Alpha Cyclodextrin Synthesis Essay

The synthesis of gold nanoparticles (core size less than 2.0 nm) capped by thiolate α-cyclodextrin (α-CD-SH) has been studied and characterized by infrared spectroscopy, UV−visible absorption spectroscopy, high-resolution transmission electron microscopy, and photoluminescence spectroscopy. Hydrogen tetrachloroaurate(III) trihydrate (HAuCl4•3H2O) is reduced by NaBH4 in the presence of α-CD-SH to produce thiolate α-cyclodextrin-stabilized gold nanoparticles (α-CD-S-AuNPs). The particle size of the as-synthesized α-CD-S-AuNPs is highly dependent on the initial molar ratio of α-CD-SH to AuCl4 (α-CD-SH/Au) precursors. When the α-CD-SH/Au is kept greater than or equal to 1, α-CD-S-AuNPs (core size < 2.0 nm) are acquired, and their size increases with increasing α-CD-SH/Au. It is postulated that the increase in particle size is attributed to the interhydrogen bond between the α-CD-SH molecules at higher concentrations with a concomitant decrease in the availability of free α-CD-SH to stabilize the AuNP surface. By contrast, when the α-CD-SH/Au is controlled at <1, larger α-CD-S-AuNPs (core size >2.5 nm) with typical surface plasmon bands are obtained, and the particle size increases with the decrease in α-CD-SH/Au. The average chemical compositions of such AuNPs in the empirical formula Aux(α-CD-S)y are further determined by thermogravimetric analysis, mass spectrometry, and atomic absorption spectroscopy. These α-CD-S-AuNPs (core size < 2.0 nm) display remarkably strong blue emissions at 478 nm when excited at 400 nm. The 1.4 nm-sized α-CD-S-AuNP shows photoluminescence enhancement in the presence of tetraalkylammonium ions but is strongly quenched by Hg(II). The α-CD-S-AuNP possesses ultrahigh sensitivity and good selectivity for the determination of Hg(II) with the limit of detection at 49 pM (9.7 ppt).

Materials

α-D-glucose, maltodextrin, α-CD, vinyl pivalate, vinyl benzoate, pyrene, and dimethylsulfoxide (DMSO) were purchased from Sigma Aldrich. β-CD, γ-CD, vinyl laurate, and vinyl stearate were obtained from Tokyo Chemical Industry Co., Ltd. N, N-dimethylformamide (DMF, anhydrous 99.8%) was obtained from Alfa Aesar, a Johnson Matthey Company. Organic solvents such as methanol and ethanol were of analytical reagent grade, and the water used was triply distilled. Thin-layer chromatography (TLC) was carried out on Merck Kieselgel 60 F254 analytical plates with the specified solvent system. The detection and visualization are followed by spraying 5% sulfuric acid-ethanol and heating for 2 min at 170 °C.

Self-acylation and product isolation

β-CD (100 mg, 0.09 mmol) was dissolved in 1 mL of DMF, and then vinyl laurate (24 μL, 0.09 mmol) was added. For other self-acylations of β-CD (100 mg, 0.09 mmol), vinyl pivalate (13.7 μL, 0.09 mmol), vinyl butyrate (11.7 μL, 0.09 mmol), vinyl benzoate (12.7 μL, 0.09 mmol), and vinyl stearate (28 mg, 0.09 mmol) were used. For self-laurylation with other carbohydrates, α-CD (85.6 mg, 0.09 mmol), γ-CD (114 mg, 0.09 mmol), glucose (15.8 mg, 0.09 mmol) and maltodextrin (96.3 mg, 0.09 mmol) were used. After stirring at 50 °C for 24 h, the product was isolated by chromatography on silica gel with 8:5:2 or 8:5:1 (v/v) EtOAc-MeOH-H2O as eluent15. For time course data, every 1 μL from reaction mixture was quenched and analyzed at 0.5, 1, 2, 4, 8, and 20 h. The progress of reactions was analyzed by TLC densitometric analysis using NIH ImageJ software.

Mono-2-O-butyryl β-cyclodextrin

1H NMR (600 MHz, DMSO-d6): δ 5.92-5.52 (br, O(2)H, O(3)H), 5.03 (d, 1H, H1′), 4.90-4.71 (m, 6H, H1), 4.63-4.41 (br, O(6)H), 3.89 (t, 1H, H3′), 3.66-3.22 (m, H2-6), 3.18 (d, 1H, H3′), 2.44-2.29 (m, 2H, H8), 1.58-1.51 (m, 2H, H9), 0.90 (t, 3H, H10); 13C NMR (600 MHz, DMSO-d6): δ 173.06 (C7), 101.98 (C1), 98.49 (C1′), 81.56 (C4), 80.84 (C4′), 78.23 (C2′), 73.12 (C3), 72.46 (C2), 72.09 (C5), 69.38 (C3′), 59.96 (C6), 35.13 (C8), 17.68 (C9), 13.55 (C10); MALDI-TOF MS: 1227.6432 [mono-2-O-butyryl β-cyclodextrin+Na]+.

Mono-2-O-benzoyl β-cyclodextrin

1H NMR (600 MHz, DMSO-d6): δ 8.10-7.96 (d, 2H, H9, 13), 7.64-7.58 (t, 1H, H11), 7.52-7.46 (t, 2H, H10, 12), 6.03-5.70 (br, O(2)H, O(3)H), 5.20 (d, 1H, H1′), 4.94-4.77 (m, 6H, H1), 4.68-4.45 (br, O(6)H), 4.12 (t, 1H, H2′) 3.70-3.22 (m, H2-6), 3.17 (d, 1H, H3′); 13C NMR (600 MHz, DMSO-d6): δ 165.97 (C7), 133.08 (C11), 131.29 (C8), 129.81, 129.50 (C9, 13), 128.44, 128.15 (C10, 12), 102.00 (C1), 98.20 (C1′), 81.62 (C4), 80.92 (C4′), 78.11 (C2′), 73.03 (C3), 72.54 (C2), 72.07 (C5), 69.67 (C3′), 59.97 (C6); MALDI-TOF MS: 1261.6154 [mono-2-O-benzoyl β-cyclodextrin+Na]+.

Mono-2-O-stearyl β-cyclodextrin

1H NMR (600 MHz, DMSO-d6): δ 6.60-6.10 (br, O(2)H, O(3)H), 5.01 (d, 1H, H1′), 4.88-4.69 (m, 6H, H1), 4.64-4.38 (br, O(6)H), 3.87 (t, 1H, H3′), 3.63-3.20 (m, H2-6), 2.44-2.26 (m, 2H, H8), 1.49 (m, 2H, H9), 1.23 (s, 26H, H10-23), 0.85 (m, 3H, H24); 13C NMR (600 MHz, DMSO-d6): δ 166.23 (C7), 102.23 (C1), 98.53 (C1′), 81.69 (C4), 80.96 (C4′), 78.38 (C2′), 73.12 (C3), 72.46 (C2), 72.09 (C5), 69.37 (C3′), 59.96 (C6), 33.25 (C8), 31.36 (C22), 29.12-28.53 (C10-21), 24.74 (C9), 22.16 (C23), 14.04 (C24); MALDI-TOF MS: 1423.9385 [mono-2-O-stearyl β-cyclodextrin+Na]+.

Mono-2-O-lauryl α-cyclodextrin

1H NMR (600 MHz, DMSO-d6): δ 5.84-5.41 (br, O(2)H, O(3)H), 4.97 (d, 1H, H1′), 4.85-4.67 (m, 5H, H1), 4.65-4.44 (br, O(6)H), 4.00 (t, 1H, H3′), 3.64-3.54 (m, H2′, 3-6), 3.43-3.27 (m, H2, 4), 2.42-2.29 (m, 2H, H8), 1.50 (m, 2H, H9), 1.25 (s, 18H, H10-17), 0.86 (m, 3H, H18); 13C NMR (600 MHz, DMSO-d6): δ 162.99 (C7), 102.06 (C1), 98.80 (C1′), 82.30 (C4), 81.92 (C4′), 79.40 (C2′), 73.34 (C3), 72.58 (C2), 72.15 (C5), 69.62 (C3′), 60.06 (C6), 35.84 (C8), 31.42 (C16), 29.09-28.68 (C10-15), 24.37 (C9), 22.22 (C17), 14.06 (C18); MALDI-TOF MS: 1177.6322 [mono-2-O-lauryl α-cyclodextrin+Na]+.

