Potenciálisan biológiailag aktív fémorganikus vegyületek - ferrocészubsztituált heterociklusok - és peptid-konjugátumaik szintézise, szerkezet-felderítése és komplex nagyműszeres (NMR, IR, UP, Mössbauer spektroszkópiai és Röntgen-diffrakciós) vizsgálata = Synthesis, structure determination and complex instrumental (NMR, IR, UP, Mössbauer spectroscopic and x-ray diffraction) study on organometallic compounds - ferrocenyl-substituted heterocycles - and their peptide derivatives with expected biological

Tanulmanyoztuk a ferrocen-szubsztiutucio hatasat heterociklusok kepződesere. Hatastani vizsgalatokhoz valtozatos szerkezetű fc-szarmazekok előallitasara torekedtunk. Előallitottunk (het)aril-fc kalkonokat, s pirazol/in-szarmazekaikat. Etilazido-fc-akrilatbol foszforilideken at tobbfele hetaril-vegyuletet nyertunk. Piridazinonil-fc-t es bisz-analogjat előallitva, fazistranszfer diallilezest kovető metatezissel ferrocenofanokhoz jutottunk. Hidrazinnal ket fc-hidas makrociklusokat nyertunk, tanulmanyoztuk konformaciojukat, s elkeszitettuk Pd-komplexeiket. Acilferrocenek tio/metiltio-szemikarbazonjaibol DMAD-val valtozatos heterociklusokat kaptunk. Vizsgaltuk diacil-fc-hidrazonok cikloaddicioit. A reaktivitasbeli eltereseket es NMR-uton igazolt molekuladinamikat szamitasokkal ertelmeztuk. Az uj vegyuletek szerkezetet spektroszkopiaval (IR, NMR, MS) es rontgendiffrakcioval tisztaztuk. Az uj fc-szarmazek in vitro tumorgatlo hatasat vizsgaltuk human leukemia sejteken, a leghatekonyabb vegyuletek hatasat rezisztens sejteken is es hasonloan jo novekedesgatlast eszleltunk. Oligoarginin komponensekkel előallitottuk a fc-karbonsav es a fc-akrilsav uj peptid-konjugatumait es meghataroztuk a sejtnovekedes-gatlo hatast HL-60 sejtvonalon. Előallitottunk fc-(glioxil)-aminosav- es -szteroid-kalkon-konjugatumokat Pd-katalizalt karbonilezessel. Modszert dolgoztunk ki heterodiszubsztitualt ferrocenek 1,1'-dijod-ferrocenből kiindulo homogen katalitikus szintezisere. | The effect of ferrocene (fc) substituent on the formation of heterocycles was studied. For screening we produced a variety of fc compounds. We prepared (het)aryl-fc chalcones and their pyrazol/(in)e derivatives. From ethyl-azido-fc-acrylate some aryl-heterocycles were obtained. We prepared pyridazinonyl-fc and its bis analogue, from which via phase transfer diallylation and metathesis we obtained different ferrocenophanes. The reactions with hydrazine gave macrocycles with two fc bridges. The molecular dynamics was studied and Pd-complexes were prepared. The reactions of DMAD with tio/methylthiosemicarbazones of acyl-fc's yielded new heterorings. We studied the hydrazones and their cycloadditions. The structure-reactivity relationships and the molecular dynamics revealed by NMR were interpreted by calculations. The structures of the novel compounds were cleared by spectroscopy (IR,NMR, MS) and x-ray analysis. The in vitro antitumor activity of novel fc-derivatives were investigated on human leukemia cells. The most effective ones were also studied on resistant cells and gave good results. Using oligoarginin components, peptide conjugates of fc-carboxylic and -acrylic acid were obtained, and their antiproliferative effect was determined on HL-60 cells. Fc-(glyoxyl) amino acid- and steroid-chalcone-conjugates were synthesised by Pd-catalysed carbonylation. We elaborated a homogeneous catalytic route towards heterodisubstituted fc's from 1,1'-diiodo-fc.