Helically chiral ferrocene peptides containing 1'-aminoferrocene-1-carboxylic acid subunits as turn inducers.
We present a detailed structural study of peptide derivatives of 1'-aminoferrocene-1-carboxylic acid (ferrocene amino acid, Fca), one of the simplest organometallic amino acids. Fca was incorporated into di- to pentapeptides with D- and L-alanine residues attached to either the carboxy or amino group, or to both. Crystallographic and spectroscopic studies (circular dicroism (CD), IR, and NMR) of about two dozen compounds were used to gain a detailed insight into their structures in the solid state as well as in solution. Four derivatives were characterized by single-crystal X-ray analysis, namely Boc-Fca-Ala-OMe (16), Boc-Fca-D-Ala-OMe (17), Boc-Fca-beta-Ala-OMe (18), and Boc-Ala-Fca-Ala-Ala-OMe (21) (Boc=tert-butyloxycarbamyl). CD spectroscopy is an extremely useful tool to elucidate the helical chirality of the metallocene core. Unlike in all other known ferrocene peptides, the helical chirality of the ferrocene is governed solely by the chirality of the amino acid attached to the N terminus of Fca. Depending on the degree of substitution of both cyclopentadiene (Cp) rings, different hydrogen-bonding patterns are realized. (1)H NMR and IR spectroscopy, together with the results from X-ray crystallography, give detailed information regarding not only the hydrogen-bonding patterns of the compounds, but also the equilibria between different conformers in solution. Differences in chemical shifts of NH protons in dimethyl sulfoxide ([D(6)]DMSO) and CDCl(3), that is, the variation ratio (vr), is used for the first time as a measure of the hydrogen-bonding strength of individual COHN bonds in ferrocenoyl peptides. In dipeptides with one intramolecular hydrogen bond between the pendant chains, for example, in dipeptide 16, an equilibrium between hydrogen-bonded and open forms is observed, as testified by a vr value of around 0.5. Higher peptides, such as tetrapeptide 21, are able to form two intramolecular hydrogen bonds stabilizing one single conformation in CDCl(3) solution (vr approximately 0). Due to the low barrier of Cp-ring rotation, new and unnatural hydrogen-bonding patterns are emerging. The systematic work described herein lays a solid foundation for the rational design of metallocene peptides with unusual structures and properties.
Barisić
Lidija
L
Faculty of Food Technology and Biotechnology, Pierottijeva 6, HR-10000 Zagreb, Croatia. vrapic@pbf.hr
Cakić
Mojca
M
Mahmoud
Khaled A
KA
Liu
You-nian
YN
Kraatz
Heinz-Bernhard
HB
Pritzkow
Hans
H
Kirin
Srećko I
SI
Metzler-Nolte
Nils
N
Rapić
Vladimir
V
D002264:Carboxylic Acids / Q000737:chemistry*; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D005296:Ferrous Compounds / Q000737:chemistry*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D000075163:Metallocenes; D008958:Models, Molecular; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D017550:Spectroscopy, Fourier Transform Infrared; D013237:Stereoisomerism
C504075:1'-aminoferrocene-1-carboxylic acid; D002264:Carboxylic Acids; D005296:Ferrous Compounds; D007202:Indicators and Reagents; D000075163:Metallocenes; D010455:Peptides; C004998:ferrocene