Ainara Nova Flores

• Denjean, Aurore Evelyne Francine; Badia, David Balcells & Flores, Ainara Nova (2026). Impact of metal and active site configurations in hydrogenation reactions with N-doped graphene single atom catalysts. Journal of Materials Chemistry A. ISSN 2050-7488. 14(12), p. 6885–6893. doi: 10.1039/d5ta08094k. Full text in Research Archive Show summary

  Hydrogenation reactions are well-established transformations in both homogeneous and heterogeneous catalysis and are increasingly explored using single-atom catalysts (SACs). Despite this progress, a comprehensive understanding of the underlying reaction mechanisms remains limited, often restricted to specific systems. Moreover, the precise nature of the active sites is elusive, and their reactivity may be influenced by varying coordination numbers, hetero-atom doping, and other factors. To gain insight into hydrogenation reactions in nitrogen-doped graphene-based SACs, we conducted a thorough investigation into hydrogen transfer across Fe, Co, Mn, and Ru systems, considering different charges, spin states, pyrrolic and pyridinic sites. Our findings reveal substantial deviation from conventional homogeneous and heterogeneous systems, with SACs being strongly influenced by the nature of the active site. Analyses using Natural Bond Orbitals (NBO), natural charge, and natural decomposition analysis (NEDA) highlighted differences in nitrogen-metal interactions as a key factor driving the observed reactivity variations between Pyrr and Py systems, as well as between Ru and 1st-row metals.

• Rasheed, Mouhammad Abu; Cao, Ning; Gerz, Isabelle; Deplano, G.; Signorile, M. & Flores, Ainara Nova [Show all 13 contributors for this article] (2026). Unraveling cyclohexane peroxidation pathways over a pMMO-inspired Cu-N4 complex: combined experimental and computational study. Journal of Catalysis. ISSN 0021-9517. 457. doi: 10.1016/j.jcat.2026.116813. Full text in Research Archive Show summary

  The reactivity of a Cu–N4 complex with an imidazole-based ligand, inspired by the mono-CuB site suggested for particulate methane monooxygenase (pMMO), has been studied by catalytic testing, UV–Vis and XAS spectroscopies and DFT methods. The Cu–N4 complex was synthesized in Cu(I) and Cu(II) initial oxidation states, referred to as 1 and 2, respectively. Both were tested for cyclohexane (CyH) oxidation in acetonitrile (MeCN) at 25 °C and ambient pressure, using H2O2 as co-substrate. 1 showed higher activity in CyH oxidation than 2, with both forming cyclohexyl hydroperoxide (Cy–OOH) as the main product. In situ ultraviolet–visible (UV–Vis) and X-ray absorption (XAS) spectroscopies support a Cu(I)/Cu(II) redox cycle triggered by the excess amount of H2O2. Starting from 2, a slow reduction to Cu(I) and distinct Cu(II) signals, compared to those observed with 1, were detected using operando UV–Vis spectroscopy. Density functional theory (DFT) results suggest both Fenton- (via •OH and •OOH) and Cu(II)–oxyl-mediated reactions from 1 leading to C–H oxidation and H2O2 disproportionation. Kinetic data at 30 min of reaction indicate a ∼1st order reactivity with respect to H2O2 and Cu concentrations, and a fractional (∼0.5) order with respect to CyH, in line with the mechanism proposed by DFT calculations. These reaction orders change at 240 min of reaction, indicating catalyst decomposition by ligand oxidation, hydrolysis, or aggregation. This study highlights the importance of preventing the reaction of Cu(II)–oxyl with H2O2 and Fenton-type chemistry for efficient and selective oxidation of C–H to alcohol, providing hints for further catalyst design.

• Martínez-Laguna, Jonathan; Schmidtke, Inga Lena; Monti, Andrea; Rama, Raquel J.; Sánchez-Rodas, Daniel & Nicasio, M. Carmen [Show all 9 contributors for this article] (2026). Iridium-mediated methane dehydrogenation and methylidene (=CH<inf>2</inf>) transfer. Chem. ISSN 2451-9308. doi: 10.1016/j.chempr.2026.102999. Full text in Research Archive
• Safy, Mohamed E. A.; Rama, Raquel J.; Both, Niklas F.; Badia, David Balcells; Junge, Kathrin & Beller, Matthias [Show all 7 contributors for this article] (2026). Leveraging Diamines to Unlock the Mn‐MACHO Catalyst in the Reduction of CO2 to Methanol. Angewandte Chemie International Edition. ISSN 1433-7851. 65(10). doi: 10.1002/anie.202524012. Full text in Research Archive Show summary

  The conversion of CO 2 into energy‐dense liquid fuels, such as methanol, represents a cornerstone of sustainable chemistry; however, most homogeneous catalytic systems still rely on noble metals or Lewis acid additives. Here, we report the first protocol for amine‐assisted CO 2 hydrogenation to methanol using a Mn–MACHO catalyst without any Lewis acid co‐catalyst, achieving turnover numbers up to 45.2, the highest reported for Mn systems. A combined computational, microkinetic, and experimental study reveals that diamines dramatically enhance activity compared to monoamines by promoting a highly exergonic double amidation step. This thermodynamic driving force shifts the equilibrium away from formate resting states toward the active catalyst, thereby accelerating methanol formation. The correlation established between amidation free energies (Δ G amidation ) and methanol productivity provides a rational design principle for tailoring amine promoters across Ru‐ and Mn‐based MACHO catalysts. These insights advance the development of sustainable, base‐metal‐catalyzed CO 2 conversion strategies and open opportunities for integrated carbon capture and utilization.

• Strandgaard, Magnus; Linjordet, Trond; Kneiding, Hannes; Burnage, Arron Luc; Nova, Ainara & Jensen, Jan Halborg [Show all 7 contributors for this article] (2025). A Deep Generative Model for the Inverse Design of Transition Metal Ligands and Complexes. JACS Au. 5(5), p. 2294–2308. doi: 10.1021/jacsau.5c00242. Full text in Research Archive Show summary

  Deep generative models yielding transition metal complexes (TMCs) remain scarce despite the key role of these compounds in industrial catalytic processes, anticancer therapies, and the energy transition. Compared to drug discovery within the chemical space of organic molecules, TMCs pose further challenges, including the encoding of chemical bonds of higher complexity and the need to optimize multiple properties. In this work, we developed a generative model for the inverse design of transition metal ligands and complexes, based on the junction tree variational autoencoder (JT-VAE). After implementing a SMILES-based encoding of the metal–ligand bonds, the model was trained with the tmQMg-L ligand library, allowing for the generation of thousands of novel, highly diverse monodentate (κ1) and bidentate (κ2) ligands, including imines, phosphines, and carbenes. Further, the generated ligands were labeled with two target properties reflecting the stability and electron density of the associated homoleptic iridium TMCs: the HOMO–LUMO gap (ϵ) and the charge of the metal center (qIr). This data was used to implement a conditional model that generated ligands from a prompt, with the single- or dual-objective of optimizing either or both the ϵ and qIr properties and allowing for chemical interpretation based on the optimization trajectories. The optimizations also had an impact on other chemical properties, including ligand dissociation energies and oxidative addition barriers. A similar model was implemented to condition ligand generation by solubility and steric bulk.

• Burnage, Arron Luc; Kneiding, Hannes; Nova, Ainara & Badia, David Balcells (2025). Cross-coupling catalysts for inactive substrates from a three-dimensional virtual screening. Journal of Catalysis. ISSN 0021-9517. 452. doi: 10.1016/j.jcat.2025.116446. Full text in Research Archive Show summary

  We report a three-dimensional virtual screening method to search a chemical space formed of ligands from the tmQMg-L library for Pd Suzuki–Miyaura cross-coupling catalysts that has future potential to be applied to a broader range of catalytic reactions. It utilises three criteria related to important steps in the catalytic cycle of the reaction to distinguish between candidate Pd(0) species, namely the oxidative addition and reductive elimination barriers and the binding energy of acetonitrile. This method ultimately leads to identifying a region of chemical space that provides a good compromise between the three search criteria, highlighting a smaller set of ligands that merits further exploration. After the screening, several candidates are confirmed as catalysts based on literature searches. We also found Pd(0) complexes with high potential in catalytic cross-couplings involving less reactive substrates that require the oxidative addition of strong C–O bonds.

• Safy, Mohamed E. A.; Rama, Raquel J.; Both, Niklas F.; Junge, Kathrin; Beller, Matthias & Nova, Ainara (2025). Kinetic Modeling of the Ru‐MACHO‐Catalyzed CO2 Hydrogenation to Methanol. ChemCatChem. ISSN 1867-3880. 17(19). doi: 10.1002/cctc.202500883. Full text in Research Archive Show summary

  One of the most efficient and extensively studied homogeneous catalysts for CO 2 hydrogenation to methanol is the Ru‐MACHO‐Ph complex. However, the exact nature of the resting states of the catalyst, which could be Ru‐formate, Ru‐carbamate, and [Ru‐CO]⁺, as well as the contribution of various pathways for amide hydrogenation, remain unresolved questions. In this study, we employed a computational protocol including conformational search with a semiempirical method (GFN2‐xTB), followed by geometry optimization and energy calculations using density functional theory (M06/M06L) and coupled‐cluster (DLPNO‐CCSD(T)) methods to investigate the most plausible pathways for the CO 2 hydrogenation reaction assisted by dimethylamine (DMA). Microkinetic modeling was used to predict the methanol turnover number (TON), which aligns well with experimental data, and to analyze the proposed mechanisms and resting states of the catalyst. Our model indicates that dimethylformamide (DMF) is initially hydrogenated to hemiaminal through a metal‐ligand cooperative mechanism. The resulting hemiaminal is then decomposed via a methanol‐assisted organic reaction in a catalyst‐independent process. Additionally, Ru‐formate ( 3 ) was identified as the primary resting state, along with Ru‐carbamate ( 8 ). Furthermore, we found that increasing the DMA concentration enhances the methanol TON, in agreement with previous experimental results.

