Functional involvement of src and focal adhesion kinase in a CD99 splice variant-induced motility of human breast cancer cells

Earlier report showed that expression of a splice variant of CD99 transmembrane protein increases invasive ability of human breast cancer cells. Cell motility was also significantly enhanced by the CD99 splice variant expression. In an effort to identify the cellular components that mediate a signal transduction pathway triggered by the CD99 splice variant, known signal path inhibitors were examined for their effects on the motility of the CD99 splice variant-transfected MDA-MB-231 breast cancer cells. Phenylarsine oxide, an inhibitor of phosphatase specific for focal adhesion kinase, and PP1, an inhibitor of src kinase family, significantly suppressed motility of the cells. Among different types of src transfectant clones generated, kinase-negative mutant src transfectant cells were 80% less motile than the mock cells transfected with an empty-vector, while v-src and c-src transfectants exhibited cell motility levels at or slightly above the mock transfectant. These results suggest that src and focal adhesion kinase mediate the intracellular signaling pathway of a CD99 splice variant for the induction of motility of human breast cancer cells.     

N‐(Ferrocenecarbonyl)‐N′‐(quinolin‐8‐yl)thio­urea

In the title compound, [Fe(C₅H₅)(C₁₆H₁₂N₃OS)], the 8‐am­inoquinoline and acyl­thio­urea moieties are almost planar. There are two perpendicular arrangements of the mol­ecules in the crystal with slightly different conformations. The two cyclo­penta­dienyl rings in each mol­ecule are parallel and eclipsed.     

Fused 1,2‐Dithioles. Part VII

The 1,2‐dithiolosultam derivative 14 was obtained from the (α‐bromoalkylidene)propenesultam derivative 9 (Scheme 1). Regioselective cleavage of the two ester groups (→ 1b or 2b ) allowed the preparation of derivatives with different substituents at C(3) in the dithiole ring (see 27 and 28 ) as well as at C(6) in the isothiazole ring (see 17 – 21 ; Scheme 2). Curtius rearrangement of the 6‐carbonyl azide 21 in Ac₂O afforded the 6‐acetamide 22 , and saponification and decarboxylation of the latter yielded ‘sulfothiolutin’ ( 30 ). Hydride reductions of two of the bicyclic sultams resulted in ring opening of the sultam ring and loss of the sulfonyl group. Thus the reduction of the dithiolosultam derivative 14 yielded the alkylidenethiotetronic acid derivative 33 (tetronic acid=furan‐2,4(3H,4H)‐dione), and the lactam‐sultam derivative 10 gave the alkylidenetetramic acid derivative 35 (tetramic acid=1,5‐dihydro‐4‐hydroxy‐2H‐pyrrol‐2‐one) (Scheme 3). Some of the new compounds ( 14, 22, 26 , and 30 ) exhibited antimycobacterial activity. The oxidative addition of 1 equiv. of [Pt(η²‐C₂H₄)L₂] ( 36a , L=PPh₃; 36b , L=1/2 dppf; 36c , L=1/2 (R,R)‐diop) into the S? S bond of 14 led to the cis‐(dithiolato)platinum(II) complexes 37a – c . (dppf=1,1′‐bis(diphenylphosphino)ferrocene; (R,R)‐diop={[(4R,5R)‐2,2‐demithyl‐1,3‐dioxolane‐4,5‐diyl]bis(methylene)}bis[diphenylphosphine]).     

Single‐electron‐transfer/degenerative‐chain‐transfer mediated living radical polymerization of vinyl chloride catalyzed by thiourea dioxide/octyl viologen in water/tetrahydrofuran at 25 °C

The single‐electron‐transfer/degenerative‐chain‐transfer mediated living radical polymerization (SET–DTLRP) of vinyl chloride (VC) in H₂O/tetrahydrofuran at 25 °C catalyzed by thiourea dioxide [(NH₂)₂C?SO₂] is reported. This polymerization occurs only in the presence of a basic sodium bicarbonate (NaHCO₃) buffer and the electron‐transfer cocatalyst octyl viologen. The resulting poly(vinyl chloride) (PVC) has a number‐average molecular weight of 1500–7000 and a weight‐average molecular weight/number‐average molecular weight ratio of 1.5. This PVC does not contain detectable amounts of structural defects and has both active chloroiodomethyl and inactive chloromethyl chain ends. Because of possible side reactions caused by the primary sulfoxylate anion (SO), the catalytic activity of (NH₂)₂C?SO₂ in the SET–DTLRP of VC is lower than that of the single‐electron‐transfer agent sodium dithionite. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 287–295, 2005     

