Biomimetic nitrogen fixation provides an attractive alternative for the century-old Haber-Bosch process; however, the performance of the currently available molecular biomimetic catalysts is very limited. In this work, we are aiming to understand the catalytic cycle of one of the most promising biomimetic complex families that can be the cornerstone of future computer-aided rational design of biomimetic complexes. We calculate the Gibbs free energy of all elementary reaction steps of homogeneous dinitrogen reduction to NH on single-site iron complexes with EPPP tetradentate ligands (E = B, Si). We examine all possible mechanisms and identify the dominant pathways and the critical elementary steps that can be rate-determining in the catalytic cycle of nitrogen fixation. We find that the catalytic mechanism depends on the applied ligand and that the distal pathway observed with E = B is the most favorable route regarding the catalytic performance. Our calculations also reveal the lack of thermodynamic driving force in the last steps of the catalytic cycle that can be responsible for the low catalytic activity of the studied biomimetic catalysts. Our results can serve as a starting point for the rational design of biomimetic complexes, which should focus on establishing a steadily decreasing Gibbs free energy profile, as suggested by the Sabatier principle.

Nitrogen reduction reaction (N2RR) carried out on biomimetic catalytic systems is considered to be a promising alternative for the traditional Haber–Bosch ammonia synthesis. Unfortunately, the selectivity of the currently known biomimetic catalysts is poor, as they also catalyze the unproductive hydrogen evolution reaction (HER). In the present computational study, we examine the HER activity of early N2RR intermediates in EP3 (E = B, Si) ligated single-site biomimetic iron complexes by calculating and comparing the activation Gibbs free energies of HER and N2RR elementary steps. We find that, in contrast to previous suggestions, early N2RR intermediates are not likely sources of HER under turnover conditions, as the barriers of the competing N2RR steps are significantly lower. Consequently, future research should focus on preventing other potential HER mechanisms, e.g., hydride formation, rather than accelerating the consumption of early N2RR intermediates as proposed earlier to design more efficient biomimetic catalysts.

Synthetic Fe nitrogenases are promising catalysts for atmospheric pressure ammonia synthesis. However, their catalytic efficiency is severely limited by the accompanying hydrogen evolution reaction (HER) and fast catalyst deactivation. In order to reveal the origin of these undesired transformations, we study potential reaction routes of HER, catalyst deactivation, and nitrogen reduction reaction (N2RR) by density functional theory in combination with microkinetic modeling, using a triphosphino-silyl ligated iron complex as model system. Our results show that the most favorable HER cycle is initiated by H2 molecules originated from the noncatalytic reaction of acid and reductant reagents, which can coordinate to a vacant binding site of an Fe complex. Thus, H2 coordination competes with the N2 coordination step of the desired N2RR catalytic cycle, and the resulting Fe–H2 complex can be protonated at both hydrogen atoms to release two H2 molecules. The proposed mechanism, called autocatalytic hydrogen evolution reaction (aHER), explains all experimentally observed results including catalyst deactivation, as aHER intermediates can be easily converted into thermodynamically stable, catalytically inactive monohydrides. Our results suggest that improved efficacy of synthetic Fe nitrogenases can be achieved by several ways: (i) proper ligand modifications hindering the formation of Fe–H2 complexes, (ii) suppressing the noncatalytic H2 formation in the catalytic mixture by different reagent choice, and (iii) using flow or semiflow reactor setup instead of batch reactors and keep the proton and electron reagent excess low.

The synthesis of variously substituted indolo[2,3c]quinolin-6(7H)-ones was developed via Pd-catalyzed intramolecular C−H arylation. This method highlights a strategy for preparing indoloquinoline precursors bearing versatile functional groups and provides a new approach for the synthesis of antimalarial isoneocryptolepine analogues. The plausible ring closure mechanism was examined with quantum chemical calculations, where a trigonal bipyramidal concerted metalation− deprotonation transition state is presumable.

The binding of small gas molecules such as NO and CO plays a major role in the signaling routes of the human body. The sole NO-receptor in humans is soluble guanylyl cyclase (sGC) -a histidine-ligated heme protein, which, upon NO binding, activates a downstream signaling cascade. Impairment of NO-signaling is linked, among others, to cardiovascular and inflammatory diseases. In the present work, we use a combination of theoretical tools such as MD simulations, high-level quantum chemical calculations and hybrid QM/MM methods to address various aspects of NO binding and to elucidate the most likely reaction paths and the potential intermediates of the reaction. As a model system, the H-NOX protein from Shewanella oneidensis (So H-NOX) homologous to the NO-binding domain of sGC is used. The signaling route is predicted to involve NO binding to form a six-coordinate intermediate heme-NO complex, followed by relatively facile His decoordination yielding a fivecoordinate adduct with NO on the distal side with possible isomerization to the proximal side through binding of a second NO and release of the first one. MD simulations show that the His sidechain can quite easily rotate outward into solvent, with this motion being accompanied in our simulations by shifts in helix positions that are consistent with this decoordination leading to significant conformational change in the protein.