This research has received funding from the European Union's Horizon 2020 research and innovation program under the Marie Sk&#322;odowska-Curie grant agreement H2020-MSCA-ITN-2015/674990 project "EXCILIGHT". PJS thanks the Royal Society for a Wolfson Research Merit Award.

Caution: Please review all relevant material safety data sheets (MSDS) prior to use. Several of the chemicals used in the synthesis are highly toxic and carcinogenic. When working with silica gel, a protective respiratory mask must be worn to prevent particle inhalation. Please observe all appropriate safety rules when performing a chemical reaction including the use of engineering controls (fume cupboard) and personal protective equipment (safety glasses, gloves, lab coat, full length pants, closed-toe shoes).
All reagents and solvents were purchased commercially and were used without any further purification. 1H and 13C NMR spectra were recorded on a 400 MHz NMR spectrometer using CDCl3 as the solvent. Proton NMR chemical shifts are reported as &#948; values in ppm relative to deuterated solvents: CDCl3 (7.26). Data are presented as follows: chemical shift, multiplicity and coupling constant(s) (J) are in Hz. Multiplets are reported over the range (in ppm) they appeared. Carbon NMR data were collected relative to the corresponding solvent signals CDCl3 (77.16). Melting points were measured using a melting point apparatus. Matrix assisted laser desorption ionisation-time-of-flight (MALDI-TOF) mass spectrometry were run on a Shimadzu Axima-CFR spectrometer (mass range 1-150 000 Da).
1. Synthesis of the reported compounds
<ol>
	<li>Synthesis of compound 1 (3,6-di-tert-butyl-9H-carbazole)19
	<ol>
		<li>Using 500 mL three-neck round-bottom flask, dissolve 9-H-carbazole (10.0 g, 60 mmol) in nitromethane (300 mL) under a nitrogen atmosphere. Then, add zinc (II) chloride (24.3 g, 180 mmol) to this solution.</li>
		<li>Pour 2-chloro-2-methylpropane (19.5 mL, 180 mmol) into the 100 mL addition funnel and add dropwise under vigorous stirring.</li>
		<li>Stir the resulting mixture at room temperature for 6 h.</li>
		<li>Monitor the completion of the reaction by thin layer chromatography (TLC), using dichloromethane: hexane 1:1 v/v as an eluent mixture. After the consumption of 9-H-carbazole, add 100 mL of water to neutralize the solution.</li>
		<li>Extract the product three times with 150 mL of dichloromethane each time. Separate the organic layer from the aqueous layer and additionally wash twice with 150 mL of water.
		<ol>
			<li>Dry the resulting organic layer with 15 g of magnesium sulfate, and evaporate the solvent under reduced pressure to obtain a grey powder.</li>
		</ol>
		</li>
		<li>Purify the residue by column chromatography using dichloromethane: hexane 1:1 v/v solvent mixture as an eluent provided 13.1 g (79 %) of compound 1 as a white powder. 
		Compound 1 Characterization: 
		1H NMR (400 MHz, CDCl3, 25 &#176;C, ppm): 8.12 (d, J = 1.9 Hz, 2H), 7.78 (s b, 1H), 7.5 (dd, J = 8.5, 1.9 Hz, 2H), 7.33 (dd, J = 5.6, 0.5 Hz, 2H), 1.49 (s, 18H). 
		13C NMR (400 MHz, CDCl3, 25 &#176;C, ppm): 142.4, 138.2, 123.7, 123.4, 116.3, 110.2, 34.9, 32.2. 
		MS: m/z 279.4 (M+). 
		Melting point: 233-235 &#176;C.</li>
	</ol>
	</li>
	<li>Synthesis of compound 2 (2,8-dibromodibenzothiophene)20
	<ol>
		<li>Using a 500 mL three-neck round-bottom flask, dissolve dibenzothiophene (15.0 g, 81.3 mmol) in chloroform (100 mL) under nitrogen atmosphere. Next, add dropwise bromine (9.3 mL, 180 mmol) at 0 &#176;C under vigorous stirring.</li>
		<li>After complete addition of bromine, raise the temperature to room temperature and stir the reaction mixture for 18 h.</li>
		<li>Filter off the resulting white precipitate and repeatedly wash with 50 mL water and then with 15 mL of methanol to isolate 2,8-dibromodibenzothiophene in a yield of 23 g (83%) as a white powder. 
		Compound 2 Characterization: 
		1H NMR (400 MHz, CDCl3, 25 &#176;C, ppm): 8.24 (d, J = 2.0 Hz, 2H), 7.71 (d, J = 8.0 Hz, 2H), 7.58 (d, J = 2.0 Hz, 2H). 
		13C NMR (400 MHz, CDCl3, 25 &#176;C, ppm): 138.8, 136.3, 130.5, 124.9, 124.3, 118.8. 
		MS: m/z 342.1 (M+). 
		Melting point: 227-229 &#176;C.</li>
	</ol>
	</li>
	<li>Synthesis of compound 3 (2,8-dibromodibenzothiophene-5-dioxide)21
	<ol>
