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New methoxy-substituted naphthotriazoles - synthesis and biological activity
No full textCilj ovog rada bila je sinteza novih soli tienobenzo-triazola s potencijalnom biološkom aktivnošću. Tijek sinteze praćen je nizom od četiri uzastopne reakcije.
Prvim stupnjem dobivaju se različiti derivati triazolnih aldehida reakcijom
1-(4-nitrofenil)-1H-1,2,3-triazol-4-karbaldehida, prethodno pripremljenog u našem laboratoriju, i odgovarajućeg amina. Nadalje slijedi Wittigova reakcija, općenito poznata kao reakcija dobivanja alkena. Takvom reakcijom aldehidi reagiraju s fosforovim ilidom čime se dobivaju smjese izomera triazolnih tienostilbena. Spomenuti produkti su zbog nastanka konjugiranog sustava uspješno podvrgnuti fotokemijskim reakcijama čime dolazi do ciklizacije odnosno zatvaranja prstena i sinteze tienobenzo-triazola. Posljednjim stupnjem dodatkom alkil-halogenida dobivaju se triazolne soli koje su testirane na biološku aktivnost, prvenstveno kao potencijalni inhibitori enzima kolinesteraza. Na temelju rezultata bioloških mjerenja, spoj 6 pokazuje inhibiciju enzima butirilkolinesteraze s vrijednosti IC50 od 24,3 μM dok njegova sol 10 čak IC50 od 1,83 μM, što je nekoliko puta bolja inhibicijska aktivnost od one koju pokazuje standardni reverzibilni inhibitor galantamin.The aim of this work was the synthesis of new thienobenzotriazole salts with potential biological activity. The course of the synthesis is followed by a series of four consecutive reactions. In the first stage, various derivates of triazole aldehydes are obtained by the reaction of 1-(4-(nitrophenyl)-1H-1,2,3-triazole-4-carbaldehyde, previously prepared in out laboratory, and the corresponding amine. Further follows the Wittig reaction, generally known as the alkene formation reaction. The aldehydes react with phosphorus ylide, resulting in mixtures of triazole-thienostilbene isomers. Due to the formation of a conjugated system, the mentioned products are succesfully subjected to photochemical reactions, which leads to cyclization, i.e. ring closure and synthesis of thienobenzo-triazoles. The last step is the addition of alkyl halide to obtain triazole salts that have been tested for biological activity, as potential cholinesterase enzyme inhibitor. Based on the results of biological measurements, compound 6 shows inhibition of the butyrylcholinesterase enzyme with an IC50 value of
24,3 μM, while its salt 10 even has an IC50 of 1,83 μM, which is several times better inhibitory activity than that shown by the standard reversible inhibitor galantamine
Protective properties of hydrophobic films of long-chain phosphonic acid on different metals
No full textU ovom radu ispitala su se zaštitna svojstva filmova heksadecilfosfonske kiseline na različitim metalima. U radu su se formirali hidrofobnih zaštitni filmovi na podlogama od cinka, kositra, ugljičnog i nehrđajućeg čelika. Njihova zaštitna svojstva pratila su se u vremenu metodom elektrokemijske impedancijske spektroskopije. Također, provela se karakterizacija filmova metodom kontaktnog kuta i FTIR spektroskopijom. Na ovaj način utvrdilo se u kojoj mjeri svojstva nastalih filmova fosfonske kiseline ovise o sastavu podloge na kojoj su formirani.In this work the protective properties of films hexadecylphosphonic acid were tested on different metals. Hydrophobic protective films were formed on substrate made of zinc, tin, carbon steel and stainless steel. Their protective properties were time-monitored using electrochemical impedance spectroscopy. Furthermore, the characterization of substrate was conducted by using the contact angle measurements and FTIR spectroscopy. In this way it was established to what extent the properties of formed phosphonic acid films depend on the composition of the substrate on which they were formed
Electrochemical synthesis of substituted 1,3-oxazolidines from vicinal amino alcohols
