Although thermally induced transformations of framework aluminosilicates provide unique method for synthesis of materials with advanced properties, conversion mechanism is not explained yet because ...of the complexity of the process. Because of the small unit cell (Na12Si12Al12O4827H2O) and well known framework structure and extra-framework cation distribution, zeolite Na-LTA represents ideal model for investigation of changes in the short, middle and long range order, in the processes of zeolite thermal transformation into stuffed derivatives of SiO2 polymorphs. Even though investigations showed that Na-LTA zeolite is not pure from crystallographic point of view and, depending on synthesis procedure, contains different amounts of Na, Al and Si inclusions inside α and β cages, there are no data regarding catalytic influence of these species on the mechanism of thermal conversions. Presented thesis surmises results of investigations of the influence of Na, Al and Si inclusion species on the mechanism of Na-LTA thermally induced transformations into carnegieite and nepheline polymorphs. The first chapter of thesis deals with Na-LTA synthesis procedure with different amounts of Na, Al and Si inclusions. The influence of small variations of Na2O:Al2O3:SiO2 ratio in initial reaction mixture on stoichiometry of synthesized Na-LTA zeolites and crystal grain morphology is described. Refluxing treatment at 100 ºC is suggested as method for removing extra-framework species remained after synthesis process, which does not induce amorphization or other structural changes of zeolite. The second chapter of the thesis is focused on the investigation of the influence of Na, Al and Si inclusions on zeolite Na-LTA thermal stability and conversion into carnegieite and nepheline polymorphs. Special attention is dedicated to the investigation of the mechanism of zeolite Na-LTA transformation into low-temperature carnegieite, which is presented with different conversion routes in the literature. In one aspect Na-LTA zeolite transforms directly into low-temperature carnegieite: Na-LTA → low-temperature carnegieite, while in the other, unfolds through amorphous phase: Na- LTA →Amorphous phase → low-temperature carnegieite. XRPD, DTA and IR investigations showed that Na, Al and Si inclusions catalyze zeolite Na-LTA transformation into low-temperature carnegieite, without the possibility of detection of amorphous phase, inducing rapid breaking and formations of bonds, whereby the rate of transformation increases with increasing Al content. On the other hand, in the case of reflux treated Na-LTA zeolite with ideal stoichiometry, thermal transformation into low-temperature carnegieite is preceded by collapse of LTA framework and formation of stable amorphous phase, which subsequently crystallized into low-temperature carnegieite. Characterization of amorphous NaAlSiO4 phase by IR and Raman spectroscopy showed the presence of four- and six-membered tetrahedral rings, which lead to conclusion that by the collapse of zeolite into amorphous phase, relicts of LTA frameworka are retained. This can can be used as a starting point in synthesis of perfect glasses. On higher temperatures, formation conditions of nepheline structures by reconstructive phase transformations of low-temperature carnegieite were investigated. Because of the various nepheline polymorphs with diverse symmetry, formation conditions of different nepheline structures are current problem in mineralogy. Investigation showed that Na, Al and Si inclusion species in Na-LTA zeolite, induce transformation of low-temperature carnegieite into mixture of monoclinic trinepheline and basic hexagonal nepheline, while in the process of thermally induced transformation of reflux treated samples with ideal stoichiometry, pure basic hexagonal nepheline was formed. Also, conditions of thermal conversion of monoclinic trinepheline into basic hexagonal nepheline were investigated. Intermediate phase of nepheline (“ABABAB…”) structure type, which could not be identified according to known nepheline phases, was synthesized in the presence of Na and Si inclusion species. Differences in the short and middle range order between hightemperature NaAlSiO4 polymorphs, formed by thermal conversion of Na-LTA with different stoichiometry, were ascribed to the influence of Na, Al and Si inclusions in zeolite cages.By this investigation we propose that Na-LTA is the example of much wider problem of non-stoichiometry influencing the course of zeolite thermal transformation route and can be extended to other zeolite types containing various extra-framework cations.
