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¸Ô±¾ÊÓÆµ scientists uncover the hidden chemistry of copper in human saliva


Scientists at ¸Ô±¾ÊÓÆµ Leicester (¸Ô±¾ÊÓÆµ) have uncovered new details about the way copper behaves in human saliva – findings which could help improve our understanding of how this essential metal is absorbed and perceived,  and how it can become toxic at excessive levels.

Copper is an essential trace element needed by the human body for a range of processes, including energy production, iron metabolism and the healthy functioning of the nervous and immune systems. But researchers say simply measuring how much copper is present does not tell the whole story.

A new study from ¸Ô±¾ÊÓÆµ’s Leicester School of Pharmacy has investigated the different molecular forms copper ions can take when they are present in saliva – and identified some of the naturally occurring substances to which they bind.

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This process, known as speciation, matters because the chemical form a metal takes can affect its availability to the body, its biological activity and its potential toxicity. Most people get the copper they need through their diet. Good sources include shellfish, particularly oysters, liver and other organ meats, nuts and seeds, wholegrains, beans and lentils, dark chocolate and some green vegetables. Small amounts can also be present in drinking water.

For the study, researchers collected human whole-mouth saliva and added carefully controlled amounts of copper(II) ions in laboratory conditions. Using advanced analytical techniques, including high-resolution nuclear magnetic resonance (NMR) spectroscopy, they were then able to examine how those copper ions interacted with the complex mixture of chemicals naturally present in saliva.

They found that copper formed distinct molecular complexes with a number of substances, with particularly important interactions involving the amino acids histidine and glutamine. The researchers also identified interactions with aromatic metabolites, proteins and other small organic molecules.

The findings build a more detailed picture of what happens chemically when copper ions are present in saliva.

Professor Martin Grootveld, Professor of Bioanalytical Chemistry and Chemical Pathology at ¸Ô±¾ÊÓÆµ, said: “Copper is essential to human health, but like many trace metals, at excessive levels it can also have toxic effects. What is important is that it is not simply the total amount of copper present which determines what happens biologically. We also need to understand the precise chemical form it takes and which molecules it becomes bound to.

“Saliva contains an extraordinarily complex mixture of potential copper-binding molecules, so studying these interactions gives us another piece of the puzzle in understanding how this important metal behaves in the human body. The strategy used measured NMR responses to extremely low concentrations, so it is very highly sensitive.”

The study also featured PhD students Kayleigh Hunwin, Georgina Page, Olivia Steel and Katie Hewitt, along with Dr. Oliver Megram, Dr. Wyman Chan, Nazmin Juma and Dr. Rachel  Armitage.

The work could also have implications for understanding metallic taste. Previous research has suggested that different chemical forms of copper in saliva may behave differently and could influence the reactions involved in producing the metallic sensation sometimes associated with copper.

The researchers stress that the study does not suggest normal dietary copper is harmful. Copper is an essential nutrient and the body requires small amounts to function properly. Instead, the work highlights why researchers studying trace metals need to look beyond their overall concentration and consider the molecular forms in which they are actually present.

The study forms part of a wider programme of research at ¸Ô±¾ÊÓÆµ examining how metal ions behave in biological systems. Previous work by the Leicester School of Pharmacy team has investigated the molecular forms of nickel, lanthanum and silver in human saliva, and both nickel and copper in laboratory cell-culture environments.

The research, , is published in the journal Molecules.

coppergrabFigure 7 from the paper: Morphology of Cu(II)-WMSS deposit samples: (a) circular Cu grains arising from the preliminary addition of 5 µL of a 10.00 mmol/L solution of Cu(II)(aq.). (b,c) Agglomerated Cu grains derived from the addition of 40 and 50 µL, respectively, of a 10.00 mmol/L solution of Cu(II)(aq.).
 
Posted on Tuesday 25 August 2026

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