This work implements a genetic algorithm (GA) to discover organic catalysts for photoredox CO2 reduction that are both highly active and resistant to degradation. The lowest unoccupied molecular orbital energy of the ground state catalyst is chosen as the activity descriptor and the average Mulliken charge on all ring carbons is chosen as the descriptor for resistance to degradation via carboxylation (both obtained using density functional theory) to construct the fitness function of the GA. We combine the results of multiple GA runs, each based on different relative weighting of the two descriptors, and rigorously assess GA performance by calculating electron transfer barriers to CO2 reduction. A large majority of GA predictions exhibit improved performance relative to experimentally studied o-, m-, and p-terphenyl catalysts. Based on stringent cutoffs imposed on the average charge, barrier to electron transfer to CO2, and excitation energy, we recommend 25 catalysts for further experimental investigation of viability toward photoredox CO2 reduction.
The primary objective of this work is to establish an automated discovery protocol for viable molecular organic photoredox catalysts to perform single-electron reduction of CO2. Green photoredox routes for CO2 reduction using phenylene oligomers were first developed in the 1990s.1,2 Growing emphasis on sustainable chemical transformations in recent years has renewed both general interest in organic photoredox chemistry3,4 and synthesis efforts to reduce CO2 to make amino acids and hydrocarboxylation products.5,6 Organic chromophores are very attractive as they can catalyze thermally challenging reactions via the generation of highly reactive radical species upon excitation and quenching.
Figure 1 describes the catalytic cycle for CO2 reduction with phenylene oligomers, including proposed pathways that lead to catalyst degradation. For this reaction, Matsuoka et al. found that p-terphenyl produced the most formate among o-, m-, and p-isomers.2 Higher activity of p-terphenyl is counter-intuitive as the free energy driving force for CO2 reduction is more favorable for o- and m-isomers relative to the p-isomer. Carboxylation products are observed for o- and m-isomers, indicating that this reaction is preferred to electron transfer (ET).2 Furthermore, all isomers exhibit single-digit turnover numbers. This is believed to be caused by proton capture and subsequent Birch reduction of the catalysts.7
Based on higher activity of the p-terphenyl isomer observed in this study, our group carried out an analysis of substituent electrophilicity effects on the kinetics of ET from the p-terphenyl radical anion to CO2.9 The ET process is adiabatic, and electron-donating groups (indicated by negative Hammett parameter,10 σp), symmetrically substituted at both p-ends of p-terphenyl, lead to lower ET barriers and consequently higher rate coefficients than electron-withdrawing groups. We also determined that the lowest unoccupied molecular orbital (LUMO) of the ground state catalyst is a reliable descriptor for the reaction free energy of ET. LUMO energies drop steeply with increasing electron-withdrawing character, mirrored in the sharp increase in free energy. With increasing electron-donating character, however, while LUMO energies exhibit a modest increase with a corresponding decrease in free energies, both quantities plateau beyond a certain value of σp. Our prior work, therefore, demonstrates that free energies cannot be lowered indefinitely by enhancing electron-donating character alone.
