This work was supported by the National Nature Science Foundation of China (21301104), the Fundamental Research Funds for the Central Universities (FRF-TP-16-019A3), and the State Key Laboratory of Chemical Engineering (SKL-ChE-14A04).

1. Synthesis of Mono-(2,3-dimethylbutyl)phosphinic acid 18,19
<ol>
	<li>Reaction
	<ol>
		<li>Weigh 31.80 g sodium hypophosphite hydrate, 16.00 g acetic acid, 8.42 g 2,3-dimethyl-1-butene, 0.73 g di-tert-butylnperoxide (DTBP), and 25.00 g tetrahydrofuran (THF) into a 100 mL Teflon-lined stainless steel autoclave, put a magnetic stirrer into the autoclave, and seal it.</li>
		<li>Put the autoclave in a vertical tube furnace under which is a magnetic stirringapparatus.Start the magnetic stirring apparatus and set the speed at 800 rpm.</li>
		<li>Set the heating program of the temperature controller connected to the autoclave: heat from room temperature to 120 &#176;C during 90 min, maintain at 120 &#176;C for 8 h, then cool down to room temperature naturally. Start the heating program.</li>
	</ol>
	</li>
	<li>Post-treatment
	<ol>
		<li>Transfer the products into a 250 mL one-neck round-bottom flask, wash the Teflon-lining with 50 mL THF, and add it into the same flask to ensure that all the products are transferred.</li>
		<li>Remove the THF and unreacted olefins using a rotary evaporator.</li>
		<li>Transfer the residua into a 250 mL separating funnel, wash the flask with 80 mL ethyl ether and 30 mL deionized water respectively, and add them into the same separating funnel to ensure that all the products are transferred.</li>
		<li>Add 50 mL 4% NaOH solution into the above separating funnel, shake it vigorously, and separate the aqueous phase. Extract the organic phase with 20 mL 4% NaOH solutions for three times (20 mL &#215; 3) to ensure that the aqueous phase exceeds pH 10.</li>
		<li>Combine the aqueous solutions in the above step, and transfer them into a 500 mL separating funnel.</li>
		<li>Add 90 mL of 10% H2SO4 solution and 50 mL of ethyl ether, shake vigorously, and separate the organic phase; then extract the aqueous phase with 30 mL of ethyl ether for three times (30 mL &#215; 3).</li>
		<li>Combine the ethyl ether solutions in step 1.2.6, and transfer them into another 500 mL separating funnel.</li>
		<li>Wash it with 100 mL of saturated NaCl solutions four times (100 mL &#215; 4).</li>
		<li>Add 4 g of anhydrous MgSO4 to remove any soluble water. Filter to remove the solid, and collect the liquid in a clean 250 mL one-neck round-bottom flask.</li>
		<li>Remove the ethyl ether using the rotary evaporator to obtain 17.92 g of the crude product.</li>
	</ol>
	</li>
</ol>
2. Purification of Mono-(2,3-dimethylbutyl)phosphinic Acid
<ol>
	<li>Preparation of amantadine solution
	<ol>
		<li>Dissolve 22.28 g of amantadine hydrochloride in 100 mL of deionized water in a 500 mL beaker.</li>
		<li>Add 100 mL of saturated NaOH solution, and stir for 5 min.</li>
		<li>Add 150 mL of ethyl ether, and stir until the white precipitate generated in step 2.1.2 disappears.</li>
		<li>Transfer the solutions into a 500 mL separating funnel, wash the beaker with ethyl ether for three times (50 mL &#215; 3), and combine them into the same separating funnel.</li>
		<li>Separate the aqueous phase, and wash the organic phase with saturated NaCl solutions five times (100 mL &#215; 5).</li>
		<li>Add 4 g of anhydrous MgSO4 to remove any soluble water. Filter to obtain the amantadine ethyl ether solution.</li>
	</ol>
	</li>
	<li>Preparation of amantadine &#8729; mono-(2,3-dimethylbutyl)phosphinic acid salt
	<ol>
		<li>Add drop-wise the crude mono-(2,3-dimethylbutyl)phosphinic acid product to the amantadine solution. During dropping add 150 mL of ethyl ether to ensure that it can stir properly.</li>
		<li>Wash the one-neck round-bottom flask containing the mono-(2,3-dimethylbutyl)phosphinic acid product with 50 mL of ethyl ether to ensure that all the product is transferred to the amantadine solution. Stir for 30 min, and let it sit overnight.</li>
		<li>Filter under reduced pressure, and wash the filter cake with 200 mL ethyl ether.</li>
	</ol>
	</li>
	<li>Release the mono-(2,3-dimethylbutyl)phosphinic acid
	<ol>
		<li>Transfer the filtered cake into a 500 mL beaker, add 80 mL of 1 M HCl, and stir for 5 min.</li>
