435 
tological and immunochemical reactions, it has drawn attention from 
various sides. SABBATANI') thinks, that its action might be caused by 
the diminution of the number of free calciumions; Artuus ®) and 
Guncou *) showed, that citrates have an antifloceulant action on finely 
divided suspensions, and asked whether the biological action should 
not rather be attributed to the latter. Finally M. H. Fiscumr ‘) 
proved recently that citrates inhibit to a large extent the swelling 
(imbibition) of proteids by acids and by alkalis and that some phar- 
macological properties of these salts (e.g. their influence on glaucoma) 
are related to this. Each of these theories is supported by a number 
of experiments; possibly all three contain a part of the truth; under 
these circumstances a choice between the different explanations does 
not seem possible as long as the biological action of citrates has 
not been ‘more extensively analysed. 
Analysis of the biological action of citrates by comparison 
with the action of substituted citrates. 
For such an analysis the finding of the active groups in the citrate- 
molecule seems particularly adapted. For it seems rather improbable 
that the different actions of the citrates are all caused by the same 
groups. Then this research will give an indication which actions can 
be compared, which not. 
In order to find which are these groups, I have followed the 
ordinary pharmacological method. A number of derivatives of citric acid 
were prepared in which the probably active groups were changed 
in different ways. As all acids which precipitate calcium in the 
manner of fluorides and oxalates inhibit the curdling of milk, this 
secondary complication should be excluded. On this account I have 
made a control with all acids examined in order to see if the 
solution of the neutral salt of the acid used, precipitated a diluted 
solution of calciumsalt. Only those, which did not were used for 
the investigation. As solution of calciumsalt I chose a solution of 
gypsum (saturated solution, diluted 1:5 with distilled water). 
OH ‘COOH 
NY coe eg 
Citric acid, COOH . CH, .C.CH, . COOH, contains + groups which 
may be considered as the active ones: three carboxylgroups COOH 
and one aleoholgroup OH. The hydroxylgroup can be made inactive 
1) Atti della R. Acad. di Torino 36, p. 27—53; Memorie [2] 52, p. 213—257, 
2) CG. R. Soc. de Biol. 36 (1901). 
By le s6s 
4) Das Oedem. 
29* 
