THF-Assisted CO2 Reduction Catalyzed by Electride Mg2EP: Insight from DFT Calculations.

Hydroboration and hydrogenation reductions of CO2 catalyzed by a porphyrinoid-based dimagnesium(I) electride (Mg2EP) were investigated by density functional theory calculations. Herein, the presence of potentially excess electrons located at the Mg-Mg bond endows Mg2EP with the ability to activate small molecules such as CO2, HBpin, and H2, thus opening up the possibility for further CO2 conversion. The Mg2EP-catalyzed hydroboration of CO2 to HCOOBpin is predicted to have relatively higher activity in comparison to the hydrogenation reduction to formic acid (HCOOH). Interestingly, the common solvent molecule tetrahydrofuran as an auxiliary can coordinate with the Mg center to effectively weaken the bonding interaction between the dimagnesium center and the intermediate species from the CO2 conversion, thereby promoting the catalytic cycle for the CO2 hydroboration. The present results suggest that the electride Mg2EP is promising for the molecular catalyst in the CO2 transformation.

Subpocket-Based Analysis Approach for the Protein Pocket Dynamics.

Structural and dynamic characteristics of protein pockets remarkably influence their biological functions and are also important for enzyme engineering and new drug research and development. To date, several softwares have been developed to analyze the dynamic properties of protein pockets. However, due to the complexity and diversity of the pocket information during the kinetic relaxation, further improvement and capacity expansion of current tools are required. Here, we developed a platform software AlphaTraj in which a computational strategy that divides the whole protein pocket into subpockets and examines various properties of the subpockets such as survival time, stability, and correlation was proposed and implemented. We also proposed a scoring function for the subpockets as well as the whole pocket to visualize the quality of the pocket. Furthermore, we implemented automated conformational search functions for ligand docking and ligand optimization. These functions may help us to gain a deep understanding of the dynamic properties of protein pockets and accelerate the protein engineering and the design of inhibitors and small-molecule drugs. The software is freely available at https://github.com/dooo12332/AlphaTraj.git under the GNU GPL license.

Elucidating the Enzymatic Mechanism of Dihydrocoumarin Degradation: Insight into the Functional Evolution of Methyl-Parathion Hydrolase from QM/MM and MM MD Simulations.

Methyl-parathion hydrolase (MPH), which evolved from dihydrocoumarin hydrolase, offers one of the most efficient enzymes for the hydrolysis of methyl-parathion. Interestingly, the substrate preference of MPH shifts from the methyl-parathion to the lactone dihydrocoumarin (DHC) after its mutation of five specific residues (R72L, L273F, L258H, T271I, and S193Δ, m5-MPH). Here, extensive QM/MM calculations and MM MD simulations have been used to delve into the structure-function relationship of MPH enzymes and plausible mechanisms for the chemical and nonchemical steps, including the transportation and binding of the substrate DHC to the active site, the hydrolysis reaction, and the product release. The results reveal that the five mutations remodel the active pocket and reposition DHC within the active site, leading to stronger enzyme-substrate interactions. The MM/GBSA-estimated binding free energies are about -20.7 kcal/mol for m5-MPH and -17.1 kcal/mol for wild-type MPH. Furthermore, this conformational adjustment of the protein may facilitate the chemical step of DHC hydrolysis and the product release, although there is a certain influence on the substrate transport. The hydrolytic reaction begins with the nucleophilic attack of the bridging OH- with the energy barriers of 22.0 and 18.0 kcal/mol for the wild-type and m5-MPH enzymes, respectively, which is rate-determining for the entire process. Unraveling these mechanistic intricacies may help in the understanding of the natural evolution of enzymes for diverse substrates and establish the enzyme structure-function relationship.

Elucidating the degradation mechanism of the nerve agent A-234 using various detergents: a theoretical investigation.

A-234 (ethyl N-[1-(diethylamino)ethylidene]phosphoramidofluoridate) is one of the highly toxic Novichok nerve agents, and its efficient degradation is of significant importance. The possible degradation mechanisms of A-234 by H2O, H2O2, NH3, and their combinations have been extensively investigated by using density functional theory (DFT) calculations. According to the initial intermolecular interaction and the proton transfer patterns between the detergent and the substrate A-234, the A-234 degradation reaction is classified into three categories, denoted as A, B, and C. In modes A and B, the degradation of A-234 by H2O2, H2O, and NH3 is initiated by the nucleophilic attack of the O or N atom of the detergent on the P atom of A-234, coupled with the proton transfer from the detergent to the O or N atom of A-234, whereas in mode C, the direct interaction of H2N-H with the F-P bond of A-234 triggers ammonolysis through a one-step mechanism with the formation of H-F and N-P bonds. Perhydrolysis and hydrolysis of A-234 can be remarkably promoted by introducing the auxiliary NH3, and the timely formed hydrogen bond network among detergent, auxiliary, and substrate molecules is responsible for the enhancement of degradation efficiency.

