Magnetically Separable Chiral Periodic Mesoporous Organosilica Nanoparticles

: We describe, for the first time, a successful strategy for synthesizing chiral periodic mesoporous organosilica nanoparticles (PMO NPs). The chiral PMO nanoparticles were synthesized in a sol–gel process under mild conditions; their preparation was mediated by hydrolysis and condensation of chiral-bridged organo-alkoxysilane precursor compounds, (OR ` ) 3 Si-R-Si(OR ` ) 3 , in the presence of cetyltrimethylammonium bromide (CTAB) surfactant. The resulting nanoparticles were composed merely from a chiral- bridged organo-alkoxysilane monomer. These systems were prepared by applying different surfactants and ligands that finally afforded monodispersed chiral PMO NPs consisting of 100% bridged-organosilane precursor. In addition, the major advancement that was achieved here was, for the first time, success in preparing magnetic chiral PMO NPs. These nanoparticles were synthesized by the co-polymerization of 1,1 ′ -((1 R ,2 R )-1,2-diphenylethane-1,2-diyl)bis(3-(3-(triethoxysilyl) propyl) urea) chiral monomer by an oil in water (o/w) emulsion process, to afford magnetic chiral PMO NPs with magnetite NPs in their cores. The obtained materials were characterized with high-resolution scanning electron microscopy (HR-SEM), high-resolution transmission electron microscopy (HR-TEM), energy-dispersive X-ray (EDX) spectroscopy, powder X-ray diffraction (XRD), solid-state NMR analysis, circular dichroism (CD) analysis, and nitrogen sorption analysis (N 2 -BET).


Introduction
Chirality is a fundamental research topic and of vital importance for various fields in natural sciences. Chiral biomolecules have been recognized as the basis of life on earth and many phenomena in nature could be explained through the concepts of stereoisomerism and chirality. In the last decades, the major efforts have been devoted to developing methods for creation and isolation of chiral organic molecules because of their significance in numerous applications [1][2][3]. Recently, increasing attention has been paid to the construction of chiral solid materials and chiral surfaces due to their potential to be applied in chiral adsorption, enantioseparations and catalysis [4][5][6][7][8][9][10][11][12][13]. In particular, several methods have been developed for the fabrication of chiral silica in different morphologies [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]. These methods include the utilization of chiral surfactants or polymers as template, the condensation of silane monomers containing chiral organic groups and the grafting of chiral groups on the walls of mesoporous silica materials.
A significant breakthrough in porous materials came in 1999 when three independent research groups discovered periodic mesoporous organosilicas (PMOs) [31][32][33]. PMO materials soon demonstrated their special position in the field of organic-inorganic hybrid materials [34][35][36][37][38][39], and were investigated intensively in a wide range of applications such as optical materials, adsorbents, trapping agents, drug delivery agents, and catalyst supports [40][41][42][43][44][45]. The success of these PMOs is mainly attributed to their convenient preparation. Within a few years, PMOs with myriad bridging organic groups, narrow distribution pore sizes, and well-defined pore geometries were synthesized and characterized [46][47][48][49]. Generally, PMOs are synthesized by a sol-gel process under mild conditions and their preparation is based on the hydrolysis and condensation of bridged organoalkoxysilane precursor compounds, (OR)3Si-R-Si(OR)3, in the presence of surfactants or block copolymers that assist in creating uniform pores of 2-30 nm size [50][51][52][53]. The organic moieties of the PMOs are implemented directly and distributed homogenously within the inorganic walls. This organic hybridization of the silicate network permits precise control over the surface properties, modification of the hydrophilic/hydrophobic character of the surface, alteration of the surface reactivity, protection of the surface from attack, and modification of the bulk properties of these materials [54,55]. The surface area of PMOs can reach up to 1800 m 2 /g, which makes these materials particularly attractive for the various applications mentioned above.
Magnetic nanoparticles (MNPs) have emerged as a promising class of nanomaterials that have resulted in massive advancements in many biological [103], biomedical [104,105], and catalytic applications [106][107][108][109][110][111]. Recent studies show that magnetic nanoparticles serve as excellent supports for catalysts [112,113]. The supported catalysts have proved to be effective and easily separated from the reaction media by applying an external magnetic field.
Herein we report a successful method for the preparation of chiral periodic mesoporous organosilica nanoparticles in a sol-gel process under mild conditions. Their preparation was initiated by the synthesis of chiral bis-organosilane precursors that served as chiral building blocks for the formation of chiral PMO NPs. In our project, we succeeded to synthesize and characterize different chiral bridged-silane ligands that were utilized for the preparation of the synthesis attempts were focused on the preparation of pure chiral PMO NPs that were composed merely from a chiral bridged organo-alkoxysilane monomer. The preparation of these systems was accomplished by applying different surfactants and ligands who could finally afford a monodispersed chiral PMO NPs consisted of a 100% bridged-silane precursor. Additionally, for the first time, a successful preparation of magnetic chiral PMO NPs was also accomplished. The PMO nanoparticles were synthesized by a co-polymerization of 1,1′-((1R,2R)-1,2-diphenylethane-1,2-diyl)bis(3-(3-(triethoxysilyl)propyl)urea) chiral monomer by an o/w emulsion process, to give magnetic chiral PMO NPs with magnetite NPs in their cores.

