Improved selectivity and sensitivity using covalent fluorophore–cyclodextrin analogues resulted i... more Improved selectivity and sensitivity using covalent fluorophore–cyclodextrin analogues resulted in 100% successful classification for five classes of analytes.
The use of chlorine dioxide to disinfect drinking water and ameliorate toxic components of wastew... more The use of chlorine dioxide to disinfect drinking water and ameliorate toxic components of wastewater has significant advantages in terms of providing safe water. Nonetheless, significant drawbacks toward such usage remain. These drawbacks include the fact that toxic byproducts of the disinfection agents are often formed, and the complete removal of such agents can be challenging. Reported herein is one approach to solving this problem: the use of α-cyclodextrin to affect the product distribution in chlorine dioxide-mediated decomposition of organic pollutants. The presence of α-cyclodextrin leads to markedly more oxidation and less aromatic chlorination, in a manner that is highly dependent on analyte structure and other reaction conditions. Mechanistic hypotheses are advanced to explain the cyclodextrin effect, and the potential for use of α-cyclodextrin for practical wastewater treatment is also discussed.
Reported herein is a multidisciplinary laboratory experiment for advanced undergraduate students ... more Reported herein is a multidisciplinary laboratory experiment for advanced undergraduate students that includes elements of material synthesis, in the synthesis of cyclodextrin-containing metal-organic frameworks (CD-MOFs), and environmental chemistry, in the use of these MOFs for pollutant removal. This multi-day laboratory experiment starts with the synthesis of cyclodextrin-containing metal-organic frameworks (CD-MOFs) using vapor diffusion crystal growth procedures, followed by the use of the CD-MOFs for a pollutant removal application. Specifically, the CD-MOFs were used for the removal of a methylene blue dye (a common mimic of aromatic pollutants) from an organic solution, with the monitoring of the success of the removal procedures using UV-visible spectroscopy. This experiment was implemented as part of a larger multi-day unit, and undergraduate students were particularly engaged with and excited by the CD-MOF synthesis and methylene blue removal experimental modules. As a result, the decision was made to make these two components a stand-alone multidisciplinary laboratory experiment, the results of which are reported herein.
Reported herein is the design, implementation, and evaluation of a full-day outreach program for ... more Reported herein is the design, implementation, and evaluation of a full-day outreach program for high school girls that focuses entirely on sugar-related activities. The program, which we ran in February 2016 and February 2017, included multiple hands-on sugar-based experiments to increase the participants' interest in and enthusiasm for science. The success of the program was quantitatively evaluated through the administration of pre-camp and post-camp surveys. Overall, the survey results indicated a marked improvement in responses, which corresponds to strong success in changing the participants' attitudes regarding the practical applicability of science and in increasing their interest in pursuing scientific careers.
Fluorescent organic polymers are used in a wide range of applications, including explosive sensin... more Fluorescent organic polymers are used in a wide range of applications, including explosive sensing, clean energy technologies, and biological detection schemes. However, such polymers are rarely synthesized in an undergraduate organic teaching laboratory, due to their air and moisture sensitivity. The synthesis of a fluorescent organic polymer, poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV), is described for the upper-division undergraduate organic laboratory. This polymerization is accomplished using straightforward procedures to exclude air and moisture, without requiring the use of a glovebox or strict inert-atmosphere conditions. Once synthesized, the polymer is used for two applications, the fabrication of fluorescent thin films and the formation of organic conjugated nanoparticles, and leads to a number of pedagogical opportunities about polymerization, organic fluorescence, solid-state properties, and hydrophobic nanoparticle formation.
A second, monoclinic polymorph of the title compound, C 14 H 8 Cl 2 , has been found. In addition... more A second, monoclinic polymorph of the title compound, C 14 H 8 Cl 2 , has been found. In addition to the structure of this monoclinic form, the structure of the orthorhombic form has been redetermined at low temperature and with modern methods. The low-temperature structure of the orthorhombic form is of significantly higher quality than the previously published one and additional details can be derived. A comparison of the crystal packing of the two forms with a focus on weak intermolecular C-H···Cl interactions shows the monoclinic structure to have one such interaction linking the molecules into infinite ribbons, while two crystallographically independent C-H···Cl bonds give rise to an interesting infinite three-dimensional network in the orthorhombic crystal form. Comment One of the starting materials used in context of our ongoing research about energy transfer in ternary complexes is the title compound, 1,8-dichloroanthracene. Instead of the desired reaction product, crystals of the title compound were obtained and the structure was determined to be a previously undescribed, monoclinic polymorph of 1,8-dichloroanthracene. The orthorhombic structure of the title compound had originally been reported without coordinates by Desvergne et al. (1978) and was determined in space group Pnma (with Z=4) from Weissenberg photographs collected at room temperature. This structure was later corrected by Benites et al. (1996) to space group Pna2 1 in essentially the same unit cell, determined based on point-detector data, collected at room temperature and refined against F values instead of F 2. To better compare the two polymorphs and also to redetermine the structure with current methods, low-temperature data of the orthorhombic form were collected (the original bulk sample could still be found) using a modern diffractometer equipped with an area detector. Figures 1 and
