The overarching research goal in the Levine laboratory is to utilize supramolecular organic chemistry to advance our knowledge of fundamental science and solve high-impact problems of biomedical, public health, and national security interests. To that end, we have initiated a broad-based research effort over the past 7 years with the following key components: (a) investigation of fundamental non-covalent interactions in cyclodextrin complexes; (b) detection of small molecule toxicants using cyclodextrin-promoted energy transfer and cyclodextrin-promoted fluorescence modulation; (c) development of multi-functional cyclodextrin systems for oil spill remediation efforts; (d) rational design of organic macrocycles for tailored supramolecular properties; (e) advances in organic methodology; (f) development of fluorescent polymer systems for the detection of small molecule analytes; (g) advances in chemical education; and (h) boron-based flame retardant development.

(a) Investigation of fundamental non-covalent interactions. Despite the fundamental nature and widespread applicability of non-covalent interactions, the ability of scientists to understand and predict how key forces drive intermolecular interactions in any given system remains woefully underdeveloped, especially because multiple intermolecular forces often co-exist. Our group has used cyclodextrin-promoted energy transfer and fluorescence modulation to investigate crucial intermolecular interactions. Confining the donor and acceptor in or around a macrocycle cavity and studying energy transfer in such systems provides a straightforward, tunable system to investigate these intermolecular interactions.

 

Cyclodextrin Fluorescence
Figure 1

 

(b) Detection of small molecule toxicants. Current methods for assaying individuals' exposure to toxicants rely on self-reporting, which is highly subjective. This subjectivity prevents researchers from being able to accurately correlate toxicant exposure with the risk of developing exposure-related disease. Our group has developed a fundamentally new approach for toxicant detection in complex environments, by using cyclodextrin-promoted energy transfer from the toxicant to a high quantum yield fluorophore, resulting in highly selective and sensitive fluorescence read-out signals in the presence of the toxicant. Non-photophysically active toxicants are detectable using toxicant-specific changes in the fluorescence of a high quantum yield fluorophore.

 

Toxicant Detection
Figure 2

 

› relevant publications

1. DiScenza, D. J.; Gareau, L.; Serio, N.; Roque, J.; Prignano, L.; Verderame, M.; Levine, M. “Cyclodextrin-Promoted Detection of Aromatic Toxicants and Toxicant Metabolites in Urine.” Analytical Chem. Lett. 2016, 6, 345-353.

2. DiScenza, D. J.; Verderame, M.; Levine, M. “Detection of Benzene and Alkylated Benzene Derivatives in Fuel Contaminated Environments.” Clean: Soil, Air, Water, 2016, 44, 1621-1627.

3. DiScenza, D. J.; Levine, M. “Sensitive and Selective Detection of Alcohols via Fluorescence Modulation.” Supramol. Chem., 2016, 28, 881-891.

4. DiScenza, D. J.; Levine, M. “Selective Detection of Non-Aromatic Pesticides via Cyclodextrin-Promoted Fluorescence Modulation.” New J. Chem., 2016, 40, 789-793.

5. Serio, N.; Roque, J.; Badwal, A.; Levine, M. “Rapid and Efficient Pesticide Detection via Cyclodextrin-Promoted Energy Transfer.” Analyst, 2015, 140, 7503-7507.

6. Serio, N.; Moyano, D. F.; Rotello, V. M.; Levine, M. “Array-Based Detection of Persistent Organic Pollutants via Cyclodextrin Promoted Energy Transfer.” Chem. Commun., 2015, , 11615-11618.

7. Serio, N.; Prignano, L.; Peters, S.; Levine, M. “Detection of Medium-Sized Polycyclic Aromatic Hydrocarbons via Fluorescence Energy Transfer.” Polycyclic Aromatic Compounds, 2014, 34, 561-572.

8. Serio, N.; Chanthalyma, C.; Prignano, L.; Levine, M. “Cyclodextrin-Promoted Energy Transfer for Broadly Applicable Small-Molecule Detection.” Supramol. Chem., 2014, 26, 714-721.

9. Serio, N.; Miller, K.; Levine, M. “Efficient Detection of Polycyclic Aromatic Hydrocarbons and Polychlorinated Biphenyls via Three-Component Energy Transfer.” Chem. Commun., 2013, 49, 4821-4823.

10. Mako, T.; Marks, P.; Cook, N.; Levine, M. “Fluorescent Detection of Polycyclic Aromatic Hydrocarbons in Ternary Cyclodextrin Complexes.” Supramol. Chem., 2012, 24, 743-747.

