## 2 Results
### Selectivity Studies
#### 2.3.1 Cross-Reactivity Tests  
The results for the non-competitive cross-reactivity assays are given in Supplementary Figure S21, while Table 2 shows the cross-reactivity indices (XRF) to enable a direct comparison of the uptake of each competing analyte by the MIP with respect to **1**. The XRF for an analyte is defined as the ratio of the analyte (**17**, **18**, **19** or **20**) to **1** MIP binding within the MIP. \begin{table}
\begin{tabular}{l c c c c c c} \hline \hline
**MIP** & & **1** & **17** & **18** & **19** & **20** \\ \hline \multirow{3}{*}{**E7\({}_{\text{1-MIPCHCI3}}\)**} & Bound (\%)1  & 51.5 \(\pm\) 3.4 & 6.7 \(\pm\) 0.8 & 17.4 \(\pm\) 3.1 & 74.5 \(\pm\) 5.8 & 52.1 \(\pm\) 4.9 \\  & AB (\%)2  & 33.5 \(\pm\) 2.9 & -1.3 \(\pm\) 1.8 & 5.4 \(\pm\) 3.8 & 34.8 \(\pm\) 6.2 & 27.8 \(\pm\) 5.5 \\  & XRF3  & 1.00 & 0.13 & 0.34 & 1.44 & 1.01 \\ \hline \multirow{3}{*}{**E7\({}_{\text{2-MIPCHCI3}}\)**} & Bound (\%) & 82.9 \(\pm\) 2.2 & 12.2 \(\pm\) 2.7 & 19.4 \(\pm\) 7.4 & 82.9 \(\pm\) 2.4 & 74.2 \(\pm\) 3.9 \\  & AB (\%) & 45.6 \(\pm\) 2.3 & 2.8 \(\pm\) 2.1 & 3.3 \(\pm\) 3.1 & 23.4 \(\pm\) 2.5 & 35.3 \(\pm\) 2.2 \\  & XRF & 1.00 & 0.15 & 0.23 & 1.00 & 0.90 \\ \hline \multirow{3}{*}{**T7\({}_{\text{1-MIPCHCI3}}\)**} & Bound (\%) & 43.3 \(\pm\) 3.4 & 3.5 \(\pm\) 1.1 & 18.5 \(\pm\) 2.5 & 54.9 \(\pm\) 1.2 & 35.8 \(\pm\) 4.0 \\  & AB (\%) & 31.4 \(\pm\) 3.6 & 0.6 \(\pm\) 2.3 & 9.0 \(\pm\) 2.6 & 24.6 \(\pm\) 1.2 & 14.2 \(\pm\) 4.0 \\  & XRF & 1.00 & 0.08 & 0.43 & 1.27 & 0.83 \\ \hline \multirow{3}{*}{**T7\({}_{\text{2-MIPCHCI3}}\)**} & Bound (\%) & 76.4 \(\pm\) 3.4 & 11.2 \(\pm\) 1.2 & 20.5 \(\pm\) 4.2 & 76.8 \(\pm\) 4.0 & 62.3 \(\pm\) 1.8 \\  & AB (\%) & 52.1 \(\pm\) 5.0 & 2.2 \(\pm\) 1.2 & 7.0 \(\pm\) 4.5 & 25.1 \(\pm\) 4.1 & 35.0 \(\pm\) 4.0 \\  & XRF & 1.00 & 0.15 & 0.27 & 1.01 & 0.82 \\ \hline \multirow{3}{*}{**E16\({}_{\text{MIPCHCI3}}\)**} & Bound (\%) & 26.3 \(\pm\) 2.5 & 16.8 \(\pm\) 0.7 & 11.0 \(\pm\) 2.0 & 26.0 \(\pm\) 2.2 & 18.9 \(\pm\) 1.5 \\  & AB (\%) & 17.5 \(\pm\) 3.2 & 8.9 \(\pm\) 1.4 & 1.5\(\pm\) 2.3 & 12.1 \(\pm\) 2.2 & 14.0 \(\pm\) 2.2 \\ \cline{1-1}  & XRF & 1.00 & 0.64 & 0.42 & 0.99 & 0.72 \\ \hline \multirow{3}{*}{**T16\({}_{\text{MIPCHCI3}}\)**} & Bound (\%) & 53.0 \(\pm\) 1.4 & 45.0 \(\pm\) 1.5 & 16.4 \(\pm\) 2.2 & 39.8 \(\pm\) 2.2 & 34.8 \(\pm\) 4.4 \\ \cline{1-1}  & AB (\%) & 48.5 \(\pm\) 1.9 & 41.0 \(\pm\) 1.6 & 8.5 \(\pm\) 2.3 & 36.8 \(\pm\) 4.6 & 32.1 \(\pm\) 4.5 \\ \cline{1-1}  & XRF & 1.00 & 0.85 & 0.31 & 0.75 & 0.66 \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Non-competitive cross-reactivity results for **1**-MIPs against cocaine (**17**), morphine (**18**), ephedrine (**19**) and phenylpiperazine (**20**). Figure 7: Chemical structures of illicit drugs used in competition and selectivity studies for **1**-based MIPs: cocaine (**17**), morphine (**18**), ephedrine (**19**) and phenylpiperazine (**20**). The four self-assembly MIPs (E7\({}_{\text{1-MIPCHCI3}}\), E7\({}_{\text{2-MIPCHCI3}}\), T**7\({}_{\text{1-MIPCHCI3}}\) and T**7\({}_{\text{2-MIPCHCI3}}\)) displayed high levels of cross-reactivity with **19** and **20**, with the XRFs ranging from 0.82 to 1.44, low to moderate with **18** (XRF = 0.23 to 0.43) and negligible with **17** (XRF = 0.08 to 0.15). Selective binding (\(\Delta\)B = MIP binding \(-\) NIP binding) followed the same trend. These results reflect the effect of functional group character (electronic, size), relative proximity and orientation on each analyte with respect to **1**. Analytes **17** and **18** are both large molecules that differ in shape, potential and available functional groups to **1**, leading to a poor 'fit' within the imprinted cavities (Supplementary Figure S22). Consequently, they displayed low sorption and low affinity to the MIPs. In contrast, **19** and **20** are similar in size and chemical character to **1**, consistent with the observed high XRFs (Supplementary Figure S23).