		<li>Add 70 mL ethyl acetate, and stir for another 5 min.</li>
		<li>Transfer the solutions into a 250 mL separating funnel and separate the aqueous phase.</li>
		<li>Extract the aqueous phase with 40 mL ethyl acetate again and combine the ethyl acetate solutions.</li>
		<li>Wash the ethyl acetate solution with 30 mL of 1 M HCl twice (30 mL &#215; 2) and saturated NaCl three times (80 mL &#215; 3), sequentially.</li>
		<li>Add 4 g anhydrous MgSO4 to remove any soluble water. Filter and collect the liquid in a 250 mL one-neck round-bottom flask.</li>
		<li>Remove the ethyl acetate using the rotary evaporator, and obtain 12.45 g of the pure mono-(2,3-dimethylbutyl)phosphinic acid (Yield: 82.9%).</li>
	</ol>
	</li>
</ol>
3. Synthesis of (2,3-dimethylbutyl)(2,4,4&#39;-trimethylpentyl)phosphinic Acid
<ol>
	<li>Reaction
	<ol>
		<li>Transfer all of the pure mono-(2,3-dimethylbutyl)phosphinic acid product into a 100 mL Teflon-lined stainless steel autoclave, add 4.95 g of acetic acid, 25.39 g of diisobutylene, 0.30 g of DTBP, put a magnetic stirrer into the autoclave, and seal it.</li>
		<li>Put the autoclave in a vertical tube furnace under which is a magnetic stirring apparatus, and start the magnetic stirring apparatus.</li>
		<li>Set the heating program of the temperature controller: heat from room temperature to 135 &#176;C during 90 min, maintain at 135 &#176;C for 8 h, then cool down to room temperature naturally. Start the heating program.</li>
		<li>When the reaction system cools down to room temperature, add another 0.30 g of DTBP, and restart the heating program.</li>
		<li>Repeat step 3.1.4 once.</li>
	</ol>
	</li>
	<li>Post-treatment
	<ol>
		<li>Dilute the product with 100 mL ethyl ether, and then transfer to a 250 mL separating funnel.</li>
		<li>Wash it with 30 mL of 4% NaOH three times (30 mL &#215; 3) to ensure that aqueous phase exceeds pH 10.</li>
		<li>Add 70 mL of 10% H2SO4 solution to acidify the product.</li>
		<li>Wash it with saturated NaCl solution several times (80 mL each) until the aqueous phase pH equals pH 6-7.</li>
		<li>Add 4 g of anhydrous MgSO4 to remove any soluble water. Filter to remove the solid, and collect the liquid in a clean 250 mL one-neck round-bottom flask.</li>
		<li>Remove the ethyl ether and unreacted olefins using the rotary evaporator to obtain 15.10 g of crude product.</li>
	</ol>
	</li>
</ol>
4. Purification of (2,3-dimethylbutyl)(2,4,4&#39;-trimethylpentyl)phosphinic Acid
<ol>
	<li>Obtain pure co-(2,3-dimethylbutyl)(2,4,4&#39;-trimethylpentyl)phosphinic acid complex
	<ol>
		<li>Dissolve 2.30 g of NaOH in 40 mL deionized water. Add the NaOH solution to the flask containing the crude (2,3-dimethylbutyl)(2,4,4&#39;-trimethylpentyl)phosphinic acid product, and shake it vigorously for 5 min.</li>
		<li>Add 0.5 M CoCl2 solution dropwise while shaking until no more blue precipitate is generated and the solution in the flask is pink.</li>
		<li>Filter and wash the blue precipitate with deionized water until the filter cake is colorless.</li>
		<li>Transfer the filter cake into a 250 mL beaker, add 100 mL of acetone, seal it with preservative film, and then refrigerate it at 4 &#176;C for one night.</li>
		<li>Pulverize the blue precipitate to release any impurities trapped in the bulk.</li>
		<li>Filter and wash it with 100 mL of fresh acetone. Dry the filter cake at room temperature, and then transfer it into a 250 mL separating funnel.</li>
	</ol>
	</li>
	<li>Regenerate the (2,3-dimethylbutyl)(2,4,4&#39;-trimethylpentyl)phosphinic acid
	<ol>
		<li>Add 120 mL ethyl ether and 80 mL 10% H2SO4, and shake vigorously until the blue precipitate disappears.</li>
		<li>Separate the aqueous phase,wash the organic phase sequentially with 30 mL of 10% H2SO4 once and saturated NaCl solutions several times (80 mL each) until the aqueous phase pH equals pH 6-7.</li>
		<li>Add 4 g of anhydrous MgSO4 to remove any soluble water. Filter to remove the solid and collect the liquid in a clean 250 mL one-neck round-bottom flask.</li>
		<li>Remove the ethyl ether using the rotary evaporator, and obtain 11.46 g of the pure product (Yield: 52.8%).</li>
	</ol>
	</li>
</ol>

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The authors have nothing to disclose.

