Two 14 pi cross-linked annulenes which belong to the family of dicyclopenta[a,e]pentalenes have been synthesized, 14 pi bis enol triflate ester 27 and the 3,7-diisopropylsilyl substituted 14 pi dicyclopenta[a,e]pentalene 30. The new allenic tandem Pauson-Khand reaction mediated by Mo(CO)(6) was employed as the key process to construct the core of the tetracycles. The two linear dicyclopenta[a,e]pentalenes 27 and 30 underwent significant electronic delocalization, perhaps even aromaticity, as revealed by the X-ray structure of 27. The tetracyclic rings in 27 assumed a flat geometry (Figure 4); the bond lengths of the tetracycle in 27 also fit well into the criteria for aromatic compounds. A comparison of the NMR and UV spectra of both 27 and 30 demonstrated that they both exhibited similar electronic properties, therefore, the purple colored 14 pi cross linked annulene 30 is planar as well as delocalized.

The synthetic peptide fragment containing residues 49-61 of rabbit liver metallothionein II (MT-II) (Ac-Ile-Cys-Lys-Gly-Ala-Ser-Asp-Lys-Cys-Ser-Cys-Cys-Ala-COOH), which includes the only sequential four cysteines bound to the same metal ion in Cd7MT, forms a stable, monomeric Cd-peptide complex with 1:1 stoichiometry (Cd:peptide) via Cd-thiolate interactions. This represents the first synthesis of a single metal-binding site of MT independent of the domains. The 111Cd NMR chemical shift at 716 ppm indicates that the 111Cd2+ in the metal site is terminally coordinated to four side-chain thiolates of the cysteine residues. The pH of half dissociation for this Cd-peptide derivative, approximately 3.3, demonstrates an affinity similar to that for Cd7MT. Molecular mechanics calculations show that the thermodynamically most stable folding for this isolated Cd2+ center has the same counterclockwise chirality (lambda or S) observed in the native holo-protein. These properties are consistent with its proposed role as a nucleation center for cadmium-induced protein folding. However, the kinetic reactivity of the CdS4 structure toward 5,5'-dithiobis(5-nitrobenzoate) (DTNB) and EDTA is greatly increased compared to the complete cluster (a-domain or holo-protein). The rate law for the reaction with DTNB is rate = (k(uf) + k(1,f) + k(2,f) [DTNB])[peptide], where k(uf) = 0.15 s(-1), k(1,f)= 2.59x10(-3) s(-1), and k(2,f) = 0.88 M(-1) s(-1). The ultrafast step (uf), observable only by stopped-flow measurement, is unprecedented for mammalian (M7MT) and crustacean (M6MT) holo-proteins or the isolated domains. The accommodation of other metal ions by the peptide indicates a rich coordination chemistry, including stoichiometries of M-peptide for Hg2+, Cd2+, and Zn2+, M2-peptide for Hg2+ and Au+, and (Et3PAu)2-peptide.

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