Ligand-controlled growth and stabilization of doped ZnO2 nanoparticles for dual antibacterial and enzyme inhibition

Abstract Maintaining structural stability in multifunctional nanoparticles (NPs) remain a challenge in nanomedicine. To address this limitation, organic ligand-capped pristine and doped zinc peroxide (ZnO2) NPs were synthesized via co-precipitation method for enhanced antibacterial efficacy against...

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Main Authors: Imran Ullah, Reinhard B. Neder, Huma Parwaz, Zul Kamal, Cai-Hong Zhan, Komal Qazi, Inam ud Din, Hari Pokhrel
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-15917-6
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author Imran Ullah
Reinhard B. Neder
Huma Parwaz
Zul Kamal
Cai-Hong Zhan
Komal Qazi
Inam ud Din
Hari Pokhrel
author_facet Imran Ullah
Reinhard B. Neder
Huma Parwaz
Zul Kamal
Cai-Hong Zhan
Komal Qazi
Inam ud Din
Hari Pokhrel
author_sort Imran Ullah
collection DOAJ
description Abstract Maintaining structural stability in multifunctional nanoparticles (NPs) remain a challenge in nanomedicine. To address this limitation, organic ligand-capped pristine and doped zinc peroxide (ZnO2) NPs were synthesized via co-precipitation method for enhanced antibacterial efficacy against Gram-positive bacteria (methicillin-resistant Staphylococcus aureus (MRSA) and Bacillus cereus (BC)), and inhibition of the acetylcholinesterase enzyme (AChE). The synthesized samples were characterized using complementary characterization techniques. In-situ studies confirmed citrate (cit) molecules slow down the nucleation kinetics, while manganese (Mn) and cobalt (Co) doping reduces the optical bandgap from 3.07 eV to 2.89 eV, and 2.79 eV, respectively. Critically, ligand engineering and doping substantially improved bioactivity. ZnO2 NPs exhibited dose-dependent antimicrobial activities, with 7.7 ± 0.9 mm and 8.6 ± 0.9 mm zones of inhibition (ZOIs) at 1000 µg/ml concentration against MRSA and BC, respectively. Incorporation of 3% Mn into the ZnO2 lattice improved the ZOIs to 8.9 ± 1.7 mm against MRSA and 11 ± 1.9 mm against BC at 1000 µg/ml concentration. Notably, 5% Co-doped with cit capping exhibits the ZOIs of 12.5 ± 2.0 mm against MRSA and 6.4 ± 1.5 mm BC at 1000 µg/ml. 3% Mn-doped ZnO2 NPs with dmlt as capping agent showed ZOIs of 10.3 ± 1.7 mm against MRSA and 12.3 ± 1.9 mm against BC at 1000 µg/ml concentration. Furthermore, the anti-acetylcholinesterase enzyme (AChE) activities of the synthesized NPs were assessed. At 125 µg/ml concentration, cit-capped ZnO2 NPs inhibits 75.5 ± 0.1% of AChE activity. 3% Mn-doped ZnO2 NPs show the inhibition of 73.2 ± 0.2% AChE, enhancing to 82 ± 0.3% upon pent capping. In contrast, 3% Co-doped ZnO2 NPs and dmlt-capped 5% Co-doped ZnO2 NPs exhibit modest AChE inhibition, with values of 62.4 ± 0.3% and 54.5 ± 0.2%, respectively. Molecular docking studies suggested moderate interaction of ZnO2 NPs with phenol-soluble modulins alpha2 (PSMα2), strong interaction with Phospholipase C Regulator (PlcR), and moderate interaction with 1EEA (acetylcholinesterase from Electrophorus electricus (electric eel)). This study introduced a novel approach utilizing highly stabilized ZnO2 NPs as potent antimicrobial agents and acetylcholinesterase inhibitors.
