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Diamantane derivatives are excellent guests for cucurbiturils in aqueous solutions, forming complexes with stability constants reaching above petamolar values.[1] On the other hand, their complexation with cyclodextrins has been scarcely explored. We therefore studied temperature and solvent effects on the complexation of diamantane alcohols with cucurbit[7]uril, β- and γ- cyclodextrin by means of isothermal titration calorimetry and NMR spectroscopy. The stability constant among all investigated complexes was by far the highest in the case of the diol derivate with cucurbit[7]uril in water. A pronounced temperature dependence of ΔrH° and ΔrS°, resulting in an almost complete enthalpy-entropy compensation, was observed for most studied host- guest systems. The corres-ponding complexation thermodynamics were in line with the classical rationale of the solvophobic effect at lower temperatures, and the non-classical explanation at higher ones.[2, 3] The results of 1H NMR titrations and ROESY experiments were in line with the thermodynamic studies and have revealed an interesting difference in complex formation kinetics between cucurbit[7]uril and β- cyclodextrin.

Regioisomeric mannoconjugates of naphthyl alcohols were synthesized by coupling of protected mannopyranose and corresponding esters of bromoacetic acid with 1- and 2-naphthyl moieties. Their complexation and the complexation of corresponding nonfunctionalized alcohols with cyclodextrins (α-, β- and γ-) and cucurbit[7]uril was explored by means of isothermal titration calorimetry, spectrophotometry, fluorimetry and NMR spectroscopy. The complexation of 2-naphthol with cucurbit[7]uril was thermodynamically most favorable. A pronounced temperature dependence of ΔrH° and ΔrS°, resulting in an almost complete enthalpy-entropy compensation was observed for some of the examined host-guest systems. In these cases, the complexation thermodynamics was in line with the classical rationale of the hydrophobic effect at lower temperatures, and the non- classical explanation at higher ones. The results of 1H NMR titrations and ROESY experiments were in agreement with the results obtained by other experimental methods and have revealed an interesting difference in complex formation kinetics among the investigated host molecules.

Regioisomeric mannoconjugates of naphthyl alcohols were synthesized by coupling of protected mannopyranose and corresponding esters of bromoacetic acid with 1- and 2- naphthyl moieties. Their complexation and the complexation of corresponding nonfunctionalized alcohols with cyclodextrins (α-, β- and γ-) and cucurbit[7]uril was explored by means of isothermal titration calorimetry, spectrophotometry, fluorimetry and NMR spectroscopy. The complexation of 2- naphthol with cucurbit[7]uril was thermodynamically most favorable. A pronounced temperature dependence of ΔrH° and ΔrS°, resulting in an almost complete enthalpy- entropy compensation was observed for some of the examined host-guest systems. In these cases, the complexation thermodynamics was in line with the classical rationale of the hydrophobic effect at lower temperatures, and the non-classical explanation at higher ones. The results of 1H NMR titrations and ROESY experiments were in agreement with the results obtained by other experimental methods and have revealed an interesting difference in complex formation kinetics among the investigated host molecules.

The temperature and solvent effect on the complexation of various guests (Figure 1) with α-, β- and γ-cyclodextrin and cucurbit[7]uril was explored experimentally and by means of molecular dynamics simulations. The stability constants of all investigated complexes were by far the highest with cucurbit[7]uril in water. A pronounced temperature dependence of ΔrH° and ΔrS°, resulting in almost complete enthalpy-entropy compensation was observed for most explored host-guest systems. For those systems complexation thermodynamics was in line with the classical rationale of the hydrophobic effect at lower temperatures, and the non-classical explanation at higher ones. The optimized inclusion complex structures corresponded to those deduced by means of NMR spectroscopy and the experimentally obtained and calculated ΔrG° were in very good agreement.

Diamantane derivatives are excellent guests for cucurbiturils in aqueous solutions, forming complexes with stability constants reaching above petamolar values. On the other hand, their complexation with cyclodextrins has been scarcely explored. We therefore studied temperature and solvent effects on the complexation of diamantane alcohols with cucurbit[7]uril, β- and γ- cyclodextrin by means of isothermal titration calorimetry and NMR spectroscopy. The stability constant among all investigated complexes was by far the highest in the case of the diol derivate with cucurbit[7]uril in water. A pronounced temperature dependence of ΔrH° and ΔrS°, resulting in an almost complete enthalpy- entropy compensation, was observed for most studied host-guest systems. The corresponding complexation thermodynamics were in line with the classical rationale of the solvophobic effect at lower temperatures, and the non- classical explanation at higher ones. The results of 1H NMR titrations and ROESY experiments were in line with the thermodynamic studies and have revealed an interesting difference in complex formation kinetics between cucurbit[7]uril and β-cyclodextrin.

Hydrazones serve as a valuable platform for exploring fundamental aspects of soft material engineering, owing to their straightforward preparation and chemical robustness. Naturally, insight into their behaviour propels the development of novel chemosensors, biologically active materials and catalysts. Dihydrazones, while seldom explored, offer a plethora of compelling chemical and structural scenarios. Within this study, aryl dihydrazones derived from succinic and adipic acid dihydrazide were synthesized and thoroughly investigated in the solid-state and solution. The potential of the prepared ligands for the development of coordination polymers based on molybdenum(VI) species was investigated under various reaction conditions. The isolated compounds were characterized in the solid-state and solution by appropriate spectroscopic and diffraction methods and compared with the relevant data for neutral dihydrazones. The results unveil that while neutral dihydrazones demonstrate substantial conformational flexibility in solution, crystallization or chelation effectively lodges the dihydrazone framework in a robust anti conformation.

