A comprehensive DFT study of the electrocatalytic oxidation of ammonia to dinitrogen by a ruthenium polypyridyl complex, [(tpy)(bpy)Ru II (NH 3 )] 2+ (a), and its NMe 2 -substituted derivative (b) is presented. The thermodynamics and kinetics of electron (ET) and proton transfer (PT) steps and transition states are calculated. NMe 2 substitution on bpy reduces the ET steps on average 8 kcal/mol for complex b as compared to a. The calculations indicate that N−N formation occurs by ammonia nucleophilic attack/Htransfer via a nitrene intermediate rather than a nitride intermediate. Comparison of the free energy profiles of Ru-b with its first-row Fe congener reveals that the thermodynamics are less favorable for the Feb model, especially for ET steps. The N−H bond dissociation free energies (BDFEs) for NH 3 to form N 2 show the following trend: Ru-b < Ru-a < Fe-b, indicating the lowest and most favorable BDFEs for Rub complex.

This paper reports a density functional theory study of 3d transition-metal methoxide complexes with potentially redox-noninnocent pincer supporting ligands for methane C-H bond activation to form methanol (LM-OMe + CH → LM-Me + CHOH). The three types of tridentate pincer ligands [terpyridine (NNN), bis(2-pyridyl)phenyl-C,N,N' (NCN), and 2,6-bis(2-phenyl)pyridine-N,C,C' (CNC)] and different first-row transition metals (M = Ti, V, Cr, Mn, Fe, Co, Ni, and Cu) are used to elucidate the reaction mechanism as well as the effect of the metal identity on the thermodynamics and kinetics of a methane activation reaction. Spin-density analysis indicates that some of these systems, the NNN and NCN ligands, have redox-noninnocent character. A four-centered, kite-shaped transition state, σ-bond metathesis, or oxidative hydrogen migration has been found for methane activation for the complexes studied. Calculations suggest that the d electron count is a more significant factor than the metal formal charge in controlling the thermodynamics and kinetics of C-H activation and late 3d metal methoxides, with high d counts preferred. Notably, early-to-middle metals tend toward oxidative hydrogen migration and late metals undergo a pathway that is more akin to σ-bond metathesis, suggesting that metal methoxide complexes that favor σ-bond metathesis pathways for methane activation will yield lower barriers for C-H activation.

No abstract

Density functional theory is used to analyze methane C−H activation by neutral and cationic nickel−methoxide complexes. This research seeks to identify strategies to reduce high barriers through evaluation of supporting ligand modifications, solvent polarity, overall charge of complex, metal identity, and counterion effects. A Ni−OMe pincer complex was substituted at the para positions of the phenyl and pyridine rings with different electron-donating and -withdrawing groups, and the results showed that resonance effects did not significantly change the ΔG ⧧ act and ΔG rxn compared to the reference complex, which was confirmed by frontier orbitals plots and Hammett graphs. The effect of solvent polarity is greater upon the thermodynamics more than transition state energies. Among modeled supporting ligands, bipyridine was the most promising. Overall, neutral complexes are calculated to have lower activation barriers than the cationic complexes. For both neutral and cationic complexes, the methane C−H activations proceed via a σ-bond metathesis rather than an oxidative addition/reductive elimination pathway. Barrier free energies for Ni complexes and its precious metal Pt complex congener are comparable; the thermodynamics for the latter are closer to thermoneutral than the Ni complexes. Neutralizing the cationic catalyst models by a counterion, BF 4 − , has a considerable impact on reducing the methane activation barrier free energy. Computed Ni−C bond dissociation free energies suggest radical pathways are likely competitive.

No abstract

Using density functional theory (DFT), the effects of appended s-block metal ion crown ethers upon the redox properties of the following nitridomanganese(V) salen complexes were investigated: [(salen)Mn V (N)(M n+ -crown ether)] n+ (salen = N,N′bis(salicydene)ethylenediamine; M = Na + , K + , Ba 2+ , and Sr 2+ for 1Na, 1K, 1Ba, and 1Sr, respectively; A = complex without M n+crown ether and B = without M n+ ). NBO analysis of the MnN bond orders, optimized bond lengths, and stretching frequencies changes upon oxidation for all species show that for A, B, and 1Na MnN has more nitridyl character while a nitride form is more significant for 1K, 1Ba, and 1Sr. The results reveal that ΔG rxn (e − ) and thus E 1/2 are quite sensitive to the point charge (q) of the s-block metal ions (1 for K + /Na + and 2 for Ba 2+ /Sr 2+ ). Computations suggest that the degree of delocalization of the HOMO electrons on the supporting ligand is modified by the chelated s-block metal ion. Methane activation by A •+ , 1K •+ , and 1Ba •+ complexes proceeds via a hydrogen atom transfer (HAT) pathway with reasonable barriers for all complexes with ∼4 kcal/mol difference in energy. The molecular electrostatic potential (MEP) maps indicate a shift in redox potential imposed by the nonredox active cations by altering the electrostatic potential of the complexes. Computations show that the complexes with higher point charge of the incorporated metal ions result in higher N−H bond BDFEs. Changes in predicted properties as a function of continuum solvent dielectric constant suggest that the primary effect of the appended s-block ion is via "through space" interactions.

To select the most promising screening hits from antibody and VHH display campaigns for subsequent in-depth profiling and optimization, it is highly desirable to assess and select sequences on properties beyond only their binding signals from the sorting process. In addition, developability risk criteria, sequence diversity and the anticipated complexity for sequence optimization are relevant attributes for hit selection and optimization. Here, we describe an approach for the in silico developability assessment of antibody and VHH sequences. This method not only allows for ranking and filtering multiple sequences with regard to their predicted developability properties and diversity, but also visualizes relevant sequence and structural features of potentially problematic regions and thereby provides rationales and starting points for multi-parameter sequence optimization.

No abstract