Self-Assembled Molecular Complexes of 1,10-Phenanthroline and 2-Aminobenzimidazoles: Synthesis, Structure Investigations, and Cytotoxic Properties.

Three new molecular complexes (phen)3(2-amino-Bz)2(H+)(BF4-)·3H2O 5, (phen)3(2-amino-5(6)-methyl-Bz)2(H+)(BF4-)·H2O 6, and (phen)(1-methyl-2-amino-Bz)(H+)(BF4-) 7, were prepared by self-assembly of 1,10-phenanthroline (phen) and various substituted 2-aminobenzimidazoles. Confirmation of their structures was established through spectroscopic methods and elemental analysis. The X-ray diffraction analysis revealed that the crystal structure of 7 is stabilized by the formation of hydrogen bonds and short contacts. In addition, the molecular geometry and electron structure of molecules 5 and 6 were theoretically evaluated using density functional theory (DFT) methods. According to the DFT B3LYP/6-311+G* calculations, the protonated benzimidazole (Bz) units act as NH hydrogen bond donors, binding two phenanthrolines and a BF4- ion. Non-protonated Bz unit form hydrogen bonds with the N-atoms of a third molecule phen. The molecular assembly is held together by π-π stacking between benzimidazole and phenanthroline rings, allowing for N-atoms to associate with water molecules. The complexes were tested in vitro for their tumor cell growth inhibitory effects on prostate (PC3), breast (MDA-MB-231 and MCF-7), and cervical (HeLa) cancer cell lines using MTT-dye reduction assay. The in vitro cytotoxicity analysis and spectrophotometric investigation in the presence of ct-DNA, showed that self-assembled molecules 5-7 are promising DNA-binding anticancer agents warranting further in-depth exploration.

Estrone derived 2-naphthol analogue in the diastereoselective one-pot Betti-condensation.

The utility of deoxy-isoequilenine synthesized from estrone as valuable 2-naphthol analogue is demonstrated in the three components Betti-condensation. A simple, efficient and green procedure for the synthesis of aminobenzylnaphthol analogues (so-called Betti bases) has been realized highly diastereoselectively by using (S)-phenylethylamine and 1- or 2-naphthaldehyde. The absolute configuration of the new chiral compounds obtained has been determined by means of NMR experiments and confirmed by X-ray crystallography. The chiral steroidal aminobenzylnaphthols have been evaluated as pre-catalysts for the addition of diethylzinc to aldehydes with enantioselectivities of up to 98% ee.

Controlled tautomeric switching in azonaphthols tuned by substituents on the phenyl ring.

A series of new tautomeric azonaphthols are synthesized and the possibilities for molecular switching are investigated using molecular spectroscopy, X-ray analysis and density functional theory quantum chemical calculations. Two opposite effects that influence switching are studied: attaching a piperidine sidearm, and adding substituents to the phenyl ring. On the one hand, the attached piperidine moiety stabilizes the enol form leading to a controlled shift of the equilibrium upon protonation. On the other hand, the relative stability of the azonaphthol tautomers strongly depends on the effects of the substituents on the phenyl ring: electron donors tend to stabilize the enol tautomer, whereas electron acceptors lead to stabilization of the keto form. However, these effects do not shift fully the equilibrium towards either of the tautomers. Nevertheless, the effect of the substituents can be an additional tool to affect the switching between "on" and "off" states. Electron-withdrawing substituents stabilize the keto form and impede switching to the off state, whereas electron donors stabilize the enol form. The effect of the piperidine unit is dominant overall, and with strongly electron-withdrawing substituents at the phenyl ring, the enol form exists as a zwitterion.

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

In the title compound, C(16)H(15)N(3)O(4), 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 mol-ecular geometry is stabilized by an intra-molecular 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.

Bigel Formulations of Nanoencapsulated St. John's Wort Extract-An Approach for Enhanced Wound Healing.

