Mapping reaction pathways on complex potential energy surfaces (PESs) and locating transition states (TSs) is often used for understanding chemical reaction mechanism(s). The nudged elastic band (NEB) method is widely used for this purpose, but it becomes computationally expensive for large systems due to the repeated evaluation of energies and forces. We present an active learning algorithm coupled with the nudged elastic band, AL-NEB, for efficient convergence to the TS. AL-NEB constructs a surrogate PES and actively selects training points in two phases: (a) Exploration-Exploitation and (b) Renunciation. Strategies have been introduced for making the algorithm efficient and stable. We show the efficacy of the algorithm on several 2D analytical potentials, HCN isomerization, keto-enol tautomerization, and high-dimensional heptamer island diffusion (up to 525 degrees of freedom). In all cases, AL-NEB locates the "exact" TS on the chosen model chemistry with an order-of-magnitude fewer force evaluations than the standard NEB, demonstrating its scalability and efficiency.

Over the past few decades, the field of electrochemistry has witnessed rapid advances in computational methods. This review highlights recent methodological progress in computational electrocatalysis, with a specific focus on the accurate prediction of electrochemical reaction kinetics. Particular emphasis is placed on our group's contributions using single-atom catalysts as model systems to quantitatively simulate the kinetics of energy-relevant small-molecule electrocatalytic reactions. By simultaneously capturing atomic-scale interfacial phenomena in the electric double layer, such as cation effects, explicit solvation structures, proton transfer dynamics, and potential distribution, our approach bridges the gap between idealized models and realistic electrochemical environments and predicts experimental observables, such as current density-potential curves and coverages. The current framework has also revealed previously inaccessible kinetic insights, including hydrogen-bond-mediated intermediate reorganization and its impact on transition states, and potential-driven solvent reorganization that dictates proton transfer kinetics. These advances provide both fundamental kinetic insights into electrocatalytic mechanisms and practical design principles for energy conversion catalysts.

The chemical recycling and utilization of plastic waste and its transformation into value-added chemicals are of great significance for sustainable development and have broad research prospects. Herein, we report a green, simple, mild, metal-free and efficient strategy to obtain oxygen-containing heterocyclic compounds by inducing the cleavage of the C-O and O-H bonds of polyethylene glycol (PEG) through the hydrogen bonds (HBs) of hydroxyl-functionalized ionic liquids (ILs). Through experiments and theoretical calculations, it is found that the anion and cation of IL could respectively activate the O-H bond of polyethylene glycol and the C=O double bond of PhCHO through hydrogen bonds, forming the transition state (TS) M1. Then, the activated hydroxyl O atom of PEG may attack the carbonyl C atom of benzaldehyde through a nucleophilic reaction, thereby forming intermediate I through an addition reaction. Subsequently, in intermediate I, the O atom activated by the ionic liquid anion ([OTf]-) conducts a nucleophilic attack on the C atom activated by the ionic liquid cation ([HO-EtMIm]+), causing the C-O bond to break. Thus, a depolymerization cyclization reaction occurs, forming a new C-O bond and the final target product.

This work investigates the gas-phase reactivity of fluorinated ethers CF3CHFOCF3 and CF3CH2OCF3 toward •OH radicals, corresponding to the reactions CF3CHFOCF3 + •OH → CF3C•FOCF3 + H2O (1) and CF3CH2OCF3 + •OH → CF3C•HOCF3 + H2O (2). Geometry optimizations and harmonic vibrational frequency calculations were performed at the M06-2X/6-311++G(3df,3pd) level of theory. More accurate energy estimates were obtained via single-point calculations using the CBS-QB3//M06-2X/6-311++G(3df,3pd) composite method. The potential energy profiles derived at 0 K indicate that, for both ethers, H-abstraction reactions proceed through transition states involving the formation of pre- and postreactive complexes. Rate constants were calculated over the temperature range of 200-1000 K employing canonical transition state theory (CTST), incorporating tunneling corrections via the Eckart method. The high-pressure limit Arrhenius equations derived at the CBS-QB3//M06-2X/6-311++G(3df,3pd) level can be represented by k = C exp[-(D1 - (D2/T))/T], where C = (5.9 ± 1.7) × 10-12 cm3 molecule-1 s-1, D1 = (4032 ± 1327) K, and D2 = (4.7 ± 1.1) × 105 K2 for reaction (1), and C = (1.2 ± 0.2) × 10-11 cm3 molecule-1 s-1, D1 = (2921 ± 1168) K, and D2 = (2.9 ± 0.8) × 105 K2 for reaction (2). Additionally, atmospheric lifetimes of the studied ethers were estimated and discussed.