Iako termalno indukovane transformacije mrežnih alumosilikata daju jedinstven metod za formiranje novih faza sa poboljšanim osobinama, zbog kompleksnosti samog procesa, mehanizam konverzije još uvek nije u potpunosti razjašnjen. Usled male jedinične ćelije (Na12Si12Al12O4827H2O) i dobro proučene mrežne strukture i raspodele van-mrežnih katjona, zeolit Na-LTA predstavlja model supstancu za ispitivanje promena u uređenju na kratkom, srednjem i dugom dometu u procesu termalnih transformacija zeolita u popunjene derivate SiO2 polimorfa. Iako su još prva istraživanja pokazala da svaki sintetisan Na-LTA zeolit nije čist u kristalografskom smislu i u zavisnosti od uslova sinteze sadrži različite količine Na, Al i Si inkluzija unutar i kaveza, u literaturi ne postoje podaci o katalitičkom uticaju ovih vrsta na mehanizam termalne konverzije Na-LTA zeolita. Prezentovana teza sumira rezultate istraživanja uticaja Na, Al i Si inkluzija na mehanizam termalno indukovanih transformacija Na-LTA zeolita u karnegitske i nefelinske polimorfe. U prvom delu teze opisan je potupak sinteze Na-LTA zeolita sa različitim sadržajem Na, Al i Si inkluzija. Ispitan je uticaj variranja Na2O : Al2O3 : SiO2 odnosa u polaznoj reakcionoj smeši na stehiometriju sintetisanih Na-LTA zeolita i morfologiju kristalnih zrna. Kao postupak uklanjanja inkluzija zaostalih u Na-LTA zeolitima nakon sinteze, predložen je tretman refluksovanja Na-LTA zeolita na 100 ºC, koji ne izaziva amorfizaciju i dodatne strukturne promene u Na-LTA zeolitima. Drugi deo teze fokusiran je na ispitivanje uticaja Na, Al i Si inkluzija na termalnu stabilnost Na-LTA zeolita i njegovu konverziju u karnegitske i nefelinske polimorfe. Posebna pažnja je posvećena ispitivanju mehanizma fazne transformacije Na-LTA zeolita u nisko-temperaturni karnegit koji je u literaturi prezentovan dvema različitim šemama: kao direktna topotaktička transformacija Na-LTA → nisko-temperaturni karnegit i kao dvostepeni mehanizam Na-LTA → Amorfna faza → nisko-temperaturni karnegit. Metodama XRPD, DTA i IR spektroskopije je utvrđeno da Na i Al inkluzije podstiču fazni prelaz Na-LTA zeolita u nisko-temperaturni karnegit uz nemogućnost detekcije kolapsa LTA mreže u amorfnu strukturu, izazivajući brzo raskidanje i formiranje novih veza, pri čemu brzina termalne transformacije raste sa povećanjem sadržaja Al. Sa druge strane, u slučaju faznog prelaza refluksom tretiranih Na-LTA zeolita idealne stehiometrije u niskotemperaturni karnegit, utvrđen je kolaps LTA mreže u stabilnu amorfnu strukturu iz koje je zatim kristalisala faza nisko-temperaturnog karnegita. Karakterizacijom amorfne NaAlSiO4 faze infracrvenom i ramanskom spektroskopijom, utvrđeno je prisustvo četvoročlanih i šestočlanih tetraedarskih prstenova čime je zaključeno da su kolapsom zeolita u amorfnu fazu zadržani fragmenti LTA mreže, što može biti polazna osnova u sintezi „perfektnih“ stakala. Na višim temperaturama, ispitani su uslovi formiranja nefelinskih struktura, rekonstruktivnom faznom transformacijom nisko-temperaturnog karnegita, što je usled velikog broja nefelinskih polimorfa različite simetrije, veoma aktuelna problematika. Rezultati ispitivanja su pokazali da Na, Al i Si inkluzije u Na-LTA zeolitu uslovljavaju transformaciju nisko-temperaturnog karnegita u smešu monokliničnog trinefelina i osnovnog heksagonalnog nefelina, dok se u procesu termalno indukovanih transformacija refluksom tretiranih zeolita idealne LTA stehiometrije, formira faza čistog osnovnog heksagonalnog nefelina. Takođe, ispitani su uslovi termalne konverzije monokliničnog trinefelina u osnovni heksagonalni nefelin. U prisustvu Na i Si inkluzija sintetisana je intermedijerna faza nefelinskog („ABABAB...“) strukturnog tipa koja nije mogla biti identifikovana na osnovu poznatih nefelinskih struktura. Razlike u uređenju na kratkom i srednjem dometu visokotemperaturnih NaAlSiO4 polimorfa dobijenih termalnom konverzijom Na-LTA zeolita različite stehiometrije, pripisane su uticaju Na, Al i Si inkluzija u kavezima zeolita. Ovim istraživanjem predloženo je da Na-LTA zeolit predstavlja primer mnogo šireg problema uticaja nestehiometrije na tok i mehanizam termalno indukovanih transformacija zeolita, kao i da se isti zaključci mogu primeniti i na druge tipove zeolita koji sadrže različite van-mrežne katjone.
