## Materials and Methods
### Rebinding Tests  
A mixture of polymer (2 mg) (MIP or NIP) and the corresponding template (100 \(\upmu\)M) in 2 mL of water was kept under stirring at room temperature. 400 \(\upmu\)L aliquots were taken at different times between 10 min and 24 h and centrifuged (15,100 rpm for 10 min). The supernatant was analyzed by HPLC to quantify the residual free template concentration. A Kinetex C18 250 \(\times\) 4.6 mm 5 \(\upmu\)m 100 A (Phenomenex) column was used with a column guard and a 20 \(\upmu\)L loop and a UV detector set at 220 nm. The flow was set to 1 mL/min. The eluent was solvent A: H\({}_{2}\)O + 0.05% TFA and solvent B: CH\({}_{3}\)CN + 0.05% TFA in 85:15 ratio for analysis of TY and HT, while a gradient was used for the analysis of OL (10 min 85% A and 15% B, 10 min 40% A and 60% B, 10 min 85% A and 15% B).  
Quantitative determination was performed by HPLC using the calibration curves of TY, HT and OL reported in Supplementary Materials (Figures S1 and S2). Standard stock solutions were prepared in water at 10, 30, 50, 80 and 100 \(\upmu\)M concentrations. Each solution was analyzed by HPLC in triplicate and the mean value of each solution was used for the calibration curve.  
The concentration of the free template at each time was calculated as follows:  
\[\left[\text{Templ}\right]_{t}=\frac{\text{Area}_{t}}{\text{Area}_{t0}}\times \left[\text{Templ}\right]_{t0}, \tag{1}\]  
where \(\left[\text{Templ}\right]_{t}\) is the concentration of the template at time \(t\), \(\text{Area}_{t}\) is the area (mV-s) of the chromatogram peak of the template at time \(t\), \(\text{Area}_{t0}\) is the area (mV-s) of the chromatogram peak of the template at the beginning, and \(\left[\text{Templ}\right]_{t0}\) is the concentration of the template at the beginning (100 \(\upmu\)M). The concentration of the template bound to the polymer (nmol/mg) were calculated as follows:  
\begin{table}
\begin{tabular}{c c c c c c c} \hline
**Polymer** & **Template [mg]** & **Functional Monomer [mg]** & **AlBN [mg]** & **Cononomer [mg]** & **Crosslinker [mg]** & **DMSO [mL]** \\ \hline
2 VP-TY & TY & 2 VP & 16.5 & NIPAM & MBA & 4.23 \\  & 8.3 & 5.3 & 5.7 & 36.0 & & \\
2 VP-HT & HT & 2 VP & 16.5 & NIPAM & MBA & \\  & 9.2 & 5.3 & 5.7 & 36.0 & & \\ \hline
4 VP-TY & TY & 4 VP & 16.5 & NIPAM & MBA & 4.23 \\  & 8.3 & 5.3 & 5.7 & 36.0 & & \\
4 VP-HT & HT & 4 VP & 16.5 & NIPAM & MBA & 4.23 \\ \hline
1V2P-TY & TY & 1V2P & 16.5 & NIPAM & MBA & 4.26 \\  & 8.3 & 5.6 & 5.7 & 36.0 & & \\
1V2P-HT & HT & 1V2P & 16.5 & NIPAM & MBA & 4.26 \\  & 9.2 & 5.6 & 5.7 & 36.0 & 4.26 \\ \hline IMD-TY & TY & IMD & 16.5 & NIPAM & MBA & 4.18 \\  & 8.3 & 4.7 & 5.7 & 36.0 & & \\ IMD-HT & HT & IMD & 16.5 & NIPAM & MBA & 4.18 \\ \hline OXO-TY & TY & OXO & 16.5 & NIPAM & MBA & 4.27 \\  & 8.3 & 5.7 & 5.7 & 36.0 & & \\ OXO-HT & HT & OXO & 16.5 & NIPAM & MBA & 4.27 \\  & 9.2 & 5.7 & 5.7 & 36.0 & & \\ \hline
13-TY & TY & 4 VP & 20.2 & **13** & DVB & 5.89 \\  & 8.7 & 5.6 & 23.6 & 30.0 & & \\
13-HT & HT & 4 VP & 20.7 & **13** & DVB & 5.89 \\  & 8.3 & 5.5 & 23.5 & 30.0 & & \\ \hline
14-TY & TY & 4 VP & 20.8 & **14** & DVB & 5.14 \\  & 8.4 & 7.0 & 16.7 & 30.0 & & \\
14-HT & HT & 4 VP & 20.6 & **14** & DVB & 5.14 \\  & 8.5 & 5.4 & 16.9 & 30.0 & & \\ \hline \end{tabular}
\end{table}
Table 1: Composition of the polymerization mixtures for monomers **5–9** and **13–14**.  
\[[\text{Templ}]=([\text{Templ}]_{t0}-[\text{Templ}]_{t})\times\frac{V}{M}, \tag{2}\]  
where \([\text{Templ}]\) is the concentration of the template bound to the polymer, \([\text{Templ}]_{t}\) is the concentration of the template at time \(t\), \([\text{Templ}]_{t0}\) is the concentration of the template at the beginning (100 \(\upmu\)M), \(V\) is the volume (mL) of the solution at the beginning and \(M\) is the mass (mg) of polymer used in the rebinding test.  
The imprinting factor (IF) was calculated as the ratio \([\text{Templ}]_{\text{MIP}}/[\text{Templ}]_{\text{NIP}}\).  
Cross reactivity tests with TY and HT were performed in the same manner at 50 and 100 \(\upmu\)M ligand.