		<li>Load a 500 mL one-neck round bottom flask with a suspension of 2,8-dibromodibenzothiophene (21.3 g, 60 mmol) and hydrogen peroxide solution (30 mL of 30% (w/w) in H2O) in glacial acetic acid (250 mL) and reflux for 2 h under a nitrogen atmosphere.</li>
		<li>Cool the resulting mixture to room temperature, and filter off a white precipitate.</li>
		<li>Wash three times with 15 mL of water and then 10 mL of methanol, to obtain 19.3 g (85%) of the white powder. 
		Compound 3 Characterization: 
		1H NMR (400 MHz, CDCl3, 25 &#176;C, ppm): 8.22 (d, J = 1.6 Hz, 2H), 7.70 (d, J = 8.0 Hz, 2H), 7.57 (d, J = 2 Hz, 2H). 
		13C NMR (400 MHz, CDCl3, 25 &#176;C, ppm): 133.3, 130.4, 129.1, 125.6, 124.8, 124.3. 
		MS: m/z 374.1 (M+). 
		Melting point: 360-362 &#176;C.</li>
	</ol>
	</li>
	<li>Synthesis of compound 4 (2,8-bis(3,6-di-tert-butyl-9H-carbazol-9-yl)dibenzothiophene-S,S-dioxide)22
	<ol>
		<li>Using 500 mL three-neck round-bottom flask, dissolve 2,8-dibromodibenzothiophene-S,S-dioxide (0.45 g, 1.2 mmol) and 3,6-di-tert-butyl-9H-carbazole (0.80 g, 2.86 mmol) in anhydrous toluene (250 mL) and degas by bubbling through nitrogen for 15 min under vigorous stirring.</li>
		<li>After this, add tris(dibenzylideneacetone)dipalladium(0) (0.025 g, 0.03 mmol) and 2-dicyclohexylphosphino-2&#8242;,4&#8242;,6&#8242;-triisopropylbiphenyl (XPhos, 0.06 g, 0.12 mmol) to the reaction mixture and degas the solution for another 15 min.</li>
		<li>Add sodium tert-butoxide (0.32 g, 0.834 mmol) and tert-butanol (6 mL) and degas the resulting mixture for 15 min.</li>
		<li>Heat the reaction solution at 110 &#176;C under nitrogen atmosphere for 18 h.</li>
		<li>Cool down to room temperature, add water (150 mL) and extract the organic products into dichloromethane (250 mL) and wash the organic layer twice with 150 mL of water.</li>
		<li>Dry the resulting organic layer with 15 g of magnesium sulfate and remove the solvent under reduced pressure to obtain the crude product.</li>
		<li>Purify the crude material by column chromatography (using a mixture of solvents as an eluent: dichloromethane: petroleum ether 1:1 v/v) to yield compound 4 as a white solid (0.58 g, 63%). 
		Compound 4 Characterization: 
		1H NMR (400 MHz, CDCl3, 25 &#176;C, ppm): 8.13 (d, J = 1.6 Hz, 4H), 8.11 (d, J = 8.2 Hz, 2H), 7.99 (d, J = 1.7 Hz, 2H), 7.82 (dd, J = 8.2, 1.8 Hz, 2H), 7.48 (dd, J = 8.7, 1.9 Hz, 4H), 7.40 (d, J = 8.6 Hz, 4H), 1.45 (s, 36H). 
		13C NMR (400 MHz, CDCl3, 25 &#176;C, ppm): 144.4, 144.2, 138.5, 135.8, 133.4, 128.4, 124.4, 124.3, 119.5, 116.8, 109.2, 35.0, 32.2. 
		MS: m/z 769.97 (M+). 
		Melting point: 351-353 &#176;C.</li>
	</ol>
	</li>
	<li>Synthesis of compound 5 (2,8-bis(10H-phenothiazin-10-yl)dibenzothiophene-S,S-dioxide)23
	<ol>
		<li>Using 250 mL three-neck round-bottom flask, dissolve 2,8-dibromodibenzothiophene-S,S-dioxide (0.67 g, 1.8 mmol) and phenothiazine (0.75 g, 3.77 mmol) in anhydrous toluene (60 mL) and degas by bubbling through nitrogen for 15 min under vigorous stirring.</li>
		<li>After this, add tris(dibenzylideneacetone)dipalladium(0) (0.11 g, 0.12 mmol) and 2-dicyclohexylphosphino-2&#8242;,4&#8242;,6&#8242;-triisopropylbiphenyl (XPhos, 0.12 g, 0.23 mmol) to the reaction mixture and degas the solution for another 15 min.</li>
		<li>Add sodium tert-butoxide (0.38 g, 3.94 mmol) and degas the resulting mixture for additional 15 min.</li>
		<li>Heat the reaction solution to 110 &#176;C under a nitrogen atmosphere for 18 h.</li>
		<li>Cool down the reaction mixture to room temperature, add water (150 mL) and extract organic products into dichloromethane (250 mL) and additionally wash twice with 150 mL of water.</li>
		<li>Dry the resulting organic layer was with 15 g of magnesium sulfate and remove the solvent under reduced pressure to give the crude product.</li>
		<li>Purify the crude product by column chromatography (using solvent mixture as an eluent: dichloromethane: hexane 2:1 v/v) to obtain compound 5 as a white solid (0.9 g, 55%). 
		Compound 5 Characterization: 
		1H NMR (400 MHz, CDCl3, 25 &#176;C, ppm): 7.71 (d, J = 8.2 Hz, 2H), 7.36 (dd, J = 7.7, 1.5 Hz, 4H), 7.28-7.19 (m, 8H), 7.16 (dd, J = 7.7, 1.3 Hz, 4H), 7.02 (dd, J = 8.1, 1.3 Hz, 4H). 
		13C NMR (400 MHz, CDCl3, 25 &#176;C, ppm): 148.8, 141.1, 133.2, 131.8, 129.7, 128.1, 126.9, 125.1, 125.3, 123.1, 121.2, 111.7. 
		MS: m/z 610.08 (M+). 
		Melting point: 353-355 &#176;C.</li>
	</ol>
	</li>
</ol>

