Provider: - Institution: - Data provided by Europeana Collections- This works describes synthesis, characterization and potential cytotoxity of O,O'- -dialkyl-(S,S)-ethylenediamine-N,N'-di-2-(4-methyl)-pentanoic acid, (S,S)-H4eddlCl2, as well as their corresponding palladium(II), platinum(II) and platinum(IV) complexes. Esters (S,S)-R2eddl•2HCl (R = ethyl, n-propyl, n-butyl and n-pentyl) were obtained by instillation of thionyl chloride in an appropriate absolute alcohol, and then refluxing with addition of (S,S)-ethylenediamine-N,N'-di-2-(4-methyl)-pentanoic acid. All of the esters were obtained as dihydrochlorides: (S,S)-Et2eddl•2HCl, (S,S)-Pr2eddl•2HCl, (S,S)-Bu2eddl•2HCl, (S,S)-Pe2eddl•2HCl. Esters were characterized by elemental analysis, IR and NMR spectroscopy, and in the case of (S,S)-Pr2eddl•2HCl the structure was confirmed by X-ray structural analysis. Complexes of palladium(II): PdCl2{(S,S)-Et2eddl}, PdCl2{(S,S)-Pr2eddl}, PdCl2{(S,S)-Bu2eddl} and PdCl2{(S,S)-Pe2eddl} were obtained by reaction of potassium- -tetrachloridopalladate(II) with synthesized esters and characterized by elemental analysis, IR and NMR spectroscopy. Complexes of platinum(II): PtCl2{(S,S)-Et2eddl}, PtCl2{(S,S)-Pr2eddl}, PtCl2{(S,S)-Bu2eddl} and PtCl2{(S,S)-Pe2eddl} were obtained by reaction of potassium- -tetrachloridoplatinate(II) with these esters and characterized by elemental analysis, IR and NMR spectroscopy. Complexes of platinum(IV): PtCl4{(S,S)-Et2eddl}, PtCl4{(S,S)-Pr2eddl}, PtCl4{(S,S)-Bu2eddl} and PtCl4{(S,S)-Pe2eddl} were obtained by reaction of potassium- -tetrachloridoplatinate(II) with mentioned esters and characterized by elemental analysis, IR and NMR spectroscopy. DFT calculations were performed for the synthesized complexes of platinum(II) and platinum(IV) and it was found that the (R,R)-N,N’-configuration isomer is with the lowest energy and formation of only this isomer should be expected, which is consistent with NMR spectroscopy. Cytotoxic activity of synthesized compounds was determined against chronic lymphocyte leukemia cells (CLL) and human cell lines: SW480 colorectal cancer, breast MDA-MB-361 and MDA-MB-453, Jurkat T leukemia and K562 chronic myelogenous leukemia compared with activity of cisplatin, as a reference anticancer drug. All compounds showed higher antitumoral activity then activity cisplatin against CLL calls. It was found that the most active complexes is complexes platinum(II) with n-Bu group in the ester chain. Complexes of the platinum(IV) have an exellent citotoxic activity in the inhibition of Jurkat and K562 cell lines, with is very similar to that shown by activity of cisplatin.- U ovoj doktorskoj disertaciji opisana je sinteza, karakterizacija i potencijalna citotoksičnost O,O'-dialkil estara (S,S)-etilendiamin-N,N'-di-2-(4- -metil)-pentanske kiseline, (S,S)-H4eddlCl2, kao i odgovarajućih paladijum(II), platina(II) i platina(IV) kompleksa. Estri (S,S)-R2eddl•2HCl (R = etil, n-propil, n-butil i n-pentil) su dobijeni ukapavanjem tionil-hlorida u odgovarajući apsolutni alkohol, a potom refluktovani uz dodatak (S,S)-etilendiamin-N,N'-di-2-(4-metil)-pentanske kiseline. Svi estri su dobijeni u obliku dihidrohlorida: (S,S)-Et2eddl•2HCl, (S,S)-Pr2eddl•2HCl, (S,S)-Bu2eddl•2HCl, (S,S)-Pe2eddl•2HCl. Estri su okarakterisani elementalnom analizom, IR i NMR spektroskopijom, a u slučaju (S,S)-Pr2eddl•2HCl struktura je potvrđena i rendgenskom strukturnom analizom. Kompleksi paladijuma(II): PdCl2{(S,S)-Et2eddl}, PdCl2{(S,S)-Pr2eddl}, PdCl2{(S,S)-Bu2eddl} i PdCl2{(S,S)-Pe2eddl} dobijeni su u reakciji kalijum- -tetrahloridopaladata(II) sa navedenim estrima i okarakterisani elementalnom analizom, IR i NMR spektroskopijom. Kompleksi platine(II): PtCl2{(S,S)-Et2eddl}, PtCl2{(S,S)-Pr2eddl}, PtCl2{(S,S)-Bu2eddl} i PtCl2{(S,S)-Pe2eddl} dobijeni su u reakciji kalijum- -tetrahloridoplatinata(II) sa navedenim estrima i okarakterisani elementalnom analizom, IR i NMR spektroskopijom. Kompleksi platine(IV): PtCl4{(S,S)-Et2eddl}, PtCl4{(S,S)-Pr2eddl}, PtCl4{(S,S)-Bu2eddl} i PtCl4{(S,S)-Pe2eddl} dobijeni su u reakciji kalijum- -heksahloridoplatinata(IV) sa navedenim estrima i okarakterisani elementalnom analizom, IR i NMR spektroskopijom. DFT proračuni rađeni su za sintetisane komplekse platine(II) i platine(IV) i ustanovljeno je da je (R,R)-N,N’-konfiguracioni izomer najniže energije, pri čemu je formiranje samo jednog izomera očekivano jer je u saglasnosti sa NMR spektroskopijom. Citotoksična aktivnost sintetisanih jedinjenja određena je na ćelijama hronične limfocitne leukemije (CLL) i humanim ćelijskim linijama: kolorektalnog karcinoma SW480, karcinoma dojki (MDA-MB-361 i MDA-MB-453), akutnoj T limfocitnoj leukemiji Jurkat i hroničnoj mijeloidnoj leukemiji K562 u poređenju sa aktivnošću cisplatine, kao referentnim antikancerogenim lekom. Sva jedinjenja pokazuju aktivnost veću od cisplatine prema CLL ćelijama. Nađeno je da najaktivnije jedinjenje kompleks platine(II) sa n-Bu grupom u estarskom lancu. Kompleksi platine(IV) imaju odličnu citotoksičnu aktivnost u inhibiciji Jurkat i K562 ćelijskih linija koja je veoma slična onoj koju pokazuje aktivnost cisplatine. Ključne reči: (S,S)-etilendiamin-N,N'-di-2-(4-metil)pentanska kiselina, (S,S)-R2eddl ligandi, R2edda ligandi, platina(IV) kompleksi, platina(II) kompleksi, paladijum(II) kompleksi, kristalna struktura, DFT proračuni, citotoksičnost- All metadata published by Europeana are available free of restriction under the Creative Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana