The Effects of O-Substituents of Hexahomotrioxacalix[3]arene on Potentiometric Discrimination between Dopamine and Biological Organic/Inorganic Cations

Abstract

A variety of methods for the determination of catecholamines (dopamine, noradrenaline, and adrenaline) and their metabolites in biological media have been proposed. Catecholamines are especially important because they are involved in many human physiological and biochemical processes. 1,2) Catecholamines are typically determined by HPLC analysis with electrochemical detection. [3][4][5][6] In most cases, the preliminary extraction and purification of catecholamines from biological samples are necessary. On the other hand, the direct potentiometric determination of catecholamines is extremely attractive. However, the development of ion-selective electrodes for catecholamines is difficult, considering their similar structures and relatively hydrophilic nature. Only a few reports of the potentiometric determination of catecholamines have appeared in the literature. [7][8][9][10] For the development of sensory elements for dopamine, we focused on the hexahomotrioxacalix[3]arene skeleton, which contains both ethereal and phenolic oxygens, both of which are capable of forming tripodal hydrogen bonds with the protonated primary amino group of dopamine. It has been reported that the hexahomotrioxacalix[3]arene host 1 (cone conformer), 11) when incorporated into a poly(vinyl chloride) (PVC) liquid membrane displays a high selectivity for dopamine in membrane potential changes, compared to other catecholamines (noradrenaline and adrenaline) and inorganic cations (Na ϩ and K ϩ ). 7)Guest-induced changes in membrane potential at the membrane without hosts are reflected in only the guest lipophilicity factor. On the other hand, changes in a host are reflected in two factors, i.e., the guest lipophilicity factor and the hostguest complexation factor. Mi and Bakker 12) and Ceresa and Pretsch 13) recently reported on the determination of the hostguest complexation factor (complex formation constants) in PVC membranes to characterize the binding capability of ionophores. We present here a quantitative analysis of the two factors that contribute to dopamine selectivity, in an attempt to better understand the effects of the O-substituents of hexahomotrioxacalix[3]arene hosts 2-5 (Fig. 1). The hostguest complexation factor in PVC membranes constitutes very important information for the further development of sensory elements for dopamine. As an interesting type of molecular recognition at a membrane surface, the tri-O-acetic acid ester (host 2) of hexahomotrioxacalix[3]arene, when incorporated into poly(vinyl chloride) (PVC) liquid membranes, displays a high potentiometric selectivity for dopamine over, not only other catecholamines (noradrenaline, adrenaline), but also quaternary ammonium guests (tetramethylammonium, choline, and acetylcholine) and inorganic cations (Na Results and Discussion Synthesis of Host Molecules). Interestingly, changes in membrane potential based on the host-guest complexation of host 2 that were observed dopamine/inorganic cation selectivity were not displayed by the related hosts 3 and 4, which contain ...