XVI. STABLE ISOTOPES AS TRACERS 59 1 



6. Exchange Reactions 



The application of stable isotopes to biological problems is limited 

 markedly by the ease with which a number of elements exchange posi- 

 tions between or within molecules. This type of behavior has been 

 known for a long time in the case of some elements and suspected for 

 others. Owing to the fact that this exchange is not usually observ- 

 able in ordinary chemical reactions, it had not received much atten- 

 tion prior to the availability of the isotope method for studying reac- 

 tion rates. 



The exchange of hydrogen atoms between the molecules of a solute 

 and a solvent is a most rapid process for many chemical radicals {15, 

 p. 62). This unstable condition obtains for practically all polar 

 groups, but special mention must be made of the carboxyl, hydroxyl, 

 and amino radicals that are so common in biochemical systems. As a 

 consequence, deuterium introduced into these labile groups cannot 

 be used as a tracer. In general, deuterium attached directly to car- 

 bon atoms has been found to be stably bound, particularly in methyl 

 and methylene radicals. There are exceptions, however, as in the case 

 of hydrogen atoms attached to carbon atoms adjacent to keto groups, 

 since such hydrogen atoms are known to undergo enolization. The 

 conclusion reached, at least with respect to the use of deuterium as a 

 tracer is that its stability with reference to any proposed chemical 

 system must first be confirmed. There has been no evidence to the 

 effect that an isotope that has been shown to be stably bound with 

 reference to a given chemical system in vitro, is not stable in vivo also. 

 Not only the stability of the initial compound to be synthesized but 

 also of any subsequent compounds to be isolated and analyzed for 

 the presence of deuterium must be checked. 



The ready exchange of oxygen atoms in solution {16) has made the 

 0^' and O'^ isotopes practically valueless in biological tracer work. 

 Oxygen exchange in carbonyl groups is particularly rapid, thus elim- 

 inating studies involving aldehydes and ketones. The oxygen in car- 

 boxyl groups plays a variable exchange role, depending on the com- 

 pound and on the environmental conditions, so that individual con- 

 firmations of its behavior under each given set of circumstances 

 would be indicated. The oxygen in hydroxyl groups is stable in 

 many common alcohols, at least under mild acid and alkaline condi- 

 tions, and may be found useful as a tracer. The same seems to apply 

 to the hydroxyl groups in pentoses and hexoses but not to the carbonyl 



