My basic area of research interest is Organic Synthesis. Within this broad area, I have two areas under active investigation: deep eutectic solvents and the exploration of aurones as biologically active natural products and fluorophores.

Deep eutectic solvents (DES) are extreme examples of a very common phenomenon - melting point depression. It is well known that a mixture of two compounds will exhibit a melting point depression compared to each individual pure compound. In most cases, this depression is only a few degrees. In the case of DES, however, the depression is quite extreme (deep) and is also highly dependent on the molar ratio of the two materials. Thus, the combination of choline chloride (mp >300 C) and urea (mp roughly 128 C) in a 1:2 molar ratio affords a mixture with a melting point around 10 C - a liquid at room temperature. As both starting compounds are inexpensive, non-flammable, and non-toxic, this DES is an appealing solvent alternative. My group has observed that it also can serve as a very mild catalyst for a number of different reactions. We are continuing to explore further applications in organic synthesis as well as other DES that might have additional catalytic activities.

The aurone project features the use of DES to synthesize the aurone framework by the condensation of an aldehyde with a benzofuranone. Aurones themselves have been known to be responsible for the golden yellow coloration of the flowers of many plants. As a small sub-set of the flavonoids, it is not surprising that they exhibit a wide range of biological activities. At the same time, their low natural abundance has made this potential hard to use. Via synthesis, we have been able to prepare a significant number of new aurone variations (analogs) and, by active collaboration with many faculty in the Biology department, explore activities ranging from anti-microbial and anti-fungal to anti-inflammatory and anti-cancer. Further development of this potential continues as well as extension into the area of materials and dye chemistry.

The aurones also have proven to be quite fluorescent and we have recently reported their application as a sensor for hydrogen sulfide (an environmental contaminent, a natural cell signaling species, and also the compound responsible for skunky beer and wine).  Other uses as fluorescent labels, dyes, and probes for various other biological and metallic species are under investigation.

Compound purification, identification and synthesis

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I am a Professor of Chemistry at Middle Tennessee State University and an active member of the Molecular Biosciences PhD program and the interim Director of the Tennessee Center for Botanical Medicinal Research (TCBMR).  I also am involved in the Mathematics and Science Education PhD program.

I received my undergraduate degree in Chemistry from the University of Iowa in 1991 and completed anti-HIV research with Dr. Vasu Nair while there.

My graduate work was completed at Indiana University under the direction of Dr. Paul Grieco studying usual catalytic effects of highly concentrated solutions of lithium salts in organic solvents (thus beginning my interest in unusual solvents).

From there, I completed an NIH Post-doctoral fellowship at Stanford University in the labs of Dr. Paul Wender studying diversity-oriented libraries of potential PKC activators and gaining considerable experience in conducting biological assays - work which has well prepared me for my highly collaborative efforts at MTSU.

My first academic appointment was at Binghamton University, before moving to MTSU in 2005.

Through it all, I have enjoyed music (particularly singing), bicycling, and gardening.  Diversity of interests helps to keep me sane!

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Publications since 2010 (* indicates undergraduate co-author):