The most critical step within the protocol is the mono-alkylphosphinic acid synthesis (Figure 1a). In this reaction, a higher yield and less dialkylphosphinic acid by-product is better. Increasing the molar ratio of NaH2PO2/olefin A will improve the yield and inhibit the generation of dialkylphosphinic acid by-product. However, a large NaH2PO2 dosage will also increase the cost and cause a stirring problem. The preferred molar rati...

Acidic organophosphorus extractants are widely used in the traditional hydrometallurgy field for extraction and separation of rare earth ions1,2, non-ferrous metals (like Co/Ni3,4), rare metals (such as Hf/Zr5, V6,7), actinides8, etc. In recent years, they have also attracted more attention in the fields of secondary resource recycling and high-level liquid waste disposal9. Di-(2-ethylhexyl)phosphoric acid (D2EHPA or P204), 2-ethylhexylphosphoric acid mono-2-ethylhexyl ester (EHEHPA, PC 88A, or P507), and Di-(2,4,4&#39;-trimethylpentyl)-phosphinic acid (Cyanex272), which are representatives of dialkylphosphoric acids, alkylphosphoric acid mono-alkyl esters, and dialkylphosphinic acids respectively, are the most commonly used extractants. Their acidity decreases in the following sequence: P204 &#62; P507 &#62; Cyanex 272. The corresponding extraction ability, extraction capacity, and stripping acidity are all in the order of P204 &#62; P507 &#62; Cyanex 272, and the separation performance is in the opposite order. These three extractants are effective in most cases. However, there are still some conditions where they are not so efficient: in heavy rare earths separation, of which the existing main problems are the poor selectivity and high stripping acidity for P204 and P507, low extraction capacity, and emulsion tendency during extraction for Cyanex 272. Thus, the development of novel extractants has drawn greater attention in recent years.
The class of dialkylphosphinic acid extractants is considered to be one of the most important research aspects to develop new extractants. Recent research showed that the extraction ability of dialkylphosphinic acids depends largely on the structure of the alkyl substituent10,11. It can be a wide range from significantly higher than that of P507 to lower than that of Cyanex 27212. However, the exploration of novel dialkylphosphinic acid extractants is restricted to the commercial olefin structure10,12,13,14,15,16. Though dialkylphosphinic acid extractants can also be synthesized by the Grignard-reaction method, the reaction conditions are rigorous12,17.
NSDAPA, of which the two alkyls are different, opens a door to the exploration of new extractants. It makes the structures of dialkylphosphinic acid more diverse, and its extraction and separation performance can be fine-tuned by modifying both of its alkyl structures. The traditional synthetic method of NSDAPA used PH3 as a phosphorus source, which has many drawbacks like high toxicity, rigorous reaction conditions, and difficult purification. Recently we reported a new method to synthesize NSDAPA using sodium hypophosphite as a phosphorus source (see Figure 1) and successfully synthesized three NSDAPAs18. This detailed protocol can help new practitioners repeat the experiments and master the synthetic method of NSDAPA extractants. We take (2,3-dimethylbutyl)(2,4,4&#39;-trimethylpentyl)phosphinic acid as an example. The names and structures of olefin A, the mono-alkylphosphinic acid intermediate, olefin B, and the corresponding NSDAPA are shown in Table 1.

