A Physical Mechanism for the Inactivation of Proteins by Ionizing Radiation 273 



It may also be noted that the chemical effects may be reversed, but that the 

 disorganization caused by localization in a macromolecule of several freshly 

 created electric charges cannot be; hence protection from or cure of radiation 

 damage at the molecular level cannot possibly be complete, even in principle. 



IV. THE ROLE OF EXCITATION 



Absorption of ionizing radiation leading to the formation of a certain 

 number of ion pairs must also produce a comparable number of electronically 

 excited molecules. This is true for the effects of primary charged particles as 

 well as for secondary ones, and is an elementary consequence of electromagnetic 

 theory. Indeed, the ratio of total number of excited to total number of ionized 

 molecules is, except for slow electrons, simply related to familiar optical pro- 

 perties of the absorbing matter, and the available evidence shows that this ratio 

 is unlikely to depart from unity by more than a factor of about 2, even allowing 

 for the disturbing effects of slow electrons. The ratio is known accurately, at 

 present, only for the noble gases, for which it is 0.4. For all molecular systems 

 it must be greater. 



Just as in the case of ionization, which was discussed above, excitation — 

 whether produced by absorption of ionizing radiation or of ultraviolet light — 

 does not itself 'break bonds'. The initial acts of energy transfer are all* ones 

 in which energy is communicated to the electronic systems of molecules; 

 subsequent rearrangement of atomic positions may then result in dissociation. 

 For polyatomic molecules the probability that bond rupture will follow 

 excitation is by no means unity, and may be quite small. 



In molecules like amino acids, polypeptides, and proteins, excitation 

 commonly is followed by dissociation or by internal conversion, but only very 

 rarely by luminescence (5). In general, experimental work (which has usually 

 been restricted, for practical reasons, to wavelengths greater than about 2200 A) 

 indicates small quantum yields for inactivation, of order of magnitude 10 "^ to 

 10"^. Analysis of the absorption processes has not progressed to the stage of 

 identifying them either with dissociation or with internal conversion, but the 

 following explanations for the low efficiency seem attractive. In the case of 

 dissociation, that is, cleavage of a primary (valence) bond, the secondary-bond 

 structure may prove capable of sustaining the conformation, at least until 

 activation energy becomes available for healing the rupture. (Thus the cage 

 effect is enhanced.) This proposal is supported by the fact that dissociation 

 by moderate or long-wavelength ultraviolet radiation does not provide much 

 energy in excess of the bond dissociation energy; thus at 2200 A, not more than 

 several hydrogen bonds could be broken. The structure should therefore remain 

 otherwise intact, with closure of the bond a much more likely ultimate result than 

 denaturation. Internal conversion, on the other hand, releases a substantial 

 quantity of energy to oscillational modes, but the coupling is chiefly with 

 valence oscillations (C — H, C — C, etc.); by the time the energy reaches the 

 secondary bonds it will have been dissipated too extensively to have much effect, t 



* The only direct bond breakage arises from momentum transfer to atoms from swiftly 

 mo\ing particles, in so-called nuclear collisions (17). This is usually a minor effect. 



t However, individual internal conversion processes may be responsible for isomerization, 

 and thus for such biological phenomena as gene mutation. 



