materials Article Preparation and Characterization of Novel Mixed Periodic Mesoporous Organosilica Nanoparticles Hao Li 1,2 , Laurence Raehm 2 , Clarence Charnay 2 , Jean-Olivier Durand 2, * and Roser Pleixats 1, * 1 Department of Chemistry and Centro de Innovación en Química Avanzada (ORFEO-CINQA), Faculty of Sciences, Universitat Autònoma de Barcelona. UAB Campus, C/ dels Til.lers, 08193 Cerdanyola del Vallès, Spain; Hao.Li@uab.cat 2 ICGM, CNRS, ENSCM, University of Montpellier, Case 1701, Place Eugène Bataillon, CEDEX 05, 34095 Montpellier, France; clarence.charnay@umontpellier.fr (C.C.); laurence.raehm@umontpellier.fr (L.R.) * Correspondence: jean-olivier.durand@umontpellier.fr (J.-O.D.); roser.pleixats@uab.cat (R.P.); Tel.: +34-935812067 (R.P.)  Received: 3 March 2020; Accepted: 26 March 2020; Published: 28 March 2020  Abstract: We report herein the preparation of mixed periodic mesoporous organosilica nanoparticles (E-Pn 75/25 and 90/10 PMO NPs) by sol-gel co-condensation of E-1,2-bis(triethoxysilyl)ethylene ((E)-BTSE or E) with previously synthesized disilylated tert-butyl 3,5-dialkoxybenzoates bearing either sulfide (precursor P1) or carbamate (precursor P2) functionalities in the linker. The syntheses were performed with cetyltrimethylammonium bromide (CTAB) as template in the presence of sodium hydroxide in water at 80 ◦ C. The nanomaterials have been characterized by Transmission Electron Microscopy (TEM), nitrogen-sorption measurements (BET), Dynamic Light Scattering (DLS), zeta-potential, Thermogravimetric Analysis (TGA), FTIR, 13 C CP MAS NMR and small angle X-ray diffraction (p-XRD). All the nanomaterials were obtained as mesoporous rodlike-shape nanoparticles. Remarkably, E-Pn 90/10 PMO NPs presented high specific surface areas ranging from 700 to 970 m2 g−1 , comparable or even higher than pure E PMO nanorods. Moreover, XRD analyses showed an organized porosity for E-P1 90/10 PMO NPs typical for a hexagonal 2D symmetry. The other materials showed a worm-like mesoporosity. Keywords: periodic mesoporous organosilica nanoparticles; sol-gel process; disilylated tert-butyl 3,5-dialkoxybenzoates 1. Introduction Periodic mesoporous organosilica materials, at the bulk (PMO) [1–3] and nanoscale (PMO NPs) level, are fundamentally unique because they have several advantages, such as robust porous organic-inorganic framework [4], porous channels [5], tunable pore size organization [6,7], biocompatibility [8], and the highest organic content (nano)materials [9]. Moreover, the functionalization of the inner and outer surface allows the modulation of the properties and enable dispersibility in aqueous or organic solvents [10]. The hydrophilicity/hydrophobicity of the pores is also adjustable [11,12]. The PMO (and PMO NPs) can be degraded when specific functional groups sensitive to redox, acid-base, biochemical, or photochemical reactions are present in the structure of the organic framework [13–15]. The post-modification of the organic fragment is also possible by classical organic chemistry [16,17]. Especially in nanomedicine, properties of PMO NPs such as low hemolytic behavior [18], increased biocompatibility, higher loading capacities, physico-chemical adjustability of the pores [19] and designed biodegradability [20], are particularly important when compared to mesoporous silica nanoparticles. Materials 2020, 13, 1569; doi:10.3390/ma13071569 www.mdpi.com/journal/materials Materials 2020, 13, 1569 2 of 16 PMO and PMO NPs are synthesized from organo-bridged alkoxysilanes by the sol-gel process in the presence of surfactants that act as templates. The incorporation of organic moieties as bridging components, directly and specifically into the pore walls, by using disilylated organosilica precursors, enable the preparation of a new generation of organosilica (nano)materials that combines the advantages of organic and inorganic units while overcoming their intrinsic disadvantages [6,20–23]. If there is only one bridged organosilica precursor, pure PMO NPs can be formed. When two bridged organosilica precursors with different functional groups are used, mixed PMO NPs are obtained with two different functionalities in the framework wall. Specifically, the synthesis of PMO NPs implies the careful control of a range of conditions, such as the reaction temperature, reaction time, pH, solvent, precursors, optimized reactants ratio, catalyst, mixing method and stirring speed. The experimental conditions control the template-silica interactions, the silica condensation rate, the assembly kinetics and, thus, the nucleation and growth rates. Control over the nanostructure, morphological uniformity, size distribution, porosity and compositions of PMO NPs is quite challenging. Interestingly, different types of PMO NPs can be obtained through templating strategies such as spherical nanoparticles, nanorods, nanofibers, and multipodal NPs [9,23]. Although a broad array of PMO materials have been reported, achieving the nanoscale for such materials is still challenging. The first PMO NPs with a hollow spherical morphology (HPMO NPs) were prepared from 1,2-bis(trimethoxysilyl)ethane by using the FC-4 fluorocarbon surfactant [C3 F7 O(CFCF3 CF2 O)2 CFCF3 CONH(CH2 )3 N+ (C2 H5 )2 CH3 , I− ] and CTAB cationic surfactant as co-structure directing agents [24]. In addition, by changing the ratio of FC-4 to CTAB, the shell thickness of HPMO NPs can be adjusted, and non-hollow PMO microspheres can be obtained by using only CTAB surfactant. The procedure followed to obtain phenylene-bridged PMO nanospheres was based on the use of two templates, namely, poly(ethylene oxide)-poly(DL-lactic acid-co-glycolic acid)-poly(ethylene oxide) triblock copolymer and the FC-4 surfactant [25]. Interestingly, the authors found that these two surfactants were immiscible, the core being templated by the polymer based on poly-lactic acid and the shell by FC-4 [25]. When Pluronic P123 block copolymer alone was used as template (without FC-4), hollow silica nanospheres were obtained instead of the expected PMO material [26]. Later, a variety of PMO nanospheres with different organic bridged linkers, such as methylene, ethylene, ethynylene and phenylene was reported [18,26,27]. In 2005, Lu and colleagues were the first to use Pluronic P123 triblock copolymer as a structure-directing agent to control the synthesis of ethylene bridged PMO nanorods [28]. Jaroniec and colleagues then described the use of both 1,2-bis (triethoxysilyl)ethane (BTEE) and 1,4-bis (triethoxysilyl)benzene (BTEB) as organosilica precursors, and Pluronic P123 poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) as triblock copolymer template to control the synthesis of ethylene-phenylene wide microrods with coil-like morphology [29]. In 2009, Mohanty and Landskron used the trisilylated octaethoxy-1,3,5-trisilapentane as precursor with P123 surfactant, and PMO nanorods and nanofibers were obtained with an adjustable aspect ratio from 2:1 to 20:1 by varying the concentration of the precursor [30,31]. In 2011, methylene-, ethenylene-, and phenylene-bridged PMO helical fibers were prepared using CTAB and (S)-β-citronellol as templating agents [32]. The sizes and shapes could be adjusted to obtain nanorods depending on the precursor used. In some research works, CTAB was used as the only template to prepare bridged PMO nanorods [7,11]. Interestingly, Khashab’s group reported the first controlled syntheses of para-phenylene-bridged PMO NPs with different morphologies, from nanospheres to nanorods and nanowires, with CTAB as a structure-directing agent by adjusting the organic co-solvents [33]. Multipodal PMO NPs with phenylene-bridged cores and ethenylene-bridged pods were designed by Croissant et al., which were prepared in a CTAB-templated aqueous medium with sodium hydroxide as catalyst through a one-pot two-step method [34]. While the sole condensation of the 1,4-bis(triethoxysilyl)benzene or 1,2-bis-(triethoxysilyl)ethylene precursor afforded phenylene- and ethenylene-bridged PMO nanospheres and nanorods, respectively, the addition of the ethenylene precursor