Synthesis and photophysics of oligopeptides with arginine and modified tyrosine or BODIPY carboxylic acid

U ovome radu provedena je sinteza dipeptida i tripeptida u otopini uz Boc-zaštitne skupine. Ciljne molekule su Boc-Arg(2Z)-Arg(2Z)-Tyr[m-CH2N(CH3)2]-OBn (1) i BODIPY-Arg(2Z)-Arg(2Z)-OBn (2). Tripeptid 1 u svojoj strukturi sadrži fotokemijski reaktivni tirozin koji u fotokemijskoj reakciji generira kinon-metid, dok dipeptid 2 sadrži BODIPY fluorofor. Oba peptida sadrže diargininski fragment za koji se očekuje nekovalentno vezanje na polinukleotide. Nadalje, fotokemijskim pobuđivanjem spoja 1, nekovalaletno vezanog za polinukleotide, očekuje se da će se generirati kinon-metidi koji će alkilirati polinukleotide, dok je fluorofor u spoju 2 uveden kako bi se nekovalentno vezanje vizualiziralo i kako bi se priredili fluorescentni indikatori za polinukleotide. Uspješno su sintetizirani spojevi Boc-Tyr-OH (4, η = 88 %), Boc-Tyr-OBn (5, η = 65 %), Boc-Tyr[m-CH2N(CH3)2]-OBn (6, η = 69 %), Boc-Arg(2Z)-OH (9, η = 49 %), Boc-Arg(2Z)-OMe (11, η = 25 %), Boc-Arg(2Z)-Arg(2Z)-OMe (14, η = 66 %), Boc-Arg(2Z)-ONHS (16, η = 68 %), Boc-Arg(2Z)-Arg(2Z)-OH (15, η = 27 %), Boc-Arg(2Z)-OBn (18, η = 98 %), Boc-Arg(2Z)-Arg(2Z)-OBn (20, η = 58 %), BODIPY-Arg(2Z)-Arg(2Z)-OBn (2, η = 32 %), dok je Boc-Arg(2Z)-Arg(2Z)-Tyr[m-CH2N(CH3)2]-OBn (1, η = 9 %) dobiven u smjesi s drugim spojevima. Svi sintetizirani spojevi okarakterizirani su 1H i 13C NMR spektroskopijom. Spoj 2 dodatno je okarakteriziran masenom spektrometrijom visoke rezolucije, FTIR-ATR-om i temperaturom tališta. U svrhu ispitivanja fotofizičkih svojstva, provedena su UV-Vis i fluorescencijska mjerenja. Za spoj 2 u acetonitrilnoj otopini određena je vrijednost molarnog apsorpcijskog koeficijenta (ε = 90500 dm^3 mol^-1 cm^-1, pri 499 nm), kvantni prinos fluorescencije (ՓF = 0,52) i vrijeme života singletnog pobuđenog stanja (τ = 1,21 ns).This thesis features the synthesis of a dipeptide and a tripeptide in solution using the Boc-protecting group chemistry. The target molecules were Boc-Arg(2Z)-Arg(2Z)-Tyr[m-CH2N(CH3)2]-OBn (1) and BODIPY-Arg(2Z)-Arg(2Z)-OBn (2). Tripeptide 1 contains a photochemically reactive modified tyrosine, which can generate quinone methide in the photochemical reaction, while dipeptide 2 contains a BODIPY fluorophore. Both peptides contain a diarginine fragment for which non-covalent bonding to polynucleotides is anticipated. Furthermore, upon the photochemical excitation of the compound 1 non-covalently bound to a polynucleotide, the generation of quinone methides is anticipated, leading to the alkylation of polynucleotides, whereas the fluorophore in compound 2 was introduced for the visualization of the non-covalent binding to develop fluorescent indicators for polynucleotides. We successfully synthesized Boc-Tyr-OH (4, η = 88 %), Boc-Tyr-OBn (5, η = 65 %), Boc-Tyr[m-CH2N(CH3)2]-OBn (6, η = 69 %), Boc-Arg(2Z)-OH (9, η = 49 %), Boc-Arg(2Z)-OMe (11, η = 25 %), Boc-Arg(2Z)-Arg-(2Z)-OMe (14, η = 66 %), Boc-Arg(2Z)-ONHS (16, η = 68 %), Boc-Arg(2Z)-Arg(2Z)-OH (15, η = 27 %), Boc-Arg(2Z)-OBn (18, η = 98 %), Boc-Arg(2Z)-Arg(2Z)-OBn (20, η = 58 %), BODIPY-Arg(2Z)-Arg(2Z)-OBn (2, η = 32 %), while Boc-Arg(2Z)-Arg(2Z)-Tyr[m-CH2N(CH3)2]-OBn (1, η = 9 %) was obtained in a mixture with other compounds. All synthesized compounds were characterized by 1H and 13C NMR spectroscopy. Additionally, compound 2 was characterized by high-resolution mass spectrometry, FTIR-ATR and melting point determination. To investigate photophysical properties, we conducted UV-Vis and fluorescence measurements. For compound 2 in acetonitrile solution, we determined the molar absorption coefficient (ε = 90500 dm^3 mol^-1 cm^-1 at 499 nm), fluorescence quantum yield (ՓF = 0,52) and lifetime of the singlet excited state (τ = 1,21 ns)