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We present a quantum chemistry (QM)-based method that computes the relative energies of intermediates in the Heck reaction that relate to the regioselective reaction outcome: branched (alpha), linear (beta), or a mix of the two. The calculations are done for two different reaction pathways (neutral and cationic) and are based on r2SCAN-3c single-point calculations on GFN2-xTB geometries that, in turn, derive from a GFNFF-xTB conformational search. The method is completely automated and is sufficiently efficient to allow for the calculation of thousands of reaction outcomes. The method can mostly reproduce systematic experimental studies where the ratios of regioisomers are carefully determined. For a larger dataset extracted from Reaxys, the results are somewhat worse with accuracies of 63% for beta-selectivity using the neutral pathway and 29% for alpha-selectivity using the cationic pathway. Our analysis of the dataset suggests that only the major or desired regioisomer is reported in the literature in many cases, which makes accurate comparisons difficult. The code is freely available on GitHub under the MIT open-source license: https:// github.com/jensengroup/HeckQM.

Herein, we present an investigation of the excited state dynamics of the dihydroazulene photoswitch and its photoinduced reaction to vinylheptafulvene. The focus is on how the introduction of a benzannulated ring in different sites of the structure can modify the excited state topology and thus the kinetics of the ring opening reaction of DHA by alteration of the excited state conjugation of the system. The dynamics of the systems is obtained utilizing

We present a quantum chemistry (QM)-based method that computes the relative energies of intermediates in the Heck reaction that relate to the regioselective reaction outcome: branched (α), linear (β), or a mix of the two. The calculations are done for two different reaction pathways (neutral and cationic) and are based on r2SCAN-3c single point calculations on GFN2-xTB geometries that, in turn, derive from a GFNFFxTB conformational search. The method is completely automated and is sufficiently efficient to allow for the calculation on thousands of reaction outcomes. The method can mostly reproduce systematic experimental studies where the ratios of regioisomers are carefully determined. For a larger dataset extracted from Reaxys the results are somewhat worse with accuracies of 63 % for β-selectivity using the neutral pathway and 29 % for α-selectivity using the cationic pathway. Our analysis of the dataset suggests that only the major or desired regioisomer is reported in the literature in many cases, which makes accurate comparisons difficult. The code is freely available on GitHub under the MIT open source license: https://github.com/jensengroup/HeckQM

Molecular photoswitches based on the norbornadiene–quadricylane (NBD–QC) couple have been proposed as key elements of molecular solar thermal energy storage schemes. To characterize the intrinsic properties of such systems, reversible isomerization of a charge-tagged NBD–QC carboxylate couple is investigated in a tandem ion mobility mass spectrometer, using light to induce intramolecular [2 + 2] cycloaddition of NBD carboxylate to form the QC carboxylate and driving the back reaction with molecular collisions. The NBD carboxylate photoisomerization action spectrum recorded by monitoring the QC carboxylate photoisomer extends from 290 to 360 nm with a maximum at 315 nm, and in the longer wavelength region resembles the NBD carboxylate absorption spectrum recorded in solution. Key structural and photochemical properties of the NBD–QC carboxylate system, including the gas-phase absorption spectrum and the energy storage capacity, are determined through computational studies using density functional theory.

Dihydroazulene (DHA) is a molecular photoswitch that undergoes a ring-opening reaction upon irradiation to form a vinylheptafulvene (VHF) photoisomer. This VHF isomer will in time thermally return to the DHA isomer. As the isomerization is photo-induced only in one direction, the DHA – VHF couple has attracted interest as a molecular solar thermal energy storage device (MOST system). In this author review, we cover our systematic efforts to optimize the DHA – VHF couple for this purpose, with challenges being to achieve sufficiently high energy densities, to cover broad absorptions including the visible region, and to control the energy-releasing VHF-to-DHA back-reaction. By a combination of computations and experiments, we review the consequences of various structural modifications of the system (structure – property relationships), including the influence of donor-acceptor substitution at specific positions, benzannulations, and incorporation into macrocyclic structures. Synthetic protocols to reach the various modifications will also be discussed. The bibliography includes 60 references.