<table style="border-collapse:collapse;width:687pt" width="916">
	<colgroup>
		<col style="width:185pt" width="247" />
		<col style="width:290pt" width="387" />
		<col style="width:93pt" width="124" />
		<col style="width:119pt" width="158" />
	</colgroup>
	<tbody>
		<tr height="102" style="height:76.5pt">
			<td class="xl17" height="102" style="width:185pt;height:76.5pt" width="247">sodium hypophosphite hydrate</td>
			<td class="xl17" style="width:290pt" width="387">Tianjin Fuchen Chemical Reagents Factory</td>
			<td class="xl17" style="width:93pt" width="124"></td>
			<td class="xl17" style="width:119pt" width="158">Molecular formula: NaH2PO2&#8729;H2O, purity &#8805;99.0%</td>
		</tr>
		<tr height="77" style="height:57.75pt">
			<td class="xl17" height="77" style="width:185pt;height:57.75pt" width="247">2,3-dimethyl-1-butene</td>
			<td class="xl17" style="width:290pt" width="387">Adamas Reagent Co., Ltd.</td>
			<td class="xl17" style="width:93pt" width="124"></td>
			<td class="xl17" style="width:119pt" width="158">Molecular formula: C6H12, purity &#8805;99%</td>
		</tr>
		<tr height="77" style="height:57.75pt">
			<td class="xl17" height="77" style="width:185pt;height:57.75pt" width="247">diisobutylene</td>
			<td class="xl17" style="width:290pt" width="387">Shanghai&#160;Aladdin&#160;Bio-Chem&#160;Technology&#160;Co.,&#160;LTD</td>
			<td class="xl17" style="width:93pt" width="124"></td>
			<td class="xl17" style="width:119pt" width="158">Molecular formula: C8H16, purity 97%</td>
		</tr>
		<tr height="77" style="height:57.75pt">
			<td class="xl17" height="77" style="width:185pt;height:57.75pt" width="247">acetic acid</td>
			<td class="xl17" style="width:290pt" width="387">Sinopharm Chemical Reagent Co., Ltd.</td>
			<td class="xl17" style="width:93pt" width="124"></td>
			<td class="xl17" style="width:119pt" width="158">Molecular formula: C2H4O2, purity &#8805;99.5%</td>
		</tr>
		<tr height="77" style="height:57.75pt">
			<td class="xl17" height="77" style="width:185pt;height:57.75pt" width="247">di-tert-butylnperoxide</td>
			<td class="xl17" style="width:290pt" width="387">Sinopharm Chemical Reagent Co., Ltd.</td>
			<td class="xl17" style="width:93pt" width="124"></td>
			<td class="xl17" style="width:119pt" width="158">Molecular formula: C8H18O2, purity &#8805;97.0%</td>
		</tr>
		<tr height="77" style="height:57.75pt">
			<td class="xl17" height="77" style="width:185pt;height:57.75pt" width="247">tetrahydrofuran</td>
			<td class="xl17" style="width:290pt" width="387">Beijing Chemical Works</td>
			<td class="xl17" style="width:93pt" width="124"></td>
			<td class="xl17" style="width:119pt" width="158">Molecular formula: C4H8O, purity A.R.</td>
		</tr>
		<tr height="102" style="height:76.5pt">
			<td class="xl17" height="102" style="width:185pt;height:76.5pt" width="247">amantadine hydrochloride</td>
			<td class="xl17" style="width:290pt" width="387">Shanghai&#160;Aladdin&#160;Bio-Chem&#160;Technology&#160;Co.,&#160;LTD</td>
			<td class="xl17" style="width:93pt" width="124"></td>
			<td class="xl17" style="width:119pt" width="158">Molecular formula: C10H17N&#8729;HCl, purity 99%</td>
		</tr>
		<tr height="77" style="height:57.75pt">
			<td class="xl17" height="77" style="width:185pt;height:57.75pt" width="247">ethyl ether</td>
			<td class="xl17" style="width:290pt" width="387">Sinopharm Chemical Reagent Co., Ltd.</td>
			<td class="xl17" style="width:93pt" width="124"></td>
			<td class="xl17" style="width:119pt" width="158">Molecular formula: C4H10O, purity &#8805;99.7%</td>
		</tr>
		<tr height="77" style="height:57.75pt">
			<td class="xl17" height="77" style="width:185pt;height:57.75pt" width="247">ethyl acetate</td>
			<td class="xl17" style="width:290pt" width="387">Xilong Chemical Co., Ltd.</td>
			<td class="xl17" style="width:93pt" width="124"></td>
			<td class="xl17" style="width:119pt" width="158">Molecular formula: C4H8O2, purity &#8805;99.5%</td>
		</tr>
		<tr height="77" style="height:57.75pt">
			<td class="xl17" height="77" style="width:185pt;height:57.75pt" width="247">acetone</td>
			<td class="xl17" style="width:290pt" width="387">Beijing Chemical Works</td>
			<td class="xl17" style="width:93pt" width="124"></td>
			<td class="xl17" style="width:119pt" width="158">Molecular formula: C3H6O, purity &#8805;99.5%</td>
		</tr>
		<tr height="75" style="height:56.25pt">
			<td class="xl17" height="75" style="width:185pt;height:56.25pt" width="247">sodium hydroxide</td>
			<td class="xl17" style="width:290pt" width="387">Xilong Chemical Co., Ltd.</td>
			<td class="xl17" style="width:93pt" width="124"></td>
			<td class="xl17" style="width:119pt" width="158">Molecular formula: NaOH, purity &#8805;96.0%</td>
		</tr>
		<tr height="77" style="height:57.75pt">
			<td class="xl17" height="77" style="width:185pt;height:57.75pt" width="247">concentrated sulfuric acid</td>
			<td class="xl17" style="width:290pt" width="387">Sinopharm Chemical Reagent Co., Ltd.</td>
			<td class="xl17" style="width:93pt" width="124"></td>
			<td class="xl17" style="width:119pt" width="158">Molecular formula: H2SO4, purity 95-98%</td>
		</tr>
		<tr height="75" style="height:56.25pt">
			<td class="xl17" height="75" style="width:185pt;height:56.25pt" width="247">hydrochloric acid</td>
			<td class="xl17" style="width:290pt" width="387">Beijing Chemical Works</td>
			<td class="xl17" style="width:93pt" width="124"></td>
			<td class="xl17" style="width:119pt" width="158">Molecular formula: HCl, purity 36-38%</td>
		</tr>
		<tr height="75" style="height:56.25pt">
			<td class="xl17" height="75" style="width:185pt;height:56.25pt" width="247">sodium chloride</td>
			<td class="xl17" style="width:290pt" width="387">Sinopharm Chemical Reagent Co., Ltd.</td>
			<td class="xl17" style="width:93pt" width="124"></td>
			<td class="xl17" style="width:119pt" width="158">Molecular formula: NaCl, purity &#8805;99.5%</td>
		</tr>
		<tr height="77" style="height:57.75pt">
			<td class="xl17" height="77" style="width:185pt;height:57.75pt" width="247">anhydrous magnesium sulfate</td>
			<td class="xl17" style="width:290pt" width="387">Tianjin Jinke Institute of Fine Chemical Industry</td>
			<td class="xl17" style="width:93pt" width="124"></td>
			<td class="xl17" style="width:119pt" width="158">Molecular formula: MgSO4, purity &#8805;99.0%</td>
		</tr>
		<tr height="103" style="height:77.25pt">
			<td class="xl19" height="103" style="width:185pt;height:77.25pt" width="247">Cobalt(II) chloride hexahydrate</td>
			<td class="xl19" style="width:290pt" width="387">Xilong Chemical Co., Ltd.</td>
			<td class="xl19" style="width:93pt" width="124"></td>
			<td class="xl19" style="width:119pt" width="158">Molecular formula: CoCl2&#8729;6H2O, purity &#8805;99.0%</td>
		</tr>
	</tbody>
</table>

