Designing for Non-Persistence

Congress made it clear that prevention was top priority in a hierarchy of pollution 

Industrial research and development increasingly incorporates the principles of green chemistry and development of safer substitutes, but safer has usually meant less toxic. However, persistence should also be considered in product design. Chemicals that persist remain potentially available to biota to exert toxic effects, not all of which may be known or predictable at the outset Persistent chemicals that are bioaccumu-lative are of even greater concern because levels may be achieved in organisms that 

Handbook of Green Chemistry Volume 9 Designing Safer Chemicals, First Edition. Edited by Robert Boethling and Adelina Voutchkova. 

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The musks make a good case study for illustrating biodegradability rules of thumb and their application in molecular design for non-persistence. Musk xylene appears... 

An alternative possibility is that the inhibitor attaches to the enzyme somewhere else (possibly close to the active site but not at it), and, because proteins are flexible, it causes a distortion of the active site. As a result, the substrate may be able to attach to the enzyme as usual but without any catalytic outcome, i.e. the inhibitor has sabotaged the activity from a distance (Fig. A14.2). This second pattern is known as non-competitive inhibition. It may be harder to plan for in terms of rational design of drug molecules, but on the other hand it is likely to lead to a more persistent drug effect, since accumulation of the substrate will not displace the inhibitor. 

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