Coordination ability of bradykinin with ZnII- and AgI-metal ions – Experimental and theoretical study

Electronic absorption (EAs), circular dichroic (CD), vibrational IR- and Raman-spectroscopy, nuclear magnetic resonance (NMR), electrospray ionization (ESI) and matrix assisted laser desorption/ionization (MALDI) mass spectrometry (MS) were utilized to investigate the coordination ability of bradykinin (1) with the metal ions ZnII and AgI. The experimental data were supported by the theoretical quantum chemical calculations of the electronic structures and physical properties of the isolated complexes. Since the main aim of the study is related to the design of new artificial catalysts and angiotensin converting enzyme (ACE) inhibitors, the model interactions with the active center of ACE are also designed, taking into account the coordination mode of the ZnII-ion, crystallographically determinate in the enzyme. The role of the macromolecular conformation, the enzyme cavity around the metal ion, the coordination ability of the His383.A, His353.A and Glu411.A amino acid residues, and the competitive salt-bridged processes typical for the Arg-containing ligands are discussed with a view to explain the preferred untypical C-terminus coordination mode. The data were discussed and compared with those of the angiotensin I and II (Ang-I, Ang-II). Comprehensively were described the gas-phase stabilized complex species and fragmentation modes of the complexes by the MS methods, including the imaging mass spectrometric (IMS) techniques, representing a background for the further molecular design on the base of small synthetic, semi-synthetic and naturally occurred peptides, as well as discovery of new ACE-inhibitors, since the in vivo mapping using IMS methods, provided unique opportunity for the single experiment study of the localization of molecules, including metal complexes, achievement of the important semi-quantitative, quantitative and structural information within the frame of cells, tissues, organs and whole systems.

The coordination ability of the bradykinin with the ZnII- and AgI-metal ion as well as the model angiotensin converting enzyme (ACE) interaction with the catalytic domain were studied both theoretically and experimentally. The gas-phase stabilized complex species observed by the mass spectrometric methods were discussed comprehensively in terms of the metal-to-ligand charge transfer effect, and the protein environment around the catalytic domain in ACE.Figure optionsDownload as PowerPoint slideHighlights
► Bradykinin.
► ZnII- and AgI-complexes.
► Enzyme interactions.
► Mass spectrometry.
► Quantum chemistry.