Mono-2-O-lauryl γ-cyclodextrin

1H NMR (600 MHz, DMSO-d6): δ 6.82-6.18 (br, O(2)H, O(3)H), 5.16 (d, 1H, H1′), 5.11-4.77 (m, 7H, H1), 4.75-4.45 (br, O(6)H), 3.80 (t, 1H, H3′), 3.69-3.16 (m, H2-6, 2′) 2.46-2.28 (m, 2H, H8), 1.50 (m, 2H, H9), 1.25 (s, 15H, H10-17), 0.85 (m, 3H, H18); 13C NMR (600 MHz, DMSO-d6): δ 166.29 (C7), 101.56 (C1), 97.67 (C1′), 81.35 (C4), 80.75 (C4′), 78.94 (C2′), 73.22 (C3), 72.84 (C2), 72.18 (C5), 69.85 (C3′), 59.89 (C6), 33.29 (C8), 31.34 (C16), 29.09-28.57 (C10-15), 24.32 (C9), 22.14 (C17), 14.04 (C18); MALDI-TOF MS: 1501.8729 [mono-2-O- lauryl γ-cyclodextrin+Na]+.

Nuclear magnetic resonance (NMR) spectroscopy

A Bruker Avance 600 MHz spectrometer was used to record the 1H-NMR, 13C-NMR, and DEPT spectra. The NMR analyses were performed in DMSO-d6 at room temperature. ROESY data was recorded with 256/2048 data points using Bruker Avance 500 MHz spectrometer in DMF-d7 at room temperature.

Matrix-assisted desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS)

The mass spectrum was obtained using a MALDI-TOF mass spectrometer (Voyager-DETM STR BioSpectrometry, PerSeptive Biosystems, Framingham, MA, USA) using the positive-ion mode. 2, 5-Dihydroxybenzoic acid (DHB) was used as the matrix.

Computational method

Starting coordinates for the β-CD were obtained from the Protein Data Bank (PDB id. 3CGT) and vinyl laurate was built using Maestro software (ver. 2015-3, Schrodinger Inc.). Molecular docking simulations were performed with the vinyl laurate onto the β-CD under the ligand-flexible mode using the Glide docking module45. The molecular grid was established using the receptor grid generation tool in a 20 Å sized cubic box, to estimate potential energy of the system. To archive docking accuracy, the extra precision XP mode with Glide XP scoring function was applied during the ranking process for the docked poses. The structural model for the mono-2-O-lauryl β-CD in water was calculated by Advanced Conformation Search module in the Maestro package under the mixed torsional/low-mode sampling mode. During the conformation search, the GB/SA implicit model with the OPLS2005 force field was used.

Fluorescence spectroscopy

For the fluorescence measurement, mono-2-O-lauryl β-CD or unmodified β-CD was prepared with concentrations of 0.05 to 12.5 mM in water. A small amount of a hydrophobic probe, pyrene solution in acetone, was added into each sample giving a final concentration of 1 μM in solution. Acetone was not removed, and its final content was 0.1%, v/v46. All samples were sonicated for 15 min and mixed for 15 h at 26 °C before measurement. Fluorescence emission spectra of pyrene were recorded using a fluorescence spectrophotometer (SIMADZU, RF-5310PC) at room temperature. The probe was excited at 335 nm, and the emission spectra were obtained in the range of 350–500 nm47.

Nanoprecipitation technique

Using the nanoprecipitation technique48, 1 mL of mono-2-O-lauryl β-CD (1.25 mM) dissolved in ethanol is dropped slowly through a syringe into water (1 mL) and subjected to magnetic stirring. The nanospheres were formed immediately, and the colloidal suspension obtained was submitted to evaporation under reduced pressure to remove ethanol. The resulting colloidal suspension was stored in closed vials at room temperature.

Dynamic light scattering (DLS)

The resulting colloid was measured using a Wyatt Technology DynaPro Plate Reader for the assessing the nanoarchitecture size distribution of the mono-2-O-lauryl β-CD.

Transmission electron microscopy (TEM)

The colloidal suspension by mono-2-O-lauryl β-CD was loaded onto a Formvar-coated copper grid (200 mesh) and air-dried. For negative staining, 2% uranyl acetate solution was used. Then, the self-assembled nanoarchitecture was examined using energy-filtering TEM (LIBRA 120, Carl Zeiss, Germany).

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