Structurally different ferrocene peptides I-VI exhibit considerable conformational differences. This study has explored the structural properties of VII [Y-AA-Fca-OMe; Y = di-tert-butyl dicarbonate (Boc), acetyl (Ac); AA = L-Ala, D-Ala; Fca = 1Ј-aminoferrocene-1-carboxylic acid] with an exchanged sequence of constituent amino acids relative to VI (Y-Fca-AA-OMe; Y = Boc, Ac; AA = L-Ala, D-Ala). The ferrocene peptides VII were obtained by coupling C-protected Fca with Boc-L-Ala-OH and Boc-D-Ala-OH, respectively. The Boc protecting groups of the obtained conjugates Boc-AA-Fca-OMe (2a, AA = L-Ala; 2b, AA = D-Ala) were converted to sterically less demanding Ac groups to give Ac-AA-Fca-1820 Avance 300 MHz spectrometer in CDCl 3 solutions with Me 4 Si as the internal standard. Double resonance experiments (COSY, NOESY, and HMBC) were performed in order to assist in signal assignment. CD spectra were recorded using a Jasco-810 spectropolarimeter in CH 3 CN. Molar ellipticity coefficients, [θ], are in degrees, concentration, c, is given in molL -1 , and path length, l, is given in cm, to give units for [θ] of deg cm 2 dmol -1 . Computational Details:The starting geometries of 2a and 3a were generated by the MacroModel v9.8 [26] molecular modeling program using several different search methods and force fields. The conformers were fully optimized at the B3LYP/LanL2DZ level of theory. [23] The most stable were reoptimized in chloroform (using IEF-PCM to describe implicit solvent effects) with the B3LYP method and 6-311+G(d,p) basis set. [24] Iron was modeled using the ECP set LanL2DZ. Quantum mechanical calculations were performed with Gaussian 09, v.A.02. [27] Molecules were visualized using GaussView [28] and Chem 3D (CambridgeSoft, Cambridge, MA) programs. The topological analysis of the selected compounds was performed with the AIM2000 program. [29] Boc-AA-Fca-OMe (2a/2b): The syntheses of 2a and 2b were performed according to our recent paper: [9] the fully protected ferrocene amino acid Boc-Fca-OMe [5] (1) was N-deprotected by gaseous HCl in EtOAc to give the hydrochloride salt, which was treated with NEt 3 and coupled with Boc-AA-OH (AA = l-, d-Ala, previously activated by using EDC and HOBt). After standard workup and TLC-purification, Boc-l-Ala-Fca-OMe (2a) and Boc-d-Ala-Fca-OMe (2b) were obtained as orange resins.

A series of peptides that contain homo- and heterochiral Ala-Pro sequences attached to the turn-inducing ferrocene-1,1'-diamine scaffold were synthesized. The effects of the backbone chirality and the N-terminal group (Boc/Ac) on the conformational properties of the novel peptidomimetics were thoroughly explored by IR, NMR, and CD spectroscopy and the experimental observations were corroborated by DFT studies in solution. The most stable conformers of the homochiral peptides adopted the interstrand hydrogen-bond patterns, realized through ten- and thirteen-membered rings. The common feature of the most stable conformers of the heterochiral peptides was the adoption of the turn-like structures that feature the simultaneous intra- (seven-membered) and interstrand (sixteen-membered) hydrogen-bonded rings. An exchange of two N-terminal groups had a somewhat larger influence on the distribution of the hydrogen-bond patterns in homochiral than in heterochiral derivatives. The homochiral peptides that contain pyridine moieties as metal coordination sites formed 1:1 complexes with divalent metal ions, which included Zn , Cd , Cu and Fe .

No abstract

No abstract

The organometallic amino acid 1′‐aminoferrocene‐1‐carboxylic acid (Fca) was incorporated internally into a peptide sequence by solid‐phase methods combining natural Fmoc‐protected amino acids and Boc‐Fca‐OH to give the pentapeptide Boc‐Fca‐Ala‐Gly‐Val‐Leu‐NH2 (2) and the octapeptide Ac‐Val‐Gly‐Ala‐Fca‐Ala‐Gly‐Val‐Leu‐NH2 (3). Compound 3 was found to have a helically ordered structure by NMR and CD spectroscopy, which is stabilized by intramolecular hydrogen bonding in an antiparallel β‐sheet‐like arrangement. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)