This study aimed to develop a semisolid vehicle for topical delivery of nanoencapsulated St. John's wort (SJW) extract, rich in hyperforin (HP), and explore its wound-healing potential. Four nanostructured lipid carriers (NLCs) were obtained: blank and HP-rich SJW extract-loaded (HP-NLC). They comprised glyceryl behenate (GB) as a solid lipid, almond oil (AO), or borage oil (BO) representing the liquid lipid, along with polyoxyethylene (20) sorbitan monooleate (PSMO) and sorbitan monooleate (SMO) as surfactants. The dispersions demonstrated anisometric nanoscale particles with acceptable size distribution and disrupted crystalline structure, providing entrapment capacity higher than 70%. The carrier exhibiting preferable characteristics (HP-NLC2) was gelled with Poloxamer 407 (PM407) to serve as the hydrophilic phase of a bigel, to which the combination of BO and sorbitan monostearate (SMS) organogel was added. The eight prepared bigels with different proportions (blank and nanodispersion-loaded) were characterized rheologically and texturally to investigate the impact of the hydrogel-to-oleogel ratio. The therapeutic potential of the superior formulation (HP-NLC-BG2) was evaluated in vivo on Wistar male rats through the tensile strength test on a primary-closed incised wound. Compared with a commercial herbal semisolid and a control group, the highest tear resistance (7.764 ± 0.13 N) was achieved by HP-NLC-BG2, proving its outstanding wound-healing effect.

3-Carb-oxy-phenyl-boronic acid-theophylline (1/1).

The title two-component mol-ecular crystal [systematic name: 3-(dihy-droxy-boran-yl)benzoic acid-1,3-dimethyl-7H-purine-2,6-dione (1/1)], C(7)H(7)BO(4)·C(7)H(8)N(4)O(2), comprises theophylline and 3-carb-oxy-phenyl-boronic acid mol-ecules in a 1:1 molar ratio. In the crystal, mol-ecules 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 inter-actions.

Indium silicate with an imandrite-type structure.

This work reports the synthesis and characterization of novel zeolite-like indium silicate MS-2 (Minho-Sofia, solid number 2). The structure of this material is analogous to that of the mineral imandrite (Na6Ca1.5FeSi6O18), with In instead of Fe in the octahedral position. MS-2 is the first structurally confirmed indium silicate prepared under mild hydrothermal conditions and the only synthetic indium silicate related to the lovozerite mineral group. MS-2 (Na6.23Ca1.62In0.68Si6O18) exhibits significant indium deficiency in the octahedral position thus having the highest Si/In (8.8) ratio among the known indium silicates. The framework consists of occupationally disordered InO6 octahedra interconnected by 6-membered rings of [Si6O18] tetrahedra. The three-dimensional (3D) tunnel system is occupied by Na+ and Ca2+ charge-balancing ions. The low framework density (16.2 FC/1000 Å3) and high thermal stability (up to 900 °C) are comparable to other molecular sieves.

Surface Properties of 1DTiO2 Microrods Modified with Copper (Cu) and Nanocavities.

This work deals with Cu-modified 1DTiO2 microrods (MRs) and their surface properties. The pristine lyophilized precursor Cu_1DTiO2, prepared by an environmentally friendly cryo-lyophilization method, was further annealed in the temperature interval from 500 to 950 °C. The microstructure of all samples was characterized by electron microscopy (SEM/EDS and HRTEM/SAED), X-ray powder diffraction (XRD), infrared spectroscopy, simultaneous DTA/TGA thermoanalytical measurement, and mass spectroscopy (MS). Special attention was paid to the surface structure and porosity. The 1D morphology of all annealed samples was preserved, but their surface roughness varied due to anatase-rutile phase transformation and the change of the nanocrystals habits due to nanocavities formation after releasing of confined ice-water. The introduction of 2 wt.% Cu as electronically active second species significantly reduced the direct bandgap of 1DTiO2 in comparison with undoped TiO2 and the standard Degussa TiO2_P25. All samples were tested for their UV absorption properties and H2 generation by PEC water splitting. We presented a detailed study on the surface characteristics of Cu doped 1DTiO2 MRs due to gain a better idea of their photocatalytic activity.

(4-Carbamoylphen-yl)boronic acid.

In the title compound, C(7)H(8)BNO(3), the mol-ecule lies on an inversion center leading to a statistical disorder of the B(OH)(2) and CONH(2) groups. In the crystal structure, mol-ecules are linked by N-H⋯O and O-H⋯O hydrogen bonds, forming sheets parallel to the bc plane. The B(OH)(2) and CONH(2) groups are twisted out of the mean plane of the benzene ring by 23.9 (5) and 24.6 (6)°, respectively.

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

In the title compound, NH(4) (+)·C(5)H(9)NO(5)P(-), the five-membered methyl-oxazolidin-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.

Spontaneous conversion of O-tosylates of 2-(piperazin-1-yl)ethanols into chlorides during classical tosylation procedure.

A direct conversion of piperazinyl ethanols into chlorides via a classical O-tosylation protocol is observed. The acceleration of the transformation by the piperazine unit is demonstrated. It is found that the reaction goes via the corresponding O-tosylate, which converts spontaneously into chloride with different rate depending on the substrate structure. In the case of pirlindole derivative, partially aromatized chloride formation was observed upon prolongation and/or increased excess of tosyl chloride.

