cases. The structures investigated include both achiral and chiral phosphorus compounds.^63,67–70

With this background in mind, in the current article, we synthesized chiral phosphoramide enantiomers including Si–OCH₃ segment in the achiral moiety, which is sensitive to hydrolysis condensation. This characteristic helps to immobilize silicon-based chiral phosphoric triamide (PTA) on Fe₃O₄@SiO₂, to produce composite materials which dually possess the chiral and superparamagnetic properties. The target materials include the P=O functional group which allows acting as a good selector, due to relatively strong interactions with OH and NH units. The full characterizations of prepared composites and their behavior as adsorbents in direct enantioseparation have been investigated.

Experimental

Materials

Phosphoryl chloride (POCl₃, 99%), (R)-(+)-α-methylbenzylamine (RMBA, 98%), (S)-(−)-α-methylbenzylamine (SMBA, 98%) and (±)-α-methylbenzylamine (MBA, 98%) were bought from Sigma-Aldrich. Methanol, ethanol, tetrahydrofuran (THF), sodium chloride (NaCl), ferric chloride hexahydrate (FeCl₃·6H₂O), ferrous chloride tetrahydrate (FeCl₂·4H₂O), ammonium hydroxide (25% (w/w)), glycerol, tetraethyl orthosilicate (TEOS), 3-aminopropyltrimethoxysilane (APTMS), DL-tartaric acid (99%), DL-phenylalanine (99%), DL-valine (99%) and triethylamine (TEA, 99%) were purchased from Merck.

Instruments

Fourier transformed infrared (FTIR) spectra were obtained by a Buck scientific spectrometer (model EQUINOX 55) using KBr disks. The size and morphology of nanoparticles were monitored using a transmission electron microscope (TEM) from Leo (model 920 AB) with accelerating voltage of 35 kV and resolution of 1 nm. A Tescan instrument (model Mira) was also used for scanning electron microscopy (SEM) with an accelerating voltage of 35 kV and a resolution of 4 nm. Energy-dispersive X-ray spectroscopy (EDX) was performed by an Oxford Instrument (model INCA). XRD patterns were recorded by a Bruker instrument (model D8 Advance) using Ni-filtered Cu Kα radiation. ³¹P, ¹H- and ¹³C-nuclear magnetic resonance (NMR) spectra were recorded on a Bruker instrument (model Avance 300) using DMSO-d₆/THF and CDCl₃/CH₃OH/H₂O as solvents. Circular dichroism (CD) measurements were carried out on an Aviv circular dichroism spectrometer (model 215) using solutions in THF (5 g L⁻¹). Magnetic susceptibility measurements were carried out using a vibrating sample magnetometer (VSM) (BHV-55, Riken, Japan) in the magnetic field range from −8000 to 8000 Oe at room temperature.

Synthesis of single-enantiomer phosphoric triamides

The procedures for the synthesis of P(=O)(NH-R-(+)CH(CH₃)C₆H₅)₂(NH(CH₂)₃Si(OCH₃)₃), PTA(+), and P(=O)(NH-S-(−)CH(CH₃)C₆H₅)₂(NH(CH₂)₃Si(OCH₃)₃), PTA(−), are similar and the only difference is related to the enantiomeric form of amine used. Therefore, the procedure is typically described for PTA(+) as follows: a solution of RMBA (4.6 mmol) and TEA (4.6 mmol) in dry THF (15 mL) was added dropwise to a stirring solution of POCl₃ (2.3 mmol) in dry THF (10 mL) at 0 °C. After stirring for 5 h, the obtained white solid (triethylammonium chloride salt) was filtered off and a solution of APTMS (2.3 mmol) and TEA (2.3 mmol) in dry THF (10 mL) was added dropwise to the filtrate at 0 °C. After stirring for 4 h, the generated triethylammonium chloride salt was filtered off. Since the Si(OCH₃)₃ moiety of PTA was moisture sensitive, a few amounts of THF solution were directly used for the NMR measurements, after adding two droplets of DMSO-d₆ to the NMR tube for adjustment requirement. Finally, the THF solvent was removed under vacuum and the prepared phosphoric triamide was used for the synthesis of Fe₃O₄@SiO₂@PTA. [α]^RT_D (in dry THF, 5 g L⁻¹) = +34.1°. Selected peaks in FTIR (cm⁻¹): 3396, 3248 (N–H), 3028 (C–H_aromatic), 2949 (C–H), 2844, 1190 (P=O), 1082 (Si–O). ³¹P{¹H}-NMR (THF/DMSO-d₆, ppm): 13.35. ¹³C{¹H}-NMR (THF/DMSO-d₆, ppm): 6.42 (s, C₂), 21.63 (s, C₆₊₁₁), 23.76 (s, C₆₊₁₁), 25.09 (d, C₃, ³J_P–C = 6.5 Hz), 46.22 (s, C₄), 50.10–50.90 (C₁, C₅₊₁₂), (126.26, 126.35, 126.62, 128.10, 128.53) (C_{8–10,14–16}), 146.44 (d, C₇₊₁₃), 147.70 (d, C₇₊₁₃, ³J_P–C = 7.2 Hz). ¹H-NMR (THF/DMSO-d₆, ppm): 0.56 (m, 2H, CH₂), 1.38 (m, 6H, CH₃), 1.57 (m, 2H, CH₂), 2.02 (m, 2H, CH₂), 3.40 (t, 1H, NH), 3.48 (m, 9H, CH₃), 3.88 (t, 1H, NH), 3.98–4.22 (m, 2H, CH), 4.28 (b, 1H, NH), 7.15–7.50 (10H, C–H_aromatic).

