Atoxyl
Encyclopedia
Arsanilic acid is the organoarsenic compound
also called p-aminophenylarsonic acid. This colourless solid was used as a drug in the late 19th and early 20th centuries but is now considered prohibitively toxic. Arsanilic acid is a derivative of phenylarsonic acid
with an amine
in the 4-position. It exists as a zwitterion
, H3N+C6H4AsO3H−, although it is typically represented with the non-zwitterionic formula, H2NC6H4AsO3H2.
. The original synthesis, which involved the reaction of aniline
and arsenic acid
, remains useful today:
was so high that toxic
side effects far outweighed the benefits. It frequently caused blindness
by damaging the optic nerve
and other varied disorders. Nevertheless, the discovery of arsanilic acid's activity against trypanosomes was the basis for a major advance by the bacteriologist Paul Ehrlich
. Ehrlich, who believed that the formula was incorrect, and the organic chemist Alfred Bertheim revised the structural assignment. The correct formula suggested new ways that the atoxyl molecule could be modified, and a series of such derivatives were then synthesized. Testing for anti-syphilitic
activity was performed by Sahachiro Hata
who worked in Ehrlich's lab. The result of this collaboration was the discovery of the drug Salvarsan in 1909, which also was later abandoned but which accelerated the growth of medicinal chemistry.
Although the practice is controversial, arsanilic acid and related compounds are sometimes used in treating dysentery
in swine.
Organoarsenic compound
Organoarsenic chemistry is the chemistry of compounds containing a chemical bond between arsenic and carbon. A few organoarsenic compounds, also called "organoarsenicals," are produced industrially with uses as insecticides, herbicides, and fungicides. In general these applications are declining in...
also called p-aminophenylarsonic acid. This colourless solid was used as a drug in the late 19th and early 20th centuries but is now considered prohibitively toxic. Arsanilic acid is a derivative of phenylarsonic acid
Phenylarsonic acid
Phenylarsonic acid is the chemical compound with the formula C6H5AsO2, commonly abbreviated PhAsO3H2. This colourless solid is an organic derivative of arsenic acid, AsO3, where one OH group has been replaced by a phenyl group. The compound is a buffering agent and a precursor to other...
with an amine
Amine
Amines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...
in the 4-position. It exists as a zwitterion
Zwitterion
In chemistry, a zwitterion is a neutral molecule with a positive and a negative electrical charge at different locations within that molecule. Zwitterions are sometimes also called inner salts.-Examples:...
, H3N+C6H4AsO3H−, although it is typically represented with the non-zwitterionic formula, H2NC6H4AsO3H2.
Synthesis
Arsanilic acid was first reported in 1859 by Antoine BéchampAntoine Béchamp
Pierre Jacques Antoine Béchamp was a French biologist. He studied silkworm parasites, and was the first to synthesise Atoxyl.-Biography:...
. The original synthesis, which involved the reaction of aniline
Aniline
Aniline, phenylamine or aminobenzene is an organic compound with the formula C6H5NH2. Consisting of a phenyl group attached to an amino group, aniline is the prototypical aromatic amine. Being a precursor to many industrial chemicals, its main use is in the manufacture of precursors to polyurethane...
and arsenic acid
Arsenic acid
Arsenic acid is the chemical compound with the formula H3AsO4. More descriptively written as AsO3, this colorless acid is the arsenic analogue of phosphoric acid. Arsenate and phosphate salts behave very similarly. Arsenic acid as such has not been isolated, but only found in solution where it...
, remains useful today:
- C6H5NH2 + H3AsO4 → H2O3AsC6H4NH2 + H2O
History and uses
In his reports on the chemical, Béchamp optimistically chose the name Atoxyl, referring to its reduced toxicity compared to arsenic. Atoxyl was initially used in medicine to treat simple skin diseases. In 1905, two British physicians, H.W. Thomas and A. Breinl, reported that atoxyl was active against the trypanosomes of sleeping sickness. The effect was however not very pronounced and the necessary dosageEffective dose
Effective dose may refer to:*Effective dose the dose of pharmacologic agent which will have a therapeutic effect in some fraction of the population receiving the drug...
was so high that toxic
Toxicity
Toxicity is the degree to which a substance can damage a living or non-living organisms. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver...
side effects far outweighed the benefits. It frequently caused blindness
Blindness
Blindness is the condition of lacking visual perception due to physiological or neurological factors.Various scales have been developed to describe the extent of vision loss and define blindness...
by damaging the optic nerve
Optic nerve
The optic nerve, also called cranial nerve 2, transmits visual information from the retina to the brain. Derived from the embryonic retinal ganglion cell, a diverticulum located in the diencephalon, the optic nerve doesn't regenerate after transection.-Anatomy:The optic nerve is the second of...
and other varied disorders. Nevertheless, the discovery of arsanilic acid's activity against trypanosomes was the basis for a major advance by the bacteriologist Paul Ehrlich
Paul Ehrlich
Paul Ehrlich was a German scientist in the fields of hematology, immunology, and chemotherapy, and Nobel laureate. He is noted for curing syphilis and for his research in autoimmunity, calling it "horror autotoxicus"...
. Ehrlich, who believed that the formula was incorrect, and the organic chemist Alfred Bertheim revised the structural assignment. The correct formula suggested new ways that the atoxyl molecule could be modified, and a series of such derivatives were then synthesized. Testing for anti-syphilitic
Syphilis
Syphilis is a sexually transmitted infection caused by the spirochete bacterium Treponema pallidum subspecies pallidum. The primary route of transmission is through sexual contact; however, it may also be transmitted from mother to fetus during pregnancy or at birth, resulting in congenital syphilis...
activity was performed by Sahachiro Hata
Sahachiro Hata
was a Japanese bacteriologist who developed the Arsphenamine drug in 1909 in the laboratory of Paul Ehrlich.Hata was born in Tsumo Village, Mino District, Shimane , and completed his medical education in Kyoto...
who worked in Ehrlich's lab. The result of this collaboration was the discovery of the drug Salvarsan in 1909, which also was later abandoned but which accelerated the growth of medicinal chemistry.
Although the practice is controversial, arsanilic acid and related compounds are sometimes used in treating dysentery
Dysentery
Dysentery is an inflammatory disorder of the intestine, especially of the colon, that results in severe diarrhea containing mucus and/or blood in the faeces with fever and abdominal pain. If left untreated, dysentery can be fatal.There are differences between dysentery and normal bloody diarrhoea...
in swine.
External links
- Atoxyl at Chemical Heritage More about the origins and uses of the medicine.
- Explorers of the Body Some info about sleeping sickness and atoxyl.
- Arsonic Acid poisoning information.
- Ihde, Aaron J. The Development of Modern Chemistry, Dover, New York, 1984. pp. 697-698.