Faculty Research

Synthesis of Selective Muscarinic Agonists for Alzheimer's Application

Research Objectives

The main objective of this research is to involve both chemistry and biology students at Barry University with synthetic organic research. The specific aims of the research project are:

1. To design and synthesize M1 selective muscarinic agonists. Series of heterocyclic compounds are being synthesized and tested based upon a theoretical model of the structural requirements for muscarinic receptor activity. The compounds are intended as mimics of acetylcholine and other cholinergic agonists at muscarinic receptors in the brain. Muscarinic M1 receptors are currently therapeutic targets for the symptomatic treatment of Alzheimer's disease.
2. To obtain information about the muscarinic pharmacophore by synthesizing analogs of pilocarpine, a partial muscarinic agonist currently in use to treat glaucoma.
3. To determine the binding affinity, receptor selectivity and intrinsic cellular activity of the test compounds at muscarinic m1-m5 receptor subtypes expressed in recombinant CHO cells.

Publications

1. Synthesis of Furanyl and Oxazolyl N- Substituted Piperidine and Imidazoline Salts as Potential Agonists of M1 muscarinic receptors. J. Heterocyclic. Chem., 44, 1, December 2007.
2. Synthesis of Oxazolyl-Substituted Morpholinium Salts, J. Heterocyclic Chem., 43, 1, 2006.
3. Soluble protein, Molar C:N Ratio, and Amino acid Composition in Green vs. Decayed Seagrass Leaves, Florida scientist, 68, 1, 2005.
4. Synthesis of Oxazolyl- and Furanyl- Substituted Imidazole Hydrochlorides and Methiodides, J. Heterocyclic Chem., 35, 859, 1998.

Mechanochemical Synthesis of Porphyrins

Welcome to the Hamilton Research Group at Barry University! Research in the group is performed entirely by undergraduates, who learn techniques including organic synthesis, solid-state chemistry, synthesis of air-sensitive materials, column chromatography, self-assembly, coordination chemistry, green chemistry, crystallization, NMR, UV/Vis spectroscopy, IR spectroscopy, and analysis of X-ray crystallographic data.

Our research program has two goals:

• Development of more environmentally benign syntheses of porphyrins using a solvent-free approach called mechanochemistry, where reagents are ground together using a mortar and pestle, or an automated ball mill.
• Using exo-dentate porphyrins as ligands in metal-organic assembly metal-organic polyhedra and evaluation of their efficacy as catalysts.

Solvent-free Synthesis of Porphyrins

We combine an aldehyde with pyrrole in the presence of an acid catalyst and grind using a mortar and pestle. After a few minutes grinding, a pink crystalline powder forms. Presence of a porphyrin is confirmed by UV/Vis and ¹H NMR spectroscopy. The mechanochemical process can also be automated using a ball-mill. We have shown that the approach works with a variety of aldehydes, giving yields similar to, or in some cases greater than, those available through traditional solution-based methods (Shy et al. Faraday Discuss. 2014, 170, 59-69). We are currently working on expanding the approach to include aldehydes with bulky R-groups, mixed-aldehyde syntheses, and synthesis of di-substituted porphyrins.

Current and Former Undergraduate Research Students

• Lise-Berthe Laurent, current student.
• Michaela Reyes, 2020.
• Nirva Maxi, 2017. Went on to graduate studies at the University of Georgia.
• Diana Cordero, 2017. Went on to graduate studies at MIT. National Science Foundation Graduate Research Fellow.
• Qiwen Su, 2017. Went on to graduate studies at Boston College. National Science Foundation Graduate Research Fellow.
• Suzely Alexis, 2016.
• Cindy Molina, 2016. Went on to veterinary school, Michigan State University
• Shanika Kingston, 2016. Went on to work as a research associate at the College of Pharmacy at Midwestern University, Arizona.
• Taylor Sabol, 2015.
• Victoria Hoelscher, 2015. Went on to McGovern Medical School, Houston, Texas.
• Miriam Basden, 2014. Went on to be a Nursery Wildlife Rehabilitator, South Florida Wildlife Center.
• Hannah Shy, 2013.Went on to the University of Arizona College of Medicine.
• Deepa Gharbharan, 2013. MS Program Anesthesiology Assistant, Nova Southeastern University.
• Paula Mackin, 2013. MS Program Occupational Therapy, Western University, Ontario, Canada.
• Meghan Knol, 2012. Went on to University of Michigan Medical School.
• Elvis Camacho, 2011. Went on to Columbia University Neuroscience Program.
• Cherice Boyce, 2010. Went on to MS Program in Public Health, University of West Indies.
• Vanessa Narciso, 2010. Went on to DMD Program, Nova Southeastern University.
• Megan Barnes, 2010.
• Simon Astor, 2009. Went on to MD Program, Nova Southeastern University.
• Frantzesca Belancourt, 2009. Went on to MS Program in Biomedical Sciences, Larkin Health Sciences Institute.
• Andrea Orvieto, 2009.

Links

• Our research was highlighted in Barry Magazine
• What is a porphyrin? Wikipedia entry
• The 12 Principles of Green Chemistry: EPA website

Group members at Barry's STEM Symposium, 2016 (L to R) Nirva Maxi, Qiwen Su, Dr. Hamilton, Shanika Kingston, Diana Cordero, Victoria Hoelscher.

