Copper‐Based Photosensitisers in Water Reduction: A More Efficient In Situ Formed System and Improved Mechanistic Understanding

The reduction of water has been achieved through a non‐noble‐metal‐based homogeneous catalyst system that is formed in situ. Optimisation of the ligand quantities increased catalyst turnover numbers compared to preformed complexes. Mechanistic studies confirm a heteroleptic Cu complex as the active photosensitiser (PS) and an in situ formed Fe–phosphido dimer complex as the water reduction catalyst. The in situ method has been used to screen a range of ligands for the active PS, which has led to the identification a number of structural features important to longevity and performance.     

Quantum Mechanics/Molecular Mechanics Modeling of Enzymatic Processes: Caveats and Breakthroughs

Nature has developed large groups of enzymatic catalysts with the aim to transfer substrates into useful products, which enables biosystems to perform all their natural functions. As such, all biochemical processes in our body (we drink, we eat, we breath, we sleep, etc.) are governed by enzymes. One of the problems associated with research on biocatalysts is that they react so fast that details of their reaction mechanisms cannot be obtained with experimental work. In recent years, major advances in computational hardware and software have been made and now large (bio)chemical systems can be studied using accurate computational techniques. One such technique is the quantum mechanics/molecular mechanics (QM/MM) technique, which has gained major momentum in recent years. Unfortunately, it is not a black‐box method that is easily applied, but requires careful set‐up procedures. In this work we give an overview on the technical difficulties and caveats of QM/MM and discuss work‐protocols developed in our groups for running successful QM/MM calculations.     

How a Redox‐Innocent Metal Promotes the Formal Reductive Elimination of Biphenyl Using Redox‐Active Ligands

One of the most compelling strategies for utilizing redox‐active ligands is to perform redox events at the ligands to avoid accessing prohibitively high energy oxidation states at the metal center. This has been demonstrated experimentally in many systems, yet there is little understanding of the fundamental electronic structures involved with these transformations or how to control them. Here, the reductive elimination of biphenyl from [M(isq)₂Ph₂] (M=Ti, Zr, and Hf and isq=2,4‐di‐tert‐butyl‐6‐tert‐butyliminosemiquinone) was studied computationally. It was found that the metal remains in the +IV oxidation state and all redox chemistry was mediated by the redox‐active ligands. Two types of electron‐transfer mechanisms were identified, an asymmetric unpaired electron transfer (UET) and a symmetric pairwise electron transfer (PET), the former always being lower in energy. The energetic differences between these two mechanisms were explained through simple molecular orbital theory arguments. Despite the metal’s redox‐inactivity, it still has a marked influence on the calculated energetics of the reaction, with the Ti systems being much more reactive than the Zr/Hf systems. This primarily originates from the shorter Ti?Ph bond, which leads to a stronger filled‐filled interaction between these ligands at the reactant state. This greater reactant destabilization leads to the lower activation energies.     

Reactivity and Operational Stability of N‐Tailed TAMLs through Kinetic Studies of the Catalyzed Oxidation of Orange II by H2O2: Synthesis and X‐ray Structure of an N‐Phenyl TAML

The catalytic activity of the N‐tailed (“biuret”) TAML (tetraamido macrocyclic ligand) activators [Fe{4‐XC₆H₃‐1,2‐( N COCMe₂ N CO)₂NR}Cl]^2? ( 3 ; N atoms in boldface are coordinated to the central iron atom; the same nomenclature is used in for compounds 1 and 2 below), [X, R=H, Me ( a ); NO₂, Me ( b ); H, Ph ( c )] in the oxidative bleaching of Orange II dye by H₂O₂ in aqueous solution is mechanistically compared with the previously investigated activator [Fe{4‐XC₆H₃‐1,2‐( N COCMe₂ N CO)₂CMe₂}OH₂]^? ( 1 ) and the more aggressive analogue [Fe(Me₂C{CON(1,2‐C₆H₃‐4‐X) N CO}₂)OH₂]^? ( 2 ). Catalysis by 3 of the reaction between H₂O₂ and Orange II (S) occurs according to the rate law found generally for TAML activators (v=k_Ik_II[Fe^III][S][H₂O₂]/(k_I[H₂O₂]+k_II[S]) and the rate constants k_I and k_II at pH 7 both decrease within the series 3 b > 3 a > 3 c . The pH dependency of k_I and k_II was investigated for 3 a . As with all TAML activators studied to‐date, bell‐shaped profiles were found for both rate constants. For k_I, the maximal activity was found at pH 10.7 marking it as having similar reactivity to 1 a . For k_II, the broad bell pH profile exhibits a maximum at pH about 10.5. The condition k_I?k_II holds across the entire pH range studied. Activator 3 b exhibits pronounced activity in neutral to slightly basic aqueous solutions making it worthy of consideration on a technical performance basis for water treatment. The rate constants k_i for suicidal inactivation of the active forms of complexes 3 a – c were calculated using the general formula ln([S₀]/[S_∞])=(k_II/k_i)[Fe^III]; here [Fe^III], [S₀], and [S_∞] are the total catalyst concentration and substrate concentration at time zero and infinity, respectively. The synthesis and X‐ray characterization of 3 c are also described.     