into a solution of freshly prepared phenylene-bridged NPs gave rise to multipodal nano-objects. Interesting reviews on the synthetic strategies for the preparation of PMO Materials 2020, Materials 2020, 13, 13, 1569 x FOR PEER REVIEW 33 of of 16 16 and catalysis have been published [20,23,35–37]. Furthermore, the glutathione-triggered nanomaterials and degradability of PMOtheirand applications in nanomedicine related materials and catalysis by incorporating have been disulfide published bridges [20,23,35–37]. in the structure has Furthermore, the glutathione-triggered been comprehensively reviewed [14]. degradability of PMO and related materials by incorporating disulfide The bridges synthesisin the of structure PMO NPs haswith beenlarge comprehensively and flexiblereviewed organic [14]. bridging groups within the The synthesis mesoporous wall of PMO NPs remains with largechallenge a scientific and flexible organic and bridging groups the development of within the mesoporous new mixed periodic wall remains a scientific challenge and the development of new mixed periodic mesoporous organosilica mesoporous organosilica nanoparticles is very relevant, especially for potential new applications in nanoparticles nanomedicine.is very relevant, especially for potential new applications in nanomedicine. Herein, we describe the preparation and full characterization of novel mixed PMO NPs which have been obtained by sol-gel co-condensation of E-1,2-bis(triethoxysilyl)ethylene (BTSE or E) [38] E-1,2-bis(triethoxysilyl)ethylene (BTSE with disilylated tert-butyl 3,5-dialkoxybenzoates bearing either sulfide (precursor P1) or carbamate 3,5-dialkoxybenzoates bearing (precursor P2) functionalities functionalities in in the the linker linker (Figure (Figure 1). 1). Figure Figure 1. Proposed 1. Proposed disilylated disilylated tert-butyl tert-butyl 3,5-dialkoxybenzoates 3,5-dialkoxybenzoates P2and P1 andP1 P2 for for the the preparation preparation ofPMO of mixed mixedNPs. PMO NPs. 2. Materials and Methods 2. Materials and Methods 2.1. General Remarks 2.1. General Remarks The 13C-CP-MAS solid state NMR spectra (Les Ullis, France), the BET surface areas (Mérignac, The 13 C-CP-MAS solid state NMR spectra (Les Ullis, France), the BET surface areas (Mérignac, France), Dynamic Light Scattering (DLS, Pessac, France) and Zeta potential values (Orsay, France) France), Dynamic Light Scattering (DLS, Pessac, France) and Zeta potential values (Orsay, France) were were obtained from equipments of University of Montpellier [39]. The 1H- and 13C-NMR spectroscopy obtained from equipments of University of Montpellier [39]. The 1 H- and 13 C-NMR spectroscopy (Bruker (Bruker Biospin, Rheinstetten, Germany), Mass-Spectrometry (MS, Bruker Biosciences Española, Biospin, Rheinstetten, Germany), Mass-Spectrometry (MS, Bruker Biosciences Española, Madrid, Madrid, Spain), elemental analysis, Infra-Red spectroscopy (IR, Bruker Biosciences Española, Spain), elemental analysis, Infra-Red spectroscopy (IR, Bruker Biosciences Española, Madrid, Spain), Madrid, Spain), Powder X-Ray diffraction (P-XRD, Almelo, Netherlands) and Transmission Electron Powder X-Ray diffraction (P-XRD, Almelo, Netherlands) and Transmission Electron Microscopy (TEM, Microscopy (TEM, JEOL Ltd., Akishima, Tokyo, Japan) were performed at the Universitat Autònoma JEOL Ltd., Akishima, Tokyo, Japan) were performed at the Universitat Autònoma de Barcelona (UAB) [39]. de Barcelona (UAB) [39]. When necessary, experiments were carried out with Schlenk techniques under standard high When necessary, experiments were carried out with Schlenk techniques under standard high vacuum. CTAB, NH4 NO3 , sodium hydroxide, potassium bromide and the required reagents for the vacuum. CTAB, NH4NO3, sodium hydroxide, potassium bromide and the required reagents for the preparation of P1 and P2 were purchased from Sigma-Aldrich (Madrid, Spain). Ethanol and acetone preparation of P1 and P2 were purchased from Sigma-Aldrich (Madrid, Spain). Ethanol and acetone were purchased from Fisher Chemicals (Madrid, Spain) and hydrochloric acid from VWR PROLABO were purchased from Fisher Chemicals (Madrid, Spain) and hydrochloric acid from VWR PROLABO (Barcelona, Spain). E PMO NPs were prepared as described [11]. (Barcelona, Spain). E PMO NPs were prepared as described [11]. 2.2. Synthesis of 2 2.2. Synthesis of 2 In a 250 mL Schlenk flask under nitrogen atmosphere, but-3-en-1-ol 1 (8.0 mL, 0.843 g/mL, 93.50In a 250 was mmol) mL Schlenk flask under added, dissolved innitrogen atmosphere, but-3-en-1-ol dry dichloromethane (100 mL) and1dry (8.0 triethylamine mL, 0.843 g/mL, (5.093.50 mL, mmol) was added, dissolved in dry dichloromethane (100 mL) and dry triethylamine (5.0 0.73 g/mL, 117 mmol). Then, the mixture was stirred with cooling (ice bath) over a period of 15 min. mL, 0.73 g/ mL, 117 mmol). Then, the mixture was stirred with cooling (ice bath) over a period After this time, methanesulfonyl chloride (15.0 mL, 1.48 g/mL, 193.80 mmol) was added and the of 15 min. After this time,mixture reaction methanesulfonyl was stirred chloride overnight(15.0 mL, temperature at room 1.48 g/mL, 193.80 undermmol) was added and argon atmosphere. Then,the100 reaction mL of mixture was stirred overnight at room temperature under argon atmosphere. fresh dichloromethane were added to the crude and it was washed first with HCl 5 M (50 mL Then, 100 mL of fresh × 2) dichloromethane and were added then with saturated to the aqueous crude of solution andNait2 was CO3 washed (50 mL × first withbrine 2) and HCl 5(50 MmL (50 × mL2).×The 2) and then organic with saturated fraction aqueous was dried solution ofsodium using anhydrous Na2COsulfate 3 (50 mL × 2) and brine (50 mL × 2). The organic fraction and the solvent evaporated under vacuum to afford was dried using anhydrous sodium sulfate and the solvent evaporated under vacuum to afford the Materials 2020, 13, 1569 4 of 16 the final product 2 as yellow liquid (13.80 g, 99% yield) [40]. 1 H NMR (360 MHz, CDCl3 ) δ (ppm): 5.84–5.73 (m, 1H), 5.21–5.14 (m, 2H), 4.27 (t, J = 7.2 Hz, 2H), 3.01 (s, 3H), 2.54–2.48 (m, 2H). 2.3. Synthesis of 4 To the stirred mixture of 3,5-dihydroxybenzaldehyde 3 (1.38 g, 10.0 mmol) and cesium carbonate (13.03 g, 40.0 mmol) in anhydrous DMF (80 mL) an excess of but-3-en-1-yl methanesulfonate 2 (4.50 g, 30.0 mmol) was added. The reaction was stirred at 40 ◦ C under argon atmosphere until 3,5-dihydroxybenzaldehyde was fully consumed (TLC monitoring, 48 h). Then, water was added (100 mL) and the product was extracted using hexane (200 mL × 3). The organic phase was washed with 1M NaOH, dried with anhydrous sodium sulfate and the solvent was removed under vacuum to afford the final product 4 as yellow liquid (1.93 g, 78% yield) [41]. 1 H NMR (360 MHz, CDCl3 ) δ (ppm): 9.89 (s, 1H), 7.00 (br s, 2H), 6.71 (br s, 1H), 5.93–5.84 (m, 2H), 5.20-5.11 (m, 4H), 4.05 (t, J = 7.2 Hz, 4H), 2.58–2.55 (m, 4H); 13 C NMR (91 MHz, CDCl3 ) δ (ppm): 192.0, 160.5, 138.3, 134.1, 117.3, 108.1, 107.8, 67.6, 33.5. IR (film): 3078.9, 2980.0, 2876.7, 1697.7, 1592.4, 1452.6, 1295.6, 1296.0, 1165.9, 1065.9, 1065.1, 843.9, 676.0 cm−1 . GC-MS (EI) m/z: 246.2 [M+ ], 192.1, 163.1, 150.1, 138.0, 121.1, 110.0, 91.1, 75.0, 65.1, 55.1; HRMS (ESI) m/z [M + Na]+ calcd for C15 H18 O3 Na: 269.1148, found: 269.1141. 2.4. Synthesis of 5 To a stirred solution of 3,5-bis(but-3-en-1-yloxy)benzaldehyde 4 (1.97 g, 8.0 mmol) in acetonitrile (12.0 mL) was added a solution of NaH2 PO4 ·2H2 O (374.4 mg, 2.4 mmol) in water (5.0 mL) and 30% H2 O2 (4.0 mL, 9.97 mol/L, 40.0 mmol). Finally, a solution of 80% purity NaClO2 (1.27 g, 11.2 mmol) in water (10.0 mL) was added dropwise during 2 h to the stirred mixture at room temperature. O2 evolved from the solution was monitored until the end of the reaction with a bubbler connected to the flask. A small amount of Na2 SO3 was added to destroy the excess of oxidants. The mixture was acidified with 10% aqueous HCl, and the product was extracted using ethyl acetate (60 mL × 3). The organic phase was dried with anhydrous sodium sulfate and the solvent was removed under vacuum to afford a residue which was purified by a flash column chromatography through silica gel eluting with hexane/EtOAc = 2:1, obtaining the product 5 as a colorless solid (1.78 g, 85% yield) [42]. 