Secondary reactions occurring proximate to primary metal-centered reaction sites are important reactivity control elements in enzymes. This fact suggests a parallelism that presents a largely unexplored challenge calling chemists, as individuals or in teams, to deal with its different features in synthesis, reactivity and kinetics, spectroscopy, magnetism and electrochemistry. The problem is not one of directly mimicking enzymes, but rather one of moving towards their complexity of function in small molecule reagents. To attack the challenge, it seems desirable to choose important reaction problems from nature where the requirement for a multifunctional reagent is apparent, and then to develop practical multifunctional catalytic reagents bringing more than one reaction into play to solve the reactivity puzzles. Chemists must learn how the proximate reaction sites communicate, how to compensate for enzymatic design features that Cannot be easily reproduced, how to sequence the reactions effectively, and how to exploit communication and timing to control reactivity. We launched such a program in late 1992 with NIH support, weaving in ligand design, reactivity, spectroscopy, and magnetism to pursue understanding along the multitechnique lines that have been employed to understand the enzymes that inspire the work. This proposal is the first renewal. This proposal lays out a plan to employ so-called """"""""switching ligands"""""""" to pursue monooxygenase type reactions focused on controlling oxygen binding and activation and oxygen-atom transfer at a primary site. Switching events are accomplished by the addition and removal of charged ions and electrons at secondary sites crafted close to the primary site. Here, our near fifteen-year effort in learning how to protect ligands from oxidative destruction is a comparative advantage in small molecule catalysis compensating for the loss of the protein and its reactivity-directing features. Three switching systems have been developed and crucial compounds such as a switch-off manganyl have been prepared and characterized. It is shown that individual switches exert distinctive influences on reactivity and on redox, spectroscopic and magnetic properties, validating the proposed approaches for attacking important reactivity problems with switching systems. Further development of an unexpected lead for controlling the sign and magnitude of exchange coupling in multinuclear magnetic ions is proposed, with the goal of testing and extending the proposed design principle. An extensive study in iron-catalyzed C-H bond oxidations is presented, guiding the proposed pursuit of reactive iron-oxo complexes that do not self-destruct on preparation in the absence of reducing substrates. We propose to extend our progress in preparing and characterizing benchmark high valent iron (IV) compounds. A range of protected ligands has been prepared to allow oxidized iron species to be isolated where the site of oxidation varies from the metal, to ligand-metal delocalized, to the ligand: a significant goal is to exploit this achieved control over the locus of oxidation in reactivity.
| Gupta, Sayam Sen; Stadler, Matthew; Noser, Christopher A et al. (2002) Rapid total destruction of chlorophenols by activated hydrogen peroxide. Science 296:326-8 |
