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47262-B6
Examining Hydrodynamic and Solubilization Properties of Micelles Formed by Chiral Amphiphiles with NMR

David S. Rovnyak, Bucknell University and Timothy G. Strein, Bucknell University

We have characterized the association of an atropisomeric binaphthyl compound (R,S-BNDHP) with aggregates of sodium cholate.

The relative orientation of the naphthyl planes about the ring bridging bond (indicated by the asterisk) in BNDHP prescribes non-superimposable structures corresponding to R,S-BNDHP.  We have previously found through micellar electrokinetic capillary electrophoresis (MEKC) that R,S-BNDHP interact differentially with micelles formed from sodium cholate.

In our work to date, we have utilized NMR spectroscopy of R,S-BNDHP to (i) improve our understanding of the aggregation behavior of sodium cholate and (ii) identify regions of R,S-BNDHP that experience chirally selective interactions with the micelles.

(i)  Proton (¹H) NMR of R,S-BNDHP unambiguously demonstrates the formation of a primary micelle at 15 mM cholate (pH 12), and a preliminary aggregate which forms at 7 mM cholate (figure below).  The preliminary aggregate, which may be a dimer,  contains a hydrophobic pocket that is sampled by BNDHP.  Additional ¹H and ³¹P chemical shift data (not shown) indicate the onset of progressive aggregation ca. 40-50 mM cholate (a.k.a. secondary aggregate).  The chemical shifts of H3 of BNDHP are perturbed towards high frequency by association with cholate aggregates and support a widely suspected theory that secondary aggregates contain solvent-accessible hydrophilic surfaces.

(ii) Proton (¹H) NMR has revealed that H4-H8 interact with a hydrophobic binding pocket in primary micelles of sodium cholate.  H5,H6 and H7 experience differential interactions with the cholate micelles for the R and S-BNDHP forms and are therefore reporting on slightly different local environments within the cholate micelles.

In other words, H5-H7 play a role in the chirally selective solvation of R,S-BNDHP by sodium cholate micelles.  Further work is needed and underway to localize regions on cholate that also exhibit chirally selective interactions with R,S-BNDHP.  The results to date are very encouraging progress towards better explaining the structural basis for bile salt mediated chiral solvation of hydrophobic analytes.