A series of crown boronic acids, 1−4, were synthesized and studied as carriers for catecholamine transport through bulk liquid membranes (BLMs) and supported liquid membranes (SLMs). Carrier 1 greatly facilitated the transport of primary catecholamines through BLMs; whereas, the more lipophilic analogues 3 and 4 were less effective. A combination of kinetic, mass spectral, and NMR evidence suggests that the transported species in BLMs is the cyclic, zwitterionic, 1:1 complex 7. The SLM transport studies used a liquid membrane of 2-nitrophenyl octyl ether supported by a thin, flat sheet of porous polypropylene. In the absence of carrier there was neglible dopamine transport (<5 × 10-9 mol/m2·s) at pH 7.2. When the membrane contained carrier 3 (33 mM or about 2% wt), facilitated catecholamine transport was observed in the order of dopamine (5 × 10-7 mol/m2·s) > epinephrine (1.5 × 10-7 mol/m2·s) > norepinephrine (0.8 × 10-7 mol/m2·s). SLMs containing carrier 3 were stable, implying that carrier 3 is a very good candidate for transport mechanism studies. Crown boronic acid 4 was an even better transport carrier of primary catecholamines with a transport order of norepinephrine (4.7 × 10-6 mol/m2·s) > dopamine (3.5 × 10-6 mol/m2·s) ≫ epinephrine (3 × 10-8 mol/m2·s). It is 10 times more effective than an equimolar mixture of boronic acid 5 and crown 6, which is one of best examples of ditopic cooperativity yet observed in SLM transport. SLMs containing 4, however, did not exibit long-term stability. Overall, it is possible that a device based on SLMs containing crown boronic acid carriers can be developed to selectively extract catecholamines from clinical samples.

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A QSAR model accounting for "average" G-protein-coupled receptor (GPCR) binding was built from a large set of experimental standardized binding data (1939 compounds systematically tested over 40 different GPCRs) and applied to the design of a library of "GPCR-predicted" compounds. Three hundred and sixty of these compounds were randomly selected and tested in 21 GPCR binding assays. Positives were defined by their ability to inhibit by more than 70% the binding of reference compounds at 10 microM. A 5.5-fold enrichment in positives was observed when comparing the "GPCR-predicted" compounds with 600 randomly selected compounds predicted as "non-GPCR" from a general collection. The model was efficient in predicting strongest binders, since enrichment was greater for higher cutoffs. Significant enrichment was also observed for peptidic GPCRs and receptors not included to develop the QSAR model, suggesting the usefulness of the model to design ligands binding with newly identified GPCRs, including orphan ones.

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