Azithromycin belongs to an azalide subclass of 15- membered macrolide antibiotics. It was synthesized in the early 1980s as a semi- synthetic derivative of erythromycin.[1] With a much improved pharmacokinetic properties over erythromycin, azithromycin became the most widely used broad- spectrum antibiotic.[2] Thiosemicarbazones belong to a large group of thiourea derivatives and are well known as antibacterial, antiviral, anti- inflammatory, antifungal and anticancer therapeutics.[3] Furthermore, a new multi- functional thiosemicarbazones were designed to treat Alzheimer and malaria.[4, 5] Conjugation of the azithromycin and thiosemicarbazone derivatives resulted in novel compounds which showed good activity against some Gram positive and Gram negative bacterial strains. Modern approach to the drug impurity profiling is based on the use of hyphenated systems, such as LC-NMR and/or LC-MS. [6] One of the most efficient and powerful tools for on-line isolation and identification of compounds in complex mixtures in the pharmaceutical industry is the LC-SPE- NMR system. In this study, LC- SPE/CRYO NMR technique was used for impurity profiling of novel azithromycin conjugates.

Calixarenes are a class of supramolecular cavitands that can be easily functionalized to give receptors for ionic and neutral species. Structural evolution of these compounds has led to more selective receptors with improved physico-chemical properties. Most of the synthesized calixarene ionic receptors are not sufficiently soluble in water which makes their use quite limited [1]. Water-soluble calixarenes usually own this property to the introduced easily-ionized sulfonic groups. In the scope of this work novel neutral and water- soluble ligands 1–3 (Figure 1) were designed and prepared, and their complexation with alkali-metal cations was investigated. Glucose was embedded in the structure as hydrophilic domain whereas secondary and tertiary amides served as cation-binding sites. The latter motifs were used since the calixarene derivatives comprising such groups were previously proven to form highly stable complexes [2]. Complexation reactions with alkali-metal cations were studied in water, methanol, and formamide thus giving insight into the solvation as well as intra- and intermolecular hydrogen bonds effects. Several techniques were used, such as UV spectrophotometry, isothermal titration calorimetry and NMR spectroscopy.

Adulteration of high-priced, health beneficial hempseed oil of different geographical origin was studied by combination of 1H NMR spectroscopy and multivariate statistical analysis. The fatty acid composition of hempseed oil corresponds to the ideal ratio of essential fatty acids (EFAs) required by human body, which is roughly 3:1 of omega-6 to omega- 3. 15 hempseed oil samples were adulterated with 6 samples of sunflower oil, 4 samples of rapeseed oil and 4 samples of sesame oil. Each particular edible oil sample varies in producer and country of origin. Including binary mixtures there were altogether 105 oil samples. The aim of this study was to determine the content of each studied hempseed oil sample using established methodology regarding iodine value [1] and fatty acid composition [2], and to select optimal variables and establish optimal regression model for prediction of adulteration with already mentioned adulterant oils. Obtained results show that although hempseed oil samples vary considerably in iodine value (154.0 − 165.5) and omega-3 fatty acids (15.7 ‒ 20.0 %), interval ridge regression [3] and first-break forward interval partial-least square regression (FB- FiPLS) [4] obtain significantly lower root-mean error of prediction than PLS applied to the whole considered NMR spectral region (6 ‒ 0 ppm) in most studied cases. To the best of our knowledge merged-interval regression procedures are for the first time applied to NMR data. Obtained prediction accuracy for volume fraction of each adulterant oil in binary mixtures (1.4 ‒ 3.0 %, 0.991 < R2 < 0.998) are promising enough to conclude that 1H NMR combined with the inspected chemometric procedures can be used to effectively quantify adulteration in hempseed oils, even when many samples of different geographical origin are considered for both hempseed oil and adulterant oils. [1] Y. Miyake, K. Yokomizo, N. Matsuzaki, J. Am. Oil Chem. Soc. 1998, 75, 15. [2] R. Sacchi, F. Addeo, L. Paolillo, Magn. Reson. Chem. 1997, 35, S133. [3] O. Jović, N. Smrečki, Z. Popović, Talanta 2016, 150, 37. [4] O. Jović, Food Anal. Methods 2016, 9, 281.

The solvent influence on the complexation of amphiphilic mannosides, consisting of different non-polar moities, with β-cyclodextrin was explored in a range of temperatures (5 ≤ ϑ/ ºC ≤ 65) by means of microcalorimetry and NMR spectroscopy. The complexation was observed only in strongly hydrogen-bonded solvents (water, formamide, N-methylformamide, and ethylene glycol). The stabilities of complexes were higher in water than in investigated organic solvents, whereby all reactions were enthalpically controlled. A notable temperature dependence of ΔrH○ and ΔrS○ was noticed in water. In contrast, the standard complexation parameters in other investigated solvents exhibited relatively weak temperature dependence. As expected, the complex stability was strongly influenced by compatibilty of the guest and the β-cyclodextrin cavity sizes, as well as the flexibility and structure of the hydrophobic group of investigated mannosides. The carried out investigations provided a deeper insight into the hosting process, demonstrating that solvophobically driven formation of cyclodextrin inclusion complexes is not a water limited phenomenon.

Calixarenes are a class of supramolecular cavitands that can be easily functionalized to give receptors for ionic and neutral species. In many papers published so far their use has been tested in a wide range of applications, from simple host-guest interactions to biomimetics and catalysis. Structural evolution of these compounds has led to more selective receptors with improved physico-chemical properties. Most of the synthesized calixarene ionic receptors are not sufficiently soluble in water which makes their use quite limited [1]. Water-soluble calixarenes usually own this property to the introduced easily-ionized sulfonic groups. In the scope of this work novel neutral and water-soluble ligands 1–3 (Figure 1) were designed and prepared, and their complexation with alkali-metal cations was investigated. Glucose was embedded in the structure as hydrophilic domain whereas secondary and tertiary amides served as cation- binding sites. The latter motifs were used since the calixarene derivatives comprising such groups were previously proven to form highly stable complexes [2]. Complexation reactions with alkali-metal cations were studied in water, methanol, and formamide thus giving insight into the solvation as well as intra- and intermolecular hydrogen bonds effects. Several techniques were used, such as UV spectrophotometry, isothermal titration calorimetry and NMR spectroscopy.

