The optical properties of 3 + 3 macrocyclic Schiff base thin material obtained by the Molecular Beam Epitaxy method.

3 + 3 optically active macrocyclic Schiff bases were synthesized in the reaction between 4-tert-butyl-2,6-diformylphenol with (1R,2R)-(+)-1,2-diphenylethylenediamine (S1) or (1S,2S)-(-)-1,2-diphenylethylenediamine (S1a). The new compounds were spectroscopically characterised by NMR, IR, X-ray (S1a), UV-Vis and fluorescence spectroscopy. The S1a molecule creates channels with distances between oxygen atoms ranging from 5.8-6.3 Å and sufficiently large to host acetonitrile molecule. Both compounds exhibit green-yellow emission in solution and solid state. Thin layers of the S1 compound obtained via Molecular Beam Epitaxy (MBE) were characterised by scanning electron microscopy with energy-dispersive X-ray spectroscopy SEM/EDS and atomic force microscopy (AFM). The optical properties of the S1/Si thin material were analysed using spectroscopic ellipsometry (SE), fluorescence spectroscopy and synchrotron radiation (SR). The time constant for the decay investigated under SR, denoted by τ1, was determined to be approximately 1.02 ns, suggesting a fast deactivation process of the excited electronic state in the S1/Si material. The ellipsometric analysis of the S1/Si layer showed semiconducting behaviour with pronounced absorption features in the UV range, attributed to π â†’ π* and n â†’ π* transitions, characteristic of Schiff bases. The band-gap energy, determined using the Tauc method, is 3.46 ± 0.01 eV. These analyses highlight the material's potential in applications requiring precise control of optical properties. In the emission spectrum of S1a, a significant emission peak of approximately 561 nm indicates the presence of a prominent emissive process within this wavelength. The S1a compound is emissive in the yellow-green region of the spectrum and has a longer decay time, which suggests that it can be used in sensing optical technologies.

New Dinuclear Macrocyclic Copper(II) Complexes as Potentially Fluorescent and Magnetic Materials.

Two dinuclear copper(II) complexes with macrocyclic Schiff bases K1 and K2 were prepared by the template reaction of (R)-(+)-1,1'-binaphthalene-2,2'-diamine and 2-hydroxy-5-methyl-1,3-benzenedicarboxaldehyde K1, or 4-tert-butyl-2,6-diformylphenol K2 with copper(II) chloride dihydrate. The compounds were characterized by spectroscopic methods. X-ray crystal structure determination and DFT calculations confirmed their geometry in solution and in the solid phase. Moreover, intermolecular interactions in the crystal structure of K2 were analyzed using 3D Hirshfeld surfaces and the related 2D fingerprint plots. The magnetic study revealed very strong antiferromagnetic CuII-CuII exchange interactions, which were supported by magneto-structural correlation and DFT calculations conducted within a broken symmetry (BS) framework. Complexes K1 and K2 exhibited luminescent properties that may be of great importance in the search for new OLEDs. Both K1 and K2 complexes showed emissions in the range of 392-424 nm in solutions at various polarities. Thin materials of the studied compounds were deposited on Si(111) by the spin-coating method or by thermal vapor deposition and studied by scanning electron microscopy (SEM/EDS), atomic force microscopy (AFM), and fluorescence spectroscopy. The thermally deposited K1 and K2 materials showed high fluorescence intensity in the range of 318-531 nm for K1/Si and 326-472 nm for the K2/Si material, indicating that they could be used in optical devices.

Factors Affecting the Stability of Platinum(II) Complexes with 1,2,4-Triazolo[1,5-a]pyrimidine Derivatives and Tetrahydrothiophene-1-Oxide or Diphenyl Sulfoxide.

The platinum(II) complexes of general formula [PtCl2(dstp)(S-donor)] were dstp 5,7-dimethyl-1,2,4-triazolo[1,5-a]-pyrimidine (dmtp), 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp), 5-methyl-7-isobutyl-1,2,4-triazolo[1,5-a]pyrimidine (ibmtp) or 5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine (dptp), whereas S-tetrahydrothio-phene-1-oxide (TMSO) or diphenyl sulfoxide (DPSO) were synthesized in a one-pot reaction. Here, we present experimental data (1H, 13C, 15N, 195Pt NMR, IR, X-ray) combined with density functional theory (DFT) computations to support and characterize structure-spectra relationships and determine the geometry of dichloride platinum(II) complexes with selected triazolopyrimidines and sulfoxides. Based on the experimental and theoretical data, factors affecting the stability of platinum(II) complexes have been determined.

Synthesis and Structure of Novel Copper(II) Complexes with N,O- or N,N-Donors as Radical Scavengers and a Functional Model of the Active Sites in Metalloenzymes.

To evaluate the antioxidant activity of potential synthetic enzyme mimetics, we prepared new five copper(II) complexes via a self-assembly method and named them [Cu(2-(HOCH2)py)3](ClO4)2 (1), [Cu(2-(HOCH2)py)2(H2O)2]SiF6 (2), [Cu2(2-(HOCH2CH2)py)2(2-(OCH2CH2)py)2](ClO4)2 (3), [Cu(pyBIm)3](BF4)2·1.5H2O (4) and [Cu(py2C(OH)2)2](ClO4)2 (5). The synthetic protocol involved N,O- or N,N-donors: 2-(hydroxymethyl)pyridine (2-(HOCH2)py), 2-(hydroxyethyl)pyridine (2-(HOCH2CH2)py), 2-(2-pyridyl)benzimidazole (pyBIm), di(2-pyridyl)ketone (py2CO). The obtained Cu(II) complexes were fully characterised by elemental analysis, FTIR, EPR, UV-Vis, single-crystal X-ray diffraction and Hirshfeld surface analysis. Crystallographic and spectroscopic analyses confirmed chromophores of both monomeric ({CuN3O3} (1), {CuN2O4} (2), {CuN6} (4), {CuN4O2} (5)) and dimeric complex ({CuN2O3} (3)). Most of the obtained species possessed a distorted octahedral environment, except dimer 3, which consisted of two copper centres with square pyramidal geometries. The water-soluble compounds (1, 3 and 5) were selected for biological testing. The results of the study revealed that complex 1 in solutions displayed better radical scavenging activity than complexes 3, 5 and free ligands. Therefore, complex 1 has been selected for further studies to test its activity as an enzyme mimetic. The chosen compound was tested on the erythrocyte lysate of two groups of patients after undergoing chemotherapy and chemoradiotherapy. The effect of the tested compound (1) on enzyme activity levels (TAS, SOD and CAT) suggests that the selected complex can be treated as a functional mimetic of the enzymes.

New dinuclear zinc(ii) complexes with Schiff bases obtained from o-phenylenediamine and their application as fluorescent materials in spin coating deposition.

Two Zn(ii) complexes, K1 and K2, obtained from the template reaction of zinc(ii) acetate dihydrate with o-phenylenediamine and 2-hydroxy-5-methylisophthalaldehyde (K1) or 2-hydroxy-5-tert-butyl-1,3-benzenedicarboxaldehyde (K2), respectively, were characterized by X-ray crystallography, spectroscopic (UV-vis, fluorescence and IR), and thermal methods. In the complex [Zn2(MeO)1.4(OH)0.6(L1)]·2H2O K1, there are two binding sites in the macrocyclic ligand and they are occupied by zinc(ii) cations found in slightly distorted square pyramidal environment. The zinc(ii) cations are connected by slightly asymmetric oxo bridges with a Zn1-O14-Zn1[-x, -y + 1, -z + 1] angle of 104.8(2)°. In the dimer [Zn2(CH3COO)2(L2)]·2EtOH K2, there are two crystallographically independent binding sites both occupied by zinc(ii) cations. There is a significant difference between both complexes, since in K1 only one site is independent and the second is occupied due to the application of symmetry rules, and the geometry of both sites is identical. Thin layers of the obtained Zn(ii) complexes were deposited on Si(111) by the spin coating method and studied by scanning electron microscopy (SEM/EDS), atomic force microscopy (AFM), fluorescence spectroscopy and ellipsometry. In the non-absorbing range, the value of the refractive index exhibits normal dispersion between 1.8 and 2.1 for K1_1-K1_3; and between 2.3 and 2.6 for the K2 series of samples established for long wavelengths (longer than 500 nm). The Zn(ii) complexes and their thin layers exhibited fluorescence between 534-573 nm and 495-572 nm for the compounds and the layers, respectively. The highest quantum yield of fluorescence was achieved for K2 in benzene and in the solid state ϕ = 0.78 and 0.58, respectively. The influence of the solvent polarity on the fluorescence properties of the obtained complexes was studied. Additionally, DFT calculations were performed to explain the structures and electronic spectral properties of the complexes.