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We have nothing to disclose.

The purpose of this paper is to show the large-scale synthesis of highly efficient organic materials (Figure 1) for OLED applications from commercially available starting materials. Due to the fact that previous reports only describe the final cross-coupling reaction step and refer to some of the outdated publications, we report the detailed step-by-step synthesis of all the materials together with their full NMR and mass-spectrometry characterization for improved reproducibility of the experiments.
Both emitters bear the same dibenzothiophene-5-dioxide electron acceptor core. The first step in the preparation of compound 3 (Figure 2) is the bromination of the commercially available dibenzothiophene molecule.20 The larger scale reaction occurs overnight with a yield of 83%. The resulting dibrominated compound 2 can be further oxidized with a solution of hydrogen peroxide in glacial acetic acid, yielding 19.3 g of a white powder after filtration and washing.21 Compound 3 was used in the cross-coupling reaction without any further purification.
The difference in photophysical characteristics between the compound 4 and 5 lies in the electron-donating properties of the amine units. One of the compounds has peripheral alkylated carbazole units while the other has phenothiazine groups. The phenothiazine molecule can be purchased from chemical vendors and used without any modifications. However, in the case of compound 4 tert-butyl groups need to be introduced onto the aromatic ring of the carbazole unit in order to increase solubility in organic solvents. It was reported that in the absence of suitable alkyl groups, the solubility of the product drops, which results in a significantly lower reaction yield.24 Alkyl groups can be introduced into each phenyl ring using a Friedel-Crafts reaction between tert-butyl chloride and 9-H-carbazole in the presence of zinc (II) chloride in nitromethane based on the electrophilic aromatic substitution mechanism.19 It was found that the purity of the resulting product is not high enough and several by-products are present in the mixture; therefore the crude grey powder must be additionally purified by column chromatography resulting in isolation of 13.1 g of compound 1 recovered as a white powder.
The desired TADF emitters 4 and 5 were synthesized via palladium-catalyzed carbon-nitrogen cross-coupling reactions using previously described literature procedures.22,23 We found that increasing the amounts of the starting materials does not negatively influence the yield of the desired product, suggesting that further increases to the reaction scale are possible. Compounds 4 and 5 can be obtained in 63% and 55% yield, respectively.
In conclusion, a detailed guideline on how to prepare highly efficient organic molecules for light emitting applications, starting from readily available materials, with the possibility to scale up the whole synthetic procedure has been demonstrated. Through this work, the intention is that large-scale synthesis of many other TADF emitters will ensure a fast transition of the technology from the laboratory bench to industrial applications.

Over the past few decades, researchers have investigated the utilization of organic molecules and their derivatives in organic light-emitting diodes (OLEDs) since their first introduction in 1987.1 The discovery of electroluminescence (EL) has led to organic materials finding a wide range of applications in displays and lighting.2 Enormous interest in producing new organic compounds and studying their photophysical properties are driven by the advantages of OLEDs over the existing technologies; most notably as they are more energy-efficient and can offer superior device performance whilst maintaining high flexibility, small thickness, and low weight. Nevertheless, in comparison to inorganic light-emitting diodes (LEDs), OLEDs still suffer disadvantages that prevent this technology from large scale commercial production, including shorter lifetimes, and low efficiencies. Until recently, most research was based on first generation OLEDs and emission relied on the fluorescence of the organic materials. Due to the fact that fluorescence can occur only from the singlet state, the maximum theoretical internal quantum efficiency (IQE) of the device is only 25%.3,4,5 By utilizing heavy-metal containing organic complexes (such as Ir, Pt), researchers could overcome the 25% efficiency barrier by harvesting the electrons from both the singlet and triplet states by a radiative transition process.6,7,8 Thus, the maximum theoretical efficiency of second generation phosphorescent OLEDs (PHOLEDs) can be as high as 100%.9,10 Nowadays, many commercial OLED devices utilize green and red phosphorescent emitting organometallic complexes based on iridium.11 Although these materials have gained widespread use in mobile displays and other electronic applications, the cost of the heavy-metal precursor salts and their short lifetimes have pushed researchers to look for alternatives.
There are several objectives that must be achieved for widespread commercialization of OLED technology, such as high stability, efficient power consumption and low production cost of the device. In recent years, it has been shown that thermally activated delayed fluorescence (TADF) emitters can be an effective substitute to PHOLED materials to reach the same IQE value, with these materials now considered as third generation OLED materials.12,13,14 Purely organic TADF emitters can be prepared in a few steps from readily available starting materials making the overall device fabrication commercially attractive to the market. To date, there are several comprehensive literature reviews covering all the aspects from material synthesis to the device fabrication.15,16,17,18 The main issue with TADF material preparation is the use of Pd-containing catalysts for the cross-coupling reactions. In order to show the potential for TADF material preparation on an increased scale. we scaled-up the synthesis of TADF emitters from starting materials to the desired products 4 and 5 (Figure 1).22,23 This detailed protocol is intended to help new practitioners in the field to understand the information associated with the synthesis of TADF materials.

