Cubane protonation

Iron Sulfur Compounds. Many molecular compounds (18—20) are known in which iron is tetrahedraHy coordinated by a combination of thiolate and sulfide donors. Of the 10 or more stmcturaHy characterized classes of Fe—S compounds, the four shown in Figure 1 are known to occur in proteins. The mononuclear iron site REPLACE occurs in the one-iron bacterial electron-transfer protein mbredoxin. The [2Fe—2S] (10) and [4Fe—4S] (12) cubane stmctures are found in the 2-, 4-, and 8-iron ferredoxins, which are also electron-transfer proteins. The [3Fe—4S] voided cubane stmcture (11) has been found in some ferredoxins and in the inactive form of aconitase, the enzyme which catalyzes the stereospecific hydration—rehydration of citrate to isocitrate in the Krebs cycle. In addition, enzymes are known that contain either other types of iron sulfur clusters or iron sulfur clusters that include other metals. Examples include nitrogenase, which reduces N2 to NH at a MoFe Sg homocitrate cluster carbon monoxide dehydrogenase, which assembles acetyl-coenzyme A (acetyl-CoA) at a FeNiS site and hydrogenases, which catalyze the reversible reduction of protons to hydrogen gas. 

Fig. 3. Ground state spin (S) and valence delocalization schemes for the known oxidation states of [Fe3S4] clusters. Discrete [Fe3S4] clusters have not been observed in siny protein, but they have been identified as fragments in heterometallic cubane clusters. Reduction of the [Fe3S4]+ cluster by three electrons, to yield a putative aU-ferrous cluster, occurs with the concomitant addition of three protons. Key S , grey Fe +, black Fe +, white Fe, white with central black dot.

Ethyl triflate and benzyl triflate react with the cubane at room temperature and yield phosphonium salts. Upon protonation even di- and trications could be observed [88,89]. 

A different type of dynamic process involving a polynuclear metal system has been identified in [(CH C H,)ltRul)Sl(]2+, which has a distorted cubane-like structure with three Ru—Ru bonds in the crystalline state (Fig. 15.56). By following its methyl and ring proton resonances over a temperature range from +70 to —43 BC (Fig. 1537), the complex is shown to undergo a dynamic process involving the metal-metal bonds. At the low-temperature limit, the spectrum contains features predicted for the static structure two lines of equal intensity for the methyl protons... 

Cubylcarboxonium ions have been also studied by Prakash, Olah, and co-workers.579,580 The parent cation 281 prepared under superacid conditions was stable at low temperature but decomposed to cubylacylium cation 282 as a result of further protonation and dehydration [Eq. (3.71)]. In addition to cation 281, di- and tetra-carboxonium ions and the corresponding protonated methyl esters were also observed as long-lived species stable under superacidic conditions. Experimental evidence and theoretical data indicated that the strained cubyl system effectively stabilizes the carbocationic centers through C—C bond hyperconjugation (283). On the basis of 13C data, three conformers of protonated dimethyl cubane-l,4-dicarboxylate (284-286) could be identified. 

For a long time Fe/S clusters in the enzyme complexes of the respiratory chain of oxidative phosphorylation have been suggested to be directly involved in energy transduction, e.g., in the generation of a proton-motive force. A specific example is the putative cubane, center N2, in NADH Q oxidoreductase [6], One could formally write the process as a catalysis of the reaction H+in -> H+out. 

Despite enormous strain, cubane is kinetically stable because breaking just one C—C bond causes only minor structural changes and hence only little relief of strain. A computational study shows that protonation occurs to give edge-protonated cubane.28 Cleavage of a second C—C bond is highly exothermic and this is followed by a further series of rapid exothermic molecular rearrangements (Scheme 16). 

The possible catalytic mechanism of [FeFe] hydrogenases is not well established, since there are fewer redox states accessible to spectroscopy (e.g. by EPR), the proton-accepting base is still being debated, and the protein structure shows a larger variability. Also, the DFT modeling of the reaction cycle is more complicated because the covalently attached cubane [4Fe-4S] subcluster, which seems to play an important role in the electron shuffling, is difficult to include in the calculations. 

Cubane- 1,2-dicarboxylic acid 12 (see Fig. 2.19), a precursor for 1,2-dihalocubanes was prepared from commercially available cubane-1,4-dicarboxylic acid in 65% yield. The other acids 14a and 14c were similarly prepared from the cubane-l,4-dicarboxylic acid 14b according to the literature procedures. 1H NMR spectra of the compound 13a showed a broad singlet at 4.41 for the clibyl protons, whereas compound 13b showed two multiplets. Conversion of bridgehead carboxylic acids to the corresponding halides using Pb(OAc)4 and iodine in refluxing benzene under illumination is reported. This is considered to be an alternative to Barton s method, because of its simplicity and ease of preparation, but it involves toxic lead compounds. 

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