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Rhenium complexes merit particular attention in the area of metallodrug design due to rhenium’s broad spectrum of oxidation states and consequently, the possibility to design compounds of great structural diversity [1,2]. Thus, the synthesis, chemical characterization, and antitumor activity in vitro of the six Re(V) complexes are described. Novel compounds were obtained via reaction of [ReOCl3(PPh3)2] with corresponding ligands (pyridine-2- carboxylic acid, 3-methylpyridine-2-carboxylic acid, 6-methylpyridine-2-carboxylic acid, 2,3- pyridinedicarboxylic acid, 2,5-pyridinedicarboxylic acid, and 2,6-pyridinedicarboxylic acid) in acetonitrile or dichloromethane/methanol at 78 °C for 3h. The complexes were fully characterized using NMR, IR, MS, and elemental analysis. Results of X-ray diffraction analysis for three of these compounds confirmed the proposed octahedral geometry with bidentate coordinated ligands, via both oxygen and nitrogen atoms. The antiproliferative effect was determined by MTT assay. All complexes expressed moderate to low cytotoxic potential. Complex with pyridine-2-carboxylic acid showed dose-dependent cytotoxic potential, particularly toward triple-negative breast adenocarcinoma cells MDA-MB-231 and pancreatic adenocarcinoma cells PANC-1. Drug combination studies in PANC-1 cells with that complex and Verapamil hydrochloride (VRP) showed a slight arrest of the cell cycle in the S phase and also increase its antiproliferative potential.

Metal-based compounds are rarely good antimicrobial compounds. Here we report synthesis, chemical characterization and antimicrobial potency of fourteen Ru(II) arene complexes with pyridine-based ligands. The structures and purity of synthesized compounds were confirmed using 1H and 13C NMR spectroscopy, IR spectroscopy, MS, and EA. A micro-well dilution assay was used to determine the minimum inhibitory concentration (MIC), and minimum bactericidal concentration. of evaluated compounds. Streptomycin and chloramphenicol were used as a positive control. The best activity of all tested bacteria was observed against E. coli, with a MIC value of 1.25 mg/mL, for complexes with 2,4- i 2,5-pyridinedicarboxylic ligands. Also, all synthesized complexes showed the same activity against C. Albicans., Kompleksi metala retko se koriste kao potencijalni antimikrobni agensi. U ovom radu smo prikazali sintezu, hemijsku karakterizaciju i antimikrobnu aktivnost 14 arenskih Ru(II) kompleksa sa piridinskim ligandima. Strukturu i čistoću dobijenih jedinjenja potvrdili smo koristeći 1H, 13C NMR i IC spektroskopiju, MS i EA. Mikrodilucioni esej je korišćen za određivanje minimalne inhibitorne koncentracije (MIC) i minimalne baktericidne koncentracije sintetisanih jedinjenja. Streptomicin i hloramfenikol su korišćeni kao standard. Najbolja aktivnost prema ispitivanim sojevima bakterija zapažena je na soju E. coli, sa MIC vrednošću 1,25 mg/mL, kompleksa sa 2,4- i 2,5-piridindikarboksilnim ligandima. Svi sintetisani kompleksi pokazali su podjednako dobru aktivnost prema C. Albicans.

Eleven new and three reported half-sandwich Ru(II) arene complexes were synthesized using [Ru(g6-benzene)Cl(l-Cl)]2 and [Ru(g6-toluene)Cl(l-Cl)]2 and four pyridine carboxylic acid-based ligands (dicarboxylic acids and halogen derivatives). The structures and purity of synthesized compounds were confirmed using 1H and 13C NMR spectroscopy, infrared spectroscopy, mass spectrometry, and elemental analysis. The stability of synthesized compounds in dimethyl sulfoxide solution was confirmed using 1H NMR spectroscopy. The seven ligands, two complex precursors (CP1 and CP2), and 14 half-sandwich Ru(II) picolinate complexes (C1–C14) were evaluated for in vitro antibacterial and antifungal activity against pathogens, such as Staphylococcus aureus, Bacillus cereus, Proteus mirabilis, Klebsiella pneumoniae, Ecsherichia coli, Pseudomonas aeruginosa, Salmonella enteritidis, Enterobacter aerogenes, and yeast Candida albicans, using the microwell-dilution method. Among the tested samples, the ligands showed better inhibitory effect against Gram-positive bacteria when compared to the metal complexes. The most susceptible Gram-negative bacteria was Ecsherichia coli, with a MIC value of 1.25 mg/mL, for C3, C6, and C10. All synthesized complexes showed similar, slightly better activity against Candida albicans.

