Computational Examination of Water Adduction to Lithiated Cannabinoids (2024)

Undergraduate: Conner Baucom

Faculty Advisor: Gary Glish
Department: Chemistry

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Lithium cationized isomers can often be differentiated by a simple water adduction reaction in quadrupole ion trap mass spectrometry. We have previously used this approach with carbohydrates (pentoses, hexoses and disaccharides). Subsequently we have determined cannabinoid isomers can also be identified via water adduction to the lithium cationized cannabinoids (CBD, various THC isomers). Experimentally, CBD shows very little water adduction while for the THC isomers 60-85% water adductions is observed. The cannabinoids are different than the carbohydrates though because the potential sites of lithiations are much fewer but with greater chemical variety with the possibility of cation-pi interactions. With carbohydrates, DFT calculations suggest that water adduction is observed when lithium is bound in a bidentate interaction, but not for tri or tetra dentate interactions. For the cannabinoids however, there has not yet been a tridentate binding conformation observed for any of the compounds tested. In this work, we use high level double hybrid theory to elucidate the nature of water adduction for lithiated cannabinoids