Maria Gdaniec

Synthesis, structural characterization and antitumor activity of novel 2,4-diamino-1,3,5-triazine derivatives

The syntheses, structural elucidation based on NMR spectroscopy and X-ray analysis of 8 as well as antitumor activities of novel 2,4-diamino-1,3,5-triazine derivatives 5 and 7-22 are described. Screenings performed at NCI showed that most derivatives possessed a moderate to strong growth inhibition activity on various tumor panel cell lines between 0.148 and 56.2 microM concentrations. 2-Amino-6-bromomethyl-4-(3,5,5-trimethyl-2-pyrazoline)-1,3,5-triazine 11 showed the most potent antitumor activity with the mean midpoint values of log(10) GI50, log(10) TGI50 and log(10) LC50 of all tests equal to -5.26, -4.81 and -4.37, respectively and therefore, it can be considered as a lead structure for further development of anticancer agents.

Nickel(II)-, cobalt(II)-, copper(II)-, and zinc(II)-phthalate and 1-methylimidazole coordination compounds: synthesis, crystal structures and magnetic properties

Three new coordination polymers [M(Pht)(1-MeIm)2]n (where M=Cu (1), Zn (2), Co (3); Pht2−=dianion of o-phthalic acid; 1-MeIm=1-methylimidazole) and two compounds [M(1-MeIm)6](HPht)2 · 2H2O (M=Co (4), Ni (5)) have been synthesized and characterized by X-ray crystallography. The structures of 1–3 (2 is isostructural to 3) consist of [M(1-MeIm)2] building units connected by 1,6-bridging phthalate ions to form infinite chains. In complex 1, each copper(II) center adopts a square coordination mode of N2O2 type by two O atoms from different phthalate ions and two N atoms of 1-MeIm, whereas in 3 two independent metal atoms are tetrahedrally (N2O2) coordinated to a pair of Pht ligands and a pair of 1-MeIm molecules. There are only van der Waals interactions between the chains in 1, while the three-dimensional network in 3 is assembled by C–H⋯O contacts. In contrast to polymers 1–3 the structures of 4 and 5 (complexes are also isostructural) are made up of the [M(1-MeIm)6]2+ cation, two hydrogen phthalate anions (HPht−) and two H2O solvate molecules. The coordination around each metal(II) atom is octahedral with six nitrogen atoms of 1-MeIm. Extended hydrogen bonding networks embracing the solvate water molecules and a phthalate residue as well as the weak C–H⋯O interactions stabilize the three-dimensional structures. Magnetic studies clearly show that the magnetic ions do not interact with each other. Furthermore, in compound 4 we have another example of a highly anisotropic Co2+ ion with a rhombic g-tensor and large zero-field-splitting. The complexes were also characterized by IR and 1H NMR spectroscopy, thermogravimetric analysis, and all data are discussed in the terms of known structures.

Synthesis, characterization and spectra of lanthanide(III) hydrazone complexes: The X-ray molecular structures of the erbium(III) complex and the ligand

Abstract A series of nine new lanthanide(III) complexes of the type [Ln(PBH)2(NO3)2]NO3·xH2O (PBH=2-pyridinecarboxaldehyde benzoylhydrazone) have been prepared and studied by IR, UV–Vis and mass spectra. In addition the crystal structures of PBH·H2O and [Er(PBH)2(NO3)2]NO3·1.5H2O have been solved. Erbium atom is ten-coordinate and the coordination polyhedron is best described as a distorted bicapped square antiprism.