Two new Schiff base cobalt(III) ([Co(LH)Cl2], 1) and nickel(II) ([Ni(LH)ClO4], 2) complexes with a diimine-dioxime ligand, (4,9-diaza-3,10-diethyl-3,9-dodecadiene-2,11-dione bis oxime (LH2)), were synthesized and characterized. The compounds were obtained in MeOH from corresponding metal salts and LH2 in molar ratio 1:1 and further characterized by mass spectrometry, IR spectroscopy, electrochemistry, and elemental analysis. Previously reported copper(II) analog, ([Cu2(LH)2]·(ClO4)2, 3) was joined to 1 and 2, and the three metal analogs, 1-3, were further investigated in terms of their electrochemical behavior. The binding studies of the complexes with deoxyribonucleic acid (DNA) and human serum albumin (HSA) were carried out using both spectrophotometric and electrochemical methods. All three complexes exhibit binding affinity towards the DNA chain through intercalative interaction. The binding reaction with HSA showed for 1 and 3 complexes decrease in the peak current obtained in the case of complexes before the addition of HSA, while resulted compound obtained from Ni complex – HSA possesses the same electroactivity as starting complex. Furthermore, the cytotoxicity of LH2 as well as its metal complexes, and cisplatin were evaluated on CT-26 mouse colon carcinoma and human LS174T cancer cell lines employing MTT assay. The copper(II) complex exhibited very promising anticancer activity compared with cisplatin.

The versatile chemistry of ruthenium complexes involves thousands of compounds aimed for different applications related to e.g. homogenous catalysis, cancer therapy, tumor diagnosis, and advanced materials.1 Thus, the synthesis and full (electro)chemical characterization of three new Ru(II) complexes carrying acetylpyridine (acpy) ligand unitis is described. The complexes were obtained via reaction of three ligand equivalents (2-, 3-, and 4-acpy) with an equimolar amount of metal precursor, [RuCl2(bpy)2] in methanol. After the overnight reflux, the reaction mixture was left to cool when equimolar amount of NH4PF6 was added. The products were isolated in a form of dark red powder. The complexes were characterized by IR, NMR and MS revealing bidentate coordination of 2- acpy and monodentate binding of 3- and 4-acpy. Their electrochemical profile was studied by cyclic voltammetry which confirmed rich redox chemistry., Raznovrsna hemija kompleksa rutenijuma obuhvata hiljade jedinjenja namenjenih za različite primene, npr. homogenu katalizu, terapiju kancera, dijagnozu tumora i moderne materijale.1 S tim u vezi se opisuje sinteza i kompletna (elektro)hemijska karakterizacija tri nova Ru(II) kompleksa sa acetilpiridinskim ligandom (acpy). Kompleksi su dobijeni reakcijom tri ekvivalenta liganda (2-, 3-, i 4-acpy) sa ekvimolarnom količinom prekursora metala, [RuCl2(bpy)2] u metanolu. Nakon refluksa preko noći, reakciona smeša je ostavljena da se ohladi kad je dodata ekvimolarna količina NH4PF6. Produkti su izolovani u obliku tamnocrvenog praha. Kompleksi su okarakterisani IC, NMR i MS pokazujući bidentatnu koordinaciju 2-acpy i monodentatno vezivanje 3- i 4-acpy. Njihov elektrohemijski profil je ispitan cikličnom voltametrijom koja je potvrdila bogatu redoks hemiju.

