THE PHARMACEUTICAL JOURNAL AND TRANSACTIONS. 
[August 24, 1872. 
144 
NOTE ON CYSTINE. 
BY JAMES DEWAR.* 
The following observations on Cystine are a continua¬ 
tion of those formerly communicated to the Society by 
Dr. Arthur Gamgee and myself, during the course of the 
session 1869-70, and reprinted with addition in the ‘Jour¬ 
nal of Anatomy and Physiology ’ for that year; and al¬ 
though really little of a novel nature to present to the 
society, still it is necessary to show some additional facts 
have been observed tending towards the synthesis of this 
interesting substance. 
The most important fact ascertained with regard to the 
chemical relation of cystine in the memoir referred to was 
the production of pyruvic acid, when it was treated with 
nitrous acid. In this reaction the amido residue was not 
alone eliminated, the sulphur also separating as sulphuric 
acid, however carefully the experiment was performed. 
The fear of allowing the action to proceed too far, on 
the necessary small quantity of substance operated upon, 
prevented us from purifying the product thoroughly, and 
consequently, the analysis differed slightly from that of 
pure pyru'gic acid. We had no hesitation in saying, 
however, tile acid agreed better with the chemical cha¬ 
racters of the syrupy modification of pyruvic acid than 
with that of Wischelhaus’s carbacet oxylic acid, that we 
had anticipated would be produced, and that in all pro¬ 
bability cystine would be found to be an amido-sulpho 
pyruvic. 
If cystine is directly related to pyruvic acid, it must 
contain five instead of seven hydrogen atoms (and this 
supposition agrees well with the published analysis). The 
formula of the compound will then be, C 3 H 5 N0 2 S. On 
this supposition, we may derive from pyruvic acid at 
least five isomers, that will all have the general charac¬ 
ters of cystine, although there are many other possible 
constitutional formulae. 
Pyruvic Acid. 
l. 
0 
& • 
ch 3 
ch 2 nh 2 
CILNH, 
CO 
CO 
CO ' 
CO.OH 
CO.SH 
CSOH 
3. 
4. 
5. 
CHo (NH 2 ) 
CH & 
CHS 
cs 
CO 
n NHo 
0 H" 
CO.OH 
CO.OH 
CO.OH 
Of the five possible cystines formulated, it is impossible 
to select that of the natural substance, because of our 
ignorance of the intermediate sulpho-acid. All attempts 
to replace the amido group alone by the action of nitrous 
acid having failed, I have tried several experiments, with 
the object of replacing the sulphur alone, with the small 
quantity of cystine at my disposal. 
If cystine is one of the above five substances, the re¬ 
placement of the sulphur by hydrogen will generate very 
different bodies. Theory enables us to predict that, in 
the case of bodies having the constitutional formula? of 
No. (5), we ought to obtain alanine. In that of (3) (0) 
alanine, and in that of (4) amido-lactic acid (serine), and 
in that of (2) amido-glycerine; whereas it is diflicult to 
imagine the sulphur in (1) being replaced. A successful 
experiment in this direction ought to restrict the selec¬ 
tion to two possible constitutional formula? in the worst 
case, and synthetical processes might then be attempted. 
It was formerly observed that nascent hydrogen gene¬ 
rated in an acid solution, readily liberated sulphuretted 
hydrogen, and might be used as a test for this substance. 
