The Color of Cation-π Interactions: Subtleties of Amine-Tryptophan Interaction Energetics Allow for Radical-like Visible Absorbance and Fluorescence

Abstract

Several peptides and a protein with an inter- or intramolecular cation-π interaction between tryptophan (Trp) and an amine cation are shown to absorb and fluoresce in the visible region of the spectrum. Titration of indole with sodium hydroxide or ammonium hydroxide yields an increasing visible fluorescence as well. Visible absorption and multi-peaked fluorescence excitation spectra correlate with experimental absorption spectra and the vibrational modes of calculated absorption spectra for the neutral Trp radical. The radical character of the cation-indole interaction is predicted to stem from the electrostatic dislocation of indole highest occupied molecular orbital (HOMO) charge density towards the cation with a subsequent electronic transition from the HOMO-2 to the HOMO. Because this is a vertical transition, fluorescence is possible. Hydrogen bonding at the indole amine most likely stabilizes the radical-like state. These results provide new spectroscopic tools for the investigation of cation-π interactions in numerous biological systems, among them, proteins and their myriad ligands, and show that one, or at most, two, point mutations with natural amino acids are all that is required to impart visible fluorescence to proteins.

Cation−π Interaction Induced Excimer Formation: A New Strategy for High‐Efficiency Organic Solid‐State Luminescence

“…Electrostatic potential (ESP) distribution maps for an energy minimization of the interaction between SPH dimers are investigated, which have often been used to explore the origin for different strengths of cation–π interactions. [ 11,18 ] For SP monomer, the charge density over the benzene ring and pyridine ring plane is fairly evenly distributed and negatively charged, as shown by the yellow‐blue color (negative) over the ring surface ( Figure a). In contrast, positive charge is concentrated on the pyridium ring as indicated by the blue‐green color and benzene ring turns green (Figure 4b), demonstrating the pyridium cations can distort the π electron density of benzene.…”

“…[ 9 ] In fact, cation−π interaction is extensive in proteins, peptides, and other complex biological molecule structures and is proven to play an essential role in different biological systems. [ 10 ] Especially, the weak fluorescence signals have been found in the aforementioned biological molecule systems, [ 11 ] which provides an important clue for the realizing of highly efficient solid‐state luminescence induced by cation–π. So far, there have been rare successful demonstrations of such molecule design.…”

UV oxidation of cyclic AMP receptor protein, a global bacterial gene regulator, decreases DNA binding and cleaves DNA at specific sites

“…Proteins are also major UV absorbing species in biological systems due to both their abundance (5-10 mM in mammalian cells; 1-3 mM in plasma), and significant UVB absorption bands in the 270-290 nm region from Trp, Tyr and cystine residues [12][13][14][15] . Some proteins have longer wavelength absorptions arising from interaction of Trp residues with metal cations or charged side-chains 21 , or the presence of co-factors 12 . The high abundance of proteins makes these major targets for oxidants 16 , with Trp, Tyr, Cys, cystine, His, and Met side-chains being particularly prone to modification 13,14,16 .…”

“…In contrast, Trp residues typically have λ max values at ~280 nm with a significant tail up to ~310 nm. However, λ max for Trp residues varies with solvent polarity, pH, metal ion, cations and nearby charged groups; thus some Trp residues show absorption bands in the visible region 21 . These data indicate that the Trp residues in CRP are the likely UV-absorbing chromophores.…”

A reversible, colorimetric, pH-responsive indole-based hydrogel and its application in urea detection

“…Indole, the side chains of the Trp, could participate non-covalent interactions both hydrogen bonding and cation-p interaction via indole amine and the p electric system, respectively. In this procedure, cation ions (e.g., Na + and NH 4 + ) oriented above the indole ring plane forming cation-indole complex, and the p electron density of indole shied toward the cations, 37,38 leading to a charge decit in the indole highest occupied molecular orbital (HOMO). Subsequently, the electron in HOMO-2 of indole transferred to the HOMO, and the radical character of cation-p interaction stemming from the electrostatic dislocation, [39][40][41] which resulted in a visible absorption at 500 nm (curve (1) in Fig.…”