Reported herein is the detection of highly toxic polycyclic aromatic hydrocarbons (PAHs) and poly... more Reported herein is the detection of highly toxic polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) via proximity-induced non-covalent energy transfer. This energy transfer occurs in the cavity of γ-cyclodextrin, and is efficient even with the most toxic PAHs 10 and least fluorescent PCBs. The low limits of detection and potential for selective detection using array-based systems, combined with the straightforward experimental setup, make this new detection method particularly promising. Polycyclic aromatic hydrocarbons (PAHs) 1 and polychlorinated 15 biphenyls (PCBs) are two of the ten most toxic classes of compounds according to the Center for Disease Control's ranking in 2011; 2 as such, the development of sensitive and selective detection methods remains a top priority. PAHs are formed from the incomplete combustion of petroleum, and their presence has 20 been detected in human blood and breast milk, 3 and in Gulf water seafood following the Gulf of Mexico oil spill. 4 Some examples of PAHs and the FDA-recommended concentration limits of PAHs in seafood are shown in Figure 1. 5 PCBs were historically used as refrigerator coolants and in a 25 variety of manufacturing products. 6 Although the use of PCBs was banned in the United States in 1979, 7 their atmospheric stability means that PCBs still persist in the environment. 8 Some examples of PCBs are shown in Figure 1; the FDA-recommended concentration limits for PCBs in food ranges from 0.2-3.0 parts 30 per million (ppm). 9 Current methods for the detection of PAHs and PCBs generally rely on separation using chromatography, followed by detection via mass spectrometry (for PAHs 10 and PCBs 11) or fluorescence spectroscopy (for PAHs). The development of new 35 methods for the detection of these compounds remains a high priority, especially if such methods have improved sensitivity and/or selectivity. We previously reported that energy transfer occurs between anthracene and a squaraine fluorophore inside the cavity of γ-40 cyclodextrin, with up to 35% energy transfer observed from anthracene excitation compared to direct squaraine excitation. 12 The energy transfer efficiency is defined as: % Efficiency = (I DA /I D)*100% (1) 45 where I DA is the integrated emission of the fluorophore from PAH excitation and I D is the integrated fluorophore emission from direct excitation. Although examples of energy transfer with covalently-modified cyclodextrins have been reported, 13 non-covalent 50 energy transfer inside cyclodextrin cavities is much less developed, 14 even though such energy transfer is substantially easier to tune and optimize. 15 anthracene py rene benzo [ a ]py rene 1846 pp m 185 pp m 0.132 pp m 1 2 3 fluorene 246 pp m 5 Cl Cl 4,4'-dichlorobiphenyl PCB29 Cl Cl Cl 6 7 ph enanthrene conc. limit not determined 4 Figure 1: PAHs and PCBs used as energy donors, together with the FDA-55 recommended concentration limits for PAHs in parts per million (ppm) Reported herein is the development of a widely applicable non-covalent energy transfer system between PAH and PCB energy donors and fluorophore acceptors. These fluorophores (Figure 2) were chosen because of their high quantum yields, 16 60 and established use in a variety of sensing schemes. 17 Compound 8 is commercially available, and compounds 9 and 10 were synthesized following known procedures. 18 Energy transfer from the analytes to the fluorophores in the presence of cyclodextrin was measured by mixing the analyte and 65 fluorophore in a γ-cyclodextrin solution in phosphate-buffered saline (PBS) to generate a ternary complex. The complex was then excited near the absorbance maximum of the analyte and near the maximum of the fluorophore, and energy transfer efficiencies were calculated. 70 Control experiments were also done in which the fluorophore was excited at the analyte's excitation wavelength in the absence of any analyte, to determine whether peaks previously identified as energy transfer peaks might be due to fluorophore emission from excitation at a wavelength where it has non-zero 75 absorbance.
Reported herein is the development of non-covalent, proximity-induced energy transfer from small-... more Reported herein is the development of non-covalent, proximity-induced energy transfer from small-molecule toxicants to organic fluorophores bound in the cavity of γ-cyclodextrin. This energy transfer occurs with exceptional efficiency for a broad range of toxicants in complex biological media, and is largely independent of the spectral overlap between the donor and acceptor. This generally applicable phenomenon has significant potential in the development of new turn-on detection schemes.
Journal of Polymer Science A: Polymer Chemistry, 2013
Reported herein is the highly efficient quenching of fluorescent organic nanoparticles by 2,4-din... more Reported herein is the highly efficient quenching of fluorescent organic nanoparticles by 2,4-dinitrotoluene (DNT) and 2,4,6-trinitrotoluene (TNT). These fluorescent nanoparticles are formed from the hydrophobic collapse of fluorescent polymer chains, and display quenching efficiencies that are in line with the best reported literature values. Moreover, the fluorescent quenching occurs only for the fluorescent nanoparticles, and not for the precursor polymer solutions, which display marked insensitivity to the presence of nitroaromatics. This aggregation-dependent fluorescent quenching has numerous applications for the detection of small-molecule electron-deficient analytes.
The use of aromatic organic macrocycles as supramolecular hosts for non-covalent energy transfer ... more The use of aromatic organic macrocycles as supramolecular hosts for non-covalent energy transfer is reported herein. These macrocycles lead to stronger binding and more efficient energy transfer compared to commercially available γ-cyclodextrin. This energy transfer was particularly efficient for the highly toxic benzo[a]pyrene with a fluorescent BODIPY acceptor, with up to a 5-fold increase in the fluorophore emission observed.