Narrowband emission from fully-bridged triphenylamine derivatives: insights into effects of structure modification and pressure.

Triphenylamine derivatives with narrowband emission have attracted growing attention in purely organic thermally-activated fluorescence (TADF) materials owing to their enhanced color purity and flexible molecular design strategy. Combined time-dependent density functional theory (TD-DFT) and ONIOM (QM/MM) calculations indicate that the excellent planarity of the experimentally developed DQAO could result in gradually decreased intermolecular interactions in the aggregated state at ambient pressure and upon compression, which is unfavorable for suppressing structural relaxation and achieving narrowband emission in its non-doped practical application. Therefore, three structure-modified derivatives, DQAO-Cb, DQAO-Ph, and DQAO-PhCb, were theoretically designed by introducing the spherical o-carborane and dangling phenyl units positioned para to the N atom of the DQAO to provide additional geometrical distortion and steric hindrance. The explorations on the reported DQAO, OQAO, and SQAO found that small structural relaxations, suppressed low-frequency vibrations, and noticeable short-range charge-transfer (SR-CT) natures of DQAO and OQAO are responsible for their much narrower emission spectral full-width at half-maxima (FWHMs) compared to that of SQAO. Introducing the o-carborane unit directly at the para position of the N atom could result in additional scissoring and stretching vibrations of the corresponding DQAO-Cb while the presence of the phenyl unit in DQAO-Ph is beneficial for suppressing the high-frequency vibrations of the pristine DQAO. More importantly, the bridged phenyl unit incorporated in DQAO-PhCb is of particular importance to inhibit the undesired low-frequency scissoring and high-frequency stretching vibrations of the o-carborane unit, which is crucial to reduce the reorganization energy of DQAO-PhCb and achieve narrowband emission. Also, the phenyl unit in DQAO-Ph and DQAO-PhCb helps to shorten charge transfer distances and improve ISC and RISC processes. Since the o-carborane unit is an adopted building block to achieve piezochromic behaviors, the theoretically structure-modified DQAO-PhCb is expected to exhibit narrowband emission, TADF, and piezochromic features all together. Our findings will hopefully provide ideas for designing triphenylamine-based TADF emitters with narrowband emission and piezochromic behaviors.

Enhancing CO2 Hydrogenation Using a Heterogeneous Bimetal NiAl-Deposited Metal-Organic Framework NU-1000: Insights from First-Principles Calculations.

The hydrogenation of CO2 to high-value-added liquid fuels is crucial for greenhouse gas emission reduction and optimal utilization of carbon resources. Developing supported heterogeneous catalysts is a key strategy in this context, as they offer well-defined active sites for in-depth mechanistic studies and improved catalyst design. Here, we conducted extensive first-principles calculations to systematically explore the reaction mechanisms for CO2 hydrogenation on a heterogeneous bimetal NiAl-deposited metal-organic framework (MOF) NU-1000 and its catalytic performance as atomically dispersed catalysts for CO2 hydrogenation to formic acid (HCOOH), formaldehyde (H2CO), and methanol (CH3OH). The present results reveal that the presence of the NiAl-oxo cluster deposited on NU-1000 efficiently activates H2, and the facile heterolysis of H2 on Ni and adjacent O sites serves as a precursor to the hydrogenation of CO2 into various C1 products HCOOH, H2CO, and CH3OH. Generally, H2 activation is the rate-determining step in the entire CO2 hydrogenation process, the corresponding relatively low free energy barriers range from 14.5 to 15.9 kcal/mol, and the desorption of products on NiAl-deposited NU-1000 is relatively facile. Although the Al atom does not directly participate in the reaction, its presence provides exposed oxygen sites that facilitate the heterolytic cleavage of H2 and the hydrogenation of C1 intermediates, which plays an important role in enhancing the catalytic activity of the Ni site. The present study demonstrates that the catalytic performance of NU-1000 can be finely tuned by depositing heterometal-oxo clusters, and the porous MOF should be an attractive platform for the construction of atomically dispersed catalysts.

