Professor of Medicinal Chemistry
Department of Pharmaceutical & Administrative Sciences
Office: CSP 326
Office Hours: By appointment
2003 Ph.D., in Organic Chemistry. McGill University of Montreal, Quebec, Canada.
1998 B.Sc., in Chemistry. University of Northern British Columbia, Prince George, British Columbia, Canada.
Adherence to self-monitoring of blood glucose using the common finger-prick-method is significantly lower than desired. It has been reported that for diabetic’s, adherence levels are in the 20-66% range and thus is the largest cause of diabetic complications. There are numerous explanations for this low compliance; however the prominent rationale is that it is an invasive, moderately painful procedure which the individual must endure between 4-12 times a day, every day, for the remainder of their lives. There has however been reports that there is a correlation with breath acetone and blood glucose. New England Breath Technologies, LLC (www.newenglandbreath.com) is developing a technology that specifically detects breath acetone using a nanotechnology approach. This will represent the first truly non-invasive medical device for detecting and monitoring diabetes. Our technology has been highlighted in international media outlets (e.g. WebMD, FOX News, Diabetes Health, etc.).
SMALL MOLECULE DESIGN FOR THE DISRUPTION OF AMYLOID PLAQUE FORMATION
Alzheimer’s Disease (AD) is a devastating neurological degenerative disease that affected 4.5 million Americans in 2000, but is predicated to rise to 13.2 million by 2050. Causes of AD are general classified into three areas; 1) hyperphosphorylation of Tau, 2) insulin insensitivity, and 3) accumulation of the beta-amyloid (A-beta) peptide. The most prevalent theory is the Amyloid Cascade Hypothesis. It is postulated that when the APP protein is digested, initially with beta-secretase followed by gamma-secretase, the A-beta fragment is formed. This leads to aggregation of amyloid beta-peptide oligomers, also known as amyloid beta-derivatized diffusible ligands (ADDLs). These oligomers further congregate to form the characteristic plaques of AD patients.
Although, research on AD has been underway for decades, very few drugs are currently available and in all cases the drug is designed not to inhibit the progression of the disease, but to help in alleviating some of the symptoms. There are three areas for which a drug could possibly be designed to stop the progression of AD. They are i) beta-secretase inhibitors; ii) gamma-secretase inhibitors; or iii) prevention of A-beta monomer aggregation. This latter approach is the thrust of this research. Some known inhibitors of A-beta monomer aggregation are curcumin, found in curry; homotaurine, found in seaweeds; meclocycline sulfosalicylate, hemin, hematin, o-vanillin, hexadecyltrimethylammonium bromide, trimethyl(tetradecyl) ammonium bromide, neocuproine, lacmoid, rifamycin SV, 2,2’-dihydroxybenzophenone, rhodamine B, phenol red, and eosin Y. Examining the structural similarities of known A-beta monomer aggregation inhibitors provided with five library scaffolds. We have synt hesized some compounds from each library and have already begun testing using Thioflavine T fluorescence assay. One particular library has already yielded very promising results. Of the compounds tested within this set, three showed fibrillogenic inhibition between 70-85% after incubation of 3½ days. The remaining three compounds of this library demonstrated inhibition of ~95%.
NEW ANTIMICROBIAL AGENTS
The development of new antibiotics has become increasingly important as more and more strains of drug-resistant bacteria are being discovered. It is well known that phenol and many of its derivatives are antimicrobial agents. However, a comprehensive study of the structure-activity-relationship (SAR) has not been undertaken. Our research is to initial examine how modification of the acidity and lipophilicity of phenol derivatives alters biological activity to ultimately elucidate a SAR profile. This will provide a foundation to synthesize additional derivatives to further increase biological activity.
TYPE II DIABETES
Diabetes is a disease that affects 18.2 million Americans. Approximately 90-95% of these cases are type II diabetes. It has been found that this disease is directly linked to an over activity of protein tyrosine phosphatase 1B (PTP1B), which dephosphorylates the multiple tyrosine residues within the insulin receptor (IR) protein. Our research project is to develop a library of compounds which may act as inhibitors towards PTP1B.
