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U hemijskom svetu kompjuterska hemija ima važnu ulogu u proračunavnju hemijske strukture i različitih osobina molekula. Spoj teorijske hemije i kompjuterskih programa približava korisniku izuzetno komplikovanu ali neophodnu za izračunavanje, kvantnu mehaniku. Zbog kompleksnosti Šredingerove jednačine, neophodno je korišćenje funkcija koje priblizno opisuju Šredingerovu jednačinu. One se nazivaju aproksimacije. One se takođe upotrebljavaju i u metodama računarske hemije. Aproksimacije pojednostavljuju rešenje ali su i jedini način rešavanja Šredingerove jednačine. Iako pojednostavljeno, i dalje je neophodno dosta matematičkih računanja i kompjuterskih snaga. Kvantno hemijske računarske metode su podeljene na ab initio i semiempirijske, u zavisnosti od količine koriščenih parametara. ab initio metode mogu biti svrstane u jedno od dva glavna carstva, metode zasnovane na talasnoj funkciji ili metode zasnovane na funkcionalu gustine. Kako sam naziv nagovestava latinski ab initio znači od samog početka, ove metode izračunavaju Šredingerovu jednačinu direktno iz početnih principa kvantne mehanike bez upotrebe eksperimentalnih podataka . Za razliku od njih semiempirijske metode koriste veći broj aproksimacija i eksperimentalne podatke. Za veoma tačne i pouzdnane metode smatraju se ab initio, sa izrazitom manom u zahtevnosti sistema i potrebnom kompjuterskom vremenu. Obzirom da semiempirijske metode koriste već poznate parametre, to ih čini bržim od ab initio metoda i komjuterski manje zahtevnije.

U disertaciji su prikazani rezultati luženja halkopirita vodonik−peroksidom u rastvoru hlorovodonične i sumporne kiseline. Ispitan je uticaj brzine agitacije, odnosa čvrsto:tečno, koncentracije kiseline i oksidansa, reakcione temperature, kao i uticaj polarnih organskih rastvarača (metanol i 2-propanol) na izluženje bakra i gvožđa iz halkopiritnog koncentrata. Ustanovljeno je da se u sistemu HCl−H2O2 intenzivna oksidacija halkopirita odigrava u prvih 60 minuta reakcije, nakon čega se brzina reakcije znatno smanjuje usled brzog katalitičkog razlaganja vodonik−peroksida. Utvrđeno je da brzina mešanja i reakciona temperatura imaju neznatan uticaj na rastvaranje halkopirita dok je odnos čvrsto:tečno značajno uticao na izluženje bakra i gvožđa. Porast koncentracije hlorovodonične kiseline (0,1–3,0 mol/dm3) i vodonik-peroksida (0,5–3,0 mol/dm3) u rastvorima ima pozitivan uticaj na oksidaciono luženje halkopirita. Određen je red reakcije od 0,30 u odnosu na koncentraciju kiseline, odnosno 0,53 u odnosu na koncentraciju vodonik-peroksida. Poredeći rezultate ispitivanja u sistemu HCl−H2O2 sa ostvarenim rezultatima u sistemu H2SO4-H2O2, utvrđeno je da je sistem H2SO4−H2O2 pogodniji sistem za luženje halkopirita u pogledu dobijenih stepena izluženja metala. Reakciona temperatura ima uticaja na brzinu rastvaranja halkopirita u početnom stadijumu luženja, dok odnos čvrsto:tečno i u ovom sistemu značajno utiče na izluženje bakra i gvožđa. Porast koncentracije sumporne kiseline (0,3–3,0 mol/dm3) i vodonik-peroksida (0,5–3,0 mol/dm3) ima uticaja na oksidaciono luženje halkopirita (red reakcije 0,10 odnosno 0,24 u odnosu na koncentraciju kiseline i oksidansa, respektivno). Kinetika rastvaranja halkopirita u oba ispitana sistema se uspešno opisuje jednačinom kinetike prvog reda X=Xm(1−e−kt). Vrednosti energije aktivacije u hloridnim rastvorima iznose 19,6 kJ/mol (preko Cu), odnosno 17,1 kJ/mol (preko Fe), dok su u sulfatnim rastvorima dobijene veće vrednosti energije aktivacije koje iznose ~40 kJ/mol (preko Cu i preko Fe) što ukazuje na to da difuzija kroz sloj proizvoda limitira brzinu procesa... The dissertation presents the results of leaching of chalcopyrite with hydrogen peroxide in a solution of hydrochloric and sulfuric acid. The effect of agitation rate, solid to liquid ratio, acid and oxidant concentration, reaction temperature, as well as the effect of polar organic solvents (methanol and 2-propanol) on the copper and iron extraction from the chalcopyrite concentrate, have been