Chemical Bonding and Activity of Atomically Dispersed Silicon in Two- and Three-Dimensional Materials.

On the basis of the especially tunable electronic property of Si, several kinds of nanomaterials with atomically dispersed Si were constructed and characterized by extensive first-principles calculations and ab initio molecular dynamics (AIMD) simulations. The new-type Si(X≡Y)n wide-bandgap semiconductors featuring through-space d-π* hyperconjugation exhibit unique properties in photoelectric conversion, photoconductivity, structural mechanics, etc. The SiC8 siligraphene with the planar tetracoordinate Si (ptSi) has a high lithium-storage capacity and comparably facile surface migration behaviors of both Li and Li+, making it a promising anode material for high-performance Li-ion batteries. The atomically dispersed Si sites of 2D monolayer materials, such as ptSi and three- and four-coordinated Si atoms, generally exhibit remarkable catalytic activity toward CO2 activation with different electron mechanisms, resulting in different scaling relations between the activity and the p-band center. The computational findings enrich the understanding of structural and chemical properties of silicon and open up avenues for developing Si-based functional materials.

Correction: Multiple correlations between spin crossover and fluorescence in a dinuclear compound.

Correction for 'Multiple correlations between spin crossover and fluorescence in a dinuclear compound' by Chun-Feng Wang et al., Chem. Commun., 2016, 52, 14322-14325, https://doi.org/10.1039/C6CC07810A.

QM/MM and MM MD Simulations on Enzymatic Degradation of the Nerve Agent VR by Phosphotriesterase.

V-type nerve agents are hardly degraded by phosphotriesterase (PTE). Interestingly, the PTE variant of BHR-73MNW can effectively improve the hydrolytic efficiency of VR, especially for its Sp-enantiomer. Here, the whole enzymatic degradation of both Sp and Rp enantiomers of VR by the wild-type PTE and its variant BHR-73MNW was investigated by quantum mechanics/molecular mechanics (QM/MM) calculations and MM molecular dynamics simulations. Present results indicate that the degradation of VR can be initiated by the nucleophilic attack of the bridging OH- and the zinc-bound water molecule. The QM/MM-predicted energy barriers for the hydrolytic process of Sp-VR are 19.8 kcal mol-1 by the variant with water as a nucleophile and 22.0 kcal mol-1 by the wild-type PTE with OH- as a nucleophile, and corresponding degraded products are bound to the dinuclear metal site in monodentate and bidentate coordination modes, respectively. The variant effectively increases the volume of the large pocket, allowing more water molecules to enter the active pocket and resulting in the improvement of the degradation efficiency of Sp-VR. The hydrolysis of Rp-VR is triggered only by the hydroxide with an energy span of 20.6 kcal mol-1 for the wild-type PTE and 20.7 kcal mol-1 for the variant BHR-73-MNW PTE. Such mechanistic insights into the stereoselective degradation of VR by PTE and the role of water may inspire further studies to improve the catalytic efficiency of PTE toward the detoxification of nerve agents.

Formation and reactivity of NHC-boryl radicals: insight into substituent effect from theoretical calculations.

Substituent modification effects of N-heterocyclic carbene (NHC) boranes on their hydrogen atom abstraction (HAA) reactions and the chemical reactivities of corresponding NHC-boryl radicals have been investigated by density functional theory calculations. The substituent modification of NHC-boranes may notably affect the HAA reaction, both kinetically and thermodynamically, and shows remarkable substitution position dependence. The multi-site-modification of NHC-boranes is proved to be more effective for reduction of the B-H bond dissociation energy (BDE), promotion of the HAA reaction, and the reactivity regulation of their corresponding NHC-boryl radicals. Computational screening reveals that the spin density and the charge population of the radical boron center have good correlation with the B-H BDEs of NHC-boranes and the chemical reactivities of NHC-boryl radicals, and they can be considered as property and reactivity descriptors of these boron-based systems. The present results and established scaling relationships are beneficial to promote the advancement of design of NHC-boryl radical catalysis.

How the Conformational Movement of the Substrate Drives the Regioselective C-N Bond Formation in P450 TleB: Insights from Molecular Dynamics Simulations and Quantum Mechanical/Molecular Mechanical Calculations.