No full textU ovom radu opisan je dizajn i razvoj nove, ekonomične i brze elektrokemijske sinteze supstituiranih 1,3-oksazolidina iz vicinalnih amino-alkohola. Priređeni su derivati oksazolidina fuzionirani na desozamin (6 - 8) ili makrolaktonski prsten (11) azitromicina, koji su već ranije priređeni klasičnim metodama organske sinteze. Spomenuti spojevi pokazali su veliki potencijal za protuupalne primjene, stoga je ova efikasnija „zelena“ metoda odlična alternativa za sintezu ovih obećavajućih spojeva. Također, ova metoda testirana je i na manjim molekulama, pri čemu su uspješno priređeni (4S,5R)-N-benzil-3,4-dimetil-5-fenil-oksazolidin-2-imin 14 i N-benzil-1,3a,4,8b-tetrahidroindeno[1,2-d]oksazol-2-imin 17, kao nove potencijalno biološki aktivne molekule. Polazni materijali (odgovarajući amino-alkoholi) za sintezu makrolidnih oksazolidina (6, 7, 8 i 11) bili su demetilirani derivati azitromicina 1, 2 i 9, dok su za sintezu malih molekula 14 i 17 korišteni efedrin-hidroklorid 12 i
(1S,2R)-1-amino-2-indanol 15. Elektrociklizaciji je prethodila klasična sinteza odgovarajućih intermedijera metodama ranije opisanim u literaturi. Korišteni su benzil-izotiocijanat ili fenil-kloroformat kao reagensi, a reakcije su provođene u acetonitrilu uz trietilamin na sobnoj ili povišenoj temperaturi. Sve elektrociklizacijske reakcije provođene su u nepodijeljenoj ćeliji uređaja IKA ElectraSyn 2.0 uz C(+) – C(-) sustav elektroda i acetonitril kao otapalo te koncentraciju elektrolita (LiBr ili NaI) od 0.1 mM. Reakcije su provođene pri konstantnoj struji 5 – 10 mA s promjenom polariteta svakih 15 min. Za elektrokemijsku sintezu spojeva 6 i 14 isproban je i one-pot pristup polazeći od odgovarajućeg vicinalnog amino-alkohola (1 ili 12). Izvedba ovih one-pot reakcija provođena je na povišenoj temperaturi što je znatno usporilo sam korak ciklizacije. Ova metoda pokazala se boljom ne samo zbog svoje brzine i „zelenijeg“ pristupa, već je rezultirala i boljim iskorištenjima od klasičnih procesa. Strukture svih priređenih spojeva potvrđene su 1D i 2D NMR tehnikama.This paper describes the design and development of a new, economical and rapid electrochemical synthesis of substituted 1,3-oxazolidines from vicinal amino alcohols. Using this method, oxazolidine derivatives fused to desosamine (6 - 8) or macrolactone ring (11) of azithromycin, which had prior been prepared by classical methods, were synthesized. These compounds showed great potential for anti-inflammatory applications; therefore, this more efficient "green" method is an excellent alternative for the synthesis of these promising agents. Moreover, to test this method on smaller molecules,
(4S,5R)-N-benzyl-3,4-dimethyl-5-phenyloxazolidin-2-imine 14 and
N-benzyl-1,3a,4,8b-tetrahydroindeno[1,2-d]oxazol-2-imine 17 were prepared, as new potentially biologically active molecules. Starting materials (corresponding amino alcohols), for the synthesis of macrolide oxazolidines (6, 7, 8 and 11), were demethylated derivatives of azithromycin 1, 2 and 9, whereas for the synthesis of small molecules 14 and 17, ephedrine hydrochloride 12 and (1S,2R)-1-amino-2-indanol 15 were used. Electrocyclization was preceded by the classical synthesis of the corresponding intermediates, using methods previously described in the literature. Benzyl isothiocyanate or phenyl chloroformate were used as reagents, and reactions were carried out in acetonitrile with triethylamine at room or increased temperature. All electrocyclization reactions were carried out in an undivided cell of the IKA ElectraSyn 2.0 device with a C(+) – C(-) electrode system, acetonitrile as solvent and an electrolyte concentration (LiBr or NaI) of 0.1 mM. Reactions were carried out at a constant current of 5-10 mA with a change of polarity every 15 min. For the electrochemical synthesis of compounds 6 and 14, one-pot approach, starting from the corresponding vicinal amino alcohol (1 or 12), was tested as well. These one-pot reactions were carried out at an increased temperature, which significantly slowed down the cyclization step itself. This method proved itself to be better than classical synthesis not only because of its speed and "greener" approach, but also due to its greater yields. The structures of all compounds were confirmed by 1D and 2D NMR techniques
Structure and electrical properties of phosphate glasses with transition metal and alkali oxides
No full textU uvjetima stalno rastuće potrošnje energije važnu ulogu u ljudskom životu imaju elektrokemijski uređaji, a posebno litij- i natrij-ionske baterije. Pri tome je razumijevanje odnosa strukture i električnih svojstava materijala ključno za njihov razvoj. U tu svrhu su metodom naglog hlađenja taline pripravljena fosfatna stakla množinskog sastava
