Crownphyrins: Metal-Mediated Transformations of the Porphyrin-Crown Ether Hybrids.

Crownphyrins are hybrid macrocycles combining structural features of porphyrin and crown ethers. The molecular architecture renders them an intriguing class of hosts capable of binding neutral, and ionic guests. The presence of dynamic covalent imine linkages connecting the dipyrrin segment with the ether chain enables unusual coordination behavior of crownphyrins, as demonstrated by the formation of two classes of strikingly different complexes. The remarkable metal-mediated expansion to the helical [2+2] macrocyclic complex is reversible. The reaction of the figure-eight mercury(II) assembly with [2.2.2]cryptand results in ring contraction providing the metal-free crownphyrin macrocycle.

Mixed-Generation PAMAM G3-G0 Megamer as a Drug Delivery System for Nimesulide: Antitumor Activity of the Conjugate Against Human Squamous Carcinoma and Glioblastoma Cells.

Polyhydroxylated dendrimer was synthesized from poly(amidoamine) (PAMAM) dendrimer generation 3 by addition of glycidol (G3gl). G3gl megamer was further modified by binding PAMAM G0 dendrimers by activation of G3gl with p-nitrophenylchloroformate, followed by the addition of excess PAMAM G0 and purification using dialysis. The maximum G0 binding capacity of G3gl was 12 in the case when G0 was equipped with two covalently attached nimesulide equivalents. Nimesulide (N) was converted into N-(p-nitrophenyl) carbonate derivative and fully characterized using X-ray crystallography and spectral methods. Nimesulide was then attached to G0 via a urea bond to yield G02N. The mixed generation G3gl-G02N megamer was characterized using 1H NMR spectroscopy, and its molecular weight was estimated to be 22.4 kDa. The AFM image of G3gl-G02N deposited on mica demonstrated aggregation of nimesulide-covered megamer. The height of the deposited megamer was 8.5 nm. The megameric conjugate with nimesulide was tested in vitro on three human cell lines: squamous cell carcinoma (SCC-15) and glioblastoma (U-118 MG) overexpressing cyclooxygenase-2 (COX-2), and normal skin fibroblasts (BJ). The conjugate efficiently penetrated into all cells and was more cytotoxic against SCC-15 than against BJ. Moreover, the conjugate produced a strong and selective antiproliferative effect on both cancer cell lines (IC50 < 7.5 µM).

Light-stable polypyridine silver(i) complexes of 1,3,5-triaza-7-phosphaadamantane (PTA) and 1,3,5-triaza-7-phosphaadamantane-7-sulfide (PTA[double bond, length as m-dash]S): significant antiproliferative activity of representative examples in aqueous media.

A series of novel silver(i) 2,2':6',2''-terpyridine (tpy), 4'-(4-methylphenyl)-2,2':6':2''-terpyridine (tpy-Ph-Me) and 1,10-phenanthroline-5,6-dione (dione) derivatives containing PTA (1,3,5-triaza-7-phosphaadamantane) or 1,3,5-triaza-7-phosphaadamantane-7-sulfide (PTA[double bond, length as m-dash]S) have been synthesized and fully characterized. Two types of complexes have been obtained, monocationic [Ag(tpy)(PTA)](NO3) (1), [Ag(tpy-Ph-Me)(PTA)](NO3) (2), [Ag(dione)(PTA[double bond, length as m-dash]S)](BF4) (4) and [Ag(dione)2](PF6) (5) and neutral [Ag(dione)(PTA[double bond, length as m-dash]S)(NO3)] (3). The solid-state structures of four complexes have been determined by single-crystal X-ray diffraction. Complexes 1 and 2 are luminescent at room temperature and 77 K while 5 shows emission only at 77 K. Compounds 3 and 4 are not emissive. Furthermore, representative light-stable and water-soluble 1 and 3 were evaluated for their cytotoxic activities on the normal human dermal fibroblast (NHDF) cell line and their antitumor activity using the human lung carcinoma (A549), epithelioid cervix carcinoma (HeLa) and human breast adenocarcinoma (MCF-7) cell lines. Interactions between the complexes and human serum albumin (HSA) using UV-Vis, fluorescence and circular dichroism spectroscopy (CD) were also investigated.

New γ-Halo-δ-lactones and δ-Hydroxy-γ-lactones with Strong Cytotoxic Activity.

This paper presents the synthesis of γ -halo- δ -lactones, δ -iodo- γ -lactones and δ -hydroxy- γ -lactones from readily available organic substrates such as trans-crotonaldehyde and aryl bromides. Crystal structure analysis was carried out for lactones that were obtained in crystalline form. All halo- δ -lactones and δ -hydroxy- γ -lactones were highly cytotoxic against gastric cancer AGS cells with I C 50 values in the range of 0.0006-0.0044 mM. Some lactones showed high bactericidal activity against E. coli ATCC 8739 and S. aureus ATCC 65389, which reduced the number of CFU/mL by 70-83% and 87% respectively.

Preparation of Enantiomeric ß-(2',5'-Dimethylphenyl)Bromolactones, Their Antiproliferative Activity and Effect on Biological Membranes.