Two new Schiff base cobalt(III) ([Co(LH)Cl2], 1) and nickel(II) ([Ni(LH)ClO4], 2) complexes with a diimine-dioxime ligand, (4,9-diaza-3,10-diethyl-3,9-dodecadiene-2,11-dione bis oxime (LH2)), were synthesized and characterized. The compounds were obtained in MeOH from corresponding metal salts and LH2 in molar ratio 1:1 and further characterized by mass spectrometry, IR spectroscopy, electrochemistry, and elemental analysis. Previously reported copper(II) analog ([Cu2(LH)2]·(ClO4)2, 3) was joined to 1 and 2, and the three metal analogs, 1–3, were further investigated in terms of their electrochemical behavior. Binding studies of the complexes with deoxyribonucleic acid (DNA) and human serum albumin (HSA) were carried out using both spectrophotometric and electrochemical methods. All three complexes exhibit binding affinity towards the DNA chain through intercalative interactions. The binding reaction with HSA showed for 1 and 3 decrease in the peak current obtained in the case of complexes before the addition of HSA, while the Ni complex–HSA possesses the same electroactivity as starting complex. The cytotoxicity of LH2 as well as its metal complexes, and cisplatin were evaluated on CT-26 mouse colon carcinoma and human LS174T cancer cell lines employing MTT assay. The copper(II) complex exhibited very promising anticancer activity compared with cisplatin.

Pyridine (carboxylate) type of molecules has been intensively studied since early 2000s as it provides diverse design capabilities in terms of coordination to metal ions. Several structural motifs featuring mono-, bi-, and pentadentate binding modes are discussed in a combination with a variety of different substituents with the pyridine unit. In this context, the current review underlines a brief summary of advances on metal complexes with pyridine-based ligands aimed for further development as metallodrug. In line with this, we also highlight their key properties, different synthetic strategies employed in the preparation, and possible structure–property correlations, indicating advantages and limitations of the applied methods used within documented studies.

Three new ruthenium(II)-arene halido complexes, [(η 6 -p-cymene) RuX(L)] (1–3), were synthesized in a reaction of [(η 6 -p-cymene)RuX 2 ] 2 with 5-chloro-1H-benzimidazole-2-carboxylic acid (HL) in ethanol (X – = Cl – (1), Br – (2), I – (3)). The complexes were characterized by elemental analysis, mass spectrometry, IR, 1 H and 13 C NMR spectroscopy. The cytotoxic activity of the ligand precursor and its ruthenium complexes was tested by MTT assay in human cancer cell lines: lung adenocarcinoma (A549), myelogenous leukemia (K562) as well as in one normal human fetal lung fibroblast cell line (MRC-5). The results show that ruthenium(II)-arene complexes possess enhanced cytotoxicity when compared to HL in the range of concentrations up to 300 µM. In terms of halido ligand substitution, cytotoxic activity toward A549 and K562 cell lines in 1–3 serie significantly increased (e.g., IC 50 values for K562: 1: 205.76 µM; 2: 174.77 µM; 3: 83.97 µM). All studied compounds were found to be ineffective toward MRC-5. Hydrolysis of 1–3 was followed by UV-vis spectroscopy at 25 °C, revealing ligand-substitution reactions at the Ru(II) center. Compounds 2 and 3 underwent rapid hydrolysis ranging from a few minutes for the aquation to ca. 20 min, confirming typical Ru-arene behavior in aqueous solutions.

The electrochemical behavior of four dialkyl esters (methyl, ethyl, n-propyl and n-butyl) of (S,S)-α,α ′-(1,2-ethanediyldiimino)- bis[cyclohexanepropanoic acid] with moderate antitumor activity has been studied by cyclic voltammetry. I-E curves recorded at boron-doped diamond electrode in -2.00 < Ep < 0.00 V range show a single oxidative peak located in the -0.95 < Ep,a < -0.52 V region in a form of one-electron wave. The electrochemical processes appear to be irreversible for all compounds except for the compound with methyl substituent which demonstrates well-defined reversible electron transfer. Derivatives with bulkier moieties are easier to oxidize. For all investigated compounds an amine-centered redox process is dominant. Further investigation indicates that electrochemical reaction is diffusion controlled, chemically irreversible process. The results are discussed in terms of linking their electrochemical activity to antitumor effect. © 2018 The Electrochemical Society.

