# Safe Functional Modified CuO Nanoparticles?
## 3 Safe(r)-By-Design and Functionality  
[PERSON] et al. [68] have pointed out that safe(r)-by-design modifications may impact functionality. This is highly relevant to the use of CuO nanoparticles as biocides. The biocidal properties of Cu nanoparticles have been shown to involve the induce generation of reactive oxygen species and the release of Cu ions [69; 70; 71; 72; 73; 74; 75], and these are the properties targeted by safe(r)-by-design modifications as discussed in Sections 2.1 and 2.2.  
Only one of the safe(r)-by-design studies discussed here addressed the impact of the safe(r)-by-design modifications on the biocidal functionality of CuO nanoparticles. [PERSON] et al. [54] found that coatings of CuO with PEG and carboxylate reduced the cytotoxicity in the human cell lines THP1 and HACAT and improved the ratio of activity against _Escherichia coli_ strain MG1655 versus human cell line cytotoxicity, when compared with pristine CuO nanoparticles. The significance of the results obtained by [PERSON] et al. [54] would seem to be limited. _Escherichia coli_ strain MG1655 is not a known pathogen. Extrapolation of the cytotoxicity tests performed by [PERSON] et al. [54] to the impact on human organisms is subject to uncertainty [49; 50; 51]. Furthermore, extrapolations to other organisms are problematic as tests with earthworms [43], _Daphnia magna_[53] and mussels [48] suggested that coatings with carboxylates and PEG might also increase toxicity. Other studies regarding the impact of coating or capping CuO nanoparticles with organic compounds on biocidal activity have shown variable outcomes, which may be dependent on differences in interactions with cells and impacts on toxicity mechanisms [23]. [PERSON] et al. [74] found that capping CuO nanoparticles with cetyl trimethyl ammonium bromide reduced the antibacterial activity against _Staphylococcus lentus_. [PERSON] et al. [76] did show that the coating of biosynthetically produced Cu nanoparticles coated with polyamine increased the antifungal effect against _Aspergillus parasitic_.  
The proposed applications of CuO nanoparticles may also have functionalities that might be impacted by the safe(r)-by-design modifications considered here. The creation of electron holes which underlies sensing responses [16] might, e.g., be affected by shifting the edge of the Fermi energy (which dominates charge transfer) far away from the valence band energy edge, which is instrumental in hazard reduction by doping studied by [PERSON] et al. [40]. As to the proposed application of CuO nanoparticles as catalysts, it may be noted that adsorption of reactants to CuO nanoparticles is important in catalytic activity [11; 77]. This property might be impacted by coating or capping. As shown by [PERSON] et al. [78] electron transfer can be implicated in the catalytic activity of CuO nanoparticles. It seems plausible that doping with Fe and Zn and coating or capping might affect such electron transfer.  
The CuO functionalities' high thermal conductivity and absorbing solar radiation can be exploited in solar stills [17]. As the doping of CuO nanoparticles may, by changing the bandgap, impact the absorption of solar radiation [79], the functionality of doped CuO nanoparticles for use in solar stills may be affected. Furthermore, thermal conductivity may be negatively affected by doping by a metal [80], which may affect functionality in solar stills and collectors. As to the application of CuO particles as fuel additives, coating or capping with organic substances to improve safety is not a good option as organic substances will be degraded during combustion. [PERSON] et al. [20] suggested that the reduction of NOx emissions by CuO nanoparticles in diesel combustion was linked to improved heat transfer, which, as pointed out above, might be affected by doping.  
In view of the forgoing, there is a case to complement studies regarding safe-by-design modifications of CuO nanoparticles with studies regarding the implications thereof for functionality.