1 H NMR (360 MHz, CDCl3 ) δ (ppm): 7.25 (d, J = 3.6 Hz, 2H), 6.70 (br s, 1H), 5.94–5.85 (m, 2H), 5.21–5.11 (m, 4H), 4.05 (t, J = 7.2 Hz, 4H), 2.58–2.53 (m, 4H); 13 C NMR (91 MHz, CDCl3 ) δ (ppm): 171.7, 160.0, 134.2, 130.9, 117.2, 108.4, 107.6, 67.5, 33.5. 2.5. Synthesis of 6 In a 10 mL round bottom flask, 3,5-bis(but-3-en-1-yloxy)benzoic acid 5 (1.31 g, 5.0 mmol), di-tert-butyl dicarbonate (2.18 g, 10.0 mmol) and 4-dimethylaminopyridine (183.3 mg, 1.5 mmol) were dissolved in tert-butanol (40 mL). The reaction mixture was stirred at room temperature under argon atmosphere until 3,5-bis(but-3-en-1-yloxy)benzoic acid 5 was fully consumed (TLC monitoring, 48 h). Then, the solvent was removed under reduced pressure and the residue was purified by flash column chromatography through silica gel eluting with hexane/AcOEt = 15:1, obtaining the pure product 6 as colorless oil (1.38 g, 87% yield) [43]. 1 H NMR (360 MHz, CDCl3 ) δ (ppm): 7.13 (d, J = 3.6 Hz, 2H), 6.62 (t, J = 3.6 Hz, 1H), 5.94–5.84 (m, 2H), 5.20–5.10 (m, 4H), 4.03 (t, J = 7.2 Hz, 4H), 2.56–2.53 (m, 4H), 1.58 (s, 9H); 13 C NMR (91 MHz, CDCl3 ) δ (ppm): 165.5, 159.8, 134.3, 133.9, 117.1, 107.8, 105.9, 81.2, 67.4, 33.5, 28.2. IR (film): 3078.7, 2977.7, 1711.7, 1594.3, 1445.8, 1300.5, 1159.9, 1049.1, 915.6, 767.2 cm−1 . GC-MS (EI) m/z: 318.2 [M]+ , 262.1, 245.2, 208.1, 190.1, 166.1, 154.0, 136.0, 55.1; HRMS (ESI) m/z [M + Na]+ calcd for C19 H26 O4 Na: 341.1723, found: 341.1707. 2.6. Synthesis of P1 In a 50 mL Schlenk tube under nitrogen, tert-butyl 3,5-bis(but-3-en-1-yloxy)benzoate 6 (954.5 mg, 3.0 mmol) and 2,2-dimethoxy-1,2-diphenylethanone (DMPA) (153.8 mg, 0.6 mmol) were dissolved in anhydrous THF (12.0 mL). Then (3-mercaptopropyl)triethoxysilane (1.5 g, 6.3 mmol) was added and Materials 2020, 13, 1569 5 of 16 the stirred mixture was irradiated with a UV lamp at 365 nm under argon atmosphere until tert-butyl 3,5-bis(but-3-en-1-yloxy)benzoate 6 was fully consumed (TLC monitoring, 16 h). Then, the solvent was removed under vacuum and the crude product was purified by a flash column chromatography through silica gel eluting with hexane/AcOEt = 10:1, obtaining the pure product P1 as colorless oil (1.66 g, 70% yield) [44]. 1 H NMR (360 MHz, CDCl3 ) δ (ppm): 7.09 (br s, 2H), 6.58 (br s, 1H), 3.97 (t, J = 7.2 Hz, 4H), 3.82 (q, J = 7.2 Hz, 12H), 2.56 (apparent q, J = 7.2 Hz, 8H), 1.88-1.76 (m, 4H), 1.74–1.70 (m, 8H), 1.57 (s, 9H), 1.21 (t, J = 7.2 Hz, 18H), 0.74 (t, J = 7.2 Hz, 4H); 13 C NMR (91 MHz, CDCl3 ) δ (ppm): 165.6, 159.9, 133.8, 107.6, 105.7, 81.2, 67.6, 58.4, 35.1, 31.6, 28.4, 28.1, 26.2, 23.2, 18.3, 9.9. IR (film): 2972.2, 2925.1, 1713.7, 1594.6, 1445.3, 1389.1, 1326.1, 1248.8, 1161.9, 1074.2, 956.6, 768.1 cm−1 . MS (ESI) m/z: 817.4 [M + Na]+ , 749.4, 647.3, 425.3, 393.3; HRMS (ESI) m/z [M + Na]+ calcd for C37 H70 O10 S2 Si2 Na: 817.3841, found: 817.3846. 2.7. Synthesis of 9 To a solution of propane-1,3-diol 8 (7.60 g, 100 mmol) in 200 mL of anhydrous THF was added NaH (4.40 g, 60% dispersion in mineral oil, 110 mmol) portionwise. The mixture was stirred at room temperature for 30 min, then benzyl bromide (18.90 g, 110 mmol) was added dropwise, then tetrabutylammonium iodide (7.40 g, 20 mmol) was added in one portion. The mixture was heated to 60 ◦ C and stirred overnight. After cooling, an equal volume of water was added, and the mixture was extracted with diethyl ether. The combined organic layer was washed with brine, dried over anhydrous Na2 SO4 , and filtered. The solvent was evaporated, and the resulting residue was purified by flash column chromatography on silica gel with hexane/EtOAc = 5:1 to afford a yellow liquid (13.80 g, 83% yield) [45]. 1 H NMR (360 MHz, CDCl3 ) δ (ppm): 7.38–7.28 (m, 5H), 4.53 (s, 2H), 3.80 (apparent q, J = 7.2 Hz, 2H), 3.67 (t, J = 7.2 Hz, 2H), 2.28 (t, J = 3.6 Hz, 1H), 1.91–1.84 (m, 2H). 2.8. Synthesis of 10 To a solution of 3-(benzyloxy)propan-1-ol 9 (9.30 g, 56.0 mmol) in 180 mL of CH2 Cl2 was added PPh3 (15.42 g, 58.8 mmol) and imidazole (4.57g, 61.6 mmol), followed by the portionwise addition of iodine (15.63 g, 61.6 mmol) at 0 ◦ C (ice bath). Then the reaction mixture was stirred at rt for 16 h and then quenched with aqueous Na2 SO3 solution. The organic phase was separated, and the aqueous phase was extracted with CH2 Cl2 . The combined organic layer was dried with Na2 SO4 and then filtered. The solvent was evaporated, the residue was purified by flash column chromatography through silica gel eluting with hexane, obtaining a colorless liquid (12.1 g, 78% yield) [45]. 1 H NMR (360 MHz, CDCl3 ) δ (ppm): 7.38–7.27 (m, 5H), 4.52 (s, 2H), 3.54 (t, J = 7.2 Hz, 2H), 3.31 (t, J = 7.2 Hz, 2H), 2.13–2.06 (m, 2H). 2.9. Synthesis of 11 An excess of [(3-iodopropoxy)methyl]benzene 10 (10.35 g, 37.5 mmol) was added to a stirred solution of 3,5-dihydroxybenzaldehyde 6 (2.07 g, 15 mmol) and cesium carbonate (24.44 g, 75.0 mmol) in anhydrous DMF (120 mL). The reaction was stirred at 40 ◦ C under argon atmosphere until 3,5-dihydroxybenzaldehyde 6 was fully consumed (TLC monitoring, 41 h). Then, water was added (60 mL) and the crude product was extracted with EtOAc (80 mL × 3). The organic phase was washed with water (3 times), dried with anhydrous Na2 SO3 and the solvent was removed under vacuum to afford the crude product as yellow liquid. The pure product was obtained by a flash column chromatography through silica gel eluting with hexane/EtOAc = 5:1, colorless oil (6.07 g, 93% yield) [45]. 1 H NMR (360 MHz, CDCl3 ) δ (ppm): 9.88 (s, 1H), 7.33–7.27 (m, 10H), 7.00 (d, J = 3.6 Hz, 2H), 6.69 (t, J = 3.6 Hz, 1H), 4.53 (s, 4H), 4.12 (t, J = 7.2 Hz, 4H), 3.66 (t, J = 7.2 Hz, 4H), 2.13–2.05 (m, 4H); 13 C NMR (91 MHz, CDCl3 ) δ (ppm): 192.1, 160.6, 151.8, 138.3, 128.4, 127.7, 127.6, 108.0, 107.7, 73.1, 66.6, 65.3, 29.6. IR (film): 3029.5, 2932.3, 1696.8, 1591.9, 1452.1, 1295.4, 1164.7, 1094.2, 734.2, 696.7 cm−1 . ESI-MS m/z: 457.2 [M + Na]+ , 306.9, 249.9, 181.1, 165.1, 141.1, 91.1; HRMS (ESI) m/z [M + Na]+ calcd for C27 H30 O5 Na: 457.1985, found: 457.1984. Materials 2020, 13, 1569 6 of 16 2.10. Synthesis of 12 3,5-Bis[3-(benzyloxy)propoxy]benzaldehyde 11 (3.70 g, 8.5 mmol) was dissolved in acetonitrile (20 mL), then a solution of NaH2 PO4 ·2H2 O (358.0 mg, 2.30 mmol) in water (5.0 mL) and 30% H2 O2 (1.1 mL, 9.97 mol/L, 10.97 mmol) was added. Finally, a solution of 80% purity NaClO2 (1.36 g, 12.0 mmol) in water (12 mL) was added dropwise during 2 h to the stirred mixture at room temperature. The O2 produced from the solution was monitored until the end of the reaction with a bubbler connected to the flask. A little amount of Na2 SO3 was added to destroy the unreacted oxidants. The mixture was acidified with 10% aqueous HCl, and the product was extracted using ethyl acetate (80 mL × 3). The organic phase was dried with anhydrous sodium sulfate and the solvent was removed under vacuum to afford the crude product, which was purified by a flash column chromatography through silica gel eluting with hexane/EtOAc = 1:2, white solid (3.78 g, 99% yield) [42]. 1 H NMR (360 MHz, CDCl3 ) δ (ppm): 7.32–7.24 (m, 12H), 6.67 (br s, 1H), 4.53 (s, 4H), 4.12 (t, J = 7.2 Hz, 4H), 3.67 (t, J = 7.2 Hz, 4H), 2.18–2.05 (m, 4H); 13 C NMR (91 MHz, CDCl3 ) δ (ppm): 160.1, 152.7, 138.3, 129.8, 128.4, 127.7, 127.6, 108.3, 107.4, 73.1, 66.6, 65.2, 29.6. IR (film): 3651.4, 3024.9, 2861.2, 1686.4, 1593.5, 1445.7, 1393.4, 1297.5, 1169.4, 1091.7 cm−1 . ESI-MS m/z: 473.2 [M + Na]+ , 433.2, 283.1, 239.1, 181.1, 122.1; HRMS (ESI): m/z [M + Na]+ calcd for C27 H30 O6 Na: 473.1935, found: 473.1937. 2.11. Synthesis of 13 In a 10-mL round bottom flask, 3,5-bis[3-(benzyloxy)propoxy]benzoic acid 12 (5.40 g, 12.0 mmol), di-tert-butyl dicarbonate (5.24 g, 24.0 mmol) and 4-dimethylaminopyridine (439.8 mg, 3.6 mmol) were dissolved in tert-butanol (80 mL). The reaction mixture was stirred at 40 ◦ C under argon atmosphere until 3,5-bis[3-(benzyloxy)propoxy]benzoic acid 12 was fully consumed (TLC monitoring, 48 h). Then, the solvent was removed under vacuum and the crude product was purified by flash column chromatography through silica gel eluting with hexane/AcOEt = 10:1, obtaining the pure product 13 as colorless oil (4.25 g, 70% yield) [43]. 