Synthetic Model Compounds

The synthesis of a compound with a [Fe3S4l core analogous to that found in proteins proved to be a challenging task that was finally accomplished by Zhou and Holm in 1995 (49). This was the result of an extensive research program initiated by the Holm group soon after the discovery of biological 3Fe centers in 1980. A brief overview of the different stages of this work is presented next. 

Summary of Predicted and Observed Ground-State Properties of Protein-Bound 

Cluster Metsd ion Cluster fragment Ground state Ref. 

For heterometallic clusters with [Fe3S4] couples, the order potentials can be summarized as follows  

These studies of protein-bound heterometallic cubanes have amply demonstrated that the heterometal site is redox active and able to bind small molecules. Although they have yet to be identified as intrinsic components of any protein or enzyme (except as part of the nitrogenase FeMo cofactor cluster (254)), they are clearly attractive candidates for the active sites of redox enzymes. 

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Treatment of the precursors with decylamine resulted in a high level of chemiluminescence activity. Taking the activity obtained with decylamine as 100%, the activities obtained with other amines were methylamine, 5% hexylamine, 23% octylamine, 39% and dode-cylamine, 55%. For comparison, the Panellus precursors, PS-A and PS-B, are best activated with methylamine, and a synthetic model compound, K-l, is best activated with hexylamine. 

Although this spectrum had never been observed for any Fe-S protein, it was reminiscent of, and indeed nearly identical to the EPR spectrum of the synthetic model compound [FeeSeiLIe] where L = Cl, Br, I, RS, or RO (S). The spectrum of this synthetic cluster. 

IRON SEQUESTRATION BY SMALL MOLECULES THERMODYNAMIC AND KINETIC STUDIES OF NATURAL SIDEROPHORES AND SYNTHETIC MODEL COMPOUNDS... 

Synthetic model compounds - how chemists mimic nature... 

Figure 17. Synthetic model compounds having generalized structure 13 to assess the bilayer cation flux. 6, OE Oxyethylene, Monoaza-18-crown-6. 

Iron Sequestration by Small Molecules Thermodynamic and Kinetic Studies of Natural Siderophores and Synthetic Model Compounds Alvin L. Crumbliss and James M. Harrington... 

NMR positions were determined on 11 synthetic model compounds and dimers for comparison, and the data are recorded in Table I. The chemical shift positions of the protons are given in r values, and the multiplicity follows in parentheses. 

Several tetrapyrroles are employed by Nature to carry out fundamental biological functions and synthetic models compounds have been extensively used in order to understand the mechanisms of action of natural systems. 

For the C, 5 Nuphar alkaloids containing quinolizidine rings, deoxynupharidine (14), 7-epideoxynupharidine (15), nupharolutine (50), and 7-epinupharolutine (60), and also for the synthetic model compounds 3(e)-methyl-3(a)-methylthio-methylquinolizidine (68) and 3(a)-methyl-3(e)-methylthiomethylquinolizidine (69), the diagnostic carbon atoms that determine the conformation of the methyl and methylthiomethyl substituents are the carbon atoms of those groups as well as the carbon atoms of the quinolizidine ring at which the substituents are situated (67). For substituents in an axial conformation, the above-mentioned carbon... 

Comparisons between R- and T-state hemoglobins on the one hand and a variety of synthetic model compounds on the other have allowed an evaluation of the possible occurrence and importance of electronic, proximal-base tension, and distal-side steric effects on the kinetics of ligation of CO and 02. Although all of these effects could influence the reactivities of hemoproteins, we conclude that hemoglobin reactivity and cooperativity are controlled predominantly by the presence or absence of proximal-base tension. 

There are now good theoretical descriptions of the electronic structures contributing to the optical absorption bands in spectra of porphyrin radicals and ferryl species [160,167] most charge-transfer bands in the latter are due to a transition from a porphyrin p orbital to an Fe-0 tt orbital [167], However, in the absence of a prior knowledge of the structure around the Felv site (and/or spectra of a variety of synthetic model compounds) it is not straightforward to assign an optical spectrum to a ferryl species. Thus the intermediate assumed to be the ferryl species in the binuclear haem c /Cub centre of cytochrome c oxidase [168] has a spectrum at 580 nm essentially identical [169] to that of low-spin ferric haem a3 compounds (e.g. cyanide). 

Mossbauer spectra has been extensively used to probe the structure of the iron nucleus in biological FeIV=0 compounds. These include horseradish peroxidase compoundl[134,180,181], horseradish peroxidase compound II [182,183], horseradish peroxidase compound X [181], Japanese-radish peroxidase compounds I and II [184], chloroperoxidase compound I [185], cytochrome c peroxidase compound I [186] and ferryl myoglobin [183]. Examples of Mossbauer spectra attributed to non-porphyrin-bound FeIV are only available from synthetic model compounds. These include compounds with [130] and without [4-8] an FeIV=0 bond. 

Biomimetic Reactions Using Synthetic Model Compounds... 

Thanks to extensive studies of electronic spectra, Mdssbauer, infrared, resonance Raman, H and nO nmr spectroscopies, magnetism, EXAFS and X-ray crystallography, among others, on both the natural proteins or on synthetic model compounds, a lot is known about the active sites. 

Despite extensive studies, the enzymic formation of (D-glucosyl-amine)uronic acids as a result of the transformation of amino compounds in vivo, and the susceptibility of this type of conjugate towards hydrolysis by /3-D-glucosiduronase, are still the subject of controversial results. It should be emphasized that the high lability of (D-glucosyl-amine)uronic acids in general, and the lack of adequately characterized, synthetic model-compounds, create problems in obtaining reliable results. 

Figure 40. a) Structure of cytochrome c oxidase and (i) synthetic model compound (c) mechanism... 

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