examined. It has been found that an intensive chalcopyrite oxidation occurs in the HCl−H2O2 system in the first 60 minutes of reaction, after which the reaction rate significantly decreases due to the rapid catalytic decomposition of hydrogen peroxide. The stirring speed and reaction temperature have a slight effect on chalcopyrite dissolution, while the solid to liquid ratio has a significant effect on copper and iron extraction. The increase in the concentrations of hydrochloric acid (0.1–3.0 mol/dm3) and hydrogen-peroxide (0.5–3.0 mol/dm3) in solutions has a positive effect on the oxidative leaching of chalcopyrite. A reaction order of 0.30 was determined in relation to the acid concentration, that is, 0.53 in relation to the hydrogen peroxide concentration. Comparing the results of the HCl−H2O2 system with the results obtained in the H2SO4−H2O2 system, it has been established that the H2SO4−H2O2 system is more suitable system for the chalcopyrite leaching with respect to the obtained metal extraction degrees. The reaction temperature has an effect on the rate of chalcopyrite dissolution at the initial stage of the leaching, while the solid to liquid ratio significantly affects the extraction of copper and iron in this system as well. The increase in the sulfuric acid concentration (0.3-3.0 mol/dm3) and hydrogen-peroxide concentration (0.5-3.0 mol/dm3) has an effect on the oxidative leaching of chalcopyrite (reaction order of 0.10 and 0.24 in relation to the concentration of acid and oxidant, respectively). The kinetics of chalcopyrite dissolution in both examined systems is successfully described by the first-order kinetics equation X=Xm(1−e−kt). The activation energy values in the chloride solutions are 19.6 kJ/mol (over Cu) and 17.1 kJ/mol (over Fe), while the higher activation energy values are obtained in the sulphate solutions, ~40 kJ/mol (over Cu and over Fe), indicating that the diffusion through a product layer limits the reaction rate...

Psihotični poremećaji predstavljaju heterogene kliničke sindrome u čijoj etiopatogenezi ključno mesto imaju interakcija gena i uticaja poreklom iz spoljašnje sredine. Prema neurorazvojnoj teoriji, ova grupa poremećaja se smatra kasnom manifestacijom oštećenog neurorazvoja. Usled postepenog zastoja u usklađivanju funkcija određenih regiona mozga, osobe koje će tek u ranom odraslom dobu ispuniti kriterijume za dijagnozu već tokom perioda odrastanja imaju suptilne izmene u ponašanju, neuromotornim i saznajnim funkcijama. Poremećaj saznajnih funkcija - kognicije (neurokognicije i socijalne kognicije) nastaje kao posledica suptilnih oštećenja tokom neurorazvoja. Ovo jezgrovno obeležje psihotičnih poremećaja je relativno uočljivo u premorbidnom periodu, kada se ispoljava kao diskretna maladaptacija u detinjstvu i u ranoj adolescenciji. Nakon pojave kliničke forme bolesti, poremećaj kognicije je upadljiv i zbog svojih karakteristika (visoka učestalost, postojanost u svim fazama bolesti) deficiti neurokognicije i socijalne kognicije su prepoznati kao potencijalni kandidati za prelazne fenotipove. Ispitivanje prelaznih fenotipova može se vršiti analizom osoba sa različitim jačinama rizika za psihozu, na primer prvostepenih srodnika obolelih koji u većoj meri dele nepovoljne nasledne i sredinske faktore nego što je to slučaj sa opštom populacijom. Međutim, nalazi dosadašnjih studija koje su ispitivale kognitivne i adaptivne kapacitete zdravih prvostepenih srodnika psihotičnih pacijenata relativno su retki i nekonzistentni, zbog čega postoji potreba za daljim izučavanjem navedenih fenotipova kod osoba pod različitim naslednim rizikom za psihozu. Primenom genetski senzitivnog dizajna u aktuelnom istraživanju su ispitivane razlike u kognitivnim sposobnostima (IQ, sposobnost prepoznavanja emocija) i uspešnosti razvojne adaptacije kod osoba pod različitim rizikom za psihozu (pacijenata, njihovih zdravih prvostepenih srodnika i kontrola), kao i grupisanje i ukrštena kovarijacija navedenih svojstava unutar porodica psihotičnih pacijenata (identifikacija prelaznih fenotipova)...