The electrochemical behavior of four dialkyl esters (methyl, ethyl, n-propyl and n-butyl) of (S,S)-alpha,alpha'-(1,2-ethanediyldiimino)-bis[cyclohexanepropanoic acid] with moderate antitumor activity has been studied by cyclic voltammetry. I-E curves recorded at boron-doped diamond electrode in -2.00 lt E-p lt 0.00 V range show a single oxidative peak located in the -0.95 lt E-p,E-a lt -0.52 V region in a form of one-electron wave. The electrochemical processes appear to be irreversible for all compounds except for the compound with methyl substituent which demonstrates well-defined reversible electron transfer. Derivatives with bulkier moieties are easier to oxidize. For all investigated compounds an amine-centered redox process is dominant. Further investigation indicates that electrochemical reaction is diffusion controlled, chemically irreversible process. The results are discussed in terms of linking their electrochemical activity to antitumor effect. (C) 2018 The Electrochemical Society.

U ovom radu sintetisano je četiri nova arenska kompleksa Ru(II) sa dva nesteroidna antiimflamatorna leka, indometacin i mefenaminskom kiselininom. Kompleksi su sintetisani polazeći od metanolnog rastvora polaznog Ru(II) polusendvič jedinjenja i baznog metanolnog rastvora odgovarajućeg liganda. Strukture novih kompleksa određene su NMR i IC spektroskopijom, kao i masenom spektrometrijom. Pokazano je da se ligandi koordinuju monodentatno preko karboksilnih kiseonika. Citotoksična aktivnost liganada i kompleksa ispitana je na tri ćelijske linije humanog kancera i zdravih humanih fibroblastnih ćelija, korišćenjem MTT metode. IC50 vrednosti dobijene na ćelijama leukemije K562 bile su uporedive sa onim za cisplatinu (10.3 µM (cisplatina), 11.9 µM (kompleks 1) i 13.2 µM (kompleks 3)). Korišćenjem protočne citometrije pokazano je da ovi kompleksi pri IC50 koncentracijama zaustavljaju ćelijski ciklus u S fazi. Merenje produkcije reaktivnih kiseoničnih DCFH-DA metodom potvrdilo je njihov potencijal da povećavaju ROS više od cisplatine., Two non-steroidal antiinflammatory drugs, indomethacin and mefenamic acid, were coordinated to Ru(II)-arenes to give four new complexes. These four complexes were synthesized by mixing methanolic solution of starting half-sandwich Ru complexes with base solution of ligand in methanol. Structures of complexes were determinated by NMR, IR spectroscopy and mass spectrometry. It was shown that they coordinates monodentatly via carboxylic oxygen. The cytotoxic activity of the ligands and ruthenium complexes was tested in three human cancer cell lines and non-tumour human fetal lung fibroblast cells by MTT assay. The IC50 values obtained in leukemia K562 cells, were comparable to cisplatin (10.3 µM (CDDP), 11.9 µM (1) and 13.2 µM (3)). Flow cytometric analysis of these conplexes, showed that at IC50 concentrations, they arrested cell cycle progression in the S phase. Measurement of reactive oxygen species (ROS) production, by DCFH-DA staining, confirmed their potential to increase ROS even more than cisplatin.