We present a computational methodology for the screening of a chemical space of 10²⁵ substituted norbornadiene molecules for promising kinetically stable molecular solar thermal (MOST) energy storage systems with high energy densities that absorb in the visible part of the solar spectrum. We use semiempirical tight-binding methods to construct a dataset of nearly 34,000 molecules and train graph convolutional networks to predict energy densities, kinetic stability, and absorption spectra and then use the models together with a genetic algorithm to search the chemical space for promising MOST energy storage systems. We identify 15 kinetically stable molecules, five of which have energy densities greater than 0.45 MJ/kg and the main conclusion of this study is that the largest energy density that can be obtained for a single norbornadiene moiety with the substituents considered here, while maintaining a long half-life and absorption in the visible spectrum, is around 0.55 MJ/kg.

We present RegioML, an atom-based machine learning model for predicting the regioselectivities of electrophilic aromatic substitution reactions. The model relies on CM5 atomic charges computed using semiempirical tight binding (GFN1-xTB) combined with a light gradient boosting machine (LightGBM). The model is trained and tested on 21 201 bromination reactions with 101k reaction centers, which are split into training, test, and out-of-sample datasets with 58k, 15k, and 27k reaction centers, respectively. The accuracy is 93% for the test set and 90% for the out-of-sample set, while the precision (the percentage of positive predictions that are correct) is 88% and 80%, respectively. The test-set performance is very similar to that of the graph-based WLN method developed by Struble et al. (React. Chem. Eng., 2020, 5, 896–902) though the comparison is complicated by the possibility that some of the test and out-of-sample molecules are used to train WLN. RegioML out-performs our physics-based RegioSQM20 method (Nicolai Ree, Andreas H. Göller, Jan H. Jensen, J. Cheminf., 2021, 13, 10) where the precision is only 75%. Even for the out-of-sample dataset, RegioML slightly outperforms RegioSQM20. The good performance of RegioML and WLN is in large part due to the large datasets available for this type of reaction. However, for reactions where there is little experimental data, physics-based approaches like RegioSQM20 can be used to generate synthetic data for model training. We demonstrate this by showing that the performance of RegioSQM20 can be reproduced by a ML-model trained on RegioSQM20-generated data.

We present RegioSQM20, a new version of RegioSQM (Chem. Sci. 2018, 9, 660), which predicts the regioselectivities of electrophilic aromatic substitution (EAS) re- actions from the calculation of proton affinities. The following improvements have been made: The open source semiempirical tight binding program xtb is used instead of the closed source MOPAC program. Any low energy tautomeric forms of the input molecule are identified and regioselectivity predictions are made for each form. Finally, RegioSQM20 offers a qualitative prediction of the reactivity of each tautomer (low, medium, or high) based on the reaction center with the highest proton affinity. The inclusion of tautomers increases the success rate from 90.7% to 92.7%. RegioSQM20 is compared to two machine learning based models: one developed by Struble et al. (React. Chem. Eng. 2020, 5, 896) specifically for regioselectivity predictions of EAS reactions (WLN) and a more generally applicable reactivity predictor (IBM RXN) de- veloped by Schwaller et al. (ACS Cent. Sci. 2019, 5, 1572). RegioSQM20 and WLN offers roughly the same success rates for the entire data sets (without considering tau- tomers), while WLN is many orders of magnitude faster. The accuracy of the more general IBM RXN approach is somewhat lower: 76.3%-85.0%, depending on the data set. The code is freely available under the MIT open source license and will be made available as a webservice (regiosqm.org) in the near future.

Electrochemical processes drive many chemical and biochemical reactions. Theoretical methods to accurately predict redox potentials are therefore crucial for understanding these reactions and designing new chemical species with desired properties. We have investigated a theoretical methodology using electronic structure methods based on density functional theory and continuum solvation models. These methods have been validated with linear correlation plots comparing theoretical and experimental results for the redox properties of a series of azulene derivatives. The results showed excellent correlations despite only minor structural variations of the azulenes, which support this rather simple theoretical methodology for determining redox potentials of organic molecules. Furthermore, we have estimated the absolute redox potential of the ferrocene/ferrocenium redox couple to be 4.8 ± 0.1 V in dichloromethane, which is slightly lower than previous estimates.