<table><tbody><tr><td>2-Chloro-2-methylpropane, 99+%</td><td>Sigma Aldrich</td><td>19780</td><td></td></tr><tr><td>2-Dicyclohexylphosphino-2&amp;prime;,4&amp;prime;,6&amp;prime;-triisopropylbiphenyl (XPhos), 97%</td><td>Sigma Aldrich</td><td>638064</td><td>Air sensitive</td></tr><tr><td>9-H-carbazole, 95%</td><td>Alfa Aesar</td><td>A11448</td><td>Air sensitive</td></tr><tr><td>Bromine, 99.5%</td><td>Fisher</td><td>10452553</td><td>Highly toxic</td></tr><tr><td>Chloroform, anhydrous, 99%</td><td>Sigma Aldrich</td><td>288306</td><td></td></tr><tr><td>Dibenzothiophene, 98%</td><td>Sigma Aldrich</td><td>D32202</td><td></td></tr><tr><td>Dichloromethane, anhydrous, 99.8%</td><td>Sigma Aldrich</td><td>270997</td><td></td></tr><tr><td>Glacial acetic acid, 99.7+%</td><td>Alfa Aesar</td><td>36289</td><td>Corrosive to skin</td></tr><tr><td>Hexane, anhydrous, 95%</td><td>Sigma Aldrich</td><td>296090</td><td></td></tr><tr><td>Hydrogen peroxide solution (30 % (w/w) in H&lt;sub&gt;2&lt;/sub&gt;O)</td><td>Sigma Aldrich</td><td>H1009</td><td>Corrosive to skin</td></tr><tr><td>Magnesium sulfate, 99.5%</td><td>Alfa Aesar</td><td>33337</td><td></td></tr><tr><td>Nitromethane, 98+%</td><td>Alfa Aesar</td><td>A11806</td><td>Highly explosive</td></tr><tr><td>Phenothiazine, 98+%</td><td>Alfa Aesar</td><td>A12517</td><td>Air sensitive</td></tr><tr><td>Sodium tert-butoxide, 97%</td><td>Sigma Aldrich</td><td>359270</td><td></td></tr><tr><td>Tert-butanol, anhydrous, 99.5%</td><td>Sigma Aldrich</td><td>471712</td><td></td></tr><tr><td>Toluene, anhydrous, 99.8%</td><td>Sigma Aldrich</td><td>244511</td><td></td></tr><tr><td>Tris(dibenzylideneacetone) dipalladium(0), Pd 21.5% min</td><td>Alfa Aesar</td><td>12760-03</td><td>Air sensitive</td></tr><tr><td>Zinc (II) chloride, anhydrous, 98+%</td><td>Alfa Aesar</td><td>A16281</td><td></td></tr></tbody></table>

scale-up chemical synthesis of thermally-activated delayed fluorescence emitters based on the dibenzothiophene-s,s-dioxide core

We report a procedure to linearly scale-up the synthesis of 2,8-bis(3,6-di-tert-butyl-9H-carbazol-9-yl)dibenzothiophene-S,S-dioxide (compound 4) and 2,8-bis(10H-phenothiazin-10-yl)dibenzothiophene-S,S-dioxide (compound 5) using Buchwald-Hartwig cross-coupling reaction conditions. In addition, we demonstrate a scaled-up synthesis of all non-commercially available starting materials that are required for the amination cross-coupling reaction. In the present article, we provide the detailed synthetic procedures for all of the described compounds, alongside their spectral characterization. This work shows the possibility to produce organic molecules for optoelectronic applications on a large scale, which facilitates their implementation into real world devices.