Strong hydrogen bonds in 1:1 and 2:1 complexes of pyridine betaine with strong acids

Abstract The crystal structure of bis(pyridine betaine) hydrochloride- d 1 monohydrate- d 2 has been determined by X-ray analysis. The carboxylate groups of a pair of pyridine betaine molecules are bridged by a deuteron to form a centro-symmetric dimer featuring a very strong hydrogen bond of length 2.444(4) A. The geometric mass effect (Δ R ≈ 0.008 A) is well within the range observed for this type of hydrogen bond. The FT-IR spectra of polycrystalline 1:1 and 2:1 complexes of pyridine betaine with HNO 3 , HCl, HBr, HI, HO 3 SCF 3 , HClO 4 , HBF 4 , and H 2 SO 4 have been investigated in the 4000–200 cm −1 range. In the 1:1 complexes a proton is transferred from the acid to the betaine molecule, C 5 H 5 N + CH 2 COOH · A − , and both the νOH and νCO frequencies vary with the proton acceptor properties of the anion. The spectra of the 2:1 complexes show broad and intense O · H · O stretching absorptions in the 1500–200 cm −1 range which are slightly affected by the anion and are similar to that for type A acid salts of carboxylic acids. The skeletal vibrations of the betaine residue were identified by second derivative spectroscopy. Evidence based on the νCO vibration and deuteration suggests that the hydrogen bonds in [C 5 H 5 NCH 2 COO · H · OOCCH 2 NC 5 H 5 ] + A − are described by single minimum potentials; ν H = 940 cm −1 , ν H /ν D = 1.2. As betaines are widely distributed in plants and animal tissue and form complexes with strong hydrogen bonds, such bonds should be formed in biological systems.

Synthesis and X-ray diffraction study of Zn(II) complexes with o-phthalic acid and aromatic amines ☆

Abstract New zinc (II) complexes [Zn(Pht)A2], where Pht2−=dianion of o-phthalic acid, A=pyridine (1), 3-methylpyridine (2), 4-methylpyridine (3) and [Zn(Pht)A] (A=4-methylpyridine (4)) have been synthesised and characterised by X-ray crystallography. The compounds have polymeric structures due to 1,6-bridging ability of the o-phthalate ligand. Polymeric chains exhibit three types of organisation in the crystal. Complexes 1 and 2 have similar structures, where Zn atom is coordinated by two oxygen atoms of two carboxylate groups and two nitrogen atoms of N-containing ligands. Two independent Zn atoms in 3 have different environments: tetrahedral N2O2 and distorted square-pyramidal N2O3. One of the acid residues behaves as bidentate 1,6-bridge, while the other acts as tridentate (1,6-bridging and 1,3-chelating) ligand. One of the Zn atoms in 4 has a tetrahedral NO3 geometry, while the second is characterised by a distorted octahedral NO5 coordination polyhedron. Both phthalate anions are tetradentate and act as syn–syn, syn–anti and monoatomic Zn–O–Zn bridging ligands. The IR spectra are discussed in relation to the crystal structures.

Zinc(II) carboxylates with imidazole and 2-methylimidazole: unprecedented cyclic dimer and polynuclear coordination polymers based on bridging phthalate ions

Novel zinc(II) coordination polymer [Zn(Pht)(Im)2]n (1), unique cyclic dimer [Zn(Pht)(Im)(H2O)]2 (2) and coordination polymer [Zn(Pht)(2-MeIm)]n (3) (where Pht2−=dianion of o-phthalic acid, Im=imidazole, 2-MeIm=2-methylimidazole) have been synthesized and their structures characterized by X-ray crystallography. Both carboxylate groups of the phthalate dianion coordinate in a monodentate mode bridging two Zn(II) ions with formation of 1D zigzag chain in 1. Two Im ligands play a double role: they coordinate the metal atom and join the coordination polymers via NH⋯O hydrogen bonds into a 3D-network. Complex 2 represents the first example of a metallocycle in which two Zn(II) atoms are bridged by two phthalate ligands forming a 14-membered ring. The Zn(II) atom is coordinated by two O atoms of Pht2− carboxylate groups, N atom of the Im and O atom of the water molecule with formation of tetrahedral NO3 metal-binding site. The molecules of 2 form a 3D-network through NH⋯O and OH⋯O hydrogen bonds between carboxylate groups of Pht2−, Im and water molecules. Compound 3 reveals the characteristic structural features of both compounds 1 and 2. One pair of zinc atoms is linked by 1,6-bridge of two phthalate ligands, while the other is held together through syn–syn bridging carboxylate groups in a 1,3-fashion from the same phthalates. As a result, infinite chains with alternation of 14-membered and eight-membered cycles are formed. Additional hydrogen bonds link the chains to form a 2D-network. IR and 1H NMR spectra of 1–3 are also reported.