(c) Development of multifunctional cyclodextrin systems for oil spill remediation. There are numerous problems that arise after an oil spill, many of which are associated with individuals' exposure to polycyclic aromatic hydrocarbons (PAHs). The ability to efficiently remove PAHs from oil-contaminated environments would significantly advance the pace of environmental remediation. Research in our group has demonstrated that cyclodextrins can be used for the tandem extraction and detection of PAHs from a variety of contaminated oil environments, which relies on the ability of the cyclodextrins to bind PAHs in their hydrophobic interiors and facilitate PAH-to-fluorophore energy transfer.

 

Oil Spill Remediation
Figure 3

 

› relevant publications

1. Serio, N.; Levine, M. “Solvent Effects in the Extraction and Detection of Polycyclic Aromatic Hydrocarbons from Complex Oils in Complex Environments.” J. Inclusion Phenom. Macrocyclic Chem., 2016, 84, 61-70.

2. Serio, N.; Levine, M. “Efficient Extraction and Detection of Aromatic Toxicants from Crude Oil and Tar Balls Using Multiple Cyclodextrin Derivatives.” Marine Pollution Bull., 2015, 95, 242-247.

3. Serio, N.; Chanthalyma, C.; Peters, S.; Levine, D.; Levine, M. “2-Hydroxypropyl beta-Cyclodextrin for the Enhanced Performance of Dual Function Extraction and Detection Systems in Complex Oil Environments.” J. Inclusion Phenom. Macrocyclic Chem., 2015, 81, 341-346.

4. Serio, N.; Chanthalyma, C.; Prignano, L.; Levine, M. “Cyclodextrin-Enhanced Extraction and Energy Transfer of Carcinogens in Complex Oil Environments.” ACS Appl. Mater. Interfaces, 2013, 5, 11951-11957.

(d) Rational design of organic macrocycles and polymers. Although supramolecular organic chemistry is a well-established field, there is a significant knowledge gap regarding the relationship between structural features of a macrocycle, the overall macrocycle conformation, and the ability of the macrocycle to participate efficiently in targeted interactions. Our group has demonstrated that small perturbations in the macrocycle architecture translate into significant differences in the macrocycle conformation; such differences, affect the ability of the macrocycle to bind benzo[a]pyrene and to promote benzo[a]pyrene-to-BODIPY energy transfer.

 

Polymers
Figure 4

 

› relevant publications

1. Radaram, B.; Levine, M. “Rationally Designed Supramolecular Organic Hosts for Benzo[a]pyrene Binding and Detection.” Eur. J. Org. Chem., 2015, 6194-6204.

2. Gharavi, J.; Marks, P.; Moran, K.; Kingsborough, B.; Verma, R.; Chen, Y.; Deng, R.; Levine, M. “Chiral Cationic Polyamines for Chiral Microcapsules and siRNA Delivery.” Bioorg. Med. Chem. Lett., 2013, 23, 5919-5922.

3. Gharavi, J.; Marks, P.; Moran, K.; Kingsborough, B.; Verma, R.; Chen, Y.; Deng, R.; Levine, M. “Chiral Cationic Polyamines for Chiral Microcapsules and siRNA Delivery.” Bioorg. Med. Chem. Lett., 2013, 23, 5919-5922.

(e) Advances in organic methodology. A broad scope of functional group transformations has been reported in the literature, although many of these require harsh conditions and/or toxic solvents. Ways to address these limitations include the development of more environmentally friendly reaction conditions. We have developed an environmentally friendly bromination methodology that uses a commercially available disinfectant, dibromodimethylhydantoin, to brominate benzylic diols to benzylic dibromides in high yields. Moreover, we have shown that commercially available cyclodextrin derivatives accelerate Diels-Alder reactions via electronic activation of the maleimide.

 

Organic Methodology
Figure 5

 

› relevant publications

1. Chaudhuri, S.; Zaki, H.; Levine, M. “Environmentally Friendly Procedure for the Aqueous Oxidation of Benzyl Alcohols to Aldehydes with Dibromodimethylhydantoin (DBDMH) and Cyclodextrin: Scope and Mechanistic Insights.” Synth. Commun., 2016, 46, 636-644.

2. Chaudhuri, S.; Phelan, T.; Levine, M. “Cyclodextrin-Promoted Diels Alder Reactions of a Polycyclic Aromatic Hydrocarbon Under Mild Reaction Conditions.” Tetrahedron Lett., 2015, 56, 1619-1623.

3. Radaram, B.; Levine, M. “A Green Bromination Method for the Synthesis of Benzylic Dibromides.” Tetrahedron Lett.,2014, 55, 4905-4908.