General Information
X-ray powder diffraction (XRD) patterns were obtained using a D8 advanced diffractometer (Bruker AXS, Karlsruhe, Germany) with Cukα radiation. The infrared spectra were recorded using a Perkin Elmer (FTIR 65) spectrometer. Scanning electron microscopy (SEM) was performed using a Sirion SEM microscope (FEI Company), a Schottky-type emission source, and a secondary electron (SE) detector, operated at a voltage of 5 kV. Transmission electron microscopy (TEM), scanning transmission electron microscopy (STEM), and electron diffraction spectroscopy (EDS) were performed with a (S)TEM Tecnai F20 G2 (FEI Company, Fremont, CA, USA) instrument operated at 200 kV. Size distribution and zeta potential determination were performed on a Nano Series instrument, model Nano-Zetasizer ZEN3600 (Malvern Instruments, Malvern, UK). Thermogravimetric analysis (TGA) was performed on a Mettler Toledo TG 50 analyzer. Measurements were carried out at a temperature range that extended from 25 to 900 °C and at a heating rate of 10 °C/min under an inert atmosphere (N2). The specific surface areas were calculated by means of the Brunauer-Emmett-Teller (BET) equation by utilizing a high-speed gas sorption analyzer, Quantachrome Nova 1200e instrument. Gas chromatography (GC; Agilent Technologies, 7890A) with a universal capillary column (HP-5, 30 m) was used to determine the reactions' conversion and selectivity. Circular dichroism (CD) analyses were recorded with BioLogic instruments using Biokine software under a xenon lamp source on a MOS 500 spectrometer. 1 H NMR and 13 C NMR spectra were recorded using a Bruker DRX-400 and DRX-500 instrument. Sections 2.2-2.5 are cited from Arakawa et al., 2008 [114].

Preparation of the Chiral PMO Nanoparticles (Chiral PMO NPs)
The chiral PMO nanoparticles were synthesized as follows: CTAB (0.78 g), deionized water (88 mL), and ethanol (33 mL), 25% aqueous ammonia (0.5 mL) were mixed. Then, the chiral organosilane monomer (2.1 mmol), dissolved in 4 mL ethanol, was dropped into the mixture under stirring. The reaction mixture was stirred for 24 h at room temperature. The solid product was then collected by centrifuge and washed in a Soxhlet apparatus using acidic ethanol (1 mL of concentrated HCl in 100 mL of ethanol) for 24 h in order to extract the CTAB surfactant. The obtained chiral PMO NPs were dried at 54 °C for 16 h to afford a fine white-beige powder.

Preparation of Hydrophobic Magnetite Nanoparticles Coated with Oleic Acid (MNP-OA)
The magnetic nanoparticles were prepared according to the Massart procedure [115]: Briefly, 11.7 g of FeCl3·6H2O and 4.23 g of FeCl2·4H2O were dissolved in 400 mL of deionized water under nitrogen gas with vigorous mechanical stirring at 90 °C. At this temperature, 18 mL of concentrated ammonia (25%) were added quickly to the solution, and it was stirred at the same temperature for an extra 20 min. Then, 18 mL of oleic acid was added dropwise to the reaction mixture, and the resulting mixture was stirred at 90 °C for an additional hour. After being cooled to room temperature, a black precipitate was collected by applying an external magnetic field and washing several times with water and acetone. Finally, the hydrophobic magnetite nanoparticles were suspended in 100 mL of chloroform and sonicated for 60 min before further use.

Preparation of the Magnetic Chiral PMO Nanoparticles (Magnetic Chiral PMO NPs)
Magnetic chiral PMO nanoparticles were synthesized as follows: CTAB (0.78 g), deionized water (88 mL), ethanol (33 mL), and 25% aqueous ammonia (0.5 mL) were mixed. Then, the chiral organosilane monomer (2.1 mmol) dissolved in 4 mL ethanol and 1 mL of hydrophobic magnetite nanoparticles coated with oleic acid (MNP-OA) was dropped into the mixture under stirring. The reaction mixture was mechanically stirred for 24 h at room temperature. The solid product was then collected by a magnet and washed in a Soxhlet apparatus using ethanol for 24 h to extract the CTAB surfactant. The final magnetic chiral PMO NPs were dried at 54 °C for 16 h to afford a fine black-gray powder.

