Catalytic Mechanism in Artificial Metalloenzyme: QM/MM Study of Phenylacetylene Polymerization by Rhodium Complex Encapsulated in <i>apo</i>-Ferritin

Artificial metalloenzyme, composed of metal complex­(es) and a host protein, is a promising way to mimic enzyme catalytic functions or develop novel enzyme-like catalysis. However, it is highly challenging to unveil the active site and exact reaction mechanism inside artificial metalloenzyme, which is the bottleneck in its rational design. We present a QM/MM study of the complicated reaction mechanism for the recently developed artificial metalloenzyme system, <b>(Rh­(nbd)·</b><i><b>apo</b></i><b>-Fr</b>) (nbd = norbornadiene), which is composed of a rhodium complex [Rh­(nbd)­Cl]₂ and the recombinant horse L-chain <i>apo</i>-Ferritin. We found that binding sites suggested by the X-ray crystal structure, i.e., sites A, B, and C, are only precursors/intermediates, not true active sites for polymerization of phenylacetylene (PA). A new hydrophobic site, which we name D, is suggested to be the most plausible active site for polymerization. Active site D is generated after coordination of first monomer PA by extrusion of the Rh^I(PA) complex to a hydrophobic pocket near site B. Polymerization occurs in site D via a Rh^I-insertion mechanism. A specific “hydrophobic region” composed by the hydrophobic active site D, the nonpolar 4-fold channel, and other hydrophobic residues nearby is found to facilitate accumulation, coordination, and insertion of PA for polymerization. Our results also demonstrate that the hydrophobic active site D can retain the native regio- and stereoselectivity of the Rh-catalyzed polymerization of PA without protein. This study highlights the importance of theoretical study in mechanistic elucidation and rational design of artificial metalloenzymes, indicating that even with X-ray crystal structures at hand we may still be far from fully understanding the active site and catalytic mechanism of artificial metalloenzymes

DFT Study of Acceptorless Alcohol Dehydrogenation Mediated by Ruthenium Pincer Complexes: Ligand Tautomerization Governing Metal Ligand Cooperation

Metal ligand cooperation (MLC) catalysis is a popular strategy to design highly efficient transition metal catalysts. In this presented theoretical study, we describe the key governing factor in the MLC mechanism, with the Szymczak’s NNN-Ru and the Milstein’s PNN-Ru complexes as two representative catalysts. Both the outer-sphere and inner-sphere mechanisms were investigated and compared. Our calculated result indicates that the PNN-Ru pincer catalyst will be restored to aromatic state during the catalytic cycle, which can be considered as the driving force to promote the MLC process. On the contrary, for the NNN-Ru catalyst, the MLC mechanism leads to an unfavored tautomerization in the pincer ligand, which explains the failure of the MLC mechanism in this system. Therefore, the strength of the driving force provided by the pincer ligand actually represents a prerequisite factor for MLC. Spectator ligands such as CO, PPh₃, and hydride are important to ensure the catalyst follow a certain mechanism as well. We also evaluate the driving force of various bifunctional ligands by computational methods. Some proposed pincer ligands may have the potential to be the new pincer catalysts candidates. The presented study is expected to offer new insights for MLC catalysis and provide useful guideline for future catalyst design

Oxygen Vacancy Defect Migration in Titanate Perovskite Surfaces: Effect of the A‑Site Cations

Oxygen vacancy formation energies and migration barriers in (001) surfaces of CaTiO₃, SrTiO₃, and BaTiO₃ have been investigated using first principles density functional theory. The degree of distortion within the TiO₂ sublattice in the presence of defects and consequently the defect formation energies in these titanate surfaces are determined by the size of the A-site cation (Ca²⁺ < Sr²⁺ < Ba²⁺). This is notably the case for CaTiO₃, in which the presence of a vacancy defect leads to a heavily distorted local orthorhombic structure within the (001) slab depending on the defect position, despite the overall cubic symmetry of the material modelled. This effectively leads to the TiO₂ sublattice acting as a thermodynamic trap for oxygen vacancy defects in CaTiO₃. By contrast, calculated vacancy diffusion pathways in SrTiO₃ and BaTiO₃ indicate that vacancy diffusion with these larger A-site cations is kinetically and not thermodynamically controlled

Frustrated Lewis Pair Catalyzed C–H Activation of Heteroarenes: A Stepwise Carbene Mechanism Due to Distance Effect

