Calixarene‐Mediated Liquid Membrane Transport of Choline Conjugates 2: Transport of Drug‐Choline Conjugates and Neurotransmitters

Abstract

Lower rim carboxylic acid calix[n]arenes and upper rim phosphonic acid functionalized calix[4]arenes effect selective transport of distinct molecular payloads through a liquid membrane. The secret to this success lies in the attachment of a receptor-complementary handle. We find that the trimethylammonium ethylene group present in choline is a general handle for the transport of drug and drug-like species. Furthermore, neurotransmitters possessing ionizable amine termini are also transported. Some limitations to this strategy have been uncovered as payloads become increasingly lipophilic. These developments reveal new approaches to synthetic receptor-mediated selective small molecule transport in vesicular and cellular systems.

Ab initio design of drug carriers for zoledronate guest molecule using phosphonated and sulfonated calix[4]arene and calix[4]resorcinarene host molecules

“…17,[21][22][23] Drug delivery and solubilization using calix[n]arenes or calix [4]resorcinarenes have been reported. [24][25][26][27][28][29][30][31][31][32][33][34][35][36][37][38] However, the use of calixarenes and calixresorcinarenes as drug delivery is still a relatively novel concept, and the number of experimental or computational studies reported so far is relatively low, despite that these macrocyclic compounds possess several advantages such as ease of synthesis and modification and low toxicity.…”

Calixarene-mediated liquid membrane transport of choline conjugates 3: The effect of handle variation on neurotransmitter transport

“…2 and Table 1). 31 Transport was enhanced 4.6 times when HEPES buffered source and receiving phases were used. The enhanced transport in HEPES was a surprise to us.…”

“…15 Our second study examined the nature of the payload and we found many drug and drug like entities were efficiently transported through a liquid membrane – usually at rates far superior compared to controls lacking a calixarene transporter. 31 Some limits obviously emerged, but also exciting results showing that serotonin and dopamine with a smaller ammonium handle were also transported. Concurrently, we serendipitously uncovered a third useful handle in the form of an ammonium dicarboxylate.…”

“…Simultaneously we explored the role of HEPES buffer on these events as we previously noted a surprising advantage while using it for one payload. 31 …”

Research on Synthesis of New Azo Calix[4]arene and its Dyeing Properties

“…It is characterized by adjustable cavity, convertible conformation, easy chemical modification and functionalization, easy synthesis, inexpensive raw materials and so on [2] . In recent years, with in-depth study of host-guest chemistry, the functional modification and application of the calixarenes become a popular research topic in this field [3] .…”