How Useful Is Ferrocene as a Scaffold for the Design of β‐Sheet Foldamers?

Abstract

Falten erwünscht: Die ersten Tripeptid‐Ferrocen‐Foldamere, die in Lösung und im Festkörper eine ausgedehnte β‐Faltblatt‐artige Struktur einnehmen, wurden entwickelt. Bisher war man davon ausgegangen, dass die Beweglichkeit der Peptidsubstituenten in 1,n′‐Ferrocen‐Bispeptid‐Konjugaten die Bildung ausgedehnter β‐Faltblatt‐Foldamere verhindert. Die neuen Befunde lassen nun den Schluss zu, dass Ferroceneinheiten nützlich für das Design von β‐Faltblättern sind.

Diphenylacetylene‐Linked Peptide Strands Induce Bidirectional β‐Sheet Formation

“…[4] In addition, the ability to construct easily variable functionalized surfaces, in the manner of an extended b-sheet, has many potential applications in supramolecular chemistry for the formation of new materials or catalysts. [6] This broad approach of covalently linking one end of a b-sheet has been extended by others using tolan derivatives, [7] substituted biphenyl, [8] dibenzofuran, [9] oligoanthranilamide, [10] and urea scaffolds, [11] as well as more unusual motifs such as ferrocene [12] or other metal-chelating groups [13] to template the two strands. In a seminal study, Kemp and co-workers described a b-turn mimic derived from a substituted diphenylacetylene that templates intramolecular hydrogen-bonded b-sheet for-mation.…”

“…In a seminal study, Kemp and co-workers described a b-turn mimic derived from a substituted diphenylacetylene that templates intramolecular hydrogen-bonded b-sheet for-mation. [6] This broad approach of covalently linking one end of a b-sheet has been extended by others using tolan derivatives, [7] substituted biphenyl, [8] dibenzofuran, [9] oligoanthranilamide, [10] and urea scaffolds, [11] as well as more unusual motifs such as ferrocene [12] or other metal-chelating groups [13] to template the two strands. Others have exploited the simple strategy of cyclizing peptide or peptidomimetic strands [14] to form a length of b-sheet flanked by two b-turn units ( (Figure 1 c) [15] and cross-linking strands using disulfide bonds has also been employed (Figure 1 d).…”

Conformational Analysis of β‐Lactam‐Containing Ferrocene Peptides

“…[31][32][33][34][35][36][37][38][39][40][41] Indeed, this is also computed as a stable conformation of 14 with a (P)-helical ferrocene moiety (conformer 14b; NH Ala ···CO Ala 1.98 and 1.94 Å). However, additional stable conformations of 14 ( Figure 10, Scheme 4, 14a and 14c) have been observed during the geometry optimizations that feature three hydrogen bonds, namely one γ-turn (NH Alm ···CO Fc 1.89 Å), one interchain H-bond NH Ala ···CO Ala (1.86 Å), and one interchain hydrogen bond NH Ala ···CO Alm (2.03 Å) in 14a and two γ-turns (NH Alm ···CO Fc 1.87 and 2.08 Å) and one interchain H-bond NH Ala ···CO Fc (1.99 Å) in 14c.…”

“…Usually, these intramolecular hydrogen bonds are sufficiently strong to retain this C 2 -symmetrical conformation in chloroform solution. [31][32][33][34][35][36][37][38][39][40][41] As a result of their constitution, type II conjugates can only form parallel peptide strands. The feature of natural peptides to form turns by juxtapositioning their chains in an antiparallel way can be mimicked by bioorganometallics that include 1Ј-aminoferrocene-1-carboxylic acid (Fca [42] ) coupled with natural amino acids or peptides (Scheme 1, type III).…”

“…Symmetrically substituted bioconjugates of ferrocene-1,1Ј-dicarboxylic acid (Fcd) with 1-2 amino acids per substituent have been extensively studied. [31][32][33][34][35][36][37][38][39][40][41] In the solid state, the majority of these compounds form two intramolecular hydrogen bonds (independent of the number and type of the amino acid incorporated). This results in the formation of two 10-membered rings (Scheme 1, type II; β-turn-like "Herrick conformation").…”