The experimental and computational studies together demonstrate that the core challenge facing catalyst design for CO2 reduction is that it must not only be active but also exhibit high turnover numbers by being resistant to degradation via carboxylation and Birch reduction. While such a task can seem daunting, given the sheer vastness of chemical space, one can leverage emerging approaches that automate screening and search to drive materials discovery. For example, machine learning methods trained on experimental and computational hydrogen evolution activity data for a database of organic photoredox catalysts have been utilized to screen materials libraries and identify new candidates.11,12 Methods that drive discovery of novel organic molecules by utilizing common structural or latent features of known molecules are also being developed. However, with some exceptions,13 both evolutionary approaches, such as genetic algorithms, and generative models, such as variational autoencoders, have been restricted to non-catalysis applications, such as drug development and organic light-emitting diodes.14–16
This study aims to develop a genetic algorithm (GA), constructed using insights from prior experimental and computational studies, to discover novel catalysts for photoredox CO2 reduction. GA is an evolutionary approach that creates new “offsprings” by combining or modifying their “parents.”17,18 In any step of the evolution (generation), the “fitness” of individuals determines whether they constitute the parent pool for the subsequent generation. GAs have been successfully deployed across several domains ranging from art education19 to cloud security.20 This work adapts the open-source GA program developed by the Jensen group, which was originally employed to discover drug candidates based on lipophilicity, synthetic accessibility, and ring size characteristics.14
In this work, the fitness function is modified to favor candidates that possess high LUMO energy and more positive average carbon charge, chosen as descriptors for catalyst activity toward CO2 reduction and resistance to degradation via carboxylation, respectively. The relative weights of the two descriptors are systematically varied. The three isomers of terphenyl, both with and without electron-donating substituents, constitute the parent pool. GA outcomes are assessed using more rigorous calculations of catalyst excited states and ET to CO2. Most catalysts predicted by the GA show improved performance compared to the terphenyl benchmarks. The GA run with fitness biased slightly in favor of LUMO energy (60% weight) yields the largest number of viable candidates relative to their parent pool. We identify at least 25 catalyst candidates, out of the 103 unique catalysts predicted by the GA, that are promising starting points for experimental studies of photoredox CO2 reduction.
Our goal is to utilize genetic algorithms to identify substituted oligophenylenes that are both active toward CO2 reduction and resistant to degradation via carboxylation. To rigorously assess the performance of the GA approach that relies on inexpensive, approximate descriptors, ET barriers are calculated for all the catalysts predicted by the GA. The activity and degradation resistance of the new candidates are benchmarked to experimentally studied o-, m-, and p-terphenyl isomers.2
A. Genetic algorithm
We adapt the string GA developed by Jensen (github.com/jensengroup/String-GA) for catalyst discovery.14,21 The string GA was employed to identify drug-like molecules based on a fitness function that favors high lipophilicity and ease of synthesis and penalizes large ring sizes. The “string” in the name refers to the use of the SMILES (Simplified Molecular Input Line Entry System)22,23 string representation of molecules to carry out mutation and crossover operations. Our adaptation (github.com/andresmrk/Phenyl_GA) also employs the SMILES representation owing to its widespread use and ability to represent complex phenyl ring substitutions,24–26 despite some recent concerns regarding its robustness.27 The RDKit software package28 is employed to convert between SMILES representation and Cartesian coordinates. We modify the fitness function and GA procedure from the original implementation to search for catalytically active and degradation-resistant oligophenylene derivatives for one-electron CO2 reduction.
The initial population for every GA run consists of ten molecules chosen at random from a pool of 30 (Table S1 of the supplementary material). The group of 30 molecules includes the reference unsubstituted p-, m-, and o-terphenyl as well as substituted isomers where a single H in an outer phenyl ring is replaced with one of –CH3, –NH2, or –OH groups, illustrated in Fig. 2. These functional groups are chosen based on our prior finding that electron donating groups on the terminal p-position of the outer phenyl ring enhance ET rates relative to unsubstituted p-terphenyl.9 After the initial population is randomly selected, the GA is allowed to propagate ten generations. Every generation is created using crossover and mutation operations. The crossover operation “mates” two parents to produce an offspring by exchanging “genes.” The multi-point crossover operation is utilized to create one fragment (or “gene”) from every parent. Choosing points on the SMILES string at random for crossover can result in the creation of unrealistic or erroneous SMILES representations. Therefore, we employ constraints that preserve phenyl rings. In other words, the crossover operator allows only for the swapping of one or more phenyl groups (substituted/unsubstituted) between parent molecules. A selected gene from a parent molecule has an equal probability of replacing a gene in the receiving parent or being randomly appended to produce the offspring. Ten offspring are created at the end of every generation. After crossover, the mutation rate dictates the probability that a mutation will be applied to a randomly selected carbon atom in the offspring. A mutation rate of 0.1 is applied, and the mutation is selected at random from a list of 15 substituents (Table S2 of the supplementary material).
