Comparison of structurally-related alkoxide, amine, and thiolate-ligated MII (M=Fe, Co) complexes: The influence of thiolates on the properties of biologically relevant metal complexes

Abstract

Mechanistic pathways of metalloenzymes are controlled by the metal ion's electronic and magnetic properties, which are tuned by the coordinated ligands. The functional advantage gained by incorporating cysteinates into the active site of non-heme iron enzymes such as superoxide reductase (SOR) is not entirely understood. Herein we compare the structural and redox properties of a series of structurally-related thiolate, alkoxide, and amine-ligated Fe(II) complexes in order to determine how the thiolate influences properties critical to function. Thiolates are shown to reduce metal ion Lewis acidity relative to alkoxides and amines, and have a strong trans influence thereby helping to maintain an open coordination site. Comparison of the redox potentials of the structurally analogous compounds described herein indicates that alkoxide ligands favor the higher-valent Fe 3+ oxidation state, amine ligands favor the reduced Fe 2+ oxidation state, and thiolates fall somewhere in between. These properties provide a functional advantange for substrate reducing enzymes in that they provide a site at the metal ion for substrate to bind, and a moderate potential that facilitates both substrate reduction, and regeneration of the catalytically active reduced state. Redox potentials for structurally-related Co(II) complexes are shown to be cathodically-shifted relative to their Fe(II) analogues, making them ineffective reducing agents for substrates such as superoxide.

Synthesis and Structural Characterization of a Series of MnIIIOR Complexes, Including a Water-Soluble MnIIIOH That Promotes Aerobic Hydrogen-Atom Transfer

“…One equivalent of TEMPOH was required for complete disappearance of 7 (Figure S-24) or 8 (Figure S-23) indicating that a clean 1:1 stoichiometric reaction is involved. The initial products expected in these reactions [Mn II (S Me2 N 4 (tren))(ROH)] + (R= H, Me) are not observed, consistent with the electrochemical data ( vide supra ; Figures S-13 - S-14) which demonstrates that these six-coordinate reduced species are unstable 52,57 on the time-scale of these experiments. Phenoxide-bound 5 and 6 show no reaction with TEMPOH, even when excess substrate is added and the reaction mixture is monitored for prolonged periods under anaerobic conditions (~24 hrs).…”

Properties of Square-Pyramidal Alkyl−Thiolate FeIII Complexes, Including an Analogue of the Unmodified Form of Nitrile Hydratase

“…Previously we, and others, showed that gem dimethyls adjacent to the sulfur can prevent dimerization of iron thiolates 18,21,50-52. And more recently we showed that thiolate ligands reduce metal ion Lewis acidity relative to alkoxides and amines, and have a strong trans influence thereby helping to maintain an open coordination site 53. The previously reported tame-N 3 (1,1,1-triaminoethane)54,55 ligand was used in this study as a scaffold for the new complexes, since it favors a more open, less constrained, square pyramidal or octahedral geometry as illustrated in Scheme 1.…”

Characterization of Metastable Intermediates Formed in the Reaction between a Mn(II) Complex and Dioxygen, Including a Crystallographic Structure of a Binuclear Mn(III)–Peroxo Species

“…The thiolate ligand helps to maintain an open coordination site. 94 O 2 binding to 1 is found to be relatively slow compared to related biologically relevant Fe and Cu complexes. In the absence of any other kinetic data for O 2 binding to Mn(II), it would be difficult to draw any conclusions regarding the role of the metal ion in this reaction.…”