Encapsulation of metal cations by the PhePhe ligand: a cation-π ion cage

Structures and binding thermochemistry are investigated for protonated PhePhe and for complexes of PhePhe with the alkaline-earth ions Ba(2+) and Ca(2+), the alkali-metal ions Li(+), Na(+), K(+), and Cs(+), and the transition-metal ion Ag(+). The two neighboring aromatic side chains open the possibility of a novel encapsulation motif of the metal ion in a double cation-π configuration, which is found to be realized for the alkaline-earth complexes and, in a variant form, for the Ag(+) complex. Experimentally, complexes are formed by electrospray ionization, trapped in an FT-ICR mass spectrometer, and characterized by infrared multiple photon dissociation (IRMPD) spectroscopy using the free electron laser FELIX. Interpretation is assisted by thermochemical and IR spectral calculations using density functional theory (DFT). The IRMPD spectrum of protonated PhePhe is reproduced with good fidelity by the calculated spectrum of the most stable conformation, although the additional presence of the secondmost stable conformation is not excluded. All metal-ion complexes have charge-solvated binding modes, with zwitterion (salt bridge) forms being much less stable. The amide oxygen always coordinates to the metal ion, as well as at least one phenyl ring (cation-π interaction). At least one additional chelation site is always occupied, which may be either the amino nitrogen or the carboxy carbonyl oxygen. The alkaline-earth complexes prefer a highly compact caged structure with both phenyl rings providing cation-π stabilization in a "sandwich" configuration (OORR chelation). The alkali-metal complexes prefer open-cage structures with only one cation-π interaction, except perhaps Cs(+). The Ag(+) complex shows a unique preference for the closed-cage amino-bound NORR structure. Ligand-driven perturbations of normal-mode frequencies are generally found to correlate linearly with metal-ion binding energy.