This section is from the book "Research In Physiopathology As Basis Of Guided Chemotherapy With Special Application To Cancer", by Emanuel Revici. Also available from amazon: Research In Physiopathology
A similar condition is also found in the epoxide carcinogens. Carcinogenic activity has been recognized for substances having two epoxide centers in close proximity in the molecule. The epoxide center by itself can lead to a formation similar to that of carbonium ion, as seen in Figure 108 and thus to the same formation found in mustards and ethyleneimines. The analogy goes still further. The energetic center appears insufficient to accomplish biological changes without an inductive activation. In the case of epoxides, this is usually brought about by another similar epoxide group in the same molecule.
As no carcinogenic activity has been found in substances with only one epoxide center or with two epoxide centers far apart, the inductive centers seem to be of primary importance. The two energetic centers forming the epoxide group, similar to those of the ethyleneimines, do not alone appear sufficiently reactive to induce important changes. Only when enhanced by reciprocal induction is their reactivity adequate to induce either the appearance of a reactive intermediate or a sufficient charge in the ethylene carbons to produce biological activity. These changes can be measured by the reaction with thiosulfate ion and consequently can be related to the reciprocal positions of the two epoxide centers.
The biological activity of dimethanesulfonoxyalkanes can also be related to a similar energetic formation. Such a formation appears when the molecule is metabolized, with the difference that the two CH2 in this instance seem to come originally from other chains. (Fig.III) For the methylolamides, it is possible that a similar process occurs during the changes that take place in the organism.
2:4 Dinitrophenyl Ethylenimine
Fig. 110. Through the influence exerted by the nitro group upon the ethyleneimine, the imine group of 2:4 dinitro phenyl ethyleneimine, becomes dialectrophylic.
Some corroboration can be found in the fact that two forms can be observed in these last groups of carcinogens. One is electrostatically active; that is, it has a certain ionic character. The second has a dual electrophilic activity which can be related to a twin formation with molecular reactivity.
Thus, twin formation, with its special reactivity, appears common in many carcinogenic agents. To be biologically active, the twin formation has to be sufficiently strong and this is insured by an induction effect exerted by other formations in the molecule, such as double bonds in parallel position or polar groups. A twin formation as energetic center in the molecule would exert a molecular field effect. It would thus represent a center of molecular reactivity which has to be considered as such in the analysis of plural activity.
Fig. 111. Changes occurring in sulfonoxyalkancs leading to two active CH2 centers.