Design of Ferrocene-Dipeptide Bioorganometallic Conjugates To Induce Chirality-Organized Structures

Abstract

The highly ordered molecular assemblies in proteins can have a variety of functions, as observed in enzymes, receptors, and the like. Synthetic scientists are constructing bioinspired systems by harnessing the self-assembling properties of short peptides. Secondary structures such as alpha-helices, beta-sheets, and beta-turns are important in protein folding, which is mostly directed and stabilized by hydrogen bonding and the hydrophobic interactions of side chains. The design of secondary structure mimics that are composed of short peptides has attracted much attention, both for gaining fundamental insight into the factors affecting protein folding and for developing pharmacologically useful compounds, artificial receptors, asymmetric catalysts, and new materials. Ferrocenes are an organometallic scaffold with a central reverse-turn unit based on the inter-ring spacing of about 3.3 A, which is a suitable distance for hydrogen bonding between attached peptide strands. The conjugation of organometallic compounds with biomolecules such as amino acids, peptides, and DNA should provide novel systems that reflect properties of both the ferrocene and the biologically derived moieties. In this Account, we focus on recent advances in the design of ferrocene-peptide bioconjugates, which help illustrate the peptidomimetic basis for protein folding and the means of constructing highly ordered molecular assemblies. Ferrocene-peptide bioconjugates are constructed to form chirality-organized structures in both solid and solution states. The ferrocene serves as a reliable organometallic scaffold for the construction of protein secondary structures via intramolecular hydrogen bonding: the attached dipeptide strands are constrained within the appropriate dimensions. The introduction of the chiral dipeptide chains into the ferrocene scaffold induces the conformational enantiomerization of the ferrocenyl moiety; the chirality-organized structure results from intramolecular hydrogen bonding. The configuration and sequence of the amino acids are instrumental in the process. Regulation of the directionality and specificity of hydrogen bonding is a key component in the design of various molecular assemblies. Ferrocene-peptide bioconjugates also have a strong tendency to self-assemble through the contributions of available hydrogen-bonding donors in the solid state. Some ferrocene-peptide bioconjugates bearing only one dipeptide chain exhibit a helically ordered molecular assembly through a network of intermolecular (rather than intramolecular) hydrogen bonds. The propensity to form the chiral helicity appears to be controlled by the chirality of the dipeptide chains. Organization of host molecules is a useful strategy for forming artificial receptors. The conformationally regulated ferrocene-peptide bioconjugate provides the chirality-organized binding site for size-selective and chiral recognition of dicarboxylic acids through multipoint hydrogen bonds. Metal ions serve a variety of purposes in proteins, including structural stabiliza...

Organogold(I)-uracil conjugates: Synthesis and structural characterization

“…U6AuPPh 3 : yield 48%; IR (KBr) 3170,3074,2923,2852,2116,1698,1661,1574,1456,1402,1366 PAu: C,54.40;H,4.85;N,3.96. Found: C,54.37;H,4.95;N,4.02.…”

Stimuli-responsive Synthetic Metallopeptides

“…In this metallopeptide, the [Cu II (bpy)] 2+ moiety served as an alternative of a ¢-turn structure and induced interstrand hydrogen bonding to form a ¢-hairpin structure (Figure 4a). 35 In a similar way, ferrocene derivatives, that are capable of parallel pointing two strands attached to both cyclopentadienyl rings, have also been used as turn-mimics by Herrick, Jarret, and Curran, 36 Kraatz, 37 Moriuchi and Hirao, 38 Rapić and Metzler-Nolte, 39 and Heinze ( Figure 4b). 40 Similar to ¡-helix stabilization, the metal-mediated intramolecular crosslinking method is also applicable to ¢-hairpin stabilization.…”

Palladium-catalyzed reaction of 2-iodoferrocenyl alcohols with internal alkynes: Synthesis of functionally 1,2-disubstituted ferrocenes and ferroceno-pyrans

“…Compound (22e 1 ): R f ¼ 0. 58 A screw-cap Pyrex bottle was charged with ferrocenyl alcohol (2-I, 1.00 mmol, 356 mg), 4,4-dimethyl-2-pentyne (6f, 4.00 mmol, 385 mg), (dppf)PdCl 2 (0.03 mmol, 24.48 mg) and i-Pr 2 NH (7 mL). Nitrogen was bubbled through the mixture for 2 min and the bottle was tightly closed.…”