Complexes of Ni(ii) and Cu(ii) with small peptides: deciding whether to deprotonate

Abstract

The observed variety of metal-ion complexation sites offered by peptides reflects a basic tension between charge solvation of the ion by Lewis-basic chelating groups versus amide nitrogen deprotonation and formation of metal-nitrogen bonds. Gas-phase models of metal-ion coordination can illuminate the factors governing this choice in condensed-phase proteins and enzymes. Here, structures of gas-phase complexes of Ni(ii) and Cu(ii) with tri- and tetra-peptide ligands are mapped out using a combination of Infrared Multiple Photon Dissociation (IRMPD) spectroscopy and density functional theory (DFT) computations. The two binding modes give distinctive IRMPD signatures, particularly in the diagnostic region 1500-1550 cm. Previous observations have suggested that Ni(ii) complexes preferentially show the iminol rearrangement pattern (Im) giving low-spin square-planar geometries with metal-ion bonds to deprotonated amide nitrogens. In contrast, alkaline earth metal ion complexes prefer amide carbonyl oxygens chelating the metal ion with pyramidal geometry (charge-solvation, CS). Surprisingly, it is shown here that the Gly complexes are CS bound, in contrast with the expectation of Im binding. It is suggested that CS binding is actually a normal Ni(ii) and Cu(ii) binding mode to simple peptides lacking participating side chains. Three factors are suggested to influence the choice between CS and Im binding patterns: (1) presence of an accessible side-chain Lewis-basic proton interaction site (FGGF, FGG and HAA complexes); (2) short chain length of the peptide leading to a shortage of accessible carbonyl oxygen sites for CS binding, (AAA, FGG and HAA complexes); (3) outright deprotonation of the ligand giving net negatively charged Im[Ni(Gly-3H)] and Im[Ni(Ala-3H)] complexes, which have a triply-deprotonated ligand. IRMPD spectra of [CuGly] and [Cu(Gly-3H)] complexes suggest that their structures are similar to their Ni analogs.

A two-dimensional metallosupramolecular framework design based on coordination crosslinking of helical oligoamide nanorods

“…20 In case of transition metals, in particular Ni(II) and Cu(II), extensive data exist to show that coordination to peptides frequently proceeds by deprotonation of the amide and direct nitrogen-metal bond formation as opposed to charge solvation to the carbonyl oxygens, although the latter is not entirely unprecedented. [21][22][23] It should be noted that peptide-metal interaction is commonly characterized in the gas phase, and the presence of a solvent may affect the sterically accessible sites. Indeed, metal coordination is used in protein purification, where the imidazole sidechains of a polyhistidine tag coordinate to a metal, typically Ni(II), immobilized in a carrier molecule such as nitrilotriacetic acid.…”

Replacing H+ by Na+ or K+ in phosphopeptide anions and cations prevents electron capture dissociation

“…As cations for successive replacement of H + , we chose Na + and K + because they can form salt bridges with phosphates and carboxylates, and have high preference for the formation of ionic hydrogen bonds with backbone amide oxygen 33 rather than nitrogen (by replacement of the amide proton) as can be observed with divalent and trivalent metal ions. 34 – 36 Moreover, previous studies indicated that Na + and K + attachment may interfere with peptide ion dissociation into c , z ˙ or c ˙, z fragments by both ECD and ETD. 37 , 38 …”

A Kinetic Investigation of Metal-Dipeptide Complex with Ninhydrin in the Absence and Presence of CTAB Micelles

“…Another important feature noticeable in the spectrum is a small band around 425 -450 nm. This band is prominent in presence of CTAB and could represent a square planar complex of the Ni II species 20 . The condensation product resulting from ninhydrin with the complexed dipeptide is a tetradentate ligand and the probability of forming a stable square planar complex is more likely.…”