(f) Fluorescence-based detection systems. The rapid, sensitive, selective, and generally applicable detection of small-molecule analytes is of significant interest from a broad range of public health, national security, and environmental remediation efforts. Many of these detection methods rely on mass spectrometry-based methods, which provide exquisite sensitivity but often suffer from other operational disadvantages. Central Finding: We have recently developed fluorescence-based methods for the detection of (a) hydrogen peroxide, which uses the fluorescence quenching of a conjugated polyelectrolyte upon the reaction of a titanium oxalate complex; (b) cesium cations, using cesium-promoted fluorescence quenching of a squaraine fluorophore; (c) nitroaromatics, via the fluorescence quenching of fluorescent polymer-derived nanoparticles; and (d) pesticides, via the fluorescence enhancement of conjugated polymer nanoparticles.

 

Fluorescence
Figure 6

 

› relevant publications

1. Talbert, W.; Jones, D.; Morimoto, J.; Levine, M. “Turn-On Detection of Pesticides via Reversible Fluorescence Enhancement of Conjugated Polymer Nanoparticles and Thin Films.” New J. Chem., 2016, 40, 7273-7277.

2. Marks, P.; Radaram, B.; Levine, M.; Levitsky, I. A. “Highly Efficient Detection of Hydrogen Peroxide in Solution and in the Vapor Phase via Fluorescence Quenching.” Chem. Commun., 2015, 51, 7061-7064.

3. Radaram, B.; Mako, T.; Levine, M. “Sensitive and Selective Detection of Cesium via Fluorescence Quenching.” Dalton Trans., 2013, 42, 16276-16278.

4. Marks, P.; Cohen, S.; Levine, M. “Highly Efficient Quenching of Nanoparticles for the Detection of Electron-Deficient Nitroaromatics.” J. Polym. Sci. A Polym. Chem., 2013, 51, 4150-4155.

(g) Advances in chemical education. Our group has extensive experience conducting scientific outreach with students at all educational levels: elementary school, middle school, high school, and college. Our main outreach programs include (a) Chemistry Camp for Middle School Girls, a week-long program for 40-50 middle school girls to conduct hands-on experiments and interact with female scientists; and (b) Sugar Science Day, a full-day program for 40 high school girls to show them how “sweet” chemistry is by conducting hands-on experiments and demonstrations all using sugar. In addition to our outreach programs, our group has written and published several undergraduate chemistry laboratory experiments. Some of these experiments are still used in the undergraduate advanced organic chemistry laboratory!

 

Education
Figure 7

 

› relevant publications

1. Levine, M.; Serio, N.; Radaram, B.; Chaudhuri, S.; Talbert, W. “Addressing the STEM Gender Gap by Designing and Implementing an Educational Outreach Chemistry Camp for Middle School Girls.” J. Chem. Educ., 2015, 92, 1639-1644.

2. Mako, T.; Levine, M. “Synthesis of a Fluorescent Conjugated Polymer in the Undergraduate Organic Teaching Laboratory.” J. Chem. Educ., 2013, 90, 1376-1379.

3. Levine, M.; Marks, P. “Fluorophores, Fluorescent Polymers, and Energy Transfer in an Undergraduate Laboratory Setting.” ACS Symposium Series, 2012, 1108, 27-49.

4. Marks, P.; Levine, M. “Synthesis of a Near-Infrared Emitting Squaraine Dye in an Undergraduate Organic Laboratory.” J. Chem. Educ., 2012, 89, 1186-1189.

(h) Boron-based flame retardants. Optimal flame retardant materials need to be: (a) effective in stopping the spread of fire, (b) robust in maintaining efficacy for several years and for many wash cycles, (c) non-toxic to consumers, and (d) inexpensive to enable widespread commercial usage. Currently used flame retardant chemicals often fall short in achieving one or more of these objectives. A fairly new area of research in our laboratory focuses on developing boron-based flame retardant materials for use in cotton textile applications. The focus on boron is driven by the fact that boron-based compounds have been shown to be non-toxic and naturally abundant (and therefore relatively inexpensive). Flame retardants containing boron have been researched as additives to already established flame retardant products, but not as stand-alone flame retardant treatments. The focus on cotton textiles is driven by the fact that cotton children's pajamas are widely used and children are among the most vulnerable to fire-related injuries.

 

Flames
Figure 8

 

 

 

Funding

We are thrilled to be the recipients of research funding from the following internal and external funding sources:

National Science Foundation CAREER Grant

Lanxess Corporation

Council for Research Proposal Development Grant

University of Rhode Island Start-Up Funding

University of Rhode Island Undergraduate Research Initiative

NSF-EPSCOR Summer Research Funding

Completed Funding

Rhode Island INBRE Young Investigator Program

University of Rhode Island Foundation

Gulf of Mexico Research Initiative

Dreyfus Foundation Special Grant Program in the Chemical Sciences

Council for Research Proposal Development Grant

National Cancer Institute

Rhode Island Foundation

Pfizer Community Grant Program

Champlin Foundations

NSF Major Research Instrumentation Program

Rhode Island Research Alliance

Division of Organic Chemistry Travel Awards