UH Chemical Engineering professor discovers 'unexpected and remarkable' breakthrough for potentially improving medications

University of Houston Chemical Engineering professor and crystals expert Jeffrey Rimer has revealed a new method to regulate the growth of ammonium urate crystals, the substance responsible for causing the development of kidney stones in dolphins, according to a news article published by UH on Feb. 3. 

Rimer, internationally known for his breakthroughs in crystal control for malaria and kidney stone treatments, published his findings in Nature Communications.

The link between crystal growth and dolphins was first noticed thanks to the U.S. Navy Marine Mammal Program, where dolphins' ability to detect various objects has been helping the Navy locate underwater mines for decades. As a part of the program, the Navy funds extensive research on dolphin health, which often includes kidney stones. Rimer has long been at the forefront of dolphin research, previously investigating crystals associated with dolphin kidney stones made of ammonium nitrate, which is rarely found in humans. Now, Rimer leads an international team of researchers from Tianjin University China, Stockholm University Sweden, University of Pittsburgh, University of Strathclyde, Glasgow Scotland, Texas A&M University, Purdue University, Instituto Politecnico Nacional Mexico, and The Molecular Foundry at Lawrence Berkeley National Laboratory.

The team's research focuses on the manipulation of rate isomers known as tautomers to control the growth of ammonium rate crystals. While the primary goal was to aid dolphins, the findings may also have an impact on the human pharmaceutical industry.

“We found that a small fraction of urate existing as a minor tautomer can control the rate at which crystals grow to the point they can completely block crystallization,” said Rimer. “It was the most unexpected and remarkable thing to find that as you increase the concentration of urate, all of a sudden the rate of crystallization drops to almost zero and crystals do not grow in that region.”

Rimer believes that it may be possible to replicate the earlier results by diet control to get the concentration in the kidney within the acceptable range, possibly eliminating the need for medication to treat crystal-related conditions in both dolphins and humans. Additionally, Rimer's examination of rate crystals revealed that tautomers get incorporated into crystals as defects. This fact is where the research holds the largest implications for pharmaceuticals: 33 of the top 200 drugs used (including allopurinol, a kidney stone treatment) are tautomers. These medications are needed by millions of people worldwide and are prescribed for ailments such as HIV, epilepsy, COVID-19, schizophrenia, and various types of cancer.

“When we produced crystals with very few defects, they dissolved much slower whereas crystals with a higher percentage of defects dissolve faster,” said Rimer. “That is critical for pharmaceuticals because when you put medicine into your body, their effectiveness is related to how fast they dissolve."

“We are asking the question about these 33 pharmaceuticals: Do companies really know the extent to which they develop defects? The same question can be posed for nature where tautomers may impact unique properties in species that are vital to their intended function like optical properties in fish or color change in chameleons.”