Geometries and energies of the ground and transition states of tautomers of the azo dye 5-amino-4-hydroxy-3-[(2-sulfophenyl)azo]-2,7-naphthalenedisulfonic acid by the PM3 method

The diagnostic agent Evans blue which is an azo dye, has an unique arrangement of functional groups which brings into play the equilibration of several tautomeric states in solution. Since the molecule is not easily amenable to detailed quantum mechanical studies, the azo dye 5-amino-3-hydroxy-3-[(2-sulfophenyl)azo]-2,7-naphthalenedisulfonic acid which is closely related in structure to Evans blue, was chosen as a model for the study. PM3 calculations show that for the trans configuration of the azo bond there is only stable conformation, while the cis azo state has four distinct conformations. However, the trans azo form is more stable than any of the cis forms. In any given configuration (trans or cis) the azo tautomer (I) is the most stable followed by the hydrazone tautomer (II), the other tautomers IIIa, IIIb and IV are far less stable. Transition states computed for the various equilibria show that the azo-hydroazone (I = II) equilibrium has the lowest energy barrier, this is followed by the II = IV equilibrium The II = IIIb equilibrium is predicted to be the least favoured of the lot. Based on these studies, Evans blue is expected to exhibit a similar behaviour. (C) 2000 Elsevier Science B.V. All rights reserved.