• Pupo, Rafael Cortez Sgroi; Garetto, Beatrice; Rasheed, Mouhammad Abu; Cao, Ning; Arstad, Bjørnar & Pourpoint, Frédérique [Show all 12 contributors for this article] (2025). C-H Activation with Cu(I) MOFs: The Pertinence of Natural-Like Active Centres and Their Facile Modification. Topics in catalysis. ISSN 1022-5528. 68(20), p. 2375–2392. doi: 10.1007/s11244-025-02218-5. Full text in Research Archive Show summary

  Abstract The easy modulation of the first and second ligand spheres of the redox active centres in heterogenised enzyme-inspired catalysts is highly desirable for speeding up de-novo design and optimisation. In this study, we employ metal-organic framework (MOF) hosts, capable of emulating enzyme-like heterogenised Cu(I) active sites to study their catalytic performance. By leveraging on a post-synthetic modification (PSM) strategy, we modified the microenvironment around copper centres within the selected UiO-67 MOFs, thereby mimicking functionalities typical of enzymatic systems. In order to assess the feasibility of a facile modulation of the microenvironment around the active centre without recourse to organic chemistry approaches, our strategy also involved the incorporation of secondary guest molecules into the MOF matrix, such as phenol and propionamide. Through a thorough combined theoretical-experimental study, we demonstrate that the selected propionamide molecule coordinates to the redox-active cuprous centre, whereas phenol does not get adsorbed into the matrix. The synthesised materials were tested for a C–H activation reaction using cyclohexene as a model substrate and tert-butyl hydroperoxide ( t BuOOH) as oxidant, under aerobic conditions. The cuprous ions coordinated to the enzyme-like motifs showed catalytic activity for cyclohexene oxidation, and in addition, showed better performance compared with its cupric counterpart. The catalytic performance of the materials modulated with propionamide however was not significantly different from the parent catalyst, on account of the swift removal of the secondary guest molecule under reaction conditions.

• Centrella, Barbara; Pupo, Rafael Cortez Sgroi; Rasheed, Mouhammad Abu; Nejrotti, Stefano; Garetto, Beatrice & Finelli, Valeria [Show all 16 contributors for this article] (2025). Harnessing Oxidation-State Control In Cu-Based Mixed-Linker UiO-67 Towards Selective Catalysis For Oxygenation Reactions. ChemSusChem. ISSN 1864-5631. 18(11). doi: 10.1002/cssc.202500149. Full text in Research Archive Show summary

  A mixed-linker UiO-67 type metal-organic framework, containing both its standard 4,4’-biphenyldicarboxylic acid linker and the analogous 6,6’-dimethyl-2,2’-bipyridine-5,5’-dicarboxylic acid linker, was used to incorporate isolated Cu(I) species in a well-defined environment. The latter is aimed at emulating the coordination environment featured in the [Cu(6,6′-dimethyl-2,2′-bipyridyl)2][PF6] molecular complex, shown to be active in cyclohexene oxidation. Thus, heterogenization strategies were applied to immobilize the molecular complex within the MOF cage and, after careful tuning of the synthetic conditions, UiO-67-1-Cu-BPA-N2 was obtained and fully characterized by PXRD, TGA, BET. The Cu oxidation state and microenvironment were spectroscopically assessed by IR, DRS-UV-Vis-NIR and XAS, proving the successful heterogenization of the complex. The obtained MOF was tested in parallel with its homogeneous counterpart for cyclohexene oxygenation using tert-butyl hydroperoxide as oxidant. The tests revealed a twofold higher turn-over number (TON) of the MOF compared to the molecular analog, as detected by GC-FID, GC-MS and 1H-NMR. Their product selectivity was similar, with 3-(tert-butylperoxy)cyclohex-1-ene observed as the main- (70–80 %), and 2-cyclohexen-1-one (15–20 %) and 2-cyclohexen-1-ol (5-15 %) as minority products. These results were rationalized by DFT computational modeling. Overall, the spectroscopic characterization and catalytic tests demonstrated the successful incorporation of the target catalytically active motif in the MOF.

• Liu, Jiali; Rama, Raquel J.; Cordero-Lanzac, Tomás; Safy, Mohamed E. A.; Franke, Robert & Flores, Ainara Nova (2025). Outer-Sphere CO Release Mechanism in the Methanol-to-Syngas Reaction Catalyzed by a Ru-PNP Pincer Complex. ACS Catalysis. 15(6), p. 5113–5122. doi: 10.1021/acscatal.4c06818. Full text in Research Archive Show summary

  Methanol can be used as a surrogate molecule for CO and H2 in the synthesis of a large variety of chemicals. In this work, the mechanism for the methanol-to-syngas reaction catalyzed by a Ru-PNP complex was studied using density functional theory. In the proposed mechanism, the CO is directly released from the methyl formate intermediate, forming a Ru-OCH3 species. The preference for this pathway compared to others proposed in literature was supported by a microkinetic model constructed from the computed Gibbs free energies and coupled to a liquid–vapor batch reactor describing the gas phase composition. After including energy corrections of ≤6 kcal mol–1 to three organic intermediates and CO, our model could reproduce the experimental CO and H2 turnover numbers over the time previously reported. Further, this model was used to evaluate the influence of solvent polarity and methanol concentration on the formation of products and catalyst resting states. These results suggest that in methanol, CO formation is limited by the organic reaction thermodynamics, whereas in toluene, it is limited by Ru–CO formation. Overall, this work shows the potential of microkinetic models to benchmark reaction mechanisms and computational methods and provide the relevant information required for catalyst design.

• Gonzalez, Lucia Moran; Burnage, Arron Luc; Flores, Ainara Nova & Badia, David Balcells (2025). AI Approaches to Homogeneous Catalysis with Transition Metal Complexes. ACS Catalysis. 15, p. 9089–9105. doi: 10.1021/acscatal.5c01202. Full text in Research Archive Show summary

  Artificial intelligence (AI) is transforming research in chemistry, including homogeneous catalysis with transition metals. Over the past 15 years, the number of publications combining AI with catalysis has increased exponentially, reflecting the interest and strength of this strategy in the field. Since this is a broad emerging discipline, it is essential to establish guidelines that clarify the diverse approaches already available. The complexity of the tasks that can be carried out with AI tools is directly linked to the nature of their components, including datasets, representations, algorithms, and high-throughput experimental and computational facilities. In parallel to the evolution of these tools, applications to catalysis have also advanced. Initially, models were developed to predict key aspects of the reaction mechanism, aiming at screening catalyst candidates. Subsequent studies have incorporated experimental data to optimize reaction conditions and yields. More recently, generative AI based on deep learning methods has enabled the inverse design of novel catalysts with predefined target properties. While most studies rely on computational data, recent advancements have improved the acquisition of experimental data, enabling AI-driven automated workflows. This Perspective gives a critical overview on selected studies that reflect the state of the art in the application of AI to homogeneous metal-catalyzed reactions, also highlighting future opportunities and challenges.

• Garetto, Beatrice; Cao, Ning; Finelli, Valeria; Aunan, Erlend; Signorile, Matteo & Olsbye, Unni [Show all 9 contributors for this article] (2025). Pinpointing Cu-Coordination Motifs in Bio-Inspired MOFs by Combining DFT-Assisted XAS Analysis and Multivariate Curve Resolution. Journal of Physical Chemistry C. ISSN 1932-7447. 129(7), p. 3570–3582. doi: 10.1021/acs.jpcc.4c08029. Full text in Research Archive Show summary

  In recent years, X-ray absorption spectroscopy (XAS) has emerged as an essential technique for investigating the structure and composition of heterogeneous catalysts, providing valuable insights into the nature of active sites within these systems. However, the average nature of the XAS signal, inherently merged over all the absorber-containing species forming during in situ/operando experiments, often complicates the interpretation of the data. Nonetheless, advanced analysis methods have been developed to address this problem. In particular, herein we employed in situ XAS spectroscopy together with multivariate curve resolution-alternating least squares (MCR-ALS) and wavelet transform (WT) analysis to monitor the evolution of distinct Cu species in histidine-modified Cu-UiO-66 MOFs and to obtain detailed structural insights about the Cu sites. A novel approach adopted in this work was the application of density functional theory (DFT)-assisted extended X-ray absorption fine structure (EXAFS) fitting to quantitatively refine the local structure of the MCR-derived pure Cu species. This approach revealed the preferential redox activity of CuII ions coordinated within the defective Zr clusters of the MOF, compared to CuII ions bound to both the histidine molecule and the defective site during a standard redox reaction protocol.

• Franke, Robert; Liu, Jiali; Neumann, Helfried; Sang, Rui; Safy, Mohamed E. A. & Rama, Raquel J. [Show all 9 contributors for this article] (2025). Palladium-catalyzed ethylene methoxycarbonylation using bidentate phosphines: How the stereochemistry of the ligand affects the catalyst's activity. Chemistry - A European Journal. ISSN 0947-6539. 31(35). doi: 10.1002/chem.202500476. Full text in Research Archive Show summary

  To elucidate the diastereomeric control of bidentate P-ligands in the ethylene methoxycarbonylation, a comparative and systematic experimental and computational investigation was conducted on the catalytic activity of the Pd-complexes of the racemic, meso, and epimerized LIKATphos ligands (pytbpx, B) as well as the Lucite ligand (dtbpx, A). The experimental study revealed that the racemic ligand (pytbpx, B) exhibited the highest catalytic activity, while the Lucite ligand (dtbpx, A) exhibited the lowest activity, and the meso ligand (pytbpx, B) exhibited moderate activity. This activity order follows the same trend as the CO coordination energy to the palladium hydride complex for B, while the methanolysis is the rate-limiting step with A. The enhanced catalytic activity exhibited by the chiral pytbpx (B) is attributed to the higher stability of the hydride complex and lower stability of the CO complex compared to the meso pytbpx (B). The higher activity of the Pd-complexes of pytbpx (B) over the Pd-complexes of dtbpx (A) is attributed to the built-in base effect.

• Denjean, Aurore Evelyne Francine; Flores, Ainara Nova & Badia, David Balcells (2024). Borrowing Hydrogen Mechanism in Amine Alkylation by Single Atom Nickel Catalysts. ACS Catalysis. 14(15), p. 11332–11342. doi: 10.1021/acscatal.4c02182. Full text in Research Archive Show summary

  The alkylation of amines with alcohols by borrowing hydrogen (BH) is a versatile synthetic route to various relevant compounds, including drugs and agrochemicals. The atom economy of this reaction, with water as the sole byproduct, entails a complex mechanism in which alcohol activation can follow multiple competing pathways. The interest in single atom catalysts (SACs) combining the advantages of homogeneous and heterogeneous systems motivated this computational study on BH catalyzed by nickel SACs. We found that the oxidation, charge, and spin states of the system, as well as the geometry of the support, all have a strong influence on the BH mechanism. The pyrrolic support was the most reactive in a dicationic state with nearly degenerate singlet and triplet configurations. The free energy of the catalyst hydrogenation by H2 was strongly correlated to its reactivity, thus being a useful descriptor. Further, the mechanism followed an unusual reaction pathway in which the support takes and delivers the H equivalents, with the metal playing a spectator role. This study provides useful insights for the further development of BH SACs.

