A Computational Study of Charge Delocalization and Ring Fluoro Substituent Effects in 4-Fluoromethylphenoxides.

Abstract

The degree of charge delocalization in 4-fluoromethylphenoxide anions has been investigated with ab initio molecular orbital calculations at the Hartree-Fock and MP2 levels and with the B3LYP density functional using the 6-31+G(d) and 6-311+G(2d,p) basis sets. The effect of aqueous solvation on the rotational profiles has been investigated using the AM1-SM2 solvation model. These anions serve as model systems for fluorinated tyrosine derivatives, which have been used as substrates for the enzyme tyrosine phenol-lyase. The importance of the double-bond/no-bond resonance structure has been assessed through an analysis of conformational profiles, geometries and charge distribution. The effect of ring fluorination on the degree of charge delocalization was investigated to aid in the interpretation of previous experimental mechanistic studies of the tyrosine phenol-lyase enzyme. Calculations were also carried out on benzyl fluoride, and the inclusion of diffuse functions was found to result in the perpendicular conformation as the predicted lowest-energy conformation by a small margin. Previous studies with smaller basis sets found the planar structure to be the lowest-energy conformation. The results indicate that the placement of an electron-donating group (O(-)) in the para ring position acts to increase the fluoride character of the fluoromethyl group and that this effect is not substantially modulated by the placement of fluorines on the ring.