Biomimetic model complexes

The mechanistic and structural chemistry of B12 may be separated into (i) investigations of cobalamin cofactors both apart from and in complex with their enzymes, and (ii) biomimetic model complexes, both structural and functional. 

In the early 1970s it was discovered that P-450 cytochromes are irreversibly inhibited during the metabolism of xenobiotics (1). The formation of a modified heme prosthetic group is associated with enzyme inhibition and subsequent studies have identified these modified complexes as N-alkylated protoporphyrin-IX (2). The chemistry of N-sub-stituted porphyrins was comprehensively reviewed by Lavallee in 1987 (3). Since that time, there have been many significant contributions to this field by several groups. The goal of this chapter is to summarize some of this work as it relates to the mechanism of formation and reactivity of iron N-alkyl porphyrins. Biomimetic model complexes have played an important role in elucidating the chemistry of N-alkyl hemes in much the same way that synthetic iron tetraarylporphyrins have aided... 

Several heterodinuclear Fe-Cu or Co-Cu complexes that closely resemble the native enzyme active sites have recently been prepared to elucidate the catalytic mechanism of cytochrome c oxidases [231-245], The use of a covalently attached axial ligand seems essential to achieve efficient electroreduction of O2 to H2O [235, 238, 241-243], The closest structural analogs of the heme as/Cus active site of cytochrome c oxidases reported so far are Fe-Cu complexes (1 and 2) in which the Cu coordination site is provided by three imidazole ligands [242], These biomimetic model complexes afford clean electroreduction of O2 to H2O over a wide range of pH with no leakage of H2O2 [243],... 

Selective analytic and spectroscopic methods for analyzing biomimetic model complexes bound to the support are rather limited, and a detailed characterization of such hybrid materials is much more challenging than of soluble molecular complexes. If local spectroscopic probes are available, IR spectroscopy, gel-phase or solid-state NMR spectroscopy, EPR spectroscopy, or (diffuse reflectance) UV-vis spectroscopy is applicable. Useful IR spectroscopic labels include CO, C=N, E-H, M=E, and M=E stretching vibrations as long as they are either very intense or are separated from the matrix vibrations. For EPR spectroscopic analysis, metal isotopes with nuclear spin 1 0 are suitable. Biologically interesting metal ions include (7 = 7/2, 99.76%), Mn I =512, 100%), Co (7 = 7/2, 100%), 3/65cu (7 = 3/2, 69.09% 7 = 3/2, 30.91%), and (7 = 5/2, 15.72% ... 

It is probable that the negative charge induced by these three electrons on FeMoco is compensated by protonation to form metal hydrides. In model hydride complexes two hydride ions can readily form an 17-bonded H2 molecule that becomes labilized on addition of the third proton and can then dissociate, leaving a site at which N2 can bind (104). This biomimetic chemistry satisfyingly rationalizes the observed obligatory evolution of one H2 molecule for every N2 molecule reduced by the enzyme, and also the observation that H2 is a competitive inhibitor of N2 reduction by the enzyme. The bound N2 molecule could then be further reduced by a further series of electron and proton additions as shown in Fig. 9. The chemistry of such transformations has been extensively studied with model complexes (15, 105). 

Within the past 10 years, various biomimetic Fe model complexes were prepared and their catalytic activities in the electrochemical reduction of protons to H2 were investigated (Scheme 57). 

In recent years, several model complexes have been synthesized and studied to understand the properties of these complexes, for example, the influence of S- or N-ligands or NO-releasing abilities [119]. It is not always easy to determine the electronic character of the NO-ligands in nitrosyliron complexes thus, forms of NO [120], neutral NO, or NO [121] have been postulated depending on each complex. Similarly, it is difficult to determine the oxidation state of Fe therefore, these complexes are categorized in the Enemark-Feltham notation [122], where the number of rf-electrons of Fe is indicated. In studies on the nitrosylation pathway of thiolate complexes, Liaw et al. could show that the nitrosylation of complexes [Fe(SR)4] (R = Ph, Et) led to the formation of air- and light-sensitive mono-nitrosyl complexes [Fe(NO)(SR)3] in which tetrathiolate iron(+3) complexes were reduced to Fe(+2) under formation of (SR)2. Further nitrosylation by NO yields the dinitrosyl complexes [(SR)2Fe(NO)2], while nitrosylation by NO forms the neutral complex [Fe(NO)2(SR)2] and subsequently Roussin s red ester [Fe2(p-SR)2(NO)4] under reductive elimination forming (SR)2. Thus, nitrosylation of biomimetic oxidized- and reduced-form rubredoxin was mimicked [121]. Lip-pard et al. showed that dinuclear Fe-clusters are susceptible to disassembly in the presence of NO [123]. 