1. Kafle, A.; Bhattarai, S.; Miller, J.M.; Handy, S.T.  "Hydrogen-sulfide Sensing Using an Aurone Based Fluorescent Probe."  RSC Adv.  2020, 10, 45180-45188.
2. Kafle, A.; Bhattarai, S.; Handy, S.T.  “The first synthesis of peracetyl glycosyl aurone derivative and aurone glucosides.”  Tetrahedron  2020, 76, 131528.
3. Kafle, A.; Yossef, S.*; Handy, S.T.  “Synthesis of azido-substituted benzaledhydes via SNAr chemistry.”  Tetrahedron Lett.  2020, 61, 151899.
4. Kafle, A.; Bhatarai, S.; Handy, S.T.  “An Unusual Triazole Synthesis from Aurones.”  Synthesis, 2020, 52, 2337-2346.
5. Yang, D.; Taylor, Z.E.; Handy, S.; LI, S.; Liu, J.; Stabenow, J.; Zalduondo, L.; Jonsson, C.B.; Altman, E.; Kong, Y.  “Identification of Anti-tuberculosis Compounds From Aurone Analogs.”  Frontiers in Microbiol.  2020, 11, article 1004.
6. Alqahtani, F.M.; Arivett, B.A.; Taylor, Z.E.; Handy, S.T.; Farone, A.L.; Farone, M.B.  “Chemogenomic profiling to understand the antifungal action of a bioactive aurone compound.”  PLOSONE 2019, 14, e0226068.
7. Schmitt, J.; Handy, S.T.  “A golden opportunity: benzofuranone modifications of aurones and their influence on optical properties, toxicity, and potential as dyes.”  Beilstein J. Org. Chem.  2019, 15, 1781-1785.
8. Kafle, A.; Handy, S.T.  “A one-pot, copper-catalyzed azidation/click reaction of aryl and heteroaryl bromides in an environmentally friendly deep eutectic solvent.”  Tetrahedron  2017, 73, 7024-7029.
9. Gheda, A.; Almosnid, N.; Hawkins, I.; Taylor, Z.E.; Knott, D.L.; Jamdu, S.T.; Altman, E.; Gao, Y.  Evaluation of Fourteen Aurone Derivatives as Potential Anti-Cancer Agents.  Curr. Pharm. Biotech.  2017, 18, 384-390.
10. Sutton, C.L.; Taylor, Z.E.; Farone, M.B.; Handy, S.T.  “Antifungal activity of substituted aurones.”  Bioorg. & Med. Chem. Lett.  2017, 27, 901-903.
11. Taylor, K.M.*; Taylor, Z.E.; Handy, S.T. “Rapid synthesis of aurones under mild conditions using a combination of microwaves and deep eutectic solvents.” Tetrahedron Lett. 2017, 58, 240-241.
12. Park, H.S; Nelson, D.E.; Taylor, Z.E.; Hayes, J.B.; Cunningham, K.D.; Arivett, B.A.; Ghosh, R. Wolf, L.C.; Taylor, K.M.*; Farone, M.B.; Handy, S.T.; Farone, A.L. “Suppression of LPS-induced NF-kB activity in macrophages by the synthetic aurone, (Z)-2-((5-hydroxymethyl)furan-2-yl)methylene) benzofuran-3(@H)-one.” Int. Immunopharm. 2017, 43, 116-128.
13. Handy, S.T.; Westbrook, N.M.* "A mild synthesis of bis(indolyl)methanes using a deep eutectic solvent." Tetrahedron Lett. 2014, 55, 4969-4971.
14. Handy, S.T.; Wright, M.* "An acid-free Pictet-Spengler reaction using deep eutectic solvents (DES)." Tetrahedron Lett. 2014, 55, 3440-3442.
15. Hawkins, I.; Handy, S.T. "Synthesis of aurones under neutral conditions using a deep eutectic solvent." Tetrahedron 2013, 69, 9200-9204.
16. Handy, S.T.; Lavender, K. "Organic synthesis in deep eutectic solvents: Paal-Knorr reactions." Tetrahedron Lett. 2013, 54, 4377-4379.
17. Piala, A.; Mayi, D.*; Handy, S.T. "One-pot, Regioselective Double Suzuki Couplings of Dibromoquinolines." Tetrahedron, 2011, 67, 4147-4154.
18. Bailey L.;* Handy S.T. "Aromatic iodination using N-iodosaccharin in room temperature ionic liquids." Tetrahedron Lett. 2011, 52, 2413-2414.
19. Bornemann, S.; Handy, S.T. "Organic Electrochemistry in Ionic Liquids: The Viscosity Question." Molecules, 2011, 7, 5962-5974.
20. Chesak, S.; Handy, S.T. "One-pot Double Suzuki Couplings of 2,4-Dichloropyrimidine." Synthesis, 2010, 2714-2717.

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