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Porast rezistencije bakterija na antibiotike koji su trenutno na tržištu potaknuo je potrebu za otkrivanjem novih. Makrolidni antibiotik azitromicin koristi se za liječenje bolesti uzrokovanih Gram-pozitivnim i Gram-negativnim bakterijama. Makrozoni su konjugati azitromicina i tiosemikarbazona pripremljeni za liječenje infekcija uzrokovanih rezistentnim bakterijama, s potencijalom zaobilaženja razvijenih mehanizama rezistencije. Kako bi se dodatno povećala biološka aktivnost i farmakološka svojstva, napravljeni su kompleksi tiosemikarbazona s metalnim ionima. U ovom radu prvo je pripravljen tiosemikarbazon izveden iz 4- aminobenzojeve kiseline i salicilaldehida. Nakon toga, dobiveni tiosemikarbazon je vezan na 4''-aminopropilni derivat azitromicina dajući pripadajući makrozon. Istražena je mogućnost kompleksiranja s ionima bakra(II) i nikla(II). Sintetizirani spojevi karakterizirani su spektroskopijom NMR. The increase in bacterial resistance to currently marketed antibiotics has prompted the need to discover new ones. The macrolide antibiotic azithromycin is used to treat diseases caused by Gram-positive and Gram-negative bacteria. Macrozones are conjugates of azithromycin and thiosemicarbazones prepared to treat infections caused by resistant bacteria, with potential of bypassing the developed resistance mechanisms. In order to further increase biological activity and pharmacological properties thiosemicarbazone complexes with metal ions have been made. In this work, a thiosemicarbazone derived from 4-aminobenzoic acid and salicylaldehyde was prepared first. Subsequently, the resulting thiosemicarbazone was bound to the 4''-aminopropyl derivative of azithromycin. The possibility of complexation with copper (II) and nickel (II) ions was explored. The synthesized compounds were characterized by NMR spectroscopy.

U sklopu ovog rada provedene su sinteze novih derivata imidazo[4,5-b]piridina. Željeni spojevi 8-13 pripremljeni su standardnim metodama organske sinteze, kao i reakcijama potpomognutim mikrovalovima. 5-brom-N-metil-3-nitropiridin-2-amin 3 priređen je nekataliziranom aminacijom početnog 5-brom-2-klor-3-nitropiridina 1. Redukcijom 5-brom-N-metil-3-nitropiridin-2-amina 3 uz korištenje kositrovog klorida dihidrata u etanolu, priređen je diamino supstituirani prekursor 4. 2-fenil supstituirani derivati, 6-brom-3-metil-2-fenil-3H-imidazo[4,5-b]piridin 6 i 6-brom-2-fenil-3H-imidazo[4,5-b]piridin 7 priređeni su kondenzacijom diamino supstituiranih piridina 4 i 5 s benzaldehidom uz p-benzokinon. Željeni konačni 6-(p-fenil) supstituirani spojevi 8-11 priređeni su iz početnih 6-brom supstituiranih derivata imidazo[4,5-b]piridina 6 i 7 u Suzukijevoj reakciji uz korištenje tetrakis(trifenilfosin)paladija(0) kao katalizatora, kalijevog karbonata kao baze u sustavu otapala dioksan/voda. Spoj 4-(6-(metilamino)-5-nitropiridin-3-il)benzonitril 12 priređen je iz početnog spoja, 5-brom-N-metil-3-nitropiridin-2-amina 3. Spoj 13 je priređen reakcijom reduktivne ciklizacije s benzaldehidom uz korištenje natrijevog ditionita u smjesi otapala etanol i DMSO. Strukture spojeva potvrđene su 1H NMR i 13C NMR spektroskopijom. Željeni spojevi 8-13 karakterizirani su UV/Vis spektroskopijom u otapalima različitih polarnosti. Promjene u spektroskopskim svojstvima otopina spojeva promatrane su pH titracijama u puferima različitih pH vrijednosti. Na taj način provedena ispitivanja potvrdila su mogućnosti primjene ovakvih derivata kao optičkih pH senzora. This work presents the synthesis of novel imidazo[4,5-b]pyridine derivatives. Targeted compounds 8-13 were prepared using standard methods of organic synthesis, as well as by microwave-assisted reactions. 5-bromo-N-methyl-3-nitropyridin-2-amine 3 was prepared by uncatalyzed amination of starting 5-bromo-2-chloro-3-nitropyridine 1. Within the reduction of 5-bromo-N-methyl-3-nitropyridin-2-amine 3 using stannous chloride dihydrate in ethanol, the diamino substituted precursor 4 was prepared. 2-phenyl substituted derivatives, 6-bromo-3- methyl-2-phenyl-3H-imidazo[4,5-b]pyridine 6 and 6-bromo-2-phenyl-3H-imidazo[4,5- b]pyridine 7 were prepared by condensation of diamino substituted pyridines 4 and 5 with benzaldehyde with p-benzoquinone. The preferred 6-(p-phenyl) substituted compounds 8-11 were prepared from the 6-bromo substituted imidazo[4,5-b]pyridine derivatives 6 and 7 in the Suzuki reaction using tetrakis(triphenylphosine)palladium(0) as a catalyst, and potassium carbonate as a base in the dioxane/water solvent system. Compound 4-(6-(methylamino)-5- nitropyridin-3-yl)benzonitrile 12 was prepared from the starting compound, 5-bromo-Nmethyl- 3-nitropyridin-2-amine 3. Compound 13 was prepared by a reductive cyclization reaction with benzaldehyde by using sodium dithionite in a solvent mixture of ethanol and DMSO. The structures of the compounds were confirmed by 1H NMR and 13C NMR spectroscopy. Preferred compounds 8-13 were characterized by UV/Vis spectroscopy in solvents of different polarities. Changes in the spectroscopic properties of the compounds solution were observed by pH titrations using buffers of different pH values. The obtained results confirmed the possible application of these derivatives as optical pH sensors.

