Rositsa P. Nikolova

Anthracene-Derived Bis-Aminophosphonates: Crystal Structure, In Vitro Antitumor Activity, and Genotoxicity In Vivo

Abstract The X-ray crystal structures of the anthracene-derived bis-aminophosphonates 4.4′-bis[N-methyl(diethoxyphosphonyl)-1-(9-anthryl)]diaminodiphenylmethane (1) and 1,3-bis [N-methyl(diethoxyphosphonyl)-1-(9-anthryl)]diaminobenzene (3) are reported. The X-ray analyses demonstrated that both compounds crystallize in a centrosymmetric manner containing a meso-form (1) and a pair of enantiomers (3). The cytotoxic potential, genotoxicity, and antiproliferative activity of bis-aminophosphonates 1 and bis[N-methyl(diethoxyphosphonyl)-1-(9-anthryl)]benzidine (2), as well as their subcellular distribution in a tumor cell culture system, are also discussed. Compounds 1 and 2 showed optimal antiproliferative activity to human tumor cells from colon carcinoma line HT-29. In vitro and in vivo safety testing revealed that the compounds exert lower toxicity to normal cells as compared with well-known anticancer and cytotoxic agents. Supplemental materials are available for this article. Go to the publishers online edition ofPhosphorus, Sulfur, and Silicon and the Related Elementsto view the free supplemental file. GRAPHICAL ABSTRACT

A microporous titanosilicate for selective killing of HeLa cancer cells

Structural distribution of zinc(II) ions in the pore system of three silicate molecular sieves has revealed an unprecedented application of the microporous titanosilicate Zn–ETS-4 as a non toxic, highly efficient and selective inhibitor of HeLa cancer cells.

3-Carb­oxy­phenyl­boronic acid–theophylline (1/1)

The title two-component molecular crystal [systematic name: 3-(dihydroxyboranyl)benzoic acid–1,3-dimethyl-7H-purine-2,6-dione (1/1)], C7H7BO4·C7H8N4O2, comprises theophylline and 3-carboxyphenylboronic acid molecules in a 1:1 molar ratio. In the crystal, molecules are self-assembled by O—H⋯O and N—H⋯N hydrogen bonds, generating layers parallel to (-209). The layers are stacked through π–π [centroid–centroid distance = 3.546 (2) Å] and C—H⋯π interactions.

Conformational behaviour of 3-methyl-4-(4-methylbenzoyl)-1-phenyl-pyrazol-5-one: a sudden story of three desmotropes

The conformational behaviour of 3-methyl-4-(4-methylbenzoyl)-1-phenyl-pyrazol-5-one was studied using a combination of X-ray diffraction, NMR spectroscopy in solution and solid state, and DFT calculations in the gas phase. The compound can adopt four different tautomers, determined by the combination of the keto–enol tautomerism of pyrazolone and the attached 4-acyl carbonyl group. Potential energy surface simulations in gas phase show that each of the tautomeric forms has stable conformers, defined by energy minima, which could potentially be obtained in solid state. NMR analyses indicate that the keto–enol conformations with intramolecular H-bonding are preferred in solutions. Crystallization trials produced five different crystal phases; three yellow and two colorless. The single crystal XRD and solid state NMR structural analyses revealed that three desmotropes are obtained, two of them as two different conformational polymorphs. The difference in the coloration is attributed to the displacement of the double bond producing different conjugations of the pyrazolone. Studies on the effect of the solvent on the solid state structure could not produce a systematic trend and in fact most of the studied crystal phases could be obtained from acetone and ethanol–water solutions. Investigations on the factors governing the crystallization of different phases, temperature, concentration and solvent nature, are in progress.

