Synthesis of urea picket porphyrins and their use in the elucidation of the role buried solvent plays in the selectivity and stoichiometry of anion binding receptors.

The synthesis of alpha,alpha-5,10-diurea and alpha,alpha,alpha-5,10,15-triurea picket porphyrins are detailed in this report. In previous reports, these porphyrins, along with alpha,alpha,alpha,alpha-5,10,15,20-tetraurea picket porphyrin, were used to demonstrate the important role one buried solvent molecule plays in the selectivity and stoichiometry of binding inorganic anions. Building on prior work, this report discusses the results of acetate anion binding studies between tetra- and diurea picket porphyrins (the latter does not contain a buried solvent molecule in the anion-receptor complex), compares differences in thermodynamic data obtained from van't Hoff plots of a porphyrin anion receptor able to utilize buried solvent in its binding motif with one that does not, and compares the crystal structure of a tetraurea porphyrin 1-chloride anion complex that contains buried solvent with new X-ray crystal structures of tetraurea porphyrin 1-dichloride or bisdihydrogenphosphate anion complexes that contain no buried solvent. Data from our previous work, and the work described herein, demonstrates that one buried solvent molecule provides stability to the receptor-anion complex that is similar in energy to a moderately strong hydrogen bond.

Buried solvent determines both anion-binding selectivity and binding stoichiometry with hydrogen-bonding receptors.

[reaction: see text] The crystal structure of a tetraurea picket porphyrin-chloride anion complex has previously shown the anion to be situated between two adjacent ureas and hydrogen bonded via four NH protons (J. Am. Chem. Soc. 1998, 120, 11684-11692). The porphyrin receptor also binds a DMSO molecule and utilizes it as a participant in its anion recognition unit, in a manner similar to enzymes that bind water for use as part of their substrate recognition unit. The bound solvent molecule determines the anion-binding affinity, selectivity, and stoichiometry of binding. With a bound DMSO molecule, the tetraurea picket porphyrin is a highly selective receptor for chloride anion and binds all anions with a 1:1 binding stoichiometry. Absent the buried DMSO molecule, the receptor is selective for phosphate anion and binds chloride and phosphate anions with both 1:1 and 1:2 receptor-anion stoichiometries. Additionally, a remarkable reversal in the selectivity of anion complexation between various picket porphyrin receptors is observed, wherein the binding constant ratios change over 3 orders of magnitude as the receptor's number of urea pickets change from four to two. The latter receptor has no urea pickets available to bind to solvent after complexation with an anion. The results demonstrate that anion complexation with hydrogen-bonding receptors in a competitive solvent is enhanced when a ubiquitous solvent molecule is incorporated into the binding motif. In this way, competitive solvent adds to the overall complexation energy and thereby strengthens binding rather than weakens it, as commonly believed. The results are pertinent to drug design, for they suggest that pharmaceuticals need not be completely desolvated to selectively bind to their biological target when water can be included in the binding motif.