U ovom radu opisana je sinteza i strukturna karakterizacija ferocenskih dipeptida Ac−L−Ala−NH−Fn−CO−OMe (4) i Ac−D−Ala−NH−Fn−CO−OMe (5). Kopulacijom 1'-aminoferocen-1-karboksilata s Boc−L−Ala−OH odnosno Boc−D−Ala−OH dobiveni su prekursori Boc−L−Ala−NH−Fn−CO−OMe (2) i Boc−D−Ala−NH−Fn−CO−OMe (3). Potom je provedena trans- formacija tert-butilkarbamatne skupine u acetamidnu pri čemu su rezultirali ciljni Ac-dipeptidi 4 i 5. Kako bi se provela strukturna i konformacijska karakterizacija, dipeptidi 4 i 5 podvrgnuti su spektros- kopiji nuklearne magnetske rezonancije (NMR) pri čemu su analizirani ₁H-, ₁₃C-, COSY i NOESY NMR spektri. Detektirani NOE kontakti između NHFn i CH₃COOMe pripisuju se intramolekulskoj vodi- kovoj vezi (IHB) NHFnˑˑˑOCCOOMe uslijed koje dolazi do tvorbe 6-članog interlančanog IHB-prstena. This work describes the synthesis and structural characterization of the ferrocene dipeptides Ac−L−Ala−NH−Fn−CO−OMe (4) and Ac−D−Ala−NH−Fn−CO−OMe (5). 1'-Aminoferrocene-1-car-boxylate was coupled with Boc−L−Ala−OH and Boc−D−Ala−OH to give precursors Boc−L−Ala−NH−Fn−CO−OMe (2) and Boc−D−Ala−NH−Fn−CO−OMe (3), respectively. Then, the tert-butylcarbamate groups were transformed into acetamide groups of the enantiomeric dipeptides 4 and 5. For structural and conformational analysis, the goal dipeptides 4 and 5 were subjected to NMR [nu-clear magnetic resonance spectroscopy (₁H-, ₁₃C-, COSY and NOESY)]. The detected NOE contacts between NHFn and CH₃COOMe indicate the presence of intramolecular hydrogen bond (IHB) NHFnˑˑˑOCCO-OMe, i.e., the presence of a 6-membered IHB-ring.

U ovom radu opisana je sinteza novih 1,2,3-triazolom premoštenih arilimidamidnih derivata benzimidazola, poznatih i kao reverzni amidini benzimidazola, s potencijalnim antitripanosomskim djelovanjem. Za pripravu ciljanih spojeva korištene su klasične metode organske sinteze. Arilimidamidni derivati benzimidazola (23a–23c, 24a–24c, 25a–25c) pripravljeni su iz odgovarajućih 5(6)-aminobenzimidazolnih prekursora (20a–20c, 21a–21c, 22a–22c) i priređenog S-(2-naftilmetil)tiobenzimidatnog hidrobromida 4. 5(6)-aminobenzimidazolni prekursori dobiveni su reakcijom redukcije iz 5(6)-nitrobenzimidazolnih prekursora (17a–17c, 18a–18c, 19a–19c) pripravljenih kondenzacijom bisulfitnih adukata benzaldehidnih prekursora (13a–13c, 14a–14c, 15a–15c) s 4-nitro-o-fenilendiaminom 16. Benzil- (13a–13c), pikolil- (14a–14c) i etinilmorfolin- (15a–15c) 1,2,3-triazolni derivati benzaldehida pripravljeni su regioselektivnom Cu(I)-kataliziranom cikloadicijom iz priređenih 4-(prop-2-iniloksi)benzaldehida (6a–6c) i odgovarajućih azida. Strukturna i spektroskopska karakterizacija novopripravljenih spojeva provedena je 1H i 13C NMR spektroskopijom. In this work the synthesis of new 1,2,3-triazolyl bridged arylimidazole benzimidazole derivatives, also known as benzimidazole reversed amidines with potential antitrypanosomal activity is described. For the synthesis of target compounds classical methods of organic sythesis were used. Arylimidamide benzimidazole derivatives (23a–23c, 24a–24c, 25a–25c) were prepared from the corresponding 5(6)-aminobenzimidazole precursors (20a–20c, 21a–21c, 22a–22c) and prepared S-(2-naphtylmethyl)thiobenzimidate hydrobromide 4. 5(6)-Aminobenzimidazole precursors were obtained by a reduction reaction from 5(6)-nitrobenzimidazoles (17a–17c, 18a–18c, 19a–19c) prepared by condensation of bisulfite aducts of the corresponding benzaldehyde precursors (13a–13c, 14a–14c, 15a–15c) with 4-nitro-o-phenylenediamine 16. Benzyl- (13a–13c), picolyl- (14a–14c) and ethynylmorpholine- (15a–15c) 1,2,3-triazole derivatives of benzaldehyde were prepared by regioselective Cu(I)-catalyzed cycloaddition from the prepared 4-(prop-2-ynyloxy)benzaldehydes (6a–6c) and the corresponding azides. The structures of all newly synthesized compounds were confirmed by the means of 1H NMR and 13C NMR spectroscopy.