30Na2O-xFe2O3-(30-x)WO3-40P2O5 i 30Li2O-xFe2O3-(30-x)WO3-40P2O5; x = 0-30 %,
te je impedancijskom spektroskopijom ispitana njihova električna provodnost. Za obje serije stakala dobiven je nemonotoni trend istosmjerne električne provodnosti s minimumom pri
20 % množinskog udjela Fe2O3, nakon čega dolazi do ponovnog porasta električne provodnosti. Smanjenje ionske vodljivosti povezano je s promjenama strukturne mreže, odnosno pokretljivost iona alkalijskih oksida (Na+ i Li+) smanjuje se zbog njihove povećane interakcije s depolimeriziranom strukturom fosfatnog stakla i formiranja kompaktne umrežene strukturne mreže stakla. Kod svih je stakala utvrđen dominantno ionski mehanizam vodljivosti, a kod stakala s 30 % množinskog udjela Fe2O3 dokazana je miješano
ionsko-polaronski transport zbog značajnog doprinosa polaronske vodljivosti putem prijenosa elektrona između iona željeza.In conditions of constantly growing energy consumption, electrochemical systems, especially lithium- and sodium-ion batteries, play an important role in human life. Therefore, understanding the relationship between the structure and electrical properties of materials is crucial for their development. For this purpose, phosphate glasses of the composition 30Na2O-xFe2O3-(30-x)WO3-40P2O5 and 30Li2O-xFe2O3-(30-x)WO3-40P2O5;
x = 0-30 mol% were prepared by the melt-quenching technique, and their electrical conductivity was studied by impedance spectroscopy. For both series of glasses, a non-monotonic trend of DC conductivity was obtained with a minimum at 20 mol% of Fe2O3, after which the electrical conductivity increases. The decrease in ionic conductivity is associated with changes in the structural network, that is, the mobility of alkali oxide ions (Na+ and Li+) decreases due to their increased interaction with the depolymerized phosphate glass structure and formation of the compact crosslinked glass network structure. While the ionic conductivity mechanism is dominant in all glasses, in glasses with 30 mol% Fe2O3 a significant contribution of polaronic conductivity through electron transfer between iron ions has been proven
Determination of thin film bandgap by the use of Tauc's method
No full textCilj ovog rada je određivanje optičkog procijepa za direktni i indirektni prijelaz elektrona tri uzorka tankih filmova lantanova manganita (LaMnO3) korištenjem Taucove, Codyjeve i Boltzmannove metode. Uzorci su pripremljeni različitim sintetskim postupcima što utječe na iznos optičkog procijepa. Morfološke karakteristike ispitane su pretražnom elektronskom mikroskopijom (SEM), te je vidljiva nehomogenost tankih filmova na sva tri uzorka što uvelike utječe na reflektanciju i transmitanciju. Optička svojstva analizirana su UV-Vis spektroskopijom u rasponu od 380 do 800 nm. Optički procijepi teško su odredivi za većinu uzoraka, te se nalaze u rasponu od 0,3 eV do 2,5 eV. Unatoč tome što se za određivanje optičkog procijepa najčešće koriste Taucova i Codyjeva metoda, pokazalo se da Boltzmannova metoda daje reprezentativnije rezultate jer uzima u obzir cijelu krivulju, a ne vizualno određeno linearno područje. Nijedna metoda nije uspjela sigurno odrediti dolazi li do direktnog ili indirektnog prijelaza elektrona, zbog čega je potrebno provesti dodatna istraživanja ili provesti matematička modeliranja. Odabir prikladne metode za karakterizaciju optičkih svojstava novih materijala u primjeni za fotonaponske ćelije od presudne je važnosti kako bi se dobili pouzdani rezultati.The aim of this paper is to determine the band gap value for the direct and indirect electron transition of three samples of thin films of lanthanum manganite (LaMnO3) using Tauc, Cody and Boltzmann methods. The samples are prepared by different procedures which affects the band gap value. Morphological characteristics were examined by scanning electron microscopy (SEM), and the inhomogeneity of thin films on all three samples was visible, which greatly affects reflectance and transmittance. Optical properties were analyzed by