Polyethyleneimines (PEIs) are a well-studied class of polymers. 1,2 These polymers are synthesize... more Polyethyleneimines (PEIs) are a well-studied class of polymers. 1,2 These polymers are synthesized commercially via the ring opening of aziridine (Scheme 1, Reaction 2), 3-5 although this process leads to highly branched polymers 6 with significant polydispersity indexes. The controlled synthesis of linear PEIs occurs via the cationic ring opening of oxazolines, 7-9 followed by hydrolysis of the resulting formamides (Scheme 1, Reaction 1). Using chiral oxazolines as substrates for the polymerization provides straightforward access to homochiral PEIs, 10-12 with chiral centers at every polymer repeat unit. The significant interest in PEIs is driven largely by various applications of PEIs in fields including chiral catalysis, 13-16 drug delivery, 17,18 and oligonucleotide complexation and delivery. 19,20 PEIs have also been covalently linked to form PEI-derived microcapsules, 21 which have been used for site-isolated catalysis. 22,23 In one example, the Lewis basic PEI catalyzed a reaction in the same reaction vessel as a Lewis acidic nickel catalyst, which was used to catalyze the second reaction. 24,25 Use of the same PEI scaffold for multiple applications has rarely been reported, although such multipurpose polymers would have significant operational advantages. Reported herein is the use of a signle PEI scaffold for two purposes: the fabrication of covalently-linked chiral microcapsules, and the efficient delivery of siRNA to Huh7 cells. 26 The chiral PEIs were synthesized via the cationic polymerization of 4-benzyl-2-oxazoline (1a)(both R and S configurations), followed by the hydrolysis of the initially formed polyformamide (Scheme 2). The resulting polymers were characterized by 1 H NMR spectroscopy, and the results were in agreement with literature-reported spectra. 11 Using this methodology, polymers with 13 and 30 repeat units were formed, with both R and S benzyl side chains. Once synthesized, the homochiral PEIs were cross-linked to form homochiral microcapsules following the procedure developed by McQuade and co-workers. 22 Briefly, polymers 2awere dissolved in methanol,
Reported herein is the use of γ-cyclodextrin for two tandem functions: (a) the extraction of carc... more Reported herein is the use of γ-cyclodextrin for two tandem functions: (a) the extraction of carcinogenic polycyclic aromatic hydrocarbons (PAHs) from oil samples into aqueous solution, and (b) the promotion of highly efficient energy transfer from the newly extracted PAHs to a high-quantum yield fluorophore. The extraction proceeded in moderate to good efficiencies, and the resulting cyclodextrin-promoted energy transfer lead to a new, brightly fluorescent signal in the aqueous solution. The resulting dual-function system (extraction followed by energy transfer) has significant relevance in the environmental detection and cleanup of oil spill-related carcinogens. 2 Introduction:
Reported is a robust and easy method for detecting cesium metal ion (Cs+) in partially aq. solns.... more Reported is a robust and easy method for detecting cesium metal ion (Cs+) in partially aq. solns. using the fluorescence quenching of 2,4-bis[4-(N,N-dihydroxyethylamino)phenyl]squaraine. This squaraine dye was found to be both highly sensitive (low limits of detection) and selective (limited response to other metals) for cesium ion detection. The detection is likely based on the metal complexing to the dihydroxyethanolamine moieties, which disrupts the donor-acceptor-donor architecture and leads to efficient quenching.
Reported herein is the identification of a new methodology for the dibromination of benzylic diol... more Reported herein is the identification of a new methodology for the dibromination of benzylic diols. This method proceeds in moderate to good yields for a wide variety of electron-deficient, electron-neutral, and electron-rich aromatic substrates. Moreover, the reagent, 1,3-dibromo-5,5-dimethylhydantoin, and the solvent, tetrahydrofuran, are substantially more environmentally benign than traditional solvents and reagents used for bromination. The utility of this methodology was demonstrated in the high-yielding synthesis of a key intermediate in the synthesis of omeprazole
Reported herein is the use of proximity-induced non-covalent energy transfer for the detection of... more Reported herein is the use of proximity-induced non-covalent energy transfer for the detection of medium-sized polycyclic aromatic hydrocarbons (PAHs). This energy transfer occurs within the cavity of γ-cyclodextrin in various aqueous environments, including human plasma. Highly efficient energy transfer was observed, and the efficiency of the energy transfer is independent of the concentration of γ-cyclodextrin used, demonstrating the importance of hydrophobic binding in facilitating such energy transfer. Low limits of detection were also observed for many of the PAHs investigated, which is promising for the development of fluorescence-based detection schemes.
Journal of Inclusion Phenomenon and Macrocyclic Chemistry, 2015
The use of 2-hydroxypropyl-β-cyclodextrin (2-HPCD) for the tandem extraction and proximity-induce... more The use of 2-hydroxypropyl-β-cyclodextrin (2-HPCD) for the tandem extraction and proximity-induced energy transfer based detection of carcinogenic polycyclic aromatic hydrocarbons (PAHs) is described herein. Previous work investigated γ-cyclodextrin for this purpose, but the lower cost and reduced toxicity of 2-HPCD made it an attractive target for investigation. 2-HPCD was found to be highly efficient in the extraction of PAHs from oil samples, but was equally or slightly less efficient in promoting intra-cavity energy transfer to a high quantum yield fluorophore. The detection of PAHs via this system results in a new fluorescent signal that can be used to identify different PAHs in aqueous solution. This dual-function system can be very beneficial for oil spill remediation efforts.
Reported herein is the effect of cyclodextrins on the rates of aqueous Diels Alder reactions of 9... more Reported herein is the effect of cyclodextrins on the rates of aqueous Diels Alder reactions of 9-anthracenemethanol with a variety of N-substituted maleimides. These reactions occurred under mild reaction conditions (aqueous solvent, 40 o C), and were most efficient for the reaction of N-cyclohexylmaleimide with a methyl-β-cyclodextrin additive (94% conversion in 24 hours). These results can be explained on the basis of a model wherein the cyclodextrins bind the hydrophobically-substituted maleimides and activate the dienophile via electronic modulation of the maleimide double bond. The deplanarization of polycyclic aromatic hydrocarbons (PAHs) via organic reactions under mild conditions, as demonstrated herein, has significant applications in the detoxification of PAHs for oil spill cleanup and other environmental remediation efforts. 2
Herein we report the highly efficient and sensitive detection of hydrogen peroxide in both aqueou... more Herein we report the highly efficient and sensitive detection of hydrogen peroxide in both aqueous solution and in the vapor phase via fluorescence quenching (turn-off mechanism) of the amplified fluorescent conjugated polymer-titanium complex induced by hydrogen peroxide. Inter- and intra-polymer energy migration leads to extremely high sensitivity.
