Interactions of Phenol and Indole with Metal Ions in the Gas Phase:  Models For Tyr and Trp Side-Chain Binding

Abstract

The binding energies of a number of metal cations with phenol and indole in the gas phase were studied experimentally by radiative association kinetics analysis, supplemented by density functional calculations. Radiative association kinetics measurements were carried out in the Fourier transform ion cyclotron resonance mass spectrometer. Reaction in most cases resulted in adduct formation often followed by sequential addition of a second neutral molecule to the ion. The association kinetics were analyzed to yield binding energy values either by using a variational transition state theory-based approach, incorporating quantum-chemical calculations of vibrational frequencies and infrared intensities, or by using the semiquantitative standard hydrocarbon approach. The competitive collision-induced dissociation (CID) technique was used to confirm the order of relative binding energies for several complexes. Calculations of the structures and energies of a number of complexes were performed, by means of the B3LYP-density functional approach, both to complement and compare with the experimental binding energies and also to address the question of π versus heteroatom bonding. With phenol, the two binding sites are close in energy for nontransition metals, but the π-site is relatively more favorable for Fe + and probably Cr + . Experimental, literature, and calculated values were combined to give best-estimate binding energies for a variety of metal ions. For the nontransition-metal ions characterized, phenol binding is similar to benzene binding, whereas for Cr + and especially Fe + phenol binding is stronger than benzene binding. With indole, binding is always enhanced by ∼5-10 kcal mol -1 relative to benzene. Formation of dimer ML 2 + complexes followed patterns similar to those of previous benzene results, except that phenol dimer complexes with Mg + and Al + were unexpectedly observed, suggesting involvement of an oxygen binding site in these cases.

Absolute Potassium Cation Affinities (PCAs) in the Gas Phase

“…[14], reported value reduced by 6.2 kJ mol À1 , as described in text, and with thermal correction to 298 K.…”

“…Absolute affinities were obtained by threshold collisional induced dissociation (threshold CID), [2±13] radiative associative kinetics measurements, [14] and high-pressure mass spectrometric (HPMS) equilibrium measurements, [15±24] while relative affinities were obtained by Fourier transform ion cyclotron resonance (FT-ICR) ligand exchange equilibrium measurements, [25±28] and the mass spectrometric kinetic method. [29±31] Complementing the progress made in experimental measurements, quantum chemical methods have advanced to a stage that not only relative but also absolute alkali metal cation affinities can be obtained in excellent agreement (accuracy:…”

The Mighty Arginine, the Stable Quaternary Amines, the Powerful Aromatics, and the Aggressive Phosphate: Their Role in the Noncovalent Minuet

“…40 In addition, the binding energies of benzene to Na + and K + ions have been determined by CID experiments. Ryzhov and co-workers provided an elegant example of the gas phase determination of metal-ion affinities of the aromatic amino acids, 41,42 providing insight into how these constituents might interact in biological systems, as exemplified by peptide-peptide interactions, and peptide small molecules interactions. Pletneva et al 43 used NMR successfully to explore cation-π interactions in model systems between poly-Lys peptides and acidic peptides containing various aromatic residues and Waters et al 44 used circular dichroism to prove that cation-π interactions between aromatic residues and protonated amines stabilized R-helices in water.…”

Dissociations of Complexes Between Monovalent Metal Ions and Aromatic Amino Acid or Histidine

“…With free indole as a ligand, metal ions typically show a preference for binding on the aryl ring of the bicyclic system [21][22][23]; however, in metal ion-Trp complexes [16,[24][25][26], or in other environments where competing binding sites are available [27,28], additional geometrical constraints imposed by chelation with oxygens, nitrogens, or other electron-rich binding sites become important and the lowest-energy isomers, tridentate chargesolvated structures, often have the metal ion positioned away from the center of the aryl ring and toward the pyrrole ring.…”