Nucleophilic Reactions and the pi of Amino Acid Side Chains

Nucleophilic Reactions and the pi of Amino Acid Side Chains 

Each type of ionizable group in proteins will have a unique pKa based upon the theoretical value for the amino acid and modulated from that value by its own surrounding microenvironment. Minute environmental changes will cause amine containing residues at different structural locations to have different ionization potentials, even if the groups are otherwise chemically identical. 

Further implications of this equation are that at one pH unit below or above the pKa, an ionizable group will be 91 percent unionized (protonated) or 91 percent ionized (unprotonated), respectively. Two pH units below or above translate to a 99 percent unionized or 99 percent ionized state. 

According to the theory of nucleophilicity (Edwards and Pearson, 1962 Bunnett, 1963 Pearson et al., 1968), the relative order of nucleophilicity relative to the major groups in biological molecules can be summarized as follows  

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