## 2 Various PPF Strategies
### PPF of Nanoparticles Incorporated Monoliths  
Recently, [PERSON] and [PERSON] reported polymethacrylate based monolithic columns incorporated with surface modified fumed silica nanoparticles (FSNPs) for use in reversed phase chromatography (RPC) of small solutes and proteins. First, FSNPs were modified with 3-(trimethoxysilyl)propylmethacrylate (TMSPM) to yield the \"hybrid\" methacryloyl fumed silica nanoparticle (MFSNP) monomer [41]. The resulting MFSNP was then mixed with glycerolmonomethacrylate (GMM) and EDMA in a binary porogenic solvent composed of cyclohexanol and dodecanol, and the in situ copolymerization of MFSNP, GMM and EDMA was performed in a stainless steel column of 4.6 mm i.d. (see Scheme 30). The hybrid monolith thus obtained was subjected to PPF that involved the grafting of the free silanols with octadecyl ligands by perfusing the hybrid monolithic column with a solution of 4 % _w/v_ of dimethyloctadecylchlorosilane (DODCS) in toluene while the column was maintained at 110 \({}^{\circ}\)C for 6 h (in a heated HPLC oven). One of the originalities of this study was to demonstrate MFSNP as a novel derivatized \"hybrid monomer\" in making RPC monolithic columns with surface bound octadecyl ligands (Scheme 30). In this respect, the RPC behavior of the monolithic column with \"covalently\" incorporated FNSPs having surface grafted octadecyl ligands was evaluated with alkylbenzenes, aniline derivatives and phenolic compounds. The results showed that the hybrid poly(GMA-MFSNP-EDMA) having surface bound octadecyl ligands exhibited hydrophobic interactions under reversed phase elution conditions. Furthermore, six standard proteins were baseline separated on the column using a 10 min linear gradient elution at increasing ACN concentration in the mobile phase at a flow rate of 1.0 mL/min.  
In another development involving PPF of nanoparticle incorporated monoliths, [PERSON] and [PERSON] [42] reported the preparation and characterization of monolithic capillary columns with incorporated bare fumed silica nanoparticles (FSNPs) and surface coated gluconamide FSNPs and their subsequent use in hydrophilic interaction capillary electrochromatography (HI-CEC) of small relatively polar solutes. The monolithic support was based on the in situ polymerization of GMM and EDMA in the presence of FSNPs yielding the poly(GMM-_co_-EDMA) monolith with incorporated FSNPs (FSNPs-poly(GMM-_co_-EDMA) monolith), which was subsequently subjected to PPF with _N_-(3-triethoxysilypropy)glucuronamide in an on-column approach that resulted in o-glucuronamide-FSNPs-poly(GMM-_co_-EDMA) monolith see Scheme 31. This approach yielded a better CEC performance than the monolithic column with incorporated FSNPs that were treatedpre-column with \(N\)-(3-triethoxysilypropyyl)glucuronamide (p-glucuronamide-FSNPs). It is believed that while the p-glucuronamide-FSNPs was coated by an oligosiloxane gluconamide layer as was revealed by thermogravimetric analysis, the o-gluconamide-FSNPs are thought to be covered with a monomeric layer of gluconamide ligands as was manifested by the higher plate number obtained on the latter than on the former gluconamide-FSNPs incorporated monolithic columns. In the on-column modification process of FSNPs, the reaction was performed in a closed system whereby atmospheric water vapor are not available to cause the polymerization of the trifunctional organosilane \(N\)-(3-triethoxysilypropyyl)glucuronamide. Additionally, the fact that the o-glucuronamide-FSNPs incorporated monoliths were made from bare-FSNPs incorporated monoliths may indicate that the bare FSNPs were better dispersed into the monolithic matrix than the p-glucuronamide-FSNPs, a condition that might have further contributed to the lower plate count obtained on p-glucuronamide- than o-glucuronamide-FSNPs incorporated monolithic columns. Overall, o-glucuronamide-FSNPs stationary phases and to a lesser extent bare-FSNPs stationary phases proved useful in HI-CEC of small polar solutes, including DMF, formamide, thiourea, some phenols and nucleobases.