1.  In condensed phases, metal ions like Na +, K +. Ca 2+ normally bind peptides at exposed Lewis-basic sites. But active metal ions can deprotonate the amide linkages and bind the amide nitrogens. Propensities are in the order Pd 2+ > Cu 2+ > Ni 2+ > Co 2+ (I. Sovago, quoted by B. Martin, ”Peptide Bond Characteristics” in “Metal Ions in Biological Systems,” Sigel and Sigel, Eds., Marcel Dekker, 1988, Vol 38.)  We recently observed the corresponding binding mode in some gas-phase complexes of Mg 2+, Ni 2+ and Co 2+. This is the iminol binding mode, distinguished from charge-solvation (CS) binding in the IRMPD spectrum by the absence of the Amide II vibration (~1500-1550 cm -1 ) of the peptide (see example spectra below).  There is little experimental information about these binding modes for simple polyalanines because the complexes are difficult to prepare. Illustrated here are literature IRMPD spectra for the tripeptide FGG (Dunbar, Polfer, Berden, Oomens, IJMS 330-332, 71 (2012)). The present study is a computational survey of the expected binding propensities for polyalanine ligands, AlaAla and AlaAlaAla. 1 Case Western Reserve University 2 University of Florida 3 FOM Institute for Plasma Physics, (Netherlands) 4 University of Amsterdam 5 Radboud University, Nijmegen Metal-ion Binding to Peptides – Spectroscopy and Computation A computational survey comparing the propensities for charge- solvated(CS) versus amide-nitrogen (Iminol) binding of metal ions to simple peptide chains. Purpose Survey thermodynamically preferred binding mode of attachment to simple peptides for interesting metal ions in normal oxidation states. Methods Computations were DFT/B3LYP. Basis 6-31+g(d,p). All-electron calculations up to Ga 3+, sdd effective core potential for metals heavier than Ga 3+. Conclusions  Iminol binding is more favorable vs CS for Metals with valence d electrons (Cu 2+ vs Mg 2+ ) Higher metal charge (Zn 2+ vs Cu 1+ ) Smaller metal ions (Mg 2+ vs Ca 2+ )  CS binding is universal for +1 metal ions (Cu 1+ vs Cu 2+ )  For +2 and +3 ions, governed by d electrons and size  Not much difference between dipeptide and tripeptide  Same deprotonated amide-N preferences as in solution: Pd +2 (153 kJ/mol) > Cu +2 (98) > Ni +2 (53) ≥ Co +2 (51) Robert C. Dunbar 1, Nick C. Polfer 2, Giel Berden 3, Jos Oomens 4,5 Acknowledgments This work is financially supported by the “Nederlandse Organisatie voor Wetenschappelijk Onderzoek” (NWO). We thank SARA Computing and Networking Services (www.sara.nl) for their support in using the Lisa Compute Cluster. Background Key: Full color = Preference > 50 kJ/mol Medium color = Preference 20 – 50 kJ/mol Weak color = Preference < 50kJ/mol Charge Solvated Iminol Results Introduction Note: Ba 2+ AlaAla, Sr 2+ AlaAla and Ca 2+ AlaAla spectra indicate full or partial conversion to CS/Zwitterion conformation

3. Structure Graphics