Fluoride Action Network

Fluorines make hydrogen bonds

Source: Chemical Science | September 14th, 2009 | By Nicola Wise
Industry type: Pharmaceuticals

Scientists in the US have shown that fluorine compounds can form hydrogen bonds, a finding that could have implications for the pharmaceutical industry, they say

Fluorine is often used in drug development as its presence in organic compounds can affect properties such as absorption, distribution and stability. However, exactly how it interacts with biological molecules remains a puzzle, says Julius Rebek Jr at The Scripps Research Institute, California.

While inorganic fluorides are powerful hydrogen bond-acceptors, there is not much evidence that covalently bound organofluorines form hydrogen bonds. Not much sticks to organic C-F bonds, says Rebek, which is why they have been so useful in products such as Teflon. So the group moved up the periodic table to look at the B-F bonds in fluoroborates. Fluoroborates are covalently bonded but also anionic, which makes their hydrogen bonding properties interesting for researchers.

Rebek and his team made a supramolecular tripodal receptor with three inwardly directed hydrogen donors. They used the receptor to surround the BF3- of a trifluoroborate, presenting it with available hydrogen-bond donors, and found the covalently bound fluorine did form hydrogen bonds. ‘This is the inaugural case of recognising the BF3- group,’ says Rebek.

Understanding the nature and strength of hydrogen bonding in this way could be important for drug development, says Rebek. These results could lead to ‘the CF3- groups that appear in medicines being replaced by the BF3- group to improve solubility and, perhaps, bioavailability,’ he adds.

Professor Luigi Fabbrizzi, an expert in anion binding in synthetic receptors from the University of Pavia, Italy, says the receptor could be ‘a useful tool for [finding] many drug compounds of pharmaceutical interest possessing fluorinated fragments. More sophisticated receptors could be developed, capable of interacting with fluorinated compounds in more competitive solvents including water, which would allow the monitoring of many drugs in physiological fluids.’

Rebek’s group are currently looking at commercial applications of the receptor.