UV-Vis spectroscopy ranging from 380 to 800 nm. Band gap values, ranging from 0.3 eV to 2.5 eV, were difficult to determine for most samples. Although Tauc's and Cody's methods are most commonly used to determine the optical slit, Boltzmann's method has been shown to yield more representative results because it takes into account the entire curve rather than a visually defined linear region. Neither method has been able to determine for sure whether there is a direct or indirect electron transition, which requires additional research or mathematical modeling. It is important to choose the appropriate method for characterizing the optical properties of new materials in application for photovoltaic cells in order to get the most accurate results possible
Application of waste in chemical production
No full textU današnje vrijeme, brz razvoja tehnologije, nagli porasta broja stanovništva i urbanizacija, doveli su do značajnog povećanja proizvodnje otpada, što predstavlja ozbiljan izazov za moderno društvo. Raste interes za proizvodnju kemikalija iz lignocelulozne biomase i organskog otpada kao obnovljivih prirodnih izvora kako bi se smanjila količina otpada. Lignocelulozni otpadni materijali predstavljaju obećavajuću alternativu tradicionalnim rafinerijama nafte, utirući pute biorafinerijama. Biomasa se može u potpunosti pretvoriti u vrijedne kemikalije, bioenergiju i materijale, što je čini ključnom sirovinom za razvoj kružnog bioekonomskog pristupa. Korištenje biomase za proizvodnju kemikalija od velike je važnosti za održivu budućnost kemijske industrije. Uspješan razvoj biokemikalija također ima potencijal za poticanje inovacija u područjima poput novih polimera i materijala, novih otapala te bioaktivnih spojeva. Međutim, biokemijske, termokemijske i katalitičke konvencionalne metode pretvorbe biomase imaju svoje nedostatke, što naglašava potrebu za daljnjim istraživanjima i tehnološkim napretkom u ovom području. Ovaj rad daje kratak pregled tradicionalnih tehnika obrade biomase, uključujući toplinsko zagrijavanje i biokemijske procese. Detaljnije je objašnjen postupak obrade biomase potpomognut mikrovalovima, relativno nedovoljno korištenom metodom s potencijalom da postane ključna tehnologija u budućnosti.In recent years, rapid technological advancements, population growth, and urbanization have led to a significant increase in waste generation, posing a serious challenge to modern society. In response, there has been growing interest in producing chemicals from lignocellulosic biomass and organic waste, utilizing these renewable natural resources to mitigate waste accumulation. Lignocellulosic waste materials offer a promising alternative to traditional oil refineries, paving the way for biorefineries. Biomass can be fully converted into valuable chemicals, bioenergy, and materials, making it crucial resource for promoting a circular bioeconomy. The use of biomass for chemical production is essential for ensuring the sustainability of the chemical industry's future. Furthermore, the successful development of biochemicals has the potential to drive innovations in fields such as new polymers, materials, solvents, and bioactibe compounds. However, conventional methods of biomass conversion whether biochemical, thermochemical, or catalytic have limitations, underscoring the need for further research and technological advancments in this area. This work provides a brief overview of traditional biomass processing techniques, including thermal heating and biochemical processes. It then delves into microwave-assisted biomass processing, a relatively underutilized method with the potential to become a key technology in the future
Influence of different decellularization parameters in the production of hydrogels from extracellular matrix
No full textInženjerstvo tkiva je grana inženjerstva koja u novije vrijeme poprima sve veći značaj jer pruža alternativu transplantaciji organa iz ljudskih donora. Zbog rastuće potrebe za transplantacijom organa i dugim listama čekanja te sve starijom populacijom očekuje se da će potreba za transplantacijom organa u budućnosti rasti. Inženjerstvo tkiva bi također moglo riješiti pitanje etičnosti ispitivanja lijekova na životinjama jer bi nosači nastali ovim tehnologijama trebali bolje oponašati ljudsko tkivo. U tu svrhu razvijeni su nosači napravljeni od različitih biokompatibilnih materijala koji posjeduju različita fizička i kemijska svojstva.