Bis(bipiridin)rutenijum(II) kompleksi (1-5) opšte formule [Ru(L)(bpy)2]PF6, gde je bpy = 2,2′-bipiridin; HL = 3-metilpiridin-2-karboksilna kiselina (HL1), 6-metilpiridin-2-karboksilna kiselina (HL2), 5-bromopiridin-2-karboksilna kiselina (HL3) 6-brompiridin-2-karboksilna kiselina (HL4) i piridin-2,4-dikarboksilna kiselina (HL5) su sintetisani i potpuno okarakterisani. Za jedinjenja 3, 4 and 5 urađena je difrakcionom analizom X-zraka na monokristalu..., Bis(bipyridine)ruthenium(II) complexes (1-5) of general formula [Ru(L)(bpy)2]PF6, where bpy = 2,2′-bipyridine; HL = 3-methylpyridine-2-carboxylic acid (HL1), 6-methylpyridine-2-carboxylic acid (HL2), 5-bromopyridine-2-carboxylic acid (HL3) 6-bromopyridine-2-carboxylic acid (HL4) and pyridine-2,4-dicarboxylic acid (HL5) were synthesized and fully characterized. For compounds 3, 4 and 5 single-crystal X-ray diffraction analyses were also performed...

Complexes 1-4, [Ru(L)(bpy)(2)]PF6, where bpy=2,2-bipyridine; HL=3-methylpyridine-2-carboxylic acid (HL1), 6-methylpyridine-2-carboxylic acid (HL2), 5-bromopyridine-2-carboxylic acid (HL3) and 6-bromopyridine-2-carboxylic acid (HL4), were synthesized and characterized. The electrochemical character of the complexes was investigated by cyclic voltammetry revealing two reversible reduction waves in the negative range of potentials, most likely due to a reduction of the bipyridine moiety. Cytotoxicity studies by MTT assay for 72h of drug action revealed that 2-4 exhibited moderate activity in cervical human tumor cells (HeLa). Complex 2 exhibited low activity in colon cancer LS-174 cells (180 +/- 10), while all complexes were devoid of activity in lung cancer A549 and non-tumor MRC-5 cells, up to 200M. Combinational studies of the most active complex 2, with pharmacological modulators of cell redox status, L-buthionine-sulfoximine (L-BSO) or N-acetyl-L-cysteine (NAC), showed that when L-BSO potentiated, 2 induced a sub-G1 peak of the cell cycle in the HeLa cell line. UV-vis and cyclic voltammetry were performed in order to investigate the binding mode of 2 to DNA and suggested intercalation for the complex-DNA interaction. [GRAPHICS]

A new Ru(II) bipyridyl complex with O-4-hydrogenpyridine-2,4-dicarboxylate was synthesized and characterized by IR, NMR and mass spectrometry, X-ray diffraction analysis and elemental analysis. The electrochemical characteristics of the complex were investigated by cyclic voltammetry, revealing Ru(II)/Ru(III) electron transfer in the positive range of potentials. On the opposite potential side, multiple partially reversible peaks were dominant, representing subsequent reductions of the bulky bipyridyl moiety. The cytotoxic activity of the complex was tested in two human cancer cell lines: A549 (lung cancer) and K562 (leukemia) as well as non-tumor MRC-5 cells, by MTT assays. The IC50 values were gt 300 and 177.63+/-2.28 mu M for the A549 and K562 cells, respectively.

Food texture can be improved by enzyme-mediated covalent cross-linking of different food components, such as proteins and carbohydrates. Cross-linking changes the biological and immunological properties of proteins and may change the sensitizing potential of food allergens. In this study we applied a microbial polyphenol oxidase, laccase, to cross-link peanut proteins. The size and morphology of the obtained cross-linked proteins were analyzed by electrophoresis and electron microscopy. Structural changes in proteins were analyzed by CD spectroscopy and by using specific antibodies to major peanut allergens. The bioavailability of peanut proteins was analyzed using a Caco-2 epithelial cell model. The in vivo sensitizing potential of laccase-treated peanut proteins was analyzed using a mouse model of food allergy. Finally, peanut polyphenols were analyzed by UHPLC-MS/MS, before and after the enzymatic reaction with laccase. Laccase treatment of peanut proteins yielded a covalently cross-linked material, with the modified tertiary structure of peanut proteins, improved bioavailability of Ara h 2 (by 70 fold, p lt 0.05) and modulated allergic immune response in vivo. The modulation of the immune response was related to the increased production of IgG2a antibodies 11 fold (p lt 0.05) and reduced IL-13 secretion in in vitro cultured splenocytes 7 fold (p lt 0.05). Analysis of the peanut polyphenol content and profile by HPLC-MS/MS revealed that laccase treatment depleted the peanut extract of polyphenol compounds leaving mostly isorhamnetin derivatives and procyanidin dimer B-type in detectable amounts. Treatment of complex food extracts rich in polyphenols with laccase results in both protein cross-linking and modification of polyphenol compounds. These extensively cross-linked proteins have unchanged potency to induce allergic sensitization in vivo, but certain immunomodulatory changes were observed.

