Effect of fluorine position on the coordinating ability of fluorosalicylic acids--an experimental study complemented with computations.

The complexation of 3-, 4-, and 6-fluorosalicylic acids (HL) with copper(II) was investigated in aqueous solution by pH-potentiometry combined with UV-visible spectrophotometry, and in 50 v/v % water-methanol mixture by the two-dimensional ESR simulation method. Both methods showed the formation of [CuLH(-1)] and [CuL(2)H(-2)](2-) of high stabilities, and, at low excess of ligand, the ESR-silent mixed hydroxido complex [Cu(2)L(2)H(-3)](-). Further species were also identified by the two-dimensional ESR simulation method: [CuL](+) in the acidic region, the minor dimer [Cu(2)L(2)H(-2)], and the cis and the trans isomers for [CuL(2)H(-2)](2-). The position of the fluorine atom in the aromatic ring had significant effect on the coordination abilities of the ligands, in good correlation with their reported biological activities. It was 3-fluorosalicylic acid, which formed the most stable complexes [CuLH(-1)] and [CuL(2)H(-2)](2-), while the mononuclear complexes with 6-fluorosalicylic acid were found to be the least stable. For the other ligands (including 5-fluorosalicylic acid studied recently), complexes of medium stabilities were formed. For the interpretation of these findings, ab initio and semi-empirical quantum chemical calculations were carried out for the ligand molecules, isolated and surrounded by water molecules, respectively.