Platinum(II) Complexes with Bulky Disubstitute Triazolopyrimidines as Promising Materials for Anticancer Agents.

Herein, we present dicarboxylate platinum(II) complexes of the general formula [Pt(mal)(DMSO)(L)] and [Pt(CBDC)(DMSO)(L)], where L is dbtp 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine) or ibmtp (7-isobutyl-5-methyl-1,2,4- triazolo[1,5-a]pyrimidine), as prospective prodrugs. The platinum(II) complexes were synthesized in a one-pot reaction between cis-[PtCl2(DMSO)2], silver malonate or silver cyclobutane-1,1-dicarboxylate and triazolopyrimidines. All platinum(II) compounds were characterized by FT-IR, and 1H, 13C, 15N and 195Pt NMR; and their square planar geometries with one monodentate N(3)-bonded 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidine, one S-bonded molecule of dimethyl sulfoxide and one O,O-chelating malonato (1, 2) or O,O-chelating cyclobutane-1,1-dicarboxylato (3, 4) was determined. Additionally, [Pt(CBDC)(dbtp)(DMSO)] (3) exhibited (i) substantial in vitro cytotoxicity against the lung adenocarcinoma epithelial cell line (A549) (IC50 = 5.00 µM) and the cisplatin-resistant human ductal breast epithelial tumor cell line (T47D) (IC50 = 6.60 µM); and (ii) definitely exhibited low toxicity against normal murine embryonic fibroblast cells (BALB/3T3).

Structural Insights into New Bi(III) Coordination Polymers with Pyridine-2,3-Dicarboxylic Acid: Photoluminescence Properties and Anti-Helicobacter pylori Activity.

Two novel coordination polymers, [Bi2(2,3pydc)2(2,3pydcH)2(H2O)]n (1) and {(Et3NH)2[Bi(2,3pydc)(2,3pydcH)Cl2]}n (2) were prepared using as a prolinker pyridine-2,3-dicarboxylic acid (2,3pydcH2). The obtained complexes were fully characterized by elemental analysis, TG/DTG, FT-IR, solid-state photoluminescence, DFT calculations and single-crystal X-ray diffraction. The obtained complexes crystallized in the triclinic P-1 space group (1) and comprise dimeric units with two crystallographically different Bi(III) centers (polyhedra: distorted pentagonal bipyramid and bicapped trigonal prism) and monoclinic P21/c space group (2) with a distorted monocapped pentagonal bipyramid of Bi(III) center. The various coordination modes of bridging carboxylate ligands are responsible for the formation of 1D chains with 4,5C10 (1) and 2C1 (2) topology. The photoluminescence quantum yield for polymer 2 is 8.36%, which makes it a good candidate for more specific studies towards Bi-based fluorescent materials. Moreover, it was detected that polymer 1 is more than twice as active against H. pylori as polymer 2. It can be concluded that there is an existing relationship between the structure and the antibacterial activity because the presence of chloride and triethylammonium ions in the structure of complex 2 reduces the antibacterial activity.

Ruthenium(II) and Iridium(III) Complexes as Tested Materials for New Anticancer Agents.