PHOTODYNAMIC CANCER THERAPY
Photodynamic therapy (PDT) is a very attractive technique for the treatment of cancer as it is a non-invasive procedure. This involves the use of a photosensitive compound, which in the presence of light and oxygen can induce cellular death. PDT has been known for well over one hundred years, but is just now starting to be researched more extensively and used in clinical settings.
Porfimer sodium, also known as Photofrin, was the first PDT agent approved by the FDA in 1995. This drug has been used in the treatment of cervical, stomach, esophageal, bladder, endobroncheal, skin, and lung cancers. However, Photofrin exists as a mixture of dimeric and oligomeric compounds. Other porphyrin based PDT that are commercially available are Visudyne, Foscan, Purlytin, Tookad, and Motexafin Lutetium. In addition, Metvix and 5-aminolevulinic acid have also been used as PDT agents as they behave as pro-drugs, and are metabolized to porphyrins within the body. To date, very few non-porphyrin based PDT agents have been examined. Studies have been performed on methylene blue as well as nile blue, however, both of these show dark toxicity (i.e. demonstrated cytotoxic ability in the absence of a light) which would impair their application as a PDT agent. Work has been done using a boron core in a non-porphyrin based PDT agent (aza-BODIPY) with promising results. We are further examining this approach and evaluate whether these agents are active in PDT, show minimal dark toxicity, and can lead the cell to death via apoptosis. When irradiated above 600nm these aza-BODIPY compounds react with triplet O2 in the body to form a reactive singlet oxygen species which leads to cell death. In vitro studies on HeLa cells have revealed an effective photosensitive compound with low dark cytotoxicity and promotion of apoptotic cell death when exposed to light.
Since the initial synthesis of cubane, numerous derivatives have been made with a diverse range of physical, chemical, and biological properties. An additional characteristic of these compounds is their tendency to undergo cage opening under certain conditions. In our attempt to polymerize 4-iodo-1-vinylcubane, 4-vinyl-trans-beta-iodostyrene was formed quantitatively. By examining both the thermolytic and Lewis acid-assisted rates, a possible mechanism for the rearrangement is proposed. Since other iodinated cubane derivatives have been shown to have unique thermo-stability behaviour the synthesis of a library of iodinated cubane compounds was undertaken and DSC and TGA's were run on all seven derivatives. Most iodinated cubane derivatives showed melting/decomposition with no exotherm upon cooling. 4-Iodo-1-vinylcubane was observed to rearrange to 4-vinyl-trans-b-iodostyrene and its cyclooctatetraene intermediate during DSC analysis. TGA studies on 1-iodo-4-(hydroxymethyl)-cubane suggest that this particular iodinated cubane scaffold is mostly prone to rapid thermo-decomposition. In addition, the first cubanebased Schiff base ligand was successfully synthesized and employed in asymmetric reactions. With the Henry reaction, the highest enantioselectivity was obtained with CuCl, in MeOH at 39% ee.
Our research project is for the development of a new methodology for the synthesis of the useful moiety, alpha-hydroxy carbonyl. By utilizing the ability of dialkoxy disulfide to thermally fragment to an carbonyl and an alcohol, it should be possible to convert a 1,2-diol into an alpha-hydroxy carbonyl functionality.
Our research project involves synthesizing a series of poly(4-vinylphenol) derivatives. Such polymers will be weak polyacids due to presence of the hydroxyl group attached to the phenyl ring. The aromatic character, very weak acidity, and hydrogen bonding capability of 4-vinylphenol and derivatives will yield polyelectrolytes with a rich suite of chemical and physical properties that are much different than most traditional weak polyanions. The monomers are prepared from benzaldehyde starting material, which is being further derivativized using Friedel-Crafts chemistry. The polymerization is carried out using traditional techniques. The molecular weight, thermal properties, and dissociation behavior of these polymers is also being investigated.
