Fanyang Mo

Hao Xu, Jinglong Lin, Dongxiao Zhang et al.

A new research framework is proposed to incorporate machine learning techniques into the field of experimental chemistry to facilitate chromatographic enantioseparation. A documentary dataset of chiral molecular retention times (CMRT dataset) in high-performance liquid chromatography is established to handle the challenge of data acquisition. Based on the CMRT dataset, a quantile geometry-enhanced graph neural network is proposed to learn the molecular structure-retention time relationship, which shows a satisfactory predictive ability for enantiomers. The domain knowledge of chromatography is incorporated into the machine learning model to achieve multi-column prediction, which paves the way for chromatographic enantioseparation prediction by calculating the separation probability. Experiments confirm that the proposed research framework works well in retention time prediction and chromatographic enantioseparation facilitation, which sheds light on the application of machine learning techniques to the experimental scene and improves the efficiency of experimenters to speed up scientific discovery.

Zhiyuan Yan, Chen Liu, Boxuan Zhao et al.

Molecules are graphs, but large language models~(LLMs) are usually asked to reason about them through linear strings. The most popular molecular representation, SMILES, compresses atoms, bonds, branches and rings into a compact sequence in which topology is implicit, forcing LLMs to reconstruct molecular structure before performing the requested chemical operation. Here we introduce MoleCode, an LLM-native, training-free, graph-explicit molecular language in which all molecular components are represented as typed entities with persistent identifiers and explicit relations. MoleCode makes molecular topology directly readable, editable and auditable within the language context, allowing an LLM to operate on structure rather than recover it from syntax. Across molecular reasoning, editing, generation and analysis tasks, this representational shift improves frontier LLMs most strongly when structural access is limiting: unfamiliar molecules, topology-sensitive operations, larger structures and repetitive polymers. It also changes how inference is allocated, replacing long reasoning traces devoted to implicit structural reconstruction with shorter, more chemically directed reasoning over explicit atoms and bonds. In molecular optimization, this enables localized, property-aligned edits that preserve structural similarity to the starting compounds. The same Subgraph--Node--Edge grammar extends beyond small molecules to polymers, Markush structures, mechanism-style transformations and interleaved scientific documents, including research articles and patent disclosures in which chemical information is distributed across text and images. These results suggest that the interface between scientific objects and LLMs should not treat structure as something to be decoded from text. When the object of reasoning is relational, the structure itself should be part of the language.

Chengchun Liu, Yuntian Chen, Fanyang Mo

Organic chemistry is undergoing a major paradigm shift, moving from a labor-intensive approach to a new era dominated by automation and artificial intelligence (AI). This transformative shift is being driven by technological advances, the ever-increasing demand for greater research efficiency and accuracy, and the burgeoning growth of interdisciplinary research. AI models, supported by computational power and algorithms, are drastically reshaping synthetic planning and introducing groundbreaking ways to tackle complex molecular synthesis. In addition, autonomous robotic systems are rapidly accelerating the pace of discovery by performing tedious tasks with unprecedented speed and precision. This article examines the multiple opportunities and challenges presented by this paradigm shift and explores its far-reaching implications. It provides valuable insights into the future trajectory of organic chemistry research, which is increasingly defined by the synergistic interaction of automation and AI.

Chengchun Liu, Wendi Cai, Boxuan Zhao et al.

