Use of Copper in the Detection of Sulfurous and Other Metal-coordinating Compounds

Olfaction (the sense of smell) is a chemical sense that allows for the perception and discrimination of airborne volatile chemicals, and plays an essential role for survival allowing for identification of food, predators, or toxic compounds in addition to being a means for communication. Hence clarifying the underlying mechanisms of olfaction will provide a better understanding of behaviors and actions based on this sense. Odors are detected by a large repertoire of receptors expressed in the olfactory epithelium, and since the discovery of these receptors in understating the physiological basis of olfaction. These odorants are recognized by means of a combinatorial coding scheme that explains how a few hundred different receptors can discriminate among thousands of different molecules, based on the fact that a given odorant activates or inhibits different combinations of these receptors. This complex scenario reveals the difficulty involved in modeling odor character and intensity but provides a basis for rational odorant design.


The molecular basis for odorant recognition and the conformational changes that ORs undergo upon ligand binding are still poorly understood, which in some cases odor character and intensity is connected with the presence of a particular functional group. Which the system is sensitive to the fine structure of the electron distribution of the function group, which yields the theory that a metal ion might be involved in recognition. This hypothesis proposes that this mechanism is based on inelastic electron tunneling spectroscopy which this theory of metal-ion assisted odorant recognition must assume that these olfactory receptors are metalloprotiens. There is no clear evidence that validates or disapproves the MIAOR mechanism, which further research is recommended to find the role of metal ions in olfaction. 


The research performed establishes the role of metal ions in mammalian odor perception. Several previous reports have suggested the possibility that odorant receptors that mediate odor perception function as metalloproteins whereby transition metal ions are required for the activation of the receptors by particular ligands.


In many mammals various gland secretion volatiles carry biological information (species, gender, mating status, etc.) motivating further investigations that lead to relevant social behaviors, of which copper ions are essential co-factors for the detection of thiols. 


Sulfurous compounds and other containing nitrogen do not elicit a response without copper, yet evoked a prominent response after the copper ions were added. 


Although electronic sensors to detect toxic gasses have been used for years, recent progress in understanding the mechanisms and principles underlying our sense of smell have intensified efforts to design devices capable of monitoring the ambient odorous world with applications ranging from the registration of environmental hazards and explosives to the assessment of food quality or even exhaling.


Inorganic chemists know as a rule of thumb that if a volatile compound is a good ligand for metal ion coordination complexes, it probably smells strongly.  This observation has led to recent advances in artificial olfaction. In general the human olfactory system is extremely sensitive to amines and thiols (good ligands for metal ions) but not to alcohols (which are only weak ligands). Odorants need to bind to an olfactory receptor to trigger the cascade of events which finally enables us to smell, of which different compounds have a range of intensities which that receptor can respond. Differences in Lewis basicity to metal ions can account for some of this range, and is critical to the pattern recognition processes proposed for neural recognition. 


Sulfurous compounds such as thiols and thioethers, as well as other compounds are notable in that they are extremely potent as odorants. Using a heterologous expression system for mammalian odorant receptors combined with a high-throughput odorant receptor screening platform, we identified mammalian odorant receptors that responded to an array of sulfurous and other volatile compounds only with the addition of copper ions. It was found that copper ion, but not other metal ions tested are required for robust odorant receptor activation. This is the first instance showing the crucial role of copper ions in the olfactory detection of organo-sulfur and other classes of metal coordinating compounds. It’s proposed that this and other detection platforms integrating copper ions can be applied to achieve the sensitive detection and discrimination of sulfurous and other metal coordination compounds in industrial and agricultural settings. Such as in improved methods of gas leak detection and animal traction. 


Potential Applications

  • Detection of sulfurous explosive materials in anti-terrorism context.
  • Sensitive detection and discrimination of sulfurous and other metal coordination compounds in industrial and agricultural settings, such as improved methods of gas leak detection and animal tracking.


The development of this innovation was funded in part by the National Science Foundation under grant number CHE0744578.

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