Chemical Models for Hydrolytic Reactions:
    The studies of metalloenzymes have yielded information for better design of metal complexes as models that are used as tools in several fast-growing disciplines such as DNA technology.  Conversely, the chemical models for hydrolytic metalloenzymes have provided insight into the mechanistic roles of the active-site metal ions and the coordinated nucleophilic water molecule.  However, as opposed to enzymes, these model complexes lack specific recognition toward substrates owing to the absence of a well-defined active site.  Numerous chemical model systems have been prepared for the investigation of the hydrolyses of proteins/peptides, nuclear acids, pesticide, and chemical warfare agents.  However, the efficiency and the selectivity in chemical systems are far behind those of the enzymes.  Nevertheless, chemical systems are usually more accessible to extreme pH and temperature conditions than most enzymes, thus potentially can have broader application.  A better understanding of the structure and mechanism of enzymes can assist the design of better chemical models suitable for industrial and environmental applications.

    Although proteins with different functions can have nearly identical folding and/or structural motifs, proteins possessing a single active site that exhibit different functions are not commonly seen.  We have recently observed that sAP exhibits an unexpected opportunistic activity, i.e., phosphodiesterase activity.  The detailed studies of the two different types of hydrolysis by sAP may lead to a better understanding of and unifying the mechanisms of dinuclear hydrolytic reactions in chemical and biological systems.  From a chemical viewpoint, the protein moieties in metalloproteins can be considered as “macromolecular ligands” which in many cases bind preferably only certain metal ions. Thus, the idea of using “protein ligands” for the preparation of different “macromolecular metal complexes” to serve as “natural chemical models” may point new directions for chemical modeling studies.

    Degradation of Nerve Agents:
    The United States ratified the Chemical Weapons Convention Treaty in 1997, which bans the use of chemical agents in wars and possession of the agents, and also prohibits the production and stockpiling of these agents. Thousands of tons of stockpiles of several chemical warfare agents are thus awaiting for being destroyed, which thus creates great safety and environmental concerns.  The nerve agents (see structures below), represented by the VX agent ethyl S-2-(diisopropylamino)ethyl methylphosphonothiolate, the R-VX agent isobutyl S-2-(diethyl)ethyl methylphosphonothiolate, and the “G agents” 2-propyl methylphosphonofluoridate (sarin) and 3,3-dimethyl-2-butyl methylphosphonofluoridate (soman), are potent acetylcholinesterase inhibitors which inhibit the enzyme via the formation of the indefinitely stable phosphoester with the active-site nucleophilic Ser.  Degradation of these nerve agents can be achieved by hydrolysis of the P–F and the P–OR bonds and by oxidative cleavage of the P–SR bond (to yield R–SO3–), which also represents a valuable practice of hydrolytic and oxidative chemistry.