1 H NMR (360 MHz, CDCl3 ) δ (ppm): 7.33–7.12 (m, 10H), 7.13 (d, J = 3.6 Hz, 2H), 6.60 (t, J = 3.6 Hz, 1H), 4.52 (s, 4H), 4.09 (t, J = 7.2 Hz, 4H), 3.65 (t, J = 7.2 Hz, 4H), 2.10–2.04 (m, 4H), 1.58 (s, 9H); 13 C NMR (91 MHz, CDCl3 ) δ (ppm): 165.6, 159.6, 138.4, 133.9, 128.4, 127.65, 127.60, 107.8, 105.8, 81.1, 73.1, 66.7, 65.1, 29.7, 28.2. IR (film): 3651.4, 2930.3, 2860.4, 1710.1, 1593.9, 1445.8, 1300.6, 1160.7, 1096.4, 731.9, 696.7 cm−1 . ESI-MS m/z: 529.3 [M + Na]+ , 451.3, 433.2, 283.1, 265.1, 181.1, 122.1; HRMS (ESI): m/z [M + Na]+ calcd for C31 H38 O6 Na: 529.2561, found: 529.2555. 2.12. Synthesis of 14 A mixture of tert-butyl 3,5-bis[3-(benzyloxy)propoxy]benzoate 13 (1.40 g, 2.77 mmol) and preequilibrated 10% Pd/C (0.308 g, 0.029 mmol Pd) in absolute ethanol (20 mL) was hydrogenated at room temperature and atmospheric pressure. When tert-butyl 3,5-bis[3-(benzyloxy)propoxy]benzoate 13 was fully consumed (TLC monitoring, 17 h), the reaction mixture was filtered through celite® 545, the filtrate was evaporated to give the crude product. The final pure product was obtained by flash column chromatography (silica gel eluting with hexane/EtOAc = 1:2), white solid (858 mg, 95% yield) [46]. 1 H NMR (360 MHz, CDCl3 ) δ (ppm): 7.14 (d, J = 3.6 Hz, 2H), 6.62 (t, J = 3.6 Hz, 1H), 4.16–4.12 (m, 4H), 3.85 (t, J = 7.2 Hz, 4H), 2.07–2.01 (m, 4H), 1.58 (s, 9H); 13 C NMR (91 MHz, CDCl3 ) δ (ppm): 165.4, 159.7, 134.0, 107.8, 105.8, 81.3, 65.9, 60.3, 31.9, 28.1. IR (film): 3274.5, 2967.9, 2870.6, 1705.7, 1595.1, 1447.7, 1349.7, 1299.2, 1169.9, 1058.6, 847.4, 767.4 cm−1 . ESI-MS m/z: 349.2 [M + Na]+ , 293.1, 271.1, 253.1, 195.1, 122.1; HRMS (ESI): m/z [M + Na]+ calcd for C17 H26 O6 Na: 349.1622, found: 349.1618. 2.13. Synthesis of P2 In a 100-mL Schlenk tube under nitrogen, tert-butyl 3,5-bis(3-hydroxypropoxy)benzoate 14 (1.96 g, 6.0 mmol) and 3-(isocyanatopropyl)triethoxysilane 15 (7.42 g, 7.42 mL, 1.0 g/mL, 30.0 mmol) were dissolved in dry THF (20 mL). The mixture was stirred under reflux and argon atmosphere. After 17 h, the starting material was fully consumed (TLC monitoring). Then, the solvent was removed under Materials 2020, 13, 1569 7 of 16 reduced pressure and the residue was purified by flash column chromatography through silica gel eluting with hexane/EtOAc = 2:1 to obtain the pure product P2 as colorless oil (4.90 g, 100% yield). 1 H NMR (360 MHz, CDCl ) δ (ppm): 7.12 (broad s, 2H), 6.59 (t, J = 3.6 Hz, 1H), 4.99 (br s, 2H), 4.22 3 (t, J = 7.2 Hz, 4H), 4.05 (t, J = 7.2 Hz, 4H), 3.81 (q, J = 7.2 Hz, 12H), 3.18 (q, J = 7.2 Hz, 4H), 2.09-2.04 (m, 4H), 1.72–1.61 (m, 4H), 1.57 (s, 9H), 1.21 (t, J = 7.2 Hz, 18H), 0.62 (t, J = 7.2 Hz, 4H); 13 C NMR (91 MHz, CDCl3 ) δ (ppm): 165.5, 159.7, 156.5, 133.8, 107.7, 105.8, 81.2, 64.6, 61.3, 58.4, 43.4, 28.9, 28.1, 23.3, 18.3, 7.6. IR (film): 3343.6, 2972.7, 2927.5, 1708.6, 1595.9, 15527.2, 1242.3, 1163.0, 1071.9, 953.2, 767.1 cm−1 . ESI-MS m/z: 843.1 [M + Na]+ , 775.4, 729.3, 673.3; HRMS (ESI): m/z [M + Na]+ calcd for C37 H68 N2 O14 Si2 Na: 843.4101, found: 843.4108. 2.14. General Procedure for the Preparation of E-Pn 90/10 or 75/25 PMO NPs A solution of CTAB (250 mg, 0.686 mmol) in Mili-Q water (120 mL) was placed in a 250 mL round bottom flask, then 2 M NaOH (875 µL) was added (1.75 mmol of NaOH). The mixture was stirred at 1000 rpm at 80 ◦ C for 50 min. After that, the stirring speed was increased to 1400 rpm and a mixture of 100% E-BTSE with Pn (for 90/10: 2.00 mmol E-BTSE and 0.2 mmol Pn; for 75/25: 1.65 mmol E-BTSE and 0.55 mmol Pn) was added rapidly under stirring. The condensation process was conducted for another 120 min at 80 ◦ C. Afterwards, the suspension was cooled to room temperature and the nanoparticles were collected by centrifugation (13500 rpm for 45 min). The samples were then extracted with a solution of NH4 NO3 (6 g/L in 96% EtOH) for three times and washed successively with 96% ethanol, Mili-Q water, 96% ethanol. The E-Pn PMO NPs were obtained as white solids [39]. E-P1 90/10 PMO NPs: 13 C-CP-MAS NMR (75 MHz) δ (ppm): 165, 160, 146, 134, 107, 82, 68, 58, 33, 28, 24, 17, 13. IR ν (ATR) (cm−1 ): 3311.8, 2975.4, 1692.3, 1596.5, 1449.9, 1187.3, 1033.1, 923.2, 788.5. BET: SBET = 973 m2 g−1 , Vpore = 0.66 cm3 g−1 , ∅pore = 2.73 nm. TGA (air, 5 ◦ C /min, 20–1000 ◦ C) residual mass 77%. Zeta Potential: ζ = −30.9 mV, pH = 6.80. DLS: 1122 nm. E-P2 90/10 PMO NPs: 13 C-CP-MAS NMR (75 MHz) δ (ppm): 165, 160, 146, 134, 109, 81, 63, 58, 44, 28, 24, 17, 11. IR ν (ATR) (cm−1 ): 3316.2, 1695.5, 1448.5, 1187.9, 1035.2, 923.1, 789.2. BET: SBET = 696 m2 g−1 , Vpore = 0.37 cm3 g−1 , ∅pore = 2.13 nm. TGA (air, 5 ◦ C/min, 20–1000 ◦ C) residual mass 75%. Zeta Potential: ζ = −38.2 mV, pH = 6.72. DLS: 694 nm. E-P1 75/25 PMO NPs: 13 C-CP-MAS NMR (75 MHz) δ (ppm): 165, 160, 146, 134, 107, 81, 68, 58, 34, 29, 18, 13. IR ν (ATR) (cm−1 ): 3359.1, 1709.4, 1594.2, 1447.0, 1035.6, 924.5, 790.3. BET: SBET = 259 m2 g−1 , Vpore = 0.17 cm3 g−1 , ∅pore = 2.59 nm. TGA (air, 5 ◦ C/min, 20–1000 ◦ C) residual mass 67%. Zeta Potential: ζ = −25.6 mV, pH = 9.07. DLS: 742 nm. E-P2 75/25 PMO NPs: 13 C-CP-MAS NMR (75 MHz) δ (ppm): 166, 160, 158, 146, 134, 111, 105, 81, 64, 58, 44, 28, 24, 18, 11. IR ν (ATR) (cm−1 ): 3340.1, 1692.2, 1447.3, 1188.5, 1035.8, 922.5, 791.1. BET: SBET = 329 m2 g−1 , Vpore = 0.26 cm3 g−1 , ∅pore = 2.74 nm. TGA (air, 5 o C/min, 20–1000 ◦ C) residual mass 63%. Zeta Potential: ζ = −42.3 mV, pH = 6.85. DLS: 562 nm. 3. Results and Discussion 3.1. Synthesis of the Disilylated Precursors P1 and P2 The synthesis of P1 is depicted in Scheme 1. We first converted commercial 3-buten-1-ol 1 into but-3-en-1-yl methanesulfonate 2 [40]. The dialkylation of commercial 3,5-dihydroxybenzaldehyde, 3, with the mesylate 2, in the presence of cesium carbonate in DMF at 40 ◦ C, afforded 4 in 78% isolated yield after chromatographic purification [41]. The aldehyde 4 was oxidized to the carboxylic acid 5 by using NaClO2 , 30% H2 O2 and NaH2 PO4 in aqueous acetonitrile at room temperature [42]. Subsequent treatment of 5 with Boc2 O and 4-dimethylaminopyridine (DMAP) in tert-butanol at room temperature provided the ester 6 in 85% isolated yield [43]. Finally, the precursor P1 was obtained in 70% isolated yield by the versatile thiol-alkene click reaction between dialkene 6 and (3-mercaptopropyl)triethoxysilane 7 under irradiation at 365 nm using 2,2-dimethoxy- 1,2-diphenylethanone (DMPA) as initiator [44]. Materials 2020, 13, 1569 8 of 16 Materials Materials 2020, 2020, 13, 13, xx FOR FOR PEER PEER REVIEW REVIEW 88of of16 16 Scheme 1. Scheme 1. Synthesis of precursor P1. Scheme 1.Synthesis of precursor Synthesis of precursorP1. P1. In Scheme In Scheme 2, 2, we we summarize summarize the the preparation preparation of of precursor precursor P2.P2. We We first first synthesized synthesized [(3-[(3- In Scheme 2, we summarize iodopropoxy)methyl)]benzene the preparation 10 (65% (65% overall yield) of precursor P2. We first synthesized [(3- iodopropoxy)methyl)]benzene 10 overall yield) from from thethe commercially commercially available available 1,3- 1,3- iodopropoxy)methyl)]benzene propanediol 88 through through the 10 (65% overall the monobenzylated yield) monobenzylated intermediatefrom the commercially available 1,3-propanediol propanediol intermediate 99 [45]. [45]. Then, Then, commercial commercial 3,5- 3,5- through the monobenzylated 8dihydroxybenzaldehyde intermediate 9 [45]. Then, commercial 3,5-dihydroxybenzaldehyde 3 dihydroxybenzaldehyde 33 was was dialkylated dialkylated with with thethe iodide iodide 1010 to to obtain obtain the the aldehyde aldehyde 11. 