Od tih biomaterijala, poseban se značaj pridaje decelulariziranoj izvanstaničnoj matrici jer ona ima manju mogućnost izazivanja imunološke reakcije te joj trodimenzionalna arhitektura početnih tkiva ostaje bolje očuvana nakon decelularizacije. U ovom radu ispitano je šest različitih uvjeta decelularizacije svinjske jetre kako bi se utvrdio njihov utjecaj na strukturu i sastav biomaterijala. Korištene su 1 %-tne i 0,5 %-tne otopine natrijeva lauret sulfata (SLES), kao i 0,5 %-tna otopina detergenta SLES-a u kombinaciji obrade ultrazvukom u vremenskom periodu od 1, 2, 4 i 8 h. Kako bi se procijenila očuvanost strukture dobivene izvanstanične matrice provedena je karakterizacija bioloških komponenata i analiza strukture tkiva svjetlosnim mikroskopom te stereomikroskopom. Dobiveni rezultati pokazuju da je decelularizacija uspješno provedena u svim uzorcima jer se udio DNK značajno smanjio.
Vrlo dobri uvjeti decelularizacije postižu se s 0,5 %-tnom otopinom SLES-a i 0,5 %-tnom otopinom SLES-a u ultrazvučnoj kupelji u vremenskom trajanju od 1 h. Prilikom decelularizacije u ovim uvjetima postignut je najmanji udio DNK, a struktura izvanstanične matrice je ostala očuvana. Povećanje koncentracije SLES-a imalo je blago djelovanje na strukturu tkiva te je značajan udio bioloških komponenata ostao očuvan. Nadalje, duljom ultrazvučnom obradom uzoraka nastala su značajna oštećenja strukture izvanstanične matrice. Iz dobivenih rezultata također je vidljivo da je u svim uzorcima tijekom decelularizacije udio glikozaminoglikana pao ispod granice detekcije.Tissue engineering is a branch of engineering that has recently become increasingly important because it offers an alternative to organ transplantation from human donors.
Due to the growing demand for organ transplants and the long waiting lists, as well as the aging population, the need for organ transplants is expected to increase in the future. Tissue engineering could also solve the ethical problem of drug testing on animals, as the scaffolds produced by these technologies should better mimic human tissue. To this end, scaffolds made of various biocompatible materials with different physical and chemical properties have been developed. Among these biomaterials, decellularized extracellular matrix is of particular importance because it has a lower potential to induce immune responses and its three-dimensional architecture is better preserved after decellularization. In this study, six different conditions for decellularization of porcine liver were investigated to determine their effects on the structure and composition of the biomaterial. 1 and 0.5 wt% solutions of sodium laureth sulfate (SLES) and a 0.5 wt% solution of SLES detergent in combination with sonication for 1, 2, 4, and 8 hours were used. To evaluate the preservation of the structure of the obtained extracellular matrix, the biological components were characterized, and the tissue structure was analyzed using a light microscope and a stereomicroscope. The obtained results show that decellularization was successfully performed in all samples, as the DNA content decreased significantly. Very good decellularization conditions were obtained with a 0.5% SLES solution and a 0.5% SLES solution with 1-hour sonication. Under these conditions, the lowest DNA content was obtained, and the structure of the extracellular matrix was preserved. Increasing the SLES concentration had only a minor effect on tissue structure, as a significant portion of the biological components remained intact. Moreover, prolonged ultrasonic treatment of the samples resulted in significant damage to the extracellular matrix structure. It is also evident from the results obtained that the content of glycosaminoglycans in all samples fell below the detection limit during decellularization
Determination of the optimal conditions for the biodegradation of polystyrene using the bacterium Bacillus subtilis