synthesis of high purity nonsymmetric dialkylphosphinic acid extractants

We present the synthesis of (2,3-dimethylbutyl)(2,4,4&#39;-trimethylpentyl)phosphinic acid as an example to demonstrate a method for the synthesis of high purity nonsymmetric dialkylphosphinic acid extractants. Low toxic sodium hypophosphite was chosen as the phosphorus source to react with olefin A (2,3-dimethyl-1-butene) to generate a monoalkylphosphinic acid intermediate. Amantadine was adopted to remove the dialkylphosphinic acid byproduct, as only the monoalkylphosphinic acid can react with amantadine to form an amantadine&#8729;mono-alkylphosphinic acid salt, while the dialkylphosphinic acid cannot react with amantadine due to its large steric hindrance. The purified monoalkylphosphinic acid was then reacted with olefin B (diisobutylene) to yield nonsymmetric dialkylphosphinic acid (NSDAPA). The unreacted monoalkylphosphinic acid can be easily removed by a simple base-acid post-treatment and other organic impurities can be separated out through the precipitation of the cobalt salt. The structure of the (2,3-dimethylbutyl)(2,4,4&#39;-trimethylpentyl)phosphinic acid was confirmed by 31P NMR, 1H NMR, ESI-MS, and FT-IR. The purity was determined by a potentiometric titration method, and the results indicate that the purity can exceed 96%.

31P NMR spectra were collected for the mono-(2,3-dimethylbutyl)phosphinic acid before and after purification by the amantadine method (Figure 1a-b). 31P NMR spectra, 1H NMR spectra, MS spectra, and FT-IR spectra were collected for (2,3-dimethylbutyl)(2,4,4&#39;-trimethylpentyl)phosphinic acid (see Figure 3, Figure 4, Figure 5</str...

Watch this Scientific Journal Video about Synthesis of High Purity Nonsymmetric Dialkylphosphinic Acid Extractants at JoVE.com

Synthesis of High Purity Nonsymmetric Dialkylphosphinic Acid Extractants

A protocol for the synthesis of high purity nonsymmetric dialkylphosphinic acid extractants is presented, taking (2,3-dimethylbutyl)(2,4,4&#39;-trimethylpentyl)phosphinic acid as an example.

We present the synthesis of (2,3-dimethylbutyl)(2,4,4&#39;-trimethylpentyl)phosphinic acid as an example to demonstrate a method for the synthesis of high ...

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7.4K Views.  University of Science and Technology Beijing. A protocol for the synthesis of high purity nonsymmetric dialkylphosphinic acid extractants is presented, taking (2,3-dimethylbutyl)(2,4,4'-trimethylpentyl)phosphinic acid as an example.

Video: Synthesis of High Purity Nonsymmetric Dialkylphosphinic Acid Extractants

Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides (CHIPS)

The direct functionalization of C-H bonds is an important and long standing goal in organic chemistry. Such transformations can be very powerful in order to streamline synthesis by saving steps, time and material compared to conventional methods that require the introduction and removal of activating or directing groups. Therefore, the functionalization of C-H bonds is also attractive for green chemistry. Under oxidative conditions, two C-H bonds or one C-H and one heteroatom-H bond can be transformed to C-C and C-heteroatom bonds, respectively. Often these oxidative coupling reactions require synthetic oxidants, expensive catalysts or high temperatures. Here, we describe a two-step procedure to functionalize indole derivatives, more specifically tetrahydrocarbazoles, by C-H amination using only elemental oxygen as oxidant. The reaction uses the principle of C-H functionalization via Intermediate PeroxideS (CHIPS). In the first step, a hydroperoxide is generated oxidatively using visible light, a photosensitizer and elemental oxygen. In the second step, the N-nucleophile, an aniline, is introduced by Br&#248;nsted-acid catalyzed activation of the hydroperoxide leaving group. The products of the first and second step often precipitate and can be conveniently filtered off. The synthesis of a biologically active compound is shown.

Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides CHIPS

A two-step procedure for the synthesis of pharmaceutically active indole-derivatives by C-H functionalization with anilines is described, using photo- and Br&#248;nsted acid catalysis.

The direct functionalization of C-H bonds is an important and long standing goal in organic chemistry. Such transformations can be very powerful in order ...

Synthesis of Immunotargeted Magneto-plasmonic Nanoclusters

Magnetic and plasmonic properties combined in a single nanoparticle provide a synergy that is advantageous in a number of biomedical applications including contrast enhancement in novel magnetomotive imaging modalities, simultaneous capture&#160;and detection of circulating tumor cells (CTCs),&#160;and multimodal molecular imaging combined with photothermal therapy of cancer cells. These applications have stimulated significant interest in development of protocols for synthesis of magneto-plasmonic nanoparticles with optical absorbance in the near-infrared (NIR) region and a strong magnetic moment. Here, we present a novel protocol for synthesis of such hybrid nanoparticles that is based on an oil-in-water microemulsion method. The unique feature of the protocol described herein is synthesis of magneto-plasmonic nanoparticles of various sizes from primary blocks which also have magneto-plasmonic characteristics. This approach yields nanoparticles with a high density of magnetic and plasmonic functionalities which are uniformly distributed throughout the nanoparticle volume. The hybrid nanoparticles can be easily functionalized by attaching antibodies through the Fc moiety leaving the Fab portion that is responsible for antigen binding available for targeting.

Here, we describe a protocol for synthesis of magneto-plasmonic nanoparticles with a strong magnetic moment and a strong near-infrared (NIR) absorbance. The protocol also includes antibody conjugation to the nanoparticles through the Fc moiety for various biomedical applications which require molecular specific targeting.

Magnetic and plasmonic properties combined in a single nanoparticle provide a synergy that is advantageous in a number of biomedical applications ...

Synthesis of Indoxyl-glycosides for Detection of Glycosidase Activities

Indoxyl glycosides proved to be valuable and versatile tools for monitoring glycosidase activities. Indoxyls are released by enzymatic hydrolysis and are rapidly oxidized, for example by atmospheric oxygen, to indigo type dyes. This reaction enables fast and easy screening in vivo without isolation or purification of enzymes, as well as rapid tests on agar plates or in solution (e.g., blue-white screening, micro-wells) and is used in biochemistry, histochemistry, bacteriology and molecular biology. Unfortunately the synthesis of such substrates proved to be difficult, due to various side reactions and the low reactivity of the indoxyl hydroxyl function. Especially for glucose type structures low yields were observed. Our novel approach employs indoxylic acid ester as key intermediates. Indoxylic acid esters with varied substitution patterns were prepared on scalable pathways. Phase transfer glycosylations with those acceptors and peracetylated glycosyl halides can be performed under common conditions in high yields. Ester cleavage and subsequent mild silver mediated glycosylation yields the peracetylated indoxyl glycosides in high yields. Finally deprotection is performed according to Zempl&#233;n.

Indoxyl glycosides are well-established and widely used tools for enzyme screening and enzyme activity monitoring. Especially for glucose type structures previous syntheses proved to be challenging and low yielding. Our novel approach employs indoxylic acid esters as precious intermediates to yield a considerable number of indoxyl glycosides in good yields.

Indoxyl glycosides proved to be valuable and versatile tools for monitoring glycosidase activities. Indoxyls are released by enzymatic hydrolysis and are ...

Synthesis and Characterization of Supramolecular Colloids

Control over colloidal assembly is of utmost importance for the development of functional colloidal materials with tailored structural and mechanical properties for applications in photonics, drug delivery and coating technology. Here we present a new family of colloidal building blocks, coined supramolecular colloids, whose self-assembly is controlled through surface-functionalization with a benzene-1,3,5-tricarboxamide (BTA) derived supramolecular moiety. Such BTAs interact via directional, strong, yet reversible hydrogen-bonds with other identical BTAs. Herein, a protocol is presented that describes how to couple these BTAs to colloids and how to quantify the number of coupling sites, which determines the multivalency of the supramolecular colloids. Light scattering measurements show that the refractive index of the colloids is almost matched with that of the solvent, which strongly reduces the van der Waals forces between the colloids. Before photo-activation, the colloids remain well dispersed, as the BTAs are equipped with a photo-labile group that blocks the formation of hydrogen-bonds. Controlled deprotection with UV-light activates the short-range hydrogen-bonds between the BTAs, which triggers the colloidal self-assembly. The evolution from the dispersed state to the clustered state is monitored by confocal microscopy. These results are further quantified by image analysis with simple routines using ImageJ and Matlab. This merger of supramolecular chemistry and colloidal science offers a direct route towards light- and thermo-responsive colloidal assembly encoded in the surface-grafted monolayer.

