Iodine-catalyzed one-pot synthesis of amides from nitriles via Ritter reaction

Ritter reactions of alcohols and tert-butyl acetate with various nitriles were performed using iodine as a mild and effective catalyst under heating conditions to afford the corresponding amides in good to excellent yields.     

Duality in ε-variational inequality problems

In this paper a general analysis of duality for an extended ε-variational inequality problem based on the notions of ε-convexity and ε-conjugacy is performed. Optimal solutions of both the primal and dual problems are also related to the saddle point of an associated Lagrangian. Gap functions for these problems are proposed. An existence theorem for the extended ε-variational inequality is also established by means of the KKM lemma.     

A Validated, Specific Stability-Indicating RP-LC Method for Moxifloxacin and Its Related Substances

A validated, specific, stability-indicating reversed-phase liquid chromatographic method has been developed for quantitative analysis of moxifloxacin and its related substances in bulk samples and pharmaceutical dosage forms in the presence of degradation products and process-related impurities. Forced degradation studies were performed on bulk samples of moxifloxacin, in accordance with ICH guidelines, using acidic, basic, and oxidizing conditions, and thermal and photolytic stress, to show the stability-indicating power of the method. Significant degradation was caused by oxidative stress and by basic conditions; no degradation was observed under the other stress conditions. The method was optimized by analysis of the samples generated during the forced degradation studies and sample solutions spiked with the impurities. Good resolution between the analyte peak and peaks corresponding to process-related impurities and degradation products was achieved on a C₁₈ column with a simple linear mobile phase gradient prepared from aqueous sodium dihydrogen orthophosphate dihydrate containing triethylamine, pH adjusted to 3.0 with orthophosphoric acid, and methanol. Detection was performed at 240 nm. Limits of detection and quantification were established for moxifloxacin and its process related impurities. When the stressed test solutions were assayed against moxifloxacin working standard solution the mass balance was always between 99.3 and 100.1%, indicating the method was stability-indicating. The method was validated in accordance with ICH guidelines, and found to be suitable for checking the quality of bulk samples of moxifloxacin at the time of release of a batch and during storage (long term and accelerated stability testing was conducted).     

Interaction of single-walled carbon nanotubes with poly(propyl ether imine) dendrimers

We study the complexation of nontoxic, native poly(propyl ether imine) dendrimers with single-walled carbon nanotubes (SWNTs). The interaction was monitored by measuring the quenching of inherent fluorescence of the dendrimer. The dendrimer-nanotube binding also resulted in the increased electrical resistance of the hole doped SWNT, due to charge-transfer interaction between dendrimer and nanotube. This charge-transfer interaction was further corroborated by observing a shift in frequency of the tangential Raman modes of SWNT. We also report the effect of acidic and neutral pH conditions on the binding affinities. Experimental studies were supplemented by all atom molecular dynamics simulations to provide a microscopic picture of the dendrimer-nanotube complex. The complexation was achieved through charge transfer and hydrophobic interactions, aided by multitude of oxygen, nitrogen, and n-propyl moieties of the dendrimer.     

A validated stability-indicating RP-HPLC assay method for Amsacrine and its related substances

A validated specific stability indicating reversed-phase high-performance liquid chromatography method was developed for the quantitative determination of Amsacrine as well as its related substances determination in bulk samples, in presence of degradation products, and its process related impurities. Forced degradation studies were performed on bulk samples of Amsacrine as per International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human use (ICH) prescribed stress conditions using acid, base, oxidative, thermal stress, and photolytic degradation to show the stability indicating power of the method. Significant degradation was observed during basic hydrolysis, slight degradation was observed in oxidative and thermal stress, and no degradation was observed in other stress conditions. The chromatographic method was optimized using the samples generated from forced degradation studies and the impurity spiked solution. Good resolution between the peaks corresponds to process-related impurities and degradation products from the analyte were achieved on Inertsil ODS column using the mobile phase consists a mixture of 1.0% triethyl amine in 20 mM potassium dihydrogen orthophosphate, with pH adjusted to 6.5, with ortho phosphoric acid in water and acetonitrile using a simple linear gradient. The detection was carried out at wavelength 248 nm. The mass balance in each case was in between 99.4% to 99.9%, indicating that the developed method was stability-indicating. Validation of the developed method was carried out as per ICH requirements. The developed method was found to be suitable to check the quality of bulk samples of Amsacrine at the time of batch release and also during its stability studies.     

