Fluorescent probes are routinely used for studying drug delivery, membrane activity and cellular functions. By substituting two hydrogen atoms of a commonly used fluorescent probe (naphthalimide) with iodine, researchers at the Indian Institute of Science (IISc), Bengaluru, have been able to increase the cellular uptake of the probe molecule from 5-8% to 98%. The probe molecule with two substituted iodine atoms was found to be safe.

The low ability of the probe molecules to cross the cell membrane has proved to be a challenge. Despite the limitations, naphthalimide has been routinely used as it can be easily synthesised in large quantities and its fluorescence can be altered. By substituting two hydrogen atoms with iodine, the IISc researchers, led by Govindasamy Mugesh, have addressed the problem of uptake.

The researchers substituted two hydrogen atoms of the probe molecule with chlorine, bromine and iodine. The size of probe molecule increased when the hydrogen atoms were replaced with halogen atoms. Compared to iodine, the chlorine and bromine atoms are smaller in size. “We would expect the smaller molecules to get into cells easily. But to our surprise, we observed that the transport of iodine-containing molecule, which is bigger than the other two, was better,” says Prof. Mugesh from the Institute’s Department of Inorganic and Physical Chemistry and corresponding author of a paper published in
Angewandte Chemie

The iodine forms a halogen bond with the receptor (MCT8) found on cell surface which ferries the molecule across the membrane. “The halogen bonding is better for an iodine compound compared with chlorine and bromine. This could be the reason why the iodine-containing molecule was taken up better despite its bigger size,” says Harinarayana Ungati from the Department of Inorganic and Physical Chemistry, IISc, and first author of the paper. While it reached up to 98% when two iodine atoms were substituted, the percentage transport was only 15% and 22% for chlorine and bromine, respectively.

“The probe molecule with iodine will help in studying the uptake of thyroid hormone, which is generally difficult to monitor. Traditionally, radio-labelled hormone is used for studying thyroid uptake in mammalian cells,” says Vijayakumar Govindaraj from the Department of Inorganic and Physical Chemistry, IISc, and coauthor of the paper.

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