11. The The next next was dialkylated steps were with were oxidation the oxidation to iodide to the 10 to the carboxylicobtain carboxylic acid the acid 12, aldehyde 11. The next steps were oxidation to the steps 12, formation formation of of tert-butyl tert-butyl ester ester 13, 13, followed followed by by carboxylic acidof deprotection formation 12,benzylic of tert-butyl ethers, leading ester to the followed of 13,obtention by diol deprotection 14 in highof yield benzylic ethers, [46]. leading Subsequent deprotection of benzylic ethers, leading to the obtention of diol 14 in high yield [46]. Subsequent totreatment the obtention of diol of this this 14 in high compound yield with the[46]. Subsequent silylated treatment isocyanate of this compound with the silylated treatment of compound with the silylated isocyanate 15 15 provided provided thethe disilylated disilylated carbamate carbamate isocyanate precursor 15 P2 provided in the quantitative disilylated yield. carbamate precursor P2 in quantitative yield. precursor P2 in quantitative yield. Scheme 2. Synthesis of precursor P2. Scheme 2. Scheme 2. Synthesis of precursor P2. 3.2. Preparationand 3.2. and Characterization ofof E-Pn 90/10 PMO NPs NPs and and E-Pn E-Pn 75/25 75/25 PMO NPs 3.2. Preparation Preparation and Characterization E-Pn 90/10 Characterization of E-Pn 90/10 PMO PMO NPs and E-Pn 75/25 PMO PMO NPsNPs With thoseprecursors With precursors P1and and P2 in hand, a series of of E-Pn PMO NPs were preparedby by mixing Withthose those precursorsP1 P1 andP2P2ininhand, hand,a series a series E-Pn of E-PnPMOPMO NPs NPswere wereprepared prepared mixing by mixingthe the corresponding corresponding disilylated disilylated precursor precursor and and (E)-BTSE(E)-BTSE (named(named E) E) as E) as major major reagent reagent [38] [38] The The syntheses the corresponding disilylated precursor and (E)-BTSE (named as major reagent [38]syntheses were The syntheses were performed performed in Mili-Q in Mili-Q water withas water with CTAB as template under basic catalysis (NaOH).(NaOH). The micellar were performed in Mili-Q waterCTAB with CTABtemplate under basic as template undercatalysis basic catalysis The micellar (NaOH). solution The micellar solution was was prepared prepared at5080min 80 ◦ C forat °C for 50a stirring min with a stirring speed adjusted rpm. at 1000 rpm. Then,speed the solution was at prepared 80 °C with for 50 min with speed adjusted a stirring at 1000 speed adjusted Then, at 1000the stirring rpm. Then, the stirring was speed enhanced was enhanced to 1400 rpm, a mixture of (E)-BTSE (or E) and different amounts of the stirring speed to 1400 was rpm, a mixture enhanced of (E)-BTSE to 1400 rpm, a mixture (orof and different E)(E)-BTSE (or E)amounts of theamounts and different corresponding of the corresponding disilylated precursor Pn was quickly added and the mixture was left to react for ◦ C 120 disilylated precursor corresponding Pn was disilylated quickly added precursor Pn wasand the mixture quickly added andwas the left mixture to react for was120 leftmin at 80 for to react [39]. 120 min at 80 °C [39]. E-Pn PMO NPs were collected by centrifugation. The template was then removed min at 80 °C [39]. E-Pn PMO NPs were collected by centrifugation. The template was then removed by washing with a solution of NH4NO3 (6 g/L in 96% EtOH). Herein, two different ratios of E/Pn were by washing with a solution of NH4NO3 (6 g/L in 96% EtOH). Herein, two different ratios of E/Pn were Materials 2020, 13, 1569 9 of 16 E-Pn PMO NPs were collected by centrifugation. The template was then removed by washing with a Materials 2020, 13, x FOR PEER REVIEW 9 of 16 solution of NH4 NO3 (6 g/L in 96% EtOH). Herein, two different ratios of E/Pn were prepared, namely 90/10 and 75/25, prepared, namely in order 90/10 to investigate and 75/25, in the influence order on the size, to investigate morphology the influence andsize, on the textural propertiesand morphology of the resulting nanomaterials (Scheme 3). textural properties of the resulting nanomaterials (Scheme 3). Scheme 3. Scheme 3. Preparation Preparation of of E-Pn E-Pn PMO PMONPs. NPs. All the All the mixed mixedPMO PMONPs were NPs werecharacterized characterizedby transmission electronelectron by transmission microscopy (TEM), microscopy nitrogen-sorption (TEM), measurements nitrogen-sorption measurements(BET),(BET), dynamic dynamic light lightscattering scattering (DLS), zeta-potential, (DLS), zeta-potential, thermogravimetric analysis thermogravimetric (TGA),1313C analysis (TGA), C CP CP MAS MAS solid solid state state NMR, NMR, Fourier-transform Fourier-transform infrared infrared spectroscopy (FTIR) spectroscopy (FTIR) and small-angle small-angle X-ray X-ray diffraction diffraction(p-XRD). (p-XRD).Table Table1 1shows showsthethephysical physicaldata of data these of new these newmaterials. materials. Table1.1. Some Table Some data data of of E-Pn E-PnPMO PMONPs. NPs. N N22-Sorption -Sorption Measurements Measurements Zeta Zeta Potential Potential Particles Particles Size d d Material Material SBET SBET VVpore pore ∅∅ pore pore c TGA TGA Size (nm) (nm) c pH pH (mV) (mV) 2 −1 (m g2g (m −1) ) (cm g−1−1)) a (cm3 3g (nm) b E-P190/10 E-P1 PMO NPs 90/10 PMO NPs 973 973 0.66 0.66 2.7 2.7 1122 1122 6.80 6.80 −30.9 −30.9 77% 77% E-P290/10 PMO NPs 696 0.37 2.1 694 6.72 −38.2 75% E-P175/25 PMO NPs 259 0.17 2.6 742 9.07 −25.6 67% E-P2 90/10 PMO NPs 696 0.37 2.1 694 6.72 −38.2 75% E-P275/25 PMO NPs 329 0.23 2.7 562 6.85 −42.3 63% a Determined by BET at saturation of p/p◦ = 0.98. b Pore diameter determined with BJH. c Hydrodynamic diameters, E-P1 75/25 PMO NPs 259 0.17 2.6 DLS. d Residual mass by TGA (heating rate 10 ◦ C/min, 20 to 1000 ◦ C). 742 9.07 −25.6 67% E-P2 75/25 PMO NPs 329 0.23 2.7 562 6.85 −42.3 63% The morphologies of E-Pn PMO NPs were first investigated by TEM (Figure 2). All the a Determined by BET at saturation of p/p° = 0.98. b Pore diameter determined with BJH. c Hydrodynamic nanomaterials were obtained as rodlike-shape nanoparticles, similarly to the parent pure E PMO diameters, NPs DLS. [11], with d Residual mass by.TGA (heating rate 10 °C/min, 20 to 1000 °C). the length of nanorods ranging from 400 to 600 nm. The hydrodynamic diameters were determined by DLS The morphologies and the obtained of E-Pn PMO values NPs (from were 560 firsttoinvestigated 1100 nm, Table by 1) are consistent TEM (Figure 2).with All the the sizes found by TEM. The zeta potentials (Table 1) were determined in water and gave negative nanomaterials were obtained as rodlike-shape nanoparticles, similarly to the parent pure E PMO NPs values due [11],towith the presence the length of of deprotonated silanol groups nanorods ranging from 400at the surface to 600 nm.of thehydrodynamic The nanorods. The diameters high valueswere are indicative of stability. determined by DLS and the obtained values (from 560 to 1100 nm, Table 1) are consistent with the sizes found by TEM. The zeta potentials (Table 1) were determined in water and gave negative values due to the presence of deprotonated silanol groups at the surface of the nanorods. The high values are indicative of stability. Materials 2020, 13, 1569 10 of 16 Materials 2020, 13, x FOR PEER REVIEW 10 of 16 Figure Figure2.2.TEM TEMimages imagesofofE-Pn E-PnPMO PMONPs. NPs. The Theporosity porosityofofthethenanomaterials nanomaterials was wasproved provedby by N2-sorption experiments N2 -sorption experiments (Figure 3). Note (Figure that 3). Note whereas the SBET that whereas thefor SBETmaterials formed for materials with 25% formed withof25% Pn of were foundfound Pn were between 259 and between 259329 andm3292g−1,m 2 g−1 , E-Pn 90/10 PMO PMO E-Pn 90/10 NPs NPspresented highhigh presented specific surface specific areas surface ranging areas from ranging from 696 696toto973 973m −1−1 m2g2 g (Table (Table1), 1), comparable comparable toto or or even even higher than pure E PMO nanorods nanorods (already (alreadysynthesized) synthesized)[11][11]which whichshowed showeda aspecific specificsurface surfacearea 800mm22gg−1 areaofof800 −1. E-P1 E-P1 90/10 90/10 PMO PMO NPs NPs presented presented aa type type IV IV isotherm isothermwithwithaasmall small hysteresis hysteresisin inagreement agreementwith withaamesoporous mesoporousstructure structureof ofhigh highspecific specificsurface surfacearea areaand andpore