No full textPlastika je materijal koji se često koristi u svakodnevnim predmetima, a njezino nepravilno odlaganje i nakupljanje postali su ozbiljna briga za okoliš. Mikroplastika (MP) male su čestice sintetskih organskih polimera manje od 5 mm i predstavljaju veliku prijetnju okolišu zbog svoje postojanosti i inherentne toksičnosti. Biorazgradnja polimera ovisi o različitim čimbenicima, kao što su fizikalna i kemijska svojstva polimera, uvjeti u okolišu i prisutnost mikroorganizama. Iako je biorazgradnja često korišten proces za uklanjanje MP iz okoliša, njezina učinkovitost ovisi o optimizaciji značajnih čimbenika procesa. Cilj ovog istraživanja bio je istražiti biorazgradnju čestica polistirena (PS) pomoću bakterije Bacillus subtilis, odnosno odrediti značajne čimbenike koji utječu na proces biorazgradnje te optimizirati uvjete biorazgradnje. Eksperiment je osmišljen korištenjem punog faktorskog plana (FFP) za proučavanje učinaka tri čimbenika, odnosno veličine MP, brzine okretaja i optičke gustoće (OG) bakterijske suspenzije, na tri razine. Proces biorazgradnje praćen je 30 dana tijekom kojih se pratio ukupan broj bakterijskih kolonija (eng. Colony Forming Units, CFU) i vrijednosti ukupnog (TC), organskog (TOC) i anorganskog (TIC) ugljika. LC/MS analiza je provedena kako bi se otkrilo otpuštanje aditiva iz PS MP i stvaranje potencijalno toksičnih proizvoda razgradnje. Promjene u strukturi PS-a ispitane su ATR-FTIR spektroskopijom. Ekotoksičnost filtrata procijenjena je pomoću bakterije Vibrio fischeri. Za procjenu eksperimentalnih rezultata korištena je statistička analiza varijance (ANOVA).Plastic is a material commonly used in everyday objects, and its improper disposal and accumulation have become a serious environmental concern. Microplastics (MP) are small particles of synthetic organic polymers measuring less than 5 mm and pose a significant threat to the environment due to their persistence and inherent toxicity. The biodegradation of polymers depends on various factors, such as the physical and chemical properties of the polymer, environmental conditions, and the presence of microorganisms. Although biodegradation is often used as a process to remove MP from the environment, its effectiveness relies on optimizing significant process factors. The aim of this research was to investigate the biodegradation of polystyrene (PS) particles using the bacterium Bacillus subtilis. The objective was to identify significant factors influencing the biodegradation process of PS microplastics (MP) using Bacillus subtilis and to optimize the biodegradation conditions using this bacterial culture. The experiment was designed using a full factorial design (FFD) to study the effects of three factors, namely MP size, rotational speed, and optical density (OD) of the bacterial suspension, at three levels. The biodegradation process was monitored for 30 days, during which the total colony-forming units (CFU) of bacteria and the values of total carbon (TC), organic carbon (TOC), and inorganic carbon (TIC) were measured. LC/MS analysis was conducted to detect the release of additives from PS MP and the formation of potentially toxic degradation products. Changes in the structure of PS were examined using ATR-FTIR spectroscopy. The ecotoxicity of the filtrate was assessed using the bacterium Vibrio fischeri. A statistical analysis of variance (ANOVA) was used to evaluate the experimental results
Synthesis and spectroscopic characterization of novel imidazo[4,5-b]pyridine derivatives as potential optical pH sensors
No full textU ovom radu provedena je sinteza i spektroskopska karakterizacija benzamidnih derivata imidazo[4,5-b]piridina koji se razlikuju prema položaju, odnosno redoslijedu kojim su supstituenti vezani na dušik amidne veze. Ciljani spojevi priređeni su klasičnim reakcijama organske sinteze. Korištenje polifosforne kiseline (PPA) katalizira reakciju kondenzacije iz odgovarajućih prekursora, 2,3-diaminopiridna 1 i p-aminobenzojeve kiseline 2 što rezultira stvaranjem 4-(3H-imidazo[4,5-b]piridin-2-il)anilina 3. Iz odgovarajućih benozil-klorida 4-5, te glavnog prekursora, amino derivata imidazo[4,5-b]piridina 3, reakcijom kondenzacije u apsolutnom toulenu uz trietilamin priređeni su konačni benzamidi 6-7. Reakcijom amidacije iz HATU i DIPEA aktivirane 4-nitrobenzojeve kiseline 10, te