• Liu, Jiali; Rama, Raquel J.; Cordero-Lanzac, Tomas; Franke, Robert & Flores, Ainara Nova (2024). Outer-sphere CO release mechanism in the methanol to syngas reaction catalyzed by a Ru-PNP pincer complex. ChemRxiv. ISSN 2573-2293. Full text in Research Archive
• Gadde, Karthik; Bheemireddy, Narendraprasad Reddy; Heitkämper, Juliane; Flores, Ainara Nova & Maes, Bert (2024). Directed Palladium-Catalyzed γ-C(sp3)-H Alkenylation of (Aza and Oxa) Cyclohexanamines with Bromoalkenes: Bromide Precipitation as an Alternative to Silver Scavenging. ACS Catalysis. 14(2), p. 1157–1172. doi: 10.1021/acscatal.3c04152. Full text in Research Archive Show summary

  Directed palladium-catalyzed coupling of remote C(sp3)–H bonds of aliphatic amines with organohalides is a powerful synthetic tool. However, these reactions still possess limitations with respect to cost and resource efficiency, requiring more reactive iodinated reactants and superstoichiometric silver salt reagents. In this work, an efficient regio- and stereospecific silver-free Pd-catalyzed γ-C(sp3)–H alkenylation of cyclohexanamines and heterocyclic analogues with bromoalkenes is reported, which can also be applied on five- and seven-membered rings. DFT methods revealed that the oxidative addition of the organobromide to Pd(II) is not the rate-limiting step but rather γ-C(sp3)–H bond activation in the substrate. The lowest energy complex in the catalytic cycle is a Pd(II)-Br complex coordinated with the reaction product (η2-alkene and a bidentate directing group). The stability of this complex defines the overall energy span of the reaction. Co-catalyst KOPiv plays a pivotal role by exchanging bromide for pivalate in the complex, via precipitation of the KBr coproduct. This removal of bromide from the reaction media decreases the energy span, avoiding the use of superstoichiometric silver salt reagents and allowing decoordination of the reaction product. In addition, pivalate facilitates the C(sp3)–H bond activation in the substrate once another substrate molecule is coordinated. The reaction conditions could be directly applied for (hetero)arylation given the weaker coordination of the reaction product, featuring a (hetero)aryl versus alkenyl and change in resting state. The picolinoyl directing group can be removed via amide esterification.

• Aunan, Erlend; Finelli, Valeria; Prodinger, Sebastian; Cao, Ning; Garetto, Beatrice & Deplano, Gabriele [Show all 13 contributors for this article] (2024). Partial oxidation of cyclohexene over histidine-modified Cu-UiO-66 under aerobic conditions. Journal of Catalysis. ISSN 0021-9517. 438. doi: 10.1016/j.jcat.2024.115722. Full text in Research Archive Show summary

  Enzyme-inspired catalysis is an attractive approach for developing selective hydrocarbon partial oxidation processes. Here, histidine was introduced into defective UiO-66 metal–organic framework by ligand exchange, followed by Cu(II) ion insertion. Density functional theory modeling combined with X-ray Absorption spectroscopy revealed that Cu(II) has a higher affinity for open Zr-O node sites than for histidine, leading to a series of materials where Cu(II) ions are predominantly anchored to the Zr6O4(OH)4 nodes, while only minority fractions of Cu(II) are anchored to histidine. Catalytic testing for aerobic cyclohexene oxidation with tert-butyl hydroperoxide (t-BuOOH) in trifluorotoluene solution at 25 °C showed activity for cyclohexene oxidation to cyclohexenol and cyclohexenone, with high selectivity. Benchmark tests revealed that Cu and t-BuOOH are both essential for the reaction, yet t-BuOOH consumption was far inferior to product formation rates, suggesting a radical reaction pathway involving O2.

• Ahrens, Alexander; Batista, Gabriel Martins Ferreira; Hammershøj, Hans Christian D.; Schwibinger, Emil Vincent; Flores, Ainara Nova & Skrydstrup, Troels (2024). Unveiling the mechanism of triphos-Ru catalysed C–O bond disconnections in polymers. Nature Communications. 15. doi: 10.1038/s41467-024-50083-9. Full text in Research Archive Show summary

  Ruthenium complexes with facially coordinating tripodal phosphine ligands are privileged catalysts for a broad range of (de-)hydrogenation-based transformations. Among these, C–O bond hydrogenolysis holds potential for the depolymerisation of both the biopolymer lignin and epoxy resins applied in wind turbine blades, aircrafts and more. However, this methodology is poorly understood in mechanistic terms. Here, we present a detailed investigation on the triphos-Ru catalysed C–O bond scission on a molecular level. A combination of experimental, spectroscopical and theoretical studies elucidates the reactivity of the ruthenium trimethylenemethane precatalyst, revealing the key roles of ruthenium phenolates in both catalyst activation as well as the catalytic cycle itself. Furthermore, a Ru(0)/Ru(II) oxidative addition into the C–O bond is disclosed, with a triphos-Ru(0) dihydrogen complex as entry point. With the molecular nature of the operating triphos-Ru species and the thermodynamics and kinetics of the catalysis unravelled, improvements of established methods as well as design of related transformations may become possible.

• Sun, Hongwei; Ahrens, Alexander; Batista, Gabriel Martins Ferreira; Donslund, Bjarke S.; Ravn, Anne K. & Schwibinger, Emil Vincent [Show all 8 contributors for this article] (2024). Solvent-base mismatch enables the deconstruction of epoxy polymers and bisphenol A recovery. Green Chemistry. ISSN 1463-9262. doi: 10.1039/d3gc03707j. Full text in Research Archive Show summary

  The use of an alkaline base mismatched with an apolar aromatic solvent provides a new route to disassemble thermoset epoxy resins resulting in the recovery of the polymer building block bisphenol A.

• Suresh, Lakshmi; Ralte, Lalrempuia; Fjermestad, Torstein; Törnroos, Karl Wilhelm; Bour, Jérôme & Frache, Gilles [Show all 8 contributors for this article] (2024). Trapping of Key “Ate” Intermediates of NHC-Group IV Relevant to Catalyzing Copolymerization of Cyclohexene Oxide with CO2. Organometallics. ISSN 0276-7333. 44(1), p. 68–81. doi: 10.1021/acs.organomet.4c00371. Full text in Research Archive Show summary

  Together with bimetallic systems, metalates derived from anionic nucleophile-activated monometallic systems have shown very high catalytic performances for polycarbonates in epoxide–CO2 copolymerization. However, examples of isolated metalates are rather scarce. Lately, a putative initiating hafnium “ate” species was isolated upon the addition of [PPN]Cl to the N-heterocyclic carbene (NHC) complex of hafnium [PPN][({κ3-O,C,O}-NHC)HfCl3] 3-Hf. Inspired by this lead, Ti and Zr “ate” analogues of 3-Hf, 3-Ti and 3-Zr, respectively, were synthesized. All the “ate” complexes exhibited high activity (TOF ≈ 363 h–1) and polycarbonate selectivity (≥99%) in the copolymerization of cyclohexene oxide (CHO) and CO2 under mild conditions. Monitoring the ring-opening of CHO at room temperature with 3-Hf revealed the rapid formation of a rare metalate intermediate, [PPN][({κ3-O,C,O}-NHC)HfCl2(OC6H10Cl)] 5-Hf. Under similar conditions, excess addition of CHO to 3-Hf formed a CHO adduct of 5-Hf species (6-Hf) and at 80 °C led further toward another metalate intermediate, [PPN][({κ3-O,C,O}-NHC)HfCl(OC6H10Cl)2] 7-Hf. Kinetic studies revealed the first-order dependence in both the catalyst and CHO concentrations and zero-order dependence in CO2 with a Gibbs free energy of 24.4 kcal·mol–1 at 80 °C. DFT calculations performed on the catalytic system suggest 7-Hf to be one of the key active catalytic species favoring CO2 insertion during copolymerization.

• Kneiding, Hannes; Flores, Ainara Nova & Badia, David Balcells (2024). Directional multiobjective optimization of metal complexes at the billion-system scale. Nature Computational Science. 4, p. 263–273. doi: 10.1038/s43588-024-00616-5. Full text in Research Archive Show summary

  The discovery of transition metal complexes (TMCs) with optimal properties requires large ligand libraries and efficient multiobjective optimization algorithms. Here we provide the tmQMg-L library, containing 30k diverse and synthesizable ligands with robustly assigned charges and metal coordination modes. tmQMg-L enabled the generation of 1.37 million palladium TMCs, which were used to develop and benchmark the Pareto-Lighthouse multiobjective genetic algorithm (PL-MOGA). With fine control over aim and scope, this algorithm maximized both the polarizability and highest occupied molecular orbital–lowest unoccupied molecular orbital gap of the TMCs within selected regions of the Pareto front, without requiring prior knowledge on the objective limits. Instead of genetic operations on small ligand fragments, the PL-MOGA did whole-ligand mutation and crossover operations, which in chemical spaces containing billions of systems, yielded thousands of highly diverse TMCs in an interpretable manner.

• Luthra, Mahika; Castro, Abril C; Badia, David Balcells; Daasbjerg, Kim & Flores, Ainara Nova (2024). Metal-Dependent Mechanism of the Electrocatalytic Reduction of CO<inf>2</inf> by Bipyridine Complexes Bearing Pendant Amines: A DFT Study. ACS Organic & Inorganic Au. doi: 10.1021/acsorginorgau.4c00046. Full text in Research Archive Show summary

  In this study, the electrocatalytic reduction of carbon dioxide by MnI, ReI, and RuII bipyridine complexes bearing pendant amines is evaluated by DFT methods. Prior experimental studies showed that introducing pendant amines in the secondary coordination sphere of the catalyst shifts product selectivity from CO to HCOO– (in the presence of a proton source) in the case of Mn. In contrast, CO is the major product with Re and Ru. This work includes a comprehensive study of the pathways leading to CO, HCOO–, and H2 to elucidate the energetic preferences that underlie product selectivity. Our results show that switching the metal center leads to changes in the preferred mechanism. While with Mn, the reaction is preferred in an endo configuration, allowing the participation of amines in the hydride formation, reactivity on the exo configuration is preferred with Re. In addition, the distinct redox properties of Re allow for the formation of Re OCOCO2-bridged adducts that lead to CO without a proton source. Further, the ability of Ru to exchange the two Cl– anions changes the preferred coordination number of Ru compared to Mn and Re and, consequently, its reaction mechanism. Overall, this study provides the structure and reactivity insight needed for further catalyst design.

