A Novel Approach to Molecular Recognition Surface of Magnetic Nanoparticles Based on Host–Guest Effect
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A novel route has been developed to prepared β-cyclodextrin (β-CD) functionalized magnetic nanoparticles (MNPs). The MNPs were first modified with monotosyl-poly(ethylene glycol) (PEG) silane and then tosyl units were displaced by amino-β-CD through the nucleophilic substitution reaction. The monotosyl-PEG silane was synthesized by modifying a PEG diol to form the corresponding monotosyl-PEG, followed by a reaction with 3-isocyanatopropyltriethoxysilane (IPTS). The success of the synthesis of the monotosyl-PEG silane was confirmed with1H NMR and Fourier transform infrared (FTIR) spectroscopy. The analysis of FTIR spectroscopy and X-ray photoelectron spectroscopy (XPS) confirmed the immobilization of β-CD onto MNPs. Transmission electron microscopy (TEM) indicated that the β-CD functionalized MNPs were mostly present as individual nonclustered units in water. The number of β-CD molecules immobilized on each MNP was about 240 according to the thermogravimetric analysis (TGA) results. The as-prepared β-CD functionalized MNPs were used to detect dopamine with the assistance of a magnet.
Keywordsβ-Cyclodextrin Magnetic nanoparticles Molecular recognition Dopamine
Molecular host–guest systems have captured much attention in recent years. By carefully selecting the host and guest molecules, specific properties of the resulting inclusion complexes can be targeted. Among a wide range of host molecules, an example of well-studied hosts would be the cyclodextrins (CDs) . CDs are a group of naturally cyclic oligosaccharides, with six, seven, or eight glucose subunits linked by α-(1, 4) glycosidic bonds in a cylinder-shaped structure and are denominated as α-, β-, and γ-CD, respectively . The inner surface of their molecular cavity is hydrophobic, because it is lined with the glycosidic oxygen bridges. Conversely, the outer surface of CD is hydrophilic due to the hydroxyl groups. They are able to form inclusion complexes with molecules that are hosted in the solute inner CD core due to interactions between hydrophobic moieties borne by these molecules and the internal surface of the CD cavity. It can bind a variety of guest molecules inside their torus-shaped cavities and serve as a model host site. For example, CD can form inclusion complexes with dopamine (DA) or uric acid (UA) through host–guest effect.
On the other hand, owing to containing two or more different functionalities, nanocomposites are attractive candidates for advanced nanomaterials. With controlled structure and interface interactions, these nanocomposites can exhibit novel physical and chemical properties that will be essential for future technological applications. Recently, the functionalization of nanoparticle surfaces with macrocyclic host molecules in well-defined host–guest interactions has drawn considerable attention [3–25]. The combination of the physical properties of nanostructured materials and the molecular recognition ability of host molecules adsorbed on the nanoparticles surface makes them to exhibit promising applications in different fields such as catalysis [5–7], nanotechnology [8, 9], environment , chemical sensing [11–16], and so on. However, only a few cases concerning the bonding of CDs to nanoparticles have been investigated [5–10][21–25]. At present, the research work on taking CD derivatives as capping ligands for nanoparticles is focused on the attachment of perthiolated CDs (SH-CDs) on metal nanoparticle surfaces. For instance, Liu et al. have reported the modification of gold [17–20], platinum , palladium [21–23], and CdSe-CdS  nanoparticles with SH-CDs. In addition, the work about the combination of CDs on the silica nanoparticles has also been reported .
Cyclodextrin-functionalized magnetic nanoparticles (MNPs) combining the properties of MNPs and the molecular recognition function of CD are expected to have multiple potential applications such as magnetic separation, medical diagnosis, and controlled drug delivery. Ohta and co-workers  inserted β-cyclodextrin (β-CD) derivatives onto the surface of MNPs by using self-assembly processes. However, to the best of our knowledge, there is no report about the binding of CD on the MNPs through the covalent binding. In this paper, we present a novel synthetic procedure for the synthesis of β-CD functionalized MNPs. First, a monotosyl-poly(ethylene glycol) (PEG) silane was prepared and then covalently bonded onto the surface of MNPs through the method which combines the ligand exchange reaction and condensation of the silane. Second, the tosyl termini of the PEG molecules which adsorbed on the MNPs were displaced by ethylenediamine-containing β-CD (EDA–β-CD) through the nucleophilic substitution reaction. And finally, the as-prepared β-CD functionalized MNPs were used to detect DA sensitively with the assistance of a magnet.
β-Cyclodextrin (β-CD), ethylenediamine (EDA), FeCl3 · 6H2O, FeSO4 · 7H2O, oleic acid (OA), NH3 · H2O, triethylamine (TEA), NaH2PO4, Na2HPO4, PEG (Mw = 1000 g/mol), toluene-4-sulfonyl-chloride (TsCl), KI, and Ag2O were obtained from Sinopharm Chemical Reagent Co., Ltd. DA was purchased from Aldrich Co., Ltd. 3-Isocyanatopropyltriethoxysilane (IPTS) was obtained from Diamond Advanced Material of Chemical Inc. EDA–β-CD was prepared according to the already published procedure [27–29].
All other reagents were of analytical grade and were used without further purification.
All solutions were prepared with ultrapure water obtained from a water purification system (Millipore WR600A, Yamato Co., Japan). High purity nitrogen was used for solution deaeration prior to electrochemical measurements.