Accurate molecular geometries are a prerequisite for reliable quantum-chemical predictions, yet density functional theory (DFT) optimization remains a major bottleneck for high-throughput molecular screening. Here we present GeoOpt-Net, a multi-branch SE(3)-equivariant geometry refinement network that predicts DFT-quality structures at the B3LYP/TZVP level of theory in a single forward pass starting from inexpensive initial conformers generated at a low-cost force-field level. GeoOpt-Net is trained using a two-stage strategy in which a broadly pretrained geometric representation is subsequently fine-tuned to approach B3LYP/TZVP-level accuracy, with theory- and basis-set-aware calibration enabled by a fidelity-aware feature modulation (FAFM) mechanism. Benchmarking against representative approaches spanning classical conformer generation (RDKit), semiempirical quantum methods (xTB), data-driven geometry refinement pipelines (Auto3D), and machine-learning interatomic potentials (UMA) on external drug-like molecules demonstrates that GeoOpt-Net achieves sub-milli-Å all-atom RMSD with near-zero B3LYP/TZVP single-point energy deviations, indicating DFT-ready geometries that closely reproduce both structural and energetic references. Beyond geometric metrics, GeoOpt-Net generates initial guesses intrinsically compatible with DFT convergence criteria, yielding nonzero ``All-YES'' convergence rates (65.0\% under loose and 33.4\% under default thresholds), and substantially reducing re-optimization steps and wall-clock time. GeoOpt-Net further exhibits smooth and predictable energy scaling with molecular complexity while preserving key electronic observables such as dipole moments. Collectively, these results establish GeoOpt-Net as a scalable, physically consistent geometry refinement framework that enables efficient acceleration of DFT-based quantum-chemical workflows.

Wenchao Wu, Hao Xu, Dongxiao Zhang et al.

We present an innovative of artificial intelligence with column chromatography, aiming to resolve inefficiencies and standardize data collection in chemical separation and purification domain. By developing an automated platform for precise data acquisition and employing advanced machine learning algorithms, we constructed predictive models to forecast key separation parameters, thereby enhancing the efficiency and quality of chromatographic processes. The application of transfer learning allows the model to adapt across various column specifications, broadening its utility. A novel metric, separation probability ($S_p$), quantifies the likelihood of effective compound separation, validated through experimental verification. This study signifies a significant step forward int the application of AI in chemical research, offering a scalable solution to traditional chromatography challenges and providing a foundation for future technological advancements in chemical analysis and purification.

Chengchun Liu, Fanyang Mo

Infrared (IR) spectroscopy is a pivotal technique in chemical research for elucidating molecular structures and dynamics through vibrational and rotational transitions. However, the intricate molecular fingerprints characterized by unique vibrational and rotational patterns present substantial analytical challenges. Here, we present a machine learning approach employing a Structural Attention Mechanism tailored to enhance the prediction and interpretation of infrared spectra, particularly for diazo compounds. Our model distinguishes itself by honing in on chemical information proximal to functional groups, thereby significantly bolstering the accuracy, robustness, and interpretability of spectral predictions. This method not only demystifies the correlations between infrared spectral features and molecular structures but also offers a scalable and efficient paradigm for dissecting complex molecular interactions.

Siyu Lou, Chengchun Liu, Yuntian Chen et al.

Thin-layer chromatography (TLC) is a crucial technique in molecular polarity analysis. Despite its importance, the interpretability of predictive models for TLC, especially those driven by artificial intelligence, remains a challenge. Current approaches, utilizing either high-dimensional molecular fingerprints or domain-knowledge-driven feature engineering, often face a dilemma between expressiveness and interpretability. To bridge this gap, we introduce Unsupervised Hierarchical Symbolic Regression (UHiSR), combining hierarchical neural networks and symbolic regression. UHiSR automatically distills chemical-intuitive polarity indices, and discovers interpretable equations that link molecular structure to chromatographic behavior.

Hao Xu, Jinglong Lin, Qianyi Liu et al.

As an essential attribute of organic compounds, polarity has a profound influence on many molecular properties such as solubility and phase transition temperature. Thin layer chromatography (TLC) represents a commonly used technique for polarity measurement. However, current TLC analysis presents several problems, including the need for a large number of attempts to obtain suitable conditions, as well as irreproducibility due to non-standardization. Herein, we describe an automated experiment system for TLC analysis. This system is designed to conduct TLC analysis automatically, facilitating high-throughput experimentation by collecting large experimental data under standardized conditions. Using these datasets, machine learning (ML) methods are employed to construct surrogate models correlating organic compounds' structures and their polarity using retardation factor (Rf). The trained ML models are able to predict the Rf value curve of organic compounds with high accuracy. Furthermore, the constitutive relationship between the compound and its polarity can also be discovered through these modeling methods, and the underlying mechanism is rationalized through adsorption theories. The trained ML models not only reduce the need for empirical optimization currently required for TLC analysis, but also provide general guidelines for the selection of conditions, making TLC an easily accessible tool for the broad scientific community.