Studies in Molecular Recognition: Hydrophobic Binding of Water-Soluble Guests by High Symmetry, Chiral Hosts

Citation

Shepodd, Timothy Jon (1988) Studies in Molecular Recognition: Hydrophobic Binding of Water-Soluble Guests by High Symmetry, Chiral Hosts. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/cgn8-6h63. https://resolver.caltech.edu/CaltechTHESIS:03072013-150951099

Abstract

A new class of high-symmetry, water-soluble receptors has been synthesized. The enantiomerically pure hosts are D₂-symmetric and are synthesized in 8 steps with an overall yield of 5-10%. An asymmetric Diels-Alder reaction between di-(+)-menthyl fumarate and 2,6-di-t-butyldimethylsiloxyanthracene leads to two diastereomeric Diels-Alder adducts that are elaborated to the key intermediates: (+)- and (-)-2,6-dihydroxy-11,12-dicarbomethoxy-9,10-ethenoanthracene. A number of hosts are synthesized from these intermediates when they are connected by variable linker units. These hosts possess chiral cavities (receptor sites) surrounded by an array of substituted aromatic rings.

The ability of these hosts to complex water-soluble guests with different sizes, shapes, and degrees of preorganization has been quantified by NMR. The electron-rich hosts have a general affinity for electron-deficient guests. Hosts P and M show a moderate hydrophobic-type attraction towards a variety of aromatic and aliphatic guests (3-4 kcal/mol). Host P shows an added attraction towards trimethylammonium (TMA) substituted guests. In almost all cases studied, NMR-shift patterns indicate that when the hostguest complex forms, the polar TMA group lies deepest within the electron-rich, yet hydrophobic, receptor.

Hosts P and M have a strong attraction towards adamantyltrimethylammonium iodide (ATMA). P_R and P_S have binding viaffinities of 6.6 ± 0.2 kcal/mol with ATMA and bind the guest, encapsulated within the receptor site, in one guest orientation. M_R and M_S have binding affinities of 5.5 ± 0.2 kcal/mol with ATMA and bind the guest in a non-specific fashion, yet they demonstrate a preferred attraction towards the TMA group of the guest.

Aromatic-linked hosts P_R, P_S, M_R and M_S show an enhanced ion-dipole attraction towards charged quinolinium-type, flat aromatic guests as compared to neutral ones (P ≈ 1 kcal/mol and M ≈ 2 kcal/mol). Host C, with aliphatic linkers, does not experience an enhanced attraction to the charged flat guests.

Hosts P_R and P_S demonstrate enantioselective binding with certain guests. For one case, a simple model for the cause of the enantioselectivity is presented.

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