Once a new generation is created, all individuals compete according to a user-defined fitness function. We turn to prior experimental and computational studies of CO2 reduction with phenylene catalysts to identify the most appropriate form of the fitness function. Our prior computational study on reduction of CO2 by substituted p-terphenyls revealed that the catalyst’s reduction potential or free energy of the reaction has the largest impact on ET rates.9 Furthermore, free energy is more favorable for phenylenes with higher ground state LUMO energy. Therefore, the LUMO energy of the catalyst, obtained inexpensively (albeit approximately) from density functional theory (DFT) calculations, constitutes one component of the fitness function.
To assess degradation resistance via Birch reduction, we turned to work by Zimmerman and Wang.29,30 They show that for aromatic systems, the position that is most likely to be protonated is that with the highest charge density or the most anionic carbon. However, as protonation can occur from many electronic states of the catalyst and the most favorable proton source is not yet known,31 the choice of carbon charge as a descriptor for degradation via Birch reduction is unclear. To the best of our knowledge, studies similar to those by Zimmerman and Wang for the likelihood or the position of attack of carboxylation have not yet been performed. As CO2 is an electrophile, charge density may be the determining factor for carboxylation along similar lines to Birch reduction. For the experimentally studied o-, m-, and p-terphenyl isomers, therefore, we calculate transition structures and barriers to carboxylation at various ring positions (Fig. S1 of the supplementary material). Described in Sec. 3 of the supplementary material, these calculations show that the barriers at various positions are not directly correlated with the charge on the respective carbon for either the anionic or neutral ground state of the catalyst (Fig. S2 of the supplementary material). On the other hand, both average and minimum carboxylation barriers for isomers are strongly and linearly correlated with the respective average charge on the ring carbons, both in the anionic and ground state of the catalyst (Fig. S3 of the supplementary material).Furthermore, charges on ring carbons in the anionic state of the catalyst are directly correlated (slope ≈1) with the corresponding charges in the ground state (Fig. S4 of the supplementary material), consistent with our prior work that shows that trends in anion properties closely follow those of the ground states of phenylenes.9 Therefore, the average carbon charge of the ground state catalyst is used as an approximate measure of likelihood of degradation via carboxylation, with more positive charge signifying higher resistance to degradation.
Finally, to limit the selection of catalysts to those with optical gaps close to phenylene isomers,32–34 we add a simple constraint to the fitness function that the HOMO–LUMO energy gap lies between 200 and 400 nm. Unlike prior GA studies that inspired this work,14,35 there is no need to impose a penalty for large ring sizes due to the constraint imposed on the crossover operation. There are also no constraints necessary on the overall system size as very large oligophenylenes are expected to have lower fitness scores than short-chain molecules on account of lower LUMO energies. We verify this by showing that system sizes of the candidates identified by the GA are not arbitrarily large. There is also no noticeable correlation between ET parameters and system size (Fig. S5 of the supplementary material).
Normalized fitness scores are calculated for LUMO energy (sL(i)) and average carbon charge (sC(i)) of candidate i as follows:
where is the average Mulliken ring carbon charge for candidate i. The gap contribution (sG,i) is assigned as 0 or −1 depending on whether it lies within or beyond the 200–400 nm region, respectively,
However, DFT typically underestimates HOMO–LUMO gaps.36 To assess the impact of applying an approximate orbital gap constraint using ground-state DFT, we calculate vertical excitation energies for all catalysts predicted by the GA using time-dependent DFT (TDDFT)37 with the same level of theory as ET calculations. Excitation energies confirm that the approximated gap contribution to the fitness function ensures all GA predictions possess excitation energies that lie in nearly the same range as the reference p-, m-, and o-terphenyl and the parent pool (Tables S3 and S4 of the supplementary material).
The fitness function, f(i), is given by
The weight, ω, specifies the influence of each descriptor score (LUMO or average charge) on the overall fitness score, with zero factoring only the charge, 0.5 assigning equal weighting to charge and LUMO, and unity factoring only LUMO. As the optimal value is not known a priori, we vary ω from 0 to 1 in steps of 0.1 and execute 11 GA runs.