The chemical structures of the final TADF emitters (Figure 1) are marked blue for the electron-donating groups and red for the electron-withdrawing core. An alkylated carbazole derivative and a dibrominated dibenzothiopene-S,S-dioxide acceptor molecule can be prepared from inexpensive starting materials (Figure 2). The final products can be prepared by a large-scale version of the Pd-catalyzed amination cross-coupling reaction (Figure 3).
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/56501/56501fig1.jpg" /> 
Figure 1. Chemical structures of thermally activated delayed fluorescence emitters based on the 2,8-dibenzothiophene-5-dioxide electron acceptor core (shown in red) bearing 3,6-di-tert-butyl-9H-carbazol-9-yl and 10H-phenothiazin-10-yl donor moieties of compound 4 and compound 5 respectively. Electron-donating groups are shown in blue. <a href="https://cloudflare.jove.com/files/ftp_upload/56501/56501fig1large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/56501/56501fig2.jpg" /> 
Figure 2. Chemical reaction pathways to prepare 3,6-di-tert-butyl-9H-carbazole (compound 1) by alkylation of 9-H-carbazole and 2,8-dibromodibenzothiophene-5-dioxide (compound 3) in two steps starting from commercially available dibenzothiophene. <a href="https://cloudflare.jove.com/files/ftp_upload/56501/56501fig2large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/56501/56501fig3.jpg" /> 
Figure 3. Buchwald-Hartwig cross coupling reactions between 2,8-dibromodibenzothiophene-5-dioxide (compound 3) and a corresponding secondary amine to produce compounds 4 and 5. <a href="https://cloudflare.jove.com/files/ftp_upload/56501/56501fig3large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>

Watch this Scientific Journal Video about Scale-up Chemical Synthesis of Thermally-activated Delayed Fluorescence Emitters Based on the Dibenzothiophene-S,S-Dioxide Core at JoVE.com

Scale-up Chemical Synthesis of Thermally-activated Delayed Fluorescence Emitters Based on the Dibenzothiophene-S,S-Dioxide Core

Scale-up synthesis of highly efficient thermally activated delayed fluorescence emitters is described in the presented article.

We report a procedure to linearly scale-up the synthesis of 2,8-bis(3,6-di-tert-butyl-9H-carbazol-9-yl)dibenzothiophene-S,S-dioxide (compound 4) and ...

scale-up-chemical-synthesis-thermally-activated-delayed-fluorescence

Research

JoVE Journal

Chemistry

9.5K Views.  University of Strathclyde. Scale-up synthesis of highly efficient thermally activated delayed fluorescence emitters is described in the presented article.

Video: Scale-up Chemical Synthesis of Thermally-activated Delayed Fluorescence Emitters Based on the Dibenzothiophene-S,S-Dioxide Core

Compact Quantum Dots for Single-molecule Imaging

Single-molecule imaging is an important tool for understanding the mechanisms of biomolecular function and for visualizing the spatial and temporal heterogeneity of molecular behaviors that underlie cellular biology 1-4. To image an individual molecule of interest, it is typically conjugated to a fluorescent tag (dye, protein, bead, or quantum dot) and observed with epifluorescence or total internal reflection fluorescence (TIRF) microscopy. While dyes and fluorescent proteins have been the mainstay of fluorescence imaging for decades, their fluorescence is unstable under high photon fluxes necessary to observe individual molecules, yielding only a few seconds of observation before complete loss of signal. Latex beads and dye-labeled beads provide improved signal stability but at the expense of drastically larger hydrodynamic size, which can deleteriously alter the diffusion and behavior of the molecule under study.
Quantum dots (QDs) offer a balance between these two problematic regimes. These nanoparticles are composed of semiconductor materials and can be engineered with a hydrodynamically compact size with exceptional resistance to photodegradation 5. Thus in recent years QDs have been instrumental in enabling long-term observation of complex macromolecular behavior on the single molecule level. However these particles have still been found to exhibit impaired diffusion in crowded molecular environments such as the cellular cytoplasm and the neuronal synaptic cleft, where their sizes are still too large 4,6,7.
Recently we have engineered the cores and surface coatings of QDs for minimized hydrodynamic size, while balancing offsets to colloidal stability, photostability, brightness, and nonspecific binding that have hindered the utility of compact QDs in the past 8,9. The goal of this article is to demonstrate the synthesis, modification, and characterization of these optimized nanocrystals, composed of an alloyed HgxCd1-xSe core coated with an insulating CdyZn1-yS shell, further coated with a multidentate polymer ligand modified with short polyethylene glycol (PEG) chains (Figure 1). Compared with conventional CdSe nanocrystals, HgxCd1-xSe alloys offer greater quantum yields of fluorescence, fluorescence at red and near-infrared wavelengths for enhanced signal-to-noise in cells, and excitation at non-cytotoxic visible wavelengths. Multidentate polymer coatings bind to the nanocrystal surface in a closed and flat conformation to minimize hydrodynamic size, and PEG neutralizes the surface charge to minimize nonspecific binding to cells and biomolecules. The end result is a brightly fluorescent nanocrystal with emission between 550-800 nm and a total hydrodynamic size near 12 nm. This is in the same size range as many soluble globular proteins in cells, and substantially smaller than conventional PEGylated QDs (25-35 nm).

We describe the preparation of colloidal quantum dots with minimized hydrodynamic size for single-molecule fluorescence imaging. Compared to conventional quantum dots, these nanoparticles are similar in size to globular proteins and are optimized for single-molecule brightness, stability against photodegradation, and resistance to nonspecific binding to proteins and cells.

Single-molecule imaging is an important tool for  understanding the mechanisms of biomolecular function and for visualizing the  spatial and temporal ...