The thermal behaviour of a Pt(IV) and a Ru(II) complex coordinated to dibutyl (S,S)-alpha,alpha'-(1,2-ethanediyldiimino)biscyclohexanepropanoate was investigated using thermogravimetry (TG) and differential scanning calorimetry (DSC). The study included an investigation of the thermal decomposition of these complexes in the temperature range of 30 to 590 degrees C and an evaluation of the activation energy for the first decomposition steps. For both metal complexes, broad DSC peaks indicated complex thermal transformation processes. The two-step decomposition of the Pt(IV) complex started at 175 and ended at about 418 degrees C, leaving elemental platinum as the final residue. On the other hand, the Ru(II) analogue decomposed in three stages. Thermal degradation was evident beginning at 144 degrees C and suggested the decomposition of a coordinated ligand as the dominant process. For this complex, the proposed final residue was RuO2. Kinetic parameters for the first decomposition step were obtained by means of the multi-heating rates method, in this case the Kissinger-Akahira-Sunose (KAS) method. The mean activation energy calculated for 0.2 lt alpha lt 0.8 were 122.0 kJ mol(-1) for the Pt(IV) and 118.9 kJ mol(-1) for the Ru(II) complex and decreased constantly, a characteristic of a multi-step process.

The synthesis, full characterization, and molecular structures of seven new coordination compounds that feature the 2-(4',4'-dimethyloxazolin-2'-yl)thiophenolate ligand (S-Phoz) with group 10 metals Ni, Pd, and Pt in the +II oxidation state are presented. The ML2 complexes [Pt(S-Phoz)(2)] (1a), [Pd(S-Phoz)(2)] (1b), and [Ni(S-Phoz)(2)] (2) were prepared starting from MCl2. Compound 1a was obtained isomerically pure in a trans arrangement, whereas its Pd analogue 1b exhibits a dynamic, solvent-dependent cis/trans equilibrium, and 2 adopts a tetrahedral arrangement. The reaction of LiS-Phoz with [cis-MCl2(PPh3)(2)] precursors resulted in full replacement of the PPh3 for M = Ni and in partial substitution for M = Pt, Pd to yield [Ni(S-Phoz)(2)] (2), [Pt(kappa(2)-S-Phoz)(kappa(1)-S-Phoz)-(PPh3)] (3a), and [Pd(kappa(2)-S-Phoz)(kappa(1)-S-Phoz)(PPh3)] (3b). The Pd compound 3b exhibits an interesting solvent-dependent equilibrium with 1b and PPh3 as demonstrated by H-1 and P-31 NMR spectroscopy. Compounds [{PdCl(S-Phoz)}(2)] (4) and [PdCl(S-Phoz)(PPh3)] (5) were synthesized from [PdCl2(NCMe)(2)]. Molecular structures of compounds trans-1a, trans-1b, 2, 3a, 3b, 4, and 5 were determined by singlecrystal X-ray diffraction studies. With the exception of the Ni complex 2, all compounds exhibit distorted square-planar geometries.