Herein we report the efficient extraction of aromatic analytes from crude oil and tar balls using... more Herein we report the efficient extraction of aromatic analytes from crude oil and tar balls using multiple cyclodextrin derivatives. The known propensity of the cyclodextrins to bind hydrophobic guests in their hydrophobic interiors enhanced the extraction of aromatic analytes from the oil layer to the aqueous layer, with methyl-β-cyclodextrin and β-cyclodextrin providing the most significant enhancement in extraction efficiencies of aromatic toxicants (69% aromatic toxicants in aqueous layer in the presence of methyl-β-cyclodextrin compared to 47% in cyclodextrin-free solution for tar ball oil extraction), and provide optimal tunability for developing efficient extraction systems. The cyclodextrin derivatives also promoted efficient energy transfer in the aqueous solutions, with up to 86% efficient energy transfer observed in the presence of γ-cyclodextrin compared to 50% in the absence of cyclodextrin for oil spill oil extraction. Together, this dual function extraction followed by detection system has potential in the development of environmental remediation systems.
We report herein the selective array-based detection of 30 persistent organic pollutants via cycl... more We report herein the selective array-based detection of 30 persistent organic pollutants via cyclodextrin-promoted energy transfer. The use of three fluorophores enabled the development of an array that classified 30 analytes with 100% accuracy and identified unknown analytes with 96% accuracy, as well as identifying 92% of analytes in urine. Many anthropogenic events, such as oil spills and chemical leaks, release a diverse suite of organic chemicals en masse into the environment. These persistent organic pollutants (POPs) remain in the environment for extended periods of time, and have significant environmental and health consequences both in the short-and long-term, to humans, animals, and plants living in disaster-affected areas. Widespread and long-term environmental consequences occur because of the persistent nature of organic pollutants in the environment, which enables many toxicants to affect areas beyond the immediate contamination site. 1 Health consequences from pollution occur via the exposure of individuals to the complex mixture of released toxicants. Both the unknown consequences of individuals' exposure to toxicant mixtures and the persistence and mobility of such toxicants and toxicant metabolites in the environment can make the effective monitoring and treatment of individuals living in disaster areas particularly difficult. The ability to rapidly, sensitively, and selectively identify the compound(s) involved in an anthropogenic contamination event is crucial information for first responders. In the case of an oil spill, such as 1989's Exxon Valdez and 2010's Deepwater Horizon spills, the compounds involved in the contamination event included numerous polycyclic aromatic hydrocarbons (PAHs and heterocyclic hydrocarbons. 2 There are also contamination events in which the pollutant(s) are not initially known, including the Love Canal incident in 1978 (ultimately determined to involve a complex mixture of pesticides and organochlorines), 3 and West Virginia's Elk River chemical spill in 2014 involving 4-methylcyclohexylmethanol and a mixture of glycol ethers (PPH), in which the full extent of the spill and chemicals involved was not initially disclosed. 4 These four anthropogenic disasters highlight the need for a sensing platform that can detect a wide variety of POPs with sensitivity, selectivity, generality, and rapidity. Such a detection scheme would fill a crucial knowledge gap for first responders, who currently need to wait for time-consuming laboratory tests to accurately classify the nature of the pollutants. It would work in conjunction with current methods, by allowing first responders to screen numerous samples to rapidly understand the nature of the pollutants involved and the extent of the event so that they can begin an effective response. Previous research in our groups has demonstrated that cyclodextrin-promoted energy transfer can be used for the detection of a wide range of aromatic toxicants, 5 and that array-based detection enables the sensitive, selective, and accurate identification of a wide variety of analytes. 6 We present herein the design, execution, and evaluation of an extremely accurate array-based detection system for aromatic POPs based on cyclodextrin-promoted energy transfer from the POPs to high quantum yield fluorophores. γ-Cyclodextrin promoted energy transfer uses γ-cyclodextrin as a supramolecular scaffold that enforces close proximity between the aromatic analyte energy donor and high quantum yield fluorophore acceptor. 7 Once bound in close proximity, excitation of the donor results in energy transfer to and emission from the fluorophore, generating a unique highly emissive fluorophore signal (Figure 1). Because each fluorophore-analyte combination yields a distinct signal, statistical analyses of the response patterns of multiple fluorophores in cyclodextrin to a single analyte identifies a unique "fingerprint" for each analyte of interest. Fig. 1 Illustration of γ-cyclodextrin promoted energy transfer, wherein the analyte acts as an energy donor to a high quantum yield fluorophore acceptor. The thirty analytes targeted for this study were chosen to cover a wide range of compound classes (Chart 1) that are highly toxic and identified as hazardous by multiple monitoring
Improved selectivity and sensitivity using covalent fluorophore–cyclodextrin analogues resulted i... more Improved selectivity and sensitivity using covalent fluorophore–cyclodextrin analogues resulted in 100% successful classification for five classes of analytes.
