2.B.33 The Steroidal Cholapod/Cholaphane Receptor/Carrier (SCRC) Family 

Chloride transport by a series of steroid-based 'cholapod' receptors/carriers has been studied in vesicles. The principal method involved preincorporation of the cholapods in the vesicle membranes, and the use of lucigenin fluorescence quenching to detect inward-transported Cl-. A correlation between anion affinity and transport activity was observed; changes at the steroidal 7 and 12 positions affected both properties in concert although changes at the steroidal 3-position did not. Among the steroids investigated, the bis-p-nitrophenylthiourea 3 gave measurable transport through membranes with a transporter/lipid ratio of 1:250 000 (an average of <2 transporter molecules per vesicle) (McNally et al. 2008).

Structurally related to cholapod are the trans-decalins. Transdecalins appended with two urea groups (see Fig 26 in Gale et al. 2017) were prepared, and their anion (chloride) transport activities in vesicles containing NaNO3- were studied.  This derivative was the most active one, correlating with its greater lipphilicity, and it seemed to function as an anion carrier.

Families of anion carriers were  developed by Cooper et al. 2014, based on a cyclohexane scaffold with three urea or thiourea groups in axial positions, linked by a methylene spacer. For the most active of these compounds, Cl-/NO3- exchange was 3-times more active than for cholapod. Increased flexibility appeared to be responsible for the lower anion affinity and accelerated binding kinetics (Gale et al. 2017). 1,2 bis-Urea compounds are also effective anion transporters (Gale et al. 2017).

 

 


 

References:

Cooper, J.A., S.T. Street, and A.P. Davis. (2014). A flexible solution to anion transport: powerful anionophores based on a cyclohexane scaffold. Angew Chem Int Ed Engl 53: 5609-5613.
Gale, P.A., J.T. Davis, and R. Quesada. (2017). Anion transport and supramolecular medicinal chemistry. Chem Soc Rev 46: 2497-2519.
Judd, L.W. and A.P. Davis. (2010). From cholapod to cholaphane transmembrane anion carriers: accelerated transport through binding site enclosure. Chem Commun (Camb) 46: 2227-2229.
McNally, B.A., A.V. Koulov, T.N. Lambert, B.D. Smith, J.B. Joos, A.L. Sisson, J.P. Clare, V. Sgarlata, L.W. Judd, G. Magro, and A.P. Davis. (2008). Structure-activity relationships in cholapod anion carriers: enhanced transmembrane chloride transport through substituent tuning. Chemistry 14: 9599-9606.