The oncological use of cisplatin is hindered by its severe side effects and a very important resistance problem. To overcome these problems, scientists have attempted to design new generation transition-metal anticancer complexes. In this study, we present new complexes, ruthenium(II) [(η6-p-cymene)RuCl(py2CO)]PF6 (1), iridium(III) [(η5-Cp)IrCl(py2CO)]PF6 (2), and NH4[IrCl4(py2CO)]·H2O (3), based on di-2-pyridylketone (py2CO). The prepared complexes were characterized by FTIR, 1H, 13C, 15N NMR, UV-Vis, PL and elemental analysis techniques. The single-crystal X-ray structure analysis and comparative data revealed pseudo-octahedral half-sandwich 1 and 2 complexes and octahedral tetrachloroiridate(III) 3 with a rare chelating κ2N,O coordination mode of py2CO. The compounds were tested in vitro against three cancer cell lines-colorectal adenoma (LoVo), myelomonocytic leukaemia (MV-4-11), breast adenocarcinoma (MCF-7), and normal fibroblasts (BALB/3T3). The most promising results were obtained for iridium(III) complex 3 against MV-4-11 (IC50 = 35.8 ± 13.9 µg/mL) without a toxic effect against normal BALB/3T3, which pointed towards its selectivity as a potential anticancer agent. Extensive research into their mode of binding with DNA confirmed for 1 and 2 complexes non-classical binding modes, while the 3D circular dichroism (CD) experiment (ΔTm) suggested that 3 induced the probable formation of covalent bonds with DNA. In addition, the obtained iridium complexes induce ROS, which, in synergy with hydrolysis promoting DNA bonding, may lead to cancer cell death.

Nanoencapsulation of a ruthenium(ii) complex with triazolopyrimidine in liposomes as a tool for improving its anticancer activity against melanoma cell lines.

Two types of ruthenium(ii) complexes containing 1,2,4-triazolo[1,5-a]pyrimidines of the general formulas [RuCl2(dmso)3(L)] ((1)-(3)) and [RuCl2(dmso)2(L)2] ((4)-(6)), where L represents 1,2,4-triazolo[1,5-a]pyrimidine (tp for (1)), 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine (dmtp for (2)), 7-isobutyl-5-methyl-1,2,4-trizolo[1,5-a]pyrimidine (ibmtp for (3)), 5,7-diethyl-1,2,4-triazolo[1,5-a]pyrimidine (detp for (4)), 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp for (5)) and 5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine (dptp for (6)), have been synthesized and characterized by elemental analysis, infrared, multinuclear magnetic resonance spectroscopic techniques (1H, 13C, and 15N), and X-ray (for (3), (4), and (5)). All these complexes have been thoroughly screened for their in vitro cytotoxicity against melanoma cell lines A375 and Hs294T, indicating cis,cis,cis-[RuCl2(dbtp)2(dmso)2] (5) as the most active representative, in addition to being non-toxic to normal human fibroblasts (NHDF) and not inducing hemolysis of human erythrocytes. In order to develop an intravenous formulation for (5), liposomes composed of soybean phosphatidylcholine (SPC), cholesterol (Chol) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG2000) were prepared and subsequently characterized. (5)-Loaded liposomes, with spherical morphology, assessed by transmission electron microscope (TEM), exhibited satisfactory encapsulation efficiency and stability. In in vitro experiments, PEG-modified (5)-loaded liposomes were more effective (10-fold) than free (5) for growth inhibition of both human melanoma cell lines. Furthermore, such an approach resulted in the reduction of cancer cell viability that was even 10-fold greater than that observed for free cisplatin.

Synthesis, structure and biological evaluation of ruthenium(III) complexes of triazolopyrimidines with anticancer properties.

Six novel ruthenium(III) complexes of general formula [RuCl3(L)3] (1,3,5) and [RuCl3(H2O)(L)2] (2,4,6), where L stands for three different triazolopyrimidine-derived ligands, are reported. The compounds have been structurally characterized (IR, EPR, SCXRD), and their magnetic moments have been determined. The single-crystal X-ray diffraction study revealed a slightly distorted octahedral geometry of the Ru(III) complexes with mer configuration in 1 and 5, and fac configuration in 3. In 2 and 4, three chloride ions are in mer configuration and the two triazolopyrimidines are oriented trans mutually with the water molecule playing the role of the sixth ligand. All complexes have been thoroughly screened for their in vitro cytotoxicity against human breast cancer cell line MCF-7, human cervical cancer cell line HeLa, and L929 murine fibroblast cells, uncovering among others that the most lipophilic complexes 5 and 6, containing the bulky ligand dptp (5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine), display high cytotoxic activity against MCF-7, and HeLa cells. Moreover, it was also revealed that during the interaction of the complexes 1-6 with the cancer MCF-7 cell line, reactive oxygen species are released intracellularly, which could indicate that they are involved in cell apoptosis. Furthermore, extensive studies have been carried out to reveal the mechanism by which complexes 1-6 interact with DNA, albumin, and apotransferrin. The biological studies were complemented by detailed kinetic studies of the hydrolysis of the complexes in the pH range 5-8, to determine the stability of the complexes in solution. Six novel ruthenium(III) complexes with triazolopyrimidine derivatives demonstrated the potential for use as anticancer agents by maintaining the toxic effect on MCF-7 and HeLa cells.