U priloţenoj disertaciji su opisane sinteze, karakterizacija i oksido-redukciona svojstva dialkil estara N,N'-metilen-(S,S)-etilendiamin-N,N'-di-2-(3-cikloheksil) propanske kiseline, njima odgovarajućih kompleksa Pt(IV) kao i kompleksa Pt(II) sa tiofenolat-oksazolinskim ligandom.Spektroskopska karakterizacija sintetisanih jedinjenja je uraĊena standardnim metodama: infracrvenom i Ulj/Vid spektroskopijom, masenom spektrometrijom i NMR spektroskopijom (1D-1H i 13C; 2D-COSY, HSQC, HMBC tehnikama) dok je sastav jedinjenja potvrĊen elementalnom analizom. Struktura kompleksnih jedinjenja platine(II), [Pt(S-Phoz)2] i [Pt(η2S-Phoz)(η1S-Phoz)(PPh3)], odreĊena je i primenom rendgenske strukturne analize.Dialkil estri N,N'-metilen-(S,S)-etilendiamin-N,N'-di-2-(3-cikloheksil)propanske kiseline su dobijeni u reakciji reduktivnog metilovanja dialkil estara (S,S)-etilendiamin-N,N'-di-2-(3-cikloheksil)propanske kiseline triacetoborhidridom i formaldehidom u odgovarajućem stehiometrijskom odnosu. Sintetisani ligandi su reakcijom sa kalijum-heksahloridoplatinatom(IV) dali odgovarajuće komplekse platine(IV), oktaedarske geometrije sa N,N bidentatno vezanim ligandima. Dodatno je za ovu klasu jedinjenja ispitana citotoksiĉna aktivnost na razliĉitim ćelijskim linijama (A375, B16, CT26CL25, HCT116, PC3 i U251).Tiofenolat-oksazolinski ligand, Li(SPh-oz), je s obzirom na prisustvo dva razliĉita donorska atoma (azota i sumpora) pokazao razliĉite naĉine koordinovanja za platinski metalni centar. Prvobitno je reakcijom Li(SPh-oz) sa kalijum-tetrahloridoplatinatom(II) sintetisan [Pt(S-Phoz)2] kompleks deformisane kvadratno-planarne geometrije. Izolovani monokristalni produkt ovog jedinjenja je ukazao na S,S-trans raspored liganada oko metalnog centra. Zatim je u reakciji istog liganda sa cis-bis(trifenilfosfin)platina(II)-hloridom dobijen [Pt(η2S-Phoz)(η1S-Phoz)(PPh3)]..., An enclosed dissertation describes the synthesis, characterization and oxidoreductive properties of dialkyl esters of N,N′-methylene-(S,S)-ethylenediamine-N,N′-di-2-(3-cyclohexyl)propanoic acid, their corresponding Pt(IV) complexes as well as Pt(II) complexes with thiophenolate-oxazoline ligand.Spectroscopic characterization of the synthesized compounds was performed by standard methods: infrared and UV/Vis spectroscopy, mass spectrometry and NMR spectroscopy (1D-1H and 13C and 2D-COSY, HSQC, HMBC techiques) while the compounds' content was confirmed by elemental analysis. The structures of Pt(II) species, [Pt(S-Phoz)2] and [Pt(η2S-Phoz)(η1S-Phoz)(PPh3)], were determined using X-ray structural analysis.Dialkyl esters of N,N′-methylene-(S,S)-ethylenediamine-N,N′-di-2-(3-cyclohexyl)propanoic acid were obtained by reductive methylation of the parent compounds (dialkyl esters of (S,S)-ethylenediamine-N,N′-di-2-(3-cyclohexyl)propanoic acid) adding triacetoxyborohydride and formaldehyde in appropriate stoichiometric amounts. A reaction between synthesized ligands and potassium tetrachloroplatinate(II) afforded octahedral Pt(IV) complexes giving rise to N,N bidentate coordination. The cytotoxic activity toward various cancer cell lines (A375, B16, CT26CL25, HCT116, PC3 and U251) was additionally investigated for this class of compounds.Thiophenolate-oxazoline ligand, Li(SPh-oz) demonstrated different coordination modes due to the presence of two donor atoms (nitrogen and sulphur). Primarily, [Pt(S-Phoz)2] complex of distorted square planar geometry was obtained in a reaction of Li(SPh-oz) with potassium hexachloroplatinate(IV). The isolated monocrystal product of the specie indicated on S,S-trans arrangement of the ligands around the metal center. Nonetheless, a reaction between the identical ligand and cis-bis(triphenylphosphine)platinum(II) chloride afforded [Pt(η2S-Phoz)(η1S-Phoz)(PPh3)] complex for which 31P NMR spectroscopy and X-ray structural analysis confirmed...