Attributed to the high conductivity of the () face of 4H-SiC, understanding the HF-assisted wet etching mechanism of this crystal face is crucial for semiconductor processing by clarifying the influence of surface terminations and functional groups on the etching process. In this study, we performed a first-principles investigation of the stepwise HF etching process on the () face with OH or coexisting F and OH terminations. By elucidating the etching reaction pathway, we identified key transition states, intermediates, and rate-determining steps. Analysis of adsorption configurations, charge transfer, and bonding characteristics reveals that HF dissociation strongly depends on surface termination, with the activation energy on the F-OH coterminated surface (2.51 eV) markedly lower than that on the OH-terminated surface (2.86 eV). In both cases, etching favors Si over C, with Si preferentially volatilized as SiF4 rather than SiHF3, highlighting a strong selectivity for complete fluorination. Importantly, the Pt-Ni-C-N4 dual-atom catalyst, distinguished by excellent stability and economic advantage over pure Pt, lowers the energy barrier by ∼1 eV, rendering etching possible at ambient temperature. These findings shed light on termination-dependent etching behavior and guide the design of efficient low-temperature etching strategies for the nonpolar face of 4H-SiC.

To simulate enzyme reactions, multiscale quantum mechanics/molecular mechanics (QM/MM) approaches are well established and popular. However, accurately and efficiently estimating enzyme activity is a challenge, because in general, precise methods are too computationally expensive. Here, we demonstrate that enzyme catalysis can be captured by coupling efficient, reactive machine-learned potentials (MLPs) trained on gas phase data to the wider enzyme environment using electrostatic machine learning embedding (EMLE). The EMLE scheme is first applied to the natural Diels-Alderase AbyU, showing that it correctly differentiates the catalytic action on different enzyme-substrate conformations. Then, we show that training a reaction-specific EMLE model allows us to accurately capture the enzyme catalytic effects of the conversion of chorismate to prephenate, a reaction with a highly polarizable and charged transition state. In both cases, in contrast to mechanical embedding approaches, the EMLE scheme allows accurate and efficient predictions of enzyme catalysis, agreeing with high-level QM/MM reference calculations. This approach facilitates the use of gas phase-trained MLPs in MLP/molecular mechanics (ML/MM) simulations and should thus be highly beneficial for computational activity screening of enzyme biocatalysts.

Herein, we report that nitroalkanes are competent electrophiles for the enantioselective copper hydride (CuH)-catalyzed alkene hydrofunctionalization of vinyl(hetero)arenes to generate hydroxylamines in good yields and with high levels of enantioselectivity. Control experiments and density functional theory (DFT) calculations suggest that the nitro group constitutes the active electrophile. The direct addition of the enantioenriched alkyl copper intermediate to the nitro group outcompetes competitive reduction or deprotonation of the nitroalkane. DFT calculations indicate that the addition of the stereoenriched alkyl copper intermediate to nitroalkane electrophiles occurs through a six-membered cyclic transition state featuring dearomatization of the vinyl arene. Overall, this process constitutes a one-step route to access enantioenriched N-alkylhydroxylamine from vinylarenes and nitroalkanes.