During the GA runs, LUMO energies and charges are calculated in the gas phase using the ab initio quantum chemistry software, Q-Chem (version 5.4.2),38 at the B3LYP/def2-SVP level of theory.39–41 Ten fittest candidates in every generation are passed to the next generation. From a randomly chosen initial population, every GA run evolves the catalysts over ten generations. At the end of ten generations, the top ten fittest structures are selected. ET rates and excitation energies are calculated for these structures (procedure described below) and contrasted with the phenylene oligomers examined in prior studies.2 Although the corresponding studies of degradation pathways are also necessary, they entail computationally intensive calculations of transition structures for carboxylation (and protonation) across multiple catalysts. This is a topic of ongoing and future work in our group. For the purpose of assessing GA performance, we continue to use average carbon charge as a descriptor of susceptibility to degradation.
B. Electron transfer barriers
GA predictions are rigorously analyzed by quantifying catalyst activity toward CO2 reduction. The computational procedure is very similar to our previous work.9 We use constrained density functional theory (CDFT)42–44 to calculate initial and final states for ET where the negative charge is localized on the catalyst and substrate fragment, respectively. The guess reactant (initial state) structures for optimization are created by placing linear CO2 slightly above and near the center of every predicted catalyst. Our prior work shows that upon optimization, CO2 relaxes closer toward the center of the catalyst for most substituted p-terphenyls even if the guess structure is created with CO2 off-center. Product (or final) states are calculated with CDFT using the optimized reactant geometries as guesses and by switching charges between fragments. In some cases, the CO2 fragment is manually bent to accelerate convergence to the final state. While it is possible that there are multiple local minima corresponding any reactant or product state, our prior work predicts similar ET parameters across at least some of these local minima. Therefore, we employ a single representative geometry for each of the reactant and product states for a given catalyst. The state-specific model for non-equilibrium solvation is employed to calculate vertically excited charge transfer states.45–49 We find that the donor–acceptor pairs are electronically strongly coupled for most predicted catalysts based on the values of the diabatic coupling constant calculated with CDFT configurations interaction (CDFT-CI) (Table S5 of the supplementary material).50 Therefore, the adiabatic expression51 for rate coefficients can be employed,
where ν is a weighted average of vibrational frequencies for modes that contribute to the reaction coordinate ( s−1)51 and R is the molar equivalent of Boltzmann’s constant, kB. ΔG* is the effective barrier to ET obtained from Marcus theory,52
where λ is the reorganization energy and ΔG is the free energy change for the ET step. All simulations are carried out using Q-Chem at the ωB97X-D/def2-TZVP level of theory.53,54 The conductor-like polarizable continuum model (C-PCM) for implicit solvation55–57 is used for all electronic structure calculations with dichloromethane (dielectric = 8.93 and optical dielectric = 2.028 34)as the solvent. Vertical excitation energies of catalysts are calculated using TDDFT at the same level of theory with non-equilibrium solvation.
III. RESULTS AND DISCUSSION
A. GA predictions
Eleven GA runs generate 103 unique catalysts (with seven duplicates) that vary widely in size and structure in comparison to the parent population (Figs. S6–S7 of the supplementary material). The smallest are biphenyls, while the largest contain seven phenyl rings, composed of various o-, p-, and m-terphenyl sub-structures. Quaterphenyls (four phenyl rings) are observed for every LUMO weight, and terphenyls are observed in all but the case where ω = 1. The smallest predicted catalyst contains 23 atoms, while the largest contains 82 atoms. Two largest structures include o-, m-, and p-terphenyl as sub-structures in the arrangement of the seven phenyl rings. The p-sub-structure is found in only 7 of the 103 catalysts, while o- and m-are observed in ∼80 and 65 catalysts, respectively, with some catalysts containing multiple o- or m-terphenyl sub-structures. Nine substituents are found in the GA catalysts: –OH: 97 catalysts, –NH2: 19, –OCH3: 11, –NHCH3: 11, and –CH3, –SCH3, –NO2, –F, and –N(CH3)2 each occurring in <10 catalysts. Hydroxyl groups are by far the most common. Other substituents are only represented in specific weights; for example, all catalysts for LUMO weight of 50% (ω = 0.5) include OCH3. Only one other OCH3 is found in a catalyst predicted in the 20% LUMO weighted (ω = 0.2) GA run.