P450 TleB catalyzes the oxidative cyclization of the dipeptide N-methylvalyl-tryptophanol into indolactam V through selective intramolecular C-H bond amination at the indole C4 position. Understanding its catalytic mechanism is instrumental for the engineering or design of P450-catalyzed C-H amination reactions. Using multiscale computational methods, we show that the reaction proceeds through a diradical pathway, involving a hydrogen atom transfer (HAT) from N1-H to Cpd I, a conformational transformation of the substrate radical species, and a second HAT from N13-H to Cpd II. Intriguingly, the conformational transformation is found to be the key to enabling efficient and selective C-N coupling between N13 and C4 in the subsequent diradical coupling reaction. The underlined conformational transformation is triggered by the first HAT, which proceeds with an energy-demanding indole ring flip and is followed by the facile approach of the N13-H group to Cpd II. Detailed analysis shows that the internal electric field (IEF) from the protein environment plays key roles in the transformation process, which not only provides the driving force but also stabilizes the flipped conformation of the indole radical. Our simulations provide a clear picture of how the P450 enzyme can smartly modulate the selective C-N coupling reaction. The present findings are in line with all available experimental data, highlighting the crucial role of substrate dynamics in controlling this highly valuable reaction.

Biodegradation of 2,5-Dihydroxypyridine by 2,5-Dihydroxypyridine Dioxygenase and Its Mutants: Insights into O-O Bond Activation and Flexible Reaction Mechanisms from QM/MM Simulations.

2,5-Dihydroxypyridine dioxygenase (NicX) from Pseudomonas putida KT2440 is a mononuclear non-heme iron oxygenase responsible for the biodegradation of 2,5-dihydroxypyridine (DHP) to N-formylmaleamic acid (NFM). Here, extensive quantum mechanical-molecular mechanical (QM/MM) calculations and molecular dynamics (MD) simulations are used to elucidate the degradation mechanism of DHP by wild-type NicX and its H105F variant (NicXH105F) and the roles of key residues. In particular, NicX and NicXH105F can catalyze the ring opening degradation of DHP to NFM, but flexible mechanisms are adopted therein. Both reactions of NicX and NicXH105F are initiated by the attack of FeIII superoxide species onto the substrate, during which a proton-coupled electron transfer (PCET) process is involved. For wild-type NicX, the PCET reaction is mediated by the adjacent His105, while the further proton transfer from His105 to the peroxo species can remarkably enhance the following O-O cleavage. However, for the NicXH105F mutant, a water molecule replaces the role of residue His105, which not only stabilizes the substrate binding via a H bonding network but also functions as a base to mediate the PCET process. For the NicXH105A mutant, MD simulations show that the disruption of the H bonding network can displace the substrate binding, leading to the loss of enzyme activity. These findings can expand our understanding of the PCET-mediated O-O bond activation and the flexible catalytic routes in various mutants, which have general implications on enzyme catalysis.

RBD spatial orientation of the spike protein and its binding to ACE2: insight into the high infectivity of the SARS-CoV-2 Delta variant from MD simulations.

The spike glycoprotein on the surface of the SARS-CoV-2 envelope plays an important role in its invasion into host cells. The binding of the spike glycoprotein RBD to the angiotensin-converting enzyme 2 (ACE2) receptor as a critical step in the spread of the virus has been explored intensively since the outbreak of COVID-19, but the high transmissibility of the virus such as the Delta variant is still not fully understood. Here, molecular simulations on the binding interactions of the wild-type spike protein and its four variants (Beta, Kappa, Delta, and Mu) with ACE2 and the antibody were performed, and the present results reveal that the residue mutations will not strengthen the binding affinity of the variant for ACE2, but remarkably influences the spatial orientation of the spike protein. Only the up-right conformational receptor binding domain (RBD) can bind ACE2, which is stabilized by the nearby RBDs in the down state, revealing that the RBD bears dual functional characteristics. The present results provide new insights into plausible mechanisms for high infectivity of the virus variants and their immune escape.

Unraveling the Catalytic Performance of the Nonprecious Metal Single-Atom-Embedded Graphitic s-Triazine-Based C3N4 for CO2 Hydrogenation.