The use of chlorine dioxide to disinfect drinking water and ameliorate toxic components of wastew... more The use of chlorine dioxide to disinfect drinking water and ameliorate toxic components of wastewater has significant advantages in terms of providing safe water. Nonetheless, significant drawbacks toward such usage remain. These drawbacks include the fact that toxic byproducts of the disinfection agents are often formed, and the complete removal of such agents can be challenging. Reported herein is one approach to solving this problem: the use of α-cyclodextrin to affect the product distribution in chlorine dioxide-mediated decomposition of organic pollutants. The presence of α-cyclodextrin leads to markedly more oxidation and less aromatic chlorination, in a manner that is highly dependent on analyte structure and other reaction conditions. Mechanistic hypotheses are advanced to explain the cyclodextrin effect, and the potential for use of α-cyclodextrin for practical wastewater treatment is also discussed.
Reported herein is a multidisciplinary laboratory experiment for advanced undergraduate students ... more Reported herein is a multidisciplinary laboratory experiment for advanced undergraduate students that includes elements of material synthesis, in the synthesis of cyclodextrin-containing metal-organic frameworks (CD-MOFs), and environmental chemistry, in the use of these MOFs for pollutant removal. This multi-day laboratory experiment starts with the synthesis of cyclodextrin-containing metal-organic frameworks (CD-MOFs) using vapor diffusion crystal growth procedures, followed by the use of the CD-MOFs for a pollutant removal application. Specifically, the CD-MOFs were used for the removal of a methylene blue dye (a common mimic of aromatic pollutants) from an organic solution, with the monitoring of the success of the removal procedures using UV-visible spectroscopy. This experiment was implemented as part of a larger multi-day unit, and undergraduate students were particularly engaged with and excited by the CD-MOF synthesis and methylene blue removal experimental modules. As a result, the decision was made to make these two components a stand-alone multidisciplinary laboratory experiment, the results of which are reported herein.
Reported herein is the design, implementation, and evaluation of a full-day outreach program for ... more Reported herein is the design, implementation, and evaluation of a full-day outreach program for high school girls that focuses entirely on sugar-related activities. The program, which we ran in February 2016 and February 2017, included multiple hands-on sugar-based experiments to increase the participants' interest in and enthusiasm for science. The success of the program was quantitatively evaluated through the administration of pre-camp and post-camp surveys. Overall, the survey results indicated a marked improvement in responses, which corresponds to strong success in changing the participants' attitudes regarding the practical applicability of science and in increasing their interest in pursuing scientific careers.
Fluorescent organic polymers are used in a wide range of applications, including explosive sensin... more Fluorescent organic polymers are used in a wide range of applications, including explosive sensing, clean energy technologies, and biological detection schemes. However, such polymers are rarely synthesized in an undergraduate organic teaching laboratory, due to their air and moisture sensitivity. The synthesis of a fluorescent organic polymer, poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV), is described for the upper-division undergraduate organic laboratory. This polymerization is accomplished using straightforward procedures to exclude air and moisture, without requiring the use of a glovebox or strict inert-atmosphere conditions. Once synthesized, the polymer is used for two applications, the fabrication of fluorescent thin films and the formation of organic conjugated nanoparticles, and leads to a number of pedagogical opportunities about polymerization, organic fluorescence, solid-state properties, and hydrophobic nanoparticle formation.
A second, monoclinic polymorph of the title compound, C 14 H 8 Cl 2 , has been found. In addition... more A second, monoclinic polymorph of the title compound, C 14 H 8 Cl 2 , has been found. In addition to the structure of this monoclinic form, the structure of the orthorhombic form has been redetermined at low temperature and with modern methods. The low-temperature structure of the orthorhombic form is of significantly higher quality than the previously published one and additional details can be derived. A comparison of the crystal packing of the two forms with a focus on weak intermolecular C-H···Cl interactions shows the monoclinic structure to have one such interaction linking the molecules into infinite ribbons, while two crystallographically independent C-H···Cl bonds give rise to an interesting infinite three-dimensional network in the orthorhombic crystal form. Comment One of the starting materials used in context of our ongoing research about energy transfer in ternary complexes is the title compound, 1,8-dichloroanthracene. Instead of the desired reaction product, crystals of the title compound were obtained and the structure was determined to be a previously undescribed, monoclinic polymorph of 1,8-dichloroanthracene. The orthorhombic structure of the title compound had originally been reported without coordinates by Desvergne et al. (1978) and was determined in space group Pnma (with Z=4) from Weissenberg photographs collected at room temperature. This structure was later corrected by Benites et al. (1996) to space group Pna2 1 in essentially the same unit cell, determined based on point-detector data, collected at room temperature and refined against F values instead of F 2. To better compare the two polymorphs and also to redetermine the structure with current methods, low-temperature data of the orthorhombic form were collected (the original bulk sample could still be found) using a modern diffractometer equipped with an area detector. Figures 1 and