Strategies for overcoming tropical disease by ruthenium complexes with purine analog: Application against Leishmania spp. and Trypanosoma cruzi.

Tropical diseases currently constitute a major health problem and thus a challenge in the field of drug discovery. The current treatments show serious disadvantages due to cost, toxicity, long therapy duration and resistance, and the use of metal complexes as chemotherapeutic agents against these ailments appears to be a very attractive alternative. Herein, we describe three newly synthesized ruthenium complexes with a bioactive molecule, the purine analogue 5,6,7-trimethyl-1,2,4-triazolo[1,5-a]pyrimidine (tmtp): cis,fac-[RuCl2(dmso)3(tmtp)] (1), mer-[RuCl3(dmso)(H2O)(tmtp)]·2H2O (2) and fac,cis-[RuCl3(H2O)(tmtp)2] (3). Their structures were characterized using X-ray and spectroscopic methods (IR, NMR or EPR). The stability of the synthesized complexes 1-3 in various buffered solutions (pH=3-7.4) was monitored using conventional and stopped-flow techniques. The in vitro antiproliferative activity of all ruthenium complexes against promastigote forms of Leishmania spp. (L. infantum, L. braziliensis, and L. donovani) and epimastigote forms of Trypanosoma cruzi was investigated. Notably, the results showed that the activity of 1 against L. brasiliensis was more than three-fold higher than that of glucantime, and 1 showed no appreciable toxicity towards J774.2 macrophages. Additionally, 2 displayed even 141-fold lower toxicity against host cells than glucantime, demonstrating significantly higher selectivity than the reference drug. Therefore, 1 and 2 appear to be excellent candidates for further development as potential drugs for the effective treatment of leishmaniasis and Chagas disease. All novel complexes were also shown to be potent inhibitors of Fe-SOD in the studied species, while their effects on human CuZn-SOD were very low.

Rational design of dicarboxylato platinum(II) complexes with purine-mimetic ligands as novel anticancer agents.

Six novel platinum(II) complexes containing purine-mimetic ligands (5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine (dmtp), 7-isobutyl-5-methyl-1,2,4-triazolo[1,5-a]pyrimidine (ibmtp), 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp)) and dicarboxylato ligands (glutarato (glut) or cyclobutane-1,1-dicarboxylato (CBDC)) have been prepared and characterized with multinuclear magnetic resonance (1H, 13C, 15N, 195Pt) NMR, infrared (IR) and X-ray crystallography. Spectroscopic data in solid state and in solution unambiguously confirm the square-planar geometry of Pt(II) with two monodentate N3-bonded 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidine ligands and one O-chelating dicarboxylato ligand. Next, the effect of all the platinum(II) compounds on the viability of normal or cancer cells and their putative mechanisms of action have been investigated. Of the studied platinum(II) complexes, two ([Pt(glut)(dbtp)2] and [Pt(CBDC)(dbtp)2]) overcame the cisplatin resistance in human ovarian tumor cells (A2780cis or OVCAR-3) and arrested the cell cycle at S phase in mice mammary gland cancer cells (4T1), which indicates a mechanism of action different from that of cisplatin. Interestingly, preliminary in vivo toxicity assays revealed that both compounds tested in mice ([Pt(glut)(dbtp)2] 3 and [Pt(CBDC)(dbtp)2] 6) were less toxic in vivo than cisplatin or oxaliplatin. Additionally, compound 6 did not cause myelosuppression and showed over fivefold less accumulation in the liver than its glutarato analog 3.