Analysis of B3LYP and MP2 conformational population distributions in trans‐nicotine,acetylcholine, and ABT‐594

This work presents an analysis of the equivalence of MP2 and DFT (B3LYP functional) conformational populations. As a test case, we select three cholinergic agents (trans‐nicotine, acetylcholine, and the nicotinic analgesic ABT‐594), where the minima on the conformational energy hypersurfaces expand a large range of energies (～0–30 kJ mol^?1). From energetic and structural data obtained in vacuo at the MP2 and B3LYP/cc‐pVDZ levels, we build conformational partition functions, including the effect of the conformational kinetic energy and the rotovibrational coupling. Our results at a physiological temperature (37°C) show qualitative agreement in all cases. Quantitative agreement, however, is only found for trans‐nicotine and ABT‐594. In the first case, energy minima differ by <0.2 kJ mol^?1. Therefore, the equivalence of structural results translates in the equivalence of the conformational distribution. For ABT‐594, the minima are separated by as much as 8.0 kJ mol^?1, and the conformational energy determines the conformational distribution. In this case, the slight relative variation of conformational energy, between B3LYP and MP2, does not affect the population, since the secondary minima are high in energy and very low in population. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005     

Cadmium(II) and mercury(II) complexes of an NO2S2-donor macrocycle and its ditopic xylyl-bridged analogue

The NO2S2-donor macrocycle (L1) was synthesised from the ring closure reaction between Boc-N-protected 2,2'-iminobis(ethanethiol) (3) and 2,2'-(ethylenedioxy)bis(benzyl chloride) (4) followed by deprotection of the Boc-group. alpha,alpha'-Dibromo-p-xylene was employed as a dialkylating agent to bridge two L1 to yield the corresponding N-linked product (L2). The X-ray structure of L2 (as its HBr salt) is described. A range of Cd(II) and Hg(II) complexes of L1 (6-9) and L2 (10-12) were prepared and characterised. Reaction of HgX2 (X = Br or I) with L1 afforded [Hg(L1)Br]2[Hg2Br6].2CH2Cl2 6 and [Hg(L1)I(2)] 7, respectively. For 6, the Hg(II) ion in the complex cation has a distorted tetrahedral coordination environment composed of S2N donor atoms from L1 and a bromo ligand. In 7 the coordination geometry is highly distorted tetrahedral, with the macrocycle coordinating in an exodentate manner via one S and one N atom. The remaining two coordination sites are occupied by iodide ions. [Hg(L1)(ClO4)]ClO4 8 was isolated from the reaction of Hg(ClO4)2 and L1. The X-ray structure reveals that all macrocyclic ring donors bind to the central mercury ion in this case, with the latter exhibiting a highly distorted octahedral coordination geometry. The O2S2-donors from the macrocyclic ring define the equatorial plane while the axial positions are occupied by the ring nitrogen as well as by an oxygen from a monodentate perchlorato ion. Reaction of Cd(NO3)(2).4H2O with L1 afforded [Cd(L1)(NO3)2](.)0.5CH2Cl2 9 in which L1 acts as a tridentate ligand, binding exo-fashion via its S2N donors. The remaining coordination positions are filled by two bidentate nitrate ions such that, overall, the cadmium is seven-coordinate. Reactions of HgX2(X = Br or I) with L2 yielded the isostructural 2 : 1 (metal : ligand) complexes, [Hg2(L2)Br4] 10 and [Hg2(L2)I(4)] 11. Each mercury ion has a distorted tetrahedral environment made up of S and N donors from an exodentate L2 and two coordinated halides. Contrasting with this, the reaction of L2 with Cd(NO3)(2).4H2O yielded a 1-D coordination network, {[Cd2(L2)(NO3)4].2CH2Cl2}n 12 in which each ring of L2 is exo-coordinated via two S atoms and one N atom to a cadmium ion which is also bound to one monodentate and one bidentate nitrate anion. The latter also has one of its oxygen atom attached to a neighboring cadmium via a nitroso (mu2-O) bridge such that the overall coordination geometry about each cadmium is seven-coordinate. The [Cd(L2)0.5(NO3)2] units are linked by an inversion to yield the polymeric arrangement.     

