The mitochondrial adenosine triphosphate (ATP) synthase produces most of the ATP required by mammalian cells. We isolated porcine tetrameric ATP synthase and solved its structure at 6.2-angstrom resolution using a single-particle cryo–electron microscopy method. Two classical V-shaped ATP synthase dimers lie antiparallel to each other to form an H-shaped ATP synthase tetramer, as viewed from the matrix. ATP synthase inhibitory factor subunit 1 (IF1) is a well-known in vivo inhibitor of mammalian ATP synthase at low pH. Two IF1 dimers link two ATP synthase dimers, which is consistent with the ATP synthase tetramer adopting an inhibited state. Within the tetramer, we refined structures of intact ATP synthase in two different rotational conformations at 3.34- and 3.45-Å resolution.

It is now well established that mammalian heme proteins are reactive with various nitrogen oxide species and that these reactions may play significant roles in mammalian physiology. For example the ferrous heme protein myoglobin (Mb) has been shown to reduce nitrite (NO2−) to nitric oxide (NO) under hypoxic conditions. We demonstrate here that the distal pocket histidine residue (His64) of horse heart metMbIII (i.e., ferric MbIII) has marked effects on the mode of nitrite ion coordination to the iron center. X-ray crystal structures were determined for the mutant proteins metMbIII H64V (2.0 Å resolution) and its nitrite ion adduct metMbIII H64V-nitrite (1.95 Å resolution), and metMbIII H64V/V67R (1.9 Å resolution) and its nitrite ion adduct metMbIII H64V/V67R-nitrite (2.0 Å resolution). These are compared to the known structures of wild type hh metMbIII and its nitrite ion adduct hh metMbIII-nitrite, which binds NO2− via an O-atom in a trans-FeONO configuration. Unlike wt metMbIII, no axial H2O is evident in either of the metMbIII mutant structures. In the ferric H64V-nitrite structure, replacement of the distal His residue with Val alters the binding mode of nitrite from the nitrito (O-binding) form in the wild-type protein to a weakly bound nitro (N-binding) form. Reintroducing a H-bonding residue in the H64V/V67R double mutant restores the O-binding mode of nitrite. We have also examined the effects of these mutations on reactivities of the metMbIIIs with cysteine as a reducing agent and of the (ferrous) MbIIs with nitrite ion under anaerobic conditions. The MbIIs were generated by reduction of the MbIII precursors in a second order reaction with cysteine, the rate constants for this step following the order H64V/V67R > H64V >> wt. The rate constants for the oxidation of the MbIIs by nitrite (giving NO as the other product) follow the order wt > H64V/V67R >> H64V and suggest a significant role of the distal pocket H-bonding residue in nitrite reduction.

Although nitrogen-containing group-directed cyclopalladation reactions have been well-known, Pd(II) insertion into C-H bonds promoted by coordination of an oxygen-only group to the palladium remains rather rare. In the present study, the first cyclopalladation complex formed from a simple phenol ester was characterized by X-ray crystallography. A promising protocol for the ortho C-H activation/aryl-aryl coupling of phenol esters that was not sensitive to moisture or air was then established. The utility of the reaction was demonstrated for the synthesis of useful phenol derivatives.

The nitrite anion is known to oxidize and degrade hemoglobin (Hb). Recent literature reports suggest a nitrite reductase activity for Hb, converting nitrite into nitric oxide. Surprisingly, no structural information about Hb-nitrite interactions has been reported. We have determined the crystal structure of the ferric Hb-nitrite complex at 1.80 A resolution. The nitrite ligand adopts the uncommon O-nitrito binding mode. In addition, the nitrito conformations in the alpha and beta subunits are different, reflecting subtle effects of the distal His in orienting the nitrite ligand in the O-nitrito binding mode.

Good solubility alone does not explain the performance of organic ionic bases in the room‐temperature coupling of aryl iodides and even bromides with aliphatic and aromatic amines and N‐heterocycles (NuH; see scheme). Conductivity measurements show that these organic ionic bases, which contain tetraalkylammonium or ‐phosphonium cations, are readily ionized in organic solvents.

New carbon–carbon bond formation reactions expand our horizon of retrosynthetic analysis for the synthesis of complex organic molecules. Although many methods are now available for the formation of C(sp2)–C(sp3) and C(sp3)–C(sp3) bonds via transition metal-catalyzed cross-coupling of alkyl organometallic reagents, direct use of readily available olefins in a formal fashion of hydrocarbonation to make C(sp2)–C(sp3) and C(sp3)–C(sp3) bonds remains to be developed. Here we report the discovery of a general process for the intermolecular reductive coupling of unactivated olefins with alkyl or aryl electrophiles under the promotion of a simple nickel catalyst system. This new reaction presents a conceptually unique and practical strategy for the construction of C(sp2)–C(sp3) and C(sp3)–C(sp3) bonds without using any organometallic reagent. The reductive olefin hydrocarbonation also exhibits excellent compatibility with varieties of synthetically important functional groups and therefore, provides a straightforward approach for modification of complex organic molecules containing olefin groups.

A copper-promoted trifluoromethylation reaction of aromatic amines is described. This transformation proceeds smoothly under mild conditions and exhibits good tolerance of many synthetically relevant functional groups. It provides an alternative approach for the synthesis of trifluoromethylated arenes and heteroarenes. It also constitutes a new example of the Sandmeyer reaction.

The translocase of the outer mitochondrial membrane (TOM) complex is the main entry gate for mitochondrial precursor proteins synthesized on cytosolic ribosomes. Here we report the single-particle cryo-electron microscopy (cryo-EM) structure of the dimeric human TOM core complex (TOM-CC). Two Tom40 β-barrel proteins, connected by two Tom22 receptor subunits and one phospholipid, form the protein-conducting channels. The small Tom proteins Tom5, Tom6, and Tom7 surround the channel and have notable configurations. The distinct electrostatic features of the complex, including the pronounced negative interior and the positive regions at the periphery and center of the dimer on the intermembrane space (IMS) side, provide insight into the preprotein translocation mechanism. Further, two dimeric TOM complexes may associate to form tetramer in the shape of a parallelogram, offering a potential explanation into the unusual structural features of Tom subunits and a new perspective of viewing the import of mitochondrial proteins.