Friedrich Theodor von Frerichs
Friedrich Theodor von Frerichs

Bernhard Naunyn
Bernhard Naunyn

Marcel V. Nencki
Marcel V. Nencki

Oxidation

The discovery of the ability of living organisms to oxidize compounds grew out of the conjugation experiments of Ure and, subsequently, Erdmann and Marchand. These scientists observed that acids other than benzoic could lead to the excretion of hippuric acid in the urine—necessitating the postulation of the intermediate step of oxidation. Erdmann and Marchand administered 5 to 6 g of cinnamic acid to volunteers and isolated what appeared to be hippuric acid from the urine; however, the glycine conjugate of cinnamic acid could not be excluded. The postulated oxidation of cinnamic acid to benzoic acid was confirmed by Wöhler and Frerichs when they isolated hippuric acid in the urine of dogs after administration of cinnamic acid. When these authors administered benzaldehyde to dogs and rabbits, they were also able to isolate hippuric acid in the urine.

It was in the clinical labs of Friedrich Frerichs where the next major discovery regarding chemical oxidation occurred. Bernhard Naunyn was predominantly interested in various types of disease pathology, but he was also keenly interested in using the experimental laboratory to investigate interesting questions arising in the course of his work. In his studies on stomach fermentation he found that benzene had the ability to “counteract” fermentation. He began to wonder about the effect of benzene on patients, and in studying this found that phenol was eliminated after the administration of benzene. Schultzen, who also worked in Frerichs’ clinic and who had greater chemical experience, joined with Naunyn to study what happened in the body to hydrocarbons associated with benzene, namely toluene, xylene etc. Their paper on “The behavior of benzene-derived hydrocarbons in the animal organism” unveiled entirely new capabilities of the body to perform chemistry that, to that time, had been impossible for chemists to accomplish in the lab.

Another student in Frerichs’ clinic was Marcel Nencki, who had come to Berlin to study physics but changed to chemistry after being inspired by the work of Naunyn and Schultzen. Nencki went on to perform many pioneering studies in the field of metabolism. In his 1870 thesis devoted to studies on the oxidation of aromatic compounds in animals, Nencki also defined the guiding principle of drug metabolism research performed so that “...one will on the one hand be able to establish laws allowing predictions on the fate of new compounds, and on the other hand gain increasing insight into the organism as a ‘chemical agent.’”

          


Index | Intro | The Beginning | Oxidation
Sulfation | Glucuronides | Acetylation, Methylation
Reduction | Mercapturic Acid | Founding of the Field
Drug Metabolism Methodology | In Vitro Technology | P-450
The Future

BAS Home