Microwave assisted synthesis and X-ray structure of a novel anthracene-derived aminophosphonate. Enantioseparation of two α-aminophosphonates and genotoxicity in vivo

GRAPHICAL ABSTRACT ABSTRACT A novel anthracene-derived α-aminophosphonate has been synthesized through a classical addition reaction of dimethyl phosphite to a Schiff base and via a microwave assisted Kabachnik–Fields reaction. The compound has been characterized by elemental analysis, TLC, IR, NMR, and fluorescent spectra. The X-ray analysis showed that the compound crystallizes in the orthorhombic space group Pbca (N° 61) with one molecule per asymmetric unit. The enantioseparation of two racemic aminophosphonates (5 and 6) into enantiomers (5a, 5b and 6a, 6b, respectively) has been performed. Data about genotoxicity and antiproliferative activity in vivo of the racemic compounds and their enantiomeric forms is also presented. The studied racemic α-aminophosphonates 5 and 6 and their enantiomers have weak genotoxic effect. Both pairs of enantiomers did not show a significant inhibition of cell dividing processes in the bone marrow cells compared to 5 and 6. The hematopoietic function of the bone marrow will not be discontinued after exposure of the tested compounds.

3-[2-(5-tert-Butyl-1,2-oxazol-3-yl)hydrazinyl­idene]chroman-2,4-dione

In the title compound, C16H15N3O4, the dihedral angle between the chromane and isoxazole rings [r.m.s. deviations = 0.042 and 0.007 Å, respectively] is 20.33 (12)°. The molecular geometry is stabilized by an intramolecular N—H⋯O hydrogen bond. In the crystal, N—H⋯O hydrogen bonds generate chains along the c-axis direction. The crystal studied was a non-morohedral twin.

(4-Carbamoylphen­yl)boronic acid

In the title compound, C7H8BNO3, the molecule lies on an inversion center leading to a statistical disorder of the B(OH)2 and CONH2 groups. In the crystal structure, molecules are linked by N—H⋯O and O—H⋯O hydrogen bonds, forming sheets parallel to the bc plane. The B(OH)2 and CONH2 groups are twisted out of the mean plane of the benzene ring by 23.9 (5) and 24.6 (6)°, respectively.

Synthesis of 4-acetyl-2(3H)-benzothiazolone: Sulfur bioisostere of benzoxazolone allelochemicals

GRAPHICAL ABSTRACT ABSTRACT A multi-step methodology for the synthesis of 4-acetyl-2(3H)-benzothiazolone was developed in order to prepare a new biomimetic analogue of benzoxazolone allelochemicals. The compound was prepared from commercially available o-toluidine in 23% overall yield. The structure of 4-acethyl-2(3H)-benzothiazolone was confirmed by NMR spectroscopy and X-ray crystallography.

Synthesis of MOFs from Zn,Cd,Ni-4-carboxyphenylboronic acid with DMF solvent

Synthesis and characterization of porous metal organic frameworks (MOFs) has prompted considerable interest because of the possibility to design the pore size and physical/chemical properties by suitable selection of the organic linkers (ligands). In this work, we have chosen a classical solvothermal synthesis strategy involving 4-carboxyphenylboronic acid, a molecule that is analogic to the terephthalic acid, ZnCdNi-OAc metal salts and DMF as solvent. It is known that during solvothermal synthesis DMF decomposes to dimethylamine which is easily incorporated in MOF’s [1], [2]. The obtained MOFs are characterized by single-crystal X-ray diffraction, X-ray powder diffraction, TG analyses, IR spectroscopy and BET analyses. Preliminary X-ray single crystal diffraction results showed that a new type of structure may be produced in function of the temperature. The Cdstructure crystalizes in the hexagonal Space group P6222, with respective parameters of a = 14.4113(12), c = 13.0416(7) Å (Fig. 1). The cadmium ion is tetra coordinated by the oxygens of the B(OH)2 and COOmoieties. The 4-carboxyphenylboronic acid is disorder and attempts to lower the symmetry to model the disorder resulted in unstable refinement. In the studied systems in addition to the reported new compound isotypical structures to MOF-5 containing 4-carboxyphenylboronic acid instead of 1,4-benzenedicarboxylate were also obtained.

Ammonium hydrogen (RS)-[(5-methyl-2-oxo-1,3-oxazolidin-3-yl)meth-yl]phospho-nate.

In the title compound, NH4 +·C5H9NO5P−, the five-membered methyloxazolidin-2-one unit is disordered over two positions, the major component having a site occupancy of 0.832 (9). A three-dimensional network of O—H⋯O and N—H⋯O hydrogen bonds stabilizes the crystal structure.