Preparation and Characterization of Chiral PMO NPs
The preparation of chiral PMO nanoparticles was initiated by synthesizing a small library of chiral-bridged organosilane monomers that could serve as chiral building blocks of the periodic mesoporous organosilica nanoparticles. These chiral ligands were synthesized by reacting to different chiral amines and amino acids with a silane compound in a molar ratio of 1:2 under an inert atmosphere as illustrated in Scheme 1.

Scheme 1. Synthesis of chiral-bridged organosilane ligands.
After the chiral building blocks were prepared, the chiral PMO NPs were prepared by emulsifying the oil phase containing the chiral-bridged silane precursor in an ethanol/water mixture containing cetyltrimethylammonium bromide (CTAB) or a cetyltrimethylammonium chloride (CTAC) surfactant as a structure-directing agent. Under these conditions, the chiral ligands 1-3 yielded in the presence of CTAB or CTAC either aggregates or fused nanoparticles as was observed by scanning electron microscopy (SEM) analysis (Figures 1-3). On the other hand,1,1′-((1R,2R)-1,2diphenylethane-1,2-diyl)bis(3-(3-(triethoxysilyl)propyl)urea) chiral ligand (4) was the best chiral candidate for preparing chiral PMO nanoparticles, which afforded chiral PMO NPs with uniform shape and size as shown in the SEM images ( Figure 4). In addition, a representative transmission electron microscopy (TEM) image of this system exhibited very well-ordered spherical nanoparticles with a very low resolution of their mesoporous texture (Figure 4).    In addition to the cationic surfactants, the contribution of other polymeric surfactants to the system was tested with a ligand (4). Apparently, non-ionic and polymeric surfactants were not highly favored in these systems and according to the obtained results, it was concluded that a cationic CTAB surfactant was the best candidate for preparing chiral PMO nanoparticles. The resulting SEM images of different systems that were prepared by utilizing different surfactants are summarized in Table 1. As seen in entries 1-3, when Trition X-100, Igepal CO-520, and Pluronic P123 surfactants were used, nanometric sized PMO NPs were obtained, but they were highly fused and some aggregates were observed. The use of Brij 78 surfactant (Table 1, entry 4) yielded very smooth submicron PMO particles but they were also fused. However, the utilization of a cationic surfactant was much favored because it yields smooth and spherical nanoparticles.

Preparation and Characterization of Magnetic Chiral PMO NPs
In the same manner, we prepared magnetic chiral PMO NPs based on the same interfacial polycondensation techniques. As illustrated in Scheme 2, the hydrophobic magnetic nanoparticles, together with the chiral-bridged organosilane ligand (4), were added to the aqueous phase, which includes water, ethanol, and ammonium hydroxide (25%). By the end of this sol-gel process, spherical nanoparticles composed of 100% bridging chiral organosilane monomers filled with magnetite (Fe3O4) in their cores were formed.

Scheme 2. Preparation of magnetic chiral PMO nanoparticles.
The resulting nanoparticles were analyzed by TEM and STEM spectroscopy, accompanied by energy-dispersive X-ray analysis (EDX). The representative TEM and STEM images in Figure 5 provided clear evidence of the special composition and ordering of the magnetite nanoparticles inside the core of the spherical nanoparticles. Moreover, the EDX spectrum confirms the elemental composition of the obtained chiral magnetic nanoparticles because it exhibits all the relevant peaks of carbon, nitrogen, oxygen, silicon, and iron in the detected organosilica network.

