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Synthesis of Intrinsically Blue-Colored bis-Nitronyl Nitroxide Peptidomimetic Templates and Their Conformational Preferences as Revealed by a Combined Spectroscopic Analysis

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journal contribution
posted on 31.08.2017, 00:00 by Marta De Zotti, Karen Wright, Edouard d’Aboville, Antonio Toffoletti, Claudio Toniolo, Giovanna Longhi, Giuseppe Mazzeo, Sergio Abbate, Fernando Formaggio
The intrinsically blue-colored Ullman imidazolinyl nitronyl nitroxide (NN) mono-radicals have found various applications, in particular as spin probes and organic magnetic materials. Here, we present the solution-phase synthesis, extensive characterization, and conformational analysis of the first peptidomimetics with two pendant, chiral nitronyl nitroxide free radical units. Two (R)-Aic­(NN) residues, where Aic­(NN) is 2-amino-5-nitronylnitroxide-indan-2-carboxylic acid, have been inserted at positions i and i+3 of the pentapeptide Boc-(R)-Aic­(NN)-(Ala)2-(R)-Aic­(NN)-Ala-OMe and the hexapeptide Boc-[Ala-(R)-Aic­(NN)-Ala]2-OMe as well. The two compounds were obtained in good yields and high purities. Thanks to a combination of several spectroscopic techniques (IR absorption, NMR, VCD, and EPR) we gained clear evidence that both compounds adopt a right-handed 310-helical conformation with both nitronyl nitroxide pendants positioned on the same side of the helix. This peptidomimetic/free radical system is a potentially excellent template for the preparation of a set of appropriate analogs with exciting applications in the area of host–guest organic chemistry, or to spectroscopically evaluate in-depth the intramolecular exchange interactions in this type of probe.