Figure 3 demonstrates that the GA discovery procedure successfully identifies a diverse range of structures by seeking to increase both the average carbon charge and LUMO energy. As is desired, most of the predicted catalysts (green circles) are located to the left of and higher than the parent population (black squares). Vertical and horizontal lines represent the reference unsubstituted o-, m-, and p-terphenyl systems. p-Terphenyl has the most positive of the three isomers, in agreement with its lower susceptibility to degradation via carboxylation in experiments.2 As a result, despite its lower LUMO energy (higher ET barrier), it is the isomer that exhibits activity toward CO2 reduction via ET. Most predicted catalysts are above and to the left of p-terphenyl, suggesting that they may exhibit improved performance relative to the experimentally studied system. To assess whether the LUMO energy is indeed a reliable descriptor of catalytic activity, we carry out more computationally intensive ET calculations, describedbelow.
B. Impact of LUMO weight on catalyst performance
Reaction energy (ΔG), reorganization energy (λ), and the resulting free energy barrier [ΔG*, Eq. (5)] are calculated for all catalysts predicted by the GA. Figure 4 depicts the variation of these quantities and with varying LUMO weighting parameter (ω) in the fitness function. The corresponding data are presented in Table S6 of the supplementary material. Four predicted catalysts for ω = 0 yield ΔG* values higher than 120 kJ/mol and are excluded from this and all other figures to enhance readability. High ΔG* values are the likely outcome of GA search based exclusively on charge and no weight assigned to LUMO energies. In other words, even though the predicted catalysts are expected to be resistant to degradation, they exhibit no activity toward CO2 reduction.
At the other end of the fitness spectrum where only LUMO is weighted (ω = 1), values are more negative than those for most intermediate values of ω. We note, however, that these observations are purely qualitative. Quantitative comparisons are precluded by random processes inherent to the GA, in addition to the fact that the initial population is distinct for every ω. Trends in barriers ΔG* closely follow those for ΔG as reorganization energies lie within a narrow range for most systems (with only a few exceptions for ω of 0.4, 0.7, 0.8, and 0.9). This indicates that in most cases, ΔG calculations are sufficient to predict trends in ET rate coefficients for CO2 reduction with these catalysts. In addition, Fig. 5 demonstrates that LUMO energies serve as reliable descriptors for reaction free energies and, therefore, ET barriers. Although the degree of correlation between ΔG* and LUMO energy is slightly lower (R2 = 0.64) than what is normally desirable, the additional scatter compared to ΔG vs LUMO energy (R2 = 0.73) likely originates in the incorporation of λ [Eq. (5)]. Nevertheless, pursuing higher LUMO energies via the fitness function yields systems that possess lower ET barriers. Most predicted catalysts (purple circles) yield lower ET barriers to CO2 reduction relative to both the parent population (black squares) as well as p-terphenyl.
Figure 6 depicts ΔG* vs for each weight of LUMO, with labels that represent the ranking of that catalyst within its weight pool. The horizontal blue line on each figure reflects the average barriers of the initial pool fed into that GA run, while the vertical blue line reflects the average carbon charge of the initial pool. Overall, around 90 candidates generated by the GA outperform their respective initial populations. In all cases including the one in which charge is not taken into account in the fitness (ω = 1), the GA predicts catalysts with more positive . Most catalysts also yield lower ET barriers as well, although weights of less than 50 percent LUMO (ω < 0.5) often yield higher ΔG*’s relative to the initial pool. All the candidates generated in GA runs with ω values of 0.6 and 0.7, where the fitness is slightly more biased in favor of LUMO energy, possess more positive and lower barriers than their respective initial pools. LUMO weights of 0.2 and 0.3 yield many catalysts that exhibit poor activity toward CO2 reduction and are possibly more susceptible to degradation compared to other GA runs. For these two runs, in particular, the initial pools have higher average barriers and lower , which may be partially responsible for the poor outcomes. As structural diversity of the initial pool also affects the quality of GA predictions, we analyze counts of isomers, functional groups, and positions of attachment in initial pools (Figs. S9–S11 and Table S8 of the supplementary material). For instance, 6 out of 10 parents have a single substituent (–OH) in the parent pool of ω = 0.3, unlike the remaining pools where the distributions are less skewed toward a single substituent. Further exploration of the dependence of predicted structural diversity on parent population is a topic for future work as it will require multiple GA runs for a given value of ω.