=
Further elemental determination was conducted by X-ray powder diffraction (XRD) analysis utilized for identifying the structure of this system. The XRD pattern of the magnetic PMO nanoparticles ( Figure 6) showed characteristic peaks of magnetite nanoparticles at 2θ = 30. 3, 35.7, 43, 53.8, 57.6, and 63.4, in addition to a sharp peak at 2θ = 1.8-2.7, which is attributed to the mesoscopic structure of the PMO nanoparticles. In addition, EDX-mapping analysis was also utilized to confirm the chemical composition and elemental distribution in our system. Figure 7 presents a homogeneous distribution of oxygen, carbon, and silicon throughout the organosilica network. With nitrogen, a similar distribution was also observed in a lower density. The magnetic naoparticles were concentrated in the core, which it was clearly confirmed by their narrow and specific distribution in the center of the resulting chiral PMO NPs.
The average size of both systems was determined by dynamic light scattering (DLS) analysis, which revealed an average size of 173 nm of the chiral PMO NPs and an average size distribution of 190 nm for the magnetic chiral PMO NPs (Figure 8).  The N2 adsorption-desorption isotherms of the chiral PMO NPs and the magnetic chiral PMO NPs (Figure 9) exhibit typical IV-type curves that indicate narrow pore sizes with uniform mesopores. The Brunauer-Emmett-Teller (BET) surface area of chiral PMO NPs was estimated to be 497 m 2 /g, and the calculated total pore volume was 0.39 cm 3 g −1 , whereas the BET surface area of magnetic chiral PMO NPs was estimated to be 371 m 2 /g, and the calculated total pore volume was 0.23 cm 3 g −1 . These values are indeed quite large considering the low porosity of the resulting nanoparticles and the existence of Fe3O4 cores.
The chemical composition of the magnetic chiral PMO NPs was further characterized by solidstate 29 Si and 13 C cross-polarization/magic angle spinning(CP-MAS) NMR spectroscopy. This analysis was conducted after treatment with concentrated HCl, which was used for dissolving all the magnetite nanoparticles in the detected system. The 29 Si NMR spectrum in Figure 10 exhibited a T 3 value of −67.11 ppm, which confirms the formation of the Si-C covalent bonds in the organosilica framework. In addition, the 13 C NMR spectrum of the chiral PMO NPs in Figure 10b gives clear evidence of the successful synthesis of these nanoparticles from ligand (4) because it shows all the characteristic peaks of the incorporated ligands between 10 and 66 ppm, in addition to the aromatic species, ranging from 122 to 147 ppm, and a characteristic carbonyl peak of the urea group at 167 ppm. These results clearly indicate the formation of silsesquioxane frameworks and further demonstrate the incorporation of organic units into the silica networks. FT-IR spectroscopy was employed for determining the chemical composition of chiral PMO NPs and magnetic chiral PMO NPs. Figure 11 compares the FTIR spectra of both systems to the ligand (4). Both systems were similar, displaying equivalent peaks that determine the organic content of the chiral-bridged organosilane ligand (4) in addition to the distinct absorbance peaks at 1023, 1100, and 1283 cm −1 , which can be assigned to Si-C vibrations. Moreover, the absorption bands at intervals of 3120-3700 cm -1 in both curves b and c are assigned to the Si-OH stretching vibrations in the resulting silica network. The absorbance peaks at 2790-3100 cm −1 are assigned to C-H stretching from both chiral systems. The presence of the oleate group coating on the magnetite nanoparticles can be barely observed, since its C-H and C=C stretching bands overlap with the distinct IR bands of the original chiral ligand. The synthesis of chiral PMO NPs and magnetic chiral NPs was also evident by following the organic contents in the resulting system in comparison to the as-synthesized MNP-OA nanoparticles by thermogravimetric analysis (TGA). In both systems, a slight decomposition occurred in the temperature range of 50-100 °C that could have resulted from ethanol and water residues in the detected system, and the major decomposition process that occurred between 150 and 600 °C. In Figure 12 curve a, a total weight loss of 19.2% was detected with MNP-OA, whereas chiral PMO NPs afforded a total organic loss of 68.2% ( Figure 12, curve b), compared with 75.1% with magnetic chiral PMO NPs (Figure 12, curve c). These findings confirm the successful incorporation of the chiral ligand and the magnetic cores besides the good thermal stability of the synthesized chiral systems. Circular dichroism (CD) spectra of chiral compounds are quite sensitive to their chemical and physical changes. From this spectroscopic method, we would be able to study and prove the chiral character of the as-synthesized chiral PMO NPs compared to a bare chiral bridged-silane ligand (4). As seen in Figure 13, the CD spectra of the free ligand (curve a) and the condensed ligand (curve b) are quite similar, with a slight absorbance shift that resulted from its entrapment within the silicate framework. Figure 13. Circular dichroism spectra of (a) chiral ligand (4) and (b) chiral PMO NPs.

Conclusions
In this work pure chiral PMO nanoparticles were successfully synthesized using 1,1′-((1R,2R)-1,2-diphenylethane-1,2-diyl)bis(3-(3-(triethoxysilyl) propyl) urea) chiral monomer by copolymerization and sol-gel condensations. Additionally, magnetic chiral PMO NPs with magnetite nanoparticles in their cores were synthesized for the first time using similar synthetic conditions. We believe that this facile way for preparing chiral catalysts can open new doors for preparing diverse chiral PMO nanocatalysts loaded with different metal nanoparticles that can be highly welcomed in many enantioselective reactions.