poresizesizeof of2.7 2.7 nm. nm.E-P2 E-P290/10 90/10PMO PMONPs NPsshowed showedan anisotherm isothermbetween betweentype typeI Iand andIV. IV. The Themicroporosity microporosityisispresent present with withaapore pore size size of of 2.1 2.1 nm nm and and aa lower lower specific specific surface area than E-P1 90/10 PMO NPs of 696 m22gg−1−1. . surface area Materials 2020, 13, 1569 11 of 16 Materials 2020, 13, x FOR PEER REVIEW 11 of 16 Materials 2020, 13, x FOR PEER REVIEW 11 of 16 Figure 3. a)3.N(a) Figure N2 -sorption 2-sorption isotherms isotherms of PMO of E-Pn E-Pn NPs; PMOb) BJH(b) NPs; BJH dV/dw dV/dw Pore Volume Pore Volume of E-P1 of E-P1 90/10 90/10 PMO NPs. Figure 3. a) N2-sorption isotherms of E-Pn PMO NPs; b) BJH dV/dw Pore Volume of E-P1 90/10 PMO NPs. PMO NPs. In the Inthe TGA theTGA analyses TGAanalyses (Figure analyses(Figure 4), (Figure4), the 4),the loss theloss of lossof mass ofmass corresponding masscorresponding correspondingto to adsorbed toadsorbed water adsorbedwater (up water(up to (upto 120 120◦°C) to120 °C) was In observed first. The loss of the tert-butoxycarbonyl group took place from 150 °C to 300 °C. C) Thus, was was observed observed first. first. The The loss loss of the tert-butoxycarbonyl of the tert-butoxycarbonyl group took group took place from place from at 150 150 ◦°C to 300 ◦°C. Thus, C to 300 C. Thus, this group thisgroup was groupwas found wasfound foundtoto be bevery tobe verystable stableininthe thematerials materialsin insolid soliddry drystate. state.Then, athigher Then, at highertemperatures, temperatures, this the decomposition of the very remainingstable in the organic materials part of thein solid dry materials state. Then, occurred. higher temperatures, the decomposition of the remaining organic part of the materials the decomposition of the remaining organic part of the materials occurred. occurred. Figure 4. TGA of E-Pn PMO NPs. Figure4.4. TGA Figure TGAof ofE-Pn E-PnPMO PMONPs. NPs. 13C CP MAS solid-state NMR of these new nanomaterials were also recorded. The superposition 13 13C CP MAS solid-state NMR of these new nanomaterials were also recorded. The superposition C CP MAS solid-state NMR of these new nanomaterials were also recorded. The superposition of of the the 13C ofthe 13 13 CNMR C NMRspectra NMR spectraof spectra ofPn of Pnin Pn insolution in solutionand solution andof and ofE-Pn of E-PnPMO E-Pn PMONPs PMO NPsin NPs insolid in solidstate solid stateshowed state showedaaagood showed goodmatch, good match, match, suggesting suggesting thereby thereby that that the the integrity integrity of of the the organic organic moiety moiety of of the the precursor precursor suggesting thereby that the integrity of the organic moiety of the precursor Pn had been preserved Pn Pn had had been been preserved preserved (Figure (Figure 5). (Figure5). For 5).For E-P1 ForE-P1 E-P1PMOPMO PMONPs, NPs, NPs,thethe characteristic thecharacteristic signals characteristicsignals (in signals(in ppm) (inppm) appear ppm)appearappearat at about atabout 165 about165 (C=O (C=Oof 165(C=O ofester), of ester), ester), 81 81 (Cq 81(Cq of (Cqof tBu), oftBu), 29 tBu),29 (CH 29(CH (CH33of 3 of tBu), oftBu), tBu),1313 (CH 13(CH –Si), (CH22–Si), 2 together –Si), together with together with the with the carbons the carbons carbons of of the ofthe aromatic thearomatic ring aromaticring and ringand the andthethe methylenic methylenic carbons carbons of of the the linker. linker. A A similar similar pattern pattern is is observed observed for for E-P2 E-P2 methylenic carbons of the linker. A similar pattern is observed for E-P2 PMO NPs, with additional PMO PMO NPs, NPs, with with additional additional signal signal at signalat about atabout 158 about158 (C=O (C=Oof 158(C=O ofcarbamate). of carbamate).Moreover, carbamate). Moreover, Moreover,the the theintense intense signal intensesignal signalat at about atabout about146146 ppm 146ppm ppminin inboth bothspectra both spectra spectra is due isisdue to dueto the tothe olefinic theolefinic carbons olefiniccarbons of E-BTSE. carbonsofofE-BTSE. E-BTSE. Materials 2020, 13, 1569 12 of 16 Materials 2020, 13, x FOR PEER REVIEW 12 of 16 Materials 2020, 13, x FOR PEER REVIEW 12 of 16 Figure5.5.1313C Figure C NMR NMR of of Pn Pn in in CDCl CDCl3 (above) (above) and and 13CCCP 13 CPMAS MASNMR NMRofofE-Pn E-Pn75/25 75/25PMO PMONPs NPs(below). (below). Figure 5. 13C NMR of Pn in CDCl33 (above) and 13C CP MAS NMR of E-Pn 75/25 PMO NPs (below). FTIRspectra FTIR spectra of of precursors precursors P1 and P2 (Figure (Figure 6) 6) show showthe thepresence presenceofoftert-butyl tert-butylgroup group(2974/2973 (2974/2973 −1, FTIR cm−1 spectra of precursors P1 and P2 (Figure 6) ester show in the presence of tert-butyl group (2974/2973 cm , υυ CH CH33),),carbonyl carbonylgroup group(1713 (1713cm cm−1,−1 υ , C=O of υ C=O of ester P1; broad in P1; signal broad at 1709 signal cm−1cm at 1709 in−1 P2infor P2 cm , υ CH3C=O −1 overlapped ), carbonyl fromfrom group the ester (1713 −1 cm , υ C=O and carbamate) andof silicon-oxygen ester in P1; broad bondsignal (υ −1 at 1709 Si–O cm in P2 cm−1for for overlapped C=O the ester and carbamate) and silicon-oxygen bond (υatSi–O 1076/1072 at 1076/1072 ). overlapped The−1 C=O corresponding from the signals ester are and also carbamate) visible in and E-Pn silicon-oxygen 75/25 PMO NPs bond (υ (Figure Si–O 6), at with1076/1072 a shift forcmthe −1). cm ). The corresponding signals are also visible in E-Pn 75/25 PMO NPs (Figure 6), with a shift for The corresponding carbonyl group signals are to 1709/1693 cm−1also −1visible . The in E-Pn 75/25inPMO NPs (Figure 6), PMO with aNPsshift is for the the carbonyl group to 1709/1693 cm .absorption of C=O The absorption the case of C=O of case in the E-P1of90/10 E-P1 90/10 PMO barely NPs is carbonyl visible duegroup thetoto todue 1709/1693 high cmof .the −1 Theprecursor. absorption of C=O in the andcase of E-P1 90/10 PMO NPs cmis−1 barely barely visible thedilution high dilution The of the precursor. intense The intensebroad and band broadatband1200–1000 at 1200–1000 (υcm Si–−1 visible O–Si) isdue to the characteristichigh ofdilution a well of the condensedprecursor. The material. intense and broad band at 1200–1000 cm −1 (υ Si– (υ Si–O–Si) is characteristic of a well condensed material. O–Si) is characteristic of a well condensed material. Figure 6. FTIR of Pn and E-Pn PMO NPs. Figure 6. Figure 6. FTIR FTIR of of Pn Pn and and E-Pn E-Pn PMO NPs. PMO NPs. The amall angle X-ray diffraction (p-XRD) analyses show an organized porosity for E-P1 90/10 PMO The The NPsamall amall typicalangle angle X-ray forX-ray diffraction diffraction a hexagonal (p-XRD) analyses (p-XRD) 2D symmetry analyses an organized showBragg with a sharp organized porosityandfor porosity peak [(1,0,0)] theE-P1 for two90/10 E-P1 90/10 first PMO PMO NPs NPs typical typical for aa hexagonal hexagonal 2D 2D symmetry symmetry with a with sharp a Bragg sharp peak Bragg [(1,0,0)] peak and [(1,0,0)] harmonics [(1,1,0) and (2,0,0)]. The other mixed E-Pn PMO NPs are disordered, with a broad non- the and two the first two harmonics first [(1,1,0) harmonics and [(1,1,0) (2,0,0)]. and The (2,0,0)]. other The mixed other E-Pn mixed structured band typical of worm-like mesoporosity (Figure 7). PMOPMO E-Pn NPs are NPsdisordered, are with disordered, a broad with a non- broad structured band non-structured typical band of worm-like typical mesoporosity of worm-like (Figure mesoporosity 7). 7). (Figure Materials 2020, 13, 1569 13 of 16 Materials 2020, 13, x FOR PEER REVIEW 13 of 16 Figure 7. Small Figure angle 7. Small XRDXRD angle diagram of E of diagram PMO NPs (green E PMO line), line), NPs (green E-P1 90/10 (blue line), E-P1 90/10 (blue E-P1 line),75/25 E-P1 (red line). 