This study involves the synthesis and characterization of novel cyclohexyl 1,3-propanediamine-N, N'-diacetate molecules as well as investigation of their cytotoxic action. New acid 1a was synthesized by reaction between (S)-2-amino-3-cyclohexylpropanoic acid and 1,3-dibromopropane, while the esters (1b-1e) derived from this acid were obtained by reaction of the corresponding absolute alcohol, thionyl chloride and synthesized acid. All compounds were characterized by IR, ESI-MS, (H-1, C-13 and HSQC) NMR spectroscopy and elemental analysis. The cytotoxic activity of all compounds was tested on several tumour cell lines: human (U251) and rat (C6) glioma, human promyelocytic leukaemia (HL-60), human neuroblastoma (SHSY-5Y) and mouse fibrosarcoma (L929) as well as primary rat astrocytes. The present study reveals potent antitumour activity of novel purely organic compounds (1a-1e), which was most pronounced in human glioma (U251) cells. The esterification is required for the novel compounds' cytotoxic action since the n-butyl ester 1e was the most efficient compound. Importantly, n-butyl ester 1e was more toxic to glioma cells in comparison to rat astrocytes, with 24-h IC50 values lower than those for cisplatin. n-Butyl ester 1e induced production of reactive oxygen species (ROS) and caused an oxidative- stress-derived accumulation of glioma cells in the G(0)/G(1) phase of the cell cycle, as well as caspase activation and DNA fragmentation, suggesting that apoptosis induction plays an important role in the novel compounds' antiglioma action. (C) 2014 Elsevier Inc. All rights reserved.

The synthesis of two new organic compounds, diisobutyl- and diisopentyl (S,S)-alpha(1),alpha(3)-bis(cyclohexylmethyl-1,3-imidazolidinediacetate is reported herein. The one-pot procedure was realized by the addition of the reducing agent and carbonyl compound into a methanolic solution of the parent compounds (isobutyl and isopentyl esters of (S,S)-alpha,alpha '-(1,2-ethanediyldiimino)bis[cyclohexanepropanoic acid] in appropriate stoichiometric ratios. The compounds were fully characterized by infrared, ESI-MS, 1D (H-1 and C-13) and 2D (COSY, HSQC and HMBC) NMR spectroscopy and elemental analysis. The spectral data confirmed the presence of the -CH2- group introduced between the nitrogen atoms of the ethylenediamine moiety, revealing a neutral form of the potential bidentate ligand.

Pt(IV) complexes with ethylenediamine-N,N'-diacetate-type ligands exhibit strong antitumor activity towards various cancer cell lines. In order to explain their complete mechanisms of action, we examined bioreductive character of eight compounds in total using cyclic voltammetry, differential pulse voltammetry and electrochemical impedance spectroscopy. Recorded voltammograms of all Pt(IV) complexes with methyl, ethyl, n-propyl and n-butyl esters of (S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid confirmed two successive one-electron transfer steps followed by the loss of the corresponding axial ligands. The redox potential values for Pt(IV) complexes were in the range of -0.92 V lt Ep lt -0.70 V vs. Ag/AgCl, indicating hard reduction. The obtained electrochemical data pointed to the fact that the length of alkyl substituents influences on the reduction as well as on their biological activity. In addition, the electrochemical data were correlated with the biological data but this correlation wasn't established. The reported electrochemical data well correlated with the biological results pointed to the future structural modifications among the investigated compounds and helped select the most suitable candidates for further research.