Preparation of chiral phosphoramide-modified hybrid magnetic/silica nanoparticles, Fe₃O₄@SiO₂@PTA(+) and Fe₃O₄@SiO₂@PTA(−)

Fe₃O₄, as nanoparticles, was prepared according to a previously reported method⁷² as follows: to a solution of FeCl₃·6H₂O (8.6 mmol) and FeCl₂·4H₂O (4.3 mmol) in H₂O (40 mL) at 85 °C, NH₃ (3 mL, 25%) was added (under bubbling of N₂ gas). After 20 min, the magnetic nanoparticles were separated and washed with an aqueous solution of NaCl (0.02 M, 50 mL) and then twice with deionized water (2 × 50 mL), followed by drying under vacuum at 60 °C for 5 h.

Fe₃O₄@SiO₂ was prepared according to a published sol–gel method.⁷² The synthesis procedure is as follows: Fe₃O₄ (1 g) was dispersed in deionized water (100 mL) under ultrasonication for 10 min. After that, an aqueous solution of TEOS (10% v/v, 100 mL) and then glycerol (50 mL) were added to this mixture. The pH was adjusted to 4.5 by using glacial acetic acid and the reaction mixture was stirred continuously for 2 h at 90 °C. The product was separated with a magnet and then washed four times with ethanol. Finally, the obtained Fe₃O₄@SiO₂ was dried under vacuum at 60 °C for 6 h.

At the end step, chiral phosphoric triamide was deposited on the Fe₃O₄@SiO₂ nano-composite. The procedures are similar for deposition of PTA(+) or PTA(−) and typically is given for PTA(+). For this aim, Fe₃O₄@SiO₂ (2 g) was ultrasonicated in ethanol (50 mL) for 10 min, then PTA(+) (0.5 g) in 2 mL ethanol was added under nitrogen atmosphere and the mixture refluxed for 12 h. After, the residue (Fe₃O₄@SiO₂@PTA(+)) was magnetically separated and washed with methanol/H₂O. The condensation of Si–OCH₃ in phosphoric triamide and Si–OH in Fe₃O₄@SiO₂ leads to deposition through the formation of Si–O–Si linkage.

Methods

Specific rotations of PTA(+) and PTA(−), [α], were measured with an automatic digital polarimeter (WZZ-2B, sodium lamp), using solutions in THF (5 g L⁻¹), according to the following equation:

[α] = α/(L × c) (1)

where α is the measured optical rotation in degree, L is the path length in decimetre, and c is the concentration in g/100 mL. Dextrorotation and levorotation are identifying by (+) and (−), respectively.

The averages of particle sizes for nano-adsorbents were calculated by using the Scherrer equation, as follows:⁷¹

D = Kλ/β cos θ (2)

where K is a constant in the range of 0.89–1.39 depending on the particle morphology and set as 0.90, λ is the wavelength of the radiation, β is the full-width at half-maximum (FWHM) and θ is the diffraction angle.