Preparation and characterization of organo-silica monoliths for applications in liquid chromatography

1. In-situ sol-gel synthesis of porous silica, alumina and hybrid monoliths
2. Surface modification of monoliths via photografting
3. Application of prepared monoliths in normal and reverse phase microscale-liquid chromatography

Particle packed columns have been used for more than a century for the separation of components of chemical mixtures utilizing high performance liquid chromatography. Over the past two decades, a new trend has been developing towards the improvement of the speed of analysis. The goal is to achieve sufficient resolution of analytes within the shortest possible time. High-throughput analyses are needed for rapid screening of numerous samples in fields such as drug discovery and environmental analysis.

Our attention is focused on the concept of the monolithic column which has been introduced as an alternative to particle packed columns. The advantages of the monoliths include lower back pressure, enhanced diffusional mass transfer, and operation at high flow rates, which enables faster analysis. Our research is directed towards the preparation and characterization of inorganic monolithic materials such as silica, and alumina and organic-silica hybrid. These materials are further coated with various polymer stationary phases via a novel approach called photografting which can be simply described as UV initiated radical polymerization in the presence of photoinitiator. By choosing different monomer we can alternate the surface chemistry of synthesized monoliths.

We prepare these materials inside of the fused silica capillary and we evaluate their chromatographic properties using microscale-liquid chromatography. The types of compounds suitable for chromatographic separations range from simple organic compounds to proteins and peptides. Among many facilities which would benefit from the advantages of these types of materials are chemical, biological, pharmaceutical, medical, industrial and environmental laboratories.

Undergraduate students will gain:

• Hands-on experience with the preparation and characterization of monolithic columns. Capillary preparation is low-cost, safe and requires minimal number of synthetic steps.
• Understanding of principles of sol-gel transitions and inorganic chemistry which are responsible for the formation of highly porous monoliths.
• Proficiency with photografting
• Chromatographic skills through the operation and troubleshooting of a liquid chromatograph.
• Understanding of basic separation principles applied in liquid chromatography based on observation of changes in chromatographic behavior of testing mixtures with various types of polymeric coatings.
• Sense for green chemistry. Capillary liquid chromatography allows operation in flow rates in the µL/min range (instead of mL/min) therefore minimizing the amount of solvent and analyte needed for analysis.

Undergraduate Research Assistants

Student Researchers

Sidney Vest ; Evdoxia Mastrominas; Aurora Burkus-Matesevac; Montaha Abdallah - pharmacy program, College of Pharmacy, Thomas Jefferson University, Philadelphia, PA; Silva Campos Thales - laboratory assistant, Laboratory of Fuel Tests, Belo Horizonte, Brazil; Rebecca Hernandez; Lucas Narciso Meirelles - quality control, Johnson & Johnson Health and Wellness Solutions, Inc., São José dos Campos, São Paulo, Brasil; Zulema Rodriguez - MS in nutrition for health and human performance, University of Miami; Gabriella Soto - dental school Howard University; Taylor Sabol - MS in chemistry, University of Cincinnati, Ohio; QC Chemist Nature’s Bounty, Cincinnati, Ohio; Miriam Basden - nursery wildlife rehabilitator, South Florida Wildlife Center; Denae Britsch - dental school NOVA Southeastern University, Fort Lauderdale, FL; Deepa Gharbharan - MS anesthesiologist assistant program, NOVA Southeastern University, anesthesiology assistant, Baptist Hospital Of Miami; Brittany Kuhl - research and development scientist, Beckman Coulter, Miami, FL; Brittny Randolph - MS program in medical sciences, University of South Florida, Tampa, FL; Launie Bruno; Anna-Marie Weed – graduated with BS in chemical engineering from University of Washington, Seattle, WA, process engineer challenger, BP, Houston, TX; Jill Dvornik -research associate Lawrence Berkeley National Laboratory, Berkeley, CA (2011-2013), assistant specialist University of California, San Francisco, CA, currently: associate researcher II Pharmacology and Systems Therapeutics, Mount Sinai Hospital, New York; Afua Gyapong graduated from Philadelphia College of Osteopathic Medicine, Georgia; Abraham Campos; John Jacob Stefancin - executive assistant, James A. Zavrl Financial, Wickliffe, Ohio; Marc Knezevic - M.S. program, Public Health, Florida International University; Emir D. Rubi - researcher, Irell & Manella Graduate School of Biological Sciences, Duarte, CA; operations manager, Advanced Medical Reviews, Los Angeles, CA; Joao C. Luna - obtained M.S. in Geochemistry, University of Georgia, Athens, GA 2013; currently: PhD program in Geology, University of Utah, Salt Lake City, UT; Cristina Marrero-Avila - completed D.O. program, NOVA Southeastern University, Fort Lauderdale, FL; Vanessa Narciso - D.M.D. program, NOVA Southeastern University, Fort Lauderdale, FL; Rafaela Nita - Ph.D. program Florida Institute of Technology, Melbourne, FL, National Research Council Fellow, Naval Research laboratory in Washington, D.C.; Mario Cisneros - D.O. program, Edward Via College of Osteopathic Medicine, Spartanburg, SC; Heather Shetler; Ryoko Horigami; Stefanie Thompson Criminalist, Forensic Laboratory, Miami-Dade Police Department