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Over the past decade, the widespread emergence of antibiotic resistant bacterial pathogens has resulted in a worldwide crisis. Inspired by their diverse biological activity of quinuclidine based structures, we have synthesized various enantiomeric forms and characterized class of Nbenzyl-3-amidoquinuclidinium salts to select a potent of antimicrobial agents as well as β- lactamase inhibitors. The antibacterial activity was evaluated against 18 recent clinical isolates of antibioticsusceptible Gram-positive and resistant Gram-negative pathogens by determining their zone of inhibition and minimum inhibitory concentrations. The bioactive assay showed that some of enantiomer displayed comparable or even better antibacterial efficacy in comparison with standard antibiotics. More interestingly, that target compounds are not only active against antibiotic susceptible Gram-positive bacteria, but also exhibit significant antibacterial effects against Gram-negative isolates with various antibiotic resistance profiles. The antimicrobial efficacies of N-benzyl-3-amidoquinuclidinium salts highlight the significance of stereochemistry in antimicrobial activity. The most active compound Q5 showed the lowest MIC value of 6.25 μg/mL against all Gram-negative bacteria. We further show that compound Q5 has the ability to restore antibacterial activity against ten multidrug isolates that express a wide range of β- lactamase enzymes of classes A and C. By fluorescence microscopy it was revealed that compounds Q5 interact with the negatively charged bacterial cell membrane and disrupt the membrane integrity. The cytotoxicity of compound Q5 was determined by assessing viability of human embryonic kidney (HEK293T) cell line by MTT assay. Bacterial kinetic growth after treatment was measured by quantifying cell viability at 0, 2, 4, 6, and 24 h after incubation with different concentrations of compound Q5 using time-kill assays. Our preliminary results showed that this compound has no cytotoxicity against HEK293T cells. These results may lead to development a new class of antimicrobial could potentially function as novel therapeutics to help combat antibiotic resistance.

Organophosphorus compounds (OP) used as pesticides or warfare nerve agents are strong poisons. They inhibit acetylcholinesterase (AChE) by phosphylating its catalytic site. Substrates and reversible ligands can protect cholinesterases from phosphylation. On the other hand some compounds, due to their structure (mostly oximes) protect the enzyme as well but by reactivating it and therefore act as antidotes of OP compounds. There are at present 4 known agents proven to be effective both as reactivators of the phosphylated AChE, and as antidotes in OP poisoning: PAM-2, HI-6, Toxogonin and TMB-4. It was reported that since the middle of 1970s 158 new compounds were synthesized in Croatian laboratories with potential antidotal acivities [1]. They belong to three series of structures: pyridine, imidazole and quinuclidine. Some of them were esters and were studied in their reactions with cholinesterases concerning their stereospecific properties. However, most of them containing the oxime group were tested on biological properties. In vitro studies comprised reversible inhibition of cholinesterase, protection of cholinesterases from phophylation by OP compounds, and reactivation of the phosphylated enzyme. In vivo studies were mainly concerned with oximes as antidotes in experimental poisoning by OP compounds. Of all oximes tested 32 of them were chosen as being the most promising as antidotes, and further studies of their properties have been recommended [2]. The structures of most powerful antidotes among them are presented in Fig. 1. They were shown to be effective antidotes of soman, tabun, sarin and VX when tested on mice or rats poisoned by these OP nerve agents. These antidotes protected the animals equally or even better than the standard, above mentioned oximes now in use. Some of them are also good reactivators of the human acetylcholinesterase inhibited by the agents.

The increased concern about terrorist use of nerve agents prompted us to search for new, more effective oximes against tabun poisoning. Five monoquaternary oximes, N-benzyl-4-hydroxyiminomethylpyridinium bromide (I), N-(p-bromo)benzyl-4-hydroxyiminome-thylpyridinium bromide (II), N-(p-nitro)benzyl-4-hydroxyiminomethylpyridinium bromide (III), N-(p-methyl)benzyl-4-hydroxyiminomethylpyridinium bromide (IV) and N-(p-chloro)benzyl-4-hydroxyiminomethylpyridinium bromide (V) were synthesized to examine their potency as reactivators of tabun-inhibited human erythrocyte acetylcholinesterase (AChE ; EC 3.1.1.7). Oximes were prepared by the addition of appropriate reagents for quaternization in equimolar quantities to the solution of 4-hydroxyiminomethylpyridine (100 mg, 0.819 mmol) in dry acetone (2 mL). The reaction mixtures were kept at room temperature in the dark for 2-3 days. The crystallizations were spontaneous. Acetones were removed and white crystalline compounds were washed with dry diethyl ether and were obtained in very good yields. All synthesized monoquaternary oximes were identified by IR, 1D (1H and 13C (APT)) and 2D (HETCOR) NMR spectroscopies and X-ray analysis. Inhibition of human erythrocyte AChE by tabun proceeded for 30 min, afterwards the extraction of the excess of tabun by hexane was performed. Reactivation of tabun-inhibited AChE was measured spectrophotometrically using acetylthiocholine as a substrate. Various concentrations of the oximes (0.1-1.0 mM) were used. In 24 hours the reactivation of tabun-inhibited AChE by 1 mM of the oxime reached 60% with II, III and IV, 30% with III, and less than 20 % with I. Evaluated potency of oximes as tabun-inhibited AChE reactivators were in increasing order I > III > II > V > IV based on the extent of the reactivation after 30 min. The overall reactivation rate constants were below 10 min-1M-1 for all oximes. All studied oximes were also reversible inhibitors of native AChE with increasing inhibition potency in order IV ≥ II > V > III > I. Therefore, although oxime I did not show significant reactivation ability, this oxime might be of interest as a pre-treatment drug due to its high affinity for the native AChE.

The synthesis of racemic and enantiomerically pure N-p-methylbenzyl-3-benzamidoquinuclidinium bromides (6-8) and N-p-chlorobenzyl-3-benzamidoquinuclidinium bromides (9-11) is described. These compounds were prepared from racemic or enantiomerically pure 3-benzamidoquinuclidines (3-5) with the appropriate reagents for quaternization: p-methylbenzyl bromide (1) and p-chlorobenzyl bromide (2).

Racemates as well as enantiomers of 3-amidoquinuclidine derivatives of acetic, pivalic, butyric and benzoic acid were prepared. Racemates and enantiomers of quaternary N-benzyl derivatives were synthesized as well by quaternization with benzyl bromide. Structures of all synthesized amides were established by spectroscopy (IR, MS, 1D and 2D NMR) and optical rotations measurements. Butyrylcholinesterase (BChE) was tested with a series of other enzymes as a possible biocatalyst in the hydrolysis of prepared racemic amides, but it was shown that hydrolysis did not occur. Taking into account this result and previously reported results on inhibitions of BChE by N-quaternary esters of quinuclidin-3-ol, N-benzyl amides were tested as possible inhibitors of BChE, as well. In experiments in which benzoylcholine was used as a substrate, it was shown that tested amides were inhibitors of BChE, the strongest of which was (S)-N-benzyl-3-benzamidoquinuclidinium bromide, (Ki=3.7 mikroM).

This report summarizes studies on pyridinium, imidazolium, and quinuclidinium oximes, which were prepared in laboratories in Croatia since the middle of the 1970s. The prepared compounds, 176 in all, include 157 new compounds. The majority of prepared compounds are monoquaternary and bisquaternary pyridinium oximes. In vitro studies comprised reversible inhibition of cholinesterases, protection of cholinesterases from phosphylation by organophosphorus compounds (OP), and reactivation of the phosphylated enzyme. In vivo studies of the oximes as antidotes in experimental poisoning by OP compounds are also reviewed. The OP compounds were predominantly chemical warfare (CW) nerve agents but also included some related pesticides.

Quaternary N-benzyl (R)- and (S)-esters of quinuclidin-3-ol and amides of quinuclidin-3-yl amine and pivalic, butyric and benzoic acid were synthesized. Kinetic studies revealed that (R)-enantiomers of tested esters are much better substrates than (S)-enantiomers. On the other hand, (S)-enantiomers of esters and amides showed higher affinity toward BChE except in the case of the butyric acid derivatives. In order to explain experimental data concerning reactivity of enantiomers, quantum chemical calculations (ONIOM scheme, B3LYP/3-21G ; PM3) of the stable species in the acylation step were performed. It was shown that enantiomeric preference of BChE, as well as rates of hydrolysis, are governed in large part by steric limitations and electrostatic interactions in the choline subsite.

It is known that compounds which contain quinuclidinium and imidazolium subunits possess a wide range of biological activities in the cholinergic system. Some of them were shown to be antidotes against organophosphorus, as well. In this work we describe the synthesis of N-methyl and N-(3-(2-hydrxyiminomethyl-3-methyl-1- imidazolio)-2-oxapropyl derivatives of 3-hydroxy, 3-dimethylcarbamoyloxy and 3-acetyloxy quinuclidines. Molecular modeling studies were undertaken in order to gain some insight on how different enantiomers of synthesized compounds might interact with acetylcholinesterase (AChE) binding sites. Synthesized quinuclidinium derivatives have been studied as reversible inhibitors of AChE and protectors against phosphorylation of the enzyme by some warfare agents.

The aim of this work was to develop and evaluate QSAR model for estimating biological activity of imidazolium oximes. Biological activity is characterized by acute toxicity (LD50) determined in male mice. Imidazolium oximes are characterized by molecular connectivity indices (MCI) and quantum-chemical descriptors. The semiempirical quantum mechanical method PM3 (MOPAC version 6.0) was used to calculate various quantum chemical parameters for imidazolium compounds. Multiple linear regression was used for correlations between biological activity and calculated descriptors.The scope was to determine the most important factors influencing biological activity.

Sintetiziran je niz bisimidazolijevih i imidazolio-piridinijevih aldoksima kojima su heterociklicki prstenovi povezani razlicitim lancima. Spojevima je odredena akutna toksicnost (LD 50).

Proantocijanidini iz sjemenki grožđa su polimerni fenolni spojevi koji imaju blagotvoran učinak na čovjekovo zdravlje. Najpoznatiji su po svom antioksidativnom svojstvu, a štite od bolesti tako što smanjuju količine slobodnih radikala u organizmu koji oštećuju stanice. Njihova svojstva su u mnogome određena su stupnjem polimerizacije odnosno brojem monomernih jedinica od kojih su sastavljeni. Ispitana je metoda određivanja stupnja polimerizacije proantocijanidina iz sjemenki grožđa floroglucinolom umjesto benzil merkaptana, koji je izrazito neugodnog mirisa i nezgodan za korištenje. Postupak s floroglucinolom ne zahtjeva rad u digestoru niti posebnu opremu. Uzorci su bile sjemenke autohtonih hrvatskih sorti grožđa Plavca malog, Crljenka i Babića. Uzorci su analizirani korištenjem tekućinske kromatografije visoke djelotvornosti te je iz tih podataka izračunat stupanj polimerizacije proantocijanidina. Uzorci su analizirani korištenjem tekućinske kromatografije visoke djelotvornosti., Proanthocyanidins from grape seeds are polymeric phenolic compounds that have a beneficial effect on human health. They are best known for their antioxidant properties, protecting against disease by reducing the amount of free radicals in the body that damage cells. Their properties are largely determined by the degree of polymerization, that is, by the number of monomer units of which they are composed. The method for determinination of the polymerisation degree of proantocyanidins from grape seeds with phloroglucinol instead of benzyl mercaptan, which has an extremely unpleasant smell and is inconvenient to use, was examined. The procedure with phloroglucinol does not require a digester or special equipment. The samples were seeds of indigenous Croatian grape varieties Plavac mali, Crljenak and Babić. The samples were analyzed using high performance liquid chromatography and the degree of polymerization of proanthocyanidin was calculated from these data.

Hidrotermalna sinteza potpomognuta mikrovalovima je jednostavna, brza i učinkovita metoda te je stoga privukla značajan interes među znanstvenicima u području sinteze metalnih oksida. Ovom metodom mogu se precizno kontrolirati parametri pod kojima se odvija reakcija sinteze, a o tim parametrima ovise karakteristike sintetiziranih čestica. U ovom radu korištena je za sintezu nanočestica željezovih oksida, getita (FeOOH) i hematita (\(Fe_{2}O_{3}\)), u jako lužnatom mediju, uz željezov(III) klorid (\(FeCl_{3}\)) kao prekursor. Takve nanočestice se mogu koristiti u medicini, za ciljano dopremanje lijekova, uništavanje tumorskih stanica i mnoge druge uporabe. Sintetski spojevi, poput raznih surfaktanata, mogu se koristiti kao stabilizatori nanočestica. U ovom radu su kao alternativa surfaktantima predstavljena eterična ulja, prirodni spojevi koji su netoksični i ekološki prihvatljivi. Istražen je utjecaj eteričnih ulja na veličinu, oblik i sastav konačnog produkta., Microwave-assisted hydrothermal synthesis is a simple, fast and efficient method, and therefore has attracted considerable interest among scientists in the field of metal oxide synthesis. With this method, the parameters under which the synthesis reaction takes place can be precisely controlled, and the characteristics of the synthesized particles depend on these parameters. In this work, it was used for the synthesis of nanoparticles of iron oxides, goethite (FeOOH) and hematite (\(Fe_{2}O_{3}\)), in a strongly alkaline medium, with iron(III) chloride (\(FeCl_{3}\)) as a precursor. Such nanoparticles can be used in medicine, for targeted delivery of drugs, destruction of tumor cells and many other uses. Synthetic compounds, such as various surfactants, can be used as nanoparticle stabilizers. In this paper, essential oils, natural compounds that are non-toxic and environmentally acceptable, are presented as an alternative to surfactants. The influence of essential oils on the final product's size, shape and composition was investigated.

Proantocijanidini su kondenzirani tanini koji se nalaze u sjemenkama i kožici grožđa, a u zadnje vrijeme česti su predmet istraživanja zbog pozitivnog djelovanja na ljudski organizam. Imaju ulogu u prevenciji raka i kardiovaskularnih bolesti, a upravo od te dvije bolesti umire najviše ljudi. Cilj ovog rada bio je razdvojiti proantocijanidine sjemenki grožđa s obzirom na broj jedinica od kojih su građeni na HPLC uređaju s kolonom normalne faze te odrediti stupanj polimerizacije proantocijanidina. Uspješno smo razdvojili proantocijanidine do stupnja polimerizacije n=7 te iz dobivenih rezultata smo izračunali stupanj polimerizacije. Koristeći kiselo kataliziranu reakciju tiolize s benzil merkaptanom na HPLC uređaju s kolonom reverzne faze razdvojili smo benzil tioetere katehina, epikatehina i epikatehin galata. Iz tih podataka smo također izračunali stupanj polimerizacije proantocijanidina. Stupnjevi polimerizacije dobiveni na dva načina pokazuju dobro slaganje., Proanthocyanidins are condensed tannins which are mainly found in grape seeds and skins. In the last few years proanthocyanidins have been extensively researched because of their beneficial effects on human health, they show great results in preventing cancer and cardiovascular diseases. The goal of this research is to separate grape seeds proanthocyanidins on normal phase HPLC and to determine the degree of polymerization of proanthocyanidins using two methods. We have successfully separated polymers up to n=7 and calculated the degree of polymerization using information from chromatograms. Analyzing products of acid-catalysed thiolysis reaction with benzyl mercaptan on reverse phase HPLC we have successfully separated benzyl thioethers of catechin, epicatechin and epicatechin gallate. Information from chromatograms were used to determine the degree of polymerization. The degrees of polymerization calculated in both ways coincide.

Čestice željezovih oksida mogu se pripraviti različitim metodama, najčešće korištena metoda je hidrotermička mikrovalna sinteza. Najveća prednost ove metode je mogućnost preciznog kontroliranja uvjeta sinteze. Ovaj rad daje kratki uvid u proces hidrotermičke mikrovalne sinteze čestica te je istražen utjecaj dodatka biljnih ekstrakata kamilice i brnistre na sintetizirane čestice hematita prije i nakon postupka sušenja. Sinteze su rađene pri temperaturi od 200 °C u trajanju od 20 minuta te su sintetizirane čestice čistog hematita. Dodatkom ekstrakata brnistre i kamilice prije postupka sušenja dokazan je nastanak smjese hematita i getita, dok dodatak ekstrakata nakon sušenja nije imao utjecaja na produkt sinteze. Dobivene čestice karakterizirane su infracrvenom spektroskopijom sa Fourierovom transformacijom (engl. Fourier Transform Infrared Spectroscopy, FTIR)., Iron oxide particles can be prepared by different methods, but the most commonly used method is hydrothermal microwave synthesis. The main advantage of this method is the possibility to precisely control the synthesis conditions. This thesis gives a brief insight into the process of hydrothermal microwave particle synthesis. In addition, the influence of the chamomile and broom plant extracts on the synthesized particles before and after the drying process was investigated. The syntheses were carried out at a temperature of 200 °C for 20 minutes, and the synthesized particles were pure hematite. With the addition of broom and chamomile extracts before the drying process the formation of a mixture of hematite and goethite was proved, while the addition of extracts after drying had no effect on the final product resulting pure hematite particles. The obtained particles were characterized by Fourier Transform Infrared Spectroscopy, FTIR.

Vino je kemijski složena smjesa različitih vrsta spojeva koji uključuju fenolne spojeve koji doprinose boji vina. U fenolne spojeve spadaju i tanini koji su odgovorni za trpak okus vina. Ovi spojevi u vino dospijevaju procesom maceracije. Maceracija je proces u kojem su pokožice i sjemenke grožđa u kontaktu sa sokom. Bijela vina obično nisu macerirana, a maceracijom bijelog grožđa dobiju se tzv. jantarna, orange ili macerirana vina. U ovom radu je UV-VIS spektrofotometrijom određen sadržaj tanina u uzorcima bijelog kao i u uzorcima maceriranog bijelog vina autohtone sorte vinove loze – Pošip. Dobiveni rezultati analize uzoraka iz nekoliko godina berbe pokazuju da macerirana bijela vina imaju višu koncentraciju tanina od nemaceriranih bijelih vina (4,46 g/L za orange vino, a 0,547 g/L za bijelo vino iste godine berbe). Također je uočeno kako će maceracija kod većine uzoraka uzrokovati povećanje intenziteta boje maceriranih u odnosu na nemacerirana bijela vina (0,520 i 0,190 za iste uzorke)., Wine is a chemically complex mixture of many different compounds which include phenolic compounds that contribute to wine color. Phenolic compounds include tannins which contribute to astringency. These compounds are extracted into wine through maceration. Maceration is a process in which seeds and skins of grapes are kept in contact with grape juice. White wines usually aren't macerated, if they are we obtain what are called orange or amber wines. In this thesis, UV/Vis spectrophotometry was used to determine tannin content of white and amber wines made from the autochthonous Dalmatian white variety – Pošip. Samples from several vintages showed that amber wines had higher tannin concentrations than white wine (4,46 g/L in amber wine, and 0,547 g/L in white wine from the same vintage). We also determined that maceration causes an increase in color intensity of amber wine as opposed to white (0,520 and 0,190 for the previous wine samples).

Kvarterne amonijeve soli koriste se kao biološki indikatori, surfaktanti i terapeutici te se često nalaze u sastavu raznih kozmetičkih proizvoda, primjerice šampona i sapuna. Osim toga, sve je češća primjena kvarternih amonijevih soli kao antiseptika te kao antimikrobnih agensa. U svrhu daljnjih bioloških istraživanja, sintetizirani su (R)- i (S)-enantiomeri kvarterne amonijeve soli 3-aminokinuklidina. Kinuklidin je biciklički spoj koji u premoštenju sadrži dušikov atom koji je radi svoje bazičnosti podložan reakciji kvaternizacije, a 3-aminokinuklidin je supstituirani kinuklidin s amino skupinom na trećem ugljikovom atomu. Za kvaternizaciju enantiomera korišten je 1-bromtetradekan. Navedeni alkil-halogenid ima atom broma koji je u reakciji kvaternizacije dobra izlazna skupina. Nastali enantiomeri su bijele krutine dobivene u dobrom iskorištenju. Čistoća novosintetiziranih kvarternih amonijevih soli je analizirana i potvrđena tehnikom tankoslojne kromatografije., Quarternary ammonium salts are used as biological indicators, surfactants and therapeutics, and they are commonly found in many cosmetic products such as shampoos and soaps. Furthermore, quarternary ammonium salts are increasingly used as antiseptics and antimicrobial agents. For the purpose of further biological research, the (R)- and (S)-enantiomers of the quarternary ammonium salt 3-aminoquinuclidine were synthesized. Quinuclidine is a bicyclic compound with a bridgehead nitrogen atom that is subject to quaternization due to its basicity, and 3-aminoquinuclidine is a supstituted quinuclidine with an amino group on the third carbon atom. For the quaternization of enantiomers, 1-bromotetradecane has been used. The used alkyl halide contains a bromine atom which in a reaction of quaternization acts as a good leaving group. The products are white solids obtained in good yields. The purity of the newly synthesized quarternary ammonium salts was analysed and confirmed by thin layer chromatography.

Omega-3 masne kiseline kratkog lanca su nezasićene masne kiseline i gradivne su komponente staničnih membrana. Njihov dovoljan unos je bitan za normalno funkcioniranje organizma jer ih ljudski organizma nije u mogućnosti sintetizirati. Iako potrebna količina omega-3 masnih kiselina za vrijeme trudnoće nije poznata, za pretpostaviti je da se potrebna količina povećala zbog razvoja fetusa. Eikozapentenska (EPA) i dokozaheksanska kiselina (DHA) su dugolančane omega-3 masne kiseline i važne su za normalan tijek trudnoće te za zdravlje majke i dijeteta. Omega-3 masne kiseline dugog lanca imaju utjecaj i na duljinu gestacije te mogu spriječiti razvoj bolesti poput gestacijskog dijabetesa, preeklampsije i poslijeporođajne depresije., Omega-3 short chain fatty acids are polyunsaturated fatty acids that are key components of cell membranes. Their sufficient intake is essential for the normal functioning of the organism because the human organism is not able to synthesize them. Although sufficient intake of omega-3 fatty acids during pregnancy is not known, it is to be assumed that the required amount increased due to fetal development. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are long-chain omega-3 fatty acids and are important for the normal development of pregnancy and for the health of mother and child. Omega-3 long chain fatty acids have influence on duration of gestation and can play role in prevention developments od conditions such as gestational diabetes, preeclampsia and postpartum depression.

Obična planika (Arbutus unedo L.) je vazdazeleni grm ili nisko drvo koje raste u zemljama duž Mediterana i atlantskom području zapadne Europe. Pronađeni bioaktivni spojevi u običnoj planici kao što su polifenoli, flavonoidi, vitamini (C i E), terpenoidi, organske kiseline i karotenoidi smatraju se zaslužnima za karakteristična svojstva biljke, prvenstveno antioksidativna. Pored upotrebe u tradicionalnoj medicini u liječenju gastrointestinalnih i uroloških problema, hipertenzije i srčanih bolesti, ova se biljka sve više primjenjuje u prehrambenoj industriji za izradu džemova, sirupa, alkoholnih pića i meda te šumarstvu zahvaljujući brzoj regeneraciji opožarenih površina., Strawberry tree (Arbutus unedo L.) is an evergreen shrub or low tree that grows in countries along the Mediterranean and the Atlantic area of Western Europe. The bioactive compounds found in strawberry tree such as polyphenols, flavonoids, vitamins (C and E), terpenoids, organic acids, and carotenoids are considered to be responsible for the characteristic properties of the plant, primarily antioxidant. In addition to its use in traditional medicine in the treatment of gastrointestinal and urological problems, hypertension and heart disease, this plant began to be used in the food industry for the production of jams, syrups, alcoholic beverages and honey, and forestry due to rapid regeneration of burned areas.

Željezo, cink i selen su esencijalni elementi u tragovima, bitni za normalan razvoj organizma. Željezo je sastavni dio hemoglobina i mioglobina, proteina koji dopremaju kisik tkivima. Ima važnu ulogu u procesima disanja, proizvodnji energije i sinteze DNA. Nedostatak željeza predstavlja globalni zdravstveni problem. Cink je jedan od najvažnijih elemenata u tragovima u tijelu, neophodan za rast, razvoj, diferencijaciju, homeostazu, održavanje vezivnog tkiva, sintezu DNA, transkripciju RNA, staničnu diobu i stanično aktiviranje. Manjak cinka karakterizira oslabljena imunološka funkcija, gubitak apetita i usporavanje rasta. Selen je funkcionalno važan za nekoliko aspekata ljudske biologije, uključujući središnji živčani sustav, mušku reproduktivnu biologiju, endokrini sustav, mišićnu funkciju, kardiovaskularni sustav i imunitet. Veći nedostatak selena izravno je povezan s dvije endemske bolesti: KashinBeck i Keshan bolesti., Iron, zinc and selenium are essential trace elements, important for the normal development of the organism. Iron is a component of hemoglobin and myoglobin, proteins that deliver oxygen to tissues. It plays an important role in the processes of respiration, energy production and DNA synthesis. Iron deficiency is a global health problem. Zinc is one of the most important trace elements in the body, essential for growth, development, differentiation, homeostasis, connective tissue maintenance, DNA synthesis, RNA transcription, cell division, and cell activation. Zinc deficiency is characterized by impaired immune function, loss of appetite, and growth retardation. Selenium is functionally important for several aspects of human biology, including the central nervous system, male reproductive biology, endocrine system, muscle function, cardiovascular system, and immunity. Severe selenium deficiency is directly linked to two endemic diseases: Kashin-Beck and Keshan diseases.

Aldehdi, ketoni te derivati karboksilnih kiselina su spojevi koji sudjeluju u različitim kemijskim reakcijama. Djelomična polarizacija veze ugljik - kisik u karbonilnoj skupini doprinosi jačanju elektrofilnog karaktera karbonilnog ugljikova atoma. Mnogi biološki važni spojevi esencijalni za normalno funkcioniranje organizma sintetiziraju se mehanizmima nukleofilne supstitucije, adicije te kondenzacije u kojima nastaje nova C–C veza. U reakcijama s organometalnim reagensima ugljikov atom zbog polarizacije veze dobiva nukleofilni karakter zbog čega ima sposobnost nukleofilnog napada na elektrofilne karbonilne spojeve i derivate karboskilnih kiselina pri čemu dolazi do nastanka alkohola. U α - kondenzacijskim reakcijama, pojavljuje se novo reakcijsko središte ili α – ugljikov atom koji se također ponaša kao nukleofil. U reakcijama kondenzacije dolazi do sinteze α, β – nezasićenih spojeva koji se daljnim reakcijama mogu polimerizirati u veće molekule. U svim navedenim reakcijskim mehanizmima dolazi do formiranja najmanje jedne C – C veze što u kemijskom i biološkom pogledu ima poseban značaj., Aldehydes, ketones and carboxylic acids derivatives are compounds which take part in various chemical reactions. Partial polarization of carbon-oxygen bond in carbonyl group contributes in strengthening the electrophilic character of the carbonyl carbon atom. Many important biological compounds essential for normal functioning of the organism are being synthethized using mechanisms such as nucleophilic substitution, addition and condensation. In reactions with organometallic reagents due to the bond polarization, the carbon atom becomes nucleophilic and has the ability to attack electrophilic carbonyl compounds and derivatives of carboxylic acids and create alcohols. In α-condensation reactions there is a new reaction centre or α-carbon atom that has a nucleophilic character. In condensation reactions α,β-unsaturated compounds are being formed that could be subsequently polymerized in larger molecules with additional reactions. In all reaction mechanisms listed above at least one C-C bond is created that has a significant meaning in biological and chemical reactions.

Selen je mikronutrijent koji je esencijalan za ljudsko zdravlje. Selen, u obliku selenoproteina, nezaobilazna je sastavnica u normalnom funkcioniranju organizma, a njihova je uloga sinteza aktivnog oblika hormona štitnjače i regulacija staničnog ciklusa te se upravo na taj način manifestira funkcija selena u našem organizmu. Međutim, najvažnije djelovanje selenoproteina jest njihovo antioksidativno djelovanje. Selen se nalazi u nerafiniranim namirnicama, osobito u integralnom brašnu, morskim plodovima, žumanjku, ribi, žitaricama i njihovim proizvodima te mesu i mesnim prerađevinama, a najveći sadržaj je pronađen u brazilskim oraščićima. Postoji umjereni do veliki rizik po zdravlje ako se u organizam unosi previše selena-iako je otrovanje selenom vrlo rijetko. Unos selena u prehrani odraz je koncentracije selena u tlu na kojem biljka raste, odnosno koncentraciji selena u hrani kojom se životinje hrane. Nedostatak selena je rijedak, a može negativno utjecati na antioksidativnu aktivnost selenoproteina., Selenium is a trace mineral that is essential for human health. Selenium, in the form of selenoproteins, is an indispensable component in the normal functioning of the body, and their role is the synthesis of the active form of thyroid hormones and the regulation of the cell cycle, and thus manifests the function of selenium in our body. However, the most important action of selenoproteins is their antioxidant action. Selenium is found in unrefined foods, especially in wholemeal flour, seafood, egg yolk, fish, grains and their products, and meat and meat products, and the highest content is found in Brazil nuts. There is a moderate to high health risk if too much selenium is ingested although selenium poisoning is very rare. The intake of selenium in the diet is a reflection of the concentration of selenium in the soil on which the plant grows, or the concentration of selenium in the food that the animals eat. Selenium deficiency is rare and can adversely affect the antioxidant activity of selenoproteins.

Nova pandemija koronavirusa koja je započela u Kini, proširila se u mnoge zemlje širom svijeta, a broj potvrđenih slučajeva se svakodnevno povećava. Koronavirus, SARS-CoV-2 uzrokuje teški akutni respiratorni sindrom, bolest poznatiju pod nazivom COVID-19. Zbog brzog širenja virusne infekcije među ljudskom populacijom te zbog velikog broja smrtnih ishoda, SARS-CoV-2 predstavlja problem globalnih razmjera. Kako bi se pronašle učinkovite metode liječenja potrebno je što bolje upoznati građu i razumijeti funkciju struktura koje se nalaze na površini ovojnice virusa. Stoga će u ovome radu, biti riječi o strukturi ovojnice virusa SARS-CoV-2 s posebnim naglaskom na glikoprotein S (engl.spike) kao ključnom proteinu koji posreduje ulasku virusa u stanicu domaćina. Nadalje, pojasnit će se mehanizam prepoznavanja ovog virusa i angiotenzin-konvertirajućeg enzima (engl. angiotensin converting enzyme, ACE2) koji se nalazi na membranama stanica brojnih tkiva u tijelu čovjeka. Detaljne spoznaje o načinu na koji virus ulazi u stanice domaćina te razumijevanje molekularnog mehanizma, omogućit će znanstvenicima razvoj cijepiva i/ili lijekova u borbi protiv COVID-19 pandemije., The new coronavirus pandemic, which started in China, has spread to many countries around the world, and the number of confirmed cases is increasing daily. Coronavirus, SARS-CoV-2, causes severe acute respiratory syndrome, a disease known as COVID-19. Due to the rapid spread of viral infection among the human population and due to the large number of deaths, SARS-CoV-2 is currently a major global health problem. In order to find effective methods of treatment, it is important to investigate function of structures located on the surface of the virus. Therefore, in this thesis, we will investigate the recent literature describing the structure of the SARS-CoV-2 virus envelope with special emphasis on glycoprotein S (spike) as a key element that mediates the entry of the virus into the host cell. Furthermore, the mechanism of recognition of this virus and the angiotensin-converting enzyme (ACE2) found on the cell membranes of numerous tissues in the human body will be elucidated. Detailed insights into the pathway of the virus entery itno the host cells, and detailed understanding of the molecular mechanism, will allow scientists to develop vaccines and/or drugs to combat the COVID-19 pandemic.

Masti predstavljaju koncentrirani izvor energije te služe kao izvor esencijalnih masnih kiselina. Po strukturi, masti su esteri masnih kiselina i alkohola glicerola. Masne kiseline se mogu podijeliti u četiri glavne skupine: zasićene, mononezasićene, polinezasićene i trans masti. Zasićene i trans masne kiseline su „loše masti“ i uzrokuju povećanje LDL-a i smanjenje HDL-a. „Dobre masti“, u koje spadaju mono i polinezasićene masne kiseline, od kojih se ističu ω-3 masne kiseline, snižavaju LDL te protektivno djeluju na kardiovaskularni sustav. U radu su opisane kemijske strukture i vrste masnih kiselina, njihovo djelovanje na zdravlje te prisutnost u hrani., Fats are a concentrated source of energy and source of essential fatty acids. Taking into account their chemical structure, fats are esters of fatty acids and alcohol glycerol. Fatty acids can be classified into four general categories: saturated, monounsaturated, polyunsaturated, and trans fats. Saturated and trans fatty acids are "bad fats" and cause a rise of LDL and a decrease of HDL. "Good fats", which include mono- and polyunsaturated fatty acids, among which the most important are ω-3 fatty acids, lower LDL and have a protective effect on the cardiovascular system. This thesis describes the chemical structures and types of fatty acids, their effect on health and their presence in food.

Metoda određivanja antioksidacijske aktivnosti na staničnim kulturama (engl. Cellular antioxidant activity assay, CAA assay) je standardizirana metoda koja se koristi za određivanje antioksidacijske aktivnosti fitokemikalija, dodataka prehrani i ekstrakata hrane unutar stanica. Metoda se provodi mjereći antioksidacijski potencijal standarda i/ili ispitivanog uzorka na odgovarajućem broju stanica u prisustvu izvora slobodnih radikala i florescentne probe. U stanicama, slobodni radikali oksidiraju fluorescentnu probu, pri čemu se bilježi rast intenziteta fluorescencije koji je u izravnoj vezi s koncentracijom slobodnih radikala. Ukoliko je u reakcijskoj smjesi prisutan antioksidans, on reagira sa slobodnim radikalima i tako inhibira oksidaciju probe što odgađa porast intenziteta fluorescencije. U ovom radu, uspoređeni su rezultati metode CAA dobiveni korištenjem različitih antioksidansa kao standarda, kvercetina i troloksa. Naime u metodi CAA, uobičajeno se kao standard koristi kvercetin koji se otapa u dimetilsulfoksidu (DMSO). Budući da je DMSO pri višim koncentracijama toksičan za stanice, uz kvercetin u ovom je radu ispitan učinak troloksa kao antioksidacijskog standarda topljivog u vodi. Naši rezultati pokazuju da oba antioksidansa pokazuju odličnu reproducibilnost rezultata na zdravim i na tumorskim staničnim kulturama što može biti od važnosti u primjeni ove metode kod viših koncentracija antioksidansa i DMSO-a., The Cellular Antioxidant Activity Assay (CAA assay) is a standardized method used to determine the antioxidant activity of phytochemicals, dietary supplements, and food extracts within cells. The method is performed by measuring the antioxidant potential of the standard and/or test sample on an appropriate number of cells in the presence of a free radical source and a fluorescent probe. In cells, free radicals oxidize the fluorescent probe, resulting in an increase in fluorescence intensity that is directly related to the free radical concentration. If an antioxidant is present in the reaction mixture, it reacts with free radicals and thus inhibits the oxidation of the probe, which delays the increase in fluorescence intensity. In this thesis, the results of the CAA method obtained using different antioxidants standards, namely quercetin and trolox have been compared. Namely, in the CAA method, quercetin which is commonly used as a standard is dissolved in dimethylsulfoxide (DMSO). Given that DMSO is toxic to cells at higher concentrations, the effect of trolox as a watersoluble antioxidant was investigated and compared to quercetin. Our results show that both antioxidants show excellent reproducibility of results on both, healthy and tumor cell lines which may be important in the application of this method when higher concentrations of antioxidants and concequently, DMSO are used.

Malarija je zarazna, nerijetko smrtonosna bolest najčešće na području supsaharske Afrike. Uzročnik bolesti su jednostanični organizmi, paraziti roda Plasmodium, koje prenose ženke komaraca roda Anopheles. Antimalarijski lijekovi su bitni u procesu stvaranja imuniteta protiv parazita te u liječenju zaraze malarije. Najpoznatiji antimalarijski lijek je klorokin, koji je ujedno i najsigurniji i najistraženiji lijek. Klorokin je derivat kinina, a prvi je put bio sintetiziran 1936. godine. Iako je efikasan lijek, u područjima gdje vlada rezistencija koriste se drugi lijekovi kao derivati artemisinina ili drugi derivati kinina. U radu je opisana ukratko malarija i životni ciklus uzročnika bolesti, kao i povijesni razvoj antimalarijskih lijekova i svojstva istih. Cilj rada su predstavnici antimalarijskih lijekova klorokin, hidroksiklorokin i artemisinin, njihova sinteza te objašnjenje mehanizma istih.

Utjecaj oksidativnog stresa na kardiovaskularne bolesti (KVB) i danas je predmet proučavanja. Oksidativni stres, kao rezultat znatnog povećanja koncentracije reaktivnih kisikovih vrsta (engl. Reactive Oxygen Species; ROS), dovodi do promjena u krvožilnoj funkciji kao što je disfunkcija endotela. Čimbenici koji potiču disfunkciju endotela povezuju se s razvojem KVB. Pokazano je da povećana koncentracija ROS poput \(O_{2}\)\( ^{-}\) dovodi do stvaranja aterosklerotskih plakova te smanjenja dušikova monoksida (NO) u aterosklerozi. Oksidativni stres također uzrokuje dilataciju lijeve klijetke i kontraktilnu disfunkciju mišića srca. U arterijskoj hipertenziji ima utjecaj na smanjenje koncentracije NO i povećanje angiotenzina II (engl. Angiotensin II; Ang II). Različiti faktori rizika poput dijabetesa, pušenja i zagađenog zraka potiču oksidativni stres. Čestice zagađenog zraka i dima cigareta umanjiti će plućnu obranu i izazvati oksidativni stres u većini tipova plućnih stanica. Također pokazano je da hiperglikemija, koja se inače tipično javlja u dijabetesu, izaziva oksidativni stres autooksidacijom glukoze i neenzimskom glikozilacijom proteina. Iz tog razloga, sve se više istražuje učinak biljne prehrane u svrhu prevencije KVB. Mediteranska prehrana koja obiluje polifenolima i flavonoidima pokazuje osobito povoljno djelovanje na smanjenje markera oksidativnog stresa., The role of oxidative stress on cardiovascular diseases (CVD) is still the subject of studies. Oxidative stress, as a result of a significant increase in concetration of reactive oxygen species (ROS), leads to changes in vascular function such as endothelial dysfunction. Factors that promote endothelial dysfunction are associated with the development of CVD. It has been shown that an increased concentration of ROS such as \(O_{2}\)\( ^{-}\) leads to the formation of atherosclerotic plaques and a decrease in nitric oxide (NO) in atherosclerosis. Oxidative stress also causes left ventricular dilatation and contractile dysfunction of the heart muscle. In arterial hypertension, it has the effect of reducing the concentration of NO and increasing angiotensin II (Ang II). Various risk factors such as diabetes, smoking and polluted air promote oxidative stress. Particles of polluted air and cigarette smoke will reduce lung defense mechanisms and cause oxidative stress in most lung cell types. In addition, hyperglycemia a state typically occuring in diabetes, has also been shown to cause oxidative stress by glucose autooxidation and non-enzymatic glycosylation of proteins. For this reason, the effect of plant-based diet in the prevention of CVD has been increasingly studied. A Mediterranean diet, rich in polyphenols and flavonoids shows a particularly beneficial effect in reducing markers of oxidative stress.

Cilj: Cilj ovog rada je kroz pregled literature opisati kemijska svojstva i toksikološki učinak kofeina uz osvrt na njegov forenzični značaj. Eksperimentalnom dijelu rada cilj je UV-VIS spektrometrijom odrediti koncentraciju kofeina u 19 odabranih uzoraka čajeva, osvježavajućih bezalkoholnih i energetskih pića dostupnih na hrvatskom tržištu. Također, potrebno je ispitati slažu li se dobivene koncentracije kofeina sa zakonski propisanim maksimalnim sadržajem kofeina u određenom tipu napitka. Metode: Pomoću standardnih otopina kofeina poznatih koncentracija i njihovih apsorbancija izmjerenih UV-VIS spektrometrom pri valnoj duljini 274 nm, konstruiran je baždarni dijagram i određena njegova jednadžba pravca. Infuzija uzoraka čaja izvršena je u destiliranoj vodi, nakon čega je smjesa filtrirana, a filtrat miješan s kloroformom u lijevku za odjeljivanje. Uzorci osvježavajućih bezalkoholnim i energetskih pića degazirani su zagrijavanjem do ključanja i nakon toga ekstrahirani kloroformom u lijevku za odjeljivanje. Tako dobiven ekstrakt je razrijeđen, te mu je UV-VIS spektrometrom mjerena apsorbancija pri valnoj duljini od 274 nm. Koncentracije kofeina u uzorcima izračunate su s pomoću jednadžbe pravca baždarnog dijagrama i faktora razrijeđenja ekstrakata. Rezultati: Rezultati ovog istraživanja su sukladni do sada provedenim sličnim istraživanjima. Uzorci crnih čajeva sadrže veće koncentracije kofeina u odnosu na zelene, dok čajevi skupno imaju više određene koncentracije od ostalih analiziranih napitaka. Energetska pića sadrže veću koncentraciju kofeina u odnosu na osvježavajuće bezalkoholne napitke kod kojih dijetalne inačice određenih napitaka imaju manju koncentraciju kofeina od svojih originalnih varijanti. Dva uzorka energetskih pića pokazala su veću koncentraciju kofeina od one preporučene. Ostali uzorci sadrže koncentracije kofeina u granicama zakonski dozvoljenog, a na deklaracijama proizvoda navode se sve propisane informacije. Zaključak: Budući da je kofein najčešće konzumirana psihoaktivna tvar, njegov toksikološki utjecaj na ljudski organizam dobro je istražen. Forenzični značaj kofeina je malen, ali je potrebno povećati svijest o negativnom utjecaju i mogućoj zlouporabi, na tržištu lako dostupnog, čistog kofeina. Metoda određivanja koncentracije UV-VIS spektometrijom izuzetno je jednostavna, brza, jeftina i pouzdana. Ipak, postupak ekstrakcije nije pokazao dobru ponovljivost zbog čega ga kroz buduća istraživanjima treba dodatno prilagoditi smanjenjem broja koraka u protokolu i mogućeg utjecaja ljudskog faktora na rezultate. Objective: The aim of this paper is to describe the chemical properties and toxicological effect of caffeine through a review of the literature with reference to its forensic significance. The aim of the experimental part of the paper is to determine the concentration of caffeine in 19 selected samples of teas, refreshing soft and energy drinks available on the Croatian market by UV-VIS spectrometry. Also, it is necessary to examine whether the obtained concentrations of caffeine comply with the legally prescribed maximum caffeine content in a particular type of beverage. Methods: Using standard solutions of caffeine of known concentrations and their absorbances measured by UV-VIS spectrometer at a wavelength of 274 nm, a calibration diagram was constructed and its equation was determined. The tea samples were infused in distilled water, after which the mixture was filtered and the filtrate mixed with chloroform in a separatory funnel. Samples of refreshing soft and energy drinks were degassed by heating to boiling and then extracted with chloroform in a separatory funnel. The extract thus obtained was diluted and its absorbance was measured by UV-VIS spectrometer at a wavelength of 274 nm. Caffeine concentrations in the samples were calculated using the calibration equation and the extract dilution factor. Results: The results of this research are consistent with similar research conducted so far. Samples of black teas contain higher concentrations of caffeine compared to green ones, while teas collectively have higher specific concentrations than other beverages analyzed. Energy drinks contain a higher concentration of caffeine compared to refreshing soft drinks in which the dietary versions of certain beverages have a lower concentration of caffeine than their original variants. Two samples of energy drinks showed a higher concentration of caffeine than the recommended one. Other samples contain concentrations of caffeine within the limits allowed by law, and all prescribed informations are stated on product declarations. Conclusion: Since caffeine is the most commonly consumed psychoactive substance, its toxicological impact on the human body has been well investigated. The forensic significance of caffeine is small, but there is a need to increase awareness of the negative impact and possible misuse of pure caffeine which is easily available on the market. The method of determining the concentration by UV-VIS spectrometry is extremely simple, fast, cheap and reliable. However, the extraction process did not show good repeatability, which is why it should be further adjusted through future research by reducing the number of steps in the protocol and the possible influence of the human factor on the results.

Polifenoli su sekundarni biljni metaboliti koji prvenstveno biljci služe u obrani od patogena i UV-zračenja. U prirodi postoji više od 8000 polifenolnih spojeva od kojih su flavanoidi najbrojnija skupina. Upravo zbog široke rasprostranjenosti značajno su prisutni u ljudskoj prehrani. Njihovo najvažnije svojstvo je to što djeluju na slobodne radikale, štiteći tako stanice od raznih oksidacijskih oštećenja. Osim antioksidacijskog djelovanja, polifenoli imaju značajnu ulogu u borbi protiv kardiovaskularnih bolesti, raka te neurodegenerativnih bolesti. U radu je opisana kemijska struktura polifenola, apsorpcija, antioksidacijsko djelovanje te njihova prisutnost u pojedinim namirnicama., Polyphenols are a secondary plant metabolites that primarily serve to defend plants against pathogens and UV radiation. There are more than 8000 polyphenolic compounds in nature, of which flavanoids are the most numerous group. Precisely because of their wide distribution, they are present in the human diet. Their most important property is their role in neutralization of free radicals, thus protecting cells from various oxidative damage. In addition to antioxidant activity, polyphenols play a significant role in the fight against cardiovascular disease, cancer and neurodegenerative diseases. This thesis describes the chemical structure of polyphenols, absorption, antioxidant activity and their presence in certain foods.

U ovom radu opisane su prednosti mikrovalnog zračenja prilikom sinteze amonijevih kvaternih soli. Tehnika mikrovalnog zračenja pruža jednostavnost procesa, bolje iskorištenje, smanjeno reakcijsko vrijeme, ekološku i ekonomsku prihvatljivost. Uspoređeni su uvjeti, postupci i rezultati klasične sinteze s podatcima dobivenim upotrebom mikrovalnog zračenja. Svrha usporedbe je naglasiti učinkovitost i prednosti koje pruža mikrovalno zračenje. Reakcijsko vrijeme je smanjeno na nekoliko minuta, a iskorištenja su značajno viša. Nadalje, opisana je sinteza metil karbonat amonijevih kvaternih soli i sinteza amonijevih kvaternih soli s novim ionima upotrebom dimetil karbonata. Dobivena su visoka iskorištenja, ali reakcije su se odvijale nekoliko sati. Također, opisane su različite primjene amonijevih kvaternih soli s naglaskom na njihov biološki potencijal., This thesis describes the advantages of microwave radiation in synthesis of quaternary ammonium salts. The technique of microwave radiation is simple process, resulting in better yields, decreased reaction time, better ecological and economical acceptability. A comparison has been made between the conditions, procedures and the results of classic synthesis with the dana obtained by microwave radiation. The reason for this comparison is to enhance the efficiency and the advantages that microwave radiation provides. The reaction time has been reduced to a couple of minutes, and the yields have significantly increased. Furthermore, the syntheses of methyl carbonate quaternary ammonium salts and quaternary ammonium salts with new counterions with the utilization of dimethyl carbonate have been described. The reactions proceeded obtaining products in higher yields, but at much slower rates. In addition, the different applications of quaternary ammonium salts with an emphasis on their biological potential have been described.

Karotenoidi su lipofilni pigmenti odgovorni za crvenu, narančastu i žutu boju voća i povrća. U prirodi postoje karotenoidi različite kemijske strukture, no svima je zajednički polienski lanac s višestrukim konjugiranim dvostrukim vezama. Imaju brojne biološke funkcije od kojih su najvažnije pretvorba u vitamin A, antioksidativno te fotoprotektivno djelovanje. Ističu se i po brojnim blagotvornim učincima na zdravlje. U radu je opisana kemijska struktura karotenoida, biološke funkcije, biodostupnost i metabolizam, prisutnost u hrani te učinci na zdravlje čovjeka., Carotenoids are lipophilic pigments responsible for red, orange and yellow color of fruits and vegetables. In nature, there are structurally different carotenoids, with common features such as polyenic chain with multiple conjugated double bonds. Carotenoids have numerous biological functions among which the most important is conversion to vitamin A, antioxidative and photoprotective activity. They also stand out for their numerous beneficial effects on human health. The thesis describes the chemical structure of carotenoids, biological function, bioavailability and metabolism, presence in food and health effects.

Cilj ovog istraživanja je ispitivanje antimikrobne aktivnosti kvaternih amonijevih soli kinuklidin-3-ola sa suptituiranim alkilnim lancima (8, 10, 12 C – atoma) i atomom broma na kraju lanca. Metodom mikrodilucije ispitana je aktivnost spojeva na osam vrsta bakterija (Staphylococcus aureus, uključujući MRSA , Enterococcus faecalis, Streptococcus pyogenes, Listeria monocytogenes, Bacillus cereus, Escherichia coli, Klebsiella pneumoniae) i tri gljivice (Candida albicans, Aspergillus niger, Penicillium citrinum). Spojevi su pokazali veću učinkovitost na gljivice u usporedbi sa bakterijama. Antimikrobna aktivnost spojeva raste produljenjem alkilnog lanca te je najveća kod QOH-12-Br. Najbolji antifungalni učinak ovaj spoj je imao na C. albicans s MIK\(_{50}\) 0,97 µg/mL i MIK\(_{90}\) 1,95 µg/mL Najbolju antibakterijsku aktivnost pokazao je protiv S. pyogenes s MIK i MBK 7,8 µg/mL. Ispitivanje inhibicije biofilma S. aureus ATCC 29213 sa QOH-12-Br pokazalo je znatnu inhibiciju biofilma na sub-MIK vrijednostima, primjerice 41,83% na 1/64 MIK vrijednosti odnosno koncentraciji od svega 0,48 µg/mL., The aim of this study was to investigate the antimicrobial activity of quaternary ammonium salts of quinuclidin-3-ol with substituted alkyl chains (8, 10, 12 C - atoms) and a bromine atom at the end of the chain. The activity of compounds on eight species of bacteria (Staphylococcus aureus, including MRSA, Enterococcus faecalis, Streptococcus pyogenes, Listeria monocytogenes, Bacillus cereus, Escherichia coli, Klebsiella pneumoniae) and three fungi (Candida albicans, Aspergillus niger, Penicillium citrinum) was examined by microdilution. The compounds showed greater efficacy on fungi compared to bacteria. The antimicrobial activity of the compounds increases with the extension of the alkyl chain and is highest in QOH12-Br. This compound had the best antifungal effect on C. albicans with a MIC\(_{50}\) of 0,97 µg /mL and a MIC\(_{90}\) of 1,95 µg /mL. It showed the best antibacterial activity against S. pyogenes with MIC and MBC 7,8 µg /mL. The S. aureus ATCC 29213 biofilm inhibition assay with QOH-12-Br showed significant biofilm inhibition at sub-MIC values, for example 41,83% at 1/64 MIC values or a concentration of only 0,48 µg/mL.

Voće je važni dio naše prehrane, jer ono nije samo spremnik šećera, već je i zdrava hrana s malo kalorija, puno vitamina, minerala i s velikom količinom vlakana. Zbog svega navedenog mora biti neizostavni dio naše prehrane kako bi se osigurao pravilan razvoj i tjelesna aktivnost. U ovom radu naglasak će biti na djelovanju glukoze, fruktoze i saharoze na ljudski organizam, s posebnim osvrtom na fruktozu u sirupima za koju dr. Robert H. Lustig poznati endokrinolog tvrdi da utječe na mnoge bolesti pa čak i na rak. Metabolički put glukoze i fruktoze su različiti jer fruktoza započinje svoj put u jetri stvarajući glikogen i masti. Unatoč svim polemikama oko koristi ili štetnosti uzimanja voćnih šećera ne može se zanemariti njihov doprinos u brzom postizanju energetske učinkovitosti, što ovisi o vrsti voća koje se konzumira. Pri tome treba strogo razlikovati unos fruktoze iz voća od voćnih pripravaka, fruktoznih sirupa koji se danas često konzumiraju, a koji uglavnom sadrže velike količine fruktoze, za koju se danas sa sigurnošću može reći da je uzrok nekih bolesti., Fruit is a vital part of our diet. Not only as a source of sugar, but as a healthy low calorie food filled with vitamins, minerals and fiber. Therefore, it must be a staple in our diet to ensure proper growth and to aid our physical activity. I will explain the effect of fructose,glucose and sucrose on our metabolism. In addition to that i will give my opinion on fructose syrups,for which famous endocrinologist dr. Robert H. Lustig believes are the cause of many diseases including cancer. Metabolic pathways of fructose and glucose are different, because fructose breaks down in liver and creates glycogen and fat. Despite different beliefs about health status of fruit sugars, we can't undermine ability of fructose to yield quick energy to our cells, which is directly associated with type of fruit we consume. To conclude,we need to distinguish fructose coming from fruit, fruit products and high fructose corn syrup that is widely spread in our modern diet and for which some scientists believe could be cause of different diseases.

Plod avokada nutritivno je vrlo vrijedno voće. Odličan je izvor vitamina i minerala, nezasićenih masnih kiselina te u mastima topivih tvari kao što su tokoferoli, steroli i pigmenti. U ovom radu osvrnut ću se ponajviše na lipidne komponente avokada, njihov sastav, ekstrakciju te utjecaj na ljudsko zdravlje. Što se tiče lipidnog sastava razmotrit ću utjecaj vanjskih čimbenika kao što su temperatura i podneblje rasta te varijacije u samoj sorti. Govoreći o lipidnim komponentama avokada neizbježno je spomenuti ulje i njegovu ekstrakciju. Stoga ću se kratko osvrnuti na najčešće korištene metode ekstrakcije ulja avokada i usporediti njihovu učinkovitost. Nizak udio zasićenih, a visok udio mononezasićenih masnih kiselina te prisustvo u lipidima topivih tvari najzaslužniji su za mnoge dobrobiti konzumacije avokada na ljudsko zdravlje. Razmotrit ću utjecaj konzumacije avokada na neke organske sustave, pretilost te razvoj karcinoma., Avocado is a nutritionally valuable fruit. It is an excellent source of vitamins and minerals, unsaturated fatty acids and fat-soluble substances such as tocopherols, sterols and pigments. In this paper, I will focus primarily on the lipid components of avocados, their composition, extraction, and impact on human health. In terms of lipid composition, I will consider the influence of external factors such as temperature, climate and origin of specific variety. Speaking of the lipid components of avocados, it is inevitable to mention the oil and its extraction. Therefore, I will briefly review the commonly used avocado oil extraction methods and compare their effectiveness. The low content of saturated and high levels of monounsaturated fatty acids and the presence of fat-soluble components are most responsible for many of the health benefits of consuming avocados. I will discuss the impact of avocado consumption on some organ systems, obesity, and cancer development.

Cilj ovog istraživanja je ispitivanje antimikrobne aktivnosti kvaternih soli piridinijeva-4-aldoksima. Za istraživanje je korišteno šest klinički značajnih sojeva bakterija uključujući Staphylococcus aureus, Streptococcus pyogenes, Enterococcus faecalis, Listeria monocytogenes, Streptococcus pneumoniae, E. coli, te dvije gljivice Candida albicans i Aspergillus niger. Minimalne inhibitorne koncentracije (MIK) i minimalne baktericidne koncentracije (MBK) sintetiziranih spojeva određene su metodom mikrodilucije. Ispitivani spojevi pokazuju veću učinkovitost na gljivice nego na bakterije. Najbolji antifungalni učinak pokazali su spojevi 3, 6 i 7 s vrijednostima \(MIK_{50}\) od 62,5 μg/mL i \(MIK_{90}\) 125 μg/mL na plijesan A. niger. Najbolju antibakterijsku aktivnost među ispitivanim spojevima pokazao je spoj 6 (\(Py-4-CF_{3}\)) gdje MIK i MBK tog spoja za bakterije E. faecalis, S. pyogenes i S. pneumoniae iznose 250 μg/mL. Ispitivanje inhibicije biofilma S. aureus ATCC 29213 najdjelotvornijeg spoja, spoj 6 (\(Py-4-CF_{3}\)), pokazalo je znatnu redukciju biofilma na subinhibitornim koncentracijama, poput 40% i 29,4% na četvrtini i osmini vrijednosti MIC-a., The aim was to investigate the antimicrobial activity of pyridinium-4-aldoxime quaternary salts. Six clinically relevant strains of bacteria were used for the study including Staphylococcus aureus, Streptococcus pyogenes, Enterococcus faecalis, Listeria monocytogenes, Streptococcus pneumoniae, E. coli, and two fungi Candida albicans and Aspergillus niger. The minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) of the synthesized compounds were determined by the microdilution method. The compounds tested showed greater efficacy on fungi than on bacteria. Compounds 3, 6 and 7 showed the best antifungal effect for A. niger with \(MIK_{50}\) values of 62,5 μg/mL and 125 μg/mL. The best antibacterial activity was shown by compound 6 (\(Py-4-CF_{3}\)) where the MIC and MBC of this compound for E. faecalis, S. pyogenes and S. pneumoniae bacteria were 250 μg/mL. Study of S. aureus ATCC 29213 biofilm inhibition by compound 6 (\(Py-4-CF_{3}\)) showed substantial reduction of biofilm formation at subinhibitory concentrations, including 40% and 29,4% at 1/4 and 1/8 of MIC values.

Cilj ovog istraživanja bio je utvrditi može li čestični crtež primijenjen tijekom poučavanja sadržaja o vodenim otopinama kiselina, baza i soli, utjecati na kvalitetu temeljnih znanja učenika osmih razreda osnovne škole. Glavni izvor podataka bio je kvazieksperiment proveden tijekom školske godine 2014./2015. Učenici tretmanske skupine (N=283) i komparabilne skupine (N=298) poučavani su prema istom metodičkom pristupu, s razlikom da učenici komparabilne skupine nisu koristili u nastavi čestični crtež. Rezultati završnog ispita znanja provedenog nakon poučavanja nastavnih sadržaja upućuju na različiti stupanj unapređenja konceptualnog razumijevanja u tretmanskoj i komparabilnoj skupini. Iako su obje skupine ispitanika napredovale od preliminarnog do završnog ispita znanja, rezultati statističkih testova u zadatcima završnog ispita znanja pokazali su da je konceptualno razumijevanje učenika tretmanske skupine vezano za koncept jednadžbe kemijske reakcije statistički značajno bolje u odnosu na komparabilnu skupinu. Završni ispit znanja nije utvrdio statistički značajnu razliku u konceptualnom razumijevanju disocijacije kiselina, baza i soli te neutralizacije između komparabilne i tretmanske skupine. Pogrešna shvaćanja prepoznata u preliminarnom ispitu znanja dijelom su zadržana i nakon poučavanja, ali znatno manje kod učenika tretmanske skupine., The aim of this study was to determine whether the particulate drawing applied following the instruction of aqueous solutions of acids, bases and salts affects the quality of basic knowledge of eighth grade elementary schools students. The research was conducted using a quasi-experimental design during the school year 2014–2015. Students in the treatment group (N = 283) and comparison group (N = 298) were instructed according to the same methodical approach, with the difference that the instruction of the comparison group did not include usage of particulate drawings. The results of the posttest conducted following the instruction of aqueous solutions of acids, bases and salts, showed a different rate of progress toward conceptual understanding of the treatment and comparison group. Although both groups of participants exhibited progress from pretest to posttest, the results of the statistical tests in the posttest items related to chemical equations showed that the conceptual understanding of the treatment group is statistically better compared to the comparison group. The posttest did not reveal a statistically significant difference in conceptual understanding of the dissociation of acids, bases and salts and neutralisation between the comparison and the treatment group. Misconceptions recognized in the pretest are partly retained after the instruction, but considerably less in the treatment group.

Kvaterne amonijeve soli imaju široku primjenu kao surfaktanti, antimikrobni agensi s izraženim antioksidacijskim djelovanjem, djeluju kao protuotrovi, inhibitori acetilkolinesteraze, terapeutici i sl. U cilju bioloških istraživanja, sintetizirane su dvije serije novih kvaternih amonijevih soli različitih heterocikličkih spojeva: kinuklidin-3-ola i piridinijeva-4-aldoksima koji sadrže tercijarni dušikov atom u strukturi. Kinuklidin-3-ol je biciklički alifatski spoj s atomom dušika u premoštenju, a piridinijev-4-aldoksim je aromatski planarni spoj. Za njihovu kvaternizaciju korišteni su alkilni lanci različite duljine ugljikovodičnog lanca (3, 4, 6 i 8C atoma) koji su mono- ili disupstituirani s bromom kao dobrom izlaznom skupinom u reakciji nukleofilne supstitucije tercijarnih amina navedenih heterocikličkih spojeva. Za sintezu kvaternih soli kinuklidin-3-ola korišteni su alkilni lanci: 1brompropan, 1-brombutan, 1-bromheksan, 1-bromoktan te 1,3-dibrompropan, a za sintezu kvaternih soli piridinijeva-4-aldoksima: 1,3-dibrompropan, 1,4-dibrombutan, 1,6dibromheksan i 1,8-dibromoktan. Svi sintetizirani spojevi su dobiveni kao krutine u dobrom iskorištenju. Tankoslojnom kromatografijom i talištem potvrđena je identifikacija i čistoća novosintetiziranih spojeva., Quaternary ammonium salts have wide application as surfactants, antimicrobial agents with pronounced antioxidant activity, act as antidotes, acetylcholinesterase inhibitors, therapeutics etc. In order to investigate the biological potential, two new series of quaternary ammonium salts bearing different heterocyclic compounds: quinuclidin-3-ol and pyridinium4-aldoxime containing tertiary nitrogen atom in their structure have been synthesized. Quinuclidin-3-ol is a bicyclic aliphatic compound with a nitrogen-bridged linkage, and pyridinium-4-aldoxime is an aromatic planar compound. For their quaternization, alkyl chains with different lengths of the hydrocarbon chain (3, 4, 6 and 8C atoms) were used. The hydrocarbon chains were mono- or disubstituted with bromine which is a good leaving group in the nucleophilic substitution of tertiary amines of corresponding heterocyclic compounds. For the synthesis of quinuclidin-3-ol quaternary salts, alkyl chains that were used are: 1bromopropane, 1-bromobutane, 1-bromohexane, 1-bromoctane and 1,3-dibromopropane and for the synthesis of quaternary salts of pyridinium-4-aldoxime: 1,3 dibromopropane, 1,4dibromobutane, 1,6-dibromohexane and 1,8-dibromoctane. All the synthesized compounds were obtained as solids in good yields. Thin layer chromatography and melting point confirmed the identity and purity of newly synthetized compounds.

