Excellence in Research: Near-Infrared Molecular Probes as Potential Tools for Bioimaging

With this award, the Chemical Structure, Dynamics, and Mechanism-B program is supporting Dr. Fasil Abebe at Morgan State University to develop synthetic near-infrared fluorescent probes for rapid visualization and quantification of cellular metal ions. This challenging objective first requires the synthesis of a series of structurally related organic dye molecules that are designed to undergo structural change upon metal ion coordination.

The resulting fluorophores (light-emitting structures) are expected enable the imaging of metal ions in live cells by using high-resolution fluorescence microscopy. This project will explore the synthesis, optical and electrochemical properties of these dye molecules. Fluorescent probes have become indispensable tools in modern biology and biotechnology because they provide real time information concerning the quantity of ions or molecules of interest within the living cell.

Thus, the probes developed in this project may spur significant advances in our understanding of metal-cell biology. Developing near-infrared fluorescent probes for metal ions that behave well under physiological conditions is highly desirable. The project enriches education and training of graduate and undergraduate students from underrepresented minority groups by involving them in cutting-edge research activities.

Students will develop laboratory expertise in microwave-assisted synthesis, spectroscopic analysis, and fluorescence imaging.

The central theme of this project is that principles of organic chemistry, microwave-assisted synthesis and knowledge of photochemistry can be exploited to make an array of molecular tools capable of investigating biological metal ions. Efforts will be focused on the development of cyanine-coupled dye derivatives with good water solubility, cell permeability and photostability.

This project includes the following aims: (1) to develop an efficient microwave-assisted synthesis and characterization of near-infrared dye molecules; (2) to examine the spectroscopic, computational, and electrochemical properties of cyanine-coupled dye derivatives by diverse methods; and (3) to investigate the potential of cyanine-coupled dye derivatives for imaging of metals in HeLa cells. A series of rhodamine-cyanine-coupled dyes will first be synthesized.

In the presence of metals such as copper, near infrared fluorescence of these dyes occurs by a coordination-induced spirocycle-opening reaction and photo-induced electron transfer (CIPET) process. The role of various factors affecting the analytical characteristics of near-infrared probes, their selectivity and sensitivity toward specific metal ions, as well as other important characteristics will be studied.

Metal ions of biological and environmental interest such as copper will be studied. An integral part of this project is the use of density functional theory (DFT) and time-dependent DFT to understand the fluorescence change by metal ions and the ability of metal-dye complexes to act as anion sensors. The detailed training program for underrepresented minority students, both undergraduate and graduate, in this area of research is expected to make an important contribution in the development of a diverse workforce for the nation.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.