Polyvinylphenol based polymers are weak polyacids due to the hydroxyl group attached to the phenyl ring. The aromatic character, very weak acidity, and hydrogen bonding capability of 4-vinylphenol and derivatives will yield polyelectrolytes with a rich suite of chemical and physical properties that are much different than most weak polyanions. Multilayered films of the phenol-based polymers have been prepared using the layer-by-layer assembly technique. The counter polycations investigated include polyallylamine, PDADMAC, polyaniline and derivatives. The film growth has been followed using UV-visible spectroscopy, while their thickness, roughness, swelling, and morphology will be investigated using atomic force microscopy and Interference Microscope. The combination of aromaticity, hydrogen bonding, and variable charge density is expected to produce films with unique bulk and surface properties.
42) Paolo N. Grenga, Matthew J. Nethercott, Ayeisca E. Mateo, Mathew Patenaude, Todd Hoare, David P. Weliky, Ronny Priefer “Thermal and Spectral Analysis of Novel Amide-Tethered Polymers from Poly(allylamine)”Australian Journal of Chemistry, 69, 458-466, 2016.
41) Brittany N. Dickhaus, Ronny Priefer “Determination of polyelectrolyte pKa values using surface-to-air tension measurements” Colloids and Surfaces A: Physicochem. Eng. Aspects, 488, 15–19, 2016.
40) Kimberly Han, Osakpolor E. Woghiren, Ronny Priefer “Surface tension examination of various liquid oral, nasal, and ophthalmic dosage forms” Chemistry Central Journal, 10:31,2016.
39) Ayeisca E. Mateo, Ronny Priefer “Acid-base equilibria of multilayered pseudo-polyelectrolytes” Applied Surface Science, 356, 1229–1233, 2015.
38) Kyle F. Biegasiewicz, Justin R. Griffiths, G. Paul Savage, John Tsanaktsidis, Ronny Priefer “Cubane: 50 Years Later” Chemical Reviews, 115, 6719-6745, 2015.
37) Eric G. Stoutenburg, Ganna Gryn’ova, Michelle L. Coote, Ronny Priefer “Chemical shift and coupling constant analysis of dibenzyloxy disulfides” Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 136, 1924-1931, 2015.
36) Kyle F. Biegasiewicz, James S. Gordon IV, Deana A. Rodriguez, Ronny Priefer “Development of a general approach to the synthesis of a library of isoflavonoid derivatives” Tetrahedron Letters 55, 5210–5212, 2014.
35) Deana A. Rodriguez, Ronny Priefer ”Sulfite formation versus chlorination of benzyl alcohols with thionyl chloride” Tetrahedron Letters 55, 3045–3048, 2014.
34) Eric G. Stoutenburg, Anne E. Palermo, Ronny Priefer “Thermochemical properties of dibenzyloxy disulfides” Thermochimica Acta, 551, 99-103, 2013.
33) Kyle F. Biegasiewicz, Michelle L. Ingalsbe, Jeffrey D. St. Denis, James L. Gleason, Junming Ho, Michelle L. Coote, G. Paul Savage, Ronny Priefer “Evaluation of a Chiral Cubane-Based Schiff Base Ligand in Asymmetric Catalysis Reactions” Beilstein Journal of Organic Chemistry, 8, 1814-1818, 2012.
32) Laurine R. Zupp, Veronica L. Campanella, DiAndra M. Rudzinski, François Beland, Ronny Priefer“Microwave-assisted silica-supported aluminum chloride-catalyzed Friedel-Crafts alkylation” Tetrahedron Letters, 53, 5343–5346, 2012.
31) Paolo N. Grenga, Eric G. Stoutenburg, Ronny Priefer “Photolytic decomposition of dibenzylic sulfites” Tetrahedron Letters, 53, 4933–4937, 2012.
30) Ronny Priefer, Kelly Sowers, Todd D. Krauss, Megan E. McGahan, Thomas W. Smith “Bis(trifluoromethyl)carbinol polynorbornene as a pseudo-polyelectrolyte in multilayered films” Thin Solid Films520, 6170–6173, 2012.
29) Matthew S. Pinto, Megan E. McGahan, Walter W. Steiner, Ronny Priefer “The use of the pseudo-polyelectrolyte, poly(4-vinylphenol), in multilayered films as an antimicrobial surface coating” Colloids and Surfaces A: Physicochem. Eng. Aspects, 377, 182–186, 2011.
