Jul 2026· Chemical Science· Vol 17, pp. 15580 - 15594· 0 citations· 48 references
Medicine
Abstract
Proton-coupled electron transfer (PCET) mediated by hydroquinone and related molecules is key to natural and artificial energy conversion. The reactivity of these molecules depends on their bond dissociation free energy (BDFE), but studying the relationship between structure and thermochemistry across this chemical space has been limited by challenging experimental setup and high computational expense. Here, we present the first use of the AIMNet2 neural network potential to calculate average BDFE (BDFEavg) values for the 2H+/2e− dehydrogenation of about 200 000 hydroquinone-like compounds, including vicinal diamines, diols, and dithiols. Benchmarking against DFT calculations for 168 substituted ortho-phenylenediamines (opda) shows good agreement (R2 ∼ 0.84). Our analysis finds that the BDFEavg of diamines ranges from 50 to 80 kcal mol−1 and can be systematically tuned by modifying the backbone and N-substitution: electron-withdrawing groups raise BDFEavg by up to 15 kcal mol−1, while lower aromaticity in furan and thiophene backbones decreases BDFEavg by approximately 10 kcal mol−1 compared to the phenyl systems (∼65 kcal mol−1). Validation through cyclic voltammetry and reactivity studies with quinone oxidants for selected compounds supports the computational results. This extensive thermochemical database and a web-based prediction tool developed as a result of this work will offer valuable resources for designing PCET reagents for catalysis, energy storage, and biomedical uses.
Using a combination of path-integral molecular dynamics and machine-learning techniques, we investigate the structure, energetics, and proton-transfer isomerizations in small Rydberg complexes of the form [NH4][NH3]n (n = 1, 2), at temperatures near T = 50 K. In both clusters, the unpaired negative charge resides predominantly outside the molecular framework and is localized near the unit exhibiting the strongest NH4 character. Relative to classical estimates, the combined effects of thermal and nuclear quantum fluctuations shift the computed vertical detachment energies upward, yielding improved agreement with available experimental measurements. Qualitative and quantitative distinctions emerge between the molecular-orbital Rydberg description and solvated electron scenarios in analogous isoelectronic species of the form (NH3)n-. We further characterize proton-transfer-mediated interconversions between isomeric structures. For the dimer, the reactant and product states are equivalent, whereas in the trimer, the rearrangement involves migration of the NH4 radical from a distal to a central position along a hydrogen-bonded chain. Nuclear quantum effects also substantially modify the free energy landscapes associated with proton-transfer isomerizations, most notably through pronounced tunneling induced reductions of the magnitudes of the activation barriers. At the transition states, a strong correlation is registered between the degree of quantum delocalization of the transferring proton and the spatial distribution of the unpaired electron.
D. Hunt, D. Laria· Journal of Chemical Physics· 0 citations
The complex structural effects of metal ion binding in glycans remain a topic of significant scientific interest. In this study, we implement a machine learning-driven workflow utilizing SchNet-based neural network potentials (NNPs) to efficiently map the conformational space of neutral and metalated N-acetylhexosamines (HexNAc) with near-first-principles accuracy. By constructing an extensive database of local minima for all 64 HexNAc isomers, we identify critical trends in how alkali metal ions modulate carbohydrate conformation. Our NNP-driven structural search scheme, validated against cryogenic infrared photodissociation (IRPD) spectra, successfully identifies the specific low-energy conformers responsible for experimentally observed vibrational signatures. Notably, our results reveal a diverse set of structural and energetic trends that vary significantly across the different metalated HexNAc systems. These findings underscore the necessity of explicit, automated structure searching, as the non-intuitive coordination environments of metal ions preclude the use of generalized conformational rules.
K. K. S. Custodio, Temma Yazawa, H. Phan et al.· Physical Chemistry, Chemical...· 0 citations
We provide design principles for predicting bond exchange kinetics in acylsemicarbazide (ASC)-based systems that can be applied to tuning the properties of dynamic networks. Because of their capability of dynamic and reversible bond dissociation, ASCs are promising motifs in the design of tunable dynamic covalent networks that combine mechanical robustness with reprocessability and stability. We elucidate the factors that determine the rate of bond dissociation using density functional theory in combination with detailed kinetic studies on the mechanism of the ASC dissociation. Several ASC compounds were investigated, R1─C(═O)(H)N─N(H)─C(═O)NH─R2, with R1 methyl or phenyl, and R2 methyl, phenyl, or benzoyl, that dissociate into hydrazide and isocyanate parts. The experimentally measured dissociation rate correlates with the proton affinity of the N─H bond next to R2, which could also be used to predict relative dissociation rates a priori. Proton-transfer assistance is required for efficient bond exchange. A water molecule, but also neighboring ASCs (reactant) and hydrazides (product), lowers the activation barrier for bond dissociation considerably, likely facilitating autocatalysis that can occur in polymeric ASC networks. These findings can aid in the rational design of reversible polymers based on ASC motifs and can also be generalized for other dynamic covalent networks.
