{Synthesis and characterization of palladium(II) complexes with glycine coumarin derivatives} J. Serb. Chem. Soc. 81 (12) 1383–1392 (2016) UDC 546.982+547.587.51+547.466.22: JSCS–4935 548.7:66.094.941 Original scientific paper 1383 Available on-line at: www.shd.org.rs/jscs (CC) 2016 SCS. Synthesis and characterization of palladium(II) complexes with glycine coumarin derivatives DANIJELA LJ. STOJKOVIĆ1#, ALESSIA BACCHI2, DAVIDE CAPUCCI2, MILICA R. MILENKOVIĆ3#, BOŽIDAR ČOBELJIĆ3#, SREĆKO R. TRIFUNOVIĆ1#, KATARINA ANĐELKOVIĆ3#, VERICA V. JEVTIĆ1#, NENAD VUKOVIĆ1, MILENA VUKIĆ1 and DUŠAN SLADIĆ3*# 1Department of Chemistry, Faculty of Science, University of Kragujevac, Radoja Domanovića 12, 34000 Kragujevac, Serbia, 2Dipartimento di Chimica, University of Parma, Parco Area delle Scienze 17 A, I 43124 Parma, Italy and 3Faculty of Chemistry, University of Belgrade, Studentski trg 12–16, 11000 Belgrade, Serbia (Received 15 September, revised 25 September, accepted 27 September 2016) Abstract: A Pd(II) complex with methyl 2-([1-{2,4-dioxochroman-3-ylidene}- ethyl]amino)acetate was synthesized. The structures of both the ligand and its Pd(II) complex were determined by elemental analysis, and IR and NMR spec- troscopy. Recrystallization of the Pd(II) complex from DMF/water solution resulted in its hydrolysis and the formation of the dimethylamine (2-[{1-(2,4- -dioxochroman-3-ylidene)ethyl}amino]acetato)palladium(II) complex, the struc- ture of which was determined by elemental analysis, IR, 1H- and 13C-NMR spectroscopy and X-ray analysis. Keywords: coumarin-derived ligands; crystal structure; mechanism of hydro- lysis. INTRODUCTION Coumarins (derivatives of 2H-1-benzopyran-2-one) are of great interest in medicinal chemistry because of their wide range of pharmacological activity.1–6 Metal complexes with coumarin derivatives have been investigated because of their anticoagulant,7 antimicrobial8 and antitumor activities.9–11 Among the com- plexes with coumarin derivatives, Pd(II) complexes have attracted considerable attention because of their significant antitumor activity.12–15 Following these findings, in this work the synthesis of methyl 2-([1-{2,4-dioxochroman-3-yli- dene}ethyl]amino)acetate (HL1) and its chlorido Pd(II) complex (1) are reported. Attempts to obtain monocrystals of complex 1 from DMF/water solution resulted in its hydrolysis and the formation of dimethylamine(2-[{1-(2,4-dioxochroman- * Corresponding author. E-mail: dsladic@chem.bg.ac.rs # Serbian Chemical Society member. doi: 10.2298/JSC160915087S 1384 STOJKOVIĆ et al. Available on-line at: www.shd.org.rs/jscs (CC) 2016 SCS. -3-ylidene)ethyl}amino]acetato) palladium(II) complex (2). All the obtained compounds were characterized by elemental analysis, and IR and NMR spectro- scopy. The crystal structure of complex 2 was determined by X-ray analysis. EXPERIMENTAL Materials and methods Hydrochlorides of glycine and glycine methyl ester, triethylamine, methanol, ethanol, tolu- ene, acetone and potassium tetrachloridopalladate(II) were obtained from Sigma–Aldrich. 3- -Acetyl-4-hydroxycoumarin was synthesized according to a previously described procedure.16 Elemental analyses were performed on a Vario EL III C,H,N elemental analyzer. Melting points of the ligands were determined using a Kofler hot stage apparatus. IR spectra were run on a Perkin–Elmer Spectrum One FT-IR spectrometer using the KBr pellet technique (4000– –400 cm-1). 