7-Ethyltryptophol, 2(7-ethyl-1H-indol-3- yl)ethanol, is a key starting material in the synthesis of Etodolac, a non-steroidal anti- inflammatory drug. Depending on the synthetic pathway for 7-ethyltryptophol, commercially available material comprises many different impurities which can cause formation of coproducts in the synthesis of Etodolac thus complicating the purification of the final product.[1] Therefore, to develop an optimal purification procedure of Etodolac, it is important to know the structures of impurities in 7-ethyltryptophol. Classical methods for separation and isolation of impurities, such as preparative or semi- preparative liquid chromatography, are time and solvent consuming. Nowadays, hyphenated NMR techniques are becoming faster, more efficient and more sensitive tool for determination of impurities and degradation products in pharmaceuticals and natural products. [2, 3] In this study LC-SPE (cryo)NMR methodology was used to identify impurities in 7-ethyltryptophol. Chromatographic separation was achieved on Waters XBridge Phenyl and C18 columns (150 mm x 4.6 mm ; 3.5 μm) using a combination of gradient and isocratic elution. Compounds were trapped on HySphere Resin GP cartridges in a SPE multitrapping mode. 1H, COSY, 1H-13C HSQC, 1H-13C HMBC NMR spectra and MS spectra were recorded to determine the structures of impurities. In this way 17 compounds were identified. These results show a good potential of LC-SPE (cryo)NMR technique in an identification and structural characterization of low level impurities and degradation products in pharmaceuticals. References: [1] M. C. Sekharayya, G. V. Narayana, S. Nigam, G. Madhusudhan, Indian J. Chem. 51B (2012) 1763-1766. [2] S. Singh, T. Handa, M. Narayanam, A. Sahu, M. Junwal, R. P. Shah, J. Pharm. Biomed. Anal. 69 (2012) 148-173. [3] J. W. Jaroszewski, Planta Med. 71 (2005) 795-802

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.

Synthesis of new materials is one of the very important areas of science that special chemistry deals with. High technology has requested for new materials that will be used for medical purposes, biomaterials, sensors, liquid crystalline materials and electronic materials[1]. Supramolecular chemistry has found interest in the synthesis of new materials because it provides a wide range of possibilities for generating new materials as self-organized nanomaterials because of non- covalent interactions such as hydrogen bonds, π-π stacking or Van der Waals forces. We investigated the possibility of polymerization of supramolecular gels[2] from the class of low molecular weight gelators, mono(vinyl-amino acid) fumarate with UV light and benzophenone as a photoinitiator. These compounds are gelator of various organic solvent but the but polymerization occurs only in acetonitrile. Accordingly, with this, we investigated this system by characterizing it with 1H, 13C, temperature dependent NMR spectroscopy and FTIR spectroscopy.

Organopalladium compounds, usually containing one palladium center per ligand, are one of the most popular transition-metal complexes investigated in organometallic chemistry.[1] Their rich chemistry enables easy preparation and wide scope of possible transformations in order to achieve desired physical properties that qualify them for potential application in organic synthesis and catalysis, supramolecular chemistry and as new materials.[1] As introducing the second palladium to investigated compounds broadens the scope of their applications and transformations, dicyclopalladated azobenzenes, which exhibit strong light absorption and emission in the visible region, recently became one of the main research focuses in our group.[2] In this work we have investigated exchange of solvent ligands (S = DMSO, DMF or pyridine) coordinated to palladium centers in seven dicyclopalladated azobenzenes (C1−7, Scheme 1) in DMF and DMSO by means of spectrophotometric and 1H NMR titrations. Special consideration was paid to varying substituents in 4, 4’-positions of azobenzene moiety as their electronic properties significantly influence spectral properties of the studied dicyclopalladated complexes. In the case of pyridine as a coordinated solvent, corresponding equilibrium constants have been determined. Results will be discussed in terms of solvent donor abilities as well as the electrondonating and electron-withdrawing properties of substituents in the 4, 4’-positions of the azobenzene.

The growing interest in utilization of gold nanoparticles (AuNPs) for diagnostics and treatment of various diseases [1] generates the need to examine their interactions with biological systems. Upon contact with biological media, NPs are immediately coated with a layer of adsorbed biomolecules called “corona” [2]. However, detailed knowledge still lacks about the nature and mechanisms behind the nano-bio interactions. One of the possible binding mechanisms is through the thiol groups, considering the high affinity of sulphur for metals. Endogenous biothiols such as cysteine and glutathione are therefore useful as models for studying the mechanism of nano-bio interactions [3]. In this study, 1H NMR was employed to study the interactions of AuNPs with cysteine and glutathione. Nanoparticles were synthesized by reduction of tetrachloroauric acid with sodium borohydride in the presence of cysteine or glutathione as stabilizing agents. 1H NMR spectra were recorded immediately after mixing the reagents, and subsequently every 20 minutes until AuNPs formation finished. Process of interaction between CYS and GSH with the AuNPs surface was observed by recording chemical shifts of signals corresponding to protons close to the thiol group, along with the loss of resolution and peak broadening. Furthermore, the intermediate spectra were captured, with distinct peaks corresponding to both bound and unbound biothiols. The results suggest the thiol group of CYS and GSH is the most responsible for biothiols-nanoparticle binding. In addition, AuNPs stabilized with CYS and GSH were characterized by means of size distribution, surface charge and visualized by transmission electron microscopy.

The p-tert-butyl calix[4]arenes with carbonyl- containing substituents at the lower rim are known to be effective receptors for alkali- metal cations. Apart from the chemical nature of the attached functionalities, and the cation size, the complexation thermodynamics is strongly influenced by the reactant and the product solvation.[1, 2] In the first part of the work the thermodynamic parameters of alkali-metal cation complexation with a simple calix[4]arene ketone derivative (L) in methanol, ethanol, N-methylformamide, N, N- dimethylformamide, dimethyl sulfoxide, and acetonitrile were determined.[1] The compound L was found to be rather efficient receptor for alkali-metal cations. The cation binding was enthalpically controlled with the peak affinity for Na+. To examine the possible inclusion of the investigated solvent molecules into the hydrophobic basket of the receptor and its sodium complex detailed spectro-photometric, calorimetric and 1H NMR titrations in chloroform were carried out. The solvent binding was much more favorable in the case of NaL+ when compared to free ligand. The sodium complex exhibited the highest affinity for the acetonitrile, which can, at least in part, explain the highest stability of the complexes in this solvent. In the second part of the work, the inclusion of acetonitrile molecule in the hydrophobic cavity of a more rigid tertiary amide calix[4]arene derivative and the corresponding sodium complex was investigated. The obtained data provided an insight into the influence of the calixarene flexibility on the thermodynamics of adduct formation.

The lecture will be dedicated to the role of NMR spectroscopy in the physico-chemical investigations of host-guest complexation reactions, namely the complexation of alkali- metal cations with calix[4]arenes, and the inclusion of lipophilic moieties within hydrophobic cavity of cyclodextrins. In the first part of the lecture, comprehensive investigations of calix[4]arene complexation reactions in several solvents will be described. The thermodynamic data (complex stability constants and derived standard reaction Gibbs energies, reaction enthalpies and entropies) determined by various experimental methods will be correlated with the results of structural investigations. The solvation effects on the equilibria of binding reactions will be discussed in detail. For that purpose, thermodynamic cycles involving the reactant and the complex transfers will be prepared and explained. The role of NMR spectroscopy in revealing specific solvation effects, which can influence the complexation equilibria remarkably, will be addressed. In the second part of the lecture, the thermodynamics of various guest inclusion within the nonpolar cavity of cyclodextrins in several strongly hydrogen-bonding solvents will be reviewed. The influence of the guest structure, size, and conformational freedom on the complex stability will be discussed. The effect of temperature and solvent on the complexation reactions will be analysed in detail. The importance of NMR investigations for the rationalization of the corresponding thermodynamic complexation parameters will be revealed. Finally, the thermodynamics of solvophobically driven complexation involving non-polar solutes and cyclodextrins in organic solvents and water will be addressed.

Isotopic substitution produces changes in the reactivity of a molecule and causes a redistribution of molecular internal vibrational and rotational energy. In NMR, it causes changes in chemical shifts (nuclear shielding), coupling constants and relaxation times. The most studied by far are deuterium effects on nuclear shielding owing to the large fractional change in mass on isotopic substitution and relative ease of their determination from high resolution NMR spectra. The focus of this talk will be put to unsaturated systems containing one or two bridged phenyl groups where isotopic perturbation can be transmitted many bonds away from the isotope substitution site. The sign alternation and specific magnitudes of such long range isotope effects will be discussed in terms of subtle charge shifts throughout the molecule as a consequence of bond shortening upon isotopic substitution. Moreover, the linear correlation between long-range isotope effects and molecular torsional angle can serve as a conformational probe [1] for studied type of molecules. [1] P. Novak, D. Vikić Topić, V. Smrečki, and Z. Meić, Isotope Effects in NMR Spectra as a Structural Tool for Organic Molecules, in: Atta ur Rahman (Ed.), New Advances in Analytical Chemistry, Harwood Academic Publishers, Amsterdam, 2000, 135- 168.

Excellent microbicidal properties of silver nanoparticles (AgNPs) instigated their use in medicine, cosmetics, textile and food industries. However, detailed information on their fate and effects on the human body is so far unknown. [1] When exposed to biological media, AgNPs are prone to intimate interactions with different biomolecules and biological structures.[2] This study demonstrates possible biotransformation patterns of AgNPs after in vivo exposure. Fate of AgNPs was investigated in ultrapure water, cell culture medium, phosphate buffer, artificial lysosomal fluid, artificial gastric fluid, and liver homogenates by means of agglomeration and dissolution behaviour. For this purpose size distribution, surface charge, Ag+ release and interaction with albumin and glutathione were evaluated using dynamic and electrophoretic light scattering methods, transmission electron microscopy, atomic absorption spectroscopy and proton nuclear magnetic resonance spectroscopy (1H NMR). For the first time, this study evidenced in vivo synthesis of AgNPs in the liver resulting from the interaction of Ag+ with glutathione. First, the binding of glutathione to the surface of AgNPs was investigated on the NPs synthesized by sodium borohydride reduction of silver nitrate. The process of NP formation and glutathione adsorption was tracked by 1H NMR in 20-minute time intervals. Initial and final spectra differ significantly in chemical shifts of C7, indicating the binding through the thiol group. In the second part, AgNPs were synthesized using glutathione as both the reducing and capping agent. This eliminated the interference from sodium borohydride, and demonstrated the potential mechanism of in vivo AgNP formation from ionic silver.

Asphaltenes are the heaviest, most polar and least reactive molecules in crude oil, primarily consisting of carbons and hydrogens, some heteroatoms, such as sulfur, nitrogen, oxygen and traces of transition metals. They may aggregate during the downstream and upstream processes and cause many problems in production, refining and transportation. Asphaltene aggregation highly depends on the chemical nature of the crude oil, temperature and pressure. In this research, concentration dependent diffusion measurements were carried out to determine the lowest aggregation concentration of Middle Eastern asphaltenes and to study how the addition of V(IV), Fe(III) and Ni(II) affects the aggregation process. Asphaltene components were separated by DOSY NMR technique according to their diffusion properties. The influence of T1 relaxation on average diffusion coefficients was investigated by inversion recovery experiments. Changes in diffusion coefficients reflected the formation of different asphaltene types. It is expected that the presented results could throw more light into the asphaltene aggregation mechanism.

The development of artificial anion receptors that mimic natural systems in their ability to efficiently and selectively bind a target anion has recently become an area of intense focus within supramolecular chemistry.1 Cyclic peptides present promising synthetic scaffolds for selective anion binding due to the amide group hydrogen bond properties, and also because of the macrocyclic ring flexibility and the variability of the subunits.2–4 By the combination of the thermodynamic and structural characterization of the cyclopeptide-anion complexes formed in the solution it is possible to obtain a detailed insight into the energetics of complexation and in the relationship of the receptor structure and its affinity towards particular anion. In this work, two cyclopeptide receptors were studied, L1 that contains five lysine subunits with amino groups of the side chains protected by a BOC group (Lys-BOC) and L2 that is comprised of six Lys-BOC subunits. These receptors bind anions directly through interactions with the peptide backbone or with the carbamate protons of BOC groups. Complexation affinities of L1 and L2 ligands toward halogen (Cl–, Br–, I–) and structural anions (ClO4–, HSO4–, H2PO4–, NO3–, NO2–, SCN–) in acetonitrile were investigated by means of mass spectrometry, 1H NMR and isothermal microcalorimetric titrations. More information about the structural characteristics of the cyclopeptide binding sites and microscopic image of the anion binding processes was gained by molecular dynamics simulations with explicit solvent molecules.