Engineering

Microwave-assisted Intramolecular Dehydrogenative Diels-Alder Reactions for the Synthesis of Functionalized Naphthalenes/Solvatochromic Dyes

Functionalized naphthalenes have applications in a variety of research fields ranging from the synthesis of natural or biologically active molecules to the preparation of new organic dyes. Although numerous strategies have been reported to access naphthalene scaffolds, many procedures still present limitations in terms of incorporating functionality, which in turn narrows the range of available substrates. The development of versatile methods for direct access to substituted naphthalenes is therefore highly desirable.
The Diels-Alder (DA) cycloaddition reaction is a powerful and attractive method for the formation of saturated and unsaturated ring systems from readily available starting materials. A new microwave-assisted intramolecular dehydrogenative DA reaction of styrenyl derivatives described herein generates a variety of functionalized cyclopenta[b]naphthalenes that could not be prepared using existing synthetic methods. When compared to conventional heating, microwave irradiation accelerates reaction rates, enhances yields, and limits the formation of undesired byproducts.
The utility of this protocol is further demonstrated by the conversion of a DA cycloadduct into a novel solvatochromic fluorescent dye via a Buchwald-Hartwig palladium-catalyzed cross-coupling reaction. Fluorescence spectroscopy, as an informative and sensitive analytical technique, plays a key role in research fields including environmental science, medicine, pharmacology, and cellular biology. Access to a variety of new organic fluorophores provided by the microwave-assisted dehydrogenative DA reaction allows for further advancement in these fields.

Microwave-assisted intramolecular dehydrogenative Diels-Alder (DA) reactions provide concise access to functionalized cyclopenta[b]naphthalene building blocks. The utility of this methodology is demonstrated by one-step conversion of the dehydrogenative DA cycloadducts into novel solvatochromic fluorescent dyes via Buchwald-Hartwig palladium-catalyzed cross-coupling reactions.

Functionalized naphthalenes have applications in a variety of research fields ranging from the synthesis of natural or biologically active molecules to ...

Electroactive Polymer Nanoparticles Exhibiting Photothermal Properties

A method for the synthesis of electroactive polymers is demonstrated, starting with the synthesis of extended conjugation monomers using a three-step process that finishes with Negishi coupling. Negishi coupling is a cross-coupling process in which a chemical precursor is first lithiated, followed by transmetallation with ZnCl2. The resultant organozinc compound can be coupled to a dibrominated aromatic precursor to give the conjugated monomer. Polymer films can be prepared via electropolymerization of the monomer and characterized using cyclic voltammetry and ultraviolet-visible-near infrared (UV-Vis-NIR) spectroscopy. Nanoparticles (NPs) are prepared via emulsion polymerization of the monomer using a two-surfactant system to yield an aqueous dispersion of the polymer NPs. The NPs are characterized using dynamic light scattering, electron microscopy, and UV-Vis-NIR-spectroscopy. Cytocompatibility of NPs is investigated using the cell viability assay. Finally, the NP suspensions are irradiated with a NIR laser to determine their effectiveness as potential materials for photothermal therapy (PTT).

A protocol is presented for the synthesis and preparation of nanoparticles consisting of electroactive polymers.

A method for the synthesis of electroactive polymers is demonstrated, starting with the synthesis of extended conjugation monomers using a three-step ...

Synthesis of Cyclic Polymers and Characterization of Their Diffusive Motion in the Melt State at the Single Molecule Level

We demonstrate a method for the synthesis of cyclic polymers and a protocol for characterizing their diffusive motion in a melt state at the single molecule level. An electrostatic self-assembly and covalent fixation (ESA-CF) process is used for the synthesis of the cyclic poly(tetrahydrofuran) (poly(THF)). The diffusive motion of individual cyclic polymer chains in a melt state is visualized using single molecule fluorescence imaging by incorporating a fluorophore unit in the cyclic chains. The diffusive motion of the chains is quantitatively characterized by means of a combination of mean-squared displacement (MSD) analysis and a cumulative distribution function (CDF) analysis. The cyclic polymer exhibits multiple-mode diffusion which is distinct from its linear counterpart. The results demonstrate that the diffusional heterogeneity of polymers that is often hidden behind ensemble averaging can be revealed by the efficient synthesis of the cyclic polymers using the ESA-CF process and the quantitative analysis of the diffusive motion at the single molecule level using the MSD and CDF analyses.

A protocol for the synthesis and characterization of diffusive motion of cyclic polymers at the single molecule level is presented.

We demonstrate a method for the synthesis of cyclic polymers and a protocol for characterizing their diffusive motion in a melt state at the single ...