1H-NMR (200 MHz) and 13C-NMR (50 MHz) spectra of the HL1 ligand were recorded on a Varian Gemini 200 spectrometer (Varian, Palo Alto, CA, USA) in CDCl3 using TMS as an internal standard for 1H and 13C. The 1H-NMR (500 MHz) spectrum of complex 1 was recorded on a Bruker Avance 500 spectrometer in DMSO-d6 using TMS as an internal standard. Due to the low solubility of complex 1 in DMSO, it was not possible to obtain its 13C-NMR spectrum. 1H-NMR (500 MHz), 13C NMR (125 MHz) and 2D NMR spectra (COSY, HSQC) of complex 2 were recorded on a Bruker Avance 500 spectrometer in DMSO-d6 using TMS as an internal standard for 1H and 13C. Analytical TLC was performed on silica gel (Silica gel 60, layer 0.20 mm, Alugram Sil G, Macherey–Nagel, Germany). The visualization of TLC plates was performed using a UV lamp at 254 and 365 nm (VL-4.LC, 365/254, Vilber Lourmat, France). Characterization data are of synthesized compounds are given in Supplementary material to this paper. Synthesis of methyl 2-([1-{2,4-dioxochroman-3-ylidene}ethyl]amino)acetate (HL1) A mixture of 3-acetyl-4-hydroxycoumarin (0.5 g, 2.45 mmol), the hydrochloride of glycine methyl ester (2.45 mmol) and trimethylamine (0.2 g, 2.00 mmol) in methanol (50 mL) was refluxed for 2 h. The progress of the reaction was monitored by TLC (toluene:acetone volume ratio of 8:2). After completion of the reaction, evaporation of solvent to half of the volume and addition of 5 mL of water, the obtained white solid was filtered, dried and recrystallized from 96 % ethanol. Synthesis of 2-([1-{2,4-dioxochroman-3-ylidene}ethyl]amino)acetic acid (H2L2) Into a solution of 3-acetyl-4-hydroxycoumarin (0.5 g, 2.45 mmol) in methanol (50 mL), glycine (0.18 g, 2.45 mmol) was added. The pH of the reaction mixture was adjusted by the addition of three drops of conc. HCl. The clear, colorless solution was refluxed for 3 h. After six days, a white solid precipitated from the reaction solution. Synthesis of chlorido(methyl 2-[{1-(2,4-dioxochroman-3-ylidene)ethyl}amino]acetate) palla- dium(II) complex (1) Potassium tetrachloridopalladate(II) (0.05 g, 0.153 mmol) was dissolved in 10 mL of water and the same amount of enamine HL1 (0.153 mmol) dissolved in methanol (10 mL) was added. The mixture was stirred for 3 h whereby a yellow precipitate was obtained. The pre- cipitate of complex 1 was filtered off and washed with a small amount of methanol. Synthesis of dimethylamine(2-[{1-(2,4-dioxochroman-3-ylidene)ethyl}amino]acetato)-palla- dium(II) complex (2) Recrystallization of complex 1 from DMF/water (1:1 volume ratio) during seven days at room temperature resulted in the formation of crystals of complex 2. PALLADIUM(II) COMPLEXES 1385 Available on-line at: www.shd.org.rs/jscs (CC) 2016 SCS. Crystallographic structure determination Single crystal X-ray diffraction data were collected using MoKα radiation (λ = 0.71073 Å) at T = 293 K on an APEX2 diffractometer with CCD area detector. The collected inten- sities were corrected for Lorentz and polarization factors and empirically for absorption using the SADABS program.17 Structures were solved by direct methods using SIR201118 and refined by full-matrix least-squares on all F2 using SHELXL9719 implemented in the Olex2 package.20 Hydrogen atoms were introduced in the calculated positions. Anisotropic displace- ment parameters were refined for all non-hydrogen atoms. Hydrogen bonds were analyzed with SHELXL9719 and use was made of the Cambridge Crystallographic Data Centre pack- ages21 for analysis of crystal packing. The crystal data and structure determination results are summarized in Table S-I of the Supplementary