The stability of chlorophyll on chosen oxidative stresses in disorganized aqueous medium and more organized liposomal structures is a topic of this doctoral thesis. The unique role of chlorophyll, based on its specific and very diverse chemical reactivity justifies its application in industrial technologies, food processing and pharmaceutical and cosmetic industry as well as in medicine. The question about chlorophyll stability is set as one of the preconditions for its potential applications in various areas of science and technology. In vitro oxidative stresses applied to the chlorophyll are: chemical oxidation by Fenton reagent and thermal initiator, enzyme catalyzed oxidation and photo-oxidation by continuous visible and UV-B irradiation. The stability of chlorophyll in the aqueous medium after oxidative stress was studied using absorption spectroscopy while the corresponding changes in the structure of Chl-molecules was followed by electro-spray mass spectrometry combined with UHPLC chromatography, in order to get the possible insight into the degradation-oxidation mechanisms. Changes in the physical conditions of the liposome interior (organized lipid structures), which affect the behavior of incorporated chlorophyll penetration and therefore a different degradation degree, were investigated using absorption and fluorescence spectroscopy. In addition to the presented methods, in order to evaluate some of the possible mechanisms involved in oxidative stress, two peroxide tests were performed: test of conjugated dienes and TBA-MDA test. The results show that the stability of chlorophyll depends not only on chlorophyll concentration but also the nature of the applied oxidative stress. Generally, the chlorophyll in liposomes, the same as in the aqueous medium, shows a low stability degree, which resulted in its modifications, creating oxidation-degradation products. The destructiveness of the applied oxidative stresses on chlorophyll could be ranked as follows: the effect of Fenton reagent < effect of the thermal initiator < VIS < UV-B radiation, at precisely defined conditions. Chlorophyll is more stable in liposome dispersions, which supports the conclusion that it is better to keep it in liposomes than in water. xiv Based on these results it can be concluded that the more accurate knowledge of the chlorophyll behavior under the oxidative stress, as well as its optimal concentration and stability in the potential formulations, is crucial to its further use.

Advanced pharmaceutical systems for drug delivery can provide better bioavailability, safer and more effective application of active substances, by increasing their solubility and stability while improving pharmacological activity and reducing side effects. Sulfanilamide is a broad-spectrum, synthetic antimicrobial drug whose application in therapy is limited by its poor water solubility and photosensitivity. The aim of the present doctoral dissertation was preparation and characterization of various pharmaceutical systems (inclusion complexes, hydrogels and liposomes) with sulfanilamide, in order to increase solubility and photostability while maintaining antimicrobial activity of sulfanilamide and enabling its modified delivery. For that purpose, sulfanilamide was synthesized using the conventional method, purified and characterized by using FTIR, 1H-NMR, XRD, DSC i SEM methods. Inclusion complexes of sulfanilamide with β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin were prepared using the coprecipitation method and characterized by using FTIR, 1H-NMR, XRD, DSC and SEM methods, which proved the incorporation of sulfanilamide into the cyclodextrin cavities. Phase-solubility and photostability studies have shown that solubility and stability of sulfanilamide increase after incorporation into cyclodextrin molecules, especially in the case of 2-hydroxypropyl-β-cyclodextrin. The formation of inclusion complexes with cyclodextrins also increases the potency of the sulfanilamide antimicrobial action due to the increase of its solubility in water. Homopolymeric p(NIPAM) hydrogels were synthesized using free radical polymerization process, with varying crosslinker content, and characterized using FTIR, XRD and SEM methods. The residual reactant content was determined by using HPLC method and the swelling degree of the synthesized hydrogels was determined gravimetrically. Sulfanilamide was incorporated into the synthesized and characterized hydrogels, which is proved by using FTIR, XRD and SEM methods. The effect of temperature, pH and the crosslinker content on the rate of sulfanilamide release from the hydrogels was examined. It has been shown that p(NIPAM) hydrogels can be suitable carriers for sulfanilamide. MLV liposomes with sulfanilamide were prepared by the thin film method, and unilamellar liposomes of adequate size and satisfactory stability, with a very narrow particle size distribution, were prepared by extrusion. The release of sulfanilamide from the liposomes was examined using dialysis sac method, relative to the buffer solution, indicating that sulfanilamide incorporation into liposomes halves its rate of release. The release of sulfanilamide from liposomes is best described by the Korsmeyer-Peppas model, with Fickian diffusion as predominant release mechanism. The photostability of sulfanilamide increases after incorporation into liposomes, while MLV liposomes have the greatest protective effect. The photodegradation products of sulfanilamide: sulfanilic acid, aniline and benzidine, were identified by using UHPLC-DAD-HESI-MS/MS method. The photodegradation of sulfanilamide is a free radical reaction influenced by •OH radicals and follows first order kinetics.