75/25 (red line). As the synthesis of PMO NPs with large and flexible organic bridging groups within the As mesoporous the synthesis wall is stillof aPMO NPs with challenge, large and flexible the development organic of these new bridging groupsmesoporous mixed periodic within the mesoporous wall is still a challenge, the development of these new mixed organosilica nanoparticles is growing. The subsequent hydrolysis of the tert-butyl ester groups in periodic mesoporous organosilica those materials nanoparticles would giveisrise growing. to mixed ThePMO subsequent hydrolysis NPs bearing acidicofand tert-butyl estercarboxyl the coordinating groups in those groups, materials would give rise to mixed PMO NPs bearing acidic and coordinating which are very relevant for potential applications in nanomedicine for pH-triggered drug delivery carboxyl groups, which are veryorrelevant [47,48] for potential in catalysis [49]. applications in nanomedicine for pH-triggered drug delivery [47,48] or in catalysis [49]. 4. Conclusions 4. Conclusions In summary, novel mixed E-Pn PMO NPs have been prepared by sol-gel co-condensation of E- In summary, novel mixed((E)-BTSE 1,2-bis(triethoxysilyl)ethylene E-Pn PMO or NPs have E) with been prepared previously by sol-gel synthesized co-condensation disilylated tert-butyl 3,5-of E-1,2-bis(triethoxysilyl)ethylene ((E)-BTSE or E) with previously synthesized dialkoxybenzoates bearing either sulfide (precursor P1) or carbamate (precursor P2) functionalities disilylated tert-butyl 3,5-dialkoxybenzoates in the linker. Two different bearing ratios either of sulfide E/Pn(precursor P1) or carbamate were examined, namely 90/10(precursor P2) functionalities and 75/25, in order to in the linker. the investigate Two influence different ratios on of theE/Pn were size, examined, namely morphology 90/10 andproperties and textural 75/25, in order to investigate of the resulting the influence onThe nanomaterials. thesyntheses size, morphology were performedand textural properties in Mili-Q water withof the resulting CTAB nanomaterials. as micellar template under The syntheses were(NaOH) basic catalysis performedat 80in°CMili-Q under water magnetic with CTAB as micellar template under basic catalysis stirring. (NaOH) at 80 ◦ C under magnetic stirring. The mixed E-Pn PMO NPs were characterized by TEM, DLS, zeta-potential, nitrogen-sorption The mixed(BET), measurements E-Pn PMO TGA,NPs were FTIR, 13C characterized CP MAS solidbystate TEM, DLS,and NMR zeta-potential, p-XRD. All the nitrogen-sorption nanomaterials measurements (BET), TGA, FTIR, 13 C CP MAS solid state NMR and p-XRD. All the nanomaterials were obtained as mesoporous rodlike-shape nanoparticles, similarly to the parent pure E PMO NPs, were obtained the length as mesoporous of nanorods rangingrodlike-shape from 400–600 nanoparticles, similarly toby nm as demonstrated theTEM. parentThe pure E PMOofNPs, integrity the the length of nanorods ranging from 400–600 nm as demonstrated by TEM. organic skeleton of the corresponding precursor Pn has been preserved in the nanomaterials as The integrity of the organic skeleton shown byofFTIR the corresponding and 13C CP MAS precursor solid state PnNMR.has been preserved Remarkably, in the nanomaterials whereas the specific surfaceas shown by for E-Pn FTIR and 13 C CP MAS solid state NMR. Remarkably, whereas the specific surface for E-Pn 75/25 75/25 PMO NPs were found between 260 and 330 m2g−1, E-Pn 90/10 PMO NPs presented high specific PMO surface NPs areaswere foundfrom ranging between 700 to260970and m2g330 m2 g−1 , E-Pn −1, comparable or 90/10 PMO NPs even higher thanpresented pure E PMO high specific nanorods. surface areas ranging from 700 to 970 m 2 g−1 , comparable or even higher than pure E PMO nanorods. Moreover, XRD analyses showed an organized porosity for E-P1 90/10 PMO NPs typical of hexagonal Moreover, 2D symmetry. XRDThe analyses other showed materials anwere organized porosity disordered withfora E-P1 broad90/10 PMO NPs typical non-structured band that of hexagonal indicated 2D symmetry. The worm-like mesoporosity. other materials were disordered with a broad non-structured band that indicated worm-like Mixedmesoporosity. PMO NPs bearing acidic and coordinating carboxyl groups resulting from the ester hydrolysis would be very relevant for potential applications in catalysis or in nanomedicine for pH- triggered drug delivery. Author Contributions: Conceptualization, J.-O.D. and R.P.; methodology, H.L.; formal analysis, H.L., R.P. and J.-O.D.; writing—original draft preparation, H.L., J.-O.D. and R.P.; writing—review and editing, J.-O.D., L.R., Materials 2020, 13, 1569 14 of 16 Mixed PMO NPs bearing acidic and coordinating carboxyl groups resulting from the ester hydrolysis would be very relevant for potential applications in catalysis or in nanomedicine for pH-triggered drug delivery. Author Contributions: Conceptualization, J.-O.D. and R.P.; methodology, H.L.; formal analysis, H.L., R.P. and J.-O.D.; writing—original draft preparation, H.L., J.-O.D. and R.P.; writing—review and editing, J.-O.D., L.R., C.C. and R.P.; supervision, J.-O.D., and R.P. All authors have read and agreed to the published version of the manuscript. Funding: This research was funded by China Scholarship Council (CSC) (H.L., No. 201606890025), Ministerio de Ciencia, Innovación y Universidades (MCIU) of Spain (Project RTI2018-097853-B-I00 and RED2018-102387-T), Ministerio de Economía, Industria y Competitividad (MINECO) of Spain (Projects CTQ2014-53662-P and CTQ2016-81797-REDC), DURSI-Generalitat de Catalunya (Project SGR2017-0465) and CNRS (France). Acknowledgments: The authors are grateful to China Scholarship Council (CSC) for predoctoral scholarship to H.L. Conflicts of Interest: The authors declare no conflict of interest. References 1. Hoffmann, F.; Cornelius, M.; Morell, J.; Fröba, M. Silica-Based Mesoporous Organic-Inorganic Hybrid Materials. Angew. Chem. Int. Ed. 2006, 45, 3216–3251. [CrossRef] 2. Hunks, W.J.; Ozin, G.A. Challenges and Advances in the Chemistry of Periodic Mesoporous Organosilicas (PMOs). J. Mater. Chem. 2005, 15, 3716–3724. [CrossRef] 3. Shea, K.J.; Loy, D.A. Bridged Polysilsesquioxanes. Molecular-Engineered Hybrid Organic-Inorganic Materials. Chem. Mater. 2001, 13, 3306–3319. [CrossRef] 4. Manchanda, A.S.; Kruk, M. Synthesis of Large-pore Face-centered-cubic Periodic Mesoporous Organosilicas with Unsaturated Bridging Groups. Microporous Mesoporous Mater. 2016, 222, 153–159. [CrossRef] 5. Park, S.S.; Moorthy, M.S.; Ha, C.S. Periodic Mesoporous Organosilicas for Advanced Applications. NPG Asia Mater. 2014, 6. [CrossRef] 6. Mizoshita, N.; Tani, T.; Inagaki, S. Syntheses, Properties and Applications of Periodic Mesoporous Organosilicas Prepared from Bridged Organosilane Precursors. Chem. Soc. Rev. 2011, 40, 789–800. [CrossRef] 7. Qian, K.; Liu, F.; Yang, J.; Huang, X.; Gu, W.; Jambhrunkar, S.; Yuan, P.; Yu, C. Pore Size-optimized Periodic Mesoporous Organosilicas for the Enrichment of Peptides and Polymers. RSC Adv. 2013, 3, 14466–14472. [CrossRef] 8. Chen, Y.; Meng, Q.; Wu, M.; Wang, S.; Xu, P.; Chen, H.; Li, Y.; Zhang, L.; Wang, L.; Shi, J. Hollow Mesoporous Organosilica Nanoparticles: A Generic Intelligent Framework-Hybridization Approach for Biomedicine. J. Am. Chem. Soc. 2014, 136, 16326–16334. [CrossRef] 9. Croissant, J.G.; Cattoën, X.; Durand, J.-O.; Wong Chi Man, M.; Khashab, N.M. Organosilica Hybrid Nanomaterials with a High Organic Content: Syntheses and Applications of Silsesquioxanes. Nanoscale 2016, 8, 19945–19972. [CrossRef] 10. De Canck, E.; Ascoop, I.; Sayari, A.; Van Der Voort, P. Periodic Mesoporous Organosilicas Functionalized with a Wide Variety of Amines for CO2 Adsorption. Phys. Chem. Chem. Phys. 2013, 15, 9792–9799. [CrossRef] 11. Croissant, J.G.; Cattoën, X.; Wong Chi Man, M.; Gallud, A.; Raehm, L.; Trens, P.; Maynadier, M.; Durand, J.-O. Biodegradable Ethylene-Bis(Propyl)Disulfide-Based Periodic Mesoporous Organosilica Nanorods and Nanospheres for Efficient in-vitro Drug Delivery. Adv. Mater. 2014, 26, 6174–6180. [CrossRef] [PubMed] 12. Noureddine, A.; Trens, P.; Toquer, G.; Cattoën, X.; Wong Chi Man, M. Tailoring the Hydrophilic/Lipophilic Balance of Clickable Mesoporous Organosilicas by the Copper-Catalyzed Azide-Alkyne Cycloaddition Click-Functionalization. Langmuir 2014, 30, 12297–12305. [CrossRef] 13. Corma, A.; Díaz, U.; Arrica, M.; Fernández, E.; Ortega, Í. Organic-Inorganic Nanospheres with Responsive Molecular Gates for Drug Storage and Release. Angew. Chem. Int. Ed. 2009, 48, 6247–6250. [CrossRef] [PubMed] 14. Du, X.; Kleitz, F.; Li, X.; Huang, H.; Zhang, X.; Qiao, S.Z. Disulfide-Bridged Organosilica Frameworks: Designed, Synthesis, Redox-Triggered Biodegradation, and Nanobiomedical Applications. Adv. Funct. Mater. 