Several recent computational studies have tried to explain the observed selectivity in radical damage to proteins. In this work we use Density Functional Theory and transition state theory including tunnelling corrections, reaction path degeneracy, the effect of diffusion, and the role of free radical to get further insights on this important topic. The reaction between a leucine derivative and free radicals of biological significance, in aqueous solution, have been investigated. Both thermochemical and kinetic analyses, in both hydrophilic and hydrophobic environments, have been carried out. DPPH, •OOH, •OOCH3, •OOCH2Cl, •OOCHCl2 and •OOCHCH2 radicals do not react with the target molecule. The reactions are proposed to be kinetically controlled. The leucine gamma site was the most reactive for the reactions with •N3, •OOCCl3, •OCH3, •OCH2Cl, •OCHCl2 and •OCHCH2 radicals, with rate constants equal to 1.97105, 3.24104, 6.68105, 5.98106 and 8.87108 M-1 s-1, respectively. The •OH and •OCCl3 radicals react with leucine at the beta, gamma, and delta positions at rates close to the diffusion limit being the alpha position the less reactive one. The presented results confirm that the Bell-Evans-Polanyi principle does not apply for the reactions between amino acid residues and free radicals. Regarding the influence of the environment on the reactivity of the studied series of free radicals towards leucine residues, it is concluded that hydrophilic media slightly lower the reactivity of the studied radicals, compared to hydrophobic ones, albeit the trends in reactivity are very similar.