CHEMICAL BONDS IN NUCLEIC ACIDS 419 



and physical methods for identifying the products. Recovery of the mono- 

 nucleotides as mixtures of the 2'- and 3 '-isomers (generally in the ratio 

 40:60) from alkaline hydrolysates of ribonucleic acids, in amounts ap- 

 proaching the theoretical value, have been reported. ^^■^- 



Brown and Todd^- have discussed these observations on the basis of 

 their findings with the esters of the mononucleotides (see above), and have 

 developed from them general structures for the ribonucleic acids. If the 

 linear polynucleotide sequence XVI is considered, in which the expression 

 C2' — Cs'^ — C5- is used as an abbreviation for individual nucleoside residues, 

 alkaline degradation will proceed through a cyclic intermediate (formulated 

 for simplicity as XVII) yielding cyclic nucleoside-2', 3 '-phosphates by 

 exclusive fission of the Cs- — — P bond, in strict conformity with the be- 

 havior of the fundamentally analogous simple nucleotide esters. The cyclic 

 phosphates then yield, by further hydrolysis, the mixture of nucleoside-2 '- 

 phosphates and nucleoside-3 '-phosphates which is normally isolated. This 

 postulate that cyclic nucleoside-2 ',3 '-phosphates should be produced dur- 

 ing alkaline hydrolysis of ribonucleic acids has since been substantiated by 

 their demonstration^-^ in barium carbonate (ca. pH 9 at 100°) and dilute 

 ammonia hydrolysates. Kinetic studies, too, give results consistent with 

 the proposed hydrolytic mechanism.*^ The earlier failure to recognize cyclic 

 phosphates among hydrolytic products was doubtless due to their labile 

 character. 



C2.-OH C2.-OH C2.-OH C2.-OH 



I _ /^v' _ -/^^ 



C5. c. 



XVII 



It should be noted that no such mechanism of hydrolysis can occur in 

 the case of deoxyribonucleic acids where the absence of a hydroxyl at C2' 

 in the deoxyribofuranose residues prevents the essential cyclization which 



" E. Volkin and C. E. Carter, J. Am. Chem. Soc. 73, 1516 (1951). 



83 R. Markham and J. D. Smith, Biochem. J. 52, 552 (1952). 



8^ J. E, Bacher and W. Kauzmann, J. Am. Chem. Soc. 74, 3779 (1952). 



