Enabling Molecular-Level Computational Description of Redox and Proton-Coupled Electron Transfer Reactions of Samarium Diiodide

Samarium diiodide (SmI2, Kagan’s reagent) is a one-electron reductant with applications ranging from organic synthesis to nitrogen fixation. Highly inaccurate relative energies of redox and proton-coupled electron transfer (PCET) reactions of Kagan’s reagent are predicted by pure and hybrid density functional approximations (DFAs) when only scalar relativistic effects are accounted for. Calculations including spin–orbit coupling (SOC) show that the SOC-induced differential stabilization of the Sm(III) versus the Sm(II) ground state is little affected by ligands and solvent, and a standard SOC correction derived from atomic energy levels is thus included in the reported relative energies. With this correction, selected meta-GGA and hybrid meta-GGA functionals predict Sm(III)/Sm(II) reduction free energies to within 5 kcal/mol of the experiment. Considerable discrepancies remain, however, in particular for the PCET-relevant O–H bond dissociation free energies, for which no regular DFA is within 10 kcal/mol of the experiment or CCSD(T). The main cause behind these discrepancies is the delocalization error, which leads to excess ligand-to-metal electron donation and destabilizes Sm(III) versus Sm(II). Fortunately, static correlation is unimportant for the present systems, and the error may be reduced by including information from virtual orbitals via perturbation theory. Contemporary, parametrized double-hybrid methods offer promise as companions to experimental campaigns in the further development of the chemistry of Kagan’s reagent.publishedVersio

Automated in Silico Design of Homogeneous Catalysts

Catalyst discovery is increasingly relying on computational chemistry, and many of the computational tools are currently being automated. The state of this automation and the degree to which it may contribute to speeding up development of catalysts are the subject of this Perspective. We also consider the main challenges associated with automated catalyst design, in particular the generation of promising and chemically realistic candidates, the tradeoff between accuracy and cost in estimating the catalytic performance, the opportunities associated with automated generation and use of large amounts of data, and even how to define the objectives of catalyst design. Throughout the Perspective, we take a cross-disciplinary approach and evaluate the potential of methods and experiences from fields other than homogeneous catalysis. Finally, we provide an overview of software packages available for automated in silico design of homogeneous catalysts.publishedVersio

What is the Role of Leadership in ICT Companies?

ABSTRACT While there exists a range of studies on the issue of leadership in general, research on leadership in the context of information and communication technology (ICT) firms is rather limited. This is an extremely important topic because ICT firms experience quite different circumstances of operation than those faced by non-ICT firms. Uncertainty and complexity characterize ICT firms which influence strategies of leadership. As a result, leaders typically know too little or often have volumes of unreliable information about the future. As a result, leadership of contemporary ICT firms is an extremely complex and interesting area of research. The aim of the thesis is to understand the role of leadership in ICT firms, especially in relation to issues of uncertainty and complexity. This question is approached through a blend of secondary data and theoretical analysis coupled with a limited set of interviews with leaders in Oslo. The research approach adopted was interpretive as the aim was to understand how leadership at one level is shaped by particular socio-cultural-market conditions, and at another level is a function of personality and individual issues. It was felt that such issues can not be adequately grasped through a positivist approach. Leaders of ICT firms need to motivate the employees to stay in the firm and to perform optimal work. Leaders of ICT companies also need to trust their employees to a large degree, so that the employees can use their full potential in contributing to the firm. Furthermore, leaders of ICT firms need to be playful in their approach to work because it contributes to motivation and learning. In addition, leaders of ICT firms need intelligent employees that understand technology, its implications and use. The leaders need to be intelligent themselves so that they can understand technology, the real issues their employees face, and how to organize the firm efficiently. The testing of software should be done as soon as possible after each minor piece of programming to ensure that the program works so far. Thus leaders need to install procedures which reward error-free program pieces and slightly punish the creation of noticed bugs. The development should be divided into features of the program rather than phases of the waterfall approach. In this way the most important features can be developed first, which spares confusing details to later on. Thus leaders need to organize projects, buffer times and timelines according to estimations and expectations based on what the program is to do first, then next, and so on instead of focusing on separate specification, design, programming, and testing phases. The theoretical contribution of the thesis is in the form of a model of leadership that has been inductively derived based on the empirical analysis. The model firstly identifies four key contextual conditions that influence leadership approaches. These relate to markets, technology, the physical environment and the political setting. These contextual conditions shape leadership styles. Eight dimensions of leadership style are identified and discussed. Trust, motivation, playfulness, and intelligence are seen to be opposed to power, authority, bureaucracy and risk, respectively. For example, gaining more trust implies letting go of power. While in ICT firms, the factors of trust, motivation, playfulness and intelligence seem to be more relevant, the other four are seen as relevant for leadership of non-ICT firms