Synthesis, Spectroscopic Properties, Crystal Structure And Biological Evaluation of New Platinum Complexes with 5-methyl-5-(2-thiomethyl)ethyl Hydantoin.

BACKGROUND: The accidental discovery of Cisplatin's growth-inhibiting properties a few decades ago led to the resurgence of interest in metal-based chemotherapeutics. A number of well-discussed factors such as severe systemic toxicity and unfavourable physicochemical properties further limit the clinical application of the platinating agents. Great efforts have been undertaken in the development of alternative platinum derivatives with an extended antitumor spectrum and amended toxicity profile as compared to the reference drug cisplatin. The rational design of conventional platinum analogues and the re-evaluation of the empirically derived "structure- activity" relationships allowed for the synthesis of platinum complexes with great diversity in structural characteristics, biochemical stability and antitumor properties. METHODS: The new compounds have been studied by elemental analyses, IR, NMR and mass spectral analyses. The structures of the organic compound and one of the new mixed/ammine Pt(II) complexes were studied by X-ray diffraction analysis. The cytotoxic effects of the compounds were studied vs. the referent antineoplastic agent cisplatin against four human tumour cell lines using the standard MTT-dye reduction assay for cell viability. The most promising complex 3 was investigated for acute toxicity in male and female H-albino-mice models. RESULTS: A new organic compound (5-methyl-5-(2-thiomethyl)ethyl hydantoin) L bearing both S- and Ncoordinating sites and three novel platinum complexes, 1, 2 and 3 were synthesized and studied. Spectral and structural characterization concluded monodentate S-driven coordination of the ligand L to the metal center in complexes 1 and 2, whereas the same was acted as a bidentate N,S-chelator in complex 3. Ligand L crystallizes in the tetragonal space group I41/a (No 88) with one molecule per asymmetric unit. While complex 3 crystallizes in the monoclinic space group P21/c (No 14) with one molecule per asymmetric unit. In the same complex 3, the platinum ion coordinates an L ligand, a chloride ion and an ammonia molecule. In the in vitro experiments, the tested L and complexes 1 and 2 exhibited negligible cytotoxic activity in all tumor models. Accordingly, complex 3 is twice as potent as cisplatin in the HT-29 cells and is at least as active as cisplatin on the MDA-MB-231 breast cancer cell line. In the in vivo toxicity estimation of complex 3 no signs of common toxicity were observed. CONCLUSION: The Pt(II)-bidentate complex 3 exhibited significant cytotoxic potential equaling or surpassing that of the reference drug cisplatin in all the tested tumor models. Negligible anticancer activity on the screened tumor types has been shown by the ligand L and its Pt(II) and Pt(IV) complexes 1 and 2, respectively. Our study on the acute toxicity of the most active complex 3 proved it to be non-toxic in mice models.

Combretastatin A-4 analogues with benzoxazolone scaffold: Synthesis, structure and biological activity.

In order to design and synthesize a new class of heterocyclic analogues of natural combretastatin A-4 and its synthetic derivative AVE8062, the benzoxazolone ring was selected as a scaffold for a bioisosteric replacement of the ring B of both molecules. A library of 28 cis- and trans-styrylbenzoxazolones was obtained by a modified Wittig reaction under Boden's conditions. Structures of the newly synthesized compounds bearing the 3,4,5-trimethoxy-, 3,4-dimethoxy-, 3,5-dimethoxy-, and 4-methoxystyryl fragment at position 4, 5, 6 or 7 of benzoxazolone core were determined on the basis of spectral and X ray data. The in vitro cytotoxicity of styrylbenzoxazolones against different cell lines was examined. Stilbene derivative 16Z, (Z)-3-methyl-6-(3,4,5-trimethoxystyryl)-2(3H)-benzoxazolone, showed highest antiproliferative potential of the series, with IC50 of 0.25 µM against combretastatin resistant cell line HT-29, 0.19 µM against HepG2, 0.28 µM against EA.hy926 and 0.73 µM against K562 cells. Furthermore, the results of flow cytometric analysis confirmed that 16Z induced cell cycle arrest in G2/M phase in the cell lines like combretastatin A-4. This arrest is followed by an abnormal exit of cells from mitosis without cytokinesis into a pseudo G1-like multinucleate state leading to late apoptosis and cell death. Accordingly, synthetic analogue 16Z was identified as the most promising potential anticancer agent in present study, and was selected as lead compound for further detailed investigations.