Reported herein is the detection of highly toxic polycyclic aromatic hydrocarbons (PAHs) and poly... more Reported herein is the detection of highly toxic polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) via proximity-induced non-covalent energy transfer. This energy transfer occurs in the cavity of γ-cyclodextrin, and is efficient even with the most toxic PAHs 10 and least fluorescent PCBs. The low limits of detection and potential for selective detection using array-based systems, combined with the straightforward experimental setup, make this new detection method particularly promising. Polycyclic aromatic hydrocarbons (PAHs) 1 and polychlorinated 15 biphenyls (PCBs) are two of the ten most toxic classes of compounds according to the Center for Disease Control's ranking in 2011; 2 as such, the development of sensitive and selective detection methods remains a top priority. PAHs are formed from the incomplete combustion of petroleum, and their presence has 20 been detected in human blood and breast milk, 3 and in Gulf water seafood following the Gulf of Mexico oil spill. 4 Some examples of PAHs and the FDA-recommended concentration limits of PAHs in seafood are shown in Figure 1. 5 PCBs were historically used as refrigerator coolants and in a 25 variety of manufacturing products. 6 Although the use of PCBs was banned in the United States in 1979, 7 their atmospheric stability means that PCBs still persist in the environment. 8 Some examples of PCBs are shown in Figure 1; the FDA-recommended concentration limits for PCBs in food ranges from 0.2-3.0 parts 30 per million (ppm). 9 Current methods for the detection of PAHs and PCBs generally rely on separation using chromatography, followed by detection via mass spectrometry (for PAHs 10 and PCBs 11) or fluorescence spectroscopy (for PAHs). The development of new 35 methods for the detection of these compounds remains a high priority, especially if such methods have improved sensitivity and/or selectivity. We previously reported that energy transfer occurs between anthracene and a squaraine fluorophore inside the cavity of γ-40 cyclodextrin, with up to 35% energy transfer observed from anthracene excitation compared to direct squaraine excitation. 12 The energy transfer efficiency is defined as: % Efficiency = (I DA /I D)*100% (1) 45 where I DA is the integrated emission of the fluorophore from PAH excitation and I D is the integrated fluorophore emission from direct excitation. Although examples of energy transfer with covalently-modified cyclodextrins have been reported, 13 non-covalent 50 energy transfer inside cyclodextrin cavities is much less developed, 14 even though such energy transfer is substantially easier to tune and optimize. 15 anthracene py rene benzo [ a ]py rene 1846 pp m 185 pp m 0.132 pp m 1 2 3 fluorene 246 pp m 5 Cl Cl 4,4'-dichlorobiphenyl PCB29 Cl Cl Cl 6 7 ph enanthrene conc. limit not determined 4 Figure 1: PAHs and PCBs used as energy donors, together with the FDA-55 recommended concentration limits for PAHs in parts per million (ppm) Reported herein is the development of a widely applicable non-covalent energy transfer system between PAH and PCB energy donors and fluorophore acceptors. These fluorophores (Figure 2) were chosen because of their high quantum yields, 16 60 and established use in a variety of sensing schemes. 17 Compound 8 is commercially available, and compounds 9 and 10 were synthesized following known procedures. 18 Energy transfer from the analytes to the fluorophores in the presence of cyclodextrin was measured by mixing the analyte and 65 fluorophore in a γ-cyclodextrin solution in phosphate-buffered saline (PBS) to generate a ternary complex. The complex was then excited near the absorbance maximum of the analyte and near the maximum of the fluorophore, and energy transfer efficiencies were calculated. 70 Control experiments were also done in which the fluorophore was excited at the analyte's excitation wavelength in the absence of any analyte, to determine whether peaks previously identified as energy transfer peaks might be due to fluorophore emission from excitation at a wavelength where it has non-zero 75 absorbance.
Reported herein is the development of non-covalent, proximity-induced energy transfer from small-... more Reported herein is the development of non-covalent, proximity-induced energy transfer from small-molecule toxicants to organic fluorophores bound in the cavity of γ-cyclodextrin. This energy transfer occurs with exceptional efficiency for a broad range of toxicants in complex biological media, and is largely independent of the spectral overlap between the donor and acceptor. This generally applicable phenomenon has significant potential in the development of new turn-on detection schemes.
Journal of Polymer Science A: Polymer Chemistry, 2013
Reported herein is the highly efficient quenching of fluorescent organic nanoparticles by 2,4-din... more Reported herein is the highly efficient quenching of fluorescent organic nanoparticles by 2,4-dinitrotoluene (DNT) and 2,4,6-trinitrotoluene (TNT). These fluorescent nanoparticles are formed from the hydrophobic collapse of fluorescent polymer chains, and display quenching efficiencies that are in line with the best reported literature values. Moreover, the fluorescent quenching occurs only for the fluorescent nanoparticles, and not for the precursor polymer solutions, which display marked insensitivity to the presence of nitroaromatics. This aggregation-dependent fluorescent quenching has numerous applications for the detection of small-molecule electron-deficient analytes.
The use of aromatic organic macrocycles as supramolecular hosts for non-covalent energy transfer ... more The use of aromatic organic macrocycles as supramolecular hosts for non-covalent energy transfer is reported herein. These macrocycles lead to stronger binding and more efficient energy transfer compared to commercially available γ-cyclodextrin. This energy transfer was particularly efficient for the highly toxic benzo[a]pyrene with a fluorescent BODIPY acceptor, with up to a 5-fold increase in the fluorophore emission observed.