material to this paper. RESULTS AND DISCUSSION Synthesis Reaction of equimolar amounts of 3-acetyl-4-hydroxycoumarin and hydro- chloride of glycine methyl ester in the presence of triethylamine in refluxing methanol yielded ligand HL1 (Scheme 1a). Ligand H2L2 was obtained in the reaction of 3-acetyl-4-hydroxycoumarin and glycine in methanol in the presence of a catalytic amount of hydrochloric acid (Scheme 1b). Complex 1 was syn- thesized in the reaction of ligand HL1 and potassium tetrachloridopalladate(II) in a 1:1 mole ratio in water/methanol (1:1 volume ratio) solution (Scheme 2). Com- plex 2 was obtained during the recrystallization of complex 1 from DMF/water mixture. In addition, an attempt was made to synthesize complex 2 in the react- ion of ligand H2L2, potassium tetrachloridopalladate(II) and dimethylamine or its hydrochloride in a 1:1:1 mole ratio in water/methanol (1:1 volume ratio) solution. Unfortunately, complex 2 could not be obtained in this way under any experi- mental conditions. Scheme 1. Synthesis of ligands HL1 and H2L2. 1386 STOJKOVIĆ et al. Available on-line at: www.shd.org.rs/jscs (CC) 2016 SCS. Scheme 2. Synthesis of Pd(II) complex 1. IR spectra The IR spectrum of HL1 showed a broad band at 3406 cm–1 corresponding to the stretching vibrations of the NH group. Stretching vibrations of the carbonyl group of glycine methyl ester and coumarin lactone were observed at 1748 and 1720 cm–1, respectively. In the IR spectrum of H2L2, the broad band at 3502 cm–1 corresponds to vibrations of the OH group from its carboxylic part and vibration of the NH group. This band was absent in the IR spectrum of complex 2, indicating coor- dination of ligand in deprotonated form. Instead of this, a sharp band appeared at 3227 cm–1, corresponding to stretching vibrations of NH from coordinated dimeth- ylamine. Coordination of carboxylate resulted in a bathochromic shift of ν(C=O) from 1740 cm–1 in the spectrum of the H2L2 ligand to 1690 cm–1 in the spectrum of complex 2. A band at 1650 cm–1 originating from the imino group ν(C=N) of the uncoordinated ligand was shifted to 1660 cm–1. Moreover, coordination of the deprotonated enol group of H2L2 resulted in a shift of ν(C–O) from 1224 cm–1 in the spectrum of H2L2 to 1245 cm–1 in the spectrum of complex 2. NMR spectra In the 1H-NMR spectrum of ligand HL1, the signal of the methyl protons from C2′ appeared at 2.70 ppm, while the signal of the methyl protons from the ester group (H3″) was observed at 3.86 ppm. The 1H-NMR spectrum of HL1 showed resonances at 12.51 and 14.65 ppm corresponding to the OH and NH groups of its tautomers, respectively. The observed δ value of the NH proton indicates E conformation of HL1 and intramolecular hydrogen bonding with the keto oxygen atom.22 Previously reported X-ray and DFT study of chromone derivatives showed that the keto tautomer with N–H…O hydrogen bonds is energetically more stable than the enol form containing O–H…N hydrogen bonds.23 Based on these results, it could be assumed that the keto form is the main tautomeric form of the HL1 ligand. In the 13C-NMR spectrum of ligand HL1, the C1′ carbon showed resonance at 177.5 ppm, whereas the signal of the methyl carbon C2′ was noted at 18.9 ppm. The signals of two carbonyl groups from the 2,4-dioxochroman moiety, lac- tone (C2) and ketone (C4), appeared at 162.5 ppm and 182.2 ppm, respectively. PALLADIUM(II) COMPLEXES 1387 Available on-line at: www.shd.org.rs/jscs (CC) 2016 SCS. In the 1H-NMR spectrum of complex 1, signals of hydrogen