Siebe Lekanne Deprez, Stefan J D Maessen, Angelina N. van Dam et al.· Chemistry· 0 citations
ABSTRACT This study examines the structural stability of CoFe2O4 and the energetics of Langmuir–Hinshelwood recombinative desorption of two pre-adsorbed hydrogen atoms on the CoFe2O4 (111) surface, relevant to high-temperature thermochemical hydrogen production. A pretrained universal M3GNet graph neural-network potential is used for machine-learning molecular dynamics (MLMD), combined with surface DFT calculations at the PBE level. Two-phase MLMD simulations identify an equilibrium melting temperature of approximately 1350 K, while single-phase heating of a defect-free crystal yields an apparent transition at 1700K, interpreted as a superheating-limited upper bound. Within this solid-phase temperature window, DFT calculations show that atomic H is strongly chemisorbed on Co (Eads = −2.04 eV) and O (Eads = −4.29 eV) sites, with O-H bond lengths consistent with experiment, while molecular H₂ is only weakly physisorbed (Eads = 0.001 eV). The recombinative desorption of two co-adsorbed H atoms on adjacent Co/O sites proceeds with an activation barrier of 0.46 eV and an estimated rate of 1.6 × 1010 s−1 at 1300 K, confirming that H-H recombination is fast and is not the rate-limiting step under hydrogen-rich conditions. All DFT values are reported without an explicit Hubbard U correction and represent best feasible estimates within the present computational constraints.
R. Arifin, Y. Winardi, I. Widaningrum et al.· Molecular Simulation· 0 citations
Pyridine-based compounds constitute an important class of molecules with broad pharmaceutical relevance owing to their diverse biological activities. Among these, 2-aminopyridine is widely used as a versatile precursor for the construction of heterocyclic frameworks. This work describes the growth of a proton-transfer single crystal, 2-aminopyridinium dihydrogen phosphate (2APDHP), using the slow solvent evaporation technique. Single-crystal X-ray diffraction confirmed that the crystal belongs to the monoclinic system. Structural optimization was carried out at the HF and DFT levels with the 6-311++G(d,p) basis set, providing detailed information on the molecular geometry, bond distances and bond angles. The electronic characteristics were examined through frontier molecular orbital calculations. Experimental FT-IR and Raman spectra were interpreted with the aid of theoretical vibrational calculations, yielding close agreement between the calculated and observed frequencies. Molecular docking was performed to examine the interaction of 2APDHP with α-synuclein of Parkinson’s disease, 6-hydroxymethyl-7,8 dihydropteroate synthase from Mycobacterium tuberculosis and the SARS-CoV-2 main protease.
G. Sivaraj, N. Jayamani, T. M. Viswanathan et al.· Asian Journal of Chemistry· 0 citations
This study investigates the formation and properties of three proton-transfer complexes: piperidine-picric acid (PIP–PA), piperidine-7,7,8,8-tetracyanoquinodimethane (PIP–TCNQ), and morpholine-picric acid (MOR–PA). Utilizing piperidine and morpholine as electron donors, picric acid (PA) and 7,7,8,8-tetracyanoquinodimethane (TCNQ) as strong organic electron acceptors, this research employs both experimental and computational methods to analyze their electronic structures and stability. Experimentally, equimolar quantities of the donor and acceptor were reacted in chloroform; the resulting precipitates were purified and recrystallized to yield colored crystals. Composition was confirmed via CHN elemental analysis, UV/Vis spectroscopy, and FT-IR spectroscopy, while thermal stability and phase transition behavior were assessed using a Uni-melt capillary melting point apparatus. Theoretically, quantum-chemical calculations were performed using the SE-PM6 method in the Spartan software package. The results indicate linear correlations between experimental melting points and calculated formation enthalpies, heat capacities, dipole moments, and absolute hardness values. Ultimately, this integration of experimental and theoretical approaches elucidates the proton-transfer interactions involved, providing essential insights for the development of advanced organic electronics, such as sensors and high-efficiency solar cells.
KEY WORDS: Piperidine, Morpholine, Picric acid, TCNQ, Proton-transfer complex, Experimental approach, Theoretical approach
Bull. Chem. Soc. Ethiop. 2026, 40(11), 2305-2317
DOI: https://dx.doi.org/10.4314/bcse.v40i11.2
M. Refat, R. D. de Farias, Nada A. Adam et al.· Bulletin of the Chemical Soc...· 0 citations