Polyethyleneimines (PEIs) are a well-studied class of polymers. 1,2 These polymers are synthesize... more Polyethyleneimines (PEIs) are a well-studied class of polymers. 1,2 These polymers are synthesized commercially via the ring opening of aziridine (Scheme 1, Reaction 2), 3-5 although this process leads to highly branched polymers 6 with significant polydispersity indexes. The controlled synthesis of linear PEIs occurs via the cationic ring opening of oxazolines, 7-9 followed by hydrolysis of the resulting formamides (Scheme 1, Reaction 1). Using chiral oxazolines as substrates for the polymerization provides straightforward access to homochiral PEIs, 10-12 with chiral centers at every polymer repeat unit. The significant interest in PEIs is driven largely by various applications of PEIs in fields including chiral catalysis, 13-16 drug delivery, 17,18 and oligonucleotide complexation and delivery. 19,20 PEIs have also been covalently linked to form PEI-derived microcapsules, 21 which have been used for site-isolated catalysis. 22,23 In one example, the Lewis basic PEI catalyzed a reaction in the same reaction vessel as a Lewis acidic nickel catalyst, which was used to catalyze the second reaction. 24,25 Use of the same PEI scaffold for multiple applications has rarely been reported, although such multipurpose polymers would have significant operational advantages. Reported herein is the use of a signle PEI scaffold for two purposes: the fabrication of covalently-linked chiral microcapsules, and the efficient delivery of siRNA to Huh7 cells. 26 The chiral PEIs were synthesized via the cationic polymerization of 4-benzyl-2-oxazoline (1a)(both R and S configurations), followed by the hydrolysis of the initially formed polyformamide (Scheme 2). The resulting polymers were characterized by 1 H NMR spectroscopy, and the results were in agreement with literature-reported spectra. 11 Using this methodology, polymers with 13 and 30 repeat units were formed, with both R and S benzyl side chains. Once synthesized, the homochiral PEIs were cross-linked to form homochiral microcapsules following the procedure developed by McQuade and co-workers. 22 Briefly, polymers 2awere dissolved in methanol,
Reported herein is the use of γ-cyclodextrin for two tandem functions: (a) the extraction of carc... more Reported herein is the use of γ-cyclodextrin for two tandem functions: (a) the extraction of carcinogenic polycyclic aromatic hydrocarbons (PAHs) from oil samples into aqueous solution, and (b) the promotion of highly efficient energy transfer from the newly extracted PAHs to a high-quantum yield fluorophore. The extraction proceeded in moderate to good efficiencies, and the resulting cyclodextrin-promoted energy transfer lead to a new, brightly fluorescent signal in the aqueous solution. The resulting dual-function system (extraction followed by energy transfer) has significant relevance in the environmental detection and cleanup of oil spill-related carcinogens. 2 Introduction:
Reported is a robust and easy method for detecting cesium metal ion (Cs+) in partially aq. solns.... more Reported is a robust and easy method for detecting cesium metal ion (Cs+) in partially aq. solns. using the fluorescence quenching of 2,4-bis[4-(N,N-dihydroxyethylamino)phenyl]squaraine. This squaraine dye was found to be both highly sensitive (low limits of detection) and selective (limited response to other metals) for cesium ion detection. The detection is likely based on the metal complexing to the dihydroxyethanolamine moieties, which disrupts the donor-acceptor-donor architecture and leads to efficient quenching.
Reported herein is the identification of a new methodology for the dibromination of benzylic diol... more Reported herein is the identification of a new methodology for the dibromination of benzylic diols. This method proceeds in moderate to good yields for a wide variety of electron-deficient, electron-neutral, and electron-rich aromatic substrates. Moreover, the reagent, 1,3-dibromo-5,5-dimethylhydantoin, and the solvent, tetrahydrofuran, are substantially more environmentally benign than traditional solvents and reagents used for bromination. The utility of this methodology was demonstrated in the high-yielding synthesis of a key intermediate in the synthesis of omeprazole
Reported herein is the use of proximity-induced non-covalent energy transfer for the detection of... more Reported herein is the use of proximity-induced non-covalent energy transfer for the detection of medium-sized polycyclic aromatic hydrocarbons (PAHs). This energy transfer occurs within the cavity of γ-cyclodextrin in various aqueous environments, including human plasma. Highly efficient energy transfer was observed, and the efficiency of the energy transfer is independent of the concentration of γ-cyclodextrin used, demonstrating the importance of hydrophobic binding in facilitating such energy transfer. Low limits of detection were also observed for many of the PAHs investigated, which is promising for the development of fluorescence-based detection schemes.
Journal of Inclusion Phenomenon and Macrocyclic Chemistry, 2015
The use of 2-hydroxypropyl-β-cyclodextrin (2-HPCD) for the tandem extraction and proximity-induce... more The use of 2-hydroxypropyl-β-cyclodextrin (2-HPCD) for the tandem extraction and proximity-induced energy transfer based detection of carcinogenic polycyclic aromatic hydrocarbons (PAHs) is described herein. Previous work investigated γ-cyclodextrin for this purpose, but the lower cost and reduced toxicity of 2-HPCD made it an attractive target for investigation. 2-HPCD was found to be highly efficient in the extraction of PAHs from oil samples, but was equally or slightly less efficient in promoting intra-cavity energy transfer to a high quantum yield fluorophore. The detection of PAHs via this system results in a new fluorescent signal that can be used to identify different PAHs in aqueous solution. This dual-function system can be very beneficial for oil spill remediation efforts.
Reported herein is the effect of cyclodextrins on the rates of aqueous Diels Alder reactions of 9... more Reported herein is the effect of cyclodextrins on the rates of aqueous Diels Alder reactions of 9-anthracenemethanol with a variety of N-substituted maleimides. These reactions occurred under mild reaction conditions (aqueous solvent, 40 o C), and were most efficient for the reaction of N-cyclohexylmaleimide with a methyl-β-cyclodextrin additive (94% conversion in 24 hours). These results can be explained on the basis of a model wherein the cyclodextrins bind the hydrophobically-substituted maleimides and activate the dienophile via electronic modulation of the maleimide double bond. The deplanarization of polycyclic aromatic hydrocarbons (PAHs) via organic reactions under mild conditions, as demonstrated herein, has significant applications in the detoxification of PAHs for oil spill cleanup and other environmental remediation efforts. 2
Herein we report the highly efficient and sensitive detection of hydrogen peroxide in both aqueou... more Herein we report the highly efficient and sensitive detection of hydrogen peroxide in both aqueous solution and in the vapor phase via fluorescence quenching (turn-off mechanism) of the amplified fluorescent conjugated polymer-titanium complex induced by hydrogen peroxide. Inter- and intra-polymer energy migration leads to extremely high sensitivity.
