Charge transfer in peptides. Effects of temperature, peptide length and solvent conditions upon intramolecular one-electron reactions involving tryptophan and tyrosine

Abstract

Tryptophyl-tyrosyl peptides, TrpH-(Gly)_n-TyrOH and cyclic c-TrpH-TyrOH, were oxidised selectively at the indole group with electron accepting radicals (N^˙₃ or Br^˙–₂) in aqueous solution, using pulse radiolysis techniques. Subsequent to the primary oxidation an efficient synchronous transformation of indolyl into phenoxyl radicals occurred, both in the linear peptides (n= 0, 1 and 2), [graphic omitted] and in c-TrpH-TyrOH. Rate constants of the reactions [1(n)], obtained by kinetic absorption spectroscopy, follow an empirical inverse-square distance relationship, k_1(n)/k₁₍₀₎= 1/(1 +n²/2), k₁₍₀₎= 7.3 × 10⁴ s^–1. Thermal activation of reaction [1(0)] was observed with an apparent activation energy of 0.22 eV. The addition of 1.5 mol dm^–3 urea (a modifier of hydrogen-bond structures) or of 60 mmol dm^–3 SDS (a detergent shielding the hydrophobic indole and phenol group) did not affect reaction [1(0)]. Deprotonation of the OH-group of TyrOH (pK_a= 10.1) and protonation of the indolyl radical (pK_a= 4.3) efficiently enhanced the radical transformation rates (k₁₍₀₎ > 10⁶ s^–1 at pH 11 and k₁₍₀₎≈k₁₍₂₎ > 2 × 10⁵ s^–1 at pH = 4). Intermolecular reactions between Trp and TyrOH were comparatively slow in neutral as well as in acid or alkaline solution. The low activation energy suggests that the observed intramolecular radical transformations occur by an electron-tunnelling mechanism. The (tentative) inverse square relationship and the pH effects indicate, on the other hand, that electronic (inductive) interactions between the reactants are involved. Selective one-electron oxidation of Cys-bis-TyrOH, His-TyrOH and Ser-TyrOH-βNA at the tyrosyl residue, and of Dansyl-TyrOH at the dansyl-group, did not induce comparable charge-transfer reactions.