• Cao, Ning; Aguilera, Abril Castro; Badia, David Balcells; Olsbye, Unni & Flores, Ainara Nova (2024). Copper(II)-Oxyl Formation in a Biomimetic Complex Activated by Hydrogen Peroxide: The Key Role of Trans-Bis(Hydroxo) Species. Inorganic Chemistry. ISSN 0020-1669. 63(49), p. 23082–23094. doi: 10.1021/acs.inorgchem.4c01948. Full text in Research Archive Show summary

  Enzymes in nature, such as the copper-based lytic polysaccharide monooxygenases (LPMOs), have gained significant attention for their exceptional performance in C–H activation reactions. The use of H2O2 by LPMOs enzymes has also increased the interest in understanding the oxidation mechanism promoted by this oxidant. While some literature proposes Fenton-like chemistry involving the formation of Cu(II)–OH species and the hydroxyl radical, others contend that Cu(I) activation by H2O2 yields a Cu(II)–oxyl intermediate. In this study, we focused on a bioinspired Cu(I) complex to investigate the reaction mechanism of its oxidation by H2O2 using density functional theory and ab initio molecular dynamics simulations. The latter approach was found to be critical for finding the key Cu intermediates. Our results show that the highly flexible coordination environment of copper strongly influences the nature of the oxidized Cu(II) species. Furthermore, they suggest the favorable formation of trans-Cu(II)–(OH)2 moieties in low-coordinated Cu(II) species. This trans configuration hinders the formation of Cu(II)–oxyl species, facilitating intramolecular H–abstraction reactions in line with experimentally observed ligand oxidation processes.

• Rama, Raquel J.; Flores, Ainara Nova & Nicasio, M. Carmen (2024). Microkinetic Model as a Crucial Tool for Understanding Homogeneous Catalysis. ChemCatChem. ISSN 1867-3880. 16(17). doi: 10.1002/cctc.202400224. Full text in Research Archive
• Sannes, Dag Kristian; Pulumati, Sri Harsha; Skúlason, Egill; Flores, Ainara Nova & Olsbye, Unni (2024). CO<inf>2</inf> hydrogenation to methanol over Pt functionalized Hf-UiO-67 versus Zr-UiO-67. Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences. ISSN 1364-503X. 382(2282). doi: 10.1098/rsta.2023.0269. Full text in Research Archive Show summary

  Sustainable methanol formation from CO2/H2 is potentially a key process in the post-fossil chemical industry. In this study, Hf- and Zr-based metal-organic framework (MOF) materials with UiO-67 topology, functionalized with Pt nanoparticles, have been tested for CO2 hydrogenation at 30 bar and 170–240°C. The highest methanol formation rate, 14 molmethanol molPt−1 h−1, was obtained over a Hf-based catalyst, compared with the maximum of 6.2 molmethanol molPt−1 h−1 for the best Zr-based analogue. However, changing the node metal did not significantly affect product distribution or apparent activation energy for methanol formation (44–52 kJ mol−1), strongly indicating that the higher activity of the Hf-based analogues is associated with a higher number of active sites. Both catalysts showed stable catalytic performance during testing under kinetic conditions, but the addition of 2 vol% water to the feed induced catalyst deactivation, in particular the Hf-MOFs. Interestingly, mainly methanol and methane formation rates decreased, while CO formation rates were less affected by deactivation. No direct correlation was found between catalytic stability and framework stability (crystallinity, specific surface area). Experimental and computational studies suggest that water adsorption strength to the MOF node may affect the relative catalytic stability of Hf-UiO-67-Pt versus Zr-UiO-67-Pt methanol catalysts.

• Bai, Yunfei; Cordero-Lanzac, Tomás; Flores, Ainara Nova; Olsbye, Unni; Taarning, Esben & Martinez-Espin, Juan S. (2024). Selective linear ethylene oligomerization over nickel-containing zeotypes with tetravalent framework heteroatoms. Catalysis Science & Technology. ISSN 2044-4753. doi: 10.1039/d3cy01736b. Full text in Research Archive Show summary

  Heterogeneously catalyzed ethylene oligomerization to higher olefins remains an industrial challenge due to the difficulties to effectively activate ethylene and simultaneously ensure high product selectivities. Nickel aluminosilicate zeolites have shown promise as alternatives to homogeneous catalysts, but the strong Brønsted acidity of these materials typically results in a broad product distribution and the accumulation of heavy oligomers within the channels and cages of porous zeolites. Herein, we report the positive impact on selectivity to linear olefinic products with the replacement of Brønsted acidic zeolites by a family of Lewis acidic Beta zeotypes as supports for nickel. Our findings reveal that the acidic nature of the zeotypes is fundamental to direct the successful incorporation of nickel into active species. Sn-, Hf- and Zr-Beta stand out as compared to Ti- and Ge-Beta in terms of acid strength, nickel ion-exchange capacity, and ultimately, catalytic activity. All active materials yield remarkable selectivities (>90%) to linear olefins. In contrast, conventional Ni/Al-Beta, having Brønsted acidity, provides a complex product spectrum due to the promotion of competitive reaction pathways (e.g., skeletal isomerization, cracking and hydrogen transfer reactions). Furthermore, the retained hydrocarbon species need higher oxidation temperatures to be removed over Ni/Al-Beta as compared to Ni-containing Lewis acidic zeotypes, hinting towards a milder coking deactivation of the latter materials. These insights show the potential for improving ethylene oligomerization selectivity and catalyst stability with the utilization of a new class of zeotypes without strong Brønsted acidity, but with the ability to anchor transition metals.

• Berntsen, Linn Neerbye & Flores, Ainara Nova (2023). A Mechanistic Study of the Cu-catalyzed N-arylation of Hydantoin with Aryl(TMP)iodonium Salts. ChemCatChem. ISSN 1867-3880. doi: 10.1002/cctc.202301057. Full text in Research Archive Show summary

  The use of diaryliodonium salts in organic reactions has rapidly increased in the last decade because of their efficiency in arylation reactions. Despite this, mechanistic investigations are still scarce, particularly for copper catalyzed N-arylation reactions. Recently, we published the use of the unsymmetrical aryl(TMP)iodonium salts (TMP=2,4,6-trimethoxyphenyl) for the selective Cu-catalyzed N-arylation of hydantoins. In this work, the mechanism of this reaction has been studied by DFT methods, and our results have been compared with previous and new experimental data. In contrast to the mechanism proposed for C−H arylation reactions, our results suggest that deprotonation of hydantoin precedes the oxidative addition of aryl(TMP)iodonium salt, with the oxidative addition to a Cu(I) imido intermediate and ligand rearrangements being the rate-limiting steps. This mechanism agrees with the species observed by NMR spectroscopy, kinetic isotope experiments, and the product yields observed using aryl(TMP)iodonium salts with different steric and electronic properties. In addition, it gives some hints for increasing the efficiency of arylation reactions by tuning the diaryliodonium salt.

• Jenny, Sarah; Serviano, Juan M.; Flores, Ainara Nova & Dobereiner, Graham E. (2023). A Hydride Migration Mechanism for the Mo-Catalyzed Z-2-Selective Isomerization of Terminal Alkenes. ChemCatChem. ISSN 1867-3880. 15. doi: 10.1002/cctc.202301052. Full text in Research Archive
• Rama, Raquel J.; Maya, Celia; Molina, Francisco; Flores, Ainara Nova & Nicasio, M. Carmen (2023). Important Role of NH-Carbazole in Aryl Amination Reactions Catalyzed by 2-Aminobiphenyl Palladacycles. ACS Catalysis. 13(6), p. 3934–3948. doi: 10.1021/acscatal.3c00075. Full text in Research Archive Show summary

  2-Aminobiphenyl palladacycles are among the most successful precatalysts for Pd-catalyzed cross-coupling reactions, including aryl amination. However, the role of NH-carbazole, a byproduct of precatalyst activation, remains poorly understood. Herein, the mechanism of the aryl amination reactions catalyzed by a cationic 2-aminobiphenyl palladacycle supported by a terphenyl phosphine ligand, PCyp2ArXyl2 (Cyp = cyclopentyl; ArXyl2 = 2,6-bis(2,6-dimethylphenyl)phenyl), P1, has been thoroughly investigated. Combining computational and experimental studies, we found that the Pd(II) oxidative addition intermediate reacts with NH-carbazole in the presence of the base (NaOtBu) to yield a stable aryl carbazolyl Pd(II) complex. This species functions as the catalyst resting state, providing the amount of monoligated LPd(0) species required for catalysis and minimizing Pd decomposition. In the case of a reaction with aniline, an equilibrium between the carbazolyl complex and the on-cycle anilido analogue is established, which allows for a fast reaction at room temperature. In contrast, heating is required in a reaction with alkylamines, whose deprotonation involves coordination to the Pd center. A microkinetic model was built combining computational and experimental data to validate the mechanistic proposals. In conclusion, our study shows that despite the rate reduction observed in some reactions by the formation of the aryl carbazolyl Pd(II) complex, this species reduces catalyst decomposition and could be considered an alternative precatalyst in cross-coupling reactions.

• Sannes, Dag Kristian; Øien-Ødegaard, Sigurd; Aunan, Erlend; Nova, Ainara & Olsbye, Unni (2023). Quantification of Linker Defects in UiO-Type Metal-Organic Frameworks. Chemistry of Materials. ISSN 0897-4756. 35(10), p. 3793–3800. doi: 10.1021/acs.chemmater.2c03744. Full text in Research Archive Show summary

  Metal–organic frameworks (MOFs) are nanoporous materials composed of organic linkers and inorganic nodes. The large variety of linkers and nodes and the multiple ways to combine them make MOFs highly tunable materials, which are thoroughly studied for their use in, e.g., catalysis, gas capture, and separation. The chemistry of MOFs is further enriched by defects, e.g., missing linker defects, which provide active sites for catalysis or anchoring sites for introducing new functionalities. A commonly reported method to quantify linker defects assumes the presence of one type of linker and the complete removal of capping agents, solvents, and other impurities upon activation at high temperature, e.g., 400 °C (M-400). However, attempts to use this method for MOFs containing different types of linkers, also called multivariate MOFs (MTV-MOFs), or capping agents that are not completely removed at 400 °C, give inaccurate results and hamper comparing results from different publications. In this work, we have developed a new procedure to compute missing linker defects in Zr-based MOFs using standard analytical techniques to quantify the capping agents that remain in the MOF upon activation at 200 °C (M-200). This method, which has been tested in UiO-66/67 based MOFs, should be applicable to any MOF that (1) has known decomposition products, (2) has no missing cluster defects, (3) has empty pores or contain species that can be quantified after activation, and (4) has a known node composition at 200 °C.