This study presents new mechanistic insights into the frustrated Lewis pairs (FLPs) catalyzed C–H activation of heteroarenes. Besides the generally accepted concerted C–H activation, a novel stepwise carbene type pathway is proposed as an alternative mechanism. The reaction mechanisms can be varied by tuning the distance between Lewis acid and Lewis base due to catalyst–substrate match. These results should expand the understanding of the structure and function of FLPs for catalyzed C–H activation

When Bifunctional Catalyst Encounters Dual MLC Modes: DFT Study on the Mechanistic Preference in Ru-PNNH Pincer Complex Catalyzed Dehydrogenative Coupling Reaction

Metal ligand cooperation (MLC) plays an important role in the development of homogeneous catalysts. Two major MLC modes have generally been proposed, known as the M-L bond mode and the (de)­aromatization mode. To reveal the role of the dual potential functional sites on the MLC process, we present a detailed mechanistic study on a novel-designed Ru-PNNH complex possessing dual potential MLC functional sites for the M-L bond mode and the (de)­aromatization mode, respectively. Our results indicate that the Ru-PNNH complex prefers the M-L mode exclusively during different stages of the catalytic cycle. The unusual double deprotonation process and the mechanistic preference are rationalized. The N-arm deprotonation is attributed to the small steric hindrance of the amido N-arm and the conjugation stabilization effect of the amido group. The origin of the unexpected exclusive mechanistic preference on the M-L bond mechanism is due to the conjugation effect of the amido group, which stabilizes the dearomatized complex and diminishes the driving force of the (de)­aromatization mode. This study highlights the pivotal role of the ligand’s electronic effect on the MLC mechanism and should provide valuable information for the development of highly efficient bifunctional catalysts

Sterically Encumbered Tetraarylimidazolium Carbene Pd-PEPPSI Complexes: Highly Efficient Direct Arylation of Imidazoles with Aryl Bromides under Aerobic Conditions

A series of sterically encumbered tetraarylimidazolium carbene Pd-PEPPSI complexes were conveniently prepared and fully characterized. These sterically encumbered Pd-PEPPSI complexes act as active precatalysts for the direct arylation of imidazoles with aryl bromides under aerobic conditions. The catalytic performance of Pd-PEPPSI complexes in cross-coupling processes is investigated. Under the optimal protocols, the cross-coupling reactions regioselectively produced C5-arylation products in moderate to excellent yields, which could tolerate a wide range of functional aryl bromides

Sterically Encumbered Tetraarylimidazolium Carbene Pd-PEPPSI Complexes: Highly Efficient Direct Arylation of Imidazoles with Aryl Bromides under Aerobic Conditions

A series of sterically encumbered tetraarylimidazolium carbene Pd-PEPPSI complexes were conveniently prepared and fully characterized. These sterically encumbered Pd-PEPPSI complexes act as active precatalysts for the direct arylation of imidazoles with aryl bromides under aerobic conditions. The catalytic performance of Pd-PEPPSI complexes in cross-coupling processes is investigated. Under the optimal protocols, the cross-coupling reactions regioselectively produced C5-arylation products in moderate to excellent yields, which could tolerate a wide range of functional aryl bromides

The Effect of HSAB on Stereoselectivity: Copper- and Gold-Catalyzed 1,3-Phosphatyloxy and 1,3-Halogen Migration Relay to 1,3-Dienes

The origin of stereodivergence between copper- and gold-catalyzed cascade 1,3-phosphatyloxy and 1,3-halogen migration from α-halo-propargylic phosphates to 1,3-dienes is rationalized with density functional theory (DFT) studies. Our studies reveal the significant role of the relative hardness/softness of the metal centers in determining the reaction mechanism and the stereoselectivity. The relative harder Cu­(I/III) center prefers an associative pathway with the aid of a phosphate group, leading to the (<i>Z</i>)-1,3-dienes. In contrast, the relative softer Au­(I/III) center tends to undergo a dissociative pathway without coordination to a phosphate group, resulting in the (<i>E</i>)-1,3-dienes, where the <i>E</i> type of transition state is favored due to the steric effect. Our findings indicate the intriguing role of hard–soft/acid–base (HSAB) theory in tuning the stereoselectivity of metal-catalyzed transformations with functionalized substrates