DENOPTIM: Software for Computational de Novo Design of Organic and Inorganic Molecules

A general-purpose software package, termed DE Novo OPTimization of In/organic Molecules (DENOPTIM), for de novo design and virtual screening of functional molecules is described. Molecules of any element and kind, including metastable species and transition states, are handled as chemical objects that go beyond valence-rules representations. Synthetic accessibility of the generated molecules is ensured via detailed control of the kinds of bonds that are allowed to form in the automated molecular building process. DENOPTIM contains a combinatorial explorer for screening and a genetic algorithm for global optimization of user-defined properties. Estimates of these properties may be obtained to form the fitness function (figure of merit or scoring function) from external molecular modeling programs via shell scripts. Examples of a range of different fitness functions and DENOPTIM applications, including an easy-to-do test case, are described. DENOPTIM is available as Open Source from https://github.com/denoptim-project/DENOPTIM.acceptedVersio

Pyridine-Stabilized Fast-Initiating Ruthenium Monothiolate Catalysts for Z-Selective Olefin Metathesis

Pyridine as a stabilizing donor ligand drastically improves the performance of ruthenium monothiolate catalysts for olefin metathesis in comparison with previous versions based on a stabilizing benzylidene ether ligand. The new pyridine-stabilized ruthenium alkylidenes undergo fast initiation and reach appreciable yields combined with moderate to high Z selectivity in self-metathesis of terminal olefins after only a few minutes at room temperature. Moreover, they can be used with a variety of substrates, including acids, and promote self-metathesis of ω-alkenoic acids. The pyridine-stabilized ruthenium monothiolate catalysts are also efficient at the high substrate dilutions of macrocylic ring-closing metathesis and resist temperatures above 100 °C during catalysis.publishedVersio

Synapsin-Dependent Vesicle Recruitment Modulated by Forskolin, Phorbol Ester and Ca2+ in Mouse Excitatory Hippocampal Synapses

Repeated release of transmitter from presynaptic elements depends on stimulus-induced Ca2+ influx together with recruitment and priming of synaptic vesicles from different vesicle pools. We have compared three different manipulations of synaptic strength, all of which are known to increase short-term synaptic efficacy through presynaptic mechanisms, in the glutamatergic CA3-to-CA1 stratum radiatum synapse in the mouse hippocampal slice preparation. Synaptic responses elicited from the readily releasable vesicle pool during low-frequency synaptic activation (0.1 Hz) were significantly enhanced by both the adenylate cyclase activator forskolin, the priming activator β-phorbol-12,13-dibutyrate (PDBu) and 4 mM [Ca2+]o′ whereas during 20 Hz stimulation, the same manipulations reduced the time needed to reach the peak and increased the magnitude of the resulting frequency facilitation. In contrast, paired-pulse facilitations were unchanged in the presence of forskolin, decreased by 4 mM [Ca2+]o and essentially abolished by PDBu. The subsequent delayed response enhancement (DRE) responses, elicited during continuous 20 Hz stimulations and mediated by recruited vesicles, were enhanced by forskolin, essentially unchanged by PDBu and slightly decreased by 4 mM [Ca2+]o· Similar experiments done on slices devoid of the vesicle-associated synapsin I and II proteins indicated that synapsin I/II-induced enhancements of vesicle recruitment were restricted to Ca2+-induced frequency facilitations and forskolin-induced enhancements of the early DRE phase, whereas the proteins had minor effects during PDBu-treatment and represented constraints on late Ca2+-induced responses. The data indicate that in these glutamatergic synapses, the comparable enhancements of single synaptic responses induced by these biochemical mechanisms can be transformed during prolonged synaptic stimulation into highly distinct short-term plasticity patterns, which are partly dependent on synapsins I/II

