Metallic moieties side chains

Figure 1.9 Examples of functionally important intrinsic metal atoms in proteins, (a) The di-iron center of the enzyme ribonucleotide reductase. Two iron atoms form a redox center that produces a free radical in a nearby tyrosine side chain. The iron atoms are bridged by a glutamic acid residue and a negatively charged oxygen atom called a p-oxo bridge. The coordination of the iron atoms is completed by histidine, aspartic acid, and glutamic acid side chains as well as water molecules, (b) The catalytically active zinc atom in the enzyme alcohol dehydrogenase. The zinc atom is coordinated to the protein by one histidine and two cysteine side chains. During catalysis zinc binds an alcohol molecule in a suitable position for hydride transfer to the coenzyme moiety, a nicotinamide, [(a) Adapted from P. Nordlund et al., Nature 345 593-598, 1990.)...

With ferrocenes, an alternative approach has been to attach the phosphorus moieties only to side chains. The WalPhos family (36) forms an eight-mem-bered chelate with the metal. Members of this family provide good selectivity and reactivity for the reductions of dehydroamino and itaconic acid derivatives as well as a,/ -unsaturated carboxylic acids [145, 156],... 

Annulation of aryl halides with ortho side chains bearing a pendant electi ophilic moiety via treatment with an organolithium reagent, involving halogen-metal exchange and subsequent nucleophilic cyclization to form 4- to 7-membered rings. 

CEJ1358> and the ruthenium mediated isomerization of double bonds (cf. Scheme 89, Section 8.11.7) <2007TL137> are recent examples of transition metal catalyzed manipulations at the side chain carbon atoms of 1,3-heterocycles. A novel side-chain addition reaction of aldehydes to 6-alkylidene-l,3-dioxin-4-ones was used for the construction of intermediates of lophotoxin <2006CJC1226>. An acid-catalyzed intramolecular cycloaddition of a hydroxy group to an alkene has been effected by the presence of an adjacent 1,3-dithiane moiety <2006TL4549>. 

Chls and all tetrapyrroles are heteroaromatic compounds and the aromatic character of the underlying tetrapyrrole moiety and the reactivity of the functional groups in the side chains govern their chemistry. Three different classes of tetrapyrroles, differentiated by their oxidation level, occur in nature porphyrins (11, e.g. hemes), chlorins (12, e.g. chls) and bacteriochlorins (13, e.g. bchls). As a cyclic tetrapyrrole with a fused five-membered ring, the overall reactivity of chi is that of a standard phytochlorin 7. Such compounds are capable of coordinating almost any known metal with the core nitrogen atoms. Together with the conformational flexibility of the macrocycle and the variability of its side chains, this accounts for their unique role in photosynthesis and applications ... 

Nguyen A, Top S, Vessieres A, Pigeon P, Huche M, Hillard EA, Jaouen G (2007) Organo-metallic analogues of tamoxifen effect of the amino side-chain replacement by a carbonyl ferrocenyl moiety in hydroxytamoxifen. J Organomet Chem 692 1219-1225... 

Once an alkyne moiety is introduced into a peptide, e.g., as propargyl glycine (Pgl) in place of a simple glycine in Enk, it can of course be used directly for complexation to a metal complex. Along those lines, we have reacted Co2(CO)g with the peptide Ac-Tyr-Gly-Pgl-Phe-Leu-NH2, to yield the Co2(CO)6 complexed to the Pgl alkyne side chain [32]. In a real SPPS scheme with a pre-formed metal-alkyne complex, the amino acid building block [Tp WI(CO)(ri2-Fmoc-Pgl-OH)] was incorporated to yield the side-chain substituted Enk derivative H-Tyr-Gly-[Tp W(I)(CO)(r 2-Pgl)]-Phe-Leu-OH (Tp tris(3,5-dimethylpyrazolyl)-borate) [44]. 

The term molybdenum cofactor (or Moco) refers to the metal center and its inner coordination sphere. Moco is not a single, unique, moiety, rather it is a diverse collection of protein-bound sites that have certain common features. Thus, one or two MPTs are coordinated to the metal via the dithiolene group and the remainder of the metal s coordination sphere is taken up by non-protein ligands (e.g., oxo, hydroxo, water, or sulfido groups) and, in some cases, an amino acid side chain is coordinated. Hille (1) has shown that the mononuclear Mo—MPT enzymes of molybdenum can be classified into three families, on the basis of the nature of the inner coordination sphere of the oxidized form of the enzyme (Fig. 2). 

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