## 3 Results and Discussion  
### Molecular Dynamic Simulations  
In order to have a better insight into the possible interactions and thus an explanation of our results in previous studies [7], we used a molecular dynamic simulation to see the possible interactions in the MIP synthesis pre-polymerization complex. Four molecular dynamics simulations were carried out to describe the effect of the template ratio, functional monomers (T-FMs), and the role of crosslinkers in the stability of T-FMs. MIP1 and MIP3 are systems with a 1:6 mol ratio of T:FMs with different crosslinkers, namely EgDMA or TRIM, respectively, to confirm molecular modeling calculations [7]. The other systems, MIP2 and MIP4, with a 1:4 mol ratio of T-FMs, were used as a comparison to the computational calculations. The 1:4 mol ratio of T-FMs is a more common formula used in making MIP [43]. The mean spatial distribution of all pre-polymerized components was extracted from the trajectories using the radial distribution function (RDF) calculation. The degree of proximity of SLX to HEMA is discussed from the RDF point of view. In Figure 1, the atoms that can form the interaction site are labeled. The following figure shows RDF atoms that can form interaction sites. This helps predict the state of the HEMA molecule around the SLX. As shown in Figure 2, TO (atom O labeled in SLX)-MH (atom H labeled in HEMA) atomic contact was present. From the result in Figure 2a-f, the distance of hydrogen bonding was between 1.8 and 3.3 A [44], and MIP3 showed the strongest interaction in each case, with peaks from 3.89 to 6.65. When the distance was more than 3.2 A, there was no interaction between the TO of SLX and the MH of HEMA. TO3 (the number after \"TO\" represents the different atom O in SLX) showed the strongest interaction (Figure 2c), which means that the TO3-MH site can play a dominant role in the identification imprinting process. TO6 already has an h-bond with TH4 between SL and X, and the bond interaction between TH4 and TO6 could be stronger than that of HEMA [45], so the RDF of TO6-MH was weaker than the others. The effect of the crosslinker on the interaction between SLX with HEMA, between TH (atom H labeled in SLX) and CO (atom C labeled in crosslinker), is depicted in Figure 3. EgDMA showed peaks from 1.5 to 2.86 at a distance of 1.8-3.2 A, while TRIM did not show this peak in that radius, which means that there is no hydrogen bond between the TRIM and SLX so it will not interfere with the interaction of SLX with HEMA as a functional monomer. This result indicates that the interactions between EgDMA and SLX are stronger than for TRIM. According to this result, TRIM will have a better performance as a crosslinker compared to EDGMA, as it will not affect the binding between SLX and the functional monomer [46]. Figure 1: Chemical structure of SLX (**a**), HEMA (**b**), EGDMA (**c**), and TRIM (**d**), and atoms studied with RDFs. Figure 2: RDF display the probability of SLX oxygen atoms at distinct separation distances from HEMA hydrogen atoms: (**a**) TO1-MH, (**b**) TO2-MH, (**c**) TO3-MH, (**d**) TO4-MH, (**e**) TO5-MH, (**f**) TO6-MH, (**g**) TO7-MH, and (**h**) TH1-MO; r is a certain distance between atoms. As shown in Table 1, it is not difficult to see that the strongest site of action was achieved by MIP3 with a T:FM:Cl ratio of 1:6:20 with TRIM as the crosslinker. The van der Waals (VDW) atomic radius of O-H is 2.02-3.02 [47]. The use of the summed VDW radii to determine whether a possible hydrogen bond between the donor and acceptor is suspected is an implicit assumption of atomic interpenetration [48]. The closest distance between the hydrogen bond acceptor and hydrogen bond donor atoms and the density of this distance g(r) indicate that this interaction belongs to the short form and hydrogen bonds are easily formed at the site [49]. Hydrogen bonds generally have an interaction strength of 110 kcal mol\({}^{-1}\) (4-40 kJ mol\({}^{-1}\)) [50]. The abundance of hydrogen bonds leads to a very stable structure [51].