Theoretical study on the distribution of atomic charges in the Schiff bases of 3-hydroxypyridine-4-aldehyde and alanine. The effect of the protonation state of the pyridine and imine nitrogen atoms

Abstract

The protonation state of the pyridine and imine nitrogen atoms on the “electron-sink” effect was studied by DFT(B3LYP/6-31+G ∗) calculations in the Schiff bases formed between 3-hydroxypyridine-4-aldehyde and alanine and their Cα-carbanionic counterparts. Results indicate that the protonation of pyridine nitrogen promotes the enolimine–ketoenamine tautomerism. The importance of pyridine nitrogen on the “electron-sink” effect in the carbanionic molecules clearly depends on the protonation state of the imine nitrogen: in the enolimine tautomers, where the imine nitrogen is deprotonated, a 70% of the electron charge is delocalized on the pyridine ring, whereas in the ketoenamine type structures, where the imine nitrogen is fully protonated, just a 20% of this charge is delocalized in this molecular moiety. The results are discussed in relation to the chemistry of some PLP-dependent enzymes and the structure of their active sites.