Zeolites are essential catalysts for organic transformations owing to their confined nanoporous environments. However, experimental mechanistic studies are costly, and traditional simulations lack scalability, relying on manual structural manipulation. Here we introduce pore transition-state finder (PoTS), an automated pipeline for locating transition states (TS) in zeolites. PoTS identifies gas-phase TSs via density functional theory, docks them near active sites in zeolite pores and uses their reaction modes to seed condensed-phase TS searches with the dimer method. This automation reduces user intervention, improves success rates and bypasses the need for long path-following calculations. We apply PoTS to a density functional theory-level dataset of zeolite-confined TSs, finding good experimental agreement in both cases. Last, we propose a path to address the limitations we observe regarding unsuccessful TS searches and insufficient theory in other reactions, such as alkene cracking.

Ethanol decomposition is a prototypical multichannel organic reaction in which electron correlation plays a decisive role in determining activation barriers and reaction selectivity. We use fixed-node diffusion Monte Carlo (FN-DMC) to investigate three principal decomposition pathways: dehydration, C-C bond cleavage, and H2 elimination. The obtained results are compared with those from Hartree-Fock (HF), hybrid density functional theory (B3LYP), modified Gaussian-2 composite theory, and experimental kinetic data. By recovering the missing many-body correlation, FN-DMC lowers the HF forward activation barriers by 4-15kcal mol-1 and yields barrier heights that are consistent with available Arrhenius activation parameters within expected thermal corrections. A correlation-energy analysis along the intrinsic reaction coordinate reveals a pathway-dependent modulation of dynamical correlation near the transition state, with the largest stabilization observed for the dehydration channel. The results demonstrate that FN-DMC provides a robust description of static activation barriers and offers mechanistic insight into the evolution of electron-correlation effects in complex bond-breaking reactions.

Eleven feasible stationary points have been located on the potential energy surface of the ground electronic state of (CO)2 with shapes H, I , T, V, X, and Z. The global minimum has a planar, slipped, antiparallel arrangement of the atoms with a CC contact. There is a secondary minimum with an OO contact. The first-order transition state connecting the two minima has a CO contact. The remaining feasible stationary points are higher-order transition states. At intermediate levels of electronic structure theory, one can easily become lost in the web of polytopism. The relative energies of the most important stationary points were determined with the help of the focal-point analysis scheme. The relative energies are based on calculations up to the CCSDT(Q) level of electronic structure theory, basis sets up to aug-cc-pV6Z, and the inclusion of so-called ‘small’ corrections due to core-core and core-valence correlation, relativistic effects, and the diagonal Born–Oppenheimer correction. The electronic interaction energy of the global minimum is − ( hc ) 136.8 ( 15 ) cm − 1 , while the electronic energy difference between the global and local minima is (hc)17.1(25) cm − 1 . A detailed interaction energy analysis via symmetry-adapted perturbation theory suggests that the bonding in the dimer arises primarily from dispersion rather than electrostatics.

Surface morphology is widely recognized to influence wetting behavior; however, a comprehensive understanding of how specific morphological factors govern the Cassie-Wenzel transition remains incomplete. In this work, building on a bivariate energy-minimization framework, we focus on a key structural design parameter characterizing individual surface defects and systematically investigate its effect-both independently and in conjunction with surface defect density-on three critical aspects of the Cassie-Wenzel transition: wettability, energy barrier, and static friction. Our results demonstrate that this structural design parameter exerts distinct influences on the Cassie-Wenzel transition, depending on the wetting type: in type A, the Wenzel state is energetically favored, while in type B, the Cassie state represents the global energy minimum. These findings reveal that this parameter modulates the stability and reversibility of wetting states, as well as droplet mobility, through nontrivial energy landscapes. Moreover, we uncover a previously unreported non-monotonic dependence of static friction on the morphological factors, which we attribute to a geometric constraint on the contact angle of the transition state. We anticipate that our findings can offer quantitative design guidelines for engineering surfaces with tunable wettability and droplet transport properties.