19F and 1H NMR experiments were performed to study the mechanism of selected chemical reactions. In the case of the acylation (ferrocenoylation) of purine and pyrimidine nucleobases, the attention has been focused on the regioselectivity/ regiospecificity of the respective reaction. It has been shown that the reaction centre and the product isomers ratio cannot be determined from the isolated weights alone, but the analysis of ”in situ” NMR spectra is required. In the case of chlorination of the 5-fluorouracil, “in situ” NMR data has been generated under actual reaction condition [2]. The existence of the presumed chlorinated intermediates has been confirmed spectrophotometrically, which is necessary to scheme out the full reaction profile. The two cases demonstrate that the information obtained by “in situ” NMR approach may provide the answers to challenging mechanistic or kinetic studies, or may contribute to the optimization of synthetic routes.

Calixarenes are macrocyclic oligomers consisted of four or more phenolic residues linked by methylene bridges in the ortho position and can be easily functionalized to give receptors for various ionic or neutral species. Calixarenes bearing fluorescent moieties can be considered as potentially very sensitive fluorimetric ion sensors due to the high sensitivity of fluorescence spectroscopy and high affinity of these macrocyclic ligands towards cations. [1-3] In the scope of this work, novel fluorescent phenathridine-based calix[4]arene derivatives L1 and L2 were designed and prepared (Figure 1) and their complexation properties towards metal cations in several solvents were investigated. Phenanthridine moities were introduced at a lower calixarene rim and served both as fluorescent probes and parts of cation-binding site. Stability constants of the corresponding complexes were determined by means of fluorimetry, UV spectrophotometry, NMR spectroscopy and isothermal titration calorimetry.

Self-assembly of small organic molecules is one of the most important methods of synthesis of organic nano-structured materials. Based on the rules of supramolecular chemistry, the bottom- up approach to design functional objects at nanoscale is currently producing highly sophisticated materials oriented towards a growing number of applications. These structuring features are nowadays well understood and can be finely controlled in order to introduce and tune functional properties of self-assembled nanomaterials used for a very wide range of applications. Further, such systems exhibit a complex array of morphologies and dynamics and have a huge potential for utilization in various areas of nanotechnology, in development of new materials, diagnostic or "smart" systems for drug delivery, in medicine or in tissue engineering.[1, 2] In recent years, various chiral bis (amino acid) oxamides and other structural types that include amino acid subunits have been investigated as low molecular weight gelators with a particular focus on stereochemical effects and solvent influence on gel systems. [3–5] The molecular self-assembling and supramolecular interactions in the new supramolecular systems were studied by various spectroscopic methods e.g. NMR, FTIR, CD, that proved the self-aggregation of molecules. The contribution made by using of various NMR methods in the characterization of such systems will be shown through several examples.

Calixarenes are well known as efficient cation receptors. Affinity of calixarene derivatives towards cations in different solvents has been extensively studied. However, the major drawback in their wide application as cation receptors is their insolubility or low solubility in water. In order to overcome this obstacle, calix[4]arenes with carbohydrate units attached to the lower rim, that are soluble in water, were recently synthetized [1]. In order to gain better insight in molecular basis of their affinity and selectivity towards cation complexation, conformational analyses of several such ligands that are soluble in water were performed. Their conformational space was studied in water and in methanol. Conformational searches were conducted using Monte Carlo Multiple Minimum (MCMM) algorithm available within MacroModel software [2]. Solvent effects were modelled using continuum solvent models. In some cases, explicit solvent molecules, water or methanol, were present during the simulation in order to model the competition between sodium cation and solvent molecule for complexation. Cluster analyses of obtained results, as well as detailed analyses of intramolecular hydrogen bonds were performed. Computational results were compared and validated with available experimental data which consisted of different titration methods and NMR data. [1] N. Cindro, J. Požar, D. Barišić, N. Bregović, K. Pičuljan, R. Tomaš, L. Frkanec, V. Tomišić Org. Biomol. Chem., 2018, 16, 904. [2] MacroModel, Schrödinger, LLC, New York, NY, 2017.

Acid-base reactions are ubiquitous in chemistry, often playing the key role in biological systems, in the development of new pharmaceuticals or materials, etc. Although (de)protonation reactions in water are among the most studied equilibria, analogous investigations in non-aqueous media are rather scarce. This is partly due to experimental difficulties regarding the potentiometric measurement of pH, but also because the complexity of the corresponding equilibrium systems increases in such solutions. Namely, the protonation constants are much higher in organic solvents in comparison to water, and many acids are prone to homoconjugation (interaction with their conjugated bases) and dimerization. NMR spectroscopy has been extensively used as a tool for quantitative thermodynamic characterization of diverse reactions. However, its utilization for the study of (de)protonation equilibria commonly includes measurement of pH (pD) dependence of 1H NMR spectra, and it is in most cases limited to aqueous systems. In this work, the characterization of acid-base behavior of rather important and extensively studied organic (acetic acid) and inorganic (phosphoric acid) acids in dimethyl sulfoxide and acetonitrile was carried out by means of several experimental methods (UV and NMR spectroscopies, ITC, and conductometry). In addition, the deprotonation of aromatic urea derivatives acting as anion receptors was studied in DMSO using competitive NMR titrations. The focus of the talk will be on the results obtained by NMR spectroscopy which will be compared to those gathered by other techniques. The concepts, advantages, and limitations of the NMR-spectroscopic investigations of proton transfer, homoconjugation, and dimerization equilibria of the studied systems will be discussed in detail.

