Research Article For reprint orders, please contact: reprints@futuremedicine.com Molecular aspects of core-shell intrinsic defect induced enhanced antibacterial activity of ZnO nanocrystals Suresh K Verma 1 , Ealisha Jha 2 , Pritam Kumar Panda 1 , Jugal K Das 1 , Arun Thirumurugan 3 , Mrutyunjay Suar 1 & SKS Parashar *,4 1 School of Biotechnology, KIIT University, Bhubaneswar, Orissa, 751024, India 2 Memorial University of Newfoundland, Department of Physics & Physical Oceanography, St. John’s, Newfoundland & Labrador, NL A1C 5S7 Canada 3 Advanced Materials Laboratory, Department of Mechanical Engineering, Faculty of Mathematical & Physical Sciences, University of Chile, Santiago, Chile 4 School of Applied Sciences, KIIT University, Bhubaneswar, Orissa, 751024, India * Author for correspondence: sksparashar@yahoo.com Aim: To investigate molecular aspects of the antibacterial effect of size-dependent core-shell intrinsic de- fects of nanocrystalline ZnO synthesized through high energy ball milling technique. Materials & methods: Mechanically synthesized and characterized 7, 10 and 15 h milled ZnO nanoparticles were evaluated for antibacterial activity with molecular investigation by computational molecular docking. Results: Synthe- sized ZnO nanoparticles displayed shrinkage of core and increase of shell with reduction in size of bulk ZnO particles from 250 to 80, 40 and 20 nm and increase in zeta potential up to -19 mV in 7, 10 and 15 h nano ZnO. Antibacterial activity was found increased with decrease in size due to increased reactive oxy- gen species and membrane damage in bacteria. Conclusion: Synthesized nano ZnO exhibit size-dependent antibacterial action as consequences of interactions with cell membrane proteins via hydrogen bond in- teraction with amino acid residues followed by internalization, membrane depolarization and induction of reactive oxygen species generation. First draft submitted: 20 July 2017; Accepted for publication: 30 October 2017; Published online: 27 November 2017 Keywords: antibacterial activity • core-shell model • cytotoxicity • high energy ball milling (HEBM) • membrane potential • membrane protein • molecular docking • nano ZnO • oxygen vacancies • ROS In recent time, nanomaterials have been a topic of cynosure because of their wide applications in areas like energy [1], optoelectronics [2], sensors [3], drug delivery [4], etc. Different organic and inorganic nanomaterials have been preferred over their bulk counterpart due to their stability and tunable control over their size and shape. Organic nanoparticles like graphene oxide nanoparticles, carbon nanotubes, etc. and inorganic metal nanoparticles (Ag, Au), as well as metal oxide nanoparticles like TiO 2 , CuO, Al 2 O 3 , Fe 2 O 3 , SnO 2 , MnO 2 , MgO, WO 3 , PdO, ZnO, have been explored for their usage in many physical and biomedical applications like photocatalysis [5–11], heavy metal absorbance [12–25], antibacterial application [26–28], biomedical applications [29], etc. Moreover, their composites have also been reported for many of these applications. One of the most important applications of the inorganic and organic nanomaterials is in different biological applications [30]. Among different known nanomaterials, the biological application of ZnO nanoparticle has been given a special attention over other nanomaterials like TiO 2 , MgO and Al 2 O 3 [31–36] due to its nontoxic, safe and biocompatible properties [37]. They have been reported to exhibit antibacterial [38,39], antiviral [40–43] and tissue adhesive properties [44]. Moreover, they are widely used in drug carriers [45], cosmetics [46] and for biofilling medical materials [47] because of their less cytotoxicity to biological models [48–51]. In addition, they have been proven as a promising material for biochemical sensors, food packaging, photocatalysts and anticancer drugs [52–56]. The diverse functions and application of ZnO nanoparticles are attributed to its diverse nanostructures obtained through a variety of synthesis methods. By controlling the synthesis parameters, ZnO nanoforms of different shape 10.2217/nnm-2017-0237 C  2017 Future Medicine Ltd Nanomedicine (Lond.) (Epub ahead of print) ISSN 1743-5889