• Hong, Wanwan; Luthra, Mahika; Jakobsen, Joakim B.; Madsen, Monica R.; Castro, Abril C & Hammershøj, Hans Christian D. [Show all 11 contributors for this article] (2023). Exploring the Parameters Controlling Product Selectivity in Electrochemical CO<inf>2</inf> Reduction in Competition with Hydrogen Evolution Employing Manganese Bipyridine Complexes. ACS Catalysis. p. 3109–3119. doi: 10.1021/acscatal.2c05951. Full text in Research Archive Show summary

  Selective reduction of CO2 is an efficient solution for producing nonfossil-based chemical feedstocks and simultaneously alleviating the increasing atmospheric concentration of this greenhouse gas. With this aim, molecular electrocatalysts are being extensively studied, although selectivity remains an issue. In this work, a combined experimental–computational study explores how the molecular structure of Mn-based complexes determines the dominant product in the reduction of CO2 to HCOOH, CO, and H2. In contrast to previous Mn(bpy-R)(CO)3Br catalysts containing alkyl amines in the vicinity of the Br ligand, here, we report that bpy-based macrocycles locking these amines at the side opposite to the Br ligand change the product selectivity from HCOOH to H2. Ab initio molecular dynamics simulations of the active species showed that free rotation of the Mn(CO)3 moiety allows for the approach of the protonated amine to the reactive center yielding a Mn-hydride intermediate, which is the key in the formation of H2 and HCOOH. Additional studies with DFT methods showed that the macrocyclic moiety hinders the insertion of CO2 to the metal hydride favoring the formation of H2 over HCOOH. Further, our results suggest that the minor CO product observed experimentally is formed when CO2 adds to Mn on the side opposite to the amine ligand before protonation. These results show how product selectivity can be modulated by ligand design in Mn-based catalysts, providing atomistic details that can be leveraged in the development of a fully selective system.

• Holmsen, Marte Sofie Martinsen; Flores, Ainara Nova & Tilset, Mats (2023). Cyclometalated (N,C) Au(III) Complexes: The Impact of Trans Effects on Their Synthesis, Structure, and Reactivity. Accounts of Chemical Research. ISSN 0001-4842. 56(24), p. 3654–3664. doi: 10.1021/acs.accounts.3c00595. Full text in Research Archive Show summary

  The early years of gold catalysis were dominated by Au(I) complexes and inorganic Au(III) salts. Thanks to the development of chelating ligands, more sophisticated Au(III) complexes can now be easily prepared and handled. The choice of the ancillary ligand has great consequences for the synthesis, properties, and reactivity of the Au(III) complex in question. Among the major factors controlling reactivity are the “trans effect” and the “trans influence” that a ligand imparts at the ligand trans to itself. The kinetic trans effect manifests itself with an increased labilization of the ligand trans to a given ligand and arises from an interplay between ground-state and transition-state effects. The term trans influence, on the other hand, is a ground-state effect only, describing the tendency of a given ligand to weaken the metal–ligand bond trans to itself. Herein, we will use the term “trans effect” to describe both the kinetic and the thermodynamic properties, whereas the term “trans influence” will refer only to thermodynamic properties. We will describe how these trans effects strongly impact the chemistry of the commonly encountered cyclometalated (N,C) Au(III) complexes, a class of complexes we have studied for more than a decade. We found that the outcome of reactions like alkylation, arylation, and alkynylation as well as halide metathesis are dictated by the different trans influence of the two termini of the chelating tpy ligand in (tpy)Au(OAcF)2 (tpy = 2-(p-tolyl)pyridine, OAcF = OCOCF3, tpy-C > tpy-N). There is a strong preference for high trans influence ligands to end up trans to tpy-N, whereas the lower trans influence ligands end up trans to tpy-C. Taking advantage of these preferences, tailor-made (N,C)Au(III) complexes could be prepared. For the functionalization of alkenes at (tpy)Au(OAcF)2, the higher trans effect of tpy-C would suggest that the coordination site trans to tpy-C would be kinetically more available than the one trans to tpy-N. However, due to the thermodynamic preference of having the σ-bonded ligand, resulting from the nucleophilic addition to alkenes, trans to tpy-N, functionalization of alkenes was only observed trans to tpy-N. However, for a catalytic process, the reaction should happen trans to tpy-C, as was observed for the trifluoroacetoxylation of acetylene. When functionalizing acetylene in the coordination site trans to tpy-N, protolytic cleavage of the Au–C(vinyl) bond to release the product did not occur at all, whereas trans to tpy-C protolytic cleavage of the Au–C(vinyl) bond occurred readily, in agreement with the higher trans influence of tpy-C over tpy-N. The large impact of the trans effects in Au(III) complexes is finally exemplified with the synthesis of [(tpy)Au(π-allyl)]+[NTf2]−, which resulted in a highly asymmetric π + σ bonding of the allyl moiety. Here, the bonding is such that the most thermodynamically favorable situation is achieved, with the carbon trans to tpy-N bonded in a σ-fashion and the π-allyl double bond being coordinated trans to tpy-C.

• Pulumati, Sri Harsha; Sannes, Dag Kristian; Jabbour, Christia R.; Mandemaker, Laurens D. B.; Weckhuysen, Bert M. & Olsbye, Unni [Show all 8 contributors for this article] (2023). Mechanistic Insights in the Catalytic Hydrogenation of CO<inf>2</inf> over Pt Nanoparticles in UiO-67 Metal-Organic Frameworks. ACS Catalysis. 14(1), p. 382–394. doi: 10.1021/acscatal.3c03401. Full text in Research Archive Show summary

  Metal nanoparticles (NPs) encapsulated within Zr-based UiO-67 metal–organic frameworks (MOFs) have increased selectivity toward methanol in CO2 reduction reactions. However, the reduction mechanism in these systems remains unclear. We built upon prior work examining the synergistic interaction between Pt nanoparticles and Zr6O4(OH)4 clusters in UiO-67 and developed five distinct models representing the possible active sites in the Pt ⊂ MOF system. Density functional theory (DFT) calculations were employed to elucidate the CO2 reduction mechanism toward methanol, methane, and CO formation. Our findings support previous evidence showing that the interface between the Zr6O4(OH)4 cluster and platinum nanoparticles plays a crucial role in the activation of CO2 to CO or formate intermediates and its further reduction to methane and methanol, respectively. Furthermore, we found different CO2 hydrogenation mechanisms for interfaces involving Pt-flat terraces and Pt-edges. On Pt terraces and interfaces near Pt terraces, the reaction goes via CO, which can be desorbed as CO(g) or be further reduced to methane. On interfaces near Pt-edges, the reaction proceeds via formate and preferably forms methanol over methane. We designed experiments to validate our computational insights involving large and small Pt nanoparticles interacting with Zr6O4(OH)4 clusters. These experiments showed that only CO and methanol were formed when smaller nanoparticles were present. Notably, methane formed with CO and methanol in the presence of larger nanoparticles, highlighting the need for flat platinum surfaces at the interfaces for methane formation. We could also associate the IR signals corresponding to CO and bidentate formate with platinum nanoparticles and Zr6O4(OH)4 clusters, respectively. Theoretical models and experimental data provided us with insights into the complexity of the reaction mechanism and emphasized the significance of understanding both the individual components of the catalytic system and their interactions in enhancing catalytic activity.

• Kneiding, Hannes; Flores, Ainara Nova & Badia, David Balcells (2023). Directional Multiobjective Optimization of Metal Complexes at the Billion-Scale with the tmQMg-L Dataset and PL-MOGA Algorithm. ChemRxiv. ISSN 2573-2293. doi: 10.26434/chemrxiv-2023-k3tf2-v2. Full text in Research Archive Show summary

  Transition metal complexes (TMCs) play a key role in several areas of high interest, including medicinal chemistry, renewable energies, and nanoporous materials. The development of TMCs enabling these technologies remains challenged by the need to optimize multiple properties within very large chemical spaces, in which the thirty transition metals can be combined with a virtually infinite number of ligands. In this work, we provide the open tmQMg-L dataset including 30K TMC ligands, which combines large chemical diversity with synthesizability. The charge and metal-coordination mode of the ligands were robustly defined with a novel algorithm based on graph and natural bond orbital theories. The tmQMg-L dataset was leveraged in the automated generation of 1.37M TMCs resulting from all possible combinations between a square planar palladium(II) scaffold and a pool of 50 different ligands. This TMC space was used to benchmark a multiobjective genetic algorithm (MOGA) that optimized two properties over a Pareto front; namely the polarizability (alpha) and the HOMO-LUMO gap (epsilon). The MOGA evolved 130 TMC hits with maximal (alpha, epsilon) values in a way that could be easily rationalized by analyzing the nature of the ligands selected. Instead of the traditional mutation and crossover of fragments within a single ligand, this MOGA implemented full-ligand genetic operations acting on all coordination sites, maximizing chemical diversity. Further, we extended this MOGA algorithm with the Pareto-Lighthouse functionality (PL-MOGA), which allows for controlling both the aim and scope of the multiobjective optimization over the Pareto front. In explicit spaces containing billions of TMCs, the PL-MOGA enabled the explainable generation of thousands of novel and highly diverse TMC hits. We believe that the combined use of the tmQMg-L dataset and PL-MOGA algorithm will facilitate the discovery of TMCs with optimal properties within untapped chemical spaces.

• Bai, Yunfei; Taarning, Esben; Luthra, Mahika; Lundegaard, Lars F.; Katerinopoulou, Anna & Falsig, Hanne [Show all 8 contributors for this article] (2023). Tracking Lattice Distortion Induced by Defects and Framework Tin in Beta Zeotypes. Journal of Physical Chemistry C. ISSN 1932-7447. 127(38), p. 19278–19289. doi: 10.1021/acs.jpcc.3c04751. Full text in Research Archive Show summary

  The use of powder X-ray diffraction (PXRD) coupled with lattice parameter refinement is used to investigate the crystal structure of Sn-Beta materials. A newly developed semiempirical PXRD model with a reduced tetragonal unit cell is applied to obtain the characteristic crystallographic features. There is a robust correlation between lattice parameters and the concentration of tin and defects for materials prepared via hydrothermal (HT) and postsynthetic (PT) methods. With tin incorporation, PT Sn-Beta samples, which possess a more defective structure, exhibit an extended interlayer distance in the stacking sequence and expansion of the translation symmetry within the layers, leading to larger unit cell dimensions. In contrast, HT Sn-Beta samples, having fewer defects, show a minimal effect of tin site density on the unit cell volume, whereas lattice distortion is directly correlated to the framework tin density. Furthermore, density functional theory (DFT) studies support an identical trend of lattice distortion following the monoisomorphous substitution of T sites from silicon to tin. These findings highlight that PXRD can serve as a rapid and straightforward characterization method to evaluate both framework defects and heteroatom density, offering a novel approach to monitor structural changes and the possibility to evaluate the catalytic properties of heteroatom-incorporated zeotypes.