Prion diseases are a group of fatal neurodegenerative disorders that can be of sporadic, genetic or acquired origin. The key molecular event in prion diseases is the conformational conversion of the physiological cellular prion protein, PrPC, into a disease- associated form, prion or PrPSc (scrapie PrP). Understanding of the earliest stages of the conformational changes leading to spontaneous generation of prions in genetic prion diseases, which are linked with mutations in the human prion protein gene, may benefit from structural characterization of various human (Hu) PrP variants. We determined NMR structures of the truncated recombinant HuPrPs (residues 90-231) with pathological Q212P [1] and V210I [2] mutations associated with Gerstmann- Sträussler- Scheinker (GSS) syndrome and familial Creutzfeldt- Jakob disease (CJD), respectively, and of HuPrP with naturally occurring E219K polymorphism [3] considered to act protectively against sporadic CJD. Comparison of 3D structures of HuPrP variants with the WT HuPrP revealed that mutations do not affect global architecture of the protein. However, 3D structures of HuPrPs with pathological Q212P and V210I mutations highlighted several common structural perturbations. These include disruption of hydrophobic contacts at the α2-α3 inter-helical interface, loosening of tertiary contacts between the β2-α2 loop and the C-terminus of helix α3 and increased exposure of hydrophobic residues to solvent. In addition, we determined NMR structure of HuPrP(V210I) under physiological pH conditions which was found to exhibit higher structural stability when compared to the structure of the same protein at pH 5.5 [4].

Crude oil, its residues and products are one of the most complex compound mixtures in nature. Over the past couple of years, one of the main goals in petroleum industry has been to transfer heavy crude oil residues into light crude oil distillates. Asphaltenes, which are the heaviest and least reactive molecules in crude oils, cause many problems during transport and production. Owing to complex asphaltene structures, their characterization posts a major challenge in petroleum industry. In this research, concentration dependent diffusion measurements have been performed to determine the lowest aggregation concentration of asphaltenes and influence of magnetic field strength on aggregation process. Asphaltene components were separated by DOSY NMR technique according to their different diffusion coefficients. Their hydrodynamic radii and molecular weight were then estimated by using Stokes-Einstein equation. Changes in diffusion coefficients reflected the formation of different asphaltene types. It is expected that the presented results will contribute to better understanding of asphaltene aggregation process.

The coordination chemistry of silver(I) complexes is very active research area, since these compounds possess antimicrobial and antitumor properties. The well known flexibility of the coordination sphere of the silver atom as well as different role/assistance of the nitrate ion (bridging, monodentate, bidentate ligand) provide the possibility of forming different structured compounds. The halogen atoms (Cl, Br, I) substituted on the pyridine ring (the basic scaffold for many biologically active substances), moderate compounds properties and behavior through halogen and hydrogen bonding. All this together gives rise to design structure property relationships. Presentation shows structural analysis and antibacterial activity results obtained for new AgNO3 complexes with halopyridine ligand of the general formula [Ag(NO3)(Xpy)2] and [Ag(NO3) (X2py)2]. The isolated products were characterized by means of mass spectrometry, multinuclear NMR spectroscopy (1H, 13C, 15N, 109Ag) in solution and by X-ray diffraction data on single crystal.

The Conference aims to provide an interactive forum for presenting various aspects of using NMR spectroscopy, from theory to practical applications encouraging the exchange of ideas and facilitating collaboration among people interested in NMR. It is our goal to gather researchers, application scientists, instrumentation developers and students from universities, research institutes and industry to discuss the topics on the frontiers of NMR spectrosopy.

Carbohydrazide, i.e. 1, 3-diaminourea, represents a versatile building block for the design of symmetrical and asymmetrical urea- based componds. [1] Introduction of specific groups into the structure allows one to fine- tune the desired properties of such systems. For example, pyridine functionalized carbohydrazides proved to be an effective anion receptors, with the ability to stabilize small anion-water clusters.[2] On the other hand, monosubstituted pyridine based derivatives showed to be exquisite ligands for the design of dynamic metal-organic frameworks with intriguing anion-switchable properties.[3] Within this investigation we explored the synthetic opportunities towards selected mono- and bis- substituted carbonohydrazides, both symmetrical and asymmetrical ones, derived from 2, 3- and 2, 4- dihydroxybenzaldehyde, pyridinecarbaldehyde and carbohydrazide.[4] Dihydroxybenzaldehydes in combination with carbohydrazide yielded preferably bissubstituted symmetrical products, whereas in the case of pyridine based aldehydes monosubstituted derivatives were also isolated. The latter were then utilized as starting materials for the synthesis of bissubstituted asymmetrical compounds. All isolated products were thoroughly investigated in the solid-state by means of infrared (IR) spectroscopy, thermal analysis, powder X-ray diffraction (PXRD) and when suitable via single-crystal X-ray diffraction (SCXRD). The results point out to interesting differences in conformation between the symmetrical and asymmetrical derivatives in the solid state. Finally, the obtained compounds were explored in solution by appropriate one- and two- dimensional NMR techniques

Aromatic C-nitroso compounds can exist as monomers or Z- and E-azodioxides (dimers). The preferred form in solution at ambient temperature is monomeric while lowering of temperature or crystallization favors dimerization. Azodioxides undergo solid-state photodissociation to corresponding monomers under cryogenic conditions, which again dimerize by warming. Aromatic C- nitroso compounds with two or more nitroso groups could be used as building blocks for supramolecular structures that could be disassembled or reassembled by external stimuli such as UV radiation or heat. In the present work, we studied solution-state monomer-dimer equilibrium of several new aromatic dinitroso compounds that differ in spacer between two aromatic rings (Scheme 1). In order to observe formation of dimers, we recorded 1H and COSY NMR spectra in chloroform-d5 at ambient and low temperatures. Inspection of NMR spectra revealed that by lowering of temperature new signals appear in the spectra that could be assigned to dimers. Signals of dimers disappear after warming the solution to room temperature. The NMR spectra of monomers and dimers were also modelled using density functional theory. Solution-phase (SMD) optimizations, followed by GIAO calculations, were done at the ωB97-XD/6-311G(d, p) level of theory. In case of dimers, multiple conformers had to be considered in order to obtain a good agreement (MUE < 0.1 ppm) between calculated and experimental spectra.