28) Kazushige Yokoyama, Amy L. Tran, Ronny Priefer “Self-assembly of Amyloid Beta Peptide over Dialkoxy Disulfide Functionalized Nano Gold Colloidal Particles” International Review of Biophysical Chemistry, 2, 174-183, 2011.
27) Patrick J. Heaphy, Justin R. Griffiths, Christopher J. Dietz, G. Paul Savage, Ronny Priefer “Cage opening and rearrangement of 1-iodocubane-4-carboxaldehyde” Tetrahedron Letters, 52, 6359-6362, 2011.
26) Pavel Belov, Veronica L. Campanella, Alison W. Smith, Ronny Priefer “Microwave-assisted methylation of phenols with DMF-DMA” Tetrahedron Letters 52, 2776–2779, 2011.
25) Ronny Priefer, Paolo N. Grenga, Megan E. McGahan, Danielle M. Raymond, Michael J. Gallagher “Assessment of airborne total volatile organic compounds (TVOC) of Niagara Falls residences as compared to resident lifestyle” Indoor and Built Environment, 20, 226–231, 2011.
24) Mary P. McCourt, Christopher Wirth, Josef G. Krause, Brian D. Leskiw, Robert S. Greene, Michelle L. Emery, Megan E. McGahan, Ronny Priefer “Computational Analysis of the Apoptotic Activity of a Small Library of Novel Substituted Hydroxy Ureas Designed as Potential Inhibitors of Ribonucleotide Reductase” Letters in Drug Design & Discovery, 8, 580-584, 2011.
23) Samantha Evans, Ronny Priefer "Continued Misconception Concerning Bond Breaking and Making" Chem. Educator 15, 398–400, 2010.
22) Ronny Priefer, Justin R. Griffiths, Janelle N. Ludwig, Graham Skelhorne-Gross, Robert S. Greene “Synthesis of aza-bodipy boron difluoride PDT agents to promote apoptosis in HeLa cells” Letters in Organic Chemistry, 8, 368-373, 2011.
21) Kyle F. Biegasiewicz, Jeffrey D. St. Denis, Vincent M. Carroll, Ronny Priefer “An Efficient Synthesis of Daidzein, Dimethyldaidzein, and Isoformononetin” Tetrahedron Letters, 51, 4408–4410, 2010.
20) Josef G. Krause, Brian D. Leskiw, Michelle L. Emery, Megan E. McGahan, Mary P. McCourt, Ronny Priefer“Synthesis of substituted N-hydroxyureas via the in situ generation of t-butoxy isocyanate” Tetrahedron Letters, 51, 3568–3570, 2010.
19) Jeffrey D. St. Denis, James S. Gordon IV, Vincent M. Carroll, Ronny Priefer “Novel Synthesis of the Isoflavone Genistein” Synthesis, 10, 1590-1592, 2010.
18) Justin R. Griffiths, G. Paul Savage, Ronny Priefer “Thermochemical properties of iodinated cubane derivatives” Thermochimica Acta, 499, 15-20, 2010.
17) Ronny Priefer, Paolo N. Grenga, Ashley N. Mandrino, Danielle M. Raymond, Kathryn E. Leach, Todd D. Krauss “Multilayering of a pseudo polyelectrolyte (PVPh) with a strong polyelectrolyte (PDMAC) from aqueous media” Surface Science, 604, 59-62, 2010.
16) Michelle L. Ingalsbe, Jeffrey D. St. Denis, James L. Gleason, G. Paul Savage, Ronny Priefer “Synthesis of a Novel Chiral Cubane-based Schiff-base Ligand and its Application in Asymmetric Nitro Aldol (Henry) Reactions”Synthesis, 1, 98-102, 2010.
15) Paolo N. Grenga, Brittany L. Sumbler, François Beland, Ronny Priefer “Reductive amination agents: Comparison of Na(CN)BH3 and Si-CBH” Tetrahedron Letters, 50, 6658-6660, 2009.
14) DiAndra M. Rudzinski, Mary P. McCourt, Ronny Priefer “Thermolytic decomposition of benzylic dialkoxy disulfides” Tetrahedron Letters, 50, 5520-5522, 2009.