The discovery of anticancer activity of cis-diammindichloridoplatinum(II)complexes, better known as cisplatin (cis-DDP) and related platinum complexes has stimuled the interest for obtaining more ...efficient complexes of other metals and ligands. Some the first complexes used in clinical treatments against tumors were palladium(II)complexes as analogues of cisplatin. Although the first results were not encouraging,palladium complexes have been studied to longer extent. Palladium(II) complexes show less antitumor activity than corresponding platinum complexes due to their high instability. In order to overcome these problems, many studies have been directed toward the use of chelating ligands which would reduce the reactivity of palladium(II) complexes. So far a small number of complex compounds of palladium(II) have been synthesized with O,O'-dialkyl esters edda-type ligands as bidentate ligands, as well as S-alkyl derivatives of thiosalicylic acid. Therefore, this dissertation describes the synthesis and characterization of some edda-type ligands, their esters, S-alkyl derivatives of thiosalicylic acid and corresponding palladium(II) complexes with obtained ligands. The synthesis and characterization of some ligands and corresponding palladium(II) complexes are described in this PhD thesis. Firstly, the synthesis and characterization of O,O'-dialkyl esters of ethylenediamine-N,N'-di-(S,S)-2-propanoic acid H2-(S,S)-eddp is described. These compounds were obtained by direct reaction between tetradentate ligand and the corresponding absolute alcohol (ethanol, 1-propanol, 1-butanol, 1-pentanol) in a molar ratio 1:2 with the addition of gaseous hydrogen chloride. As described above, O,O'-dialkyl esters of ethylenediamine-N,N'-di-(S,S)- -2-(3-methyl)-butanoic acid, H2-(S,S)-eddv were synthesized was also done. The synthesis of S-alkyl derivatives of thiosalicylic acid. Bidentate S,O donor ligands were obtained by direct reaction between the sodium salt of thiosalicylic acid and corresponding alkyl halides (methyl, ethyl, propyl, butyl, benzyl) in a molar ratio 1:1. The synthesis of the tetradentate ligand meso-1,2-diphenyl-ethylenediamine-N,N'-di-3- -propanoic acid is shown at the end of this dissertation. Structure and composition of the isolated ligands were assumed using by elemental microanalysis, IR, 1 H and 13C NMR spectroscopy, and confirmed by X-ray diffraction analysis in the case of meso-1,2- -diphenyl-ethylenediamine-N,N'-di-3-propanoic acid monohydrate dicholorohydrate, H2-1,2-dpheddp•2HCl•H2O. The obtained ligands were used for synthesis of the corresponding palladium(II) complexes. The composition of obtained square-planar palladium(II) complexes was confirmed by elemental microanalysis. The structure of isolated complexes is assumed on basis of infrared, 1 H and 13C NMR spectroscopy and confirmed on basis of X-ray diffraction analysis in the case of chlorido(S,S)-ethylenediamine-N- -(O-ethyl-2-(3-methyl)butanoate)-N'-2-(3-methyl)-butanoate-palladium(II) complex, PdCl(et-(S,S)-eddv) and bis-(S-benzyl-thiosalycilato)palladium(II) complex, Pd(S-bz-thiosal)2. Antimicrobial activity of synthesized ligands and corresponding palladium(II) complexes was tested by microdilution method. Minimum inhibitory concentration (MIC) and minimum microbicidal concetration (MMC) were determined in this process. Some complexes showed significant antifungal activity on pathogenic fungi Aspergillus flavus and Aspergillus fumingatus. However, synthesized palladium(II) complexes showed limited antibacterial activity. In vitro antitumor activity of the complexes cis-PdCl2(1,2-dpheddp) and s-cis-PtCl2(1,2-dpheddp) was determined on the tumor cells of the 4T1 and B16F1, and the number of cells was determined after 72 hours by using MTT technique. The study found that both compounds showed lower antitumor activity compared to cisplatin.
