Carbon-hydrogen activation of cycloalkanes by cyclopentadienylcarbonylrhodium--a lifetime enigma.

Carbon-hydrogen bond activation reactions of four cycloalkanes (C5H10, C6H12, C7H14, and C8H16) by the Cp'Rh(CO) fragments (Cp' = η(5)-C5H5 (Cp) or η(5)-C5Me5 (Cp*)) were modeled theoretically by combining density functional and coupled cluster theories, and their reaction rates were measured by fast time-resolved infrared spectroscopy. The reaction has two steps, starting with the formation of a σ-complex intermediate, followed by oxidative addition of the C-H bond by the rhodium. A range of σ-complex stabilities among the electronically unique C-H bonds in a cycloalkane were calculated and are related to the individual strengths of the C-H bond's interactions with the Rh fragment and the steric repulsion that is incurred upon forming the specific σ-complex. The unexpectedly large increase in the lifetimes of the σ-complexes from cyclohexane to cycloheptane was predicted to be due to the large range of stabilities of the different σ-complexes found for cycloheptane. The reaction lifetimes were simulated with two mechanisms, with and without migrations among the different σ-complexes, to determine if ring migrations prior to C-H activation were influencing the rate. Both mechanisms predicted similar lifetimes for cyclopentane, cyclohexane, and, to a lesser extent, cycloheptane, suggesting ring migrations do not have a large impact on the rate of C-H activation for these cycloalkanes. For cyclooctane, the inclusion of ring migrations in the reaction mechanism led to a more accurate prediction of the lifetime, indicating that ring migrations did have an effect on the rate of C-H activation for this alkane, and that migration among the σ-complexes is faster than the C-H activation for this larger cycloalkane.

Investigating the electronic structure of the Atox1 copper(I) transfer mechanism with density functional theory.

To maintain correct copper homeostasis, the body relies on ion binding metallochaperones, cuprophilic ligands, and proteins to move copper around as a complexed metal. The most common binding site for Cu(I) proteins is the CX1X2C motif, where X1 and X2 are nonconserved residues. Although this binding site motif is well established, the mechanistic and electronic details for the transfer of Cu(I) between two binding sites have not been fully established, in particular, whether the transfer is dissociative or associative or if the electron-rich Cu(I)-Cys interactions influence the transfer. In this work, we investigated the electronic structure of the Cu(I)-S interactions during the copper transfer between Atox1 and a metal binding domain on the ATP7A or ATP7B protein. Initially, three Cu(I) methylthiolate complexes, [Cu(SCH3)2](-1), [Cu(SCH3)3](-2), [Cu(SCH3)4](-3), were investigated with density functional theory (DFT) to fully elucidate the electronic structure and bonding between Cu(I) and thiolate species. The two-coordinate, linear species with a C-S-S-C dihedral angle of ∼90° is the lowest energy conformation because the filled π antibonding orbitals are stabilized in this geometry. The importance of π-overlap is also seen with the trigonal planar, three-coordinate Cu(I) complex, which is similarly stabilized. A corresponding four-coordinate species could not be consistently optimized, so it was concluded that tetrahedral coordination was not likely to be stable. The transfer of Cu(I) from the Atox1 metallochaperone to a metal binding domain of the ATP7A or ATP7B protein was then modeled by using the CGGC Atox1 binding site for the donor model and the dithiotreitol ligand (DTT) for the acceptor model. The two- and three-coordinate intermediates calculated along the five-step transfer mechanism converged to near optimal Cu-S π-overlap for the respective geometries, which demonstrates that the electronic structure in this electron-rich environment influences the intermediate's geometries in the transfer mechanism.