Schiff base protonation, hydrogen bonds

The optically active Schiff bases containing intramolecular hydrogen bonds are of major interest because of their use as ligands for complexes employed as catalysts in enantioselective reactions or model compounds in studies of enzymatic reactions. In the studies of intramolecularly hydrogen bonded Schiff bases, the NMR spectroscopy is widely used and allows detection of the presence of proton transfer equilibrium and determination of the mole fraction of tautomers [21]. Literature gives a few names of tautomers in equilibrium. The OH-tautomer has been also known as OH-, enol- or imine-form, while NH tautomer as NH-, keto-, enamine-, or proton-transferred form. More detail information concerning the application of NMR spectroscopy for investigation of proton transfer equilibrium in Schiff bases is presented in reviews.42-44... 

Measurements of the deuterium isotope effect for unsymmetrical di-Schiff bases fully confirmed the interrelation between proton transfer equilibria in both intramolecular hydrogen bonds.46... 

Asp-96, a key residue in the middle of the relatively hydrophobic cytoplasmic half-channel about 11 A from the protonated Schilf base, is protonated in the ground state. Its only polar interaction stems from a hydrogen bond to the hydroxyl of Thr-46. Otherwise it is surrounded by a hydrophobic barrel whose walls are formed by residues IleA5, Leu-223, and Leu-224, and the lids by Phe-42, Leu-99, and Leu-100 on the cytoplasmic side, and by Val-49, Leu-93, and Phe-219 Schiff base side. In the M to N transition of the photocycle, reprotonation of the Schiffbase from Asp-96 can occur only after this hydrophobic region between the Schiffbase and Asp-96 has been populated by a chain of water molecules (Luecke et al., 2000b). 

In the second half of the photocycle the Schiff base is reprotonated in a protonation equilibrium with Asp-96, and this is followed by reprotonation of Asp-96 from the cytoplasmic surface. Unlike in the extracellular region, where a three-dimensional hydrogen-bonded network already exists to facilitate the earlier events, involving transfer of protons... 

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