atoms from the OH and NH groups (12.51 and 14.65 ppm, respectively) of the ligand were abs- ent, indicating that the ligand was coordinated in the deprotonated form. Coor- dination of HL1 through the nitrogen atom from the imino group resulted in downfield shift of the signals of methyl H2′ and methylene H1″ hydrogen atoms. In the 1H-NMR spectrum of complex 1, the signal of the methyl group from the ester part of the ligand was shifted upfield, indicating that the ester carbonyl oxy- gen was involved in the coordination. Coordination of the oxygen atom from C4 of the coumarin moiety resulted in an upfield shift of the H5 signal and down- field shifts of the H6, H7 and H8 signals. From the 1H-NMR spectrum of complex 2, it could be seen that the ligand H2L2 was coordinated in the deprotonated form since the signals of acidic pro- tons were absent. The signal of the hydrogen atoms from the methylene group H1″ was shifted downfield due to coordination of the carboxylate oxygen atom. Coordination of ligand through the nitrogen atom of the imino group resulted in an upfield shift of the methyl H2′ signal. The upfield shift of the H5 signal and the downfield shift of the H6, H7 and H8 signals indicate coordination of the oxygen atom at C4 in the coumarin moiety. The signals of methyl groups and NH from dimethylamine ligand appeared at 2.40 and 2.52 ppm, respectively. Thus, the NMR spectral data indicated coordination of ligand H2L2 via the imine nitro- gen atom, the oxygen atom from C4 and the carboxylic oxygen atom. X-Ray crystallographic analysis of complex 2 In complex 2 (Fig. 1), the Pd(II) cation is coordinated by one ligand mole- cule through the oxygen atom of the keto group from the 2,4-dioxochromane moiety, through the iminic nitrogen atom, and through the carboxylic oxygen atom; one molecule of dimethylamine completes the metal environment, where the square planar coordination of the metal cation shows two oxygen atoms and two nitrogen atoms respectively opposed. A non-coordinating water molecule Fig. 1. Molecular structure and atom labeling of compound 2. Thermal ellipsoids are at the 50 % probability level. 1388 STOJKOVIĆ et al. Available on-line at: www.shd.org.rs/jscs (CC) 2016 SCS. completes the asymmetric unit. A Mogul21 check of the molecular geometry showed no significant deviations from the CCDC average values for all the bond- ing parameters, apart from the angles C4–C3–N1, O5–C6–O4 and C15–N2–C14, which are statistically smaller than the average, probably due to the mutual repulsion of C4 and O4, and to the coordination of N2. The association of molecules in the crystal is driven by intermolecular hydrogen bonds between the coordinated dimethylamine N2–H and the carbo- xylate O1 (N2…O1(i) = 2.997(8) Å, N2–H…O1(i) = 157(5)°, i = –x+2, –y+1, –z), forming a supramolecular centro-symmetric dimer; the dimers are bridged by water molecules acting as hydrogen bond donors, interacting with the carbo- xylate oxygen O1 (O6··O1 = 2.84(1) Å, O6–H…O1 = 142.1(9)°) and the carbo- nylic O4 of an adjacent molecule (O6··O4(ii) = 3.00(1)Å, O6–H…O4(ii) = = 172.1(9)°, ii = x+1/2, –y+1/2, z–1/2), forming layers which expose the dimeth- ylamine methyl groups and the water oxygens at the surfaces (Fig. 2). Fig. 2. Crystal packing of compound 2, showing hydrogen bond layers made of dimers (in orange) bridged by water molecules. Reaction mechanism Considering the mechanism of the hydrolysis reaction that occurred during the recrystallization of complex 1 in the DMF/water solution, it could be