Organotin(IV) complexes of NSAID,ibuprofen, X-ray structure of Ph3Sn(IBF), binding and cleavage interaction with DNA and in vitro cytotoxic studies of several organotin complexes of drugs

This study encompasses the synthesis and characterization of organotin(IV) derivatives of non-steroidal anti-inflammatory drug ibuprofen (IBF), viz. [(Me₃Sn)(IBF)] ( 1 ), [(Bu₃Sn)(IBF)] ( 2 ), [Ph₃Sn(IBF)] ( 3 ), {[Me₂Sn(IBF)]₂O}₂ ( 4 ) and [Bu₂Sn(IBF)₂] ( 5 ). The crystal structure of complex 3 , [Ph₃Sn(IBF)], indicates a highly distorted tetrahedral (td) geometry with anisobidentate mode of coordination of the carboxylate group with tin atom, and a similar structure has been proposed for other two triorganotin(IV) derivatives. Moreover, the DFT (density functional theory) calculation and other studies have verified a dimer distannoxane type of structure for complex 4 , {[Me₂Sn(IBF)]₂O}₂. Complex 5 has been found to exhibit a highly distorted octahedral geometry around the tin atom. To investigate the DNA binding profile of the synthesized complexes, viscosity measurement, UV–vis and fluorescence titrations were performed, which revealed an intercalative type of binding with DNA for IBF and complex 5 and external binding in case of the complexes 1 and 2 ; complexes 3 and 4 could not be studied owing to their insufficient solubility in tris buffer. Plasmid DNA fragmentation studies of IBF and complexes 1 , 2 and 5 indicate that they cleaved the pBR322 plasmid potentially. Further, the drugs IBF {2-[4-(2-methylpropyl)phenyl]propanoic acid}, MESNA (sodium 2-mercaptoethane-sulfonate), warfarin [2H-1-benzopyran-2-one,4-hydroxy-3-(3-oxo-1-phenylbutyl)], sulindac (2-{5-fluoro-1-[(4-methanesulfinylphenyl) methylidene]-2-methyl-1H-inden-3-yl}acetic acid) and their corresponding organotin(IV) complexes 1–19 (complexes 6–19 were synthesized/reported previously) were screened in vitro for cytotoxicity against human cancer cell lines viz. DU145 (prostate cancer), HCT-15 (colon adenocarcinoma), Caco-2 (colorectal adenocarcinoma), MCF-7 (mammary cancer), LNCaP (androgen-sensitive prostate adenocarcinoma) and HeLa (cervical cancer), through MTT reduction assay and the cause of cell death was investigated through acridine orange/ethidium bromide staining of cells and DNA fragmentation assay. The probable structure–cytotoxicity relationship is also discussed. The major role of apoptosis along with small necrosis was also validated by flow cytometry assay using annexin V–fluorescein isothiocyanate and propidium iodide analysis.     

Metal-Free Arylation of Benzothiophenes at C4 by Activation as their Benzothiophene S-Oxides

Benzothiophenes, activated by oxidation to the corresponding S-oxides, undergo C−H/C−H-type coupling with phenols to give C4 arylation products. While an electron-withdrawing group at C3 of the benzothiophene is important, the process operates without a directing group and a metal catalyst, thus rendering it compatible with sensitive functionalities—e.g. halides and formyl groups. Quantum chemical calculations suggest a formal stepwise mechanism involving heterolytic cleavage of an aryloxysulfur species to give a π-complex of the corresponding benzothiophene and a phenoxonium cation. Subsequent addition of the phenoxonium cation to the C4 position of the benzothiophene is favored over the addition to C3; Fukui functions predict that the major regioisomer is formed at the more electron-rich position between C3 and C4. Varied selective manipulation of the benzothiophene products showcase the synthetic utility of the metal-free arylation process.     

Unusual synthesis of azines and their oxidative degradation to carboxylic acid using iodobenzene diacetate

Reaction of 3-hydrazonobutan-2-one oxime with aromatic aldehydes resulted in the formation of 1,2-bis(arylidene)hydrazine commonly referred as azine as an unexpected product, instead of expected product 3-(aryl)methylenehydrazonobutan-2-one oxime, which were subsequently oxidized to corresponding aromatic acids with an ecofriendly oxidizing agent iodobenzene diacetate. Azines and carboxylic acids were characterized by IR and NMR (¹H, ¹³C, HMBC, and HMQC) studies.     