Phosphine-Based Z‑Selective Ruthenium Olefin Metathesis Catalysts

Whereas a number of highly Z-selective ruthenium-based olefin metathesis catalysts bearing N-heterocyclic carbene ligands have been reported in recent years, Zselectivity has so far been difficult to achieve for phosphinebased catalysts. Guided by predictive density functional theory (DFT) calculations, we have developed phosphine-based ruthenium olefin metathesis catalysts giving 70−95% of the Zisomer product in homocoupling of terminal alkenes such as allylbenzene, 1-octene, allyl acetate, and 2-allyloxyethanol. Starting from a moderately selective catalyst, [P(Cy)3](-S-2,4,6-Ph-C6H2)ClRu(==CH-o-OiPrC6H4) (4, Cy = cyclohexyl, iPr = isopropyl), obtained by substituting a chloride of the Hoveyda−Grubbs first-generation catalyst with 2,4,6- triphenylbenzenethiolate, we moved on to replace Cl and PCy3 by chelating, anionic phosphine ligands. Such ligands increase selectivity by limiting rotation around the P−Ru bond and by specifically directing the steric bulk of the phosphine substituents toward the selectivity-inducing thiolate ligand. In particular, DFT calculations predicted that o-(dialkylphosphino)phenolate ligands should improve selectivity and activity compared to 4. The most promising of these compounds (8b), based on the o-(ditert- butylphosphino)phenolate ligand, directs the two P-bonded tert-butyl substituents toward the 2,4,6-triphenylbenzenethiolate and has little steric hindrance trans to the thiolate. This compound metathesizes terminal olefins such as allylbenzene and 1- octene with Z-selectivities above 80% and allylacetate above 90%. Although these phosphine-based ruthenium monothiolate catalysts in general achieve somewhat lower activities and Z-selectivities than their second-generation counterparts, they also offer examples giving less substrate and product isomerization and thus higher yields.publishedVersio

The Janus face of high trans-effect carbenes in olefin metathesis: gateway to both productivity and decomposition

Ruthenium–cyclic(alkyl)(amino)carbene (CAAC) catalysts, used at ppm levels, can enable dramatically higher productivities in olefin metathesis than their N-heterocyclic carbene (NHC) predecessors. A key reason is the reduced susceptibility of the metallacyclobutane (MCB) intermediate to decomposition via β-H elimination. The factors responsible for promoting or inhibiting β-H elimination are explored via density functional theory (DFT) calculations, in metathesis of ethylene or styrene (a representative 1-olefin) by Ru–CAAC and Ru–NHC catalysts. Natural bond orbital analysis of the frontier orbitals confirms the greater strength of the orbital interactions for the CAAC species, and the consequent increase in the carbene trans influence and trans effect. The higher trans effect of the CAAC ligands inhibits β-H elimination by destabilizing the transition state (TS) for decomposition, in which an agostic MCB Cβ–H bond is positioned trans to the carbene. Unproductive cycling with ethylene is also curbed, because ethylene is trans to the carbene ligand in the square pyramidal TS for ethylene metathesis. In contrast, metathesis of styrene proceeds via a ‘late’ TS with approximately trigonal bipyramidal geometry, in which carbene trans effects are reduced. Importantly, however, the positive impact of a strong trans-effect ligand in limiting β-H elimination is offset by its potent accelerating effect on bimolecular coupling, a major competing means of catalyst decomposition. These two decomposition pathways, known for decades to limit productivity in olefin metathesis, are revealed as distinct, antinomic, responses to a single underlying phenomenon. Reconciling these opposing effects emerges as a clear priority for design of robust, high-performing catalysts.publishedVersio

Bimolecular Coupling in Olefin Metathesis: Correlating Structure and Decomposition for Leading and Emerging Ruthenium−Carbene Catalysts

Bimolecular catalyst decomposition is a fundamental, long-standing challenge in olefin metathesis. Emerging ruthenium–cyclic(alkyl)(amino)carbene (CAAC) catalysts, which enable breakthrough advances in productivity and general robustness, are now known to be extraordinarily susceptible to this pathway. The details of the process, however, have hitherto been obscure. The present study provides the first detailed mechanistic insights into the steric and electronic factors that govern bimolecular decomposition. Described is a combined experimental and theoretical study that probes decomposition of the key active species, RuCl2(L)(py)(═CH2) 1 (in which L is the N-heterocyclic carbene (NHC) H2IMes, or a CAAC ligand: the latter vary in the NAr group (NMes, N-2,6-Et2C6H3, or N-2-Me,6-iPrC6H3) and the substituents on the quaternary site flanking the carbene carbon (i.e., CMe2 or CMePh)). The transiently stabilized pyridine adducts 1 were isolated by cryogenic synthesis of the metallacyclobutanes, addition of pyridine, and precipitation. All are shown to decompose via second-order kinetics at −10 °C. The most vulnerable CAAC species, however, decompose more than 1000-fold faster than the H2IMes analogue. Computational studies reveal that the key factor underlying accelerated decomposition of the CAAC derivatives is their stronger trans influence, which weakens the Ru−py bond and increases the transient concentration of the 14-electron methylidene species, RuCl2(L)(═CH2) 2. Fast catalyst initiation, a major design goal in olefin metathesis, thus has the negative consequence of accelerating decomposition. Inhibiting bimolecular decomposition offers major opportunities to transform catalyst productivity and utility, and to realize the outstanding promise of olefin metathesis.publishedVersio