Graphitic carbon nitride (g-C3N4) is regarded as a promising potent photoelectrocatalyst for CO2 reduction. Here, extensive first-principles calculations and ab initio molecular dynamics (AIMD) simulations are performed to systematically explore the structural and electronic properties of nonprecious metal single-atom-embedded graphitic s-triazine-based C3N4 (M@gt-C3N4, M = Mn, Fe, Co, Ni, Cu, and Mo) monolayer materials and their catalytic performances as the single-atom catalysts (SACs) for CO2 hydrogenation to HCOOH, CO, and CH3OH. It is found that the atomically dispersed non-noble metal Mn, Fe, Co, and Mo sites anchored on gt-C3N4 can efficiently activate both H2 and CO2, and their coadsorbed state serves as a precursor to the hydrogenation of CO2 to different C1 products. Among these SACs (M@gt-C3N4, M = Mn, Fe, Co, and Mo), Co@gt-C3N4 was predicted to have the best catalytic performance for CO2 hydrogenation to C1 products, although their mechanistic details are somewhat different. The predicted energy barriers of the rate-determining steps for the conversion of CO2 into HCOOH, CO, and CH3OH on Co@gt-C3N4 are 0.58, 0.67, and 1.19 eV, respectively. The desorption of products is generally energy-demanding, but it can be facilitated remarkably by the subsequent adsorption of H2, which regenerates M@gt-C3N4 for the next catalytic cycle. The present study demonstrates that the catalytic performance of gt-C3N4 can be well regulated by embedding the non-noble metal single atom, and the porous gt-C3N4 is nicely suited for the construction of high-performance single-atom catalysts.

Accurate and Efficient Estimation of Lennard-Jones Interactions for Coarse-Grained Particles via a Potential Matching Method.

The Lennard-Jones (LJ) energy functions are commonly used to describe the nonbonded interactions in bulk coarse-grained (CG) models, which contribute significantly to the stabilization of a local binding configuration or a self-assembly system. In many cases, systematic development of the LJ interaction parameters in a CG model requires a comprehensive sampling of the objective molecules at the all-atom (AA) level, which is therefore extremely time-consuming for large systems. Inspired by the concept of electrostatic potential (ESP), we define the LJ static potential (LJSP), by which the embedding potential energy surface can be constructed analytically. A semianalytic approach, namely, the LJSP matching method, is developed here to derive the CG parameters by minimizing the LJSP difference between the AA and the CG models, which provides a universal way to derive the CG LJ parameters from the AA models without doing presampling. The LJSP matching method is successful not only in deriving the LJ interaction energy landscape in the CG models for proteins, lipids, and DNA but also in reproducing the critical properties such as intermediate structures and enthalpy contributions as exemplified in simulating the self-assembly process of the dipalmitoylphosphatidylcholine (DPPC) lipids.

Water-Regulated Mechanisms for Degradation of Pesticides Paraoxon and Parathion by Phosphotriesterase: Insight from QM/MM and MD Simulations.

The enzymatic degradation of pesticides paraoxon (PON) and parathion (PIN) by phosphotriesterase (PTE) has been investigated by QM/MM calculations and MD simulations. In the PTE-PON complex, Znα and Znß in the active site are five- and six-coordinated, respectively, while both zinc ions are six coordinated with the Znα -bound water molecule (WT1) for the PTE-PIN system. The hydrolytic reactions for PON and PIN are respectively driven by the nucleophilic attack of the bridging-OH- and the Znα -bound water molecule on the phosphorus center of substrate, and the two-step hydrolytic process is predicted to be the rate-limiting step with the energy spans of 13.8 and 14.4 kcal/mol for PON and PIN, respectively. The computational studies reveal that the presence of the Znα -bound water molecule depends on the structural feature of substrates characterized by P=O and P=S, which determines the hydrolytic mechanism and efficiency for the degradation of organophosphorus pesticides by PTE.

QM/MM and MM MD simulations on decontamination of the V-type nerve agent VX by phosphotriesterase: toward a comprehensive understanding of steroselectivity and activity.

Due to deadly toxicity and high environmental stability of the nerve agent VX, an efficient decontamination approach is desperately needed in tackling its severe threat to human security. The enzymatic destruction of nerve agents has been generally considered as one of the most effective ways, and here the hydrolysis of VX by phosphotriesterase (PTE) was investigated by extensive QM/MM and MM MD simulations. The hydrolytic cleavage of P-S by PTE is a two-step process with the free energy spans of 15.8 and 26.0 kcal mol-1 for the RP- and SP-enantiomer VX, respectively, and such remarkable stereospecificity of VX enantiomers in the enzymatic degradation is attributed to their conformational compatibility with the active pocket. The structurally less adaptive SP-enantiomer allows one additional water molecule to enter the binuclear zinc center and remarkably facilitates the release of the degraded product. Overall, the rate-limiting steps in the enzymatic degradation of VX by PTE involve the degraded product release of the RP-enantiomer and the enzymatic P-S cleavage of the SP-enantiomer. Further computational analysis on the mutation of selected residues also revealed that H257Y, H257D, H254Q-H257F, and L7ep-3a variants allow more water molecules to enter the active site, which improves the catalytic efficiency of PTE, as observed experimentally. The present work provides mechanistic insights into the stereoselective hydrolysis of VX by PTE and the activity manipulation through the active-site accessibility of water molecules, which can be used for the enzyme engineering to defeat chemical warfare agents.