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spelling doaj-art-6226e1434c5e4b14babe61baa2edf9482025-08-20T03:47:12ZengNature PortfolioScientific Reports2045-23222025-08-0115112310.1038/s41598-025-15917-6Ligand-controlled growth and stabilization of doped ZnO2 nanoparticles for dual antibacterial and enzyme inhibitionImran Ullah0Reinhard B. Neder1Huma Parwaz2Zul Kamal3Cai-Hong Zhan4Komal Qazi5Inam ud Din6Hari Pokhrel7Institute of Condensed Matter Physics, Chair of Crystallography and Structural Physics, Friedrich-Alexander UniversityInstitute of Condensed Matter Physics, Chair of Crystallography and Structural Physics, Friedrich-Alexander UniversityDepartment of Physics, University of Science and Technology BannuChongqing University of Chinese MedicinesKey Laboratory of the Ministry of Education for Advanced Catalysis Material, College of Chemistry and Materials Science, Zhejiang Normal UniversityDepartment of Biotechnology, University of Science and Technology BannuDepartment of Physics, University of PeshawarDepartment of Physics, Friedrich-Alexander UniversityAbstract Maintaining structural stability in multifunctional nanoparticles (NPs) remain a challenge in nanomedicine. To address this limitation, organic ligand-capped pristine and doped zinc peroxide (ZnO2) NPs were synthesized via co-precipitation method for enhanced antibacterial efficacy against Gram-positive bacteria (methicillin-resistant Staphylococcus aureus (MRSA) and Bacillus cereus (BC)), and inhibition of the acetylcholinesterase enzyme (AChE). The synthesized samples were characterized using complementary characterization techniques. In-situ studies confirmed citrate (cit) molecules slow down the nucleation kinetics, while manganese (Mn) and cobalt (Co) doping reduces the optical bandgap from 3.07 eV to 2.89 eV, and 2.79 eV, respectively. Critically, ligand engineering and doping substantially improved bioactivity. ZnO2 NPs exhibited dose-dependent antimicrobial activities, with 7.7 ± 0.9 mm and 8.6 ± 0.9 mm zones of inhibition (ZOIs) at 1000 µg/ml concentration against MRSA and BC, respectively. Incorporation of 3% Mn into the ZnO2 lattice improved the ZOIs to 8.9 ± 1.7 mm against MRSA and 11 ± 1.9 mm against BC at 1000 µg/ml concentration. Notably, 5% Co-doped with cit capping exhibits the ZOIs of 12.5 ± 2.0 mm against MRSA and 6.4 ± 1.5 mm BC at 1000 µg/ml. 3% Mn-doped ZnO2 NPs with dmlt as capping agent showed ZOIs of 10.3 ± 1.7 mm against MRSA and 12.3 ± 1.9 mm against BC at 1000 µg/ml concentration. Furthermore, the anti-acetylcholinesterase enzyme (AChE) activities of the synthesized NPs were assessed. At 125 µg/ml concentration, cit-capped ZnO2 NPs inhibits 75.5 ± 0.1% of AChE activity. 3% Mn-doped ZnO2 NPs show the inhibition of 73.2 ± 0.2% AChE, enhancing to 82 ± 0.3% upon pent capping. In contrast, 3% Co-doped ZnO2 NPs and dmlt-capped 5% Co-doped ZnO2 NPs exhibit modest AChE inhibition, with values of 62.4 ± 0.3% and 54.5 ± 0.2%, respectively. Molecular docking studies suggested moderate interaction of ZnO2 NPs with phenol-soluble modulins alpha2 (PSMα2), strong interaction with Phospholipase C Regulator (PlcR), and moderate interaction with 1EEA (acetylcholinesterase from Electrophorus electricus (electric eel)). This study introduced a novel approach utilizing highly stabilized ZnO2 NPs as potent antimicrobial agents and acetylcholinesterase inhibitors.https://doi.org/10.1038/s41598-025-15917-6Zinc peroxide nanoparticlesNucleationAnti-microbial activityAcetylcholinesterase enzyme inhibitionMolecular dockingDensity functional theory (DFT)
spellingShingle Imran Ullah
Reinhard B. Neder
Huma Parwaz
Zul Kamal
Cai-Hong Zhan
Komal Qazi
Inam ud Din
Hari Pokhrel
Ligand-controlled growth and stabilization of doped ZnO2 nanoparticles for dual antibacterial and enzyme inhibition
Scientific Reports
Zinc peroxide nanoparticles
Nucleation
Anti-microbial activity
Acetylcholinesterase enzyme inhibition
Molecular docking
Density functional theory (DFT)
title Ligand-controlled growth and stabilization of doped ZnO2 nanoparticles for dual antibacterial and enzyme inhibition
title_full Ligand-controlled growth and stabilization of doped ZnO2 nanoparticles for dual antibacterial and enzyme inhibition
title_fullStr Ligand-controlled growth and stabilization of doped ZnO2 nanoparticles for dual antibacterial and enzyme inhibition
title_full_unstemmed Ligand-controlled growth and stabilization of doped ZnO2 nanoparticles for dual antibacterial and enzyme inhibition
title_short Ligand-controlled growth and stabilization of doped ZnO2 nanoparticles for dual antibacterial and enzyme inhibition
title_sort ligand controlled growth and stabilization of doped zno2 nanoparticles for dual antibacterial and enzyme inhibition
topic Zinc peroxide nanoparticles
Nucleation
Anti-microbial activity
Acetylcholinesterase enzyme inhibition
Molecular docking
Density functional theory (DFT)
url https://doi.org/10.1038/s41598-025-15917-6
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