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Preparation and Conformation Analysis of N ‐(Ferrocenoyl)dipeptide Esters and Their 1′‐Acetyl Derivatives
Author(s) -
Lapić Jasmina,
Djaković Senka,
Kodrin Ivan,
Mihalić Zlatko,
Cetina Mario,
Rapić Vladimir
Publication year - 2010
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200901435
Subject(s) - chemistry , ferrocene , dipeptide , hydrogen bond , moiety , conjugate , crystallography , stereochemistry , nuclear magnetic resonance spectroscopy , proton nmr , amino acid , molecule , organic chemistry , electrochemistry , mathematical analysis , biochemistry , mathematics , electrode
Abstract Ferrocene‐containing dipeptides X‐Fn‐CO‐AA‐AA‐OMe( 3 / 4 , X = H, AA = Gly/Ala; 5 / 6 , X = Ac, AA = Gly/Ala, Fn = ferrocene‐1,1′‐diyl) were prepared in 51–67 % yields from the starting appropriate ferrocenecarboxylic acid and dipeptide ester by the HOBt/EDC protocol. Conformation analysis of these bioconjugates was performed by spectroscopic methods (IR, 1 H and 13 C NMR, CD) and by X‐ray crystal structure analysis, as well as by molecular modelling (DFT). Crystallographic analysis showed that self‐assembly processes prevailed in compound 5 , and almost exclusively hydrogen‐bonded species were also detected in all the compounds studied in the solid state by IR spectroscopy (KBr). Spectroscopic studies of conjugates 3 – 6 undertaken in solution in nonpolar solvents demonstrated formation of intra‐ and interchain weak to medium hydrogen bonds spanning NH AA2 with 1‐FcCO, 1′‐FcCO and/or N AA1 (Fc = ferrocenyl). The same experiments revealed that NH AA1 is not involved in hydrogen bonds. The interchain hydrogen bond in conjugate 6 caused a ( P )‐helical arrangement of the ferrocene moiety exhibiting a positive Cotton effect at 495 nm (246 deg M –1 cm –1 ). All of the experimental findings were corroborated by DFT calculations, which furthermore showed conformation preferences in respect to the natural amino acid side chain of conjugates 3 – 6 .