Cytotoxic malonate platinum(II) complexes with 1,2,4-triazolo[1,5-a]pyrimidine derivatives: structural characterization and mechanism of the suppression of tumor cell growth.

A series of malonate (mal) platinum(II) complexes of the general formula [Pt(mal)(L)2], where L=5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine (dmtp) (1), 7-isobutyl-5-methyl-1,2,4-triazolo[1,5-a]pyrimidine (ibmtp) (2) or 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp) (3), has been prepared and characterized using multinuclear ((1)H, (13)C, (15)N, (195)Pt) NMR, IR and electrospray ionization mass spectrometry (ESIMS). Furthermore, the crystal structures of [Pt(mal)(dmtp)2]∙4H2O (1a) and [Pt(mal)(dbtp)2]∙CHCl3 (3a) have been determined using single-crystal X-ray diffraction. The spectroscopic characterization unambiguously confirmed the square-planar geometry of Pt(II) with two monodentate N3-bonded 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidines and one O-chelating malonate. The antiproliferative activities of the compounds against the human cell lines T47D (cisplatin-resistant human ductal breast epithelial tumor cell line) and A549 (lung adenocarcinoma epithelial cell line) and the mouse cell line 4T1 (mouse breast tumor model) were assessed using an in vitro screening assay. Compounds (2) and (3) exhibited substantial antigrowth properties against T47D cells, whereas only (3) exhibited an IC50 value that was lower than cisplatin and carboplatin against the 4T1 cell line. Additionally, compounds (2, 3) are capable of arresting the cell cycle of A549 cells at the G0/G1 phase, whereas cisplatin and carboplatin arrested the cells at the G2/M phase, indicating differences in the mechanism of the suppression of tumor cell growth. Finally, in the quest for low toxicity platinum drugs, the in vitro antiproliferative activity against normal mouse fibroblast cells (BALB/3T3) was evaluated. The inhibition of BALB/3T3 cell proliferation by the evaluated Pt(II) complexes increased in the order (1)<(2)<

Synthesis, characterization and antitumor properties of two highly cytotoxic ruthenium(iii) complexes with bulky triazolopyrimidine ligands.

Two ruthenium(III) complexes composed of 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp) ligands were prepared and structurally characterized by X-ray crystallography, IR, UV-Vis, EPR spectroscopies and cyclic voltammetry (CV). The crystal structures of trans-[RuCl(3)(H(2)O)(dbtp)(2)] 1 and mer-[RuCl(3)(dbtp)(3)]·0.815OCMe(2) 2 showed slightly distorted octahedral geometries with two 1 or three 2 monodentate dbtp ligands bound in a head-to-head orientation. In both complexes, the heterocyclic dbtp ligands were bound to the ruthenium(III) ion through the N3 nitrogen atom. A cytotoxicity assay of both ruthenium(III) compounds against two human cell lines (A549 - non-small cell lung carcinoma and T47D - breast carcinoma) was performed. The ruthenium(III) complexes showed excellent cytotoxicity with IC(50) values in the range of 0.02-2.4 µM against both cancer cell lines. In addition, the in vitro cytotoxic values of the ruthenium(III) compounds were 35-times for 1 and 172-times for 2 higher against T47D than the clinically used antitumor drug cisplatin.

Structure-cytotoxicity relationship for different types of mononuclear platinum(II) complexes with 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine.

To compare the in vitro cytotoxicity of platinum(II) complexes with 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp), three complexes were prepared: cis-[PtI(2)(dbtp)(2)] (1), cis-[Pt(NO(3))(2)(dbtp)(2)] (2) and cis-[Pt(C(4)H(4)O(5))(dbtp)(2)] (3). The coordination compounds have been structurally characterized by IR; (1)H, (13)C, (15)N, (195)Pt NMR and single-crystal X-ray diffraction (1). Spectroscopic studies reveal the monodentate coordination of the heterocycle ligand (dbtp) via N(3) to platinum(II) ions. In addition, the crystal structure of (1) shows that the platinum(II) ion is located in nearly square-planar PtI(2)N(2) environments with two heterocycle ligands (dbtp) arranged in a head-to-head orientation. The complexes have been screened for their cytotoxicity against two human cells: non-small cell lung carcinoma (A549) and breast cancer (T47D). All of the complexes demonstrated a significant antiproliferative activity against both cell lines. On the basis of these results, it is concluded that the cytotoxicity of the studied compounds against T47D follows the order: (3)<(1)<(2).