In the next step, we contrast predicted catalysts with those for which experimental studies are available, specifically o-, m-, and p-terphenyl. Figure 7 depicts ΔG* vs for the initial pool as well as the GA-generated catalysts. Vertical and horizontal lines are used to represent the barriers and average carbon charge of p-, m-, and o-terphenyl, which are labeled accordingly. The overarching objective of this work is to discover catalysts that yield lower barriers as well as higher (more positive) average carbon charges than p-terphenyl, which is known to be active for CO2 reduction and is more resistant to degradation than its o- or m-isomers. Therefore, all points below and to the left of the magenta lines representing p-terphenyl in Fig. 7 constitute improvements upon known experimental successes. The majority of the predicted catalysts are, therefore, viable based on the two criteria employed in this study.
C. Selection of viable catalysts
We select a subset of GA candidates based on stricter thresholds. Represented by the green, shaded region in Fig. 7, we identify 38 candidates that have both and ΔG* ≤ 90 kJ/mol. Of the 38, 25 catalysts possess vertical excitation energies (calculated using TDDFT) that lie between the calculated excitation energies of unsubstituted p- and o-terphenyl (3.56–3.86 eV). Out of the 103 catalysts predicted by the GA, 47 meet the excitation energy criterion, with scope for future improvement by replacing the current limits for determining the gap contribution to the fitness function (sg(i)) with those determined using DFT. Constraining the excitation energy to this region helps us ensure that excitations of the predicted catalysts are achievable with similar experimental setups, and the candidates possess similar optical properties to known active catalysts.
Viable catalysts identified based on our prescribed cut-off values of ET barriers, , and excitation energies are shown in Fig. 8. Figure S12 of the supplementary material groups subsets of these catalysts by similarity in their phenylene backbone to illustrate structural features common across viable catalysts. The 26 structures in Fig. 8 represent 25 unique catalysts spanning several LUMO weights. The repeated structure is o-terphenyl that is doubly substituted with –OH on the p-terminal positions of the phenyl rings and emerges as a viable candidate in GA runs with 60% and 80% LUMO weighting. The GA with 60% weighting of LUMO energy contributes the largest pool of catalysts to the best 25 catalysts with 9 of its 10 structures fulfilling all criteria. GA runs with 70% and 80% weights introduce electron-donating NH2 groups and also contribute significantly to the final set of viable catalysts. GA runs with LUMO weights higher than 80% do not yield viable candidates. GA runs with weights lower than 50% yield a handful of viable catalysts that are structurally similar to those generated with 60% weighting. Our recommended weight for future discovery studies with this GA framework is therefore 60% in favor of LUMO energy.
The catalysts vary in length from terphenyl to oligophenylenes with seven phenyl rings. Our largest predicted catalyst is shown in the middle right of the “LUMO: 70%” box in Fig. 8. This catalyst contains every reference isomer sub-structure as well as multiple NH2 and OH substitutions and has the second-lowest barrier in this set of 25 catalysts. In the same way that o-sub-structures are the most common in the set of 103 predicted catalysts, o-sub-structures are found in 23 of the 25 catalyst structures. The o-terphenyl sub-structure substituted with at least one –OH yields three unique catalysts found with three different LUMO weights ranging from 10% to 80%.