13) Michelle L. Ingalsbe, Jeffrey D. St. Denis, Megan E. McGahan, Walter W. Steiner, Ronny Priefer“Development of a novel expression, ZIMAX/KZI, for determination of the counter anion effect on the antimicrobial activity of tetrabutylammonium salts” Bioorganic and Medicinal Chemistry Letters, 19, 4984-4987, 2009.
12) DiAndra M. Rudzinski, Ronny Priefer “Photolytic, autocatalyzed decomposition of benzylic dialkoxy disulfides” Tetrahedron Letters, 50, 1629-1632, 2009.
11) Jeanette Drapo, Ronny Priefer “Praseodymium induced pinacol formation” Synthetic Communication, 39, 85-92, 2009.
10) Vincent M. Carroll, David N. Harpp, Ronny Priefer “Thermo-cage opening of 4-iodo-1- vinylcubane to a novel styrene derivative” Tetrahedron Letters, 49, 2677-2680, 2008.
9) Ronny Priefer, Kathryn E. Leach, Todd D. Krauss, Jeanette R. Drapo, Michelle L. Ingalsbe, Mallory A. van Dongen, John C. Cadwalader, Megan A. Baumler, Matthew S. Pinto “Multilayer Film Preparation of PVPh from Aqueous Media” Surface and Coatings Technology, 202, 6109-6112, 2008.
8) Ronny Priefer, Eric Martineau, David N. Harpp “Derivatization of Dicubyl Disulfide” Journal of Sulfur Chemistry, 28, 529-535, 2007.
7) Vincent M. Carroll, Megan A. Baumler, John C. Cadwalader, Jeanette R. Drapo, Michelle L. Ingalsbe, Matthew S. Pinto, Mallory A. van Dongen, Ronny Priefer “Synthesis of Poly(4-vinylphenol) Derivatives and Preparation of Multilayered Films from Aqueous Media” Polymeric Materials: Science and Engineering, 96, 488-489, 2007.
6) Priefer, R., Nguyen, S., Farrell, P. G., Harpp, D. N. “Synthesis of Novel, Cubane-Containing Norbornene-Based Polymers” Macromolecules, 36, 5435-5436, 2003.
5) Priefer, R., Lee, Y. J., Barrios, F., Wosnick, J. H., Lebuis A.-M., Sun, A., Wu, S., Snyder, J. P., Farrell, P. G., Harpp, D. N. “Dicubyl Disulfide” Journal of the American Chemical Society, 124, 5626-5627, 2002.
4) Priefer, R., Farrell, P. G., Harpp, D. N. “Dialkoxy Disulfides from Cubylcarbinols”
Tetrahedron Letters, 43, 8781-8784, 2002.
3) Priefer, R., Farrell, P. G., Harpp, D. N. “Effective Synthetic Routes to Cubylcarbinol
Derivatives.” Synthesis, 18, 2671-2673, 2002.
2) Plourde, G. L., Priefer, R., Llewellyn, D. B. “Synthesis and Characterization of 1-hydroxy-2-methoxy-4-(3-propanoic acid) anthracene.” Synthetic Communication, 29(16), 2895-2901, 1999.
1) Bernards, M. A., Fleming, W. D., Llewellyn, D. B., Priefer, R., Yang, X., Sabatino, A., Plourde, G. L. “Biochemical Characterization of the Suberization-Associated with Anionic Peroxidase of Potato.” Plant Physiology, 121(1), 135-145, 1999.
Vincent M. Carroll, Jeffrey D. St. Denis, Kyle F. Biegasiewicz, Ronny Priefer “Chapter 5: Chemistry and Synthesis of Daidzein and its Methylated Derivatives: Formononetin, Isoformononetin, and Dimethyldaidzein” Food and Nutritional Components in Focus No. 5 Isoflavones: Chemistry, Analysis, Function and Effects, The Royal Society of Chemistry, Editor Victor R Preedy, 61-82, 2013.
Sources of Funding:
American Chemical Society-Petroleum Research Fund (ACS-PRF)
American Society of Quality (ASQ)
New York State Great Lakes Protection Fund
Rochester Academy of Science
Barbara S. Zimmer Memorial Research Endowment Award