Fe₃O₄@SiO₂@PTA(+) and Fe₃O₄@SiO₂@PTA(−) were examined for chiral separation of five racemic mixtures, i.e., (±)-α-methylbenzylamine, DL-tartaric acid, DL-alanine, DL-phenylalanine, and DL-valine. For this aim, 1 g adsorbent was mixed with 25 mL solution of each racemic mixture (5 g L⁻¹) in H₂O/CH₃OH (80/20, v/v). The mixture was continuously stirred for 1 h. After that, the adsorbent was collected with a magnet and the optical purity of supernatant was determined through measuring its optical rotatory according to the following equation:^52,53

Optical purity = [α]_supernatant/[α]_{pure enantiomer} (3)

Results and discussion

Syntheses, spectroscopic features and optical properties of PTA(+) and PTA(−)

The route of synthesis and chemical structure of P(=O)(NH-R-(+)CH(CH₃)C₆H₅)₂(NH(CH₂)₃Si(OCH₃)₃), PTA(+), and P(=O)(NH-S-(−)CH(CH₃)C₆H₅)₂(NH(CH₂)₃Si(OCH₃)₃), PTA(−), are shown in Fig. 1a and b. For the synthesis of these chiral compounds, the prepared reagents P(=O)(NH-R-(+)CH(CH₃)C₆H₅)₂Cl and P(=O)(NH-S-(−)CH(CH₃)C₆H₅)₂Cl were treated with APTMS in order to the replacement of Cl atom by (CH₃O)₃Si(CH₂)₃NH moiety in the presence of triethylamine as an HCl scavenger. The P–Cl bond in the reagent and Si–OCH₃ bond in PTA are moisture sensitive; hence, dry THF was used as the reaction medium. The usefulness of this solvent is also related to the high solubility of chiral reagent and chiral product and the low solubility of the triethylammonium chloride salt, which allows to a nearly clean reaction and easy purification.

Fig. 1 Synthesis route (a), chemical structure (b), FTIR spectrum (c) and CD spectra (d).

It should be noted that the removing of triethylammonium chloride salt (or other organic salt depending on HCl scavenger used) can be done by H₂O for the phosphoramides non-sensitive to moisture.^68,73 For the water-sensitive compounds, a solvent with different solubilities of phosphoramide and organic salt is used. For examples, the syntheses of moisture-sensitive phosphoramides rac-XP(=O)(OC₆H₅)(Cl) [X = (NHC₆H₄-p-CH₃) and (NH-cyclo-C₆H₁₁)] were reported⁶⁸ in dry chloroform, with low solubilities of p-toluidine hydrochloride and cyclohexylamine hydrochloride salts and high solubilities of phosphoramides. Moreover, the synthesis of P(=O)(NH-R-(+)CH(CH₃)C₆H₅)₂Cl and P(=O)(NH-S-(−)CH(CH₃)C₆H₅)₂Cl have been reported.⁶³

The FTIR spectrum of PTA is shown in Fig. 1c, the characteristic peaks of N–H, C–H, P=O and Si–O bonds confirm the correctness of the structure. In the ³¹P{¹H} NMR spectrum (Fig. S1†) a singlet is observed at 13.35 ppm in comparison with the value of 3.75 ppm (in DMSO-d₆) for [2,6-F₂-C₆H₃C(O)NH][R-(+)(C₆H₅)CH(CH₃)NH]₂P(=O), which is a closely related phosphoric triamide published in point of view of the chiral amine used.⁷⁴

The specific rotations of P(=O)(NH-R-(+)CH(CH₃)C₆H₅)₂(NH(CH₂)₃Si(OCH₃)₃) and P(=O)(NH-S-(−)CH(CH₃)C₆H₅)₂(NH(CH₂)₃Si(OCH₃)₃) were obtained as +34.1° and −33.5°, respectively. The circular dichroism (CD) spectra of these two enantiomers are shown in Fig. 1d. The CD spectra exhibit opposing signals, a negative peak with a minimum at 260 nm belonged to PTA(+) and a positive peak with a maximum at 252 nm for PTA(−). On the other hand, the CD patterns are almost mirrored images with respect to one another in the range of 200–400 nm.

