Interaction of ferrocenoyl-dipeptides with 3-aminopyrazole derivatives: beta-sheet models? A synthetic, spectroscopic, structural, and electrochemical study.
The use of 3-aminopyrazole derivatives as beta-sheet templates is investigated using a series of ferrocenoyl (Fc)-dipeptides (Fc-Gly(2)-OEt, Fc-Ala(2)-OBzl, Fc-Leu-Phe-OMe, Fc-Val-Phe-OMe, Fc-Phe(2)-OMe, Fc-Leu(2)-OMe, Fc-Val(2)-OMe). The synthesis and full characterization are reported. The solid-state structures of Fc-Gly(2)-OMe and Fc-Leu-Phe-OMe show extensive hydrogen bonding of the podand peptide substituents, resulting in the formation of supramolecular Fc-dipeptide assemblies. For Fc-Gly(2)-OMe, this can be described as a parallel beta-sheet, whereas intermolecular interactions in Fc-Leu-Phe-OMe result in the formation of supramolecular helical structures. The saturation titrations of Fc-dipeptides with 3-amino-5-methylpyrazole (3-AMP) and 3-trifluoroacetylamido-5-methylpyrazole (3-TFAc-AMP) show a 1:1 interaction of the Fc-peptide with the aminopyrazole derivatives. IR measurements in solution confirm binding to the top face of the Fc-dipeptide and the involvement of the Fc-C=O and the ester C=O groups in establishing H-bonding interactions with the 3-TFAc-AMP. However, binding constants in chloroform are low and range from 8 to 27 M(-1), which correspond to binding energies of 5-7 kJ mol(-1). In higher polarity solvents, such as acetonitrile or acetone, the binding constants are below 5 M(-1), emphasizing the limited utility of 3-AMP derivatives as beta-sheet templates. Electrochemical measurements confirm the weak interactions between the various Fc-dipeptides and 3-TFAc-AMP. Typical shifts in the redox potential of the Fc moiety are in the range 0-20 mV. Attempts to modify 3-AMP at the 3-position by carbodiimide coupling with amino acid derivatives and, thus, enhance the binding to the Fc-peptides resulted in 2-amino acid substituted 3-AMP derivatives. Substitution at the 2-position blocks the binding site, and no interactions with Fc-dipeptides are observed.
Saweczko
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Department of Chemistry, University of Saskatchewan, 110 Science Place, Saskatoon, Saskatchewan S7N 5C9, Canada.
Enright
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Kraatz
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D018360:Crystallography, X-Ray; D004151:Dipeptides / Q000737:chemistry*; D004563:Electrochemistry; D005296:Ferrous Compounds / Q000737:chemistry*; D006860:Hydrogen Bonding; D000075163:Metallocenes; D008956:Models, Chemical; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D011720:Pyrazoles / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared
C436945:3-aminopyrazole; D004151:Dipeptides; D005296:Ferrous Compounds; D000075163:Metallocenes; D011720:Pyrazoles; C004998:ferrocene