Novel Copolymers of Styrene. 12. Halogen Ring-Substituted Methyl 2-Cyano-3-Phenyl-2-Propenoates

Electrophilic trisubstituted ethylenes, halogen ring-substituted methyl 2-cyano-3-phenyl-2-propenoates, RPhCH=C(CN)CO₂CH₃ (where R is 3-Br-4-CH₃O, 5-Br-2-CH₃O, 2-F-5-CH₃, 2-F-6-CH₃, 4-F-3-CH₃, 4-F-3-PhO, 2-F-5-I, 2-F-6-I, 2-F₃C, 4-F₃C) were prepared and copolymerized with styrene. The monomers were synthesized by the piperidine catalyzed Knoevenagel condensation of ring-substituted benzaldehydes and methyl cyanoacetate, and characterized by CHN analysis, IR, ¹H and ¹³C-NMR. All the ethylenes were copolymerized with styrene (M₁) in solution with radical initiation (ABCN) at 70°C. The compositions of the copolymers were calculated from nitrogen analysis and the structures were analyzed by IR, ¹H and ¹³C-NMR. The order of relative reactivity (1/r ₁) for the monomers is 2-F-5-CH₃ (6.4) > 4-F-3-PhO (5.6) > 4-F₃C (4.8) > 3-Br-4-CH₃O (3.7) > 2-F-5-I (3.6) > 2-F₃C (2.2) > 2-F-6-I (2.1) > 5-Br-2-CH₃O (1.9) > 4-F-3-CH₃ (1.8) > 2-F-6-CH₃ (1.2). Relatively high T _g of the copolymers in comparison with that of polystyrene indicates a decrease in chain mobility of the copolymer due to the high dipolar character of the trisubstituted ethylene monomer unit. Decomposition of the copolymers in nitrogen occurred in two steps, first in the 200-500°C range with residue (2–21% wt), which then decomposed in the 500–800°C range.     

Development of radioimmunoassay

Therapeutic monitoring of theophylline can be accurately performed by radioimmunoassay (RIA). It is radioactive tracer as an essential reagent for the development of very sensitive RIA. Direct radiolabeling of theophylline with¹²⁵I is very difficult due to the absence of appropriate functional groups. Hence carboxylic acid of theophylline was tagged to tyrosine methyl ester and then radiolabeled. The derivatives of theophylline, bearing a propionic acid and butyric acid side chains at seventh and eight position of theophylline, were synthesised and coupled to tyrosine methyl ester. Theophylline-tyrosine methyl ester conjugates were labeled with¹²⁵I using chlora mine—T. Radiolabeled theophylline was purified by solvent extraction followed by thin layer chromatography. The purified radiolabeled compound were assessed for their radiochemical purity, specific activity and immunoreactivity. Stability studies of radiolabeled compounds were performed with different solvents at different temperatures. Theophylline serum samples analysed using developed and commercial kits showed the correlation coefficient of 0.961 (n=9).     

Effect of Head‐Group Chemistry on Surface‐Mediated Molecular Self‐Assembly

Surface molecular self‐assembly is a fast advancing field with broad applications in sensing, patterning, device assembly, and biochemical applications. A vast number of practical systems utilize alkane thiols supported on gold surfaces. Whereas a strong Au? S bond facilitates robust self‐assembly, the interaction is so strong that the surface is reconstructed, leaving etch pits that render the monolayers susceptible to degradation. By using different head group elements to adcust the molecule–surface interaction, a vast array of new systems with novel properties may be formed. In this paper we use a carefully chosen set of molecules to make a direct comparison of the self‐assembly of thioether, selenoether, and phosphine species on Au(111). Using the herringbone reconstruction of gold as a sensitive readout of molecule–surface interaction strength, we correlate head‐group chemistry with monolayer (ML) properties. It is demonstrated that the hard/soft rules of inorganic chemistry can be used to rationalize the observed trend of molecular interaction strengths with the soft gold surface, that is, P>Se>S. We find that the structure of the monolayers can be explained by the geometry of the molecules in terms of dipolar, quadrupolar, or van der Waals interactions between neighboring species driving the assembly of distinct ordered arrays. As this study directly compares one element with another in simple systems, it may serve as a guide for the design of self‐assembled monolayers with novel structures and properties.     

Candida antarctica B Lipase-Loaded Microreactor for the Automated Derivatization of Lipids

A key bottleneck in the profiling of lipids is the multistep derivatization required prior to gas chromatography (GC) analysis. A single in-vial lipid derivatization and analysis may significantly minimize sample loss and improve analytical sensitivity. A cotton fiber-supported poly(glycidylmethacrylate-co-ethylene glycol dimethacrylate) polymer microbrush microreactor loaded with Candida antarctica lipase B was developed for the facile conversion of triacylglycerols into fatty acid ethyl ester derivatives for gas chromatograph–mass spectrometry (GC–MS) analysis. The polymer microbrush microreactor was fabricated in effort to provide efficient, simplified, cost effective, and high-throughput GC–MS determination of triacylglycerols. The polymer microbrush microreactor was used as an in-vial triacylglycerol transesterification platform, with economical sample consumption of less than or equal to 100?µL and significant reduction of reagents. To evaluate the polymer microbrush microreactor performance for lipids, a triolein standard and camelina oil triacylglycerols were quantitatively transformed into ethyl oleate and fatty acid ethyl esters, respectively, following a 3?h reaction time. The lipase-loaded cotton fiber-supported poly(glycidylmethacrylate-co-ethylene glycol dimethacrylate) polymer microbrush microreactors were reusable for up to five times for quantitative transesterification with minimal loss of lipase activity.     

