n e w s of t h e w e e k
CAPTURING AN ENZYME'S ESSENCE Small molecules catalyze oxidation through same mechanism as enzyme
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hemists at Stanford University have GOase is a mononuclear copper ensynthesized a group of small, inor- zyme that oxidizes alcohols with 0 2 to ganic complexes that bind sub- give an aldehyde product and hydrostrates and catalyze a reaction in a way gen peroxide. In the natural enzyme, that closely mimics the enzyme galac- the copper has five ligands arranged in tose oxidase (GOase). The work, which a square pyramidal coordination. Four was carried out by Stanford assistant of the ligands are provided by the proprofessor of chemistry T. Daniel P. Stack tein (two tyrosine phenolates and two and coworkers, may pave the way to histidine imidazoles), and the fifth likinder, gentler industrial chemical pro- gand is a water molecule, which occucesses catalyzed with synthetic enzyme pies an equatorial site. The Stanford mimics. team's models mimic the four proteinFor years, chemists have been trying based ligands with appropriately derivato make small inorganic molecules that tized Schiff base diimine-diphenolate liapproximate the structure of enzyme ac- gands, which prefer a nonsquare planar tive sites and reproduce their catalytic geometry. function through an analogous mechaIn addition, the natural system feanism. Often, the synthetic mimics are ca- tures a covalent thioether bond between pable of only a single "turnover" (react- a cysteine sulfur atom and an aromatic ing just once), or they operate through carbon of one of the phenolate ligands; an entirely different mechanism, Stack the model complexes include similar explains. linkages. This modified phenolate ligand But graduate students Yadong Wang is thought to be oxidized to a radical durand Jennifer L. DuBois, working with ing the catalyzed reaction according to Stack and chemistry professor Keith O. the mechanism generally accepted for Hodgson's group at Stanford, have devel- the enzyme, Stack says. oped catalytically functional models of After incorporating these features into GOase that use dioxygen as the oxidant. their synthetic mimics of the GOase acWhile the reaction turnover rate is much tive site, the researchers determined slower than the native system, the cata- that, as far as "we can tell, the mechalytically active species and postulated nism by which our compounds undergo mechanism of the models closely resemble that system [Science, 279, — 537(1998)]. Synthetic mimic "It's very rare to have something of galactose oxidase that mimics the important structural features and also does the Enforces same chemistry" as an enzyme, a nonsquare planar ^ says Thomas N. Sorrell, chemistry coordination professor at the University of North geometry Carolina, Chapel Hill. The Stanford group's GOase model is "one of the very few examples of this," says Sorrell, whose own research concerns synthetic models of coppercontaining metalloenzymes. The more closely a model's structure mimics that of the enzyme's active site, he adds, the "better chance you Stabilize the phenoxyl radical have of learning what's going on in nature."
Stack: from nature to a test tube
this oxidation is identical to that proposed for the actual active site of galactose oxidase," Stack says. "Effectively, we extracted a mechanism out of an enzyme by rather simple structural mimicry," he says. This "radical oxidative reactivity has been previously unknown outside a protein matrix," Stack notes, and his team's work has in essence "moved chemistry from nature into the test tube." Stack points out that "this oxidation chemistry is very environmentally friendly relative to other synthetic alcohol oxidation procedures," because the only byproduct is hydrogen peroxide. Under the conditions investigated, however, the mimics are only capable of oxidizing benzylic or allylic alcohols, and not simple aliphatic primary alcohols. The Stanford research could have significant implications in industry, where reactions can "generate undesirable byproducts, require a lot of energy, or demand control of stringent conditions," Sorrell says. Biological systems, on the other hand, "work in water at about room temperature and neutral pH. So if you can do the same chemistry under the mild conditions used by living organisms, then industrial processes could become more environmentally and economically favorable." The Stanford work, says Sorrell, "provides evidence that we can understand biological processes by studying synthetic model systems. And that gives us hope that we're eventually going to be able to exploit biomimetic catalysis for practical applications." Sophie Wilkinson JANUARY 26, 1998 C&EN 9