Infekcije urinarnog trakta jedna su od najčešćih bolesti uzrokovanih bakterijama. Najčešće se dijagnosticiraju analizom urina test-trakicom, mikroskopskim pregledom sedimenta urina nakon centrifugiranja i urinokulturom. ¹H-NMR-metabolomska analiza urina ima brojne prednosti pred navedenim metodama. U ovom radu dan je pregled predloženih dijagnostičkih algoritama koji se temelje na spektroskopiji nuklearne magnetske rezonancije (NMR). Sastav urina je izrazito varijabilan. Najpouzdaniji biomarkeri za dijagnostiku infekcija urinarnog trakta su trimetilamin i acetat te se mjerenjem njihovih koncentracija u nativnom urinu infekcije mogu dijagnosticirati s vrlo visokom osjetljivošću i specifičnošću. Neke vrste bakterija mogu se identificirati i kvantificirati snimanjem NMR-spektara urina nakon inkubacije uzoraka urina uz dodatak reagenasa za analizu. Snimanjem NMR-spektara nativnih uzoraka urina moguće je odrediti tip bakterije uzročnika infekcije. Najvažniji biomarkeri koji se koriste za razlikovanje infekcija uzrokovanih gram-negativnim bacilima od onih uzrokovanih gram- pozitivnim kokima su trimetilamin, sukcinat, acetat, laktat i etanol. Urinary tract infections are among the most common diseases caused by bacteria. They are most commonly diagnosed by urine swabs, microscopic examination of urine sediment after centrifugation, and bacteriological urine culture. ¹H NMR metabolomic analysis of urine has many advantages over listed methods. This thesis contains a review of proposed diagnostic algorithms based on nuclear magnetic resonance (NMR) spectroscopy. The composition of urine is highly variable. The most reliable biomarkers for diagnosis of urinary tract infections are trimethylamine and acetate. Infections can be diagnosed with very high sensitivity and specificity by measuring their concentrations in native urine samples. Some bacterial species can be identified and quantified by NMR spectroscopy of urine after the urine samples have been incubated with reagents for analysis. NMR spectroscopy of native urine samples allows identification of bacterial species responsible for infection. The most important biomarkers for distinguishing infections caused by gram-negative bacilli and those caused by gram-positive cocci are trimethylamine, succinate, acetate, lactate and ethanol.

Makrolidni antibiotici koriste se u posljednjih 60 godina najčešće za liječenje infekcija gornjih i donjih dišnih puteva. Djelovanje makrolidnih antibiotika temelji se na inhibiciji sinteze bakterijskih proteina vezanjem antibiotika na 50S podjedinicu bakterijskog ribosoma. Povećanje bakterijske rezistencije na postojeće makrolidne antibiotike dovelo je do potrebe za otkrićem i razvojem novih antibiotika. Za potpuno razumijevanje bioaktivnosti makrolidnog antibiotika, potrebno je odrediti konformacije u slobodnom i vezanom stanju te istražiti interakcije s bakterijskim ribosomom. U ovom radu okarakteriziran je 9a-aminopropil derivat azitromicina, prekursor u sintezi makrozona, pomoću jedno- i dvodimenzijskih tehnika NMR. Makrozoni su konjugati azitromicina i tiosemikarbazona. Pomoću tehnike NOESY određena je konformacija prekursora u slobodnom stanju. Konformacija prekursora u vezanom stanju određena je pomoću tehnike trNOESY, dok su interakcije prekursora s ribosomom izoliranim iz bakterije Escherichia coli istražene pomoću tehnike STD. Macrolide antibiotics have been used over the past 60 years, to treat upper and lower respiratory tract infections. Macrolides inhibit bacterial protein synthesis by binding to the 50S subunit of the bacterial ribosome. Increasing bacterial resistance to existing macrolide antibiotics has speed up the process of discovery of new antibiotics. To fully understand bioactivity of macrolide antibiotics, it is necessary to determine structure and conformation in the free and bound states and to investigate the interactions with the bacterial ribosome. In this paper, the structure of 9a-aminopropyl derivative of azithromycin, a precursor in the synthesis of the corresponding macrozone, was characterized by using one- and two-dimensional NMR spectroscopy. Macrozones are conjugates of azithromycin and thiosemicarbazones. The conformation of the precursor in the free and bound states was determined by NOESY and transferred NOESY spectral analysis, while the interactions with the ribosome isolated from Escherichia coli were investigated using the STD technique.

Klaritromicin je predstavnik druge generacije makrolidnih antibiotika, u koju spada i poznatiji azitromicin. Makrolidni antibiotici (makrolidi) se koriste u liječenju infekcija uzrokovanih Gram-pozitivnim i Gram-negativnim bakterijama. Vezanjem za veliku podjedinicu bakterijskog ribosoma makrolidi inhibiraju translaciju proteina čime ubijaju bakterijske stanice. Učestalom primjenom makrolida bakterije su razvile različite mehanizme otpornosti na njihovo djelovanje. Stoga je interes znanosti preusmjeren na razvoj novih makrolidnih antibiotika. Za uspješan dizajn novog makrolida važno je razumjeti njegove interakcije s bakterijskim ribosomom. Stoga je cilj ovog rada okarakterizirati strukturu i interakcije klaritromcina s ribosomom izoliranim iz bakterije Escherichia coli u otopini primjenom jedno- i dvodimenzijskih tehnika NMR. Tehnikama NOESY (engl. nuclear Overhauser effect spectroscopy) i ROESY (engl. rotating frame Overhauser effect spectroscopy) određena je konformacija klaritromicina u slobodnom stanju, a pomoću prijenosnog NOESY određena je konformacija vezanog klaritromicina. Nadalje, metodom STD (engl. saturation transfer difference) proučene su interakcije klaritromicina s ribosomom iz bakterije E. coli i određeni su vezni epitopi. Clarithromycin is a representative of the second generation of macrolide antibiotics, which includes better-known azithromycin. Macrolides are used for treating infections caused by Gram-positive and Gram-negative bacteria. Binding of macrolides to a large subunit of the bacterial ribosome inhibits protein translation and kills bacterial cells. Due to a frequent use of macrolides, bacteria have developed different resistance mechanisms. For this reason, the interest of science has been redirected to the development of new macrolide antibiotics. For a successful design of a new macrolide, it is important to understand its interactions with the bacterial ribosome. Therefore, the purpose of this study is to characterize the structure and interactions of clarithromycin with ribosome isolated from Escherichia coli in solution using one- and two-dimensional NMR techniques. Conformational studies of clarithromycin in the free-state were carried out using NOESY and ROESY techniques, while the bound-state conformation was determined from trNOESY correlations. Furthermore, the interactions of clarithromycin with the E. coli ribosome were studied by STD method, which allowed the assessment of binding epitopes.

Niskodimenzionalni kvantni magnetizam važna je grana istraživanja u fizici kondenzirane tvari. Materijali niskodimenzionalne magnetske strukture često imaju bogate fazne dijagrame kao posljedicu kvantnih fluktuacija i prostorne ograničenosti, te nude izvrsnu platformu za testiranje teorijskih predviđanja poput kvantno-kritičnih točaka i Bose-Einstein kondenzacije. U sklopu fizike niskih dimenzija proučavani su magnetski izolirani klasteri, jednodimenzionalni lanci poput Haldaneovog lanca, spinske ljestve i dvodimenzionalne ravnine, od kojih je možda najpoznatija grupa visokotemperaturnih supravodiča. Nuklearna magnetska rezonancija, uparena s nuklearnom kvadrupolnom rezonancijom, nezaobilazna je u razumijevanju fizike takvih materijala. Tim tehnikama dobiva se direktan uvid u magnetsko i električno polje u blizini atomske jezgre od interesa. Spektroskopska i relaksacijska mjerenja tih tehnika nam omogućuju uvid u statičku i dinamičku spinsku susceptibilnost. U ovom radu proučavat ćemo dvije niskodimenzionalne magnetske strukture: spinski klaster SeCuO_3 i Haldaneov lanac m-NO_2PhBNO tehnikama nuklearne magnetske i kvadrupolne rezonancije. S obzirom da su uzorci monokristali, u sklopu ovog rada izrađen je i goniometar koji omogućuje preciznu orijentaciju uzorka. Ovisnost o orijentaciji parametar je na koji je NMR tehnika osjetljiva, stoga je mogućnost ugađanja tog parametra vrijedan dodatak već postojećoj eksperimentalnoj tehnici. Oba spoja karakterizirana su rendgenskom difrakcijom i određen im je fazni dijagram mjerenjem toplinskog kapaciteta. Glavna saznanja dobivena tijekom istraživanja koje je rezultiralo ovim radom su dublji lokalni uvid u spinsku strukturu tetramera, s posebnim naglaskom da su središnji spinovi ti koji se singletno uređuju, što je direktno potvrđeno, te na snažne fluktuacije vanjskih spinova. Za haldane sustav potvrđena je izotropnost uzorka, te je mapiran fazni dijagram. Istraživanja u području Luttingerove tekućine pokazuju da se radi o privlačnoj interakciji, kao što je i predviđeno Haldaneovom teorijom. Low-dimensional quantum magnetism is an important branch of research in the condensed matter physics. Materials that have a low-dimensional magnetic structure often have rich phase diagrams as a consequence of quantum fluctuations and spatial constraints and offer an excellent platform for testing of the theoretical predictions. Quantum transitions between phases, which can be caused by mechanical or magnetic effects, deserve special mention since they are also the subject of a lot of research. In the vicinity of such a transition, quantum fluctuations determine the physical system, and the system behaves universally, independent of the chemical and other specifics of the system itself. As a part of the low-dimensional physics, magnetically isolated clusters like one-dimensional chains such as the Haldane chain, the spin ladders, and two-dimensional planes of which perhaps the most well-known is the group of high-temperature superconductors, have been studied. Nuclear magnetic resonance technique, paired with the Nuclear quadrupole resonance technique, is indispensable in understanding the physics of such materials. These techniques provide direct insight into the magnetic and electric field near the atomic nucleus of interest. The spectroscopic and relaxation measurements of these techniques allow insight into static and dynamic spin susceptibility. Using single crystal samples for the experiment is extremely beneficial, for the NMR technique can resolve angle, and thus provide angle-related information that is lost if the sample is in a powder form. However, to be able to use the single crystal samples, a goniometer must be able to orient the sample in the desired orientation. Thus, in the scope of this thesis, a goniometer was designed and manufactured. This goniometer proved to be very reliable, made to withstand high magnetic fields and to be able to rotate in the low temperature environment. This paper will present the study of two low-dimensional magnetic structures: the spin cluster SeCuO_3 and the Haldane chain m-NO_2PhBNO (BoNO) by nuclear magnetic and quadrupole resonance techniques. Spin clusters possess simple intracluster interactions that can be well described theoretically and confirmed experimentally. SeCuO_3 compound cluster is worth studying because of its elusive simplicity. It is characterized by a wide temperature range of low-dimensional physics, from 8 K when the antiferromagnetic phase arises, to the room temperature at which it still doesn't follow the Curie-Weiss magnetism model. The behavior of a compound over a wide temperature range, from the antiferromagnetic phase to the activation behavior within tetramer spins, will be studied in the scope of this thesis. The Haldane system m-NO2PhBNO is interesting because it is a good candidate for an ideal Haldane chain, given the complete isotropy of the spin. Previous realizations of the Haldane chain of integer spin have a large anisotropy because the spin carrier is an ion of a transition metal group. In contrast, this system is a completely organic compound, where the integer spin is achieved in a molecular electron orbital. In addition, the two critical magnetic fields at which the quantum phase transitions, characteristic of such systems, occur are relatively low, with the upper field at H_c2 ≤ 40 T. We have characterized the phase diagram of the system at low magnetic fields and studied the one-dimensional physics region of the phase diagram described by the Luttinger fluid. In the first chapter of this thesis, Introduction, a brief overview of the magnetism was presented, with special emphasis on low dimensional physics regarding magnetic interactions. Motivation is given for this thesis. In the second chapter, The NMR experiment, overview of the experimental setup is given - the physics of the NMR, electronics and different measurement techniques that were used during the experimental research that is described in this thesis. Design and manufacturing, as well as using the rotator is described in details there. Third and fourth chapters cover experimental research of the tetramer compound SeCuO_3 and Haldane chain system m-NO_2PhBNO, respectively. Structural overview is described at the beginning, followed by theoretical description of expected physics and previous measurements. Main part of these chapters is the presentation of the experimental data generated in the scope of this thesis and its analysis. A vast amount of data was gathered during this doctoral research. The SeCuO_3 was characterized and its orientation determined by the crystallographic X-ray measurements. Phase transition to 3D ordered state was mapped with respect to magnetic field using homemade heat capacity method. Nuclear quadrupolar resonance spectrum was measured in the ordered phase, as well as relaxations. Small magnetic field was used as a perturbation to the quadrupolar Hamiltonian to determine the spin site responsible for the resonance signal. Nuclear magnetic resonance measurements were conducted and line shift was taken. An effort was made to completely understand complicated NMR spectrum, but to no avail at the time of the writing of this thesis. For the m-NO2PhBNO, characterisation and orientation were also done by the crystallographic X-ray. Phase diagram was mapped with homemade heat capacity method at very low temperatures, T < 0.5 K. Nuclear magnetic resonance spectrum was measured, and used to determine the best possible NMR line to conduct relaxation measurements on. Relaxation measurements were conducted at varying magnetic fields and temperatures in the phase region of Luttinger-liquid physics. Fifth chapter is the conclusion and outlook of the entire thesis. Main findings regarding SeCuO_3 are determination of the critical exponent connected to phase transition into anti-ferromagnetic state, lack of the NQR signal for the Cu2 crystal position, determination of the Cu1 crystal position to the visible NQR signal and relaxation and line shift measurements that both provide irrefutable evidence of singlet pairing of the inner tetramer spins, and their activation as the temperature is raised. This activation energy is consistent with spin interaction determined from a non-local methods. For the BoNO compound, a plethora of characterisation methods has been done, including the cooperation with chemistry department and Ruđer Bošković Institute, but also the heat capacity measurement setup made in-house. In the scope of this thesis, Luttinger liquid region of the phase diagram has been studied. It was shown that inside the Luttinger liquid region of the phase diagram the interaction is attractive, as was theoretically predicted for the Haldane chain system. These findings will provide a good basis for the start of measurements at low temperature and high magnetic field facilities, required to fully understand this compound. Additionally, Appendix A contains specifics of the calculations for the eigenvalues and eigenstates for the SeCuO_3 tetramer model.

U okviru ovog rada provedena je sinteza i spektroskopska karakterizacija novih amidino supstituiranih 1,2-fenilendiamina 8-9 i kloridnih soli benzimidazola 15-28 i benzotiazola 32- 36. Ciljani spojevi priređeni su klasičnim reakcijama organske sinteze te mikrovalovima potpomognutom sintezom. Glavni prekursori za sintezu amidino supstituiranih derivata benzimidazola 15-28, amidino supstituirani 1,2-fenilendiamini 8-9, priređeni su Pinnerovom reakcijom u kiselom mediju iz 4-amino-3-nitrobenzonitrila 4 i katalitičkom hidrogenacijom potpomogutom mikrovalovima uz 10%-tni Pd/C. Ciljani spojevi 15-26 sintetizirani su kondenzacijom priređenih prekursora 8-9 s odgovarajućim aldehidima 10-13 u apsolutnom etanolu uz korištenje p-benzokinona kao oksidansa. Također, ispitana je sintetska metoda priprave amidino supstituiranih kloridnih soli benzimidazola 27 i 28, pomoću otopina odgovarajućih aldehida 10-11 i amidina 9 u DMSO-u uz Na2S2O5, koja nije dala željene produkte. Pomoću dviju sintetskih metoda ispitana je mogućnost priprave amidino supstituiranih kloridnih soli benzotiazola 32-36. Prema metodi A, u otopinu odgovarajućeg zwitter iona 29-31 u ledenoj octenoj kiselini dodan je odgovarajući aldehid 10-11 i reakcijska se smjesa miješala pod dušikom, a nastala slobodna baza suspendirana je u etanolu i ekvimolarnoj količini 36%-tne HCl. Prema metodi B, u otopinu odgovarajućeg zwitter iona 30 u glicerolu dodan je odgovarajući aldehid 11 i ekvimolarna količina 36%-tne HCl. Navedenim sintetskim metoda nisu izolirani željeni produkti. Strukture priređenih produkata potvrđene su 1H i 13C NMR spektroskopijom. Tijek Pinnerove reakcije praćen je IR spektroskopijom. Kako bi se ispitala mogućnost primjene spojeva kao bioloških aktivnih agensa, ispitana im je antioksidativna aktivnost korištenjem DPPH, FRAP i ABTS metode. N,N-dietilamino supstituirani derivati s oba ciklička amidinska supstituenta 24 i 25 pokazuju bolju antioksidativnu aktivnost u usporedbi sa standardom BHT prema ABTS metodi. This work presents the synthesis and spectroscopic characterization of novel amidino substituted 1,2-phenylenediamines 8-9 and hydrochloride salts of benzimidazoles 15-28 and benzothiazoles 32-36. Target compounds were prepared by conventional reactions of organic syntheses as well as by microwave assisted reactions. The main precursors for the synthesis of amidino substituted benzimidazoles 15-28, amidino substituted 1,2-phenylenediamines 8-9, were prepared by Pinner reaction in acid medium starting from 4-amino-3-nitrobenzonitrile 4 and microwave-assisted catalytic hydrogenation with 10% Pd/C. Target compounds 15-26 were synthesized by condensation of the prepared precursors 8-9 with the corresponding aldehydes 10-13 using p-beznoquinone as an oxidant. Also, the synthetic method of preparation of amidino-substituted benzimidazole hydrochlorides 27 and 28 was investigated, using solutions of the corresponding aldehydes 10-11 and amidine 9 in DMSO with Na2S2O5, which did not give the desired products. The possibility of preparing amidino-substituted benzothiazole hydrochlorides 32-36 was investigated by two methods. According to method A, in a solution of the corresponding zwitter ion 29-31 in glacial acetic acid was added the corresponding aldehyde 10-11 and the reaction mixture was stirred under nitrogen to form a free base which was suspended in ethanol and an equimolar amount of 36% HCl. According to method B, in a solution of the corresponding zwitter ion 30 in glycerol was added the corresponding aldehyde 11 and an equimolar amount of 36% HCl. The desired products were not isolated by above synthetic methods. The structures of prepared products were confirmed by 1H and 13C NMR spectroscopy. The Pinner reaction was monitored by IR spectroscopy. In order to investigate the possibility of using the compounds as biologically active agents, the antioxidative activity was determined by DPPH, FRAP and ABTS method. N,N-diethylamino substituted derivatives 24-25 with both cyclic amidino supstituents showed improved activity in comparison to BHT standard.

Reakcijom srebrova(I) nitrata i derivata dijodpiridina (2,5-I2py, 3,5-I2py, 2,6-I2py) u množinskom omjeru 1 : 2 u vodeno-alkoholnom mediju pripravljena su tri nova kompleksa opće formule [Ag(NO3)(I2py)2]. Dobiveni spojevi identificirani su elementnom analizom, a njihova struktura u otopini okarakterizirana je spektrometrijom masa i spektroskopijom NMR. Od 1D tehnika NMR korištene su 1H i 13C ATP, a od 2D homonuklearni 1H-1H COSY te heteronuklearni 1H-13C HMQC i 1H-13C/15N HMBC. U čvrstom stanju, kompleksi su okarakterizirani spektroskopijom IR zračenja. Kristalna i molekulska struktura kompleksa [Ag(NO3)(2,5–I2py)2] određena je i rentgenskom strukturnom analizom. Dobiveni rezultati ukazuju na vezanje srebrovog(I) iona s dvama ligandima preko nesparenog elektronskog para atoma dušika piridinskog prstena. Rentgenska strukturna analiza monokristala spoja [Ag(NO3)(2,5–I2py)2] otkriva da su pored kovalentnih veza (Ag– Npy, Ag–O, Ag–I), u strukturu kristala uključene i nekovalentne halogenske interakcije (O···I–C) koje pridonose stvaranju polimerne strukture spoja., Three novel 1:2 complexes of general formula [Ag(NO3)(I2py)2] were prepared in water-alcohol solution by reaction of silver (I) nitrate with diiodopyridine derivatives (2,5-I2py, 3,5-I2py, 2,6-I2py). All prepared compounds were identified by elemental analysis. Their structure in solution were characterized by mass spectrometry and NMR spectroscopy (1H, 13C ATP, 1H-1H COSY, 1H-13C HMQC, 1H-13C/15N HMBC). In solid state, the complexes were characterized by IR spectroscopy. The crystal and molecular structure of the [Ag(NO3)(2,5–I2py)2] complex was revealed by single crystal X-ray analysis. The obtained results confirmed the binding of silver(I) ion with two ligands via the lone electron pair of nitrogen atoms of the pyridine ring. X-ray structural analysis of [Ag(NO3)(2,5-I2py)2] reveals that beside covalent bonds (Ag–Npy, Ag–O, Ag–I), supramolecular halogen interactions are also present in its crystal structure (O···I–C). Halogen interactions contribute to the final dimensionality by forming polymeric structure of the compound.

Važna grupa peptidomimetika su ureidopeptidi koji se dobivaju uvoĎenjem ureido-skupine kao zamjene za amidnu vezu. Sinteza ureidopeptida temelji se na kemijskoj reakciji kondenzacije ferocenskog izocijanata s prirodnim aminokiselinama. U ovom su završnom radu pripravljeni C2-simetričnih ferocenski bisureidopeptidi koji u svom sastavu imaju glicinsku, fenilalaninsku i valinsku podjedinicu. Pripravljenim spojevima biti će odreĎena kemijska struktura primjenom IR i NMR spektroskopije. An important group of peptidomimetics are ureidopeptides which are prepared by introducing ureido group replacement for the amide group. The ureidopeptide's synthesis is based on the chemical reaction condensation of the ferocene isocyanate with the natural amino acid. In this final work have been prepared C2-symmetric ferocene bisureidopeptides, which in their structure have a glycine, phenylalanine and valine subunit. All prepared compounds will be determined a chemical structure using IR and NMR spectroscopy.

Alergije na hranu velik su zdravstveni problem današnjice. Predstavljaju reakciju imunološkog sustava nastalu nakon konzumiranja određene hrane. U dijagnostičke svrhe koriste se dobro definirani i pročišćeni uzorci alergena. Najvažnije značajke koje određuju alergenost proteina iz hrane su: struktura i funkcija proteina, navike konzumiranja hrane, te genetska sklonost k razvoju alergije. Pokazalo se da se alergeni proteini ne razlikuju od ostalih proteina u pogledu karakterističnih strukturnih obilježja. Neki od alergenih proteina su: parvalbumini, kazeini, beta-laktoglobulini, Bet v 1 homologni alergeni iz hrane. Spektroskopija nuklearne magnetske rezonancije jedna je od glavnih tehnika koja se koristi za proučavanje strukturnih svojstava nativnih i denaturiranih proteina. Jedan od provedenih eksperimenata pokazao je mnoge sličnosti između alergena Mal d 3 (jabuka) i Cor a 8 (lješnjak), te su alergeni svrstani u skupine ovisno o obilježjima tercijarne strukture. Food allergies are a major health problem today. They represent the reaction of the immune system which results from eating certain foods. Well-defined and purified allergen samples are used for diagnostic purposes. The most important features that determine protein's allergenicity are: protein structure and function, eating habits, and genetic predisposition to developing allergies. It has been shown that allergenic proteins do not differ from other proteins in their specific structural characteristics. Some of the allergenic proteins are: parvalbumins, caseins, beta-lactoglobulins, Bet v 1 homologous food allergens. Nuclear Magnetic Resonance (NMR) spectroscopy is one of the main techniques used to study structural properties of native and denatured proteins. One of the experiments has shown many similarities between allergens Mal d 3 (apple) and Cor an 8 (hazel). Also, allergens are classified into particular groups depending on the features of their tertiary structure.

Reakcijom srebrova(I) nitrata s mono- i dihalogen derivatima piridina u molarnom omjeru 1 : 2 u smjesi vode i alkohola priređeno je 12 novih kompleksa srebra(I) opće formule [Ag(NO3)(Xnpy)2], X = Cl, Br, I; n = 1 – 2. Pripravljeni kompleksni spojevi identificirani su pomoću elementne analize, dok je njihova struktura u otopini okarakterizirana tehnikama višenuklearne spektroskopije NMR (1H, 13C, 15N, 109Ag) i spektrometrije masa. Kompleksi su u čvrstom stanju okarakterizirani spektroskopijom IR, a kristalna i molekulska struktura im je određena metodama rentgenske strukturne analize. Molekule liganda su u svim kompleksima na srebrov(I) ion vezane preko atoma dušika piridinskog prstena. U koordinacijskoj sferi srebra(I) dokazan je i nitratni ion koji ovisno o načinu koordiniranja na srebro omogućava stvaranje koordinacijskih polimera ili supramolekulskih struktura. Koordinacijski broj srebra kod sintetiziranih spojeva varira između tri, četiri, pet ili šest i to čak ponegdje i unutar istog spoja. Pored kovalentnih veza, Ag–N i Ag–O, u strukturama su pronađene i nekovalentne interakcije (vodikove i halogenske veze te π···π interakcije) koje pridonose konačnoj dimenzionalnosti spoja. Slaba veza Ag–Ag otkrivena je u kompleksu s 3-Ipy kao ligandom. Priređeni spojevi pokazuju bolju antibakterijsku aktivnost u uvjetima in vitro spram Gram-negativnih nego spram Gram-pozitivnih bakterijskih vrsta. Twelve 1:2 complexes of silver(I) nitrate with mono- and dihalopyridine of the general formula [Ag(NO3)(Xnpy)2], X = Cl, Br, I; n = 1–2, were prepared by reaction of AgNO3 and corresponding pyridine derivative in water-alcohol solution. All synthesized complexes were identified by elemental analysis and characterized in solution by multinuclear NMR spectroscopy (1H, 13C, 15N, 109Ag) and mass spectrometry. In solid state the complexes were characterized by IR spectroscopy, while their crystal and molecular structures were revealed by single crystal X-ray analysis. It was established that in all complexes, besides pyridine nitrogen atoms, the oxygen atoms belonging to nitrate ion are also coordinated to silver ion thus providing not only different coordination numbers of Ag(I) which vary from three, four, five and six but also a formation of coordination polymers or supramolecular structures. It is interesting that in the molecule of one complex, which is dinuclear, there are even two differently coordinated silver ions (3, 4). Beside covalent Ag–N and Ag–O bonds present in complex molecules, there are various non-covalent interactions such as hydrogen bonding, halogen bonds and halogen-halogen interactions thus contributing to final dimensionality. Moreover, a weak Ag–Ag bonding was determined in complex with 3-Ipy as a ligand. In vitro tests of all complexes gave better antibacterial activity against Gram-negative than Gram-positive strains.

Enaminoni (enamini β-dikarbonilnih spojeva) pripadaju skupini organskih molekula koje posjeduju zanimljiva biološka i farmakološka svojstva, a mogu postojati u tri tautomerne forme, s mogućnošću stvaranja intra- i intermolekulskih vodikovih veza. Detaljna strukturna karakterizacija ove skupine organskih molekula nužna je kako bi se što bolje objasnila i povezala svojstva s molekulskom strukturom i vodikovim vezama prisutnim u otopini i čvrstom stanju. U ovom radu određena je struktura derivata pentan-2,4-diona i 1-fenil-but-2-en-1-ona u otopini, pomoću različitih spektroskopskih i računskih metoda. Korištenjem jednodimenzijskih i dvodimenzijskih tehnika spektroskopije NMR, te spektroskopije UV, spektroskopije IR i Ramanove spektroskopije proučavan je utjecaj supstituenata (2-amino-3- nitrofenola i derivata 2-amino-2-metilfenola), prirode otapala (različita polarnost, različita proton-donorska odnosno proton-akceptorska svojstava) i temperature na vodikove veze (intra- i intermolekulske) i molekulsku strukturu derivata pentan-2,4-diona i 1-fenil-but-2-en1-ona. Eksperimentalni rezulatati upotpunjeni su podacima konformacijske analize pri čemu su korištene računske metode na semiempirijskoj razini (PM6) i metode funkcionala gustoće (DFT). Vodikove veze su okarakterizirane u vakuumu, kloroformu i dimetilsulfoksidu (DMSO-u). Ova istraživanja su pokazala da su svi derivati pentan-2,4-diona i 1-fenil-but-2-en-1- ona u otopini prisutni u keto-aminskoj formi, neovisno o otapalu i temperaturi. Dokazano je postojanje jakih intramolekulskih vodikovih veza tipa N–H ...O, te slabih intermolekulskih interakcija između dvije molekule spoja i/ili između molekule spoja i otapala. Enaminones (enamines of β-dicarbonyl compounds) belongs to a group of organic molecules with interesting biological and farmaceutical properties, and might exist in three tautomeric forms, with the possibility of forming intra- and intermolecular hydrogen bonds. Detailed structural characterization of this group of organic molecules is needed to establish structure acitivity ralationships with special emphasis on hydrogen bonding. In this doctoral thesis structures of pentane-2,4-dione and 1-phenyl-but-2-en-1-one derivatives has been determined in solution, by using different spectroscopic (one and two dimensional NMR spectroscopy, UV, IR and Raman spectroscopy) and computational methods. Special attention has been devoted to the influence of the substituents (2-amino-3- nitrophenol i derivatives of 2-amino-2-methylphenols), nature of the solvent (different polarity and different proton-donor and proton-acceptor abbilites) and temperature on hydrogen bonding (intra- and intermolecular) structure of pentane-2,4-dione and 1-phenylbut-2-en-1-one derivatives. The experimental results were complemented with those obtained by computational methods, performed at the semiempirical PM6 level and by using density functional theory (DFT). Hydrogen bonding were characterized in vacuum, chloroforme and dimethyl sulfoxide (DMSO). All investigated pentane-2,4-dione and 1-phenyl-but-2-en-1-one derivatives have been found to exist in the ketoamine form in solution, irrespective of the solvent and the temperature. Results showed presence of strong intramolecular hydrogen bonds of the N– H ...O type as well as weaker intermolecular interactions between two molecules or between the molecule and the solvent.

U ovome preglednom radu opisane su najznačajnije i najčešće primjenjivane jednodimenzijske i dvodimenzijske tehnike NMR u analizi biodizela. Biodizel je ekološki prihvatljivo alternativno gorivo koje se sastoji od zasićenih i nezasićenih metilnih estera masnih kiselina. Budući da analiza kemijskog sastava i proučavanje svojstava biodizela i ostalih biogoriva analitičarima predstavlja izazov, sve više se razvijaju nove i učinkovitije analitičke metode. Spektroskopija NMR jedna je od takvih metoda koja može dati niz informacija o sastavu i strukturi biodizela. Nadalje, analiza spektara NMR pruža vrijedne podatke i o sirovinama iz kojih nastaje biodizel te o procesu esterifikacije. Isto tako primjenom tehnika 1H i 13C NMR može se odrediti sastav aditiva koji se dodaju za sprječavanje rasta mikroorganizama i sastav smjese acetilglicerola i sličnih nusproizvoda sinteze biodizela. U tu svrhu se osim spektara 1H i 13C analiziraju i spektri 31P. U radu su dani karakteristični spektri biodizela, dizela, biljnog ulja tretiranog vodikom te reprezentativan spektar jednog od uzoraka biocida snimljeni u Laboratoriju za spektroskopiju NMR u INA d. d., In this review, the most important and most frequently used one and two dimensional NMR techniques for biodiesel analysis have been described. Biodiesel is an ecologically accepted alternative fuel consisting of saturated and non-saturated methyl esters of fatty acids. Owing to the fact that analysis of biodiesel chemical composition and properties pose a challenge to analytical chemists, novel and more efficient analytical techniques and methods are being developed constantly. In that respect, NMR spectroscopy is an excellent method, which can provide a wealth of information on the composition and structural properties of biodiesel. NMR can be used for determination of the iodine value of biodiesel, fatty acid profile, and percentage of fatty acid methyl esters. Furthermore, NMR spectral analysis can give valuable data on raw materials used for biodiesel production and the process of trans-esterification can be monitored. By the application of 1H and 13C NMR techniques, the composition and structure of additives for preventing the growth of microorganisms can be determined. For that purpose, apart from 1H and 13C spectra, 31P spectra are used as well. Also, composition of acetylglycerol mixtures and corresponding by-products of biodiesel synthesis can be analysed. NMR spectroscopy has proven useful in analysis of hydrotreated vegetable oils, which have better fuel properties than biodiesel produced via transesterification, and their application improves engine fuel economy. In this paper, representative NMR spectra of diesel, biodiesel and hydrotreated vegetable oil and those of biocide samples recorded in the Laboratory for NMR spectroscopy of INA d. d. are given. The advantages of using NMR spectroscopy in biodiesel analysis and determination of its properties are discussed.

Tiosemikarbazoni mogu postojati u nekoliko tautomernih oblika i konformacija, s mogućnošću stvaranja intra- i intermolekulskih vodikovih veza. Detaljna strukturna karakterizacija tiosemikarbazona, kao spojeva koji se povezuju sa širokim spektrom bioloških aktivnosti, preduvjet je za bolje razumijevanje njihove bioaktivnosti, kao i dobivanje molekula s poboljšanim farmakološkim svojstvima. Primjenom višenuklearne spektroskopije NMR (1H, 13C i 15N) u čvrstom stanju i otopini istražen je utjecaj supstituenata, prirode otapala (različitih polarnosti, odnosno različitih proton-donorskih i proton-akceptorskih svojstava) i temperature na molekulsku konformaciju, tautomeriju i prirodu vodikovih veza (intra- i intermolekulskih) derivata salicilaldehid i 2-metoksibenzaldehid tiosemikarbazona. Kombinacija poznate kristalne strukture te izmjerenih kemijskih pomaka 13C i 15N u čvrstom stanju, korištena je kao temelj za detekciju strukturnih promjena u otopini. Eksperimentalni rezultati upotpunjeni su računalnim istraživanjem konformacijskog prostora odabranih spojeva u vakuumu, i organskim otapalima (PCM pristup), kombinacijom molekulsko- i kvantno-mehaničkih metoda. Najstabilnije strukture, dobivene molekulskom mehanikom, reoptimirane su u vakuumu, CHCl3 i DMSO primjenom računskog modela B3LYP-D3/6- 311++G(2df,2p). Metodom populacijske analize QTAIM, korištenjem Koch-Popelierovih kriterija, okarakterizirane su intramolekulske vodikove veze u najstabilnijim konformerima istraživanih spojeva. Thiosemicarbazones can exist in several tautomeric forms and conformations, with the possibility of intra- and intermolecular hydrogen bonding. Detailed structural characterization of thiosemicarbazones, as compounds that are associated with a wide spectrum of biological activities, is a prerequisite for better understanding of their bioactivity and for obtaining molecules with improved pharmacological properties. Solid and solution state multinuclear NMR spectroscopy (1H, 13C i 15N) was emloyed to explore the influence of the substituents, the nature of the solvent (different polarity and different proton-donor and proton-acceptor abbilities) and temperature on the molecular conformation, tautomerism and the nature of hydrogen bonding (intra- and intermolecular) of salicylaldehyde and 2-methoxybenzaldehyde thiosemicarbazone derivatives. The combination of known crystal structures and observed 13C and 15N chemical shifts in the solid state, was used as a basis for the detection of structural changes in solution. The experimental results were complemented with computational research of conformational space of selected compounds in a vacuum, and organic solvents (PCM approach), by combination of molecular- and quantum-mechanical methods. The most stable structures, obtained by molecular mechanics, were reoptimized in vacuum, CHCl3 and DMSO with B3LYP-D3/6-311++G(2df,2p) computational model. QTAIM population analysis method, together with Koch-Popelier criteria, was used for characterization of intramolecular hydrogen bonds in most stable conformers of investigated compounds.