Here, we reported a Cu(II)-catalyst with a water-tolerant active site for the Friedel-Crafts reaction of 4-amino-6-hydroxy-2-mercaptopyrimidine with various aldehydes in aqueous medium, using a surfactant. A portion of the hydrated homogeneous copper(II) complex remains an effective Lewis acid in this reaction, consistent with the theoretical study (DFT) and various control experiments. The study revealed the involvement of a water-assisted hydrogen atom transfer (HAT), indicating the importance of surrounding water molecules. The influence of explicit water-solvation models (20- and 60-molecule shells) on the structures and energies of selected intermediates and transition states was studied. Furthermore, the gram-scale synthesis, recyclability of the reaction medium, and various green chemistry parameters demonstrated the sustainability of our process. Additionally, the structure and relative energies of the various tautomers of product bis-(2-thiopyrimidine) compounds were investigated at the DFT and SCS-MP2 levels. The water-assisted tautomerization mechanism is described, showing that the keto form is prevalent in neutral solutions. The doubly protonated and quadruple deprotonated forms exist in acidic and basic media, as confirmed by TDDFT-predicted UV-vis spectra and DFT-calculated 1H-NMR shifts, which are supported by the respective experimental spectra.

Abstract Strategies to improve ionic conductivity in solid electrolytes focus predominantly on the static interactions between polyanions and cations, while the dynamic behavior of polyanions has been largely overlooked. In this work, we employ machine-learning molecular dynamics (MLMD) to explore the coupling between Na + migration and [BH 4 ] - reorientation in Na 3 OBH 4 . The results show that polyanion reorientations occur at rates about four orders of magnitude higher than Na + migrations and exhibit only weak temporal correlation with them, indicating that Na + transport does not follow a paddle-wheel mechanism. Analysis of the atomistic energy landscape reveals that [BH 4 ] - reorientation induces localized potential fluctuations that split the Na + energy states, raising the initial-state energy while lowering the transition-state energy and thereby generating low-barrier migration pathways. Frequency analyses further identify an optimal relation between the fluctuation frequency and Na + vibrational modes that enhances low-temperature ionic diffusivity. These results confirm dynamic frustration as a central factor in polyanion-assisted cation transport, providing design guidelines for complex hydride electrolytes.

Bifurcating reactions yield multiple products from a single transition state (TS) without intervening minima, rendering product selectivity a formidable challenge, which is governed by dynamic effects rather than TS energetics. Herein, we report a rare instance of product selectivity in a bifurcating dimerization pathway of 2,3-diazacyclopentadienone. The reaction proceeds through two sequential unsymmetric bifurcations on the potential energy surface via a stepwise mechanism involving an intermediate, ultimately yielding a selectively dimerized product. The adduct formed via the N═N moiety acting as the dienophile is kinetically favored and proceeds through a closed-shell TS, while the thermodynamically controlled adduct where the C═C moiety serves as the dienophile is accessed through a singlet biradicaloid TS. The work further rationalizes the intricate interplay of the electronic structure and behavior that modulates electron flow and drives the dimerization that ultimately originates unprecedented product selectivity in a complex bifurcating landscape.

Herein, we report a one-pot dual oxyfunctionalization reaction of ubiquitous gem-dimethyl groups using a single Pd(II)/Pd(IV) catalytic system, achieving both hydroxyl-acyloxylation and diacetoxylation by employing N-pyridine ylide as a directing group. This strategy exhibits remarkable generality, tolerating a wide range of functional groups and enabling the late-stage modification of complex drug derivatives. Mechanistic studies, including 18O-labeling experiments, kinetic analysis, and DFT calculations, unveil a pathway involving sequential C-H activations. The observed heteroselectivity is governed by kinetic preferences, stemming from distinctive noncovalent interactions in key transition states. This work provides a novel solution to the intermolecular 1,3-heterodifunctionalization of C(sp3)-H bonds, offering a powerful and versatile toolkit for molecular construction.

Structural dissection of three transition states along the folding pathway of PDZ6 from PDZD2.

Mechanistic study of the steric effect of Lewis acids AlCl3 and TiBr4 on the asynchronous [4+2] cycloaddition reaction of isoprene with Aryl acid: MEDT study.

Thermo-responsive nanostructured surface: Beeswax for enhanced condensation performance across solid, liquid, and transition states

Characterization of EGCG-concentration responsive gel of tamarind seed polysaccharide.

Mutation of Pro76 affects the dynamics of Ω-loop D of yeast Iso-1-cytochrome c: Application of gated electron transfer.