Origin of the Enantioselectivity in Organocatalytic Michael Additions of β‐Ketoamides to α,β‐Unsaturated Carbonyls: A Combined Experimental,Spectroscopic and Theoretical Study

The organocatalytic enantioselective conjugate addition of secondary β‐ketoamides to α,β‐unsaturated carbonyl compounds is reported. Use of bifunctional Takemoto’s thiourea catalyst allows enantiocontrol of the reaction leading either to simple Michael adducts or spirocyclic aminals in up to 99 % ee. The origin of the enantioselectivity has been rationalised based on combined DFT calculations and kinetic analysis. This study provides a deeper understanding of the reaction mechanism, which involves a predominant role of the secondary amide proton, and clarifies the complex interactions occurring between substrates and the catalyst.     

Synthesis of Peptides by Silver‐Promoted Coupling of Carboxylates and Thioamides: Mechanistic Insight from Computational Studies

The mechanism of the recently described N→C direction peptide synthesis through silver‐promoted coupling of N‐protected amino acids with thioacetylated amino esters was explored by using density functional theory. Calculation of the potential energy surfaces for various pathways revealed that the reaction proceeds through silver‐assisted addition of the carboxylate to the thioamide, which is followed by deprotonation and silver‐mediated extrusion of sulfur as Ag₂S. The resulting isoimide is the key intermediate, which subsequently rearranges to an imide through a concerted pericyclic [1,3]‐acyl shift (O–sp²N 1,3‐acyl migration). The proposed mechanism clearly emphasises the requirement of two equivalents of Ag^I and basic reaction conditions, which is in full agreement with the experimental findings. Alternative rearrangement pathways involving only one equivalent of Ag^I or through O–sp³N 1,3‐acyl migration can be excluded. The computations further revealed that peptide couplings involving thioformamides require significant conformational changes in the intermediate isoformimide, which slow down the rearrangement process.     

Construction of Fused Pyrrolidines and β‐Lactones by Carbene‐Catalyzed C−N,C−C,and C−O Bond Formations

A carbene‐catalyzed intermolecular C−N bond formation, which initiates a highly selective cascade reaction for the synthesis of pyrrolidine fused β‐lactones, is disclosed. The nitrogen‐containing bicyclic β‐lactone products are obtained with good yields and excellent stereoselectivities. Synthetic transformations of the reaction products into useful functional molecules, such as amino catalysts, can be efficiently realized under mild reaction conditions. Mechanistically, this study provides insights into modulating the reactivities of heteroatoms, such as nitrogen atoms, in challenging carbene‐catalyzed asymmetric carbon–heteroatom bond‐forming reactions.     

Superhard silicon nanospheres

Successful deposition and mechanical probing of nearly spherical, defect-free silicon nanospheres has been accomplished. The results show silicon at this length scale to be up to four times harder than bulk silicon. Detailed measurements of plasticity evolution and the corresponding hardening response in normally brittle silicon is possible in these small volumes. Based upon a proposed length scale related to the size of nanospheres in the 20- radii range, a prediction of observed hardnesses in the range of 20- is made. The ramifications of this to computational materials science studies on identical volumes are discussed.