One-step hydroxylation of aromatic nucleus with nitrous oxide (N2O) is among recently discovered organic reactions. A high eflSciency of FeZSM-5 zeolites in this reaction relates to a pronounced biomimetic-type activity of iron complexes stabilized in ZSM-5 matrix. N2O decomposition on these complexes produces particular atomic oj gen form (a-oxygen), whose chemistry is similar to that performed by the active oxygen of enzyme monooxygenases. Room temperature oxidation reactions of a-oxygen as well as the data on the kinetic isotope effect and Moessbauer spectroscopy show FeZSM-5 zeolite to be a successfiil biomimetic model. 

There are many biomimetic model Co complexes of the cobalamins.1149 The primary criterion for an effective B12 model has been that the complex may be reduced to the monovalent state and undergo facile oxidative addition to generate a stable alkylcobalt(III) complex. The two main classes of B12 model complexes that have been investigated are Co oximes and Schiff base complexes. The former class shares the planar CoN4 array of their biological analogs whereas the majority of effective Schiff base Bi2 model complexes comprise equatorial czj-N202 donor sets. 

Dithiocarbamates, in Ru and Os half-sandwiches, 6, 493 Dithiocarbenes, Pt complexes, 8, 439 Dithiocarboxy ligands, in molybdenum carbonyls, 5, 447 Dithiolate-bridged compounds in dinuclear iron compounds with Fe-Fe bonds, 6, 238 as iron-only hydrogenase biomimetic models, 6, 239 Dithiolate diamides, with Zr(IV), 4, 784 Dithiolene—uranium complexes, synthesis and characterization, 4, 212 Ditopic receptors, characteristics, 12, 489 Ditungsten complexes, associated reactions, 5, 748 Divinyllead diacetates... 

III.D. Biomimetic Functional Model Complexes for Lignin Degradation... 

Among heteronuclear complexes, the binuclear compound 88 with the moiety Fe — C = N—Cu is interesting as a biomimetic model of cytochrome C-oxidaze [121] ... 

Among the coordination compounds obtained on the basis of polypyrazolyl-borates, it is worth emphasizing the copper chelates 235 which are still the only biomimetic model of blue copper proteins, reproducing all their physical (UV-and EPR-spectral) properties [441,446-448], Compound 236 [449] is also an example of complexes of this kind of system ... 

The main significance of the examined polycyclic ligands is in the creation of the basis of coordination chemistry for the -elements of Groups IA and IIA of the Periodic Table. Not long ago the above complexes of these elements were only represented by a few single examples at present, hundreds of them have been described. Another important aspect to be mentioned is the use of crown-ether complexes as biomimetic models of ionophores [579 581]. 

This self-assembly strategy has recently been extended to construct an interesting biomimetic model for the bacterial photosynthetic reaction center complex [97], In this system, a cofacial zinc(II) phthalocyanine dimer is formed via the interactions between K+ ions and the four 15-crown-5 units fused to the phthalocyanine ring. 

Friedle S, Reisner E, Lippard SJ. Current challenges of modeling diiron enzyme active sites for dioxygen activation by biomimetic synthetic complexes. Chem Soc Rev. 2010 39 2768-79. 

This chapter focuses on the chemistry ofbiomimetic copper nitrosyl complexes relevant to the NO-copper interactions in proteins that are central players in dissimilatory nitrogen oxide reduction (denitrification). The current state of knowledge of NO-copper interactions in nitrite reductase, a key denitrifying enzyme, is briefly surveyed the syntheses, structures, and reactivity of copper nitrosyl model complexes prepared to date are presented and the insight these model studies provide into the mechanisms of denitrification and the structures of other copper protein nitrosyl intermediates are discussed. Emphasis is placed on analysis of the geometric features, electronic structures, and biomimetic reactivity with NO or NOf of the only structurally characterized copper nitrosyls, a dicopper(II) complex bridged by NO and a mononuclear tris(pyrazolyl)hydroborate complex having a Cu(I)-NO formulation. 

Over the past 25 years, biomimetic model systems have been extensively studied and a wide variety of interesting oxidation processes such as the epoxidation of olefins, the hydroxylation of aromatics and alkanes, the oxidation of alcohols to ketones, etc., have been accomplished some of these are also known in enantioselective versions with spectacular ee s. The vast majority of these transformations were obtained using monooxygen donors such as those mentioned above as primary oxidants. The complexity of the catalysts and the practical impossibility to use dioxygen as the terminal oxidant have so far prevented the use of such systems for large industrial applications, but some small applications in the synthesis of chiral intermediates for pharmaceuticals and agrochemicals, are finding their way to market. 

Biomimetic and bioinspired synthetic model complexes were very useful in providing information about basic functional principles and mechanistic aspects... 

---