Synthesis of the Monotosyl-PEG Silane
Next, the monotosyl-PEG silane was synthesized from monotosyl-PEG and 3-IPTS using dibutyltin dilaurate as a catalyst. In brief, 5.8 g of dried monotosyl-PEG (5 mmol) was dissolved in 20 mLN,N-dimethylformamide (DMF). IPTS and dibutyltin dilaurate, a catalyst, were added to the monotosyl-PEG solution. The molar ratios of IPTS and dibutyltin dilaurate to monotosyl-PEG were 2.5 and 0.1, respectively. After adding chemical reagents, the mixture was stirred continuously for 6 h at 80 °C under dry nitrogen. After the reaction, the monotosyl-PEG silane was precipitated from DMF with cold diethyl ether twice and dried in vacuum. Yield: 5.5 g (81%);1H NMR (CDCl3): δ7.76 (d, Ar), 7.31 (d, Ar), 5.05 (br, OC(O)NH), 4.15 (t,CH2OTs), 4.09 (t,CH2OC(O)NH), 3.75 (t, OCH2CH3), 3.53–3.82 (m, (CH2CH2O) n ), 3.08 (m,CH2CH2CH2Si), 2.42 (s, Me tosyl), 1.53 (m, CH2CH2CH2Si), 1.15 (t, OCH2CH3), 0.54 (t,CH2Si).
Preparation of β-CD Functionalized MNPs
In order to introduce β-CD on the MNPs, EDA–β-CD was used to react with the monotosyl termini of the PEG adsorbed on MNPs. In brief, 5-mL DMF based monotosyl-PEG–MNPs dispersion, 0.1 g EDA–β-CD, and 10-mL DMF were added into a 50-mL round-bottom flask. The mixture was stirred for 12 h at 70 °C. Then the resultant β-CD immobilized nanoparticle precipitate was isolated by centrifugation after the addition of a small portion of diethyl ether and washed three times with DMF to remove residual EDA–β-CD and then dried in vacuum. Finally, β-CD–PEG–MNPs were stored in DMF.
Electrochemical measurements were performed on Arbin Instruments (MSTAT4+, USA) at room temperature (25 °C). A three-electrode single-compartment cell was used for cyclic voltammogram (CV). An Indium Tin Oxides (ITO, 1.0 cm2) electrode was used as working electrode, a platinum wire as the counter electrode, and a saturated calomel electrode as the reference electrode. And all potentials were relative to the reference electrode. ITO was sonicated in 1:1 methylene chloride/acetone, rinsed thoroughly with ultrapure water, and then allowed to dry at room temperature under high purity nitrogen. A 0.1 mol L−1phosphate buffer (pH 7.0) was used as an electrolyte solution. Phosphate buffer solution (0.1 mol L−1) was prepared by mixing stock standard solutions of 0.1 mol L−1Na2HPO4and 0.1 mol L−1NaH2PO4. And the concentration of DA was 1 mmol L−1. A magnet of 1.1 T was used for absorbing the β-CD–PEG–MNPs from solution toward the ITO.
1H NMR spectra were measured on a JEOL JNM EX270 NMR spectrometer (300 MHz).
Fourier transform infrared (FTIR) spectra were measured on a Nicolet 200SXV-1 FTIR spectrometer. The acetone dispersion of MNPs was coated on the potassium bromide pellet.
X-ray photoelectron spectroscopy (XPS) was carried out on an XSAM-800 electron and take-off angle of 20° was used with X-ray source.
Transmission electron microscopy (TEM) was carried out on a JEM-100CX instrument operating an acceleration voltage of 80 kV. TEM specimens were prepared by aspirating an aqueous sample onto a copper EM grid.
Thermogravimetric analysis (TGA) was performed on a TA instrument Q50, at a scan rate of 10 °C/min. The temperature was from room temperature up to 800 °C under nitrogen atmosphere.
Electrochemical measurements were performed on Arbin Instruments (MSTAT4+, USA) at room temperature.
Results and Discussion
Characterization of the Monotosyl-PEG Silane
Characterization of the MNPs
Application of β-CD–PEG–MNPs in the Detection of DA
Figure 8B(a) shows the CV of 1.0 mM DA in 0.1 M phosphate buffer solution (pH 7) at ITO. TS–PEG–MNPs were added to the electrolyte solution containing 1.0 mM DA. Then the MNPs were absorbed onto ITO by using a magnet and the CV was obtained (Fig. 8B(b)). The oxidation peak current enhanced obviously by comparing curve b with curve a. This behavior is attributed to the electrocatalytic effect of MNPs . In another experiment, β-CD–PEG–MNPs were added to the electrolyte solution containing 1.0 mM DA and stirred for 10 min. Then β-CD–PEG–MNPs were absorbed onto ITO by an exterior magnet and the CV was obtained (Fig. 8B(c)). The oxidation peak current is higher than curve b. This result must be in accordance with the fact that the DA apparent concentration in curve c is much higher than the bulk concentration owing to the formation of inclusion complex between β-CD and DA . Therefore, due to both the electrocatalytic effect of MNPs and host–guest effect of β-CD to DA, β-CD–PEG–MNPs modified electrode can detect DA sensitivity with the assistance of an exterior magnet.
In summary, a simple and straightforward synthetic method has been developed for the preparation of β-CD functionalized MNPs that combine magnetic and molecular recognition properties. Various techniques have been utilized to characterize the β-CD functionalized MNPs, and the results showed the desired properties as designed. Its application in magnetic responsive detecting of DA has been demonstrated well. And its detailed application in sensor is under research.
This work was financially supported by the National Nature Science Foundation of China (No. 50673091) and the Nature Science Foundation of Jiangsu Province, China (No. BK20080668).