Gas-Phase Structures of Pb 2+ -Cationized Phenylalanine and Glutamic Acid Determined by Infrared Multiple Photon Dissociation Spectroscopy and Computational Chemistry Michael B. Burt and Travis D. Fridgen* Department of Chemistry, Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada, A1B 3X7 * S Supporting Information ABSTRACT: Infrared multiple photon dissociation (IRMPD) spectroscopy in the 3200-3800 cm -1 region was used to determine the gas-phase structures of bare and monohydrated [Pb(Phe-H)] + and [Pb(Glu-H)] + . These experiments were supported by infrared spectra calculated at the B3LYP/6- 31+G(d,p) level of theory as well as 298 K enthalpies and Gibbs energies determined using the MP2(full)/6-311++G- (2d,2p)//B3LYP/6-31+G(d,p) method. The gas-phase structure of [Pb(Phe-H)] + has Pb 2+ bound in a tridentate fashion between Phe’s amine nitrogen, one oxygen of the deprotonated carboxyl group, and the aromatic ring. The IRMPD spectrum of [Pb(Glu- H)] + can be assigned to a structure where the side chain carboxyl group is deprotonated. The structure of [Pb(Phe-H)H 2 O] + is simply the hydrated analogue of [Pb(Phe-H)] + where water attaches to Pb 2+ in the same hemisphere as the ligated amino acid. The spectrum of [Pb(Glu-H)H 2 O] + could not be assigned a unique structure. The IRMPD spectrum shows features attributed to symmetric and antisymmetric O-H stretching of water and a broad band characteristic of a hydrogen bonded O-H stretching vibration. These features can only be explained by the presence of at least two isomers and agree with the computational results that predict the four lowest energy structures to be within 6 kJ mol -1 of one another. 1. INTRODUCTION Gas-phase amino acids primarily exist as their canonical forms, but zwitterionic tautomers can often be stabilized through metal chelation. 1-21 The extent to which a metal cation alters the structure of an amino acid is dictated by its size and valency. 6,20,22-28 Most of the research into the structures of metal-cationized amino acids has focused on complexes of the form [M(Aa)] +/2+ . 4-10,15-31 These experiments have revealed that, in general, amino acids with nonpolar side chains are more sensitive to the polarizability of the metal cation, whereas those with more functionalized side chains are dependent on the effective shielding of the cation due to the greater degree of charge solvation. This means that increasing the size of the metal cation will have opposite effects on aliphatic and functionalized amino acids. For example, when arginine (Arg) is complexed with the alkali metals, Li + forms a charge-solvated complex, [Na(Arg)] + exists as a mixture of both conformers, and [K(Arg)] + , [Cs(Arg)] + , and [Rb(Arg)] + are zwitterionic. 32 A similar trend exists for serine (Ser); Li + , Na + ,K + , and Rb + each produce three-coordinate charge-solvated structures where the metal is bound between the amine nitrogen, carbonyl oxygen, and side chain hydroxyl group. Starting with K + ,a bidentate charge-solvated structure begins to contribute to the gas-phase population as the cation size increases, and [Cs(Ser)] + is partly zwitterionic. 6 In contrast, proline (Pro) and N-methylalanine both form salt bridges with Li + and Na + , and their charge-solvated isomers become increasingly stable as the cation size increases through K + , Cs + , and Rb + . 20 Recently, we have focused on using IRMPD spectrosco- py 33-37,52 to characterize bare and hydrated Pb 2+ complexes with amino acids. 1,3 Lead is unique among p-block metals in that it chelates with every amino acid, and the resulting complexes are deprotonated and of the form [Pb(Aa-H)] + . Lead chelation also plays an important role in biochemical processes ranging from heme synthesis to hypertension and anemia, making the characterization of these complexes Special Issue: Peter B. Armentrout Festschrift Received: June 29, 2012 Revised: September 4, 2012 Article pubs.acs.org/JPCA © XXXX American Chemical Society A dx.doi.org/10.1021/jp306420e | J. Phys. Chem. A XXXX, XXX, XXX-XXX