A protocol for the synthesis and characterization of colloids coated with supramolecular moieties is described. These supramolecular colloids undergo self-assembly upon the activation of the hydrogen-bonds between the surface-anchored molecules by UV-light.

Control over colloidal assembly is of utmost importance for the development of functional colloidal materials with tailored structural and mechanical ...

Hydroquinone Based Synthesis of Gold Nanorods

Gold nanorods are an important kind of nanoparticles characterized by peculiar plasmonic properties. Despite their widespread use in nanotechnology, the synthetic methods for the preparation of gold nanorods are still not fully optimized. In this paper we describe a new, highly efficient, two-step protocol based on the use of hydroquinone as a mild reducing agent. Our approach allows the preparation of nanorods with a good control of size and aspect ratio (AR) simply by varying the amount of hexadecyl trimethylammonium bromide (CTAB) and silver ions (Ag+) present in the "growth solution". By using this method, it is possible to markedly reduce the amount of CTAB, an expensive and cytotoxic reagent, necessary to obtain the elongated shape. Gold nanorods with an aspect ratio of about 3 can be obtained in the presence of just 50 mM of CTAB (versus 100 mM used in the standard protocol based on the use of ascorbic acid), while shorter gold nanorods are obtained using a concentration as low as 10 mM.

This paper describes a protocol for the synthesis of gold nanorods, based on the use of hydroquinone as reducing agent, plus the different mechanisms for controlling their size and aspect ratio.

Gold nanorods are an important kind of nanoparticles characterized by peculiar plasmonic properties. Despite their widespread use in nanotechnology, the ...

Synthesis of Hierarchical ZnO/CdSSe Heterostructure Nanotrees

A two-step chemical vapor deposition procedure is here employed to prepare tree-like hierarchical ZnO/CdSSe hetero-nanostructures. The structures are composed of CdSSe branches grown on ZnO nanowires that are vertically aligned on a transparent sapphire substrate. The morphology was measured via scanning electron microscopy. The crystal structure was determined by X-ray powder diffraction analysis. Both the ZnO stem and CdSSe branches have a predominantly wurtzite crystal structure. The mole ratio of S and Se in the CdSSe branches was measured by energy dispersive X-ray spectroscopy. The CdSSe branches result in strong visible light absorption. Photoluminescence (PL) spectroscopy showed that the stem and branches form a type-II heterojunction. PL lifetime measurements showed a decrease in the lifetime of emission from the trees when compared to emission from individual ZnO stems or CdSSe branches and indicate fast charge transfer between CdSSe and ZnO. The vertically aligned ZnO stems provide a direct electron transport pathway to the substrate and allow for efficient charge separation after photoexcitation by visible light. The combination of the abovementioned properties makes ZnO/CdSSe nanotrees promising candidates for applications in solar cells, photocatalysis, and opto-electronic devices.

Here, we prepare and characterize novel tree-like hierarchical ZnO/CdSSe nanostructures, where CdSSe branches are grown on vertically aligned ZnO nanowires. The resulting nanotrees are a potential material for solar energy conversion and other opto-electronic devices.

A two-step chemical vapor deposition procedure is here employed to prepare tree-like hierarchical ZnO/CdSSe hetero-nanostructures. The structures are ...

Chemical Precipitation Method for the Synthesis of Nb2O5 Modified Bulk Nickel Catalysts with High Specific Surface Area

We demonstrate a method for the synthesis of NixNb1-xO catalysts with sponge-like and fold-like nanostructures. By varying the Nb:Ni ratio, a series of NixNb1-xO nanoparticles with different atomic compositions (x = 0.03, 0.08, 0.15, and 0.20) have been prepared by chemical precipitation. These NixNb1-xO catalysts are characterized by X-ray diffraction, X-ray photoelectron spectroscopy, and scanning electron microscopy. The study revealed the sponge-like and fold-like appearance of Ni0.97Nb0.03O and Ni0.92Nb0.08O on the NiO surface, and the larger surface area of these NixNb1-xO catalysts, compared with the bulk NiO. Maximum surface area of 173 m2/g can be obtained for Ni0.92Nb0.08O catalysts. In addition, the catalytic hydroconversion of lignin-derived compounds using the synthesized Ni0.92Nb0.08O catalysts have been investigated.

Chemical Precipitation Method for the Synthesis of Nb2O5 Modified Bulk Nickel Catalysts with High Specific Surface Area

A protocol for the synthesis of sponge-like and fold-like Ni1-xNbxO nanoparticles by chemical precipitation is presented.

We demonstrate a method for the synthesis of NixNb1-xO catalysts with sponge-like and fold-like nanostructures. By varying the Nb:Ni ratio, a series of ...