In the ¹³C{¹H}-NMR spectrum (Fig. 2a), two sets of signals are observed for the carbon atoms of two NHCH(CH₃)C₆H₅ groups. Typically, two singlets at 21.63 and 23.76 ppm are related to methyl carbon atoms and two doublets at 146.44 and 147.70 ppm correspond to the ipso-carbon atoms. The corresponding peaks for the (CH₃O)₃SiCH₂CH₂CH₂ moiety are the singlets at 6.42, 46.22 and 50.10 ppm and a doublet at 25.09 ppm. The ortho, meta and para carbon atoms of two phenyl rings appear in the range of 126.26–128.53 ppm. For the assignment of the signals of chiral amine, the NMR spectra of [2,6-F₂-C₆H₃C(O)NH][R-(+)(C₆H₅)CH(CH₃)NH]₂P(=O)⁷⁴ were inspected and for the assignment of the signals of silicon-based amine, the NMR spectra of Fe₃O₄@SiO₂@–O₂(OCH₃)Si[(CH₂)₃NH₂]⁷⁵ and the newly synthesized ((CH₃O)₃SiCH₂CH₂CH₂NH)P(=O)(OC₆H₅)₂ compound were investigated. The structure, details of the synthesis procedure of ((CH₃O)₃SiCH₂CH₂CH₂NH)P(=O)(OC₆H₅)₂ and NMR data are given in the ESI (Fig. S2–S5†). The ¹H-NMR spectrum shows the characteristic peaks for chiral and silicon-based amine fragments, which includes the signals at 0.56, 1.57, 2.02 and 3.48 ppm (multiplets) and at 4.28 ppm (broad) related to three CH₂, CH₃ groups and one NH for silicon-based amine, and the signals at 1.38, 3.40, 3.88 and 3.98–4.22 ppm, respectively for CH₃, two NH units and CH groups of the chiral amine segments. The aromatic protons appeared at 7.15–7.50 ppm (Fig. 2b).

Fig. 2 The ¹³C-NMR (a) and ¹H-NMR (b) spectra of PTA. The peaks marked with * are related to triethylammonium chloride.

Syntheses and characterization of Fe₃O₄@SiO₂@PTA(+) and Fe₃O₄@SiO₂@PTA(−)

The Fe₃O₄ nanoparticles were prepared by precipitation from iron(II) and (III) ions in a basic solution under nitrogen atmosphere and then coated with a thin silica layer, formed by hydrolysis and condensation of TEOS in an acidic alcohol/water solution via a sol–gel process. Then, the immobilization of the chiral selector was carried out through the formation of Si–O–Si linkage,⁷⁶ between the silica layer and silicon-based chiral selector. The procedure for the preparation of Fe₃O₄@SiO₂@PTA(+) and Fe₃O₄@SiO₂@PTA(−) is illustrated in Scheme 1.

Scheme 1 Preparation steps for the fabrication of Fe₃O₄@SiO₂@PTA.

FTIR

Grafting of chiral phosphoric triamide on Fe₃O₄@SiO₂ was verified by FTIR. The FTIR spectra of Fe₃O₄, Fe₃O₄@SiO₂, and Fe₃O₄@SiO₂@PTA(+) are shown in Fig. 3, respectively. In all spectra, the broad peak in the range of 540–578 cm⁻¹ is attributed to the Fe–O vibration. For silicon-containing nanoparticles, the strong and broad bands at about 1000–1100 cm⁻¹ demonstrate the presence of Si–O–Si and Si–OH stretching vibrations.^77,78 In the IR spectrum of Fe₃O₄@SiO₂@PTA(+), the band at 1214 cm⁻¹ is related to the P=O stretching vibration of PTA(+) and the peaks in the range 2840–3248 cm⁻¹ are related to C–H and N–H stretches. These peaks confirmed the occurrence of immobilization.

Fig. 3 The FTIR spectra of Fe₃O₄, Fe₃O₄@SiO₂, and Fe₃O₄@SiO₂@PTA(+).

VSM

The magnetic properties of Fe₃O₄, Fe₃O₄@SiO₂, and Fe₃O₄@SiO₂@PTA were studied by the hysteresis loops at room temperature by using vibrating sample magnetometry (VSM), with the magnetization curves as shown in Fig. 4. The magnetization curves exhibited superparamagnetic properties of Fe₃O₄ and Fe₃O₄@SiO₂ with the saturation magnetizations of about 80 emu g⁻¹ and 76 emu g⁻¹, respectively. For Fe₃O₄@SiO₂@PTA(+), the saturation magnetizations were measured before and after using in the chiral separation process, giving to be about 47 emu g⁻¹ and 45 emu g⁻¹, respectively, showing the stability of superparamagnetic property during the separation process.

Fig. 4 Magnetization curves for Fe₃O₄, Fe₃O₄@SiO₂, and Fe₃O₄@SiO₂@PTA(+) nanoparticles before and after using as an adsorbent.

