Synthesis and biological evaluation of 3-amino-propan-1-ol based poly(ether imine) dendrimers

A general synthetic strategy for the rapid construction of poly(ether imine) dendrons and dendrimers with a nitrogen core, originating from 3-amino-propan-1-ol, is described. A new trifunctional monomer, namely, 3-[bis-(3-hydroxypropyl)amino]propan-1-ol, was used in a divergent synthesis of dendrimers up to the third generation. This method permitted installation of, either alcohol, amine, nitrile, ester or carboxylic acid groups at the peripheries the dendrimers. Cytotoxicity studies on water-soluble carboxylic acid terminated dendrimers were conducted and these studies revealed that poly(ether imine) dendrimers were non-toxic. These results illustrate that poly(ether imine) dendrimers are useful for biological studies.     

A new dendrimer scaffold for preparing dimers or tetramers of biologically active molecules

Synthesis of a new scaffold derived from iminodipropionic acid for the preparation of peptide dimers and tetramers is described.     

Self aggregation of binary mixtures of sodium dodecyl sulfate and polyoxyethylene alkyl ethers in aqueous solution

The mixed micelles of sodium dodecyl sulphate (SDS) with Brij35 and Brij 97 were studied separately by fluorescence measurement using pyrene as fluorescent probe. In the range of 0–1.0 mole fraction (X) of added SDS to Brij solutions, the cmc value of the mixed micelles varies from 0.085 to 8 mmol with Brij 35 and 0.04 to 8 mmol with Brij 97. The aggregation number also changes. A measure of the stability of mixed micelles is also presented. The interaction parameter ₁₂ and the chain–chain contribution parameter (B₁) are extracted from the analysis of the results. This parameter B₁ is related to the standard free energy change associated with the introduction of one ionic species into a nonionic micelle coupled with the release of one nonionic species from the micelle. The clouding behaviour of Brij 97 in the presence of SDS was investigated and the associated thermodynamic parameters of clouding were generated and discussed.     

Iridium mediated methyl and phenyl C-H activation of 2-(arylazo)phenols. Synthesis, structure, and spectral and electrochemical properties of some organoiridium complexes

Reaction of 2-(2′,6′-dimethylphenylazo)-4-methylphenol with [Ir(PPh₃)₃Cl] in refluxing ethanol in the presence of a base (NEt₃) affords an organoiridium complex 5, where the 2-(2′,6′-dimethylphenylazo)-4-methylphenol is coordinated to iridium, via C-H activation of a methyl group, as a dianionic tridentate C,N,O-donor. Two triphenylphosphines and a hydride are also coordinated to the metal center. A similar reaction carried out in toluene affords complex 5 along with a similar complex 7, where a chloride is coordinated to iridium instead of the hydride. Reaction of 2-(2′-methylphenylazo)-4-methylphenol with [Ir(PPh₃)₃Cl] in refluxing ethanol in the presence of a base (NEt₃) affords an organoiridium complex 12, where the 2-(2′-methylphenylazo)-4-methylphenol is coordinated to iridium, via C-H activation at the ortho position of the phenyl group in the 2′-methylphenylazo fragment, as a dianionic tridentate C,N,O-donor. Two triphenylphosphines and a hydride are also coordinated to the metal center. A similar reaction carried out in toluene affords a complex 12 along with a similar complex 13, where a chloride is coordinated to iridium instead of the hydride. Structures of complexes 5, 12 and 13 have been determined by X-ray crystallography. In all these complexes, the two triphenylphosphines are trans. All these complexes show intense MLCT transitions in the visible region. Cyclic voltammetry on all the complexes shows an Ir(III)-Ir(IV) oxidation within 0.60-0.73 V vs. SCE, followed by an oxidation of the coordinated 2-(arylazo)phenolate ligand within 1.08-1.39 V vs. SCE. A reduction of the coordinated 2-(arylazo)phenolate ligand is observed within −1.10 to −1.26 V vs. SCE.     

Dual behavior of masked o-benzoquinones in intramolecular Diels-Alder reactions. Expedient synthesis of highly functionalized cis-decalins from 2-methoxyphenols

[Reaction: see text]. The potential dual behavior as dienes and dienophiles of the diene moieties of masked o-benzoquinones (MOBs) 10a-e-12a-e, generated upon oxidation of 2-methoxyphenols 1-3 with BTIB in the presence of appropriate dienols, in their intramolecular Diels-Alder (IMDA) reactions has been examined. The IMDA reactions of MOBs 10a-d, 11a,b,d, and 12a,b,d resulted in highly functionalized oxatricyclic compounds 18a-d, 19a,b,d, and 20a,b,d, respectively, with concomitant formation of cis-decalin derivatives 21a-d, 22a,b,d, and 23a,b,d in a highly regio- and stereoselective manner. However, the MOBs 10e-12e provided exclusively oxatricyclic compounds 18e-20e. The formation of cis-decalins in these IMDA reactions illustrates the dienophilic character of MOBs, in addition to their behavior as dienes. The ratio of the two cycloadducts obtained in each reaction as a result of the dual character of MOBs depends on the nature and/or position of the substituents on both the cyclohexadienone moiety and the added 2,4-dienol. The majority of the cycloadducts resulted from the diene property of MOBs in intramolecular Diels-Alder reactions smoothly underwent Cope rearrangement to furnish cis-decalins as sole products in excellent to quantitative yields that provides a short and efficient entry to polyfunctionized cis-decalins from 2-methoxyphenols. Furthermore, the variation of dienophilic and diene characters of MOBs in the IMDA reactions with the electron-donating or electron-withdrawing substituent of both cyclohexadienone moiety and the added conjugated acyclic diene or 2,4-dienol has been studied in detail.     