Otkriće antitumorskih osobina cis-diamindihloridoplatina(II)kompleksa, poznatijeg pod imenom cisplatina (cis-DDP) i sličnih kompleksa platine povećalo je interesovanje za dobijanje još efikasnijih kompleksa drugih metala i liganada. Među prvim kompleksima korišćenim u kliničkim ispitivanjima protiv tumora bili su paladijum(II) analozi cisplatine. Iako prvobitni rezultati nisu bili ohrabrujući, kompleksi paladijuma(II) su mnogo šire proučavani. Paladijum(II) kompleksi su skoro uvek pokazivali manju antitumorsku aktivnost u odnosu na odgovarajuće komplekse platine zbog njihove velike labilnosti. Da bi se ovi problemi prevazišli, mnoga istraživanja su bila usmerena ka upotrebi helatnih liganada koji bi umanjili reaktivnost paladijum(II) kompleksa. Do sada je sintetisan mali broj kompleksnih jedinjenja paladijuma(II) sa O,O'-dialkil estrima liganada edda-tipa kao bidentatnim ligandima, kao i sa S-alkil derivatima tiosalicilne kiseline. Stoga je u okviru ove Doktorske disertacije opisana sinteza i karakterizacija nekih liganada edda-tipa, njihovih estara, kao i S-alkil derivata tiosalicilne kiseline i odgovarajućih kompleksa paladijuma(II). U ovoj Doktorskoj disertaciji opisana je sinteza i karakterizacija većeg broja liganada i odgovarajućih kompleksa paladijuma(II). Prvo je opisana sinteza i karakterizacija O,O'-dialkil estara etilendiamin-N,N'-di-(S,S)-2-propanske kiseline (H2-(S,S)-eddp). Ova jedinjenja su dobijena direktnom reakcijom između tetradentatnog liganda i odgovarajućeg apsolutnog alkohola (etanol, 1-propanol, 1-butanol, 1-pentanol) u molskom odnosu 1:2, uz uvođenje gasovitog hlorovodonika. Na prethodno opisan način sintetisani su i O,O'-dialkil estri etilendiamin- N,N'-di-(S,S)-2-(3-metil)-butanske kiseline (H2-(S,S)-eddv). Takođe, prikazana je i sinteza S-alkil derivata tiosalicilne kiseline. Pomenuti bidentatni S,O donorski ligandi dobijeni su direktnom reakcijom između natrijumove soli tiosalicilne kiseline i odgovarajućih alkil halogenida (metil-, etil-, propil-, butil- i benzil) u molskom odnosu 1:1. Na kraju prikazana je i sinteza tetradentatnog liganda meso-1,2-difenil-etilendiamin-N,N'-di-3-propanske kiseline. Strukture i sastav izolovanih liganada pretpostavljene su primenom elementalne mikroanalize, infracrvene, 1 H i 13C NMR spektroskopije, a potvrđene na bazi rezultata rendgenske strukturne analize u slučaju: meso-1,2- -difenil-etilendiamin-N,N′-di-3-propanske kiseline dihlorhidrata monohidrata, (H2-1,2-dpheddp•2HCl•H2O). Dobijeni ligandi su upotrebljeni za sintezu odgovarajućih kompleksa paladijuma(II). Sastav dobijenih kvadratno-planarnih kompleksa paladijuma(II) potvrđen je elementalnom mikroanalizom. Struktura izolovanih kompleksa pretpostavljena je na osnovu infracrvene, 1 H i 13C NMR spektroskopije, a potvrđena je na bazi rendgenske strukturne analize u slučaju hlorido((S,S)-etilendiamin-N-(O-etil-2-(3-metil)-butanoat)-N'-2-(3- -metil)-butanoatopaladijum(II) kompleksa, PdCl(et-(S,S)-eddv) i bis-(S-benzil- -tiosalicilato)paladijum(II) kompleksa, Pd(S-bz-thiosal)2. In vitro antimikrobna aktivnost sintetisanih liganada i odgovarajućih kompleksa paladijuma(II) testirana je mikrodilucionom metodom. Tom prilikom određene su minimalne inhibitorne (MIK) i minimalne mikrobicidne koncentracije (MMK) nagrađenih jedinjenja. Pojedini kompleksi su pokazali značajnu antifungalnu aktivnost na patogenim gljivama Aspergillus flavus i Aspergillus fumigatus. Međutim, sintetisani paladijum(II) kompleksi su pokazali umerenu antibakterijsku aktivnost. In vitro antitumorska aktivnost kompleksa cis-PdCl2(1,2-dpheddp) kao i s-cis-PtCl2(1,2-dpheddp), ispitivana je na ćelijama tumora 4T1 i B16F1, a broj ćelija određivan nakon je 72 sata korišćenjem MTT tehnike. Ispitivanjem je utvrđeno da oba jedinjenja pokazuju nižu antitumorsku aktivnost u poređenju sa cisplatinom.
