Priprava, konformacijska analiza i kirooptička svojstva peptidnih derivata aminoferocena

U okviru ove doktorske disertacije provedena je sinteza i konformacijska analiza peptidnih konjugata aminoferocena [Boc–(AA)n–NH–Fc, Fc = ferocenil, AA = D(L)–Pro, D(L)–Ala, Boc (tert–butoksikarbonil), Aib (α–aminoizobutirična kiselina), n = 2–4] kao i dinuklearnih ferocenskih derivata [Fc–CO–(AA)2–NH–Fc, AA = D(L)–Pro, D(L)–Ala] kako bi se istražio utjecaj nabiranja aminokiselinskog slijeda na kirooptička svojstva organometalnog kromofora. Konformacijskom analizom (IR–spektroskopija, spektroskopija NMR i CD, kristalografska analiza, računalno modeliranje) utvrđeno je da su pripravljeni spojevi, u otopini i u čvrstom stanju, stabilizirani unutarmolekulskim vodikovim vezama koje podržavaju okrete i uzvojnice slične onima u prirodnim peptidima. Kombiniranim teorijskim i eksperimentalnim pristupom pokazano je kako kiralno uređenje peptidnog segmenta inducira Cottonov efekt u blizini UV/Vis apsorpcijskog maksimuma ferocena čiji je predznak u korelaciji s diedarskim kutom koji opisuje rotaciju oko veze između ferocenskog kromofora i peptidnog segmenta. In this PhD thesis peptide derivatives of aminoferrocene [Boc–(AA)n–NH–Fc, Fc = ferrocenyl, AA = D(L)–Pro, D(L)–Ala, Aib, Boc (tert–butoxycarbonyl), Aib (α– aminoisobutyric acid), n = 2–4] as well as the dinuclear ferrocene derivatives [Fc–CO– (AA)2–NH–Fc, AA = D(L)–Pro, D(L)–Ala] were synthesized. The novel compounds were subjected to conformational analysis in order to investigate the influence of folding of amino acid sequence on the chiroptical properties of organometallic chromophore. Conformational analysis (IR, NMR, and CD spectroscopy, crystallographic analysis, computational modeling) of the prepared compounds revealed that they are stabilized by intramolecular hydrogen bonds, that support turns and helices similar to those in natural peptides, in solution as well as in solid state. The combined theoretical and experimental approach has shown that the chiral arrangement of the peptide segment induces Cotton effect near the UV/Vis absorption maximum of ferrocene, whose sign is in correlation with dihedral angle which describes rotation around ferrocene–peptide linkage.