Traditional synthetic procedures in organic chemistry are generally very successful but global problems of pollution and growing energy demand have compelled the chemical industry to search for new, more efficient and “greener” synthetic methods. Mechanochemical reactions are induced by the direct absorption of mechanical energy and they are mainly promoted by hand grinding or mechanochemical milling. Mechanochemical organic reactions are carried out without the need for solvents or conventional catalysts, and most often feature higher product yield in shorter reaction time. [1] Contrary to the wide knowledge about organic reactions in solution, mechanisms of mechanochemical reactions are still mostly unknown. Only the recently developed in situ monitoring techniques[3] started to unveil the mechanisms of organic mechanochemical reactions, leading to wider application of this methodology in modern material and pharmaceutical industry. [4] Here we present mechanochemical reactions between acyl azide and primary amine as a model nucleophilic substitution reaction on the carbonyl group. We have examined the influence of different additives on reaction time and yields using in situ Raman spectroscopy monitoring and the products were confirmed by 1H and 13C NMR spectroscopy. As amide derivatives are widely investigated as receptors for anions, [5] we studied affinity of the prepared compounds towards biologically important acetate and dihydrogen phosphate anions in solution using 1H NMR spectroscopy.

Calixarenes are macrocyclic oligomers which consist of four or more phenolic residues linked by methylene group in the ortho position. Many calixarene derivatives are known to be very efficient, and, in some cases, selective binders of ions and neutral molecules. In this lecture the comprehensive investigation of several calix[4]arene complexation reactions will be described. The thermodynamic data (complex stability constants and derived reaction Gibbs energies, reaction enthalpies and entropies) determined by means of UV and NMR spectroscopies, fluorimetry, potentiometry, conductometry, and microcalorimetry will be correlated with structural results obtained by X- ray crystallography, NMR, and computational methods (DFT and molecular dynamics). The intra- and intermolecular hydrogen-bonding and solvent effects (especially specific solvent-solute interactions) on the equilibria of binding reactions will be particularly addressed. The results of the above-mentioned studies have clearly indicated how remarkable and complex the influence of the solvent on the ion-hosting abilities of the calixarene derivatives, and macrocycles in general, can be. They have also suggested that integrated and comprehensive experimental and computational investigations can provide a rather detailed insight into the ligand properties and reactivities, i.e. the factors governing the complexation processes. This can serve as a basis for targeted design of efficient and selective supramolecular receptors.

U okviru proučavanja fotokemijskih reakcija heterostilbenskih spojeva [1] studirani su stiriltiofeni [2], kao i utjecaj položaja sumpora [3] u tiofenskom prstenu na sam tijek reakcije. U ovom radu pripravljeni su novi 2- i 3- ditiofenski derivati o-divinilbenzena i podvrgnuti fotokemijskom ispitivanju. Tijekom osvjetljavanja 2, 2'-(1, 2-fenilendivinilen)ditiofena (1), nakon primarne cis/trans- izomerizacije, kao posljedica [1, 6] elektrociklizacije i 1, 5 H pomaka formira se dihidronaftalenska struktura 2 kao glavni produkt, uz tragove više neidentificiranih dimernih produkata. Za razliku od spoja 1, 3, 3'-(1, 2-fenilendivinilen)ditiofen (3) fotokemijski reagira na potpuno drugi način i nastaje biciklo[3.2.1.]oktadienska struktura 4 kao glavni fotoprodukt, uz tragove dimernih produkata. Ovaj fotokemijski pristup, ovisno o položaju heteroatoma u prstenu i strukturi početnih spojeva, omogućuje nastajanje novih kompliciranih heteropolicikličkih struktura, koje se inače klasičnim sintetskim postupkom mnogo teže dobivaju.

Phenyl-silsesquioxanes are hybrid organic- inorganic compounds that can thermally soften, and whose softening temperature depends on the level of condensation, which can be controlled by conditions of synthesis [1]. Phenyl-silsesquioxane particles find application in preparation of transparent thick films or matrices for functional thin films. Other polysilsesquioxanes also can have softening temperature, which has been shown to depend on the size of organic supstituent [2]. In order to control the softening temperature and thermal stability of the phenyl-silsesquioxane particles, they were modified with alkyl chains of varying lengths. Polysilsesquioxane hybrid particles were prepared by two-step acid-base catalysed sol-gel process, with ethanol as solvent. Alkyl-triethoxysilanes, R-Si(OC2H5)3, R = CH3, C2H5, C5H11 and C8H17, were mixed with phenyl-triethoxysilane, C6H5-Si(OC2H5)3, in a constant 1:4 ratio, hydrolysed with aqueous solution of HCl and then condensed with aqueous solution of NH4OH. Resulting particles were dried, investigated by scanning electron microscopy, differential scanning calorimetry and combined differential thermal and thermogravimetric analysis. Pentyl- and octyl- modified particles were found to have less homogeneous size distribution, presumably because long alkyl chains were less miscible with other components resulting in less homogeneous initial mixture. Increased size of alkyl chains also presents greater sterical hindrance to condensation of phenyl- silsesqui-oxanes, so the softening temperature decreases from 380 °C for methyl-modified particles to 50-100 °C for octyl-modified ones. Thermal stability of alkyl-modified particles was expected to decrease, since alkyl-silsesquioxanes degrade at much lower temperatures. Methyl- and ethyl-modified particles start to degrade at 400 °C, same as unmodified phenyl-silsesquioxane, while pentyl- and octyl-modified particles start to degrade at 250 °C, which corresponds to degradation of pentyl- and octyl-silsesquioxanes. Therefore it can be supposed that longer alkyl chains are exposed on the surface of the particles while shorter ethyl and methyl groups are in some way shielded by phenyl groups.