Synthesis of 32‐phenyl‐substituted methyl E/Z‐pyropheophorbide‐a's from methyl E/Z‐pyropehophorbide‐a 131‐ketoximes

Methyl E/Z‐pyropheophorbide‐a 13¹‐ketoximes 2a,b and their O‐acetyl derivatives 3a,b were oxidized with osmium(VIII) oxide to give aldehydes 4a,b and 5a,b , respectively. The Wittig reactions of the aldehyde chlorines 4a,b and 5a,b with benzyltriphenylphosphonium chloride were performed to form the corresponding methyl (3¹E/Z,13¹E/Z)‐3²‐phenylpyropheophorbide‐a 13¹‐ketoximes 6aa‐bb and their O‐acetyl derivatives 7aa‐bb ; hydrolysis of these ketoximes 6aa,ba and 6ab,bb in formic acid produced methyl (E/Z)‐3²‐phenylpyropheophorbide‐a's 8a,b .     

Synthesis and Characterization of [(1,4‐diamine)dichloro]platinum(II) Compounds Preliminary Studies on their Biological Activity

Two 1,4‐diamine ligands were synthesized having 1,2‐bis(aminomethyl)‐cyclohexane and 1,2‐bis(aminomethyl)‐benzene structures. The two ligands have different electron density in the six‐membered ring: a cyclohexane versus a phenyl ring. The organic synthesis of the ligands was carried out by synthetic pathways of seven and four steps, respectively, starting from 1,2,3,6‐tetrahydrophthalic anhydride and diethyl phthalate. The coordination of platinum to these ligands afforded platinum(II) complexes which are analogue to the clinical drug cisplatin but form a seven‐membered chelate ring. The interaction of the platinum compounds with DNA was studied in order to know the relationship between the electron density of ligands and their capability to chelate DNA, by using three techniques: Circular Dichroism, Agarose Gel Electrophoresis and Atomic Force Microscopy. The degree of interaction of both compounds with DNA was slightly different, but both complexes showed a cisplatin‐like behaviour and are promising candidates to follow an extensive study of their cytotoxic activity.     

Complexation of Eu3+ and Am3+ with soil humic acid extracted from Okchon Basin of Korean Peninsula

The complexation of Eu³⁺ and Am³⁺ ions with the humic acids has been investigated at various pH (4.0, 4.5, 5.0, 5.4) in 0.1M NaClO₄ solution using solvent extraction technique. Two humic acids are used in this study: humic acid extracted from the soil of Taejon on the Okchon Basin of Korea (TJHA) and commercially available one from Aldrich Chemical Co. (AHA). The total carboxylate group concentrations were determined to be 3.58 meq/g and 4.59 meq/g for Taejon and Aldrich humic acids, respectively. The conditional stability constants (log ₁ and log ₂), dependent on the pH of the solution, of the complexes of Eu³⁺ and Am³⁺ ions with the humic acids have been determined at the ionic medium of 0.1M NaClO₄. The values of stability constants with the degree of ionization of TJHA for Eu and Am complexes are quite well agreed with those of Lake Bradford humic acid (LBHA), indicating that structural characteristics of TJHA and LBHA may be quite similar to one another.     

Estimation of the optimal concentrations of residual sugar and cell growth rate for a fed-batch culture ofSaccharomyces cerevisiae

Estimation of the optimal concentrations of residual sugar in medium for a fed-batch culture of Baker’s yeast has been studied and practiced. The concentrations, however, depended on different species and targets of the biomass, which was expected to be made. Kinetic changes of the residual phosphate salt in the medium conformed to a logarithmic process until the fourth hour during an 11-h culture. The parabolic method (see ref. 9 later in article) might be qualified to maintain the concentrations of residual sugar around 0.15 g/L. It was demonstrated that cell growth followed a sigmoid process during a fed-batch culture, because the cells consumed the nutrient with two metabolic pathways, one was for cell conversion and another was for non-cell conversion. With the parabolic method, we can estimate kinetics of cell growth and cell growth rate during the culture.