Synthesis and Characterization of a Hypