Remotely Bonded Bridging Dioxygen Ligands Enhance Hydrogen Transfer in a Silica-Supported Tetrairidium Cluster Catalyst.

A longstanding challenge in catalysis by noble metals has been to understand the origin of enhancements of rates of hydrogen transfer that result from the bonding of oxygen near metal sites. We investigated structurally well-defined catalysts consisting of supported tetrairidium carbonyl clusters with single-atom (apical iridium) catalytic sites for ethylene hydrogenation. Reaction of the clusters with ethylene and H2 followed by O2 led to the onset of catalytic activity as a terminal CO ligand at each apical Ir atom was removed and bridging dioxygen ligands replaced CO ligands at neighboring (basal-plane) sites. The presence of the dioxygen ligands caused a 6-fold increase in the catalytic reaction rate, which is explained by the electron-withdrawing capability induced by the bridging dioxygen ligands, consistent with the inference that reductive elimination is rate-determining. Electronic-structure calculations demonstrate an additional role of the dioxygen ligands, changing the mechanism of hydrogen transfer from one involving equatorial hydride ligands to that involving bridging hydride ligands. This mechanism is made evident by an inverse kinetic isotope effect observed in ethylene hydrogenation reactions with H2 and, alternatively, with D2 on the cluster incorporating the dioxygen ligands and is a consequence of quasi-equilibrated hydrogen transfer in this catalyst. The same mechanism accounts for rate enhancements induced by the bridging dioxygen ligands for the catalytic reaction of H2 with D2 to give HD. We posit that the mechanism involving bridging hydride ligands facilitated by oxygen ligands remote from the catalytic site may have some generality in catalysis by oxide-supported noble metals.

NHC Carbene-Metal Complex Ligand Binding Energies.

The ligand binding energies (LBEs) of N-heterocyclic carbenes (NHCs) and CH2 and CF2 adducts with group 1, 2, 10, and 11 metals and complexes with metals from these groups are predicted at the coupled cluster CCSD(T) level of theory by using density functional theory optimized geometries. The differences in LBEs as a function of the metal and the types of bonding interactions as well as the type of carbene are described. The bonding between the alkali cations and alkaline earth dications is predominantly ionic with a linear correlation between the LBEs and the cation hardness. In contrast, the bonding behaviors of the group 10 and 11 metals and metal complexes have only a weak, indirect correlation between the LBEs and the metal hardness. The difference in bonding behavior between the groups of metals arises due to the accessibility of electron donation between the ligand and the metal in the transition metal complexes, which results in more covalent-like bonding behavior. The presence of the methyl groups on the NHC nitrogen results in only slightly more delocalized charge from the metal onto the ring, but there is significant redistribution of the charge on the ring. Saturation of the NHC ring had a much smaller effect on how the charge was distributed on the ring. The analysis of the bonding behavior of NHCs with various metal groups enables improved understanding of carbene-metal interactions to inform rational design of NHC-based systems.

Computational Predictions of the Hydrolysis of 2,4,6-Trinitrotoluene (TNT) and 2,4-Dinitroanisole (DNAN).

Hydrolysis is a common transformation reaction that can affect the environmental fate of many organic compounds. In this study, three proposed mechanisms of alkaline hydrolysis of 2,4,6-trinitrotoluene (TNT) and 2,4-dinitroaniline (DNAN) were investigated with plane-wave density functional theory (DFT) combined with ab initio and classical molecular dynamics (AIMD/MM) free energy simulations, Gaussian basis set DFT calculations, and correlated molecular orbital theory calculations. Most of the computations in this study were carried out using the Arrows web-based tools. For each mechanism, Meisenheimer complex formation, nucleophilic aromatic substitution, and proton abstraction reaction energies and activation barriers were calculated for the reaction at each relevant site. For TNT, it was found that the most kinetically favorable first hydrolysis steps involve Meisenheimer complex formation by attachment of OH- at the C1 and C3 arene carbons and proton abstraction from the methyl group. The nucleophilic aromatic substitution reactions at the C2 and C4 arene carbons were found to be thermodynamically favorable. However, the calculated activation barriers were slightly lower than in previous studies, but still found to be ΔG‡ ≈ 18 kcal/mol using PBE0 AIMD/MM free energy simulations, suggesting that the reactions are not kinetically significant. For DNAN, the barriers of nucleophilic aromatic substitution were even greater (ΔG‡ > 29 kcal/mol PBE0 AIMD/MM). The most favorable hydrolysis reaction for DNAN was found to be a two-step process in which the hydroxyl first attacks the C1 carbon to form a Meisenheimer complex at the C1 arene carbon C1-(OCH3)OH-, and subsequently, the methoxy anion (-OCH3) at the C1 arene carbon dissociates and the proton shuttles from the C1-OH to the dissociated methoxy group, resulting in methanol and an aryloxy anion.