assumed that the cationic complex 3 was initially formed in the substitution reaction between the chlorido ligand and a water molecule (Scheme 3). In complex 3, Pd(II) acts as a Lewis acid, which polarizes the ester carbonyl group and activates its carbon atom toward attack by a water molecule from the solvent. Hyd- rolysis of the ester group of complex 3 leads to the formation of the neutral complex 4, which catalyzes the hydrolysis of the amide bond of dimethylform- amide. There are two possible reaction pathways (A and B) for the hydrolysis of dimethylformamide by complex 4 (Scheme 4). One of them (pathway A) involves the substitution of water molecule with carbonyl group of dimethylformamide, which is followed by an external attack of the polarized amide carbon atom by a PALLADIUM(II) COMPLEXES 1389 Available on-line at: www.shd.org.rs/jscs (CC) 2016 SCS. Scheme 3. Mechanism of ester bond hydrolysis in complex 1. Scheme 4. Mechanism of amide bond hydrolysis catalyzed by complex 4. 1390 STOJKOVIĆ et al. Available on-line at: www.shd.org.rs/jscs (CC) 2016 SCS. water molecule from the solvent. In the second possible reaction pathway (path- way B), coordination of water molecule to Pd(II) in complex 4 enhances its nuc- leophilicity and facilitates its attack of the amide carbon atom of uncoordinated dimethylformamide. The replacement of the water molecule in complex 4 by the dimethylamine formed in the hydrolysis reaction led to the formation of complex 2. CONCLUSIONS The synthesis and structural characterization of methyl 2-([1-{2,4-dioxo- chroman-3-ylidene}ethyl]amino)acetate (HL1) and 2-([1-{2,4-dioxochroman-3- -ylidene}ethyl]amino)acetic acid (H2L2) are presented herein for the first time. Complex 1 was synthesized in the reaction of the HL1 ligand and potassium tetrachloridopalladate(II) (mole ratio 1:1). Recrystallization of complex 1 from a DMF/water solution produced complex 2. X-Ray crystallographic analysis of complex 2 showed that the Pd(II) cation was coordinated by one HL1 ligand molecule through the oxygen atom of the keto group from the 2,4-dioxochro- mane moiety, through the iminic nitrogen atom, and through the carboxylic oxy- gen atom. The square planar environment around the metal ion was completed with one molecule of dimethylamine. During the in situ synthesis starting from potassium tetrachloridopalladate(II), ligand H2L2 and dimethylamine or its hyd- rochloride complex 2 were not obtained. Considering the mechanism of the hyd- rolysis reaction that occurred during the recrystallization of complex 1 from the DMF/water solution, two possible reaction pathways (A and B) for the hydrolysis of dimethylformamide catalyzed by Pd(II) were proposed. SUPPLEMENTARY MATERIAL Crystallographic data (excluding structure factors) for compound 2 were deposited with the Cambridge Crystallographic Data Centre as supplementary publication No. CCDC 1503280. Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: (+44) 1223-336-033; e-mail: deposit@ccdc.cam.ac.uk). Crystal data, structure refinement for 2 and the IR and NMR data for the synthesized compounds are available electronically at the pages of journal website: http:// //www.shd.org.rs/JSCS/, or from the corresponding author on request. Acknowledgements. This work was supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia (Grant OI 172055 and Grant OI 172016). PALLADIUM(II) COMPLEXES 1391 Available on-line at: www.shd.org.rs/jscs (CC) 2016 SCS. И З В О Д СИНТЕЗА И КАРАКТЕРИЗАЦИЈА КОМПЛЕКСА ПАЛАДИЈУМА(II) СА ГЛИЦИНСКИМ КУМАРИНСКИМ ДЕРИВАТИМА ДАНИЈЕЛА Љ. СТОЈКОВИЋ1, ALESSIA BACCHI2, DAVIDE CAPUCCI2, МИЛИЦА Р. МИЛЕНКОВИЋ3, БОЖИДАР ЧОБЕЉИЋ3, СРЕЋКО Р. ТРИФУНОВИЋ1, КАТАРИНА АНЂЕЛКОВИЋ3, ВЕРИЦА В. ЈЕВТИЋ1, НЕНАД ВУКОВИЋ, МИЛЕНА ВУКИЋ1 и ДУШАН СЛАДИЋ3 1Институт за хемију, Природно–математички факултет, Универзитет у Крагујевцу, Радоја Домановића 12, 34000 Крагујевац, 2Dipartimento di Chimica, University of Parma, Parco Area delle Scienze 17 A, I 43124 Parma, Italy и 3Хемијски факултет, Универзитет у Београду, Студентски трг 12–16, 11000 Београд Синтетисан је комплекс паладијума(II) са метил-2-([1-{2,4-диоксохроман-3-или- ден}етил]амино)ацетатом. Структуре како лиганда тако и комплекса паладијума(II) одређене су елементалном анализом, IC и NMR спектроскопијом. Прекристализација комплекса паладијума(II) из смеше DMF/вода резултује у његовој хидролизи и форми- рању комплекса диметиламин-(2-[{1-(2,4-диоксохроман-3-илиден)етил}амино]ацетато)- -паладијум(II), чија структура је одређена елементалном анализом, IC, 1H и 13C-NMR спектроскопијом, као и рендгенском структурном анализом. (Примљено 15. септембра, ревидирано 25. септембра, прихваћено 27. септембра 2016) REFERENCES 1. S. Emami, S. Dadashpour, Eur. J. Med. Chem. 102 (2015) 611 2. J. Nawrot-Modranka, E. Nawrot, J. Graczyk, Eur. J. Med. Chem. 41 (2006) 1301 3. V. S. Satyanarayan, P. Sreevani, A. Sivakumar, Arkivoc 2008 (2008) 221 4. A. G. Kidane, H. Salacinski, A. Tiwari, K. R. Bruckdorfer, A. M. Seifalian, Biomacro- molecules 5 (2004) 798 5. A. A. H. Kadhum, A. A. Al-Amiery, A. Y. Musa, A. B. Mohamad, Int. J. Mol. Sci. 12 (2011) 5747 6. G. B. Bubols, D. R. Vianna, A. 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Phys. 297 (2004) 235. << /ASCII85EncodePages false /AllowTransparency false /AutoPositionEPSFiles true /AutoRotatePages /None /Binding /Left /CalGrayProfile (Dot Gain 20%) /CalRGBProfile (sRGB IEC61966-2.1) /CalCMYKProfile (U.S. Web Coated \050SWOP\051 v2) /sRGBProfile (sRGB IEC61966-2.1) /CannotEmbedFontPolicy /Error /CompatibilityLevel 1.4 /CompressObjects /Tags /CompressPages true /ConvertImagesToIndexed true /PassThroughJPEGImages true /CreateJobTicket false /DefaultRenderingIntent /Default /DetectBlends true /DetectCurves 0.0000 /ColorConversionStrategy /CMYK /DoThumbnails false /EmbedAllFonts true /EmbedOpenType false /ParseICCProfilesInComments true /EmbedJobOptions true /DSCReportingLevel 0 /EmitDSCWarnings false /EndPage -1 /ImageMemory 1048576 /LockDistillerParams false /MaxSubsetPct 100 /Optimize true /OPM 1 /ParseDSCComments true /ParseDSCCommentsForDocInfo true /PreserveCopyPage true /PreserveDICMYKValues true /PreserveEPSInfo true /PreserveFlatness true /PreserveHalftoneInfo false /PreserveOPIComments true /PreserveOverprintSettings true /StartPage 1 /SubsetFonts true /TransferFunctionInfo /Apply /UCRandBGInfo /Preserve /UsePrologue false /ColorSettingsFile () /AlwaysEmbed [ true ] /NeverEmbed [ true ] /AntiAliasColorImages false /CropColorImages true /ColorImageMinResolution 300 /ColorImageMinResolutionPolicy /OK /DownsampleColorImages true /ColorImageDownsampleType /Bicubic /ColorImageResolution 300 /ColorImageDepth -1 /ColorImageMinDownsampleDepth 1 /ColorImageDownsampleThreshold 1.50000 /EncodeColorImages true /ColorImageFilter /DCTEncode /AutoFilterColorImages true /ColorImageAutoFilterStrategy /JPEG /ColorACSImageDict << /QFactor 0.15 /HSamples [1 1 1 1] /VSamples [1 1 1 1] >> /ColorImageDict << /QFactor 0.15 /HSamples [1 1 1 1] /VSamples [1 1 1 1] >> /JPEG2000ColorACSImageDict << /TileWidth 256 /TileHeight 256 /Quality 30 >> /JPEG2000ColorImageDict << /TileWidth 256 /TileHeight 256 /Quality 30 >> /AntiAliasGrayImages false /CropGrayImages true /GrayImageMinResolution 300 /GrayImageMinResolutionPolicy /OK /DownsampleGrayImages true /GrayImageDownsampleType /Bicubic /GrayImageResolution 300 /GrayImageDepth -1 /GrayImageMinDownsampleDepth 2 /GrayImageDownsampleThreshold 1.50000 /EncodeGrayImages true /GrayImageFilter /DCTEncode /AutoFilterGrayImages true /GrayImageAutoFilterStrategy /JPEG /GrayACSImageDict << /QFactor 0.15 /HSamples [1 1 1 1] /VSamples [1 1 1 1] >> /GrayImageDict << /QFactor 0.15 /HSamples [1 1 1 1] /VSamples [1 1 1 1] >> /JPEG2000GrayACSImageDict << /TileWidth 256 /TileHeight 256 /Quality 30 >> /JPEG2000GrayImageDict << /TileWidth 256 /TileHeight 256 /Quality 30 >> /AntiAliasMonoImages false /CropMonoImages true /MonoImageMinResolution 1200 /MonoImageMinResolutionPolicy /OK /DownsampleMonoImages true /MonoImageDownsampleType /Bicubic /MonoImageResolution 1200 /MonoImageDepth -1 /MonoImageDownsampleThreshold 1.50000 /EncodeMonoImages true /MonoImageFilter /CCITTFaxEncode /MonoImageDict << /K -1 >> /AllowPSXObjects false /CheckCompliance [ /None ] /PDFX1aCheck false /PDFX3Check false /PDFXCompliantPDFOnly false /PDFXNoTrimBoxError true /PDFXTrimBoxToMediaBoxOffset [ 0.00000 0.00000 0.00000 0.00000 ] /PDFXSetBleedBoxToMediaBox true /PDFXBleedBoxToTrimBoxOffset [ 0.00000 0.00000 0.00000 0.00000 ] /PDFXOutputIntentProfile () /PDFXOutputConditionIdentifier () /PDFXOutputCondition () /PDFXRegistryName () /PDFXTrapped /False /CreateJDFFile false /Description << /ARA /BGR /CHS /CHT /CZE /DAN /DEU /ESP /ETI /FRA /GRE /HEB /HRV (Za stvaranje Adobe PDF dokumenata najpogodnijih za visokokvalitetni ispis prije tiskanja koristite ove postavke. Stvoreni PDF dokumenti mogu se otvoriti Acrobat i Adobe Reader 5.0 i kasnijim verzijama.) /HUN /ITA /JPN /KOR /LTH /LVI /NLD (Gebruik deze instellingen om Adobe PDF-documenten te maken die zijn geoptimaliseerd voor prepress-afdrukken van hoge kwaliteit. De gemaakte PDF-documenten kunnen worden geopend met Acrobat en Adobe Reader 5.0 en hoger.) /NOR /POL /PTB /RUM /RUS /SKY /SLV /SUO /SVE /TUR /UKR /ENU (Use these settings to create Adobe PDF documents best suited for high-quality prepress printing. Created PDF documents can be opened with Acrobat and Adobe Reader 5.0 and later.) >> /Namespace [ (Adobe) (Common) (1.0) ] /OtherNamespaces [ << /AsReaderSpreads false /CropImagesToFrames true /ErrorControl /WarnAndContinue /FlattenerIgnoreSpreadOverrides false /IncludeGuidesGrids false /IncludeNonPrinting false /IncludeSlug false /Namespace [ (Adobe) (InDesign) (4.0) ] /OmitPlacedBitmaps false /OmitPlacedEPS false /OmitPlacedPDF false /SimulateOverprint /Legacy >> << /AddBleedMarks false /AddColorBars false /AddCropMarks false /AddPageInfo false /AddRegMarks false /ConvertColors /ConvertToCMYK /DestinationProfileName () /DestinationProfileSelector /DocumentCMYK /Downsample16BitImages true /FlattenerPreset << /PresetSelector /MediumResolution >> /FormElements false /GenerateStructure false /IncludeBookmarks false /IncludeHyperlinks false /IncludeInteractive false /IncludeLayers false /IncludeProfiles false /MultimediaHandling /UseObjectSettings /Namespace [ (Adobe) (CreativeSuite) (2.0) ] /PDFXOutputIntentProfileSelector /DocumentCMYK /PreserveEditing true /UntaggedCMYKHandling /LeaveUntagged /UntaggedRGBHandling /UseDocumentProfile /UseDocumentBleed false >> ] >> setdistillerparams << /HWResolution [2400 2400] /PageSize [612.000 792.000] >> setpagedevice