The transition from fossil fuels to renewable energy sources requires technologies that are capable of both producing and storing energy. Attractive candidates that combine these two features are molecular photoswitches used for molecular solar thermal (MOST) energy storage. One of the most promising MOST systems is the norbornadiene/quadricyclane (NBD/QC) couple. We present the first density functional theory benchmark study of a NBD/QC derivative in vacuum with respect to novel gas-phase experiments. It was found that the M06-2X/def2-TZVP and M06-2X/6-311+G(d) level of theories produced the most accurate results with respect to the maximum absorption wavelength and the energy density.

The introduction of various photochromic units into the same molecule is an attractive approach for the development of novel molecular solar thermal (MOST) energy storage systems. Here, we present the synthesis and characterisation of a series of covalently linked norbornadiene/dihydroazulene (NBD/DHA) conjugates, using the Sonogashira coupling as the key synthetic step. Generation of the fully photoisomerized quadricyclane/vinylheptafulvene (QC/VHF) isomer was found to depend strongly on how the two units are connected - by linear conjugation (a para-phenylene bridge) or cross-conjugation (a meta-phenylene bridge) or by linking to the five- or seven-membered ring of DHA - as well as on the electronic character of another substituent group on the NBD unit. When the QC-VHF system could be reached, the QC-to-NBD back-reaction occurred faster than the VHF-to-DHA back-reaction, while the latter could be promoted simply by the addition of Cu(i) ions. The absence or presence of Cu(i) can thus be used to control whether heat releases should occur on different or identical time scales. The experimental findings were rationalized in a computational study by comparing natural transition orbitals (NTOs). Moreover, the calculations revealed an energy storage capacity of 106-110 kJ mol-1 of the QC-VHF isomers, which is higher than the sum of the capacities of the individual, separate units. The major contribution to the energy storage relates to the energetic QC form, while the major contribution to the absorption of visible light originates from the DHA photochrome; some of the NBD-DHA conjugates had absorption onsets at 450 nm or beyond.

The gain and loss of aromaticity plays a key role in organic chemistry and in the prediction of rate-determining steps. Herein, we explore the concept of aromaticity in photoisomerization reactions. Benzannulated derivatives of the dihydroazulene-vinylheptafulvene (DHA-VHF) photoswitch were investigated using transient absorption spectroscopy and time-dependent density functional theory to elucidate the effect of built-in aromaticity on the switching properties. We found that benzannulation hampered the switching ability by enhancing an already existing barrier on the excited state surface. This enhancement was found to arise from a significant loss of aromaticity in the DHA-to-VHF transition state on the excited state potential energy surface. The VHF was found to be highly aromatic on the excited state surface, showing a reversal of aromaticity compared to the ground state. The barrier was found to be dependent on the position of benzannulation, since one derivative was found to switch as fast as the non-benzannulated molecule although with lower efficiency, whereas another derivative completely lost the ability to undergo reversible photoswitching. The findings herein provide novel principles for the design of molecular photoswitches, shedding new light on excited state aromaticity, as previous discussions have mainly considered excited state aromaticity to be beneficial to switching. Our findings show that this view must be reconsidered.

Creating input files to atomistic simulations and quantum chemical calculations in the CP2K software package can be a challenge. Here, we present a new graphical user interface to reduce the complexity of the work needed to run a CP2K calculation as well as the risk for making mistakes. The program is called CP2K Editor, and it provides a user-friendly interface for both new and experienced users. CP2K Editor keeps the construction of the input file simple and manageable. The input files are similarly structured, so they are easy to recognize and adjust if more advanced configurations are needed. Furthermore, we have implemented several methods for analyzing the output data, and a routine to test the best cut-off values. In our group, CP2K Editor has clearly been of great help when creating input files to the CP2K software package.

Former work has improved the energy storage capacity of the dihydroazulene/vinyl- heptafulvene photo-/thermoswitch by substitution with NH 2 and NO 2 in vacuum. This work extends the former by investigating the solvent effects systematically using cyclo- hexane, toluene, dichloromethane, ethanol, and acetonitrile and comparing them with the inclusion of vacuum calculations. The investigation includes more than 8000 cal- culations using density functional theory for comparison of energy storage capacities, activation energies for the thermal conversion of vinylheptafulvene to dihydroazulene, and UV-Vis absorption spectra. We thereby establish design and solvent guidelines in order to obtain an optimal performance of the dihydroazulene/vinylheptafulvene system for use in a solar energy harvesting and storing device.