The covalent bond in selective toxicity

2 Cephalosporins. Other -lactam inhibitors of the formation of new walls. 562 

Although the majority of biologically active substances combine only loosely with receptors and are easily released by washing, a few agents combine by covalent bonds which are of a more durable character (see Section 8.0). Covalent bonds involving carbon can be broken by great heat and also by powerful chemicals, but usually not by mild reagents at temperatures compatible with life. 

Marginally easier to break are some covalent bonds that link atoms other than carbon, although a swamping excess of the reagent is usually required. Two examples the restoration by mercaptan antidotes of cells poisoned by arsenicals (exchange of one As—S bond for another), and rescue of a victim poisoned by an acetylcholinesterase inhibitor, using an oxime antidote (exchange of one P—O bond for another), as described in Sections 12.0 and 12.3 respectively. 

One aspect of covalent bond formation has already been adequately treated, namely the degradation of a pro-drug to the true active agent (see Section 3.6). Also, many covalent bonds are made and broken by enzymes in the normal metabolic reactions of the cell, and also in disposing of foreign materials (see Section 3.5). However, the present chapter is concerned solely with the formation of a covalent bond between an agent and the complementary atoms of its receptor. 

Although Ehrlich had found that pentavalent arsenicals did not act in the body until reduced to arsenoxides, it had not occurred to him that arseno-benzenes acted only after oxidation to arsenoxides. This was established between 1920 and 1925 by Swiss-born Carl Voegtlin and his co-workers in the United States Public Health Service (for a review, see Voegtlin, 1925). 

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