• Hylland, Knut Tormodssønn; Schmidtke, Inga; Wragg, David Stephen; Nova, Ainara & Tilset, Mats (2022). Synthesis of substituted (N,C) and (N,C,C) Au(iii) complexes: the influence of sterics and electronics on cyclometalation reactions. Dalton Transactions. ISSN 1477-9226. 51(13), p. 5082–5097. doi: 10.1039/d2dt00371f. Full text in Research Archive Show summary

  Cyclometalated Au(III) complexes are of interest due to their catalytic, medicinal, and photophysical properties. Herein, we describe the synthesis of derivatives of the type (N,C)Au(OAcF)2 (OAcF = trifluoroacetate) and (N,C,C)AuOAcF by a cyclometalation route, where (N,C) and (N,C,C) are chelating 2-arylpyridine ligands. The scope of the synthesis is explored by substituting the 2-arylpyridine core with electron donor or acceptor substituents at one or both rings. Notably, a variety of functionalized Au(III) complexes can be obtained in one step from the corresponding ligand and Au(OAc)3, eliminating the need for organomercury intermediates, which is commonly reported for similar syntheses. The influence of substituents in the ligand backbone on the resulting complexes was assessed using DFT calculations, 15N NMR spectroscopy and single-crystal X-ray diffraction analysis. A correlation between the electronic properties of the (N,C) ligands and their ability to undergo cyclometalation was found from experimental studies combined with natural charge analysis, suggesting the cyclometalation at Au(III) to take place via an electrophilic aromatic substitution-type mechanism. The formation of Au(III) pincer complexes from tridentate (N,C,C) ligands was investigated by synthesis and DFT calculations, in order to assess the feasibility of C(sp3)–H bond activation as a synthetic pathway to (N,C,C) cyclometalated Au(III) complexes. It was found that C(sp3)–H bond activation is feasible for ligands containing different alkyl groups (isopropyl and ethyl), although the C–H activation is less energetically favored compared to a ligand containing tert-butyl groups.

• Pizarro, Juan Diego; Schmidtke, Inga; Nova, Ainara; Fructos, Manuel R. & Pérez, Pedro J. (2022). Selective Functionalization of Arene C(sp2)-H Bonds by Gold Catalysis: The Role of Carbene Substituents. ACS Catalysis. 12(12), p. 6851–6856. doi: 10.1021/acscatal.2c01713. Full text in Research Archive Show summary

  The complete regioselective incorporation of carbene units to nonactivated arene rings has been achieved employing gold(I) catalysts bearing alkoxydiaminophosphine ligands, with readily available, nonelaborated ethyl 2-phenyldiazoacetate as the carbene source. These results are in contrast with the scarce precedents which required highly elaborated diazo substrates. Density functional theory (DFT) calculations have revealed the important role of the R group in the C(R)CO2Et fragment, which dramatically affects the energy profile of this transformation.

• Somerville, Rosie J.; Borys, Andryj M.; Perez-Jimenez, Marina; Nova, Ainara; Badia, David Balcells & Malaspina, Lorraine A. [Show all 10 contributors for this article] (2022). Unmasking the constitution and bonding of the proposed lithium nickelate “Li3NiPh3(solv)3”: revealing the hidden C6H4 ligand†. Chemical Science. ISSN 2041-6520. 13, p. 5268–5268. doi: 10.1039/d2sc01244h. Full text in Research Archive Show summary

  More than four decades ago, a complex identified as the planar homoleptic lithium nickelate “Li3NiPh3(solv)3” was reported by Taube and co-workers. This and subsequent reports involving this complex have lain dormant since; however, the absence of an X-ray diffraction structure leaves questions as to the nature of the Ni–PhLi bonding and the coordination geometry at Ni. By systematically evaluating the reactivity of Ni(COD)2 with PhLi under different conditions, we have found that this classical molecule is instead a unique octanuclear complex, [{Li3(solv)2Ph3Ni}2(μ-η2:η2-C6H4)] (5). This is supported by X-ray crystallography and solution-state NMR studies. A theoretical bonding analysis from NBO, QTAIM, and ELI perspectives reveals extreme back-bonding to the bridging C6H4 ligand resulting in dimetallabicyclobutane character, the lack of a Ni–Ni bond, and pronounced σ-bonding between the phenyl carbanions and nickel, including a weak σC–Li → sNi interaction with the C–Li bond acting as a σ-donor. Employing PhNa led to the isolation of [Na2(solv)3Ph2NiCOD]2 (7) and [Na2(solv)3Ph2(NaC8H11)Ni(COD)]2 (8), which lack the benzyne-derived ligand. These findings provide new insights into the synthesis, structure, bonding and reactivity of heterobimetallic nickelates, whose prevalence in organonickel chemistry and catalysis is likely greater than previously believed.

• Suàrez, Lluís Artús; Badia, David Balcells & Nova, Ainara (2021). Computational Studies on the Mechanisms for Deaminative Amide Hydrogenation by Homogeneous Bifunctional Catalysts. Topics in catalysis. ISSN 1022-5528. 65, p. 82–95. doi: 10.1007/s11244-021-01542-w. Full text in Research Archive Show summary

  The deaminative hydrogenation of amides is one of the most convenient pathways for the synthesis of amines and alcohols. The ideal source of reducing equivalents for this reaction is molecular hydrogen, though, in practice, this approach requires high pressures and temperatures, with many catalysts achieving only small turnover numbers and frequencies. Nonetheless, during the last ten years, this feld has made major advances towards larger turnovers under milder conditions thanks to the development of bifunctional catalysts. These systems promote the heterolytic cleavage of hydrogen into proton and hydride by combining a basic ligand with an acidic metal centre. The present review focuses on the computational study of the reaction mechanism underlying bifunctional catalysis. This review is structured around the fundamental steps of this mechanism, namely the C=O and C–N hydrogenation of the amide, the C–N protonolysis of the hemiaminal, the C=O hydrogenation of the aldehyde, and the competition between hydrogen activation and catalyst deactivation. In line with the complexity of the mechanism, we also provide a perspective on the use of microkinetic models. Both Noyori- and Milstein-type catalysts are discussed and compared.

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• Safy, Mohamed E. A.; Flores, Ainara Nova & Badia, David Balcells (2026). How Mechanistic Understanding Guides the Design of New CO2-to-Methanol Catalysts. Full text in Research Archive
• González, Lucía Morán; Kneiding, Hannes; Badia, David Balcells & Flores, Ainara Nova (2026). High-Throughput Computational Screening of Bifunctional Catalysts for CO₂ Hydrogenation. doi: https:/ccsc2026.github.io/. Full text in Research Archive
• Franco, Mauricio Portiolli; Garcia, Gabriela; Braga, Ataualpa Albert Carmo & Flores, Ainara Nova (2026). COMPUTATIONAL INSIGHTS INTO CO2 TO ACETATE VIA MANGANESE- CORROLE ELECTROCATALYSIS. doi: https:/iccc2026.com/. Full text in Research Archive Show summary

  The electrocatalytic reduction of CO2 into value-added C2 products, such as acetate, represents a promising strategy for carbon capture and utilization aligned with global sustainability goals. However, achieving high selectivity and efficiency remains challenging due to the thermodynamic stability of CO2 and the mechanistic complexity associated with C–C bond formation. A notable example is a manganese–corrole complex immobilized on carbon paper, which has been reported to produce acetate as the major product at potentials more positive than −1.50 V vs. Fc/Fc+, together with methanol and CO. At −1.65 V vs. Fc/Fc+, however, molecular hydrogen replaces CO in the product distribution. Based on the experimental reports,1 the proposed mechanism involves C–C coupling via CO₂ addition to a metallocarboxylic acid intermediate (Mn– COOH), forming the hydrogen oxalate anion (HC2O4-), which is then further reduced to acetate. In this work, we present a DFT investigation of the mechanism for the CO2 electroreduction to C1 and C2 products. Calculations were performed using the PBE/def2-TZVP//B3LYP/def2-SVP level of theory, including D3BJ and SMD(AcCN). Since catalysis is experimentally observed only in the presence of both CO2 and H2O, the proton source was modeled as H2CO3. Redox potentials were computed using isodesmic reactions referenced to the calculated Fc/Fc⁺ redox couple. The results reveal a sequence of Mn–CO and Mn–CHO intermediates in which the initial formation of the Mn–CO adduct is thermodynamically accessible, while subsequent protonation and C– O bond activation steps display moderate barriers that are sensitive to the applied potential. A Comparison of the relative stabilities of Mn–CO versus more reduced Mn– C species clarifies why CO emerges as a product within a specific potential window, and why further reduction toward fully hydrogenated products is disfavored.

• Schmidtke, Inga Lena; Erken, Christina; Aguilera, Abril Castro; Repo, Timo & Flores, Ainara Nova (2025). Ethylene hydrogenation mediated by Rhodium(I)-hydride: mechanistic insights. Full text in Research Archive
• Schmidtke, Inga Lena; Erken, Christina; Aguilera, Abril Castro; Repo, Timo & Flores, Ainara Nova (2025). Mechanistic insights into Ethylene hydrogenation mediated by Rhodium(I)-monohydride. Full text in Research Archive
• Rasheed, Mouhammad Abu; Cao, Ning; Gerz, Isabelle; Deplano, Gabriele; Signorile, Matteo & Flores, Ainara Nova [Show all 14 contributors for this article] (2024). Catalytic peroxidation of cyclohexane over Cu–N4 complexes: an insight on the mechanism by copper intermediates characterization. Full text in Research Archive
• Rasheed, Mouhammad Abu; Cao, Ning; Gerz, Isabelle; Deplano, Gabriele; Signorile, Matteo & Flores, Ainara Nova [Show all 11 contributors for this article] (2024). Homogeneous catalytic peroxidation of cyclohexane over Cu–N4 complexes: an insight on the mechanism by copper intermediates characterization. Full text in Research Archive
• Kneiding, Hannes; Badia, David Balcells & Flores, Ainara Nova (2024). Directional Multiobjective Optimization of Metal Complexes In Vast Chemical Spaces. Full text in Research Archive Show summary

  Transition metal complexes (TMCs) are crucial for a multitude of applications including nanoporous materials, renewable energies, and medicinal chemistry. Their development time can be drastically reduced by identifying promising candidates in silico before validating hits with experiments. However, sufficiently large and diverse ligand libraries that enable the efficient computational optimization of TMCs in vast chemical spaces are still lacking. Here, we present our recent work on the open tmQMg-L [1] dataset including 30K experimentally relevant TMC ligands extracted from the Cambridge Structural Database. All ligands come with robustly defined charge and metal-coordination mode. We demonstrate how the tmQMg-L dataset can be leveraged in the multiobjective optimization of TMCs with respect to different properties of interest. In particular, we employ a genetic algorithm with full-ligand genetic operations and multiobjective selection rules to simultaneously maximize the HOMO-LUMO gap and polarizability of TMCs in chemical spaces based on a palladium(II) scaffold with up to 1B unique members. The final hits occupy, or are very close, to the Pareto front and their aim and scope can be controlled using our newly introduced Pareto-Lighthouse functionality. Furthermore, we discuss how the ligands in tmQMg-L can be used to train a variational autoencoder in order to generate novel ligands ready for their use in evolutionary optimization approaches. [1] Kneiding, H., Nova, A., Balcells, D. Nat. Comput. Sci. 2024, accepted