Platinum(II) complexes with 5,7-disubstituted-1,2,4-triazolo [1,5-a]pyrimidines: spectroscopical characterization and cytotoxic activity in vitro.

Complexes of the types: cis-[PtI(2)(dptp)(2)] (1), cis-[PtI(2)(NH(3))(dptp)] (2), trans-[PtI(2)(dptp)(dmso)] (3) and trans-[PtI(2)(dbtp)(dmso)] (4), where dptp=5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine (dptp), dbtp=5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine have been synthesized and characterized by infrared and multinuclear magnetic resonance spectroscopic techniques ((1)H, (13)C, (15)N, (195)Pt). In (195)Pt NMR, the cis-diiodo complexes were observed between -2601 ppm and -3261 ppm, while the trans coordination compounds were found at higher field (ca. -4389 ppm). In all cases significant (15)N NMR shielding (92-95 ppm) were observed for N(3) atom indicating this nitrogen atom as a coordination site. The cis complexes have been assayed for antitumor activity in vitro against two human cell lines: A549 (non-small cell lung carcinoma) and T47D (breast cancer). The results indicate a moderate antiproliferative activity of (2) against human cancer lines.

Platinum(IV) coordination compounds containing 5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one as nonleaving ligand. Molecular and cytotoxicity in vitro characterization.

Novel platinum(IV) coordination compounds with 5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one (HmtpO): cis-trans-[PtCl(2)(OH)(2)(NH(3))(HmtpO)] (1), cis-trans-[PtCl(5)(HmtpO)][(CH(3))(2)NH(2)] (2) have been prepared and structurally characterized by spectroscopic methods ((1)H, IR and X-ray crystallography (2)). The X-ray results indicate that the local geometry around the platinum(IV) centre approximates a typical octahedral arrangement with nitrogen atom N3 of the HmtpO and three chloride atoms in equatorial positions. The remaining two axial positions are occupied by two chlorides. The preliminary assessment of antitumor properties of (1) was performed as an in vitro antiproliferative activity against HL-60 human acute promyelocytic leukemia and HCV29T bladder cancer. The cis-trans-[PtCl(2)(OH)(2)(NH(3))(HmtpO)] (1) exhibits higher cytotoxic activity against HL-60 (IC(50)=6.4 µM) than cisplatin.

Mono- and dinuclear platinum(II) compounds with 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine. Structure, cytotoxic activity and reaction with 5'-GMP.

Mono- and dinuclear platinum(II) coordination compounds of formula cis-[PtCl(2)(NH(3))(dmtp)], 1, cis-[PtCl(2)(dmtp)(2)], 2 and {H(+)[C(28)H(32)Cl(2)N(16)Pt(2)](2+)(NO(3))(3)(H(2)O)(6)}, 3, in which dmtp is 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine have been synthesized and characterized by infrared and by (1)H, (13)C, (195)Pt NMR spectroscopy. The coordination units of the cationic species of formula [Pt(2)(mu-dmtp)(2)Cl(2)(dmtp)(2)](2+) are built up by two platinum atoms in a square-planar environment. Two sites are occupied by two 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine (dmtp) bridging ligands which are linked to both metal atoms through their nitrogen atoms in positions 3 and 4. The other two positions are occupied by one monodentate 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine (dmtp) molecule and a coordinated chloride. This compound is the first in which the same triazolopyrimidine ligand (dmtp) coordinates to a metal ion in two different ways, i.e. bridging bidentate and non-bridging monodentate. In addition, the interaction of compounds 1 and 2 with 5'-GMP was investigated in solution by (1)H NMR spectroscopy. The cytotoxicity of all the new platinum(II) compounds were studied by using two different cell lines: T47D (breast cancer) and HCV29T (bladder cancer).

