Molecular Imprinting of Benzylpiperazine: A Comparison of the Self-Assembly and Semi-Covalent Approaches
Molecularly imprinted polymers (MIPs) for benzylpiperazine (BZP, <b>1</b>), an illicit designer drug, were developed by using both self-assembly and semi-covalent approaches. From an array of potential functional monomers (FMs) and using a combination of pre-synthetic interaction studies...
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| Format: | Article |
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/6/5117 |
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| author | Kathleen M. Wright Michael C. Bowyer Adam McCluskey Clovia I. Holdsworth |
| author_facet | Kathleen M. Wright Michael C. Bowyer Adam McCluskey Clovia I. Holdsworth |
| author_sort | Kathleen M. Wright |
| collection | DOAJ |
| description | Molecularly imprinted polymers (MIPs) for benzylpiperazine (BZP, <b>1</b>), an illicit designer drug, were developed by using both self-assembly and semi-covalent approaches. From an array of potential functional monomers (FMs) and using a combination of pre-synthetic interaction studies (by molecular modelling and NMR analysis) and binding assays, the highest performing self-assembly <b>1</b>-MIPs were confirmed to result from methacrylic acid (<b>7</b>) as FM, ethylene glycol dimethacrylate (EGDMA) or trimethylolpropane trimethacrylate (TRIM) as crosslinkers and chloroform as the porogen and rebinding solvent at template (T): FM ratios of 1:1 and 1:2, giving imprinting factors (IF) 3 to 7. The semi-covalent <b>1</b>-MIPs were designed using benzylpiperazine (4-vinylphenyl) carbamate (<b>16</b>) as the template–monomer adduct in combination with either EDGMA or TRIM. Our comparative analysis showed the semi-covalent polymers to have a stronger affinity for <b>1</b> (significantly lower K<sub>d</sub> values and higher IFs) and faster uptake than the self-assembly systems. Both approaches have comparable cross-reactivity: marginal to low against cocaine (<b>17</b>) and morphine (<b>18</b>) and high against ephedrine (<b>19</b>) and phenylpiperazine (<b>20</b>). They also have comparable selectivity: highly selective towards <b>1</b> against <b>17</b>, moderate against <b>18</b> and non-selective against <b>19</b>. EGDMA-based self-assembly MIPs displayed a greater imprinting effect (higher IFs and NIP-to-MIP K<sub>d</sub> ratios) than TRIM-based MIPs, while the TRIM-based semi-covalent MIP outperformed its EGDMA-based equivalent. By virtue of its modest selectivity against the test illicit drugs, <b>1</b>-MIPs could potentially be used as a dummy MIP for the broad-based capture and enrichment of illicit drug blends for subsequent laboratory analysis. |
| first_indexed | 2024-03-11T06:27:34Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T06:27:34Z |
| publishDate | 2023-03-01 |
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| spelling | doaj.art-ec46535bdd2c44409d24bca6cbfbcc452023-11-17T11:29:22ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01246511710.3390/ijms24065117Molecular Imprinting of Benzylpiperazine: A Comparison of the Self-Assembly and Semi-Covalent ApproachesKathleen M. Wright0Michael C. Bowyer1Adam McCluskey2Clovia I. Holdsworth3Sanitarium Health Food Company, 1 Sanitarium Drive, Berkeley Vale, NSW 2261, AustraliaAcademic Division, University of Newcastle, Ourimbah, NSW 2258, AustraliaSchool of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, AustraliaSchool of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, AustraliaMolecularly imprinted polymers (MIPs) for benzylpiperazine (BZP, <b>1</b>), an illicit designer drug, were developed by using both self-assembly and semi-covalent approaches. From an array of potential functional monomers (FMs) and using a combination of pre-synthetic interaction studies (by molecular modelling and NMR analysis) and binding assays, the highest performing self-assembly <b>1</b>-MIPs were confirmed to result from methacrylic acid (<b>7</b>) as FM, ethylene glycol dimethacrylate (EGDMA) or trimethylolpropane trimethacrylate (TRIM) as crosslinkers and chloroform as the porogen and rebinding solvent at template (T): FM ratios of 1:1 and 1:2, giving imprinting factors (IF) 3 to 7. The semi-covalent <b>1</b>-MIPs were designed using benzylpiperazine (4-vinylphenyl) carbamate (<b>16</b>) as the template–monomer adduct in combination with either EDGMA or TRIM. Our comparative analysis showed the semi-covalent polymers to have a stronger affinity for <b>1</b> (significantly lower K<sub>d</sub> values and higher IFs) and faster uptake than the self-assembly systems. Both approaches have comparable cross-reactivity: marginal to low against cocaine (<b>17</b>) and morphine (<b>18</b>) and high against ephedrine (<b>19</b>) and phenylpiperazine (<b>20</b>). They also have comparable selectivity: highly selective towards <b>1</b> against <b>17</b>, moderate against <b>18</b> and non-selective against <b>19</b>. EGDMA-based self-assembly MIPs displayed a greater imprinting effect (higher IFs and NIP-to-MIP K<sub>d</sub> ratios) than TRIM-based MIPs, while the TRIM-based semi-covalent MIP outperformed its EGDMA-based equivalent. By virtue of its modest selectivity against the test illicit drugs, <b>1</b>-MIPs could potentially be used as a dummy MIP for the broad-based capture and enrichment of illicit drug blends for subsequent laboratory analysis.https://www.mdpi.com/1422-0067/24/6/5117molecular imprintingmolecularly imprinted polymersMIPself-assembly MIPsemi-covalent MIPbenzylpiperazine |
| spellingShingle | Kathleen M. Wright Michael C. Bowyer Adam McCluskey Clovia I. Holdsworth Molecular Imprinting of Benzylpiperazine: A Comparison of the Self-Assembly and Semi-Covalent Approaches International Journal of Molecular Sciences molecular imprinting molecularly imprinted polymers MIP self-assembly MIP semi-covalent MIP benzylpiperazine |
| title | Molecular Imprinting of Benzylpiperazine: A Comparison of the Self-Assembly and Semi-Covalent Approaches |
| title_full | Molecular Imprinting of Benzylpiperazine: A Comparison of the Self-Assembly and Semi-Covalent Approaches |
| title_fullStr | Molecular Imprinting of Benzylpiperazine: A Comparison of the Self-Assembly and Semi-Covalent Approaches |
| title_full_unstemmed | Molecular Imprinting of Benzylpiperazine: A Comparison of the Self-Assembly and Semi-Covalent Approaches |
| title_short | Molecular Imprinting of Benzylpiperazine: A Comparison of the Self-Assembly and Semi-Covalent Approaches |
| title_sort | molecular imprinting of benzylpiperazine a comparison of the self assembly and semi covalent approaches |
| topic | molecular imprinting molecularly imprinted polymers MIP self-assembly MIP semi-covalent MIP benzylpiperazine |
| url | https://www.mdpi.com/1422-0067/24/6/5117 |
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