Investigation of the thiol-disulfide interchange applied to molecular self-assembly and binding of ammonium ions within aromatic pockets of metal tris(catecholate) complexes

Several trithiol and tetrathiol monomers were synthesized and investigated with regards to their ability to form disulfide-bonded dimers under equilibrium oxidizing conditions in the presence of 2-hydroxyethyl disulfide (ME ox). Only trithiol 2.2 was found to form a stable tris(disulfide) dimer under equilibrium conditions. All the other thiols were found to form oligomeric or polymeric products under both kinetic oxidizing conditions with I₂ and equilibrium oxidizing conditions with MEox. Equilibrium studies between tetrathiol cavitand 2.26 and unsymmetrical tetrakis(disulfide) cavitand 2.28 yielded the variably substituted cavitands 2.34, 2.35, and 2.36 rather than tetrakis(disulfide) carcerand 2.27. The inability to form 2.27 under equilibrium conditions in dilute solution was attributed to steric hindrance at the benzyl sulfur atom.; Numerous metal tris(catecholate) complexes were synthesized using the known phenyl-substituted terephthalamide ligand 4.6 and the new naphthyl-substituted terephthalamide ligand 4.7. X-ray diffraction data of Fe/(S)-Ph,choline (S)-4.11 and Fe/(S)-Naphth,Me₄N (S)- 4.19 revealed that the ammonium counterions are bound within the aromatic pockets of the complexes in the solid state. 1H NMR dilution studies of numerous Al+3 and Ga+3 tris(catecholate) complexes revealed that the ammonium ions are also bound within the aromatic pockets of the complexes in solution. Binding constants of the ammonium ions were determined from the 1H NMR dilution study data. The binding data indicated that Me₄N+, BnNMe₃ +, and choline are all bound to the Al/(S)-Ph complex nearly equally in CD₃OD whereas BnNMe₃+ is bound significantly stronger to the Al/(S)-Naphthyl complex in CD₃OD due to additional π-π interactions between the aromatic ammonium ion and the naphthyl rings. An increased binding was not observed for Me₄N+ which was found to bind both the Al/( S)-Ph complex and Al/(S)-Naphthyl complex equally in CD₃OD. Choline was shown to be bound within the aromatic pockets of metal tris(catecholate) complexes both in the solid state and in solution. Additionally, preliminary dilution studies have shown that (R)-epinephrine can also bind to the aromatic pockets of a metal tris(catecholate) complex. Therefore, these metal tris(catecholate) complexes can be used as models for the binding of ammonium neurotransmitters to the aromatic pockets of biological neurotransmitter receptors.