## 5 Coating Materials with Embedded Antibiotics and Other Antibofilm Agents
### N-halamine Compounds  
\(N\)-halamines (see Figure 2 for the general chemical structure) have biocidal properties due to the oxidation state of +1 of the halide atom [39]. [PERSON] et al. [40] prepared novel antibacterial nanoparticles by the immobilization of \(N\)-halamines onto polystyrene (PS)-coated silica nanoparticles. For the covalent attachment of PS to the surface of the silica nanoparticles, the authors used the \"grafting through\" methodology. In this synthetic strategy, the surface of the silica nanoparticles is first functionalized with a coupling reagent like 3-(methacryloxy)propyltrimethoxysilane (MPS) in order to introduce polymerizable vinyl groups, which in the presence of a suitable initiator like azobisisobutyronitrile (AIBN) will serve as comonomers in the early stages of further polymerization of styrene [41]. Increasing the MPS grafting density, hybrid silica-PS nanoparticles with well-defined core-shell morphology could be obtained [42]. The higher the MPS grafting density, the higher the probability of oligomeric radicals derived from styrene to be captured by silica, thereby promoting the formation of a PS shell around silica. The synthetic pathway is presented in Scheme 9. In brief, silica nanoparticles were synthesized by the classical method of St\(\ddot{\text{o}}\)ber through base-catalyzed hydrolysis and condensation of tetraethylorthosilicate (TEOS). Next, MPS was added dropwise to the reaction mixture to afford MPS-modified silica nanoparticles (MPS-SiO\({}_{2}\) NPs). The silica nanoparticles surface-modified with vinyl groups were mixed with styrene in toluene, and radical polymerization was initiated by adding AIBN. The polymerization reaction was allowed to proceed at 80 \({}^{\circ}\)C for 12 h to afford polystyrene coated silica nanoparticles (SiO\({}_{2}\)@PS NPs). Next, the 2,2,6,6-tetramethyl-4-piperidinol (TMP) moiety was covalently immobilized on SiO\({}_{2}\)@PS NPs in two steps. First, the benzene rings of PS were chloromethylated using the noncarcinogenic chloromethylation reagent 1,4-bis(chloromethyloxy)butane (BCMB) in the presence of the Lewis acid catalyst SnCl\({}_{4}\). Second, the chloromethylated product was treated with TMP in anhydrous tetrahydrofuran (THF) in the presence of NaH to obtain SiO2@PS/TMP NPs. Eventual chlorination was carried out by reacting SiO2@PS/TMP NPs with sodium hypochlorite in a buffered solution at pH 7. The antimicrobial activity of the SiO\({}_{2}\)@PS/N-halamine NPs was assessed by the plate counting method using _E. coli_ as a model bacterium. After incubation, the colonies grown on the plates were counted, and the percent survival was calculated as the ratio between the number of surviving bacterial colonies of the test sample and that of the control _E. coli_ without antibacterial treatment. No bacterial survival was seen on the culture plate corresponding to the sample that was exposed for 1 h to the SiO\({}_{2}\)@PS/N-halamine NPs [40]. As one can expect, the antibacterial activity was dependent on  
Figure 2: General chemical structure of an \(N\)-halamine. the oxidative chlorine content of the nanoparticles, which was determined by iodometric/thiosulfate titration procedure according to the following equations:  
\[> \text{N-Cl}+2\Gamma^{-}+\text{H}^{+}\rightarrow> \text{N-H}+\text{I}_{2}+\text{Cl}^{-} \tag{1}\] \[\text{I}_{2}+2\text{S}_{2}\text{O}_{3}{}^{2-}\to 2\Gamma^{-}+ \text{S}_{4}\text{O}_{6}{}^{2-} \tag{2}\]  
**Scheme 9. ** Synthetic pathway to antimicrobial \(N\)-halamine-functionalized silica nanoparticles [40]. Adapted from an open access source. The highest oxidative chlorine content of 2.37% in the SiO2@PS/N-halamine NPs was achieved using a concentration of 5 wt % NaClO in the final step and conducting the chlorination reaction at a temperature of 25 \({}^{\circ}\)C for 2 h [40].