Potentiometric, enantioselective sensors for alkyl and aryl ammonium ions of pharmaceutical significance, based on lipophilic cyclodextrins

Abstract

Lipophilic α, β and γ cyclodextrins (CDs) have been systematically analysed in order to establish their selective binding to onium ions. They have been identified as excellent ionophores for a range of ions of vital importance in clinical, pharmaceutical and forensic analysis. From the results obtained we found the following. A peroctylated cyclodextrin provides a size-selective cavity for the binding and detection of onium ions. Potentiometric α, β and γ cyclodextrin-based electrodes selectively sense NH₄⁺, NMe₄⁺ and NEt₄⁺ ions respectively. These experiments were performed in order to enable us to understand the nature of analyte recognition by the lipophilic cyclodextrins. Peroctylated αCD is a suitable ionophore for dopamine hydrochloride, -log[C] = 5.4, -log K = 2.0 (in serum level of Na⁺, K⁺, Ca²⁺) whereas peroctylated and 2,6 didodecyl βCD sense acetylcholine chloride, -log[C] = 5.0, -log K = 4.2 (in serum level of Na⁺, K⁺, Ca²⁺) and creatinine hydrochloride, -log K = 2.7 (in serum level of Na⁺, K⁺, Ca²⁺), respectively. The 2,6 didodecyl βCD responds to more bulky aryl ammonium ions such as the anaesthetics procaine, prilocaine and lignocaine hydrochlorides, -log K = 4.2 (in serum level of Na⁺, K⁺, Ca²⁺). Partially octylated αCD has been identified as an enantioselective sensor for ephedrine hydrochloride, -log K = 4.5 (in serum level of Na⁺, K⁺, Ca²⁺), -log K^pot± = 2.6, and related compounds such as amphetamine hydrochloride. The 2,6 didodecyl βCD is enantioselective for propranalol hydrochloride, -log K = 4.2 (in serum level of Na⁺, K⁺, Ca²⁺), -log K^pot± = 2.7. Complexation has also been studied by electrospray mass spectrometry (ESMS).

Key Words:

• anaesthetics
• chiral sensors
• drugs
• electrospray mass spectrometry
• ion-selective electrodes
• neurotransmitters