Probabilistic finite element analysis of a non-gasketed flange

Stress analysis of a non-gasketed flange was computationally simulated by a finite-element method and probabilistically evaluated in view of several uncertainties in the performance parameters. Cumulative distribution functions and sensitivity factors were computed for overall heat transfer rate due to the structural and thermodynamic random variables. These results can be used to quickly identify the most critical design variables in order to optimize the design and make it cost effective. The analysis leads to the selection of the appropriate measurements to be used in structural and heat transfer analysis and to the identification of both the most critical measurements and parameters Published in Prikladnaya Mekhanika, Vol. 44, No. 5, pp. 133–143, May 2008.     

Heat transfer and pressure drop studies in a circular tube fitted with straight full twist

Experimental investigation of heat transfer characteristics of circular tube fitted with straight full twist insert has been presented. The heat transfer coefficient increases with Reynolds number and decreasing spacer distance with maximum being 2 in. spacer distance for both the type of twist inserts. Also, there is no appreciable increase in heat transfer enhancement in straight full twist insert with 2 in. spacer distance. Experiments were carried out in turbulent flow using straight full twist insert with 4 in. spacer and similar trend of increasing Nusselt number with Reynolds number was observed. Performance evaluation analysis was made and the maximum performance ratio was obtained for each twist insert corresponding to the Reynolds number of 2550.     

Kinetics of the reaction of methyl 4‐nitrobenzenesul‐fonate + Br− in ethanol amine based surfactants

The kinetics of the reaction of methyl 4‐nitrobenzenesulfonate + Br^? ions has been studied in ethanol amine based (alkyldimethylethanolammonium bromide and alkyldiethylethanolammonium bromide) surfactant solutions. The observed first‐order rate constants increase monotonically with surfactant concentration, with hydrophobic chain length and with head group bulk in a manner similar to other quaternary ammonium surfactants. The results were analyzed using the pseudophase model of micellar rate effects in conjunction with a Langmuir form to describe micellar binding of bromide ion. An attempt to estimate activation parameters of the reaction from temperature variance of micellar pseudophase rate constants has also been made. © 2006 Wiley Periodicals, Inc. Int J Chem Kinet 38: 303–308, 2006     

DABCO-mediated aza-Michael addition of 4-aryl-1H-1,2,3-triazoles to cycloalkenones. Regioselective synthesis of disubstituted 1,2,3-triazoles

Aza-Michael addition of 4-aryl-1H-1,2,3-triazoles to 2-cycloalken-1-ones has been studied in the presence of DABCO as organic base. The reactions were carried out in acetonitrile at room temperature to provide 2,4-disubstituted 2H-1,2,3-triazoles as major adducts and 1,4-disubstituted 1H-1,2,3-triazoles as minor adducts. Though the reaction times are longer (4–8 days), the two regioisomers were separated by using column chromatography and the adducts were obtained in very good to excellent combined chemical yields. The electron-rich and electron-poor substituents on aryl moiety of 4-aryl-triazoles could tolerate the reaction conditions to afford the title adducts.     

A Novel Fusion Protein Diphtheria Toxin–Stem Cell Factor (DT-SCF)—Purification and Characterization

Fusion toxins are an emerging class of targeted therapeutics for the treatment of cancer. Diphtheria toxin-stem cell factor (DT-SCF) is one such novel fusion toxin designed to target malignancies expressing c-kit. Since, c-kit overexpression has been reported on many types of cancers, it appeared to be a reasonably good molecule to target. In the present study, we report construction, expression, purification, and characterization of DT-SCF. DT-SCF gene coding for 1–387 amino acids of diphtheria toxin, His-Ala linker, 2–141 amino acids of SCF was cloned into expression vector with C terminal His tag. The induced DT-SCF protein was exclusively expressed in insoluble fraction. Purification of DT-SCF was achieved by inclusion body isolation and metal affinity chromatography under denaturing and reducing conditions. Purified DT-SCF was renatured partially on-column by gradually reducing denaturant concentration followed by complete refolding through rapid dilution technique. Cell viability assay provided the evidence that DT-SCF is a potent cytotoxic agent selective to cells expressing c-kit. The novelty of this study lies in employing SCF as a ligand in construction of fusion toxin to target wide range of malignancies expressing c-kit. Efficacy of DT-SCF fusion toxin was demonstrated over a range of malignancies such as chronic myeloid leukemia (K562), acute lymphoblastic leukemia (MOLT4), pancreatic carcinoma (PANC-1), and cervical carcinoma (HeLa 229). This is the first study reporting specificity and efficacy of DT-SCF against tumor cells expressing c-kit. There was significant correlation (P = 0.007) between c-kit expression on cells and their sensitivity to DT-SCF fusion toxin.