HISTORICAL INTRODUCTION 5 



range of hydrogen ion concentration as a dibasic acid and hence, it 

 should require as many cubic centimeters of 0.1 N H 2 SO 4 as it 

 requires cubic centimeters of 0.1 N HC1 to bring the same 1 per 

 cent solution of gelatin from a hydrogen ion concentration of 

 N/50,000 to one of N/1,000. Titration experiments proved the 

 correctness of these and similar conclusions, not only in the case 

 of gelatin but also of other proteins, thus leaving no doubt that 

 proteins combine with acids or alkalies according to the stoichio- 

 metrical laws of general chemistry. 1 



It was merely an unfortunate historical accident that the 

 colloidal behavior of proteins was investigated before the con- 

 venient methods of measuring the hydrogen ion concentration 

 were developed; otherwise, we should probably never have heard 

 of the idea that the chemistry of colloids differs from the chemistry 

 of crystalloids, at least as far as the proteins are concerned. It 

 was this methodical error of not measuring the hydrogen ion 

 concentration of colloidal solutions and of gels which prevented 

 the development of an exact theory of colloidal behavior and 

 which gave rise to the statement of Zsigmondy quoted in the 

 preface. 



The reason that measurements of the hydrogen ion concentra- 

 tion are paramount for the understanding of the chemical and 

 physical behavior of the proteins lies in the fact that proteins are 

 amphoteric electrolytes capable of forming ionizable salts with 

 acids as well as with alkalies, according to the hydrogen ion 

 concentration. When the hydrogen ion concentration exceeds a 

 certain critical value (which varies for different proteins) the 

 protein behaves as if it were a base, like NH 3 , capable of forming 

 salts with acids; while when the hydrogen ion concentration of 

 the solution is below this critical value the protein behaves as 

 if it were a fatty acid, e.g., CH 3 COOH, capable of forming salts 

 with bases. At the critical value of the hydrogen ion concentra- 

 tion the protein can practically combine neither with an acid nor 

 a base nor a neutral salt. 2 This critical hydrogen ion concen- 

 tration is called the " isoelectric " point of the protein. More- 

 over, we shall see that the fraction of 1 gm. of originally isoelectric 



1 LOEB, J., J. Gen. Physiol, vol. 3, pp. 85, 547, 1920-21. 



2 LOEB, J., J. Gen. Physiol., vol. 1, pp. 39, 237, 1918-19. Science, vol. 52, 

 p. 449, 1920, /. chim. physique, vol. 18, p. 283, 1920. 