4-(3H-imidazo[4,5-b]piridin-2-il)anilina 3 sintetiziran je benzamidni nitro derivat 11. Reakcija ciklokondenzacije 2,3-diaminopiridina 1 s 4-formilbenzojevom kiselinom 14 i natrijevim metabisulfitom u DMSO daje 4-(3H-imidazo[4,5-b]piridin-2-il)benzojevu kiselinu 15 koja potom u reakciji nukleofilne supstitucije s tionilkloridom u toulenu daje
4-(3H-imidazo[4,5-b]piridin-2-il)benzoil klorid 16. Reakcijom kondenzacije spoja 16 s odgovarajućim aromatskim aminima 17-19 u apsolutnom toulenu uz trietilamin priređena je druga vrsta benzamida 20-22. Amidino-supstituirani benzamidi 8-9 i 25-26 priređeni su iz nitrilnih benzmida 7, odnosno 22, Pinnerovom reakcijom u dva stupnja u kiselom mediju. Amino-supstituirani derivati 12 i 23 priređeni su reakcijom redukcije s SnCl2×2H2O, te su s klorovodičnom kiselinom prevedeni u hidrokloridne soli 13 i 24. Priređenim derivatima ispitana je i antiproliferativna aktivnost in vitro na nekoliko staničnih linija humanih karcinoma. Derivati 12 i 23 dodatno su spektroskopski okarakterizirani u nekoliko otapala različite polarnosti, te su provedene spektroskopske UV/Vis pH titracije kako bi se ispitala mogućnost primjene kao optičkih pH senzora. Strukture svih priređenih produkata potvrđene su
1H i 13C NMR spektroskopijom, a nekih i masenom spektrometrijom. Tijek Pinnerovih reakcija za pripravu amidino-supstituiranih benzamida praćen je IR spektroskopijom.This work presents the synthesis and spectroscopic characterization of
imidazo[4,5-b]pyridine benzamides, which differ according to the position, or the order in which the substituents are attached to the nitrogen of the amide bond. Targeted compounds were prepared by conventional reactions of organic synthesis. The use of polyphosphoric acid (PPA) catalyzes a condensation reaction from the precursors, 2,3-diaminopyridine 1 and p-aminobenzoic acid 2 leading to the formation of 4-(3H-imidazo[4,5-b]pyridin-2-yl)aniline 3. From the corresponding benzoyl chlorides 4-5 and the main precursor, amino derivative of imidazo[4,5-b]pyridine 3 by a condensation in absolute toluene with triethylamine, target benzamides 6-7 were synthesized. Nitro benzamide derivative 11 was synthesized by the amidation using HATU and DIPEA activated 4-nitrobenzoic acid 10 and
4-(3H-imidazo[4,5-b]pyridin-2-yl)aniline 3. Cyclocondensation of 2,3-diaminopyridine 1, 4-formylbenzoic acid 14 and sodium metabisulfite in DMSO produces
4-(3H-imidazo[4,5-b]pyridin-2-yl)benzoic acid 15 which then in a nucleophilic substitution with thionyl chloride in toluene gives 4-(3H-imidazo[4,5-b]pyridin-2-yl)benzoyl chloride 16.
By condensation of compound 16 with the corresponding aromatic amines 17-19 in absolute toluene with triethylamine, another class of benzamide was prepared 20-22.
Amidino-substituted benzamides 8-9 and 25-26 were prepared starting from corresponding nitrile benzamides 7 and 22, by a two-step Pinner reaction in an acidic medium.
Amino-substituted derivatives 12 and 23 were prepared by a reduction with SnCl2×2H2O and converted into hydrochloride salts 13 and 24. All prepared benzamides were tested for their antiproliferative activity in vitro on several human cancer cells. In addition, the spectroscopic properties of derivatives 12 and 23 were studied by UV/Vis spectroscopy and pH titrations in order to determine the possibility of application as optical pH sensors. The structures of all prepared products were confirmed by 1H and 13C NMR spectroscopy, and some by mass spectrometry. The Pinner reaction for the preparation of amidino-substituted benzamides was monitored by IR spectroscopy
Development and validation of a chromatographic method for the determination of N-nitrosamines
No full textN-nitrozamini su organski kemijski spojevi koji se klasificiraju kao kancerogeni za ljudsko zdravlje. Pojavljuju se svuda oko nas u raznim prehrambenim i kozmetičkim proizvodima, no posljednjih godina je otkriveno kako se u značajnoj količini javljaju kao nusprodukti dezinfekcije vode za piće korištenjem procesa poput kloriranja i kloraminacije. Vrlo je važno postići njihovu jednostavnu i brzu detekciju u vodi kako bi se odredila njezina prikladnost za piće. Cilj ovog rada je razviti metodu tekućinske kromatografije visoke djelotvornosti koja koristi detektor s nizom dioda za određivanje N-nitrozamina te provesti validaciju kako bi se