Herein we report the efficient extraction of aromatic analytes from crude oil and tar balls using... more Herein we report the efficient extraction of aromatic analytes from crude oil and tar balls using multiple cyclodextrin derivatives. The known propensity of the cyclodextrins to bind hydrophobic guests in their hydrophobic interiors enhanced the extraction of aromatic analytes from the oil layer to the aqueous layer, with methyl-β-cyclodextrin and β-cyclodextrin providing the most significant enhancement in extraction efficiencies of aromatic toxicants (69% aromatic toxicants in aqueous layer in the presence of methyl-β-cyclodextrin compared to 47% in cyclodextrin-free solution for tar ball oil extraction), and provide optimal tunability for developing efficient extraction systems. The cyclodextrin derivatives also promoted efficient energy transfer in the aqueous solutions, with up to 86% efficient energy transfer observed in the presence of γ-cyclodextrin compared to 50% in the absence of cyclodextrin for oil spill oil extraction. Together, this dual function extraction followed by detection system has potential in the development of environmental remediation systems.
We report herein the selective array-based detection of 30 persistent organic pollutants via cycl... more We report herein the selective array-based detection of 30 persistent organic pollutants via cyclodextrin-promoted energy transfer. The use of three fluorophores enabled the development of an array that classified 30 analytes with 100% accuracy and identified unknown analytes with 96% accuracy, as well as identifying 92% of analytes in urine. Many anthropogenic events, such as oil spills and chemical leaks, release a diverse suite of organic chemicals en masse into the environment. These persistent organic pollutants (POPs) remain in the environment for extended periods of time, and have significant environmental and health consequences both in the short-and long-term, to humans, animals, and plants living in disaster-affected areas. Widespread and long-term environmental consequences occur because of the persistent nature of organic pollutants in the environment, which enables many toxicants to affect areas beyond the immediate contamination site. 1 Health consequences from pollution occur via the exposure of individuals to the complex mixture of released toxicants. Both the unknown consequences of individuals' exposure to toxicant mixtures and the persistence and mobility of such toxicants and toxicant metabolites in the environment can make the effective monitoring and treatment of individuals living in disaster areas particularly difficult. The ability to rapidly, sensitively, and selectively identify the compound(s) involved in an anthropogenic contamination event is crucial information for first responders. In the case of an oil spill, such as 1989's Exxon Valdez and 2010's Deepwater Horizon spills, the compounds involved in the contamination event included numerous polycyclic aromatic hydrocarbons (PAHs and heterocyclic hydrocarbons. 2 There are also contamination events in which the pollutant(s) are not initially known, including the Love Canal incident in 1978 (ultimately determined to involve a complex mixture of pesticides and organochlorines), 3 and West Virginia's Elk River chemical spill in 2014 involving 4-methylcyclohexylmethanol and a mixture of glycol ethers (PPH), in which the full extent of the spill and chemicals involved was not initially disclosed. 4 These four anthropogenic disasters highlight the need for a sensing platform that can detect a wide variety of POPs with sensitivity, selectivity, generality, and rapidity. Such a detection scheme would fill a crucial knowledge gap for first responders, who currently need to wait for time-consuming laboratory tests to accurately classify the nature of the pollutants. It would work in conjunction with current methods, by allowing first responders to screen numerous samples to rapidly understand the nature of the pollutants involved and the extent of the event so that they can begin an effective response. Previous research in our groups has demonstrated that cyclodextrin-promoted energy transfer can be used for the detection of a wide range of aromatic toxicants, 5 and that array-based detection enables the sensitive, selective, and accurate identification of a wide variety of analytes. 6 We present herein the design, execution, and evaluation of an extremely accurate array-based detection system for aromatic POPs based on cyclodextrin-promoted energy transfer from the POPs to high quantum yield fluorophores. γ-Cyclodextrin promoted energy transfer uses γ-cyclodextrin as a supramolecular scaffold that enforces close proximity between the aromatic analyte energy donor and high quantum yield fluorophore acceptor. 7 Once bound in close proximity, excitation of the donor results in energy transfer to and emission from the fluorophore, generating a unique highly emissive fluorophore signal (Figure 1). Because each fluorophore-analyte combination yields a distinct signal, statistical analyses of the response patterns of multiple fluorophores in cyclodextrin to a single analyte identifies a unique "fingerprint" for each analyte of interest. Fig. 1 Illustration of γ-cyclodextrin promoted energy transfer, wherein the analyte acts as an energy donor to a high quantum yield fluorophore acceptor. The thirty analytes targeted for this study were chosen to cover a wide range of compound classes (Chart 1) that are highly toxic and identified as hazardous by multiple monitoring
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Papers by Mindy Levine
method proceeds in moderate to good yields for a wide variety of electron-deficient, electron-neutral, and
electron-rich aromatic substrates. Moreover, the reagent, 1,3-dibromo-5,5-dimethylhydantoin, and the
solvent, tetrahydrofuran, are substantially more environmentally benign than traditional solvents and
reagents used for bromination. The utility of this methodology was demonstrated in the high-yielding
synthesis of a key intermediate in the synthesis of omeprazole
method proceeds in moderate to good yields for a wide variety of electron-deficient, electron-neutral, and
electron-rich aromatic substrates. Moreover, the reagent, 1,3-dibromo-5,5-dimethylhydantoin, and the
solvent, tetrahydrofuran, are substantially more environmentally benign than traditional solvents and
reagents used for bromination. The utility of this methodology was demonstrated in the high-yielding
synthesis of a key intermediate in the synthesis of omeprazole