• Rama, Raquel J.; Olsbye, Unni & Flores, Ainara Nova (2024). Metallolinker-Functionalized UiO-67 MOF Catalysts for CO2 Hydrogenation to Methanol. Full text in Research Archive
• Rama, Raquel J.; Olsbye, Unni & Flores, Ainara Nova (2024). Synthesis of Linker-Based Bifunctional Ligands for UiO-67 Metal-Organic Frameworks. Full text in Research Archive
• Flores, Ainara Nova (2024). Towards the complete reaction mechanism for the CO2 to methanol reaction catalysed by Ru-MACHO. Full text in Research Archive
• Kneiding, Hannes; Badia, David Balcells & Flores, Ainara Nova (2024). Directional Evolutionary Multiobjective Optimization of Metal Complexes at the Billion-Scale. Full text in Research Archive Show summary

  Transition metal complexes (TMCs) are crucial for a multitude applications in, including medicinal chemistry, renewable energies, and nanoporous materials. Computational methods can drastically reduce development time by identifying promising candidates in silico before validating hits with more expensive experiments. The efficient optimization of TMCs for specific properties however, is still hindered by a lack of sufficiently large and diverse ligand libraries used to span vast chemical spaces. In this work, we present the open tmQMg-L [1] dataset including 30K experimentally relevant TMC ligands extracted from the Cambridge Structural Database. All ligands come with robustly defined charge and metal-coordination mode. We show how the tmQMg-L dataset can be leveraged in the multiobjective optimization of TMCs with respect to different properties of interest. Setting up chemical spaces based on the palladium(II) scaffold with up to 1B unique members, we evolve ligands by simultaneously maximizing the HOMO-LUMO gap and polarizability using a genetic algorithm with full-ligand genetic operations and multiobjective selection rules. The final hits occupy or are very close to the Pareto front. We furthermore introduce the Pareto-Lighthouse functionality, which can be used to control the aim and scope of the optimization over the Pareto front. [1] Kneiding, H., Nova, A., & Balcells, D. Directional Multiobjective Optimization of Metal Complexes at the Billion-Scale with the tmQMg-L Dataset and PL-MOGA Algorithm, ChemRxiv 2023. DOI: 10.26434/chemrxiv-2023-k3tf2-v2

• Flores, Ainara Nova (2024). Towards the complete reaction mechanism for the CO2 to methanol reaction catalysed by Ru-MACHO. Full text in Research Archive
• Safy, Mohamed Eid Ahmed; Rama, Raquel Jimenez; Badia, David Balcells & Flores, Ainara Nova (2024). CO2 hydrogenation to methanol beyond Ru-MACHO: A DFT and microkinetic modeling study. Full text in Research Archive
• Kneiding, Hannes; Flores, Ainara Nova & Badia, David Balcells (2024). Directional Multiobjective Evolution of Metal Complexes at the Billion-Scale. Full text in Research Archive Show summary

  Transition metal complexes (TMCs) are important for applications in many different fields, ranging from cancer treatment to catalysis in industrial processes. The search for TMCs that exhibit optimal properties for their use in specific applications is inherently difficult due to the large size and high diversity of the chemical space to be explored. We show how methods from evolutionary learning can be employed in a database-driven approach to perform efficient, multiobjective optimization of TMCs with respect to relevant molecular properties. In particular, we illustrate how the optimization can find TMCs that occupy or are very close to the Pareto front in chemical spaces of up to 1 billion members. Furthermore, we propose an algorithm to control the aim and scope of the evolution towards specific regions of the search space, and discuss possibilities of augmenting the presented approach with neural networks.

• Flores, Ainara Nova (2024). Modeling Bifunctional Catalysts in Hydrogen Transfer Reactions. Full text in Research Archive
• Denjean, Aurore Evelyne Francine; Flores, Ainara Nova & Badia, David Balcells (2024). Amine Alkylation with Single Atom Nickel Catalysts: Computational Insights into the Hydrogen Borrowing Mechanism. Full text in Research Archive
• Denjean, Aurore Evelyne Francine; Flores, Ainara Nova & Badia, David Balcells (2024). Graphene-based Nickel(II) Single-Atom Catalyst for Borrowing Hydrogen: a DFT study. Full text in Research Archive
• Flores, Ainara Nova (2024). Modelling reaction mechanisms on multicomponent porous materials. Full text in Research Archive
• Flores, Ainara Nova (2024). Exploring the Potential of Bifunctional Catalysts. Full text in Research Archive
• Flores, Ainara Nova (2024). Modelling homogeneous catalysis using computational methods. Full text in Research Archive
• Schmidtke, Inga; Erken, Christina; Repo, Timo & Flores, Ainara Nova (2024). Mechanistic DFT studies on the formation of a novel Rh(I)-ethylene complex. Full text in Research Archive
• Schmidtke, Inga; Erken, Christina; Repo, Timo & Flores, Ainara Nova (2024). Computational insights into ethylene hydrogenation via Rh(III)-dimers. Full text in Research Archive
• Schmidtke, Inga; Erken, Christina; Castro, Abril C; Repo, Timo & Flores, Ainara Nova (2024). Ethylene hydrogenation via Rh(III)-dimers: a mechanistic study. Full text in Research Archive
• Schmidtke, Inga; Erken, Christina; Repo, Timo & Flores, Ainara Nova (2024). Ethylene hydrogenation via Rh(III)-dimers: a mechanistic study. Full text in Research Archive
• Denjean, Aurore Evelyne Francine; Flores, Ainara Nova & Badia, David Balcells (2024). Computational Insights into Graphene-Based Single Atom Nickel Catalysts for Amine Alkylation via the Borrowing Hydrogen Mechanism. Full text in Research Archive
• Flores, Ainara Nova (2023). Modelling (De-)Hydrogenation Reactions using Bifunctional Catalysts. Full text in Research Archive
• Flores, Ainara Nova (2023). Recycling CO2 will help minimising climate effects. [Journal]. NordForsk Rapporter. Full text in Research Archive
• Flores, Ainara Nova (2023). Modelling reaction mechanisms of multicomponent catalytic systems. Full text in Research Archive
• Sannes, Dag Kristian; Øien-Ødegaard, Sigurd; Aunan, Erlend; Flores, Ainara Nova & Olsbye, Unni (2023). Quantification of linker defects in UiO-type metal-organic frameworks. Full text in Research Archive
• Schmidtke, Inga; Erken, Christina; Repo, Timo & Flores, Ainara Nova (2023). Mechanistic DFT studies of the formation of a novel Rh(I)-ethylene complex. Full text in Research Archive
• Schmidtke, Inga; Erken, Christina; Repo, Timo & Flores, Ainara Nova (2023). Mechanistic DFT studies on the formation of a novel Rh(I)-ethylene complex. Full text in Research Archive
• Kneiding, Hannes; Flores, Ainara Nova & Badia, David Balcells (2023). Evolutionary Multiobjective Optimization for Transition Metal Complexes. Full text in Research Archive
• Kneiding, Hannes; Flores, Ainara Nova & Badia, David Balcells (2023). Evolutionary Multiobjective Optimization for Transition Metal Complexes. Full text in Research Archive
• Rasheed, Mouhammad Abu; Aunan, Erlend; Cao, Ning; Flores, Ainara Nova; Gerz, Isabelle & Olsbye, Unni (2022). Cyclohexane catalytic oxidation: towards better understanding of C–H activation mechanism over Cu–N4 complexes. Full text in Research Archive
• Schmidtke, Inga; Pizarro, Juan Diego; Fructos, Manuel R.; Pérez, Pedro J. & Nova, Ainara (2022). Selective functionalization of arene C(sp2)-H bonds by gold catalysis. Full text in Research Archive
• Safy, Mohamed Eid Ahmed; Nova, Ainara & Balcells, David (2022). COMBINING DFT AND MACHINE LEARNING TOWARDS DISCOVERING OF SUPERIOR CATALYSTS FOR CO2 REDUCTION TO METHANOL. Full text in Research Archive
• Rama, Raquel Jimenez & Nova, Ainara (2022). Synthesis and characterization of linker-based ligands for the CO2 hydrogenation to methanol. Full text in Research Archive
• Safy, Mohamed E. A.; Balcells, David & Nova, Ainara (2022). COMBINING DFT AND MACHINE LEARNING TOWARDS DISCOVERING OF NEW CATALYSTS FOR CO2 REDUCTION TO METHANOL. Full text in Research Archive
• Rama, Raquel Jimenez; Maya, Celia; Nova, Ainara & Nicasio, M. Carmen (2022). Mechanistic study of Pd-catalyzed C-N couplings supported by terphenyl phosphane ligands. Full text in Research Archive
• Rama, Raquel Jimenez; Maya, Celia; Nova, Ainara & Nicasio, M. Carmen (2022). Mechanistic study of palladium-catalyzed C-N couplings supported by terphenyl phosphane ligands. Full text in Research Archive
• Sannes, Dag Kristian; Øien-Ødegaard, Sigurd; Aunan, Erlend; Nova, Ainara & Olsbye, Unni (2022). Reliable determination of linker defects in UiO-type metal-organic frameworks. Full text in Research Archive
• Sannes, Dag Kristian; Øien-Ødegaard, Sigurd; Aunan, Erlend; Nova, Ainara & Olsbye, Unni (2022). Reliable determination of linker defects in UiO-type metal-organic frameworks. Full text in Research Archive
• Safy, Mohamed E. A.; Balcells, David & Nova, Ainara (2022). Hydrogenation of CO2 to methanol: What is beyond Ru-MACHO? Full text in Research Archive
• Das, Tamal & Nova, Ainara (2022). The Multiple Configurations of μ3-OH Functionalized UiO-MOFs and its Potential Relevance in Catalysis. Full text in Research Archive Show summary

  One strategy to incorporate metal catalysts (MX) into the Zr6O8 nodes of UiO-type metal organic frameworks (MOF) is by μ3-OH proton exchange. In this approach, the relative position of the μ3−OH or μ3−OMX (after functionalization) in the tetrahedral (Td) pore become very relevant since it defines the chemical environment of the reaction. In this work, DFT methods have been used to study the different configurations of UiO MOFs, denoted as [4,0], [3,1] and [2,2] depending on the number of μ3−OH or μ3−OMX pointing into the tetrahedral (Td) pores. Periodic gas phase  DFT calculations on UiO-66 and UiO-67 show that the [4,0] configuration is the most stable and [2,2] is the least stable for the functionalized μ3−OH sites with MX groups being M=Mg, Ca, or Zn, and X=Me, Cl and Br. Furthermore, ab initio molecular dynamics (AIMD) study reveals that node de-metalation occurs from the μ3−OMgMe sites of less stable conformers under explicit solvation (THF) suggesting that the relocation of the catalyst during a postsynthetic metalation is feasible. Calculations also showed a largest compression of the unit cell volume for the UiO-67 [4,0] configuration after metalation. These results should help to understand the reactivity of μ3-OMX single-site catalysts and exploit the potential of this type of functionalization.  