odredila njezina prikladnost za tu namjenu. Ispitivanja su provedena na osam N-nitrozamina: N-nitrozodi-n-propilamin (NDPA), N-nitrozopirolidin (NPYR), N-nitrozodietilamin (NDEA), N-nitrozomorfolin (NMOR), N-nitrozo-di-n-butilamin (NDBA), N-nitrozopiperidin (NPIP), N-nitrozodifenilamin (NDPhA) i N-nitrozodimetilamin (NDMA). Kako bi se izabrala najprikladnija pokretna faza, najprije su provedena izokratna eluiranja s acetonitrilom, etanolom i metanolom kao B fazom, dok je u sva tri slučaja MilliQ voda činila A fazu. Dobiveni su rezultati pokazali kako je kombinacija acetonitrila i MilliQ vode najbolji izbor pokretne faze za određivanje N-nitrozamina te su upravo oni korišteni u daljnjem istraživanju. Za razvoj metode ispitivano je više gradijenata te se u konačnici kao najbolji izbor pokazao gradijent čije vrijeme analize traje 20 minuta uz protok 0,5 mL min^-1. Razvijena HPLC-DAD metoda je potom validirana pri čemu su ispitane izvedbene karakteristike metode: selektivnost, linearnost, ponovljivost, međupreciznost, istinitost, granica detekcije, granica kvantifikacije te je definirano radno područje metode. Metoda se analizom uzoraka vodovodne vode pokazala selektivnom što omogućuje njezinu primjenu za određivanje N-nitrozamina u vodi. Postignuta je dobra linearnost (R^2 ≥ 0,995) te je također zadovoljen kriterij za ponovljivost i međupreciznost (RSD ≤ 10 %) za sve N-nitrozamine. Zadovoljavajuće iskorištenje postignuto je pri višim koncentracijama, dok za niže koncentracije nije zadovoljen kriterij prihvatljivosti za sve N-nitrozamine. Rezultati su pokazali kako je razvijenom HPLC-DAD metodom moguće uspješno odrediti osam ispitivanih N-nitrozamina te provesti njihovu kvantifikaciju. Provedenom validacijom metode potvrđena je njezina primjenjivost u svrhu određivanja N-nitrozamina što omogućuje primjenu ove metode za analizu uzoraka vode.N-nitrosamines are organic chemical compounds which are classified as cancerogenic for humans. They appear all around us, such as food and cosmetic products but in recent years it was discovered that they appear in significant amounts as byproducts of water disinfection, such as chlorination and chloramination. It's important to achieve their simple and fast detection in water, in order to confirm water suitability for drinking. Aim of this research is to develop a high-performance liquid chromatography method with diode array detection for the determination of N-nitrosamines and to perform method validation to determine its fitness for purpose. Research has been carried out on eight N-nitrosamines: N-nitrosodipropylamine (NDPA), N-nitrosopyrrolidine (NPYR), N-nitrosodiethylamine (NDEA), N-nitrosomorpholine (NMOR), N-nitrosodibutylamine (NDBA), N-nitrosopiperidine (NPIP), N-nitrosodiphenylamine (NDPhA) and N-nitrosodimethylamine (NDMA). To determine the best choice of the mobile phase, isocratic elution was performed with acetonitrile, ethanol, and methanol as B phase, while A phase was MilliQ water for all three cases. Obtained results have shown that combination of acetonitrile and MilliQ water was the best choice of mobile phase for N-nitrosamines determination, and they were used in further research. More than few gradients were tested and ultimately as the best choice was proved gradient whose analysis time lasts 20 minutes with flow rate of 0,5 mL min^-1. Developed HPLC-DAD method was then validated whereby the following performance characteristics were tested: selectivity, linearity, repeatability, intermediate precision, trueness, detection limit, quantification limit, and the working range. The method was proved to be selective by analyzing tap water samples, which enables its application for the determination of N-nitrosamine in water. The method achieved good linearity (R^2 ≥ 0.995) and also met the criteria for repeatability and intermediate precision (RSD ≤ 10%) for all N-nitrosamines. Satisfactory recovery was achieved at higher concentrations, while the acceptance criteria for all N-nitrosamines was not achieved at lower concentration level. Validation results confirmed applicability of the developed HPLC-DAD method for quantitative determine of all eight tested N-nitrosamines in water samples