2018, 28, 1707325. [CrossRef] Materials 2020, 13, 1569 15 of 16 15. Omar, H.; Moosa, B.; Alamoudi, K.; Anjum, D.H.; Emwas, A.H.; El Tall, O.; Vu, B.; Tamanoi, F.; AlMalik, A.; Khashab, N.M. Impact of Pore-Walls Ligand Assembly on the Biodegradation of Mesoporous Organosilica Nanoparticles for Controlled Drug Delivery. ACS Omega 2018, 3, 5195–5201. [CrossRef] [PubMed] 16. Bürglová, K.; Noureddine, A.; Hodačová, J.; Toquer, G.; Cattoën, X.; Wong Chi Man, M. A General Method for Preparing Bridged Organosilanes with Pendant Functional Groups and Functional Mesoporous Organosilicas. Chem. Eur. J. 2014, 20, 10371–10382. [CrossRef] 17. Gomes, A.C.; Lourenço, M.A.; Bruno, S.M.; Ferreira, P.; Valente, A.A.; Pillinger, M.; Gonçalves, I.S. Post-synthetic Modification of Crystal-like Periodic Mesoporous Phenylene-silica with Ferrocenyl Groups. J. Organomet. Chem. 2014, 751, 501–507. [CrossRef] 18. Urata, C.; Yamada, H.; Wakabayashi, R.; Aoyama, Y.; Hirosawa, S.; Arai, S.; Takeoka, S.; Yamauchi, Y.; Kuroda, K. Aqueous Colloidal Mesoporous Nanoparticles with Ethenylene-Bridged Silsesquioxane Frameworks. J. Am. Chem. Soc. 2011, 133, 8102–8105. [CrossRef] 19. Doustkhah, E.; Mohtasham, H.; Farajzadeh, M.; Rostamnia, S.; Wang, Y.; Arandiyan, H.; Assadi, M.H.N. Organosiloxane Tunability in Mesoporous Organosilica and Punctuated Pd Nanoparticles Growth; Theory and Experiment. Microporous Mesoporous Mater. 2020, 293, 109832. [CrossRef] 20. Du, X.; Li, X.; Xiong, L.; Zhang, X.; Kleitz, F.; Qiao, S.Z. Mesoporous Silica Nanoparticles with Organo-bridged Silsesquioxane Framework as Innovative Platforms for Bioimaging and Therapeutic Agent Delivery. Biomaterials 2016, 91, 90–127. [CrossRef] 21. Croissant, J.G.; Fatieiev, Y.; Almalik, A.; Khashab, N.M. Mesoporous Silica and Organosilica Nanoparticles: Physical Chemistry, Biosafety, Delivery Strategies, and Biomedical Applications. Adv. Healthc. Mater. 2018, 7, 1700831. [CrossRef] [PubMed] 22. Kumar, P.; Guliants, V.V. Periodic Mesoporous Organic-inorganic Hybrid Materials: Applications in Membrane Separations and Adsorption. Microporous Mesoporous Mater. 2010, 132, 1–14. [CrossRef] 23. Croissant, J.G.; Cattoën, X.; Man, M.W.C.; Durand, J.-O.; Khashab, N.M. Syntheses and Applications of Periodic Mesoporous Organosilica Nanoparticles. Nanoscale 2015, 7, 20318–20334. [CrossRef] [PubMed] 24. Djojoputro, H.; Zhou, X.F.; Qiao, S.Z.; Wang, L.Z.; Yu, C.Z.; Lu, G.Q. Periodic Mesoporous Organosilica Hollow Spheres with Tunable Wall Thickness. J. Am. Chem. Soc. 2006, 128, 6320–6321. [CrossRef] [PubMed] 25. Cho, E.-B.; Kim, D.; Jaroniec, M. Preparation of Mesoporous Benzene-silica Nanoparticles. Microporous Mesoporous Mater. 2009, 120, 252–256. [CrossRef] 26. Liu, J.; Bai, S.; Zhong, H.; Li, C.; Yang, Q. Tunable Assembly of Organosilica Hollow Nanospheres. J. Phys. Chem. C 2010, 114, 953–961. [CrossRef] 27. Guan, B.; Cui, Y.; Ren, Z.; Qiao, Z.; Wang, L.; Liu, Y.; Huo, Q. Highly Ordered Periodic Mesoporous Organosilica Nanoparticles with Controllable Pore Structures. Nanoscale 2012, 4, 6588–6596. [CrossRef] 28. Qiao, S.Z.; Yu, C.Z.; Xing, W.; Hu, Q.H.; Djojoputro, H.; Lu, G.Q. Synthesis and Bio-adsorptive Properties of Large-pore Periodic Mesoporous Organosilica Rods. J. Am. Chem. Soc. 2005, 17, 6172–6176. [CrossRef] 29. Cho, E.-B.; Kim, D.; Jaroniec, M. Monodisperse Particles of Bifunctional Periodic Mesoporous Organosilica. J. Phys. Chem. C 2008, 112, 4897–4902. [CrossRef] 30. Mohanty, P.; Landskron, K. Periodic Mesoporous Organosilica Nanorice. Nanoscale Res. Lett. 2009, 4, 169–172. [CrossRef] 31. Mohanty, P.; Landskron, K. Simple Systematic Synthesis of Periodic Mesoporous Organosilica Nanoparticles with Adjustable Aspect Ratios. Nanoscale Res. Lett. 2009, 4, 1524–1529. [CrossRef] [PubMed] 32. Zhang, M.; Li, Y.; Bi, L.; Zhuang, W.; Wang, S.; Chen, Y.; Li, B.; Yang, Y. Preparation of Helical Mesoporous Ethenylene-silica Nanofibers with Lamellar Mesopores on Their Surface. Chin. J. Chem. 2011, 29, 933–941. [CrossRef] 33. Fatieiev, Y.; Croissant, J.G.; Alamoudi, K.; Khashab, N.M. Cellular Internalization and Biocompatibility of Periodic Mesoporous Organosilica Nanoparticles with Tunable Morphologies: From Nanospheres to Nanowires. ChemPlusChem 2017, 82, 631–637. [CrossRef] [PubMed] 34. Croissant, J.G.; Cattoën, X.; Man, M.W.C.; Dieudonne, P.; Charnay, C.; Raehm, L.; Durand, J.-O. One-Pot Construction of Multipodal Hybrid Periodic Mesoporous Organosilica Nanoparticles with Crystal-Like Architectures. Adv. Mater. 2015, 27, 145–149. [CrossRef] 35. Teng, Z.; Li, W.; Tang, Y.; Elzatahry, A.; Lu, G.; Zhao, D. Mesoporous Organosilica Hollow Nanoparticles: Synthesis and Applications. Adv. Mater. 2019, 31, 1707612. [CrossRef] Materials 2020, 13, 1569 16 of 16 36. Chen, Y.; Shi, J. Chemistry of Mesoporous Organosilica in Nanotechnology: Molecularly Organic-Inorganic Hybridization into Frameworks. Adv. Mater. 2016, 28, 3235–3272. [CrossRef] 37. Doustkhah, E.; Rostamnia, S.; Imura, M.; Ide, Y.; Mohammadi, S.; Hyland, C.J.T.; You, J.; Tsunoji, N.; Zeynizadeh, B.; Yamauchi, Y. Thiourea Bridged Periodic Mesoporous Organosilica with Ultra-small Pd Nanoparticles for Coupling Reactions. RSC Adv. 2017, 7, 56306–56310. [CrossRef] 38. Vercaemst, C.; Ide, M.; Wiper, P.V.; Jones, J.T.A.; Khimyak, Y.Z.; Verpoort, F. Ethenylene-Bridged Periodic Mesoporous Organosilicas: From E to Z. Chem. Mater. 2009, 21, 5792–5800. [CrossRef] 39. Li, H.; Gascó, C.; Delalande, A.; Charnay, C.; Raehm, L.; Midoux, P.; Pichon, C.; Pleixats, R.; Durand, J.-O. Periodic Mesoporous Organosilica Nanoparticles with BOC Group, towards HIFU Responsive Agents. Molecules 2020, 25, 974. [CrossRef] 40. Hu, X.; Nguyen, K.T.; Jiang, V.C.; Lofland, D.; Moser, H.E.; Pei, D. Macrocyclic Inhibitors for Peptide Deformylase: A Structure-Activity Relationship Study of the Ring Size. J. Med. Chem. 2004, 47, 4941–4949. [CrossRef] 41. Beil, J.B.; Zimmerman, S.C. Synthesis of Nanosized “Cored” Star Polymers. Macromolecules 2004, 37, 778–787. [CrossRef] 42. Dalcanale, E.; Montanari, F. Selective Oxidation of Aldehydes to Carboxylic Acids with Sodium Chlorite-hydrogen Peroxide. J. Org. Chem. 1986, 51, 567–569. [CrossRef] 43. Takeda, K.; Akiyama, A.; Nakamura, H.; Takizawa, S.; Mizuno, Y.; Takayanagi, H.; Harigaya, Y. Dicarbonates: Convenient 4-Dimethylaminopyridine Catalyzed Esterification Reagents. Synthesis 1994, 10, 1063–1066. [CrossRef] 44. Killops, K.L.; Campos, L.M.; Hawker, C.J. Robust, Efficient, and Orthogonal Synthesis of Dendrimers via Thiol-ene “Click” Chemistry. J. Am. Chem. Soc. 2008, 130, 5062–5064. [CrossRef] 45. Sun, F.G.; Li, M.; Gu, Z.H. Pd/norbornene-Catalyzed Sequential ortho-C-H Alkylation and ipso-Alkynylation: A 1,1-dimethyl-2-alkynol Strategy. Org. Chem. Front. 2016, 3, 309–313. [CrossRef] 46. Heathcock, C.H.; Ratcliffe, R. A Stereoselective Total Synthesis of the Guaiazulenic Sesquiterpenoids α-Bulnesene and Bulnesol. J. Am. Chem. Soc. 1971, 93, 1746–1757. [CrossRef] 47. Park, S.S.; Jung, M.H.; Lee, Y.S.; Bae, J.H.; Kim, S.H.; Ha, C.S. Functionalised Mesoporous Silica Nanoparticles with Excellent Cytotoxicity against Various Cancer Cells for pH-Responsive and Controlled Drug Delivery. Mater. Des. 2019, 184, 108187. [CrossRef] 48. Xie, M.; Shi, H.; Ma, K.; Shen, H.J.; Li, B.; Shen, S.; Wang, X.S.; Jin, Y. Hybrid Nanoparticles for Drug Delivery and Bioimaging: Mesoporous Silica Nanoparticles Functionalized with Carboxyl Groups and a Near-Infrared Fluorescent Dye. J. Colloid Interface Sci. 2013, 395, 306–314. [CrossRef] 49. Dutta, S.; Kao, H.M.; Wu, K.C.W. Effect of Carboxylic Acid of Periodic Mesoporous Organosilicas on the Fructose-to-5-Hydroxymethylfurfural Conversion in Dimethylsulfoxide Systems. APL Mater. 2014, 2, 113314. [CrossRef] © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).