The action goes on, however, very slowly, and it was 
found extremely difficult to get anything like the theo¬ 
retical quantity of sulphur evolved. With this experi¬ 
ence, sodium amalgam suggested itself as being more 
powerful, and equally likely to act. When cystine is 
dissolved in caustic soda, and sodium amalgam added, in 
Read bsf<? v etke Royal Society of Edinburgh, February 5. 
a few minutes it is easy to detect the presence of a sul¬ 
phide by the nitro-prusside test. The action was allowed 
to proceed for several days, being occasionally rendered 
acid by the addition of hydrochloric acid, and the amal¬ 
gam renewed. Ultimately the alkaline solution, after 
being neutralized with hydrochloric acid, was evaporated 
and treated with boiling alcohol to separate the chloride 
of sodium, and to dissolve any hydrochlorate of alanine 
that might be formed. After the filtrate was evaporated 
the residue still contained sulphur, from the presence of 
hydrochlorate of cystine. This was separated by treat¬ 
ing with water, and the filtrate was boiled with oxide of 
lead, treated'afterwards with sulphuretted hydrogen to 
precipitate the dissolved lead, and evaporated. The re¬ 
sidue was then heated to 200° C. in a tube, with the object 
of subliming the alanine. No crystalline sublimate was 
observed; it is probable, therefore, that substances of 
the constitutional formula? of 5 do not express the con¬ 
stitution of normal cystine. This result is subject to a 
certain amount of reservation, from the difficulty of se¬ 
parating a small quantity of substance from a very large 
amount of secondary material accumulated in the course 
of the experiment. The battery is far better adapted to 
give a supply of nascent hydrogen in this case; and an 
experiment made in this way looks promising, if suffi¬ 
cient material was to be had. 
The small quantity of substance left I have employed 
for the purpose of corroborating the production of pyru¬ 
vic acid, when it is treated with hydrate of baryta. 
Took a decigramme of cystine, Heated it in a tube 
with a solution of hydrate of baryta, and heated it all 
night to a temperature of 130° C., opened it, and trans¬ 
ferred contents to a beaker, boiled to expel the ammonia 
produced, then added an exactly equivalent quantity of 
sulphuric acid, filtered from the sulphate of baryta ; after 
boiling to expel the sulphuretted hydrogen, the filtrate 
evaporated contained a yellowy syrupy acid, which con¬ 
tained a few crystals under the microscope, having the 
appearance of Finch’s uvitic acid. Ammonia was added, 
and gave a yellow solution, which was evaporated on the 
water-bath ; it was dissolved in v> r ater, and gave a white 
precipitate, with nitrate of silver, which was not dis¬ 
tinctly crystalline ; it also gave a white precipitate with 
subnitrate of mercury, and a red colour with a crystal 
of sulphate of iron, and no precipitate with sulphate of 
copper. The barium salt was also found to be non-crys¬ 
talline, the acid lost the power of giving a red colour 
with ferric salts after treatment with sodium amalgam, 
and the composition of the silver salt agreed better with 
pyruvic acid than formerly. 
Considerable progress has been made in an examination 
of the chemical characters and relations of the thio-peru- 
vic acids. Normal thio-peruvic acid has been obtained 
from the di-chlorpropionic ether. When this ether is 
treated with excess of alcoholic sulphide of potassium, 
we obtain at once a precipitate of chloride of potassium 
and a solution of the potash salt of the new acid. When 
this is diluted with water, acidulated with sulphuric acid, 
and shaken up with ether, the acid is obtained in yellow 
crystalline plates, part of it seems to remain a viscid 
fluid. The lead and silver salts are white and insoluble, 
blacken when heated. It precipitates mercurous salts, 
black from the first. The calcium, barium, iron, cad¬ 
mium, and copper salts are all soluble. The potassium 
and sodium salts are intensely yellow, and decompose 
slightly on exposure to the air. When treated with tin 
and sulphuric acid, they evolve sulphuretted hydrogen. 
The thio-carboxyl pyruvic acid has not yet been ob¬ 
tained in a pure state. When pyruvic acid is treated 
with pentasulphide of phosphorus, a violent action takes 
place, associated with much frothing; and when the pro¬ 
duct is distilled, a large mass of carbon is left in the re¬ 
tort, and a very small quantity of distillate is obtained,. 
It is probable that chloro-pyruvil, when treated with 
sulphide of potassium, will give a more satisfactory yield. 
It is the author’s intention to nuke a careful comparison 