Synthesis of Substrate-Bound Au Nanowires Via an Active Surface Growth Mechanism

Advancing synthetic capabilities is important for the development of nanoscience and nanotechnology. The synthesis of nanowires has always been a challenge, as it requires asymmetric growth of symmetric crystals. Here, we report a distinctive synthesis of substrate-bound Au nanowires. This template-free synthesis employs thiolated ligands and substrate adsorption to achieve the continuous asymmetric deposition of Au in solution at ambient conditions. The thiolated ligand prevented the Au deposition on the exposed surface of the seeds, so the Au deposition only occurs at the interface between the Au seeds and the substrate. The side of the newly deposited Au nanowires is immediately covered with the thiolated ligand, while the bottom facing the substrate remains ligand-free and active for the next round of Au deposition. We further demonstrate that this Au nanowire growth can be induced on various substrates, and different thiolated ligands can be used to regulate the surface chemistry of the nanowires. The diameter of the nanowires can also be controlled with mixed ligands, in which another &#34;bad&#34; ligand could turn on the lateral growth. With the understanding of the mechanism, Au nanowire-based nanostructures can be designed and synthesized.

We report a solution-based method to synthesize substrate-bound Au nanowires. By tuning the molecular ligands used during the synthesis, the Au nanowires can be grown from various substrates with different surface properties. Au nanowire-based nanostructures can also be synthesized by adjusting the reaction parameters.

Advancing synthetic capabilities is important for the development of nanoscience and nanotechnology. The synthesis of nanowires has always been a ...

Solid-phase Synthesis of [4.4] Spirocyclic Oximes

A convenient synthetic route for spirocyclic heterocycles is well sought after due to the molecule&#39;s potential use in biological systems. By means of solid-phase synthesis, regenerating Michael (REM) linker strategies, and 1,3-dipolar cycloaddition, a library of structurally similar heterocycles, both with and without a spirocyclic center, can be constructed. The main advantages of the solid-support synthesis are as follows: first, each reaction step can be driven to completion using a large excess of reagents resulting in high yields; next, the use of commercially available starting materials and reagents keep the costs low; finally, the reaction steps are easy to purify via simple filtration. The REM linker strategy is attractive because of its recyclability and traceless nature. Once a reaction scheme is completed, the linker can be reused multiple times. In a typical solid-phase synthesis, the product contains either a part of or the whole linker, which can prove undesirable. The REM linker is &#34;traceless&#34; and the point of attachment between the product and the polymer is indistinguishable. The high diastereoselectivity of the intramolecular 1,3-dipolar cycloaddition is well documented. Limited by the insolubility of the solid support, the reaction progression can only be monitored by a change in the functional groups (if any) via infrared (IR) spectroscopy. Thus, the structural identification of intermediates cannot be characterized by conventional nuclear magnetic resonance (NMR) spectroscopy. Other limitations to this method stem from the compatibilities of the polymer/linker to the desired chemical reaction scheme. Herein we report a protocol that allows for the convenient production of spirocyclic heterocycles that, with simple modifications, can be automated with high-throughput techniques.

Here we present a protocol to demonstrate an efficient method for the synthesis of spirocyclic heterocycles. The five-step process utilizes solid-phase synthesis and regenerating Michael linker strategies. Generally difficult to synthesize, we present a customizable method for the synthesis of spirocyclic molecules otherwise inaccessible to other modern approaches.

A convenient synthetic route for spirocyclic heterocycles is well sought after due to the molecule&#39;s potential use in biological systems. By means of ...

Synthesis and Characterization of Amphiphilic Gold Nanoparticles

Gold nanoparticles covered with a mixture of 1-octanethiol (OT) and 11-mercapto-1-undecane sulfonic acid (MUS) have been extensively studied because of their interactions with cell membranes, lipid bilayers, and viruses. The hydrophilic ligands make these particles colloidally stable in aqueous solutions and the combination with hydrophobic ligands creates an amphiphilic particle that can be loaded with hydrophobic drugs, fuse with the lipid membranes, and resist nonspecific protein adsorption. Many of these properties depend on nanoparticle size and the composition of the ligand shell. It is, therefore, crucial to have a reproducible synthetic method and reliable characterization techniques that allow the determination of nanoparticle properties and the ligand shell composition. Here, a one-phase chemical reduction, followed by a thorough purification to synthesize these nanoparticles with diameters below 5 nm, is presented. The ratio between the two ligands on the surface of the nanoparticle can be tuned through their stoichiometric ratio used during synthesis. We demonstrate how various routine techniques, such as transmission electron microscopy (TEM), nuclear magnetic resonance (NMR), thermogravimetric analysis (TGA), and ultraviolet-visible (UV-Vis) spectrometry, are combined to comprehensively characterize the physicochemical parameters of the nanoparticles.

Amphiphilic gold nanoparticles can be used in many biological applications. A protocol to synthesize gold nanoparticles coated by a binary mixture of ligands and a detailed characterization of these particles is presented.

Gold nanoparticles covered with a mixture of 1-octanethiol (OT) and 11-mercapto-1-undecane sulfonic acid (MUS) have been extensively studied because of ...