Redox-state-dependent complex formation between pseudoazurin and nitrite reductase

Bacterial copper-containing nitrite reductase catalyzes the reduction of nitrite to nitric oxide as part of the denitrification process. Pseudoazurin interacts with nitrite reductase in a transient fashion to supply the necessary electrons. The redox-state dependence of complex formation between pseudoazurin and nitrite reductase was studied by nuclear magnetic resonance spectroscopy and isothermal titration calorimetry. Binding of pseudoazurin in the reduced state is characterized by the presence of two binding modes, a slow and a fast exchange mode, with a K(d)(app) of 100 microM. In the oxidized state of pseudoazurin, binding occurs in a single fast exchange mode with a similar affinity. Metal-substituted proteins have been used to show that the mode of binding of pseudoazurin is independent of the metal charge of nitrite reductase. Contrary to what was found for other cupredoxins, protonation of the exposed His ligand to the copper of pseudoazurin, His81, does not appear to be involved directly in the dual binding mode of the reduced form. A model assuming the presence of a minor form of pseudoazurin is proposed to explain the behavior of the complex in the reduced state.     

A stabilized beta-oxaphosphoniumbetaine: an elusive zwitterion

A beta-oxaphosphoniumbetaine stabilized by two tert-butyl groups at the phosphonium part of the betaine and two trifluoromethyl groups at the carbon adjoined to the oxa part of the betaine was isolated and structurally characterized. Additional stabilization results from the solvation of the betaine by a parent phosphonium salt, as in 4, or by protonation with methanol, as in 10. According to X-ray analysis, the betaine exhibits a sterically strained "gauche" conformeric form, with torsion angles in the P-C-C-O moiety of 32.2 degrees for 4 and 28.1 degrees for 10. The P...O separations of 3.121 A for 4 and 3.086 A for 10 are just under the sum of the O and P van der Waals radii (3.32 A). The fast H/D exchange of alpha hydrogen atoms to the phosphonium center was observed in the solution of 10 in deuterium oxide and MeOH-d4. The beta-oxaphosphoniumbetaine has long been suspected as an intermediate in the Wittig reaction, but this is the first time a stabilized derivative has been isolated.     

(+)-saxitoxin: a first and second generation stereoselective synthesis

A stereoselective synthesis of the bis-guanidinium toxin (+)-saxitoxin (STX), the agent infamously associated with red tides and paralytic shellfish poisoning, is described. Our approach to this unique natural product advances through an unusual nine-membered ring guanidine intermediate 39 en route to the tricyclic skeleton that defines STX. The effectiveness of this strategy is notable, as only four steps are needed to transform 39 into the target molecule, including a four-electron alkene oxidation catalyzed by OsCl3. Construction of the critical monocyclic guanidine has been achieved through two channels, the first of which makes use of Rh-catalyzed C-H amination and highlights a novel class of heterocyclic N,O-acetals as iminium ion equivalents for crafting functionalized amines. A second route to 39 relies on a stereoselective acetylide dianion addition to a serine-based nitrone, thereby facilitating the preparation of STX in just 14 linear steps from commercial material.     

Rational design and synthesis of catalytically driven nanorotors

We report the design and synthesis of nanorotors based upon on-wire lithography. Because of their asymmetric structure, the nanorotors exhibit rotation in a H2O2 bath instead of linear motion. By observing the leading edge of rotation and comparing this result to the nanorotor design, we have concluded that the driving force for motion is dynamic catalytic decomposition of H2O2 which propels, rather than pulls, the nanorotor.