XRD

The crystalline structures of Fe₃O₄, Fe₃O₄@SiO₂, Fe₃O₄@SiO₂@PTA(+) and Fe₃O₄@SiO₂@PTA(−) were analyzed via XRD (Fig. 5). Characteristic diffraction peaks for Fe₃O₄ were observed at 30.1° (202), 35.5° (311), 43.1° (400), 53.6° (422), 57° (511), 62.6° (440), 71° (602) and 74° (533), in agreement with the crystalline cubic spinel Fe₃O₄ structure (JCPDS no. 19-0629).⁷⁹ The similar characteristic peaks observed for Fe₃O₄@SiO₂, Fe₃O₄@SiO₂@PTA(+) and Fe₃O₄@SiO₂@PTA(−) indicated the stability of the crystalline phase of Fe₃O₄ in the composite materials. The averages of particle sizes for nano-composites were calculated by using the Scherrer equation, which yielded the values of 17, 18, 36 and 43 nm for Fe₃O₄, Fe₃O₄@SiO₂, Fe₃O₄@SiO₂@PTA(+) and Fe₃O₄@SiO₂@PTA(−), respectively, in good agreement with microscopy results. The expanded XRD spectra and related details have been shown in Fig. S6–S9.†

Fig. 5 X-Ray powder diffraction patterns for (a) Fe₃O₄, (b) Fe₃O₄@SiO₂, (c) Fe₃O₄@SiO₂@PTA(+) and (d) Fe₃O₄@SiO₂@PTA(−). The expanded spectra and related details have been shown in Fig. S6–S9.†

TEM, SEM, and EDX

The morphologies of Fe₃O₄, Fe₃O₄@SiO₂, Fe₃O₄@SiO₂@PTA(+) and Fe₃O₄@SiO₂@PTA(−) were identified with SEM and TEM, as shown in Fig. 6. The images exhibit a nearly mono-dispersed structure for Fe₃O₄, with a rough surface because of the numerous reunited nanoparticles. After coating with SiO₂, the surface of nanoparticles became smooth, and a SiO₂ layer was observed around the Fe₃O₄ core. Deposition of chiral phosphoric triamide causes an increase in the particles' diameters. The averages of particle sizes are about 20, 23, 47 and 52 nm for Fe₃O₄, Fe₃O₄@SiO₂, Fe₃O₄@SiO₂@PTA(+) and Fe₃O₄@SiO₂@PTA(−), respectively.

Fig. 6 SEM and TEM images of Fe₃O₄, Fe₃O₄@SiO₂, Fe₃O₄@SiO₂@PTA(+) and Fe₃O₄@SiO₂@PTA(−).

EDX spectra of Fe₃O₄, Fe₃O₄@SiO₂, Fe₃O₄@SiO₂@PTA(+) and Fe₃O₄@SiO₂@PTA(−) were recorded. In Fe₃O₄@SiO₂@PTA(+) and Fe₃O₄@SiO₂@PTA(−) nanocomposites energetic lines for silicon, iron, carbon, oxygen, and phosphorus have been observed that confirm the immobilization of chiral selectors on the surface of Fe₃O₄@SiO₂ (Fig. 7).

Fig. 7 EDX images of Fe₃O₄, Fe₃O₄@SiO₂, Fe₃O₄@SiO₂@PTA(+) and Fe₃O₄@SiO₂@PTA(−).

Direct separation of racemic compounds

Enantioseparation was carried out according to details specified in the experimental section for five racemic compounds (±)-α-methylbenzylamine, DL-tartaric acid, DL-alanine, DL-phenylalanine, and DL-valine. Before treatment with adsorbent, all five racemic compounds showed no optical activity because of the equal amounts of optical (+) and (−) enantiomers in the solutions. The results of enantioseparation processes are given in Table 1 and the chemical structures of racemic compounds are shown in Scheme 2. The optical rotations for supernatants showed that Fe₃O₄@SiO₂@PTA(+) adsorbed (−) enantiomers of valine, alanine, tartaric acid and phenylalanine, and (+) enantiomer of α-methylbenzylamine, while Fe₃O₄@SiO₂@PTA(−) separated the other enantiomers (optical purities 18–82%). To study the possibility of cleavage of chiral selector in the presence of racemic mixture, NMR spectroscopy was typically done for the supernatant of the enantioseparation experiment including Fe₃O₄@SiO₂@PTA(+) in the presence of (±)-MBA solution. The ¹H-NMR and ¹³C-NMR spectra merely showed the signals of α-methylbenzyl amine and the ³¹P-NMR spectrum did not show any signal, which confirmed the stability of adsorbent in the racemic mixture. The ¹H-NMR spectrum is shown in Fig. S10.† The recycling of nano-composite adsorbents was also checked after ending the separation process. So, adsorbents were gathered by an external magnet, washed in a mixture of H₂O/CH₃OH under ultrasonic radiation for 10 min and dried in a vacuum oven for 12 h in 25 °C. Due to the release of the adsorbed enantiomer, the washing solution showed the optical rotatory.