Influence of a novel platinum compound--cis-dichloro (dimethylsulphoxide) (1-beta-D-rybofuranosyl-1,2,4-triazolo-3-arboxyamide) platinum (II)--"Pt-rib-1"--on cell cycle and apoptosis in ClS91 and B16 mouse melanoma in vitro.

Cisplatin has a significant role in the treatment of selected human tumors including advanced melanoma, but new platinum compounds are still in focus of search for better properties. Modern drug design is often based on studies detecting the abilities of tested drug to induce apoptosis and disturb cell cycle. Aim of the study was to establish the influence of a platinum complex Pt-rib-1 on cell cycle and apoptosis occurrence in mouse melanoma B16 and ClS91 cells. Pt-rib-1 is a ribavirin derivative. previously characterized and described as cytotoxic to B16 and ClS91 mouse melanoma cells in vitro. The new platinum complex (Pt-rib-1); cis- dichloro (dimethylsulphoxide) (1- beta- D-ribofuranosyl- 1,2,4-triazolo -3- carboxyamide) platinum (II) was supplied. Cisdiaminodichloroplatinum (II), (cisplatin) was used in control groups. To detect apoptotic and necrotic cells, Annexin V- conjugated with fluorescein isothiocyanate (Annexin V-FITC, Immunotech) and propidium iodide (IP, Immunotech) were used. Apoptosis detection were done using fluorescence microscopy and flow cytometry. The total DNA content within the cell indicated phase of the cell cycle. DNA content was measured using flow cytometry. Values given represent the mean from three determinations. Results were presented as mean +/- standard deviation (SD). Statistical analysis was done using t-Student test. There were 70.4% of apoptotic cells in the ClS91 culture after 24 h incubation with Pt-rib-1 at a concentration of 2.04 x 10(-3) M (4 x IC50). In B16 group, 83.2 per cent of apoptotic cells was found after 24h incubation with Pt-rib-1 at high concentration (2.30 x 10(-3) M). A 24-h experiment shows a threshold at a concentration higher than 3 x IC50 responsible for apoptosis induction in B16 and ClS91 cells. After 48 h incubation with Pt-rib-1 the per cent of apoptotic cells increased gradually with rising concentrations of Pt-rib-1 up to a final concentration of 2.04 x 10(-3) M and 0.92 x 10(-3) M in ClS91 and B16 groups, respectively. Cell accumulation was observed in S phase after 48 h incubation with Pt-rib-1. The per cent of cells in S phase increased from 31 to 51.1% and 38.8 to 50.0% in ClS91 and B16 culture, respectively. There were no B16 and ClS91 cells in G2/M phase after incubation with higher concentrations of Pt-rib-1 (from 0.2 to 2.0 x 10(-5) M/dm3). Pt-rib-1 partially exhibits action of cisplatin. which has no specific influence on cell cycle and ribavirin. probably responsible for DNA synthesis delay.

Multinuclear NMR spectroscopy and antitumor activity of novel platinum(II) complexes with 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidines.

Novel platinum(II) complexes with 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidines have been synthesized and characterized by infrared and multinuclear magnetic resonance spectroscopic techniques (1H, 13C, 15N, 195Pt). The complexes are of two types: [PtCl2(L)2] and [PtCl2(NH3)(L)], where L=5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine (dptp) and 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp). Significant 15N NMR upfield shifts (92-95 ppm) were observed for N(3) atom indicating this nitrogen atom as a coordination site. The molecular structure suggest that Pt(II) ion has the square planar geometry with N(3) bonded 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidines, N-bonded second ligand (NH3 for cis-[PtCl2(NH3)(L)] or, respectively, 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidines for cis-[PtCl2L2]) and two cis chloride anions. The antiproliferative activity in vitro of complexes (1-4) have been tested against the cells of four human cell lines: SW707 rectal adenocarcinoma, A549 non-small cell lung carcinoma, T47D breast cancer and HCV29T bladder cancer. The results indicate a moderate antiproliferative activity of (4) against the cells of rectal, breast and bladder cancer and a marked and selective cytotoxic effect of (1-3) against the cells of all studied human cancer lines.