Self-assembling Morphologies Obtained from Helical Polycarbodiimide Copolymers and Their Triazole Derivatives

A facile method for the preparation of polycarbodiimide-based secondary structures (e.g., nano-rings, &#34;craters,&#34; fibers, looped fibers, fibrous networks, ribbons, worm-like aggregates, toroidal structures, and spherical particles) is described. These aggregates are morphologically influenced by extensive hydrophobic side chain-side chain interactions of the singular polycarbodiimide strands, as inferred by atomic force microscopy (AFM) and scanning electron microscopy (SEM) techniques. Polycarbodiimide-g-polystyrene copolymers (PS-PCDs) were prepared by a combination of synthetic methods, including coordination-insertion polymerization, copper(I)-catalyzed azide alkyne cycloaddition (CuAAC) &#34;click&#34; chemistry, and atom transfer radical polymerization (ATRP). PS-PCDs were found to form specific toroidal architectures at low concentrations in CHCl3. To determine the influence of a more polar solvent medium (i.e., THF and THF/EtOH) on polymer aggregation behavior, a number of representative PS-PCD composites have been tested to show discrete concentration-dependent spherical particles. These fundamental studies are of practical interest to the development of experimental procedures for desirable architectures by directed self-assembly in thin film. These architectures may be exploited as drug carriers, whereas other morphological findings represent certain interest in the area of novel functional materials.

Here, we present a protocol to prepare and visualize secondary structures (e.g., fibers, toroidal architectures, and nano-spheres) derived from helical polycarbodiimides. The morphology characterized by both atomic force microscopy (AFM) and scanning electron microscopy (SEM) was shown to depend on molecular structure, concentration, and the solvent of choice.

A facile method for the preparation of polycarbodiimide-based secondary structures (e.g., nano-rings, &#34;craters,&#34; fibers, looped fibers, fibrous ...

Time-resolved Photophysical Characterization of Triplet-harvesting Organic Compounds at an Oxygen-free Environment Using an iCCD Camera

Here, we present a sensible method of the acquisition and analysis of time-resolved photoluminescence using an ultrafast iCCD camera. This system enables the acquisition of photoluminescence spectra covering the time regime from nanoseconds up to 0.1 s. This enables us to follow the changes in the intensity (decay) and emission of the spectra over time. Using this method, it is possible to study diverse photophysical phenomena, such as the emission of phosphorescence, and the contributions of prompt and delayed fluorescence in molecules showing thermally activated delayed fluorescence (TADF). Remarkably, all spectra and decays are obtained in a single experiment. This can be done for solids (thin film, powder, crystal) and liquid samples, where the only limitations are the spectral sensitivity of the camera and the excitation wavelength (532 nm, 355 nm, 337 nm, and 266 nm). This technique is, thus, very important when investigating the excited state dynamics in organic emitters for their application in organic light-emitting diodes and other areas where triplet harvesting is of paramount importance. Since triplet states are strongly quenched by oxygen, emitters with efficient TADF luminescence, or those showing room temperature phosphorescence (RTP), must be correctly prepared in order to remove any dissolved oxygen from solutions and films. Otherwise, no long-lived emission will be observed. The method of degassing solid samples as presented in this work is basic and simple, but the degassing of liquid samples creates additional difficulties and is particularly interesting. A method of minimizing solvent loss and changing the sample concentration, while still enabling to remove oxygen in a very efficient and a repeatable manner, is presented in this work.

Here, we present a method of the spectroscopic characterization of organic molecules by means of time-resolved photoluminescence spectroscopy on the nanosecond-to-millisecond timescale in oxygen-free conditions. Methods to efficiently remove oxygen from the samples and, thus, limit luminescence quenching are also described.

Here, we present a sensible method of the acquisition and analysis of time-resolved photoluminescence using an ultrafast iCCD camera. This system enables ...

Production and Characterization of Vacuum Deposited Organic Light Emitting Diodes

A method for producing simple and efficient thermally-activated delayed fluorescence organic light-emitting diodes (OLEDs) based on guest-host or exciplex donor-acceptor emitters is presented. With a step-by-step procedure, readers will be able to repeat and produce OLED devices based on simple organic emitters. A patterning procedure allowing the creation of personalized indium tin oxide (ITO) shape is shown. This is followed by the evaporation of all layers, encapsulation and characterization of each individual device. The end goal is to present a procedure that will give the opportunity to repeat the information presented in cited publication but also using different compounds and structures in order to prepare efficient OLEDs.

A protocol for the production of simple structured organic light-emitting diodes (OLEDs) is presented.

A method for producing simple and efficient thermally-activated delayed fluorescence organic light-emitting diodes (OLEDs) based on guest-host or exciplex ...

Constructing Thioether/Vinyl Sulfide-tethered Helical Peptides Via Photo-induced Thiol-ene/yne Hydrothiolation