High performance liquid chromatographic analysis of phytoplankton pigments using a C16-amide column

In this study, a reverse-phase HPLC method incorporating a ternary solvent system was developed to analyze most polar and non-polar chlorophylls and carotenoids present in phytoplankton. The method is based on an RP-C₁₆-Amide column and provided excellent peak resolution of most taxonomically important pigments and an elution profile different than C₈ or C₁₈ columns provide. Analysis of mixed pigment standards, extracts of phytoplankton monocultures, and field samples showed that this method was able to resolve more than sixty pigments, ranging from very polar acidic chlorophylls to the non-polar hydrocarbon carotenes in less than 36 min. This included chlorophylls c₁, c₂ and c₃, divinyl chlorophylls a and b, the carotenoids lutein and zeaxanthin and some recently discovered pigments. The ability of this method to resolve divinyl chl b from monovinyl chl b and divinyl chl a from monovinyl chl a is particularly important for the quantification and identification of the marine cyanobacteria Prochlorococcus spp. in oceanic waters. The described protocol is sensitive and reproducible and can be used to assess the distribution and dynamics of major phytoplankton groups in marine and freshwater ecosystems.     

Physicochemical and solvatochromic analysis of an imidazole derivative as NLO material

Bioactive imidazole derivative, 2-(2,4-difluorophenyl)-1-phenyl-1H-imidazo[4,5-f][1,10]phenanthroline, has been synthesized and characterized by IR, UV-vis, NMR and elemental (CHN) analysis. The electric dipole moment (μ) and the hyperpolarizability (β) have been studied both experimentally and theoretically, which reveals that the synthesized imidazole derivative possesses non-linear optical (NLO) behavior. This chromophore possess more appropriate ratio of off-diagonal versus diagonal β tensorial component (r=β(xyy)/β(xxx)=-0.19) which reflects the in plane nonlinearity anisotropy. Since they have largest μβ(0) value, the reported imidazole can be used as potential NLO material. Within this context, reasonable conclusions concerning the steric hindrance in the chromospheres, push-pull character, hyperpolarizability of the imidazole and their application as NLO materials will be drawn. The solvent effect on the absorption and fluorescence bands was analyzed by a multi-component linear regression in which several solvent parameters were analyzed simultaneously.     

A programmable microfluidic cell array for combinatorial drug screening

We describe the development of a fully automatic and programmable microfluidic cell culture array that integrates on-chip generation of drug concentrations and pair-wise combinations with parallel culture of cells for drug candidate screening applications. The device has 64 individually addressable cell culture chambers in which cells can be cultured and exposed either sequentially or simultaneously to 64 pair-wise concentration combinations of two drugs. For sequential exposure, a simple microfluidic diffusive mixer is used to generate different concentrations of drugs from two inputs. For generation of 64 pair-wise combinations from two drug inputs, a novel time dependent variable concentration scheme is used in conjunction with the simple diffusive mixer to generate the desired combinations without the need for complex multi-layer structures or continuous medium perfusion. The generation of drug combinations and exposure to specific cell culture chambers are controlled using a LabVIEW interface capable of automatically running a multi-day drug screening experiment. Our cell array does not require continuous perfusion for keeping cells exposed to concentration gradients, minimizing the amount of drug used per experiment, and cells cultured in the chamber are not exposed to significant shear stress continuously. The utility of this platform is demonstrated for inducing loss of viability of PC3 prostate cancer cells using combinations of either doxorubicin or mitoxantrone with TRAIL (TNF-alpha Related Apoptosis Inducing Ligand) either in a sequential or simultaneous format. Our results demonstrate that the device can capture the synergy between different sensitizer drugs and TRAIL and demonstrate the potential of the microfluidic cell array for screening and optimizing combinatorial drug treatments for cancer therapy.     

A microfluidic device for high throughput bacterial biofilm studies

Bacteria are almost always found in ecological niches as matrix-encased, surface-associated, multi-species communities known as biofilms. It is well established that soluble chemical signals produced by the bacteria influence the organization and structure of the biofilm; therefore, there is significant interest in understanding how different chemical signals are coordinately utilized for community development. Conventional methods for investigating biofilm formation such as macro-scale flow cells are low-throughput, require large volumes, and do not allow spatial and temporal control of biofilm community formation. Here, we describe the development of a PDMS-based two-layer microfluidic flow cell (μFC) device for investigating bacterial biofilm formation and organization in response to different concentrations of soluble signals. The μFC device contains eight separate microchambers for cultivating biofilms exposed to eight different concentrations of signals through a single diffusive mixing-based concentration gradient generator. The presence of pneumatic valves and a separate cell seeding port that is independent from gradient-mixing channels offers complete isolation of the biofilm microchamber from the gradient mixer, and also performs well under continuous, batch or semi-batch conditions. We demonstrate the utility of the μFC by studying the effect of different concentrations of indole-like biofilm signals (7-hydroxyindole and isatin), either individually or in combination, on biofilm development of pathogenic E. coli. This model can be used for developing a fundamental understanding of events leading to bacterial attachment to surfaces that are important in infections and chemicals that influence the biofilm formation or inhibition.