Bond Dissociation Energies of Carbene-Carbene and Carbene-Main Group Adducts.

A range of carbene structures and their adducts with one another and with a selection of small-molecule electrophiles and nucleophiles were examined at the composite correlated molecular orbital theory G3MP2 level to explore ground-state "carbenic" structures, their stabilities, and reactivities. Differences between carbene general classification as a singlet electrophilic carbene or singlet nucleophilic carbene and their given reactivity are discussed. A key quantity is the carbon-carbon bond dissociation energy for carbene dimers or the carbene-adduct dissociation energy for other species. The carbene dimer bond dissociation energies span a wide range from 10 to 170 kcal/mol. The hydrogenation energies and singlet-triplet splitting were found to correlate best with the carbene's self-dimerization energy, whereas other descriptors do not. The proton and fluoride affinities of the carbenes alone prove inadequate for classifying reactivity among classes of carbenes. The self-dimerization bond dissociation energy, hydrogenation energy, and singlet-triplet splitting of various carbenes, despite sometimes large differences in proton affinity and other indicators of reactivity, provide usable metrics to correlate substantial amounts of thermodynamic and kinetic (reactivity) information regarding these structures.

Fluoro-nitrogen Cations.

The crystal structures of [NH3 F]+ [CF3 SO3 ]- , [NH2 F2 ]+ [SbF6 ]- , and [N2 F3 ]+ [Sb3 F16 ]- have been determined, representing the first structural characterizations of these simple fluoro-nitrogen cations. The influences of the hybridization of the central nitrogen atom and of the number of fluorine substituents on the N-F bond lengths are evaluated for the series N2 F+ , N2 F3 + , NF2 O+ , NH3 F+ , NH2 F2 + , and NF4 + . It is shown that the N-F bond length decreases from 1.40 Što 1.26 Šwith increasing fluorine substitution and increasing s-character of the nitrogen atom, and that unusual N-F bond lengths reported in the previous literature are caused by disorder problems.

Low-molecular-weight chromium-binding substance (LMWCr) may bind and carry Cr(III) from the endosome.

Trivalent chromium has been proposed to be transported in vivo from the bloodstream to the tissues via endocytosis by transferrin (Tf), the major iron transport protein in the blood. While Cr(III) loss from the Tf/Tf receptor complex after acidification to pH 5.5 has recently been shown to be sufficiently rapid to be physiologically relevant, the released Cr(III) still must exit the endosome during the time of the endocytosis cycle (circa 15 min). Cr(III) binds too slowly to small ligands such as citrate or ascorbate, or even EDTA, for such complexes to form and be transported from the endosome, while no trivalent ion transporters are known. However, the apo form of the peptide low-molecular-weight chromium-binding substance (LMWCr) can remove Cr(III) from Cr(III)2-Tf at neutral pH, albeit slowly, and LMWCr is known to be transported from cells after binding Cr(III), although the transporter is not known. LMWCr subsequently carries Cr(III) to the bloodstream ultimately for removal from the body in the urine. The rate of binding of Cr(III) to apoLMWCr was significantly enhanced in the presence of the Tf/Tf receptor complex. These results suggest that apoLMWCr may function to bind Cr(III) released in the endosomes for ultimate removal from the body as part of a Cr(III) detoxification process.

Electron paramagnetic spectrum of dimanganic human serum transferrin.

An EPR signal for Mn(III) bound to the metal transport protein transferrin has been detected for the first time. The temperature dependence and simulations of the EPR signal are consistent with the Mn(III) centers being six-coordinate in an elongated tetragonal environment. Thus, the incorporation of Mn(III) within the Tf active site does not vastly alter the coordination number or active site geometry relative to native Fe(III)2-Tf. This parallel mode EPR signal for Mn(III)2-Tf could prove valuable for future studies aimed at determining the physiological relevance of Mn(III)2-Tf.

X-ray structure of chromium(III)-containing transferrin: First structure of a physiological Cr(III)-binding protein.

Transferrin, the Fe(III) transport protein in mammalian blood, has been suggested to also serve as a Cr(III) transporter and as part of a Cr(III) detoxification system; however, the structure of the metal-binding sites has never been fully elucidated with bound Cr(III). Chromium(III)-transferrin was crystallized in the presence of the synergistic anion malonate. In the crystals, the protein exists with a closed C-terminal lobe containing a Cr(III) ion and an open, unoccupied N-terminal lobe. The overall structure and the metal ion environments are extremely similar to those of Fe(III)- and Ti(IV)-containing transferrin crystallized under comparable conditions. The octahedral coordination about the Cr(III) is comprised of four ligands provided by the protein (two tyrosine residues, a histidine residue, and an aspartate residue) and a chelating malonate anion. This represents the first crystal structure of a Cr(III)-containing protein that binds Cr(III) as part of its physiological function.