Here, we describe a detailed protocol for the preparation of thioether-tethered peptides using on-resin intramolecular/intermolecular thiol-ene hydrothiolation. In addition, this protocol describes the preparation of vinyl-sulfide-tethered peptides using in-solution intramolecular thiol-yne hydrothiolation between amino acids that possess alkene/alkyne side chains and cysteine residues at i, i+4 positions. Linear peptides were synthesized using a standard Fmoc-based solid-phase peptide synthesis (SPPS). Thiol-ene hydrothiolation is carried out using either an intramolecular thio-ene reaction or an intermolecular thio-ene reaction, depending on the peptide length. In this research, an intramolecular thio-ene reaction is carried out in the case of shorter peptides using on-resin deprotection of the trityl groups of cysteine residues following the complete synthesis of the linear peptide. The resin is then set to UV irradiation using photoinitiator 4-methoxyacetophenone (MAP) and 2-hydroxy-1-[4-(2-hydroxyethoxy)-phenyl]-2-methyl-1-propanone (MMP). The intermolecular thiol-ene reaction is carried out by dissolving Fmoc-Cys-OH in an N,N-dimethylformamide (DMF) solvent. This is then reacted with the peptide using the alkene-bearing residue on resin. After that, the macrolactamization is carried out using benzotriazole-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBop), 1-hydroxybenzotriazole (HoBt), and 4-Methylmorpholine (NMM) as activation reagents on the resin. Following the macrolactamization, the peptide synthesis is continued using standard SPPS. In the case of the thio-yne hydrothiolation, the linear peptide is cleaved from the resin, dried, and subsequently dissolved in degassed DMF. This is then irradiated using UV light with photoinitiator 2,2-dimethoxy-2-phenylacetophenone (DMPA). Following the reaction, DMF is evaporated and the crude residue is precipitated and purified using high-performance liquid chromatography (HPLC). These methods could function to simplify the generation of thioether-tethered cyclic peptides due to the use of the thio-ene/yne click chemistry that possesses superior functional group tolerance and good yield. The introduction of thioether bonds into peptides takes advantage of the nucleophilic nature of cysteine residues and is redox-inert relative to disulfide bonds.

We present a protocol for the construction of thioether/vinyl sulfide-tethered helical peptides using photo-induced thiol-ene/thiol-yne hydrothiolation.

Here, we describe a detailed protocol for the preparation of thioether-tethered peptides using on-resin intramolecular/intermolecular thiol-ene ...

Synthesis and Calibration of Phosphorescent Nanoprobes for Oxygen Imaging in Biological Systems

Oxygen measurement by phosphorescence quenching [1, 2] consists of the following steps: 1) the probe is delivered into the medium of interest (e.g. blood or interstitial fluid); 2) the object is illuminated with light of appropriate wavelength in order to excite the probe into its triplet state; 3) the emitted phosphorescence is collected, and its time course is analyzed to yield the phosphorescence lifetime, which is converted into the oxygen concentration (or partial pressure, pO2). The probe must not interact with the biological environment and in some cases to be 4) excreted from the medium upon the measurement completion. Each of these steps imposes requirements on the molecular design of the phosphorescent probes, which constitute the only invasive component of the measurement protocol. Here we review the design of dendritic phosphorescent nanosensors for oxygen measurements in biological systems. The probes consist of Pt or Pd porphyrin-based polyarylglycine (AG) dendrimers, modified peripherally with polyethylene glycol (PEG's) residues. For effective two-photon excitation, termini of the dendrimers may be modified with two-photon antenna chromophores, which capture the excitation energy and channel it to the triplet cores of the probes via intramolecular FRET (F&ouml;rster Resonance Energy Transfer). We describe the key photophysical properties of the probes and present detailed calibration protocols.

We present principles of oxygen measurements by phosphorescence quenching and review design of porphyrin-based dendritic nanosensors for oxygen imaging in biological systems.

Oxygen measurement by phosphorescence quenching [1, 2] consists of the following steps: 1) the probe is delivered into the medium of interest (e.g. blood ...

Biology

Synthesis of pH Dependent Pyrazole, Imidazole, and Isoindolone Dipyrrinone Fluorophores using a Claisen-Schmidt Condensation Approach

Methine-bridged conjugated bicyclic aromatic compounds are common constituents of a range of biologically relevant molecules such as porphyrins, dipyrrinones, and pharmaceuticals. Additionally, restricted rotation of these systems often results in highly to moderately fluorescent systems as observed in 3H,5H-dipyrrolo[1,2-c:2',1'-f]pyrimidin-3-ones, xanthoglows, pyrroloindolizinedione analogs, BODIPY analogs, and the phenolic and imidazolinone ring systems of Green Fluorescent Protein (GFP). This manuscript describes an inexpensive and operationally simple method of performing a Claisen-Schmidt condensation to generate a series of fluorescent pH dependent pyrazole/imidazole/isoindolone dipyrrinone analogs. While the methodology illustrates the synthesis of dipyrrinone analogs, it can be translated to produce a wide range of conjugated bicyclic aromatic compounds. The Claisen-Schmidt condensation reaction utilized in this method is limited in scope to nucleophiles and electrophiles that are enolizable under basic conditions (nucleophile component) and non-enolizable aldehydes (electrophile component). Additionally, both the nucleophilic and electrophilic reactants must contain functional groups that will not inadvertently react with hydroxide. Despite these limitations, this methodology offers access to completely novel systems that can be employed as biological or molecular probes.

The Claisen-Schmidt condensation reaction is an important methodology for the generation of methine-bridged conjugated bicyclic aromatic compounds. Through utilizing a base-mediated variant of the aldol reaction, a range of fluorescent and/or biologically relevant molecules can be accessed through a generally inexpensive and operationally simple synthetic approach.