U radu je opisano ispitivanje NMR spektroskopskih značajki trovafloksacin (TVA) mesilata, pefloksacin (PFX) mesilata i ciprofloksacin (CIP) hidroklorida u DMSO-d6 otopini s ciljem da se istraži ...utjecaj supstituenata i tip soli na NMR parametre bicikličkog fluorokinolonskog i fluoronaftiridonskog prstenastog sustava. Analizom jedno- i dvo-dimenzijskih, homo- i hetero-nuklearnih 1H- i 13C-NMR spektara potvrđena je struktura ispitivanih fluorokinolonskih soli.
1H- i 13C-NMR kemijski pomaci (, ppm) temeljnih prstenastih sustava korelirani su s izračunatim molekulskim opisivačima (relativnom molekulskom masom, Mr, topologijskom polarnom površinom, TPSA, lipofilnošću, miLogP i s volumenom, V) te s parametrima sličnosti s lijekovima poznate biološke aktivnosti, tj. s ligandom G protein-spregnutog receptora (GPCR ligand), ligandom ionskih kanala (ICL), inhibitorom kinaze (KI) i ligandom nuklearnog receptora (NRL) koji su izračunati za monoprotonske katione ispitivanih fluorokinolonskih soli (TVAH+, PFXH+ and CIPH+).
13C-NMR kemijski pomaci (/ppm) C4, C5 i C11 atoma i 1H-NMR kemijski pomaci (/ppm) protona u COOH, H5 i NHn+ ispitivanih fluorokinolonskih soli pokazali su se kao dobri parametri za istraživanje odnosa svojstvo-svojstvo i svojstvo-sličnost s lijekovima poznate biološke aktivnosti.
Tako je otkriven kolinearan odnos između 13C-NMR kemijskih pomaka (/ppm) C4, C5 i C11 atoma i izračunatih parametara za sličnost s kinaza inhibitorom (KI-ls) i ligandom nuklearnog receptora (NRL-ls) pored kolinearnosti s TPSA, miLogP, Mr i V (C4 /ppm s TPSA, R = 0,9964; C4 /ppm s miLogP, R = 0,9487; C4 /ppm s Mr, R = 0,9629; C4 /ppm s V, R = 0,8547; C4 /ppm s KI-ls, R = 0,9461 i C4 /ppm s NRL-ls, R = 0,9996; C5 s miLogP, R = 0,9994; C5 s KI-ls, R = 0,9990 i C5 s NRL-ls, R = 0,9510; C11 s TPSA, R = 0,9958; C11 /ppm s KI-ls, R = 0,9481 i C11 /ppm s NRL-ls, R = 0,9994).
1H-NMR kemijski pomaci (/ppm) protona COOH, H5 i NHn+ pokazali su kolinearanost odnosa s TPSA i miLogP, te s izračunatim parametrima za sličnost s kinaza inhibitorom (KI-ls), ligandom nuklearnog receptora (NRL-ls) i GPCR ligandom (GPCRl-ls) (/ppm H u COOH s TPSA, R = 0,9421; /ppm H u COOH s NRL-ls, R = 0,9216; H5 /ppm s miLogP, R = 0,9962; /ppm H5 s KI-ls, R = 0,9969; /ppm NHn+ s TPSA, R = 0,9875; /ppm NHn+ s NRL-ls, R = 0,9948; /ppm NHn+ s GPCR ligandom, R = 0,9873).
Rezultati istraživanja su pokazali razliku u eksperimentalnim i izračunatim parametrima za trovafloksacin mesilat u usporedbi s pefloksacin mesilatom i ciprofloksacin hidrokloridom, te je nađena značajna kolinearnost među ispitivanim parametrima ovih fluorokinolonskih antibiotika.
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