Clear Research Lab

Bioorganic and Supramolecular Chemistry

Kasey J. Clear

Assistant Professor
Department of Chemistry
Murray State University
1232 Jesse D. Jones Hall (office)
1233 Jesse D. Jones Hall (lab)
(270) 809-6597 (office phone)
kclear@murraystate.edu

Biography:
Dr. Clear is a native of Niles, Michigan and was awarded his B.S. in Chemistry from Indiana University South Bend in 2011. He completed his Ph.D. in 2016 at the University of Notre Dame under the supervision of Professor Bradley D. Smith, where he studied anion and biomembrane molecular recognition using synthetic receptors and fluorescent dyes. As a graduate student, Dr. Clear co-authored six peer-reviewed articles and one book chapter. He began his independent career in academia at Murray State University in fall of 2016. His research interests include the design and study of synthetic receptors for biologically important anions that will have application in separations, imaging, and chemical biology.

Teaching

Dr. Clear primarily teaches organic chemistry at both the undergraduate and graduate level. During the 2016-2017 academic year, he is teaching the following courses:

CHE 210 - Brief Organic Chemistry
CHE 215 - Brief Organic Chemistry Laboratory
CHE 325 - Organic Chemistry II Laboratory
CHE 517/617 - Advanced Organic Chemistry

In addition, Dr. Clear is the seminar coordinator for the chemistry department (CHE 601/602) starting in Spring 2017.

Research

Research in the Clear Lab integrates themes from organic, physical, and analytical chemistry to address questions regarding recognition of biologically important anions. The emphasis of projects currently underway in the group is on the development of synthetic receptors for solution and membrane recognition of inositol phosphates and phosphatidylinositide lipids, a class of molecues that are important for cell communication. The results of this research will contribute to the scientific knowledge that will be both directly and indirectly beneficial to biological or biochemical separations, understanding of signaling pathways and lipid dynamics, molecular imaging, and therapeutic applications. Importantly, students participating in research will be exposed to a range of techniques, from traditional organic synthesis to binding studies requiring repetitive measurement and extensive data analysis. As a result, this research experience will help train students for graduate and professional studies as well as careers in industry.

1. Solution Anion Recognition

2. Membrane Anion Recognition

3. Assays for Lipid Receptor Affinity & Selectivity

1. Solution recognition of the inositol phosphates using zinc(II) coordination complexes.
The underlying hypothesis is that synthetic receptors with multiple anion recognition units and appropriate scaffolds will exhibit high affinity and selectivity for particular isomers of the inositol phosphates. To test this, a series of bivalent synthetic receptors containing zinc(II)-cyclen and zinc(II)-dipcolylamine anion recognition units presented on a chiral scaffold will be synthesized and the binding toward a series of inositol triphosphate isoforms will be evaluated using isothermal titration calorimetry (ITC). ITC is a technique which measures the heat generated upon association of the two molecules and gives detailed information on the thermodymaics of the binding event.

2. Membrane recognition of the phosphitidylinositol phosphate lipids using zinc(II)-cyclen complexes
The membrane is known to play an important role in molecular recognition mechanisms. The project will use methods like ITC to compare the binding thermodynamics of a bivalent zinc(II)-cyclen receptor with phosphatidylinositol(4,5)bisphosphate (PI(4,5)P2) to association of the same receptor with a soluble analog of PI(4,5)P2, inositol(1,4,5)triphosphate.

3. Assay for evaluating the lipid affinity and selectivity of biological and synthetic receptors.
A new fluorescent indicator displacement assay (IDA) will be developed to facilitate fast and accurate evaluation of the affinity of unlabeled receptors for lipid-bound inositol phosphates while consuming fewer resources than techniques such as ITC. The assay is expected to be useful for studying the lipid selectivity of both synthetic and biological (protein) receptors for various phosphatidylinositides. This project uses instrumentation for fluorescence measurements in both cuvettes and microplates.

Publications

Graduate Publications:
7. Harmatys, K. M., Musso, A. J., Clear, K. J., Smith, B. D. (2016) Small molecule additive enhances cell uptake of 5-aminolevulinic acid and conversion to protoporphyrin IX. Photochem. Photobiol. Sci. Advance Article, DOI: 10.1039/C6PP00151C Link
6. Rice, D. R., Clear, K. J., Smith, B. D. (2016) Imaging and therapeutic applications of zinc(ii)-dipicolylamine molecular probes for anionic biomembranes. Chem. Commun. 52, 8787-8801 Link
5. Clear, K. J., Virga, K., Gray, L., and Smith, B. D. (2016) Using membrane composition to fine-tune the pKa of an optical liposome pH sensor. J. Mater. Chem. C 4, 2925-2930 Link
4. Clear, K. J., Harmatys, K. M., Rice, D. R., Wolter, W. R., Suckow, M. A., Wang, Y., Rusckowski, M., and Smith, B. D. (2016) Phenoxide-bridged zinc(II)-bis(dipicolylamine) probes for molecular imaging of cell death. Bioconjugate Chem. 27, 363-375 Link
3. Clear, K. J. and Smith, B. D. (2015) Synthetic Receptors for Polar Lipids. Synthetic Receptors for Biomolecules, Monographs in Supramolecular Chemistry, Royal Society of Chemistry: pp 405-436 Link
2. Plaunt, A. J., Clear, K. J., and Smith, B. D. (2014) 19F NMR indicator displacement assay using a synthetic receptor with appended paramagnetic relaxation agent. Chem. Commun. 50, 10499-10501 Link
1. Clear, K. J., Stroud, S., and Smith, B. D. (2013) Dual colorimetric and luminescent assay for dipicolinate, a biomarker of bacterial spores. Analyst 138, 7079-7082 Link

Group Members

The group is currently seeking undergraduate and graduate students who are interested in doing research. If you are interested, contact Dr. Clear by e-mail (kclear@murraystate.edu) or just stop by his office (1232 CB).

Current Students:
Jacob Meadows, B.S. Chemistry, Class of 2017