Inclusion Complexations of Levamisole and Cocaine With Molecular Baskets. Fluorescence Displacement Assay for Detection of Cocaine and Its Adulterant Levamisole in Aqueous Media
- 1Department of Chemistry & Biochemistry The Ohio State University Columbus Ohio USA
Abstract
We investigated inclusion complexation of levamisole (LEV+), a common adulterant of cocaine (COC+), with six molecular baskets 1 3− –6 18− of increasing cavity depth and anionic charge at the portal. 1H NMR and mass spectrometry showed that 1 3− to 6 18− bind to LEV+ to form binary complexes in water, with the stability increasing across the series and highest for dendritic basket 6 18− (K d = 10 µM). From 1H NMR magnetic shielding and OPLS4 calculations, we deduced that LEV+ inserts its benzene in the binding pocket of 1 3−–6 18− while the protonated heterocycle remains near the anionic portal. The stability of [LEV⊂6]17− arises from C−H…π/cation…π/π−π contacts, ion pairing, and hydrophobic effect (ΔH°< 0, ITC). Dendritic basket 6 18− was subsequently used to develop a fluorescent displacement assay (FDA) for the detection of LEV+ with alizarin red S (ALZ−) as a fluorescence reporter. LEV+ displaced the dye to generate a fluorescence response suitable for its detection in water over circa 10–300 µM range. In contrast, COC+ bound more strongly to basket 6 18−, forming binary (K d = 1 µM) and ternary complexes (1H NMR, calorimetry, and FDA). The binding mode of COC+ differs from that of LEV+, with the drug's cationic fragment occupying the basket's cavity.
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BibTeX
@article{mortensen2026inclusion,
title = {{Inclusion Complexations of Levamisole and Cocaine With Molecular Baskets. Fluorescence Displacement Assay for Detection of Cocaine and Its Adulterant Levamisole in Aqueous Media}},
author = {Christopher T. Mortensen and Carson E. Ward and Nitesh Kumar and Logan Willemann and Ryan Lutz and Kailey Hughes and Zheng Zheng and Jovica D. Badjić},
journal = {Chemistry (Weinheim an Der Bergstrasse, Germany)},
year = {2026},
month = jun,
doi = {10.1002/chem.71216},
url = {https://doi.org/10.1002/chem.71216},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Inclusion Complexations of Levamisole and Cocaine With Molecular Baskets. Fluorescence Displacement Assay for Detection of Cocaine and Its Adulterant Levamisole in Aqueous Media
AU - Christopher T. Mortensen
AU - Carson E. Ward
AU - Nitesh Kumar
AU - Logan Willemann
AU - Ryan Lutz
AU - Kailey Hughes
AU - Zheng Zheng
AU - Jovica D. Badjić
PY - 2026
DA - 2026/06/03
JO - Chemistry (Weinheim an Der Bergstrasse, Germany)
DO - 10.1002/chem.71216
UR - https://doi.org/10.1002/chem.71216
AB - We investigated inclusion complexation of levamisole (LEV+), a common adulterant of cocaine (COC+), with six molecular baskets 1 3− –6 18− of increasing cavity depth and anionic charge at the portal. 1H NMR and mass spectrometry showed that 1 3− to 6 18− bind to LEV+ to form binary complexes in water, with the stability increasing across the series and highest for dendritic basket 6 18− (K d = 10 µM). From 1H NMR magnetic shielding and OPLS4 calculations, we deduced that LEV+ inserts its benzene in the binding pocket of 1 3−–6 18− while the protonated heterocycle remains near the anionic portal. The stability of [LEV⊂6]17− arises from C−H…π/cation…π/π−π contacts, ion pairing, and hydrophobic effect (ΔH°< 0, ITC). Dendritic basket 6 18− was subsequently used to develop a fluorescent displacement assay (FDA) for the detection of LEV+ with alizarin red S (ALZ−) as a fluorescence reporter. LEV+ displaced the dye to generate a fluorescence response suitable for its detection in water over circa 10–300 µM range. In contrast, COC+ bound more strongly to basket 6 18−, forming binary (K d = 1 µM) and ternary complexes (1H NMR, calorimetry, and FDA). The binding mode of COC+ differs from that of LEV+, with the drug's cationic fragment occupying the basket's cavity.
SN - 0947-6539
SN - 1521-3765
ER -