Four-coordinate copper(I) iodide complexes with triphenylphosphine and heterocyclic thione ligands. The crystal structure of [Cu(PPh3)2(pymtH)I]

Abstract [Cu(PPh3)I]4 reacts with heterocyclic thiones (L) [L = pyrimidine-2-thione (pymtH), 1,3-thiazoline-2-thione (tzdtH), 1,3-imidazoline-2-thione (imtH), benz-1,3-imidazoline-2-thione (bzimtH2) and benz-1,3-thiazoline-2-thione (bztztH)] in the presence of triphenylphosphine to give mononuclear complexes of the general formula [Cu(PPh3)2 (L)I]. These complexes have been characterized by various physicochemical methods. The crystal structure of [Cu(PPh3)2(pymtH)I] has been determined by single-crystal X-ray diffraction methods. The molecule is mononuclear, with a distorted tetrahedral geometry and bond lengths CuS = 2.338(4), CuI = 2.674(2), CuP = 2.296(4) and 2.303(4) A.

Synthesis, molecular structure and anticancer activity of 1-allyl-3-amino-2-(4-chloro-2-mercaptobenzenesulphonyl)guanidine derivatives.

A series of 3-allylamino-6-chloro-7-R-1,1-dioxo-1,4,2-benzodithiazines (2a-e) was obtained by the reaction of 6-chloro-3-methylthio-1,4,2-benzodithiazine-1,1-dioxides (1a-e) with allylamine. Selective hydrazinolysis of the allylaminobenzodithiazines (2a-e) gave the appropriate 1-allyl-3-amino-2-(4-chloro-2-mercaptobenzenesulphonyl)guanidines (3a-e) in good yields. The reaction of 3a with dimethylsulphate under alkaline conditions provided the methylthio derivative 4. The structures of these compounds were confirmed on the basis of elemental analysis, spectral data (IR, 1H- and 13C-NMR) and X-ray analysis. Screening data indicated that the compounds 3a and 3d exhibited significant in vitro activities against numerous human tumour cell lines, whereas compounds 3b and 3c showed a moderate activity.

Enantioselective Inclusion Complexation of N‐Nitrosopiperidines by Steroidal Bile Acids

N-nitrosamines, whose chirality is solely due to hindered rotation about the N-N bond, are enantioselectively enclathrated by the crystal host matrices of cholic or deoxycholic acid, as evidenced by X-ray crystallography (see structure in picture) and CD spectra.

Phthalocyanine Derivatives Possessing 2-(Morpholin-4-yl)ethoxy Groups As Potential Agents for Photodynamic Therapy

Three 2-(morpholin-4-yl)ethoxy substituted phthalocyanines were synthesized and characterized. Phthalocyanine derivatives revealed moderate to high quantum yields of singlet oxygen production depending on the solvent applied (e.g., in DMF ranging from 0.25 to 0.53). Their photosensitizing potential for photodynamic therapy was investigated in an in vitro model using cancer cell lines. Biological test results were found particularly encouraging for the zinc(II) phthalocyanine derivative possessing two 2-(morpholin-4-yl)ethoxy substituents in nonperipheral positions. Cells irradiated for 20 min at 2 mW/cm(2) revealed the lowest IC50 value at 0.25 μM for prostate cell line (PC3), whereas 1.47 μM was observed for human malignant melanoma (A375) cells. The cytotoxic activity in nonirradiated cells of novel phthalocyanine was found to be very low. Moreover, the cellular uptake, localization, cell cycle, apoptosis through an ELISA assay, and immunochemistry method were investigated in LNCaP cells. Our results showed that the tested photosensitizer possesses very interesting biological activity, depending on experimental conditions.