N-o-Vanillylidene-l-histidine: Experimental Charge Density Analysis of a Double Zwitterionic Amino Acid Schiff-Base Compound

Abstract

A double zwitterionic Schiff base was synthesized using the amino acid l-histidine and o-vanillin (2-hydroxy-3-methoxy benzaldehyde). Both the phenol and carboxyl groups are deprotonated, and the imine nitrogen atom and histidine-imidazole ring are protonated to give the double zwitterion with an intramolecular (imine)N−H+···−O(phenol) hydrogen bond (ketoamine form). Such a ketoamine form in a double zwitterion is assumed in the catalytic cycle of enzymatic transformations of amino acids with the cofactor (vitamin B6) pyridoxal-5′-phosphate (PLP). A high-resolution, low-temperature, single-crystal X-ray diffraction data set on N-o-vanillylidene-l-histidine (also named 3-methoxysalicylidene-l-histidine or N-(2-oxy-3-methoxy-benzylidene)-l-histidine, OVHIS) is used in the analysis of molecular electrostatic properties and intermolecular interactions. All oxygen atoms in the molecule (four in total) are mutually almost coplanar and located (externally) on the same side of molecule. These four O atoms carry s...