Three novel enantiomeric pairs of bromolactones possesing a 2,5-dimethylphenyl substituent at the ß-position of the lactone ring have been synthesized from corresponding enantiomeric (E)-3-(2',5'-dimethylphenyl)hex-4-enoic acids (4) by kinetically controlled bromolactonization with N-bromosuccinimide (NBS). γ-Bromo-δ-lactones (5) were isolated as the major products. Absolute configurations of stereogenic centers of γ-bromo-δ-lactones (5) were assigned based on X-ray analysis; configurations of cis δ-bromo-γ-lactones (6) and trans δ-bromo-γ-lactones (7) were determined based on mechanism of bromolactonization. Synthesized compounds exhibited significant antiproliferative activity towards the four canine cancer cell lines (D17, CLBL-1, CLB70, and GL-1) and one human cancer line (Jurkat). Classifying the compounds in terms of activity, the most active were enantiomers of trans δ-bromo-γ-lactones (7) followed by enantiomers of cis isomer (6) and enantiomeric γ-bromo-δ-lactones (5). Higher activity was observed for all stereoisomers with S configuration at C-4 in comparison with their enantiomers with 4R configuration. Synthesized compounds did not induce hemolysis of erythrocytes. The results of the interaction of bromolactones with red blood cell membranes suggest that these compounds incorporate into biological membranes, concentrating mainly in the hydrophilic part of the bilayer but have practically no influence on fluidity in the hydrophobic region. The differences in interactions with the membrane between particular enantiomers were observed only for γ-lactones: stronger interactions were found for enantiomer 4R,5R,6S of cis γ-lactone (6) and for enantiomer 4S,5R,6S of trans γ-lactone (7).

HS⇄LS transition in iron(II) two-dimensional coordination networks containing tris(tetrazol-1-ylmethyl)methane as triconnected building block.

Novel tripodal ligand 1,1',1''-tris(tetrazol-1-ylmethyl)methane (111tz) and products of its reactions with perchlorate as well as with tetrafluoroborate salts of iron(II) are presented. The isostructural complexes, [Fe(111tz)2](ClO4)2 and [Fe(111tz)2](BF4)2, were isolated as two-dimensional (2D) coordination networks revealing a honeycomb-like pattern with cages occupied by disordered anions. 111tz molecules act as a tridentate ligand bridging three adjacent Fe(II) ions, and the nitrogen N4 atom of six tetrazole rings (tz) is placed in octahedron vertices of FeN6 chromophores. The complexes, crystallizing in the P3 space group, were characterized by variable-temperature single-crystal X-ray diffraction and variable-temperature magnetic susceptibility measurements. Variable-temperature magnetic susceptibility measurements show that both systems undergo abrupt and complete spin transition with T(1/2)(↑) = T(1/2)(↓) = 176 K for perchlorate and T(1/2)(↑) = 193.8 and T(1/2)(↓) = 192.8 K for the tetrafluoroborate analogue. Change of spin state in both complexes is accompanied by a thermochromic effect. The HS→LS transition in [Fe(111tz)2](ClO4)2 involves shortening of the Fe-N4 bond lengths from 2.171(2) Å (293 K) to 2.002(1) Å (100 K). In [Fe(111tz)2](BF4)2, lowering of temperature from 293 to 100 K is accompanied by shortening of the Fe-N4 distances from 2.179(2) to 1.987(2) Å, respectively. Perchlorate in [Fe(111tz)2](ClO4)2 or tetrafluoroborate anions in [Fe(111tz)2](BF4)2 are engaged in the formation of intermolecular contacts within as well as with the neighboring 2D layer.

Microbial Baeyer-Villiger oxidation of steroidal ketones using Beauveria bassiana: Presence of an 11α-hydroxyl group essential to generation of D-homo lactones.

This paper demonstrates for the first time transformation of a series of 17-oxo steroidal substrates (epiandrosterone, dehydroepiandrosterone, androstenedione) by the most frequently used whole cell biocatalyst, Beauveria bassiana, to 11α-hydroxy-17a-oxa-d-homo-androst-17-one products, in the following sequence of reactions: 11α-hydroxylation and subsequent Baeyer-Villiger oxidation to a ring-D lactone. 11α-Hydroxyprogesterone, the product of the first stage of the progesterone metabolism, was further converted along two routes: hydroxylation to 6ß,11α-dihydroxyprogesterone or 17ß-acetyl chain degradation leading to 11α-hydroxytestosterone, the main metabolite of the substrate. Part of 11α-hydroxytestosterone underwent a rare reduction to 11α-hydroxy-5ß-dihydrotestosterone. The experiments have demonstrated that the Baeyer-Villiger monooxygenase produced by the strain catalyzes solely oxidation of C-20 or C-17 ketones with 11α-hydroxyl group. 17-Oxo steroids, beside the 11α-hydroxylation and Baeyer-Villiger oxidation, also underwent reduction to 17ß-alcohols; activity of 17ß-hydroxysteroid dehydrogenase (17ß-HSD) has significant impact on the amount of the formed ring-D δ-lactone.

2-(4-Bromo-phen-yl)-6-methyl-4H-1-benzopyran-4-one (4'-bromo-6-methyl-flavone).

Planar (r.m.s. deviation from the plane through all non-H atoms = 0.036 Å) mol-ecules of the title compound, C(16)H(11)BrO(2), form a layered structure stabilized by C-H⋯O hydrogen bonds and π-π stacking inter-actions.