By Michael Lucibella

sucralose

Sucralose: Bad for the biome?

Researchers are looking more closely at molecular mechanisms in commercial chemicals that lead to potentially damaging effects on the human body and the environment. Two of these investigations — one on the artificial sweetener sucralose, the other on a class of fluids called ionic liquids — were highlighted at the APS March Meeting 2015 in San Antonio, Texas.

Sucralose, an artificially modified sucrose molecule, is a common sugar substitute used in products like Splenda. The molecule is a calorie-free sweetener because the body can’t metabolize it. Early research has raised the possibility of serious implications for the complex and poorly understood ecosystem of intestinal bacteria.

Though the research is thin and results have been inconsistent, a few preliminary health studies hint at some negative health impacts of high-artificial sweetener diets. “What we’re finding is that sucralose is not an inert molecule, and it’s interacting strongly with biomolecular structures,” said Cristina Othon of Wesleyan University.

She and her team used optical absorption spectroscopy to study how the presence of this modified sugar can affect a protein molecule’s ability to fold. They found that in a solution of concentrated sucralose, the protein began to fold at much lower temperatures.

“What we think is happening is sucralose [changes] the electronic properties of the molecule,” Othon said. “[The protein and the sweetener are] going to interact with each other and create a torque.”

The team tested the effects on two common lab proteins, bovine serum albumin and streptococcal nuclease, chosen because of their very different structures. But the effects did not depend on protein’s arrangement of amino acids. “This is a generalized mechanism; it’s not sequence-specific whatsoever,” Othon said.

In addition they found that the sweetener seems to interact with cell membranes. In a different set of tests, the researchers found that the lipids that make up cell membranes thinned out and weakened when exposed to high levels of sucralose. Othon added that the sucralose concentrations they were studying were far in excess of those used in food.

It is not yet clear exactly how these effects of sucralose might impact the overall health of someone who consumes it. Othon said that it would probably have minimal direct effects on a person’s body, because little would be absorbed into the bloodstream, but that it might affect the micro-biome of a person’s gut bacteria.

“There’s not a lot of physical data on its interactions,” Othon added. “If you were to look for an effect, you would look for it somewhere in the intestinal tract. … Hopefully we can get some insight into how these gut bacteria might be affected by it.”

In another example where damage starts at the molecular level, researchers at Notre Dame discovered the source of the toxicity for a class of substances that is starting to find applications in industry.

Ionic liquids are salts whose molecules form long, poorly coordinated chains, keeping them liquid at room temperatures. Although the subject of much academic interest in recent years, they haven’t yet been widely adopted by industry. However, because they resist evaporation at relatively high temperatures, they show much potential as industrial solvents.

Previous studies of their impact on living things have shown that these liquids can be a potential threat to the environment. Even low concentrations of different ionic liquids in water have been shown to kill microorganisms at high rates.

“We have to be very careful about how we treat these new chemicals,” said Brian Yoo, a graduate student at the University of Notre Dame. “If we compare ionic liquids with conventional organic solvents, we can see that ionic liquids are much more toxic.”

Yoo and his team used computer simulations to discover how ionic liquids kill an organism’s cells. “Essentially what happens is ionic liquids insert [themselves] into a cell membrane,” Yoo said. The molecules of the liquid penetrate through the outer layers of a cell’s membrane, causing it to deform and buckle, destroying its integrity.

“Using our computer simulations we’ve essentially identified the precursor to toxicity,” Yoo explained. “With our experiments we’ve also seen complete disruption.”

His team found also that the molecular structure of different liquids played a role in how toxic they are. Ionic liquids with longer molecular chains seemed to be particularly damaging to the cell membrane.

“The concentrations at which the bilayer gets disrupted are in the millimolar concentrations,” Yoo said, referring to the small amounts that can get into the environment. He added that for some liquids with the longest molecular chains, his team saw the effect in even micromolar concentrations.

In both sucralose research and in the studies of ionic liquids, researchers hope that the knowledge gained might lead to chemical variants that are safer, as well as a better handle on how chemicals affect health.

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