Table 1 Chiral separation of five racemic compounds with Fe₃O₄@SiO₂@PTA(+) and Fe₃O₄@SiO₂@PTA(−) adsorbents

Samples	[α]^RTλ (°)/O.P. (%)
	Fe3O4@SiO2@PTA(+)	Fe3O4@SiO2@PTA(−)
(±)-MBA	−16.8/82	+14.7/72
DL-Alanine	+8.9/79	−8.0/71
DL-Valine	+16.4/72	−14.1/62
DL-Tartaric acid	+2.4/19	−2.3/18
DL-Phenylalanine	+18.4/58	−20.1/63

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Scheme 2 Chemical structures of racemic mixtures.

Typically, the dried (+)-adsorbent was added to 25 mL of (±)-MBA solution (5 g L⁻¹, water/methanol 80/20, v/v) and continuously stirred for 1 h. After that, the specific rotation of solution changed to −10.1° showing that the chiral adsorbent can be recycled with little loss of activity. This slight loss of activity may be due to a few changes in the morphology of nanoparticles in the presence of H₂O/CH₃OH/(±)-MBA, which is usual for nano-compounds in the presence of chemicals, however, it was not further investigated.^53,80

A comparison of chiral adsorbents presented here with other chiral Fe₃O₄@SiO₂-based adsorbents is given in Table 2. The Fe₃O₄@SiO₂@PTA(+) and Fe₃O₄@SiO₂@PTA(−) possess competitive advantages, such as high selectivity and recycling in the direct enantioseparation. Furthermore, we examined the racemic samples belonging to both acid and base families, which were successfully separated by these adsorbents. Preparation of both chiral (+) and (−) adsorbents is another advantage of this work, which helps to facilitate the separation process.

Table 2 Comparison of chiral Fe₃O₄@SiO₂-based nano-adsorbents

Chiral adsorbents	Examined racemates	Optical purity (%)	Reference
Cellulose derivative-modified magnetic silica	(±)-2-Phenoxypropionic acid, benzoin methyl ether, promethazine hydrochloride	Above 80	57
Teicoplanin-modified magnetic silica microspheres	DL-Tryptophan, DL-phenylalanine, DL-mandelic acid, N-benzoyl-DL-alanine	8–35	53
β-CD modified magnetic silica microspheres	Dansyl DL-valine, dansyl DL-phenylalanine, dansyl DL-leucine	10–12	81
HSA modified magnetic silica microspheres	DL-Tryptophan	10–38	82 and 83
Fe3O4@SiO2@PNCD	DL-Tryptophan	80	28
Fe3O4@SiO2@PTA(+)	(±)-MBA, DL-alanine, DL-valine, DL-tartaric acid, DL-phenylalanine	18–82	This work
Fe3O4@SiO2@PTA(−)

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Conclusion

Two single enantiomer nano-composites Fe₃O₄@SiO₂@PTA(+) and Fe₃O₄@SiO₂@PTA(−) were prepared and used for direct enantioseparation of some racemic mixtures. The racemates examined belong to both acid and base families. Excellent separation was achieved for examined basic racemic mixtures and comparative results were obtained for acidic ones with regard to previously reported Fe₃O₄@SiO₂-based adsorbents. The nanocomposites were characterized by FTIR, TEM, SEM, EDX, XRD, and VSM. The nanoparticles have a uniform shape with an average diameter of around 40–50 nm. The superparamagnetic property is observed in nano-composites and is also stable after enantioseparation.

Conflicts of interest

The authors have no conflicts of interest regarding this work.

Acknowledgements

Authors gratefully acknowledge the financial support for this study by Ferdowsi University of Mashhad (Project No. 41927/3).

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c9ra03260f

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