A proposal for experimental detection of amplitude nth-power squeezing

Recently, in several theoretical investigations, amplitude nth-power squeezing has been studied with n = 2, 3, 4, 5. In the present paper, we give a proposal for experimental detection of amplitude nth-power squeezing using ordinary homodyning with coherent light for arbitrary power n and discuss in detail its theory. The proposed scheme requires only repeated measurements of the factorial moments of number of photons in the light obtained after homodyning, with various shifts of phase of coherent light, and involves no approximations, whatsoever. This has advantage over the method proposed by Shchukin and Vogel [Phys. Rev. A 72 (2005) 043808] in that our method requires only one beam splitter and only one photodetector, and also lesser number of repetitions of experiment with phase-shifted coherent light.     

A categorical invariant for cubic threefolds

We prove a categorical version of the Torelli theorem for cubic threefolds. More precisely, we show that the non-trivial part of a semi-orthogonal decomposition of the derived category of a cubic threefold characterizes its isomorphism class.     

Synthesis and antibacterial activity of some 5-hydroxy-5-trifluoromethyl-4,5-dihydropyrazol-1-thiocarboxamides, 3-trifluoromethylpyrazol-1-thiocarboxamides and 4-aryl-2-(5(3)-trifluoromethyl-1-pyrazolyl)thiazoles

5-Hydroxy-5-trifluoromethyl-4,5-dihydropyrazol-1-thiocarboxamides 3 and 3-trifluoromethylpyrazol-1-thiocarboxamides 4, regioselectively obtained by the condensation of trifluoromethyl-β-diketones with thiosemicarbazide under neutral and acidic conditions, on further reaction with phenacyl bromides 5 afforded 4-aryl-(5-trifluoromethyl-pyrazol-1-yl)thiazoles 6 and 4-aryl-(3-trifluoromethyl-pyrazol-1-yl)thiazoles 7, respectively. Five 4,5-dihydropyrazoles (3a–e) and two pyrazolylthiazoles (6a and 6c) were tested against one Gram-positive and one Gram-negative bacteria to assess their in vitro antibacterial activity. Compounds 3a, 3b and 3e showed moderate antibacterial activity against Gram-positive bacterium, Bacillus pumilus.     

Branching on hyperplane methods for mixed integer linear and convex programming using adjoint lattices

We present branching-on-hyperplane methods for solving mixed integer linear and mixed integer convex programs. In particular, we formulate the problem of finding a good branching hyperplane using a novel concept of adjoint lattice. We also reformulate the problem of rounding a continuous solution to a mixed integer solution. A worst case complexity of a Lenstra-type algorithm is established using an approximate log-barrier center to obtain an ellipsoidal rounding of the feasible set. The results for the mixed integer convex programming also establish a complexity result for the mixed integer second order cone programming and mixed integer semidefinite programming feasibility problems as a special case. Our results motivate an alternative reformulation technique and a branching heuristic using a generalized (e.g., ellipsoidal) norm reduced basis available at the root node.     

Efficient Synthesis of Some New 2,3-Dimethylquinoxaline-1-oxides Using Bis(acetoxy)phenyl-λ 3-iodane as an Oxidant

A series of 2-(arylimino)-3-(hydroxyimino)butanes 3a–g, easily accessed by the condensation of variously substituted anilines 1a–g with biacetyl monoxime 2, were efficiently cyclized to afford 2,3-dimethylquinoxaline-1-oxides 4a–g using bis(acetoxy)phenyl-λ ³-iodane as an oxidant. This methodology utilizes a commercially available and environmental benign oxidant to achieve the title compounds in excellent yields under mild conditions.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

US Coast Guard air station location with respect to distress calls: A spatial statistics and optimization based methodology

We study the problem of suitably locating US Coast Guard air stations to respond to emergency distress calls. Our goal is to identify robust locations in the presence of uncertainty in distress call locations. Our analysis differs from the literature primarily in the way we model this uncertainty. In our optimization and simulation based methodology, we develop a statistical model and demonstrate our procedure using a real data set of distress calls. In addition to guiding strategic decisions of placement of various stations, our methodology is also able to provide guidance on how the resources should be allocated across stations.     

A branch-and-cut method for 0-1 mixed convex programming

We generalize the disjunctive approach of Balas, Ceria, and Cornuéjols [2] and devevlop a branch-and-cut method for solving 0-1 convex programming problems. We show that cuts can be generated by solving a single convex program. We show how to construct regions similar to those of Sherali and Adams [20] and Lovász and Schrijver [12] for the convex case. Finally, we give some preliminary computational results for our method. Received January 16, 1996 / Revised version received April 23, 1999?Published online June 28, 1999