Biomimetic Model Studies

The intriguing structure of the GAOX active site has raised a challenge to the held of bioinorganic chemistry and inspired the synthesis of an array of molecular models. Models for the isolated Tyr-Cys side chain have yielded important information on the chemistry and spectroscopy of the dissected cofactor, as described earlier (Section VI) (Whittaker 2/., 1993 lioh etal., 1993, 1997 Gerfen 2/., 1996). More recently, attention has been directed at mimicking the complex structure, spectroscopy, and even the catalytic reactivity of the intact radical-copper complex in model chemistry. 

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In all three classes of ribonucleotide reductases, a cysteinyl radical (in the E. coli RNRl sequence at position Cys ) abstracts a hydrogen atom from the C3 position of the carbohydrate moiety of the ribonucleotide substrate [3]. Biomimetic model studies of this enzymatic process were designed, achieving intramolecular hydrogen transfer within a tetrahydrofurane-appended thiyl radical (Scheme 3.4 Reactions (3.27) and (3.28) [75, 76]. 

Iron porphyrins have been studied extensively over the past 30 + years as model systems of cytochrome P450.13 Biomimetic model studies included variants in axial ligands (thiolate and other bases), the oxidation of alkanes, olefins, sulfides, and amines, and utilization of several oxidants such as hypochlorite (bleach), iodoso-benzene (ArlO), hydrogen peroxide, and organic peroxides (ROOH). The first-generation models employed the mevo-tetraary I porphyrins (Figure 3.5). These were... 

Support for the aromatic h> othesis comes from model studies and protein crystal structure analysis. In biomimetic model studies, Dougherty has shown that cation-x interactions can stabilize both ground and transition states (44), and has used these results to predict the involvement of aromatic sidechains in receptors and enzymes that operate on cationic species (45,46). In the structural realm, the widespread occurrence of amino-aromatic interactions have been noted (47). In addition, a cocrystal structure shows that the myeloma protein McPC603 interacts with tile quaternary ammonium ion of its ligand phosphorylcholine through the... 

Conventional MS in the energy domain has contributed a lot to the understanding of the electronic ground state of iron centers in proteins and biomimetic models ([55], and references therein). However, the vibrational properties of these centers, which are thought to be related to their biological function, are much less studied. This is partly due to the fact that the vibrational states of the iron centers are masked by the vibrational states of the protein backbone and thus techniques such as Resonance Raman- or IR-spectroscopy do not provide a clear picture of the vibrational properties of these centers. A special feature of NIS is that it directly reveals the fraction of kinetic energy due to the Fe motion in a particular vibrational mode. 

Until a recent x-ray diffraction study (17) provided direct evidence of the arrangement of the pigment species in the reaction center of the photosynthetic bacterium Rhodopseudomonas Viridis, a considerable amount of all evidence pertaining to the internal molecular architecture of plant or bacterial reaction centers was inferred from the results of in vitro spectroscopic experiments and from work on model systems (5, 18, 19). Aside from their use as indirect probes of the structure and function of plant and bacterial reaction centers, model studies have also provided insights into the development of potential biomimetic solar energy conversion systems. In this regard, the work of Netzel and co-workers (20-22) is particularly noteworthy, and in addition, is quite relevant to the material discussed at this conference. 

Porphyrin quinones serve as biomimetic models for fundamental studies on photo-induced ET. Most studies have been performed with the well-known porphyrin p-quinones and the isomeric porphyrin o-quinones have been mostly neglected due to their higher chemical reactivity but in fact they should be better electron acceptors. Speck et al. synthesized several porphyrin o-quinones and have shown that a facile and simple variation of AGEt can be achieved by using in situ formed semiquinones for metal chelation230. 

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. 

Other Complexes. Before we turn to a discussion of other complexes, it is worth making a few general comments about the biomimetic systems studied to date. The model systems are much slower ( 105-fold) than the enzyme (33). All peroxovanadium complexes, whether competent to catalyze bromide oxidation reactions or not, contain tj2-coordinated peroxide (4). Little is known about the binding of peroxide in the enzyme (see above), but one wonders whether the enhanced reactivity is derived from an alternative binding mode, such as end-on peroxide or hydroperoxide. The rapid enzymatic rate could also arise from the nature or configuration of the ligands to the vanadium ion. 

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... 

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. 

Porphyrin synthesis and functionalization based on the chemistry of Mannich bases, briefly mentioned in previous chapters, are recalled here. As far as porphyrin synthesis is concerned, studies of biomimetic models of photochemically active reaction centers are worth noting. The synthetic procedure involves amino group replacement of the pyrrole bis-Mannich base with formation of the tetrapyrrole ring of porphyrin (see 360, Chap. 11). 

Despite the obvious versatility of light-activated key steps and their numerous advantages for the biomimetic modeling of natural systems, up to now, only very few examples are known, where such types of photosensitized processes have been successfully combined to complete reaction cycles with reasonable catalytic turnovers 6). In the last section, we are therefore briefly presenting two case studies which describe some recent work performed in our own group focusing on bioinspired catalytic systems that can be controlled and driven by visible light. 

Further insights into the biosynthesis of manzamines came from the synthetic studies made on the conversion of 3-alkyl-dihydropyridinium salts to the unstable 3-alkyldihydropyridine reported in Fig.(24) [39]. Similar compounds were used in model studies towards a biomimetic synthesis of the alkaloids keramaphidin A and halicyclamine A [40]. 

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