306 RIBOFLAVIN 



point, a temporary concentration of I mg. per milliliter is said to be at- 

 tained. The supersaturated solution of riboflavin is fairly stable; it requires 

 days to crystallize. 



In order to obtain more concentrated solutions, riboflavin has been dis- 

 solved together with other compomids which are capable of increasing its 

 solubility. N-Methylacetamide, L-tyrosine amide, ^^ tryptophan," sodium 

 acetyltryptophan, urea, nicotinamide, aliphatic amidines, sodium desoxy- 

 cholate, veratryl alcohol, salts of boric, ^^' ""^ mono- and dihydroxybenzoic, 

 gallic, aminobenzoic, adenyhc, and other acids,^^ kynurenic and 2-phenyl- 

 quinoline-4-carbonic acid,^*^ and propylene glycol with or without the addi- 

 tion of a monohydroxymonoalkoxybenzaldehyde^^ have been used. Solu- 

 tions containing a concentration of riboflavin up to about 0.6% can 

 be prepared in this way. The solubility of riboflavin in nicotinamide solu- 

 tions at pH 5 increases from about 0.1 % to about 2.5 %, when the nicotin- 

 amide concentration is increased from 5 to 50 %.^'' When riboflavin is fused 

 with an amide such as urea, urethan, or nicotinamide, products are ob- 

 tained which yield aqueous solutions containing up to 6 % of the flavin.^^a 

 Recently a method of solubilizing riboflavin with sodium-3-hydroxy-2- 

 naphthoate has been developed; the solubility of riboflavin is as high as 7.9 % 

 in a 10 % solution of the solubilizer.^^ Borax and alkali are said to give a 

 complex with riboflavin of the formula Ci7Hi906N4Na-Na2B407- 10H.2O.^^ 



Water-soluble derivatives of riboflavins^ include esters with phosphoric, 

 sulfuric,^^^ gallic, aminoacetic, phthalic, succinic,^^ citric, malic, tartaric, 

 and levulinic acids, and methyl ol and acetal derivatives.^^ In the synthesis 

 of methylol derivative, preparations with as high as 55 % microbiological 

 activity can be obtained in short reaction time, when only 1 mole of formal- 

 dehyde is combined with 1 mole of riboflavin. Upon addition of 2 or more 



le Wyeth Inc., U. S. Pat. 2,445,208 (Sept. 13, 1948) [C.A. 42, 6496 (1948,)]. 



" R. A. Harte and J. L. Chen, /. Am. Pharm. Assoc. Sci. Ed. 38, 568 (1949). 



i^'' D. V. Frost, J. Biol. Chern. 145, 693 (1942). 



'* For literature references, see K. Schoen and S. M. Gordon, Archives Biochem. 22, 



149 (1949). 

 '8'' C. S. Runti, Farm. sci. e tec. {Pavia) 7, 344 (1952). 



19 American Cyanamid Co., U. S. Pat. 2,449,041 (Sept. 7, 1948) [('..1. 42, 9094 (1948)]; 

 Wyeth Inc., U. S. Pat. 2,449,640 (Sept. 21, 1948) [C.A. 42, 9094 (1948)]. 



20 D. V. Frost, J. Am. Chem. Sac. 69, 1064 (1947); Abbott Laboratories U. S. Pat. 

 2,407,412 (Sept. 10, 1946) [C.A. 41, 254 (1947)]. 



20" Merck and Co., U. S. Pat. 2,480,517 (Aug. 30, 1949). [C.A. 43, 9088 (1949)]. 

 2' A. Arnold, M. E. Auerbach, J. R. Shepherd, and S. D. Sobell of Sterling-Winthrop 

 Research Institute; see Chem. Emj. NewsSO, 1414 [1952) ;Pouliry Sci. 31,350 (1952). 



22 Winthrop Chemical Co., British Pat. 560,631, (April 13, 1944) [C.A . 40, 2593 (1946)]; 

 U. S. Pat. 2,332,548 (Oct. 26, 1943) [C..1. 38, 1849 (1944)]. 



22a G. B. Stone, Science 111, 283 (1950). 



23 M. F. Furter, G. J. Haas, and S. H. Rubin, J. Biol. Chem. 160, 293 (1945); Merck 

 and Co., U. S. Pat. 2,358,356 (Sept. 19, 1944) [C.A. 39, 1514 (1945)]. 



I 



