This physiological activity was noted years ago with the inorganic compounds of selenium and Berzelius[(15)] described the poisonous effect of hydrogen selenide quite impressively; “In order to get acquainted with the smell of this gas I allowed a bubble not larger than a pea to pass into my nostril; in consequence of its smell I so completely lost my sense of smell for several hours that I could not distinguish the odor of strong ammonia even when held under my nose. My sense of smell returned after five or six hours, but severe irritation of the mucous membrane set in and persisted for a fortnight.” The writer has been working on the gas for some time and was also quite seriously affected once, the injury persisting for many days. That it is more poisonous than the hydrogen sulphide is well known.
Bruere[(16)] showed that when hydrogen sulphide was passed into blood solution sulphemoglobin was produced in considerable quantity, due to the chemical action of sulphur and hematin. He stated further that sulphemoglobin may be found in animal blood when a large amount of the gas has been inhaled. He made selenhemoglobin in the same manner. Sixteen years later, Clarke and Hurtley also proved that selenhemoglobin may be made by passing hydrogen selenide into blood[(17)]. These experiments may be interpreted to mean that the oxy-hemoglobin is transformed into an organic complex of sulphur or selenium, and that the transference may be more rapid and powerful in the case of hydrogen selenide.
Biological investigations have sufficiently proved that dyestuffs of the phenazine, oxazine, thiazine, acridine series show an injurious effect on protozoa, especially those dyes containing substituted amino groupings and of a simple structure[(18)]. In the case of the thiazine dyes of the methylene blue class, the physiological importance has well recognized in their use as feeble antiseptics and analgesics. Ehrlich and Guttmann[(19)] initiated the use of methylene blue as an antiperiodic and its use in that line has been continued.
In the field of the selenazine dyes, pharmacologists have not yet paid much attention to them, on account of the newness of the discovery, but P. Karrer claims that they are indisputably “vital dyestuffs”[(20)]. The prospect of synthesizing selenazine dyes and their use as drugs seems to be bright, judging from the fact that they are easily prepared and capable of many combinations, especially of the ease with which they form organic complexes with arsenic compounds.
Formula (I) is known, as 1, 3-dinitrobenzoselenazine[(21)], which was obtained by the action of picryl chloride on the zinc salt of o-aminoselenophenol; the product (picrylaminoselenophenol) being then treated with alkali and thus converted to the dye, which upon experimentation showed marked effects upon protozoa and bacteria.
Formula (II), known as 3-(p-phenylarsonic)-aminoselenazine, is red in dilute alkali and green in mineral acid, and is a typical dye in a series from the coupling of selenodiphenylamine with arsenic compounds. All possess similar toxicity as the thiazine dyes[(20)]. Other selenazines are listed in the bibliography[(22)].
No less than half dozen thioureas are commonly used as drugs. Thiourea itself paralyzes the nerve centers, and is employed commercially for photograph fixing and for removing stains from negatives; thiuret, C6H7N3S2, serves as a substitute for iodoform; thiosinamine-ethyliodide, or tiodine, IH5C2H2NCSNHC3H5, is used for relief of lesions of the central nervous system; allylthiourea or thiosinamine, (NH2)SC.NHCH2CH:CH2, for aiding the absorption of connective tissues, for treatment of burns, keloids, urethral diseases, sclerotic conditions of the ear[(23)].