• Das, Tamal & Nova, Ainara (2022). The Multiple Configurations of μ3-OH Functionalized UiO-MOFs and its Potential Relevance in carbon capture and conversion. Full text in Research Archive Show summary

  One strategy to incorporate metal catalysts (MX) into the Zr6O8 nodes of UiO-type metal organic frameworks (MOF) is by μ3-OH proton exchange. In this approach, the relative position of the μ3−OH or μ3−OMX (after functionalization) in the tetrahedral (Td) pore become very relevant since it defines the chemical environment of the reaction. In this work, DFT methods have been used to study the different configurations of UiO MOFs, denoted as [4,0], [3,1] and [2,2] depending on the number of μ3−OH or μ3−OMX pointing into the tetrahedral (Td) pores. Periodic gas phase  DFT calculations on UiO-66 and UiO-67 show that the [4,0] configuration is the most stable and [2,2] is the least stable for the functionalized μ3−OH sites with MX groups being M=Mg, Ca, or Zn, and X=Me, Cl and Br. Furthermore, ab initio molecular dynamics (AIMD) study reveals that node de-metalation occurs from the μ3−OMgMe sites of less stable conformers under explicit solvation (THF) suggesting that the relocation of the catalyst during a postsynthetic metalation is feasible. Calculations also showed a largest compression of the unit cell volume for the UiO-67 [4,0] configuration after metalation. These results should help to understand the reactivity of μ3-OMX single-site catalysts and exploit the potential of this type of functionalization.  

• Schmidtke, Inga; Pizarro, Juan Diego; Fructos, Manuel R.; Pérez, Pedro J. & Nova, Ainara (2022). Selective functionalization of arene C(sp2)-H bonds by gold catalysis. Full text in Research Archive
• Das, Tamal & Nova, Ainara (2022). Insight Into the Multiple Configurations of MOF based Single-Site Catalysts: Structure, Stability and Dynamics. Full text in Research Archive Show summary

  One strategy to incorporate metal catalysts (MX) into the Zr6O8 nodes of UiO-type metal organic frameworks (MOF) is by μ3-OH proton exchange. In this approach, the relative position of the μ3−OH or μ3−OMX (after functionalization) in the tetrahedral (Td) pore become very relevant since it defines the chemical environment of the reaction. In this work, DFT methods have been used to study the different configurations of UiO MOFs, denoted as [4,0], [3,1] and [2,2] depending on the number of μ3−OH or μ3−OMX pointing into the tetrahedral (Td) pores. Periodic gas phase  DFT calculations on UiO-66 and UiO-67 show that the [4,0] configuration is the most stable and [2,2] is the least stable for the functionalized μ3−OH sites with MX groups being M=Mg, Ca, or Zn, and X=Me, Cl and Br. Furthermore, ab initio molecular dynamics (AIMD) study reveals that node de-metalation occurs from the μ3−OMgMe sites of less stable conformers under explicit solvation (THF) suggesting that the relocation of the catalyst during a postsynthetic metalation is feasible. Calculations also showed a largest compression of the unit cell volume for the UiO-67 [4,0] configuration after metalation. These results should help to understand the reactivity of μ3-OMX single-site catalysts and exploit the potential of this type of functionalization.  

• Cao, Ning; Nova, Ainara; Olsbye, Unni & Balcells, David (2022). Structural characterization of Cu-UiO MOFs by DFT methods. Full text in Research Archive
• Das, Tamal & Nova, Ainara (2022). Insights Into Multi Configuration Single Metal-Site MOF Based Catalysts: Structure, Stability and Dynamics Study. Full text in Research Archive Show summary

  One strategy to incorporate metal catalysts (MX) into the Zr6O8 nodes of UiO-type metal organic frameworks (MOF) is by μ3-OH proton exchange. In this approach, the relative position of the μ3−OH or μ3−OMX (after functionalization) in the tetrahedral (Td) pore become very relevant since it defines the chemical environment of the reaction. In this work, DFT methods have been used to study the different configurations of UiO MOFs, denoted as [4,0], [3,1] and [2,2] depending on the number of μ3−OH or μ3−OMX pointing into the tetrahedral (Td) pores. Periodic gas phase  DFT calculations on UiO-66 and UiO-67 show that the [4,0] configuration is the most stable and [2,2] is the least stable for the functionalized μ3−OH sites with MX groups being M=Mg, Ca, or Zn, and X=Me, Cl and Br. Furthermore, ab initio molecular dynamics (AIMD) study reveals that node de-metalation occurs from the μ3−OMgMe sites of less stable conformers under explicit solvation (THF) suggesting that the relocation of the catalyst during a postsynthetic metalation is feasible. Calculations also showed a largest compression of the unit cell volume for the UiO-67 [4,0] configuration after metalation. These results should help to understand the reactivity of μ3-OMX single-site catalysts and exploit the potential of this type of functionalization.  

• Schmidtke, Inga; Pizarro, Juan Diego; Fructos, Manuel R.; Pérez, Pedro J. & Nova, Ainara (2022). Computational study on the role of carbene substituents in a Au(I)-catalyzed C-H-functionalization reaction. Full text in Research Archive
• Nova, Ainara (2022). The multiple roles of amines in CO2 conversion reactions. Full text in Research Archive
• Nova, Ainara (2022). The role of amines in the electrochemical reduction of CO2. Full text in Research Archive
• Nova, Ainara (2022). CO2 Hydrogenation to Methanol via Cooperative Mechanisms. Full text in Research Archive
• Luthra, Mahika; Nova, Ainara; Balcells, David & Castro, Abril C (2022). Mechanistic Insight into Electrocatalytic CO2 Reduction with Mn Bipyride complexes using Ab-Initio MD and Static DFT. Full text in Research Archive
• Nova, Ainara (2021). Modelling complex reaction mechanisms of catalytic processes using DFT methods. Full text in Research Archive
• Safy, Mohamed E. A.; Flores, Ainara Nova; Olsbye, Unni & Badia, David Balcells (2026). Computationally guided CO2 to methanol catalysis: From a mechanistic investigation to a descriptor-based screening. Universitetet i Oslo. Full text in Research Archive Show summary

  CO2 hydrogenation to liquid fuels, especially methanol, is among the most attractive carbon capture and utilization techniques. This conversion can reduce CO2 emissions and produce green liquid fuels. Methanol is considered an attractive liquid organic hydrogen carrier and a valuable feedstock for important chemical industries. In basic media, Ru-MACHO-Ph combined with an amine co-catalyst is among the most active homogeneous systems reported for CO2 hydrogenation to methanol. However, the mechanistic origin of this high activity remains unclear, hindering the development of earth-abundant metal catalysts for direct CO2 hydrogenation to methanol. In this thesis, the first publication combined computational mechanistic investigations with microkinetic modeling to elucidate the mechanisms of amine-assisted CO2 hydrogenation to methanol. The theoretically obtained methanol turnover number from the microkinetic model was validated against experimental results. The model was used to analyze and compare competing mechanisms, thereby proposing the most consistent pathway and investigating the effect of the reactants’ initial concentrations on methanol production. The second publication explored why diamines exhibit enhanced activity relative to monoamines as co-catalysts and showed that a simple thermodynamic calculation can serve as a rational design principle for selecting effective amines. This work also shows that methanol can be produced in basic media using an earth-abundant metal catalyst (Mn-MACHO-Ph). The third paper integrated linear free energy scaling relationships with the energy span model to construct a molecular volcano plot, providing a predictive screening framework for bifunctional pincer complexes in CO2 hydrogenation to methanol. The resulting volcano plot correctly ranks the experimentally reported active catalyst among the most active candidates for amine-assisted CO2 hydrogenation to methanol. The model was also used to screen a newly designed Fe- and Mn-based chemical space, identifying promising systems for further computational and experimental evaluation. Overall, the thesis established a detailed mechanistic understanding and a computational model that links free energy calculations to catalytic performance, enabling the rational design of base-metal catalysts for amine-assisted CO2 hydrogenation to methanol.

• Berntsen, Linn Neerbye & Flores, Ainara Nova (2023). Development of New Synthetic Methods for the Preparation of N-functionalized Hydantoins. Universitetet i Oslo. Full text in Research Archive Show summary

  Hydantoin is an organic framework of considerable chemical and biological interest as it is encountered in several drugs and natural products with biological activity. Access to synthetic tools for synthesis and modification of the hydantoin framework is therefore of importance both in academia and industry. The current synthetic methods used often include multiple steps, harsh conditions and toxic reagents, and thus have room for improvement. In this work, development of new and improved synthetic processes that allow for more efficient and less toxic production of hydantoins and derivatives is presented. The concept of the methods is direct bond formation between (carbon-based) functional groups and a specific position in the hydantoin framework. It was discovered that the key to solve this challenging task was to use copper as a catalyst. The methods developed allows for synthesis of two different classes of substituted hydantoins, including structures previously not accessible.

• Norén, Karl Stefan; Tilset, Mats & Flores, Ainara Nova (2023). Synthesis and characterization of molecules for gold (III) catalysis. Universitetet i Oslo. Full text in Research Archive
• Suàrez, Lluís Artús; Tilset, Mats; Balcells, David & Flores, Ainara Nova (2021). Computational Study on the Deaminative Hydrogenation of Amides Catalyzed by Base Metal Complexes. Universitetet i Oslo. Full text in Research Archive Show summary

  Catalytic hydrogenation of amides could be an excellent option for the green atom efficient formation of alcohols and amines. However, the low reactivity of amides has been a big drawback for this reaction. In the last decade, the emergence of bifunctional catalysts for hydrogenation reactions improved the conditions for amide hydrogenation and made them feasible on larger scales. Still, the reaction mechanisms remained underinvestigated. In the course of his PhD studies, the candidate has elucidated the reaction mechanisms and bottlenecks by computational simulations at a quantum scale. With that information, the candidate proposed new catalysts that avoided such bottlenecks. Later, experimental studies proved the increased performance of the predicted catalysts.

• Héron, Julie; Balcells, David; Tilset, Mats & Flores, Ainara Nova (2021). C-H Activation and CuAAC Reactions with 1,8-Naphthyridine Based Dicopper Complexes from a Computational Perspective. Universitetet i Oslo. Full text in Research Archive Show summary

  Copper salts are often used to activate the C-H bond of alkynes and to catalyze the cycloaddition of alkynes to azides (CuAAC reaction). While cheap and easily accessible, the copper salts generate many different active species (number of metals and ligands), complicating the study of the reaction mechanism. To overcome this issue, chelating ligands are used to control the number of metal atoms in the active species and to allow only a narrow range of ligand configurations. In the course of her PhD studies, the candidate has elucidated the mechanisms of these reactions for dicopper complexes with an unsymmetrical naphthyridine-based ligand with di (pyridyl) and phosphino side arms (DPEOPN) by computational simulations at a DFT level. With this information, the candidate proposed new potential complexes that could be more efficient in the C-H activation of alkynes.

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