ArticleACS omega2024
Revisiting Aspirin Polymorphic Stability Using a Machine Learning Potential.
Article in ACS omega, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Chemical intuition on bond-dissociation energies as an emergent ability of universal machine-learning interatomic potentials.Nature communications · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In this study, we present a systematic computational investigation to analyze the long-debated free energy stability of two well-known aspirin polymorphs, denoted as Form I and Form II. Specifically, we developed a strategy to collect training configurations covering diverse interatomic interactions between representative functional groups in aspirin crystals. Utilizing a state-of-the-art neural network interatomic potential (NNIP) model, we trained an accurate machine learning potential to simulate aspirin crystal dynamics under finite temperature conditions with ∼0.46 kJ/mol/molecule accuracy. Employing the trained NNIP model, we performed thermodynamic integration to assess the free energy difference between aspirins I and II, accounting for the anharmonic effects in a large supercell consisting of 512 molecules. For the first time, our results convincingly demonstrated that Form I is more stable than Form II at 300 K, ranging from 0.74 to 1.83 kJ/mol/molecule, aligning with experimental observations. Unlike the majority of previous simulations based on (quasi)harmonic approximations in a small super cell, which often found degenerate energies between aspirins I and II, our findings underscore the importance of anharmonic effects in determining polymorphic stability ranking. Furthermore, we proposed the use of the rotational degrees of freedom of methyl and ester/phenyl groups in aspirin crystals as characteristic motions to highlight rotational entropic contribution that favors the stability of Form I. From the structural perspective, we also found that the subtle free energy difference can be used to explain the distinct thermal expansion responses as observed in both experimental and simulation data. Beyond the aspirin polymorphism, we anticipate that such entropy-driven stabilization can be broadly applicable to many other organic systems, suggesting that our approach holds great promise for stability studies in small-molecule drug design.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.