Significance of conformation changes during the binding and release of chromium(III) from human serum transferrin.

Trivalent chromium has been proposed to be transported in vivo from the bloodstream to the tissues via endocytosis by transferrin (Tf), the major iron transport protein in the blood. While both Cr(III) binding and release from Tf have been proposed to be too slow to be physiologically relevant, recent kinetic studies under physiological conditions demonstrate that Cr(III) binding and release are sufficiently fast to occur during the time of the endocytosis cycle (circa 15 min). Consequently, the release of Cr(III) from human and bovine serum Tf has been examined under conditions mimicking an endosome during endocytosis. These studies have also found that Cr(III)2-Tf can exist in multiple conformations giving rise to different spectroscopic properties and different rates of Cr(III) release. Time-dependent spectroscopic studies of the binding and release of Cr(III) from human serum Tf have been used to identify three different conformations of Cr(III)2-Tf. The conformation of Cr(III)2-Tf used in most previous studies forms too slowly to be physiologically relevant and slowly releases Cr(III) in endosomal pH range. The conformation formed between 5 min to 60 min after the addition of Cr(III) to apoTf at pH 7.4 in 25 mM bicarbonate resembles the conformation of Cr(III)2-Tf in its complex with Tf receptor (TfR) and loses Cr(III) rapidly at endosomal pH, although not as fast as the Tf-TfR complex. The significance of these conformations and the potential role of Tf in detoxification of Cr(III) are described.

Release of trivalent chromium from serum transferrin is sufficiently rapid to be physiologically relevant.

Transferrin, the major iron transport protein in the blood, apparently also transports trivalent chromium in vivo via endocytosis. Recent in vitro studies have, however, suggested that the release of chromic ions from serum transferrin is too slow to be biologically relevant. Consequently, the release of chromium(III) from human serum transferrin has been examined under conditions mimicking an endosome during endocytosis. At pH 4.5 and 5.5, the release of Cr(III) from transferrin occurs rapidly from the weak binding site. While appreciably slower, the release of Cr(III) from the tighter site in the presence of biological chelating agents is potentially sufficiently fast to be physiologically relevant. When Cr(III)-loaded transferrin is added to soluble transferrin receptor, the interaction with the receptor results in Cr(III) in both the weak and tight binding sites giving rise to an EPR signal similar to that of the weak binding site; concurrently, the loss of Cr(III) from both binding sites becomes rapid at acidic pH, more rapid than from either site in the absence of the receptor. Loss of Cr(III) from the transferrin-transferrin receptor complex, thus, is easily sufficiently rapid for transferrin to serve as the physiological transporter of Cr(III) from the bloodstream to the tissues. However, detailed studies of conformational changes of transferrin associated with the binding and release of chromium along with investigations of how and at what rate Cr(III) is transported from the endosome will be required before this question of whether transferrin transport Cr(III) in vivo can be definitively resolved.

The use of chromium(III) complexes to enhance peptide protonation by electrospray ionization mass spectrometry.

The addition of trivalent chromium, Cr(III), reagents to peptide solutions can increase the intensity of doubly protonated peptides, [M + 2H]2+ , through electrospray ionization (ESI). Three model heptapeptides were studied: neutral (AAAAAAA), acidic (AAEEEAA), and basic (AAAKAAA). The neutral and acidic peptides form almost no 2+ ions in the absence of Cr(III). Twenty Cr(III) complexes were used as potential enhanced protonation reagents, including 11 complexes with nonlabile ligands and nine with labile ligands. The complexes that provide the most abundant [M + 2H]2+ , the greatest [M + 2H]2+ to [M + H]+ ratio, and the cleanest mass spectra are [Cr(H2 O)6 ](NO3 )3 ·3H2 O and [Cr(THF)3 ]Cl3 . Anions in Cr(III) reagents can also affect the intensity of [M + 2H]2+ and the [M + 2H]2+ to [M + H]+ ratio through cation-anion interactions. The influence of anions on the extent of peptide protonation follows the trend ClO4 -  Ëƒ SO4 2-  Ëƒ Br-  Ëƒ Cl-  Ëƒ F-  ≈ NO3 - . Solvent effects and complexes with varying number of water ligands were investigated to study the importance of water in enhanced protonation. Aqueous solvent systems and Cr(III) complexes that have at least one bound water ligand in solution must be used for successful increase in the intensity of [M + 2H]2+ , which indicates that water is involved in the mechanism of Cr(III)-induced enhanced protonation. The ESI source design is also important because no enhanced protonation was observed using a Z-spray source. The current results suggest that this Cr(III)-induced effect occurs during the ESI desolvation process.