Visoka razina atmosferskog ozona onečišćujuće i snažno utječe na kvalitetu zraka posebno u ljetnim mjesecima, te utječe na ljudsko zdravlje, vegetaciju i ostale tvari.

Atomic force microscopy (AFM) in combination with other well established techniques such as transmission electron microscopy (TEM), infrared spectroscopy (FT-IR), X-ray diffraction (XRD), Differential thermal gravimetry (DTG), electron diffraction (ED), scanning electrom microscopy (SEM), were used to investigate the very early stages of nucleation and crystallization on the surface of gel precursor in the synthesis of zeolite A and silicalite-1. Analysis of the precipitated sodium aluminosilicate /silicate precursor (gel) has shown that predominantly true amorphous phase of the gel contains small proportions of partially crystalline (“quasi-crystalline”) or even fully crystalline phase. In the case of the gel precursor for the synthesis of zeolite A is also found that the freshly prepared gel is mainly composed of disc-shaped primary particles, but also partially or even fully crystalline entities were observed by AFM analysis. AFM analysis of the solids separated from the hydrogel at various stages of its hydrothermal treatment (heating at 80o C) indicates that the particles of the partially and/or fully crystalline phase are nuclei for further crystallization of zeolite [1]. In this study is also monitored the behavior of the silicate species in relation with the structure directing agent TPABr during the formation of nuclei for the crystallization of silicalite 1. It is found that TPA+ cations linked together with silicate species by Vand der Waals forces and form short range ordered units having size below 10 nm that correspod to primary building units. The units agglomerate and form particles having size about 10 nm that was confirmed by AFM and TEM. These entities acts as the nucleation centers for the crystallization of silicalite-1 [2]. [1] Kosanović, C., Bosnar, S., Subotić, B., Svetličić, V., Mišić, T., Drazić, G. Havancsak, K., Microporous and Mesoporous Materials, 110 (2008)177-185. [2] De Moor, P-P. E. A., Beleen, TPM, Komanschek, B. U. , Beck, L. W., Wagner, P, Davis, M. E., Van Santen, R. A., Chem Eur. 1999, 5, 2083-2088.

Hematite (a-Fe2O3) is widespread mineral in nature (rocks, sediments, soils). It is also important material in many technological applications. Chemical and physical properties of a-Fe2O3 depend on the route of chemical synthesis. In the present work, the hydrothermal crystallization of a-Fe2O3 from dense b-FeOOH suspensions was investigated. a-Fe2O3 particles in the form of double spheres with the ring were formed at 160 oC for 24 h. The orientation effect of a-Fe2O3 subunits in double spheres with the ring was observed. a-Fe2O3 double spheres with the ring also showed two narrow particle size distributions. b-FeOOH transformed to a-Fe2O3 by the dissolution/repreciptation mechanism. The influence of inorganic anions on the phase composition, size and morphology of the particles during the transformation b-FeOOH to a- Fe2O3, was also investigated. With increased concentration of phosphate anion the crystallization of a-Fe2O3 was strongly suppressed. Tendency to the formation of ferrihydrite was noticed. The size and morphology of a-Fe2O3 particles were strongly influenced with added ammonium amidosulphonate (AAS). Up to 24 h of autoclaving the peanut-type a-Fe2O3 particles of good uniformity were obtained. They consisted of laterally arrayed primary a-Fe2O3 particles. Porosity of peanut-type a-Fe2O3 particles was visible. With prolonged autoclaving time up to 72 h and starting concentration 0.1 M AAS, a gradual formation of interconnected (with neck) double cupolas was observed. The cross-section of these cupolas showed that they consisted of linear chains of small interconnected a-Fe2O3 particles directed from the center towards the surface of cupola.

Različite voltametrijske tehnike karakterizirane su različitim eksperimentalnim parametrima (vremenskim i potencijalnim), dok suvremene živine elektrode (statična živina kap, SMDE) uključuju osim toga i mogućnost odabira veličine kapi. Poznato je da se neki parametri mogu podešavati, neki se ne mogu mijenjati ali se zna njihova vrijednost, dok se neki parametri ne mogu niti podešavati, niti im se zna točna vrijednost (vrijeme stvaranja kapi, a u nekim slučajevima i način uzorkovanja struje). Za potpunu interpretaciju eksperimentalnih rezultata i pripadajuće matematičke simulacije, potrebno je poznavati sve veličine koje utječu na oblik voltamograma. Iz tog razloga, pokazalo se potrebnim ispitati utjecaj različitih skrivenih parametara na rezultate voltametrijskih mjerenja, kao i moguće određivanje istih.

Kemija heterocikla smatra se jednom od najkompleksnijih grana organske kemije [1]. Oksazoli su peteročlani aromatski spojevi sa dva heteroatoma, kisikom i dušikom, pojavljuju se u velikom broju u prirodi prisutnih spojeva [2] i zanimljivi su zbog visoke biološke aktivnosti [3].Novi, 4, 5-diaril-2[2-(2- vinilfenil)etenil]oksazoli sintetizirani su u svrhu istraživanja njihovih intramolekularnih reakcija cikloadicija uz korištenje svjetla kao reagensa. Spojevi su priređeni nizom reakcija, od zatvaranja heterocikločkog prstena do produženja konjugiranog sustava [4, 5], te osvjetljavani u kemijskom reaktoru. Dobiveni su novi, zanimljivi heterociklički derivati koji su okarakteriztirani modernim spektroskopskim metodama. [1] A.Katrizky, C. Rees, Comprehensive oxazole and bis-oxazole heterocyclic chemistry, 1984, Volume 6, 177 - 234 [2] Vince S.C. Yeh, Tetrahedron, 2004, 60, 11995 - 12042 [3] P. Wipf, Chemical Review, 1995, 95, 2115 – 2134 [4] W. Pei, S. Li, X. Nie, J. Pei, B. Chen, J. Wu, X. Ye, Synthesis, 1998, 1298 – 1304 [5] M. Šindler-Kulyk, D.Vojnović, N. Defterderović, Ž. Marinić, D. Srzić, Heterocycles, 1994, 38, 1791 - 1796