Quaterphenyls represent the highest fraction of the best 25 catalysts and are found across the span of LUMO weights. Almost every structural isomer of quaterphenyl is represented in these 25 catalysts and most are found at least twice, with the sole exception of the p-terphenyl substructure. As quaterphenyls with p-sub-structures yield ET barriers higher than 90 kJ/mol, they do not meet our viability requirements. The quaterphenyls consisting of p-substituted OH-groups illustrated in Fig. 8 are expected to be easier to synthesize as it is often more straightforward to target the same position on several phenyl groups than to target different positions of attack on neighboring phenyl groups, lowering the barrier to synthesis and testing of catalyst performance with experiments. As selective synthesis of specific structural isomers can be challenging, the fact that GA predicts simple structural isomers with comparable performance may ease synthesis efforts. An excellent instance of this is the set of viable candidates obtained with 60% LUMO weight, which are diverse (range of chain lengths) yet consist of similar features (substructures, substituents) to facilitate synthesis and testing. Although 70% LUMO weighting also contributes significantly to the pool of ideal catalysts, the candidates are larger and more complex. In addition to difficulties with synthesis, these candidates may also be less soluble as is observed in the case of longer oligo(p-phenylenes) in experiments.2
Overall, our GA protocol enables the discovery of several novel catalyst candidates for photoredox CO2 reduction by using simple DFT-based descriptors for activity (LUMO energy), degradation resistance (Mulliken charge), and excitation energy (HOMO–LUMO gap). Going forward, one way to enhance the GA’s ability to predict synthetically viable candidates is to include a synthetic accessibility score in the fitness function similar to prior GA studies.14 Other possibilities include the use of emerging machine learning approaches that predict the synthetic complexity (number of steps, costs of reactants, and so on) of organic molecules.58–60 Explicitly considering ease of synthesis will accelerate the selection of viable catalysts. To identify truly sustainable pathways for CO2 utilization, it is also important to incorporate parameters that reflect the environmental costs of catalyst synthesis routes as well as downstream processes to recycle or dispose the proposed catalysts. Recent studies assessing the greenness of various chemical reactions have identified parameters such as greenhouse gas emissions, environmental/human toxicity, and atom efficiency, which must be considered while designing catalytic reaction pathways.61–63
One of the driving hypotheses in this study that is yet to be rigorously tested is the appropriateness of obtained from Mulliken analysis as a descriptor for degradation resistance. In addition to examining substituent effects on carboxylation barriers, our group aims to examine pathways for proton transfer and Birch reduction both from the anion radical state of the catalyst as well as the excited state when complexed with the sacrificial electron donor. As our mechanistic and physical understanding of these catalysts improve, we can develop more robust discovery frameworks for viable photoredox catalysts based on the descriptors that emerge from such studies.
We present a genetic algorithm for discovery of catalysts for photoredox CO2 reduction that are both active and resistant to degradation via carboxylation. The fitness function favors candidates with higher LUMO energies and more positive average carbon charges, which represent descriptors for activity and degradation resistance, respectively. By varying relative weights on each descriptor in the fitness function, we find that biasing the function slightly in favor of LUMO energy (60%) yields the maximum number of candidates that satisfy our viability criteria. The GA successfully predicts several new structures, a majority of which promise substantial performance enhancements over previously studied o-, m-, and p-terphenyl isomers. By imposing more restrictive requirements on activity, degradation resistance, and excitation energy, we recommend 25 catalysts out of 103 GA predictions as potential first candidates for experimental studies of photoredox CO2 reduction. Going forward, we aim to enhance GA robustness by both testing the reliability of average charge as descriptor for degradation resistance as well as predicting catalysts that are synthetically viable and sustainable by identifying appropriate additional parameters for the fitness function.
The supplementary material consists of SMILES notations of parent and mutation candidates for the GA and examination of choice of descriptor for degradation using barriers to carboxylation. The material also summarizes key properties of candidates predicted by the GA—geometries, diabatic coupling constants, TDDFT excitation energies, and ET rate coefficients. Cartesian coordinates of all optimized structures are provided.
This material is based upon work supported by the National Science Foundation under Grant No. 2102044. A.R.K. acknowledges support from the Undergraduate Research Associates Program (URAP) at USC. M.N.R. and R.E. acknowledge support from USC. R.E. also acknowledges support from the USC WiSE Aerospace Fellowship. The authors are grateful to USC’s Center for Advanced Research Computing for computing resources and technical support.
Conflict of Interest
The authors have no conflicts to disclose.
The data that support the findings of this study are available within the article and its supplementary material.