Mapping Antibiotic Photocatalytic Transformation and Resistance Risks with a DFT‐Informed Machine Learning Workflow

C Chen‐Chen Zhao (State Key Laboratory of Coordination Chemistry, School of Chemistry Nanjing University Nanjing Jiangsu 210023 P.R. China) S Sihan Xing (State Key Laboratory of Coordination Chemistry, School of Chemistry Nanjing University Nanjing Jiangsu 210023 P.R. China) C Cheng Fu L Lifeng Zheng H Huaizhu Wang (State Key Laboratory of Coordination Chemistry, MOE Key Laboratory of Mesoscopic Chemistry, MOE Key Laboratory of High Performance Polymer Materials and Technology, Jiangsu Key Laboratory of Advanced Organic Materials, Suzhou Key Laboratory of Green Intelligent Manufacturing of New Energy Materials and Devices, Tianchang New Materials and Energy Technologies Research Center, Institute of Green Chemistry and Engineering, School of Chemistry and Chemical Engineering) Z Zhong Jin (State Key Laboratory of Coordination Chemistry, MOE Key Laboratory of Mesoscopic Chemistry, MOE Key Laboratory of High Performance Polymer Materials and Technology, Jiangsu Key Laboratory of Green Energy Catalysis and Intelligent Chemical Engineering, Suzhou Key Laboratory of Green Intelligent Manufacturing of New Energy Materials and Devices, Tianchang New Materials and Energy Technologies Research Center, Institute of Green Chemistry and Engineering, School of Chemistry and Chemical Engineering) S Shuhua Li S Shujuan Zhang (State Key Laboratory of Crop Genetics & Germplasm Enhancement and Utilization, Department of Plant Biology, College of Life Sciences, Nanjing Agricultural University) J Jing Ma (State Key Laboratory of Coordination Chemistry, School of Chemistry)

Abstract

Abstract The photocatalytic degradation of antibiotics is effective but may yield transformation products (TPs) that sustain or amplify ecological risks, including antibiotic resistance gene (ARG) induction. This study developed a predictive framework that couples photocatalytic experiments, high‐resolution mass spectrometry, density functional theory (DFT) calculations and machine learning (ML) to assess risks of TPs. Using tetracycline as a model compound, we constructed a reaction network over 120 steps and 9 533 reactions, and trained an ML model to rapidly predict Gibbs free energy changes with DFT accuracy. Automatic transition‐state searches were integrated to evaluate kinetic accessibility within the network. The generalizability of this approach was validated with pathways of five different antibiotics involving 545 reactions. Furthermore, a multi‐dimensional scoring system was developed that integrates diversity, ecotoxicity, biodegradability, and feasibility (DEBF) to prioritize pathways by both reactivity and sustainability. Several hydroxylated, aminated, and amide–ketone TPs were identified as high‐risk species with enhanced ARG‐binding potential. By bridging molecular energetics with ecological outcomes, this work offers a generalizable, mechanism‐anchored, and risk‐aware approach for analyzing photocatalytic transformations and deriving design principles for pollutant degradation that balance efficiency with ecological safety.

Article Details

Volume / Issue Vol. 65, Issue 9
Published February 23, 2026
ISSN 1433-7851
Publisher Wiley

Journal Info

Angewandte Chemie International Edition

Wiley

ISSN: 1433-7851 Physical Sciences

Authors (9)

C

Chen‐Chen Zhao

State Key Laboratory of Coordination Chemistry, School of Chemistry Nanjing University Nanjing Jiangsu 210023 P.R. China

S

Sihan Xing

State Key Laboratory of Coordination Chemistry, School of Chemistry Nanjing University Nanjing Jiangsu 210023 P.R. China

C

Cheng Fu

L

Lifeng Zheng

H

Huaizhu Wang

State Key Laboratory of Coordination Chemistry, MOE Key Laboratory of Mesoscopic Chemistry, MOE Key Laboratory of High Performance Polymer Materials and Technology, Jiangsu Key Laboratory of Advanced Organic Materials, Suzhou Key Laboratory of Green Intelligent Manufacturing of New Energy Materials and Devices, Tianchang New Materials and Energy Technologies Research Center, Institute of Green Chemistry and Engineering, School of Chemistry and Chemical Engineering

Z

Zhong Jin

State Key Laboratory of Coordination Chemistry, MOE Key Laboratory of Mesoscopic Chemistry, MOE Key Laboratory of High Performance Polymer Materials and Technology, Jiangsu Key Laboratory of Green Energy Catalysis and Intelligent Chemical Engineering, Suzhou Key Laboratory of Green Intelligent Manufacturing of New Energy Materials and Devices, Tianchang New Materials and Energy Technologies Research Center, Institute of Green Chemistry and Engineering, School of Chemistry and Chemical Engineering

S

Shuhua Li

S

Shujuan Zhang

State Key Laboratory of Crop Genetics & Germplasm Enhancement and Utilization, Department of Plant Biology, College of Life Sciences, Nanjing Agricultural University

J

Jing Ma

State Key Laboratory of Coordination Chemistry, School of Chemistry