Microenvironmental effects on the solvent quenching rate in constrained tryptophan derivatives

Article abstract of DOI:10.1021/ja00106a038

Solvent quenching is one of several environmentally sensitive nonradiative decay pathways available to the indole chromophore. It is characterized by 2-3-fold deuterium isotope effects and strong temperature dependence with frequency factors of 10¹⁵-10¹⁷ s^-1 and activation energies of 11-13 kcal/mol in aqueous solution. The effects of ionization state, proximity of the amino group to the indole ring, and N-methylation of indole nitrogen on the solvent quenching rate were examined in four constrained tryptophan derivatives: 1,2,3,4-tetrahydro-2-carboline, 3-amino-1,2,3,4-tetrahydrocarbazole, 3-amino-1,2,3,4-tetrahydrocarbazole-3-carboxylic acid, and 9-methyl-1,2,3,4-tetrahydro-2-carboline-3-carboxylic acid. The constrained derivatives had at most two ground-state conformations, as determined by X-ray crystallography, molecular mechanics calculations, and ¹H NMR. Fluorescence lifetimes were assigned to ground-state conformations based on relative populations of conformers and amplitudes of fluorescence decays. Solvent quenching rates were determined from the temperature dependence of the fluorescence lifetime. The solvent quenching rate is decreased by protonation of the amino group in all compounds. It is slower in the carboline derivatives, where the amino group is two bonds away from the indole ring, than in the tetrahydrocarbazole derivatives, where the amino group is three bonds away. In the tetrahydrocarbazoles, the solvent quenching rate is slower in the conformer with the ammonium in the pseudoaxial position closer to the indole ring than in the conformer with the ammonium in the pseudoequatorial position pointing away from the ring. These results suggest that the water quenching rate of tryptophans on protein or peptide surfaces is modulated by proximal ammonium groups.