Current
United States Food and Drug Administration (FDA)-approved
lithium salts are plagued with a narrow therapeutic window. Recent
attempts to find alternative drugs have identified new chemical entities,
but lithium’s polypharmacological mechanisms for treating neuropsychiatric
disorders are highly debated and are not yet matched. Thus, re-engineering
current lithium solid forms in order to optimize performance represents
a low cost and low risk approach to the desired therapeutic outcome.
In this contribution, we employed a crystal engineering strategy to
synthesize the first ionic cocrystals (ICCs) of lithium salts with
organic anions. We are unaware of any previous studies that have assessed
the biological efficacy of any ICCs, and encouragingly we found that
the new speciation did not negatively affect established bioactivities
of lithium. We also observed that lithium ICCs exhibit modulated pharmacokinetics
compared to lithium carbonate. Indeed, the studies detailed herein
represent an important advancement in a crystal engineering approach
to a new generation of lithium therapeutics.