Preparation and biological evaluation of the new chlorin photosensitizer T3,4BCPC for detection and treatment of tumors

The new water-soluble photosensitizer 5,10,15,20-tetrakis[3,4-bis(carboxymethyleneoxy)phenyl]chlorin (T3,4BCPC) has been prepared, characterized and labeled with 99mTc radionuclide. The radiotracer was evaluated for tissue distribution in Wistar rats. Accumulation of administrated activities in the liver, kidney, bladder and large intestine at 4 h post-injection indicated that the labeled ligand was largely eliminated through the renal and partly through the hepatobiliary system. In vivo biodistribution studies of the labeled compound were carried out in rodent and murine tumor models in comparison with other tumor-seeking radiopharmaceuticals such as 99mTc(V)-dimercaptosuccinic acid (DMSA), 201thallous chloride (TlCl) and 99mTc-citrate using a gamma camera computer system. In N-nitrosomethylurea (NMU)-induced rat mammary tumors, the labeled ligand showed a five-fold tumor to muscle (T/M) ratio compared to 99mTc(V)-DMSA (3-fold) and 201TlCl (3-fold). In the case of C(3)H/J virus-induced spontaneous mammary tumors, the differences were not marked. However, in the transplanted rat C(6)-glioma, the T/M ratio of the labeled compound was appreciably higher (four-fold) than that noted with 99mTc(V)-DMSA (two-fold), 201TlCl (three-fold) and 99mTc-citrate (more than three-fold). These findings suggest that the radiolabeled T3,4BCPC may have potential for the detection of cancer. In order to ascertain the efficacy of the compound for photodynamic therapy applications, a preclinical PDT study was carried out in fibrosarcoma-bearing mice after injecting 5.0 mg/kg body weight of the T3,4BCPC. A laser dose of 20 mW for 60 s resulted in 80% destruction of tumors. These data suggest that this molecule could be useful for PDT of cancer. The labeled agent could also be useful in monitoring the progression/regression of tumors before, during, and after chemotherapy, radiation therapy or PDT.     

Fabrication of a Single Layer and Bilayer Potentiometric Biosensors for Penicillin by Galvanostatic Entrapment of Penicillinase into Polypyrrole Films

A single layer and bilayer potentiometric biosensors for the detection of penicillin have been developed. The favourable conditions that were established for the polypyrrole‐penicillinase ((PPy‐P’nase) single layer biosensor were 0.03 M pyrrole, 50 U/mL P’nase, 0.01 M penicillin, applied current density of 0.9 mA/cm² and a polymerisation time of 40 s. The optimum conditions for the formation of the outer layer of the bilayer were: (a) 0.1 M Py, 19 U/mL P’nase, 0.01 M pen, current density of 0.9 mA/cm² and a polymerisation time of 40 s. The minimum detectable penicillin concentration with the bilayer potentiometric biosensor was 0.3 µM and the linear concentration range was 7.5–146 µM. The average percentage recovery of penicillin that was found in amoxycillin 500 mg was 113±24 %. The determination of penicillin in milk was fraught with problems of non‐specific binding of penicillin to the milk.     

Identification of omega hydroxy fatty acids in biological samples as their pentafluoropropyl derivatives by gas chromatography/mass spectrometry with positive and negative ion detection

A simple one-step procedure for derivatization of the omega hydroxy fatty acids 20-hydroxyeicotetraeonic acid and 12-hydroxylauric acid is presented. The procedure involves acylation of the terminal hydroxy group and esterification of the carboxylic acid with a mixture of pentafluoropropionic anhydride and pentafluoropropanol. Positive and negative ion spectra for the derivatives are presented. The procedure was used to demonstrate conversion of arachidonic acid to 20-hydroxyeicosatetraeonic acid and lauric acid to 12-hydroxylauric acid in kidney microsomal incubations. The reaction appears to be specific, since derivatives of subterminal fatty acids (secondary alcohols) could not be detected.     

Maximum stable set formulations and heuristics based on continuous optimization

 The stability number α(G) for a given graph G is the size of a maximum stable set in G. The Lovász theta number provides an upper bound on α(G) and can be computed in polynomial time as the optimal value of the Lovász semidefinite program. In this paper, we show that restricting the matrix variable in the Lovász semidefinite program to be rank-one and rank-two, respectively, yields a pair of continuous, nonlinear optimization problems each having the global optimal value α(G). We propose heuristics for obtaining large stable sets in G based on these new formulations and present computational results indicating the effectiveness of the heuristics. Received: December 13, 2000 / Accepted: September 3, 2002 Published online: December 19, 2002 RID="★" ID="★" Computational results reported in this paper were obtained on an SGI Origin2000 computer at Rice University acquired in part with support from NSF Grant DMS-9872009. Key Words. maximum stable set – maximum clique – minimum vertex cover – semidefinite program – semidefinite relaxation – continuous optimization heuristics – nonlinear programming Mathematics Subject Classification (2000): 90C06, 90C27, 90C30