Hydroboration of CO2 to Methyl Boronate Catalyzed by a Manganese Pincer Complex: Insights into the Reaction Mechanism and Ligand Effect.

The conversion of carbon dioxide to fuels, polymers, and chemicals is an attractive strategy for the synthesis of high-value-added products and energy-storage materials. Herein, the density functional theory method was employed to investigate the reaction mechanism of CO2 hydroboration catalyzed by manganese pincer complex, [Mn(Ph2PCH2SiMe2)2NH(CO)2Br]. The carbonyl association and carbonyl dissociation mechanisms were investigated, and the calculated results showed that the carbonyl association mechanism is more favorable with an energetic span of 27.0 kcal/mol. Meanwhile, the solvent effect of the reaction was explored, indicating that the solvents could reduce the catalytic activity of the catalyst, which was consistent with the experimental results. In addition, the X ligand effect (X = CO, Br, H, PH3) on the catalytic activity of the manganese complex was explored, indicating that the anionic complexes [MnI - Br]- and [MnI - H]- have higher catalytic activity. This may not only shed light on the fixation and conversion of CO2 catalyzed by earth-abundant transition-metal complexes but also provide theoretical insights to design new transition-metal catalysts.

Electron Regulation of Single Indium Atoms at the Active Oxygen Vacancy of In2 O3 (110) for Production of Acetic Acid and Acetone through Direct Coupling of CH4 with CO2.

The production of acetic acid and acetone from the direct coupling of CO2 and CH4 on the doped In2 O3 (110) surface has been studied by extensive first-principles calculations, and the Ga or Al substitution for the single In atom at the active oxygen vacancy of In2 O3 (110) can stabilize the reaction species and reduce the free energy barrier of the rate-limiting C-H activation for the conversion of CO2 and CH4 to acetic acid. Herein, the metal doping lowers the energy level of partially empty s and p orbitals of In1 at the oxygen vacancy site and manipulates its electronic properties, resulting in the activity improvement. The stable intermediate with the newly-formed CH3 COO* has the available In1 site for subsequent CH4 activation, which may initiate the direct C-C coupling of CH3 COO* and CH3 * to yield C3 species on the doped In2 O3 (110). These findings suggest that the metal doping of the active oxygen vacancy opens an avenue for the carbon-chain growth through heterogeneously catalytic coupling of CO2 and CH4 .

Rational Design of Main Group Metal-Embedded Nitrogen-Doped Carbon Materials as Frustrated Lewis Pair Catalysts for CO2 Hydrogenation to Formic Acid.

Developing efficient and inexpensive main group catalysts for CO2 conversion and utilization has attracted increasing attention, as the conversion process would be both economical and environmentally benign. Here, based on the main group element Al, we designed several heterogeneous frustrated Lewis acid/base pair (FLP) catalysts and performed extensive first-principles calculations for the hydrogenation of CO2. These catalysts, including Al@N-Gr-1, Al@N-Gr-2, and Al@C2N, are composed of a single Al atom and two-dimensional (2D) N-doped carbon-based materials to form frustrated Al/C or Al/N Lewis acid/base pairs, which are all predicted to have high reactivity to absorb and activate hydrogen (H2). Compared with Al@N-Gr-1, both Al@N-Gr-2 and Al@C2N, especially Al@N-Gr-2, containing Al/N Lewis pairs exhibit better catalytic activity for CO2 hydrogenation with lower activation energies. CO2 hydrogenation on the three catalysts prefers to go through a three-step mechanism, i.e., the heterolytic dissociation of H2, followed by the transfer of the hydride near Al to CO2, and finally the activation of a second H2 molecule. Other IIIA group element (B and Ga)-embedded N-Gr-2 materials (B@N-Gr-2 and Ga@N-Gr-2) were also explored and compared. Both Al@N-Gr-2 and Ga@N-Gr-2 show higher catalytic activity for CO2 hydrogenation to HCOOH than B@N-Gr-2. However, the CO2 hydrogenation path on Ga@N-Gr-2 tends to follow a two-step mechanism, including H2 dissociation and subsequent hydrogen transfer. The present study provides a potential solution for CO2 hydrogenation by designing novel and effective FLP catalysts based on main group elements.