The goal of this project is to develop imaging tools to visualize essential metal ions in vivo. Selective metal ion sensing probes are a crucial link toward elucidating
metal ion homeostasis and disease conditions arising from metal ion concentration imbalance. We are particularly interested in developing probes for manganese which while essential at
lower concentrations, causes neuronal deficits at higher concentrations. Manganese selective probes can facilitate tracking and quantitation of manganese ions under both
physiological and pathophysiological conditions thereby affording molecular level insights into manganese homeostasis.
Our approach in this project is two-fold and involves the development of manganese selective ‘turn-on’ small molecule and protein based fluorescent probes and testing the probes in appropriate cellular and animal models mimicking manganese induced neuronal deficits. In this project we focus on synthesis of small molecules, engineering proteins, and animal model development for in vivo imaging studies.
Manganese being paramagnetic, can affect the relaxation properties of protons within biological tissue. This property affords contrast enhancement in magnetic resonance imaging,which can be mapped to locate excess manganese pools. Estimates of Mn concentrations under pathological conditions indicate an average brain concentration of 160 µM with local concentrations in the striatum increasing to 1-5 mM under pathological conditions. MRI images of brains of patients suffering from Mn induced Parkinsonism indicate hyper-intense signals in the basal ganglionic regions of the brain, which are attributed to Mn accumulation. However, such hyper-intensity in basal ganglionic regions can also be observed in the case of carbon monoxide poisoning, hepatic failure, hyperglycemia and melatonin storage making diagnosis of Mn overload disorders difficult. In this context, coordination chemistry based MRI detection strategies for Mn2+ in biological systems become critical for early diagnosis of Mn overload induced neurological disorders.
While transition metal ions like manganese, iron, and copper are essential for biological function, heavy metal ions like mercury (Hg) are toxic to most living organisms. Exposure to Hg from environmental, industrial and food sources leads to renal dysfunction and neurological disorders. One of the major sources of Hg toxicity is contaminated potable water. The relevant speciation for Hg toxicity via drinking water is inorganic Hg in the form of labile Hg2+ ions. The WHO guideline for the tolerable limit of inorganic Hg in drinking water is 6 parts-per-billion (ppb). Therefore, a sensitive optical probe that can detect ppb levels of inorganic Hg in drinking water will be extremely useful for establishing the drinkability of water, especially in remote areas where sophisticated instrumentation for analyzing metal-content in water is not available. While there are numerous reports on optical sensors for detecting Hg2+, major shortcomings are related to limited aqueous solubility and irreversibility. Very few sensors have a combination of high aqueous solubility and reversibility along with the requisite limit of detection. We have developed a highly water-soluble, sensitive and reversible optical probe for Hg2+ that can detect as low as 10 ppb levels of mercury ion contamination in water.