For much of this century, biochemists have used chemical models as a basis for elucidating the behavior of naturally occurring macromolecules. In the last few decades, structural biochemistry has made such remarkable strides in interpreting function that it should now be possible to inaugurate a complementary program: biological molecules ought to serve as models for the design of new chemical entities. For example, chemists are intensively engaged in searches for new catalysts. The preeminent catalysts are enzymes. The molecular structure and behavior of many enzymes is known in great detail. Should it not be feasible to use this information to construct catalysts from nonliving sources?
STRATEGYAt the inception of such a program, one can plan some beginning steps on the basis of rudimentary features of enzyme kinetics. First we recognize that all enzymes are macromolecules; hence we shall assume that a polymer framework should provide a promising foundation for a synthetic catalytic entity. Secondly, we turn attention to a very elementary description of the activated-state theory of reaction rates. For a single reactant, S, the rate of transformation depends on the concentration of the activated, transition-state species, St, in the equilibrium
S = S $(1)As indicated in FIGURE I , the relative concentration of SS is small compared to s.What can an added macromolecule, M, achieve? Nothing, unless it can first bind S.But even if a complex, M -S, is formed, there will be no increase' in rate of S if the equilibrium constant foris the same (FIG. 1, column a) as that for nonbound substrate, (Eq. I). In other words, if the activation free energy for the reactant is unchanged in the complex M -S, the rate of reaction will not be modified. However, the environment in the polymer matrix, M, can be modified by chemical manipulations. If changes in macromolecular character favor ( M -S)* (FIG. 1, column b), then the rate of reaction will be increased. We shall give an illustration of such a situation later in this paper.When two reactants are involved in a transformation, the potential of a macromolecule is broader. For example (FIG. 2), if the second reactant, N, a potential catalytic entity, is covalently attached to the polymer to create M-N, then the concentration of the transition-state species ((M-N) S)$ can be raised by increasing the equilibrium constant for SisiDo, M., K. AKIYAMA, Y. IMANISHI & 1. M. KLOTZ. 1984. Dynamics and hydrophobic binding of lauryl-quaternized polyethylenimine in aqueous solution. Macromolecules 17: SOC. 100 5977-5978. 198-204.