Budući da pretilost postaje jednom od najvećih prijetnji zdravlju razvijenog svijeta, ključnu ulogu u prevenciji ima razumijevanje mehanizama regulacije apetita. Nedavna istraživanja upućuju na to da određeni hormoni imaju fiziološku ulogu u kontroli sitosti putem hipotalamusa pa su predmetom proučavanja postale zamršene interakcije između probavnih hormona i središnjeg živčanog sustava te uloge tih hormona u regulaciji unosa hrane. Hormonske terapije potencijalno nude sigurniji pristup u borbi protiv pretilosti. Ovaj rad usmjeren je na proučavanje tih hormona i poremećaja uzrokovanih nedostatkom istih., As obesity becomes one of the greatest threats to the health of the developed world, it is essential to understand the mechanisms of appetite regulation. Recent evidence suggests that certain hormones have a physiological role in controlling satiety via the hypothalamus. With this realization has come increased efforts to understand the intricate interplay between gut hormones and the central nervous system, and the role of these peptides in food intake regulation through appetite modulation. Hormone-based therapies has potential to offer a safer approach to combat the obesity epidemic. This review focuses on the study of these hormones and disorders caused by their deficiency.

Cilj ovog istraživanja je ispitati antimikrobnu aktivnost biskvaternih amonijevih spojeva koji u svojoj strukturi sadrže dva kinuklidinska prstena međusobno povezana alkilnim lancima. Duljina alkilnih lanaca je 8, 10 ili 12 ugljikovih atoma povezanih na dušikov atom kinuklidinijeva-3-ola (BIS-QOH-8, BIS-QOH-10, BIS-QOH-12). Antimikrobni učinak ispitivanih spojeva ovisan je o duljini lanca te raste s porastom broja ugljikovih atoma. Najbolji učinak je uočen protiv gljivica, uključujući oportunističku patogenu kvasnicu C. albicans te široko rasprostranjene plijesni koje uzrokuju kvarenje hrane, P. citrinum i A. niger. Obzirom da podataka o antifungalnoj aktivnosti spojeva strukturno sličnih ovima u dostupnoj znanstvenoj literaturi nema, ovi rezultati su dodatni dokaz širokog spektra biološkog djelovanja i smjernica budućeg istraživanja kvaternih amonijevih spojeva. Tijekom ovog istraživanja, uočen je bolji učinak derivata na gram-pozitivne u odnosu na gramnegativne bakterije, što se dovodi u vezu s građom njihove stanične stjenke. Ispitivanje inhibicije biofilma S. aureus ATCC 29213 pri različitom rasponu koncentracija najdjelotvornijeg derivata s najduljim lancem pokazalo je redukciju biofilma i na subinhibitornim koncentracijama. Ovi podaci potvrđuju široki spektar djelovanja kvaternih amonijevih soli i potencijal njihove široke primjene u medicini i farmakologiji, što je od interesa za znanstvenu javnost i društvo općenito., The aim of this study was to investigate the antimicrobial activity of bisquaternary ammonium compounds which contain two quinuclidine rings mutually bound by alkyl chains. The length of the alkyl chains is 8, 10 or 12 carbon atoms linked to the nitrogen atom of quinuclidinyl-3ol (BIS-QOH-8, BIS-QOH-10, BIS-QOH-12). The antimicrobial activity of the tested compounds depends on the length of the chain and increases with the increase in the number of carbon atoms. The best effect was observed against fungi, including opportunistic pathogenic yeast C. albicans and widespread molds that cause food degradation, P. citrinum and A. niger. Given that data on antifungal activity of compounds structurally similar to those in the available scientific literature are scarse, these results represent an additional evidence of a wide biological activity and guidelines for future investigation of quaternary ammonium compounds. During this study, the better effect of the derivatives on gram-positive compared to gram-negative bacteria was observed, which might be related whit their cell wall structure. Inhibition of biofilm S. aureus ATCC 29213 at a different concentration range of the most efficient derivative with the longest chain showed a reduction in biofilm even at the subinhibitory concentrations. These data confirm a wide spectrum activity of the quaternary ammonium compounds and their potential for application in medicine and pharmacology, which is of interest to the scientific public and society in general.

Biomineralizacija je složen skup biokemijskih i fizioloških procesa pomoću kojih živi organizmi stvaraju čvrste strukture - biominerale. U morskim organizmima procesi biomineralizacije započinju u ranim embrionalnim razvojnim stadijima, odvijaju se tijekom čitavog životnog ciklusa, a očituju se u kalcifikaciji, dekalcifikaciji i polimorfnim promjenama minerala u tkivima, ljušturama ili skeletima. Proces biomineralizacije ovisi o unutarnjoj aktivnosti organizma, te utjecajima okoliša. Jedan od enzima koji sudjeluju u procesu biomineralizacije je ugljična anhidraza koja katalizira reakciju hidratacije i dehidracije \(CO_2\). Proučavanje mehanizama biomineralizacije je jako popularno zbog široke primjene minerala nastalih tim procesom., Biomineralization is a complex combination of biochemical and physiological processes, during which living organisms produce solid structures - biominerals. In marine organisms, biomineralization processes begin in early embryonic developmental stages and occur throughout the entire life cycle, which is manifested in calcification, decalcification and polymorphic changes of minerals in tissues, shells or skeletons. The biomineralization process depends on endogenous activity of an organism and the exogenous environmental influence. One of the enzymes involved in the biomineralization process is carbonic anhydrase that catalyzes the reaction of hydration and dehydration of \(CO_2\). Biomineralization mechanisms are very popular because of the wide application of minerals created by this process.

Spektroskopija proučava međusobno djelovanje elektromagnetskog zračenja i tvari. To su apsorpcija, emisija, raspršenje i fluorescencija. Pošto ova četiri međudjelovanja mogu dati informaciju o građi i sastavu tvari spektroskopija se počela koristiti u mnogim prirodnim znanostima pa tako i u medicini. X-zrake su se prvo koristile u medicinskoj radiografiji da bi kasnije pomogle u otkrivanju strukture DNA i RNA. UV-VIS spektrometrija je tehnika koja omogućava istraživanje kromofornih skupina kao što je porfirin u hemoglobinu te određivanje stupnja zasićenosti hemoglobina kisikom. Infracrvena spektroskopija se koristi u analizi koronarnih i karotidnih arterija oštećenih aterosklerozom. Masena spektrometrija je pogodna za određivanje hormonskog sastava, a nuklearna magnetska rezonancija nam pruža informaciju o razini lipoproteina visoke i niske gustoće (HDL i LDL). Cilj ovog rada je kroz nekoliko spektroskopskih tehnika prikazati i objasniti njihovu veoma značajnu primjenu u medicini., Spectroscopy studies the interaction of electromagnetic radiation and matter. Interaction of radiation and matter can result in four types of answers and those are absorption, emission, scattering and fluorescence. Since these four responses can give information about structure and composition of matter, spectroscopy found its use in many sciences and also in medicine. X-rays were first used in medical radiography and later in the discovery of the structure of DNA and RNA. UV-VIS spectrometry is technique which allows study of chromophore groups like porphyrin in haemoglobin and can help in determination of haemoglobin saturation with oxygen. Infrared spectroscopy is used for analyses of coronary and carotid artery damaged by atherosclerosis. Raman spectroscopy is used for identification of molecular composition in certain tissues. Mass spectrometry is important for the detection of hormone levels and NMR is used for detection level of HDL (high density lipoprotein) and LDL (low density lipoprotein) cholesterols. Main aim of this thesis is to demonstrate and explain use of several spectroscopic tehniques in medicine.

Kristali se nalaze svugdje oko nas, od prirodnih kristalnih minerala do poluvodiča i magnetskih materijala koji se nalaze u različitim elektroničkim uređajima i računalima. Makroskopska fizikalna svojstva kristala povezana su s načinom slaganja čestica koje izgrađuju kristale. Pažljivim proučavanjem fizikalnih svojstava kristala dolazi se do korisnih spoznaja o simetriji rasporeda čestica, oblicima jediničnih ćelija, kao i rasporedu čestica u jediničnim ćelijama. Ovisno o fizikalnim svojstvima kristali se široko primjenjuju u životu suvremenog čovjeka od prijenosnih upaljača, elektroničkih dijelova različitih uređaja, do izvora snažnih magnetskih polja u nuklearnim reaktorima., The crystals are found everywhere around us, from natural crystal minerals to semiconductors and magnetic materials found in various electronic devices and computers. The macroscopic physical characteristics of crystals are related to the method of composition of the particles that the crystals are formed off. Through the study of the physical properties of the crystals, we find many insights about the symmetry of the particles arrangement, unit cell forms, and the arrangement of particles in unit cells. Depending on the physical characteristics, crystals are widely applied in the life of modern man; from portable lighter and electronic parts of different devices, to sources of powerful magnetic fields in nuclear reactors.

3-klorkinuklidin je supstituirani biciklički heterociklički spoj s atomom dušika u premoštenju, koji je u kombinaciji s različitim reagensima korišten u reakcijama sinteze njegovih kvaternih soli. U reakcijama supstitucije korištene su dvije vrste reagensa: aromatski i alifatski s bromom kao dobrom izlaznom skupinom. Od aromatskih reagensa korišteni su benzilirani i pbenzilirani bromidi i od alifatskih ugljikovodični lanci s 4, 8 i 12 ugljikovih atoma. Svi sintetizirani spojevi su kvaterne soli dobivene u velikom iskorištenju. Tankoslojnom kromatografijom i određivanjem tališta potvrđena je identifikacija i čistoća novosintetiziranih spojeva. U ispitivanju antimikrobne aktivnosti 3-klorkinuklidinijeva hidroklorida i kvaternih soli korišteni su različiti mikroorganizmi: Gram-pozitivne bakterije: Bacillus cereus, Enterococcus faecalis, Staphylococcus aureus i Gram-negativne bakterije: Escherichia coli, Pseudomonas aeruginosa, Chronobacter sakazakii.Rezultati testiranja pokazali su da sintetizirane kvaterne soli s p-benzilnim supstituentima, ali i kvaterne soli s duljim ugljikovodičnim lancima imaju puno veću antimikrobnu aktivnost od ostalih spojeva i za Gram- pozitivne, i za Gram-negativne bakterije (MIK=1,56-6,25 µg/mL). Posebno treba naglasiti da kvaterne soli s duljim alifatskim supstituentima (Cl-7 i Cl-8) pokazuju izrazitu aktivnost naročito za sve Gram-negativne bakterije, a njihova aktivnost je bolja od gentamicina (10 odnosno 20x), ali i od cefotaksima za P. aeruginosa i C. sakazakki (2 odnosno 5x)., 3-chloroquinuclidine is bicyclic heterocyclic compound with nitrogen atom in bridgehead which was combined with different reagents in reactions of synthesis of its quaternary salts. In the substitution reactions, the following two types of reagent were used: aromatic and aliphatic, with bromine as a good leaving group. There were used benzyled and p-benzyled bromides from group of aromatic reagents, and chains with 4, 8, and 12 carbon atoms from aliphatic. Newly synthesized compounds were recived in high utilization. Thin layer chromatography and melting points were used to determine identity and purity of synthesized salts. In testing antimicrobial activity of 3-chloroquinuclidine and quaternary salts were used different microorganisms: Gram-positive bacteria: Bacillus cereus, Enterococcus faecalis, Staphylococcus aureus. and Gram-negative bacteria: Escherichia coli, Pseudomonas aeruginosa, Chronbacter sakazakii. Testing results showed that quaternary salts with pbenzyl substituents and quaternary salts with longer chains, have greater antimicrobial activity than other compounds, even for Gram-positive and Gram-negative bacteria (MIK=1,56-6,25 µg/mL). Special accent is on quaternary salts with longer aliphatic substituents (Cl-7 i Cl-8), which showed great activity, especilly for, all Gram- negative bacteria. Their activity is better than gentamicine (10-20x), and cefotaxime, for P. aeruginosa and C. sakazakii (2-5x).

3-benzamidokinuklidin je pripravljen u reakciji odgovarajućeg 3-aminokinuklidina s anhidridom benzojeve kiseline i kao takav upotrijebljen u reakcijama kvaternizacije za pripravu kvaternih soli. Reagensi za kvaternizaciju su različiti para-supstituirani benzil bromidi (p-nitro, p-brom, p-fluor i p-trifluormetil). Dobivene su kvaterne soli u velikom iskorištenju, a tankoslojnom kromatografijom i određivanjem tališta potvrđena je identifikacija i čistoća novosintetiziranih spojeva: N-(p-nitrobenzil)-3-benzamidokinuklidinijeva bromida, N-(p-brombenzil)-3-benzamidokinuklidinijeva bromida, N-(p-fluorbenzil)-3-benzamidokinuklidinijeva bromida i N-(p-trifluormetilbenzil)-3-benzamidokinuklidinijeva bromida. Novosintetiziranim kvaternim solima 3-benzamidokinuklidina je ispitana antimikrobna aktivnost upotrebom različitih mikroorganizama: Gram-pozitivnih bakterija (Bacillus cereus, Enterococcus faecalis, Staphylococcus aureus) i Gram-negativnih bakterija (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Chronobacter sakazakii). Rezultati ispitivanja pokazali su da kvaterne soli 3-benzamidokinuklidina, pokazuju izrazitu aktivnost za Gramnegativne bakterije, naročito N-(p-trifluormetilbenzil)-3-benzamidokinuklidinijev bromid koji ima bolju aktivnost od gentamicina 133× i od cefotaksima 33×. Za Gram-negativnu bakteriju Escherichia coli sve ispitivane kvaterne soli, ukazuju bolju antimikrobnu aktivnost (MIK=7,81-31,25 μg/mL) od gentamicina (MIK=32,00 μg/mL)., 3-benzamidoquinuclidine was prepared by reaction of the appropriate 3-aminoquinuclidine with an anhydride of benzoic acid and as such used in quaternization reactions for the preparation of quaternary salts. Quaternization reagents are different para-substituted benzyl bromides (p-nitro, p-bromo, p-fluoro and p-trifluoromethyl). Quaternary salts are obtained in high yield, a thin-layer chromatography and melting point are used to determine identity and purity of newly synthesized compounds: N-(p-nitrobenzyl)-3-benzamidoquinuclidinium bromide, N-(p-bromobenzyl)-3-benzamidoquinuclidinium bromide, N-(p-fluorobenzyl)-3-benzamidoquinuclidinium bromide and N-(p-trifluoromethybenzyl)-3-benzamidoquinuclidinium bromide. Different microorganisms were used in biological testing antimicrobial activity of newly quaternary salts of 3-benzamidoquinuclidine: Gram-positive bacteria (Bacillus cereus, Enterococcus faecalis, Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Chronbacter sakazakii). Testing results showed that quaternary salts of 3-benzamidoquinuclidine, showed exceptional acitivity for Gram-negative bacteria, especially N-(p-trifluoromethybenzyl)-3-benzamidoquinuclidinium bromide which has 133× better activity than gentamicin and 33× than cefotaxime. For Gram-negative bacteria Escherichia coli all quaternary salts showed better antimicrobial activity (MIC=7.81-31.25 μg/mL) than gentamicin (MIC=32.00 μg/mL).

Dopamin, neurotransmiter iz skupine biogenih amina, jedan je od glavnih neurotransmitera. Uz adrenalin i noradrenalin pripada skupini katekolamina, spojeva koji nastaju iz aminokiseline tirozina. Neuroni koji stvaraju i luče dopamin smješteni su u SŽS-u posebno u dijelu mozga uključenom u impulzivno ponašanje i radnu memoriju, striatumu. Dopamin se u mozgu veže na receptore koji se dijele na dvije skupine ; D1 i D2 skupina, a dopamin ima veći afinitet za receptore koji pripadaju D2 skupini. Dopamin sudjeluje u kontroli nagrade u mozgu i centru za zadovoljstvo. Disfunkcija ovog sustava dovodi do raznih neurodegenerativnih bolesti poput Parkinsonove bolesti, ADHD a posebno razvoja raznih ovisnosti koje utječu na sustav nagrađivanja u mozgu. Razne droge djeluju različito ali imaju zajednički princip povezan s većim nakupljanjem dopamina u sinapsi. Stimulansi poput nikotina i alkohola indirektno pobuđuju neurone da oslobađaju dopamin dok kokain i metamfetamin djeluju tako da se vežu na nosač blokirajući povratak dopamina. Također, ovaj neurotransmiter ima veliku ulogu u razvoju drugih ovisnosti poput one o hrani ili internetu. Tako je ključan u kontroli apetita te su brojna istraživanja pokazala da hrana u mozgu nekih pretilih ljudi izaziva isti utjecaj na dopaminski sustav kao kokain. Korištenje interneta je, zadnjih nekoliko godina, doživjelo veliki porast u svjetu što je utjecalo na sve veće zanimanje znanstvenika za ovisnost o internetu. Dokazan je izražen gubitak dopaminske funkcije u mozgu što ovakav poremećaj dovodi u korelaciju sa raznim drugim ovisnostima koje pokazuju iste ili slične reakcije dopamina u mozgu.

Na početku ovog rada upoznali smo se s lokalnim anesteticima i njihovim mehanizmom djelovanja. Lokalni anestetici se reverzibilno vežu na natrijeve kanale i blokiraju provođenje impulsa duž živčanog vlakna. Dolazi do prekida prijenosa impulsa u senzoričkim aferentnim vlaknima što smanjuje osjet boli. Molekule lokalnog anestetika sadrže aromatski dio vezan esterskim ili amidnim vezama za bazični lanac. Postojanje esterske ili amidne veze bitno je zbog njihove podložnosti metaboličkoj hidrolizi. U esterske lokalne anestetike spada i benzokain, atipični lokalni anestetik koji nema amino skupinu intermedijarnim lancem vezanu za aromatski ostatak. Primarno se koristi u preparatima za kožu kao mast ili melem. Ne prodire dobro u tkivo i nije topljiv u vodi zato se ne koristi u injekcijama. Dobiva se direktnom esterifikacijom p–aminobenzojeve kiseline s etanolom, a za njegovu identifikaciju potrebno je korištenje spektroskopskih metoda. Tijekom godina sintetizirano je i testrirano na stotine novih lokalnih anestetika. Iz različitih razloga većina ih nije ušla u upotrebu te potraga za savršenim još traje.

Polarimetrija je tehnika za određivanje optičke aktivnosti. Optički aktivna tvar je ona tvar, koja u interakciji sa polariziranom svjetlosti zakreće njenu ravninu pod nekim kutom α, koji se naziva i kut zakretanja α. Enantiomeri su stereoizomeri koji se odlikuju svojstvom da zakreću ravninu polarizirane svjetlosti, optički su aktivni. Oni se ne razlikuju u fizikalnim svojstvima, ali se razlikuju u kojem smjeru će zakretati polariziranu svjetlost. Uređaj koji se koristi za mjerenje optičke aktivnosti neke tvari naziva se polarimetar. U polarimetar, u kivetu za postavljanje uzorka postavlja se uzorak, otopljen u odgovarajućem otapalu. Osnovni djelovi polarimetra su izvor svjetla, polarizator, kiveta i analizator. Ako dođe do zakretanja svjetla kroz tu otopinu, smještenu u kiveti, mjeri se kut zakretanja njegove ravnine i usmjerenje. Ako je to zakretanje u desno uzorak je desnozakrećući i ima oznaku (+), a ako dođe do rotacije u suprotnom smjetu uzorak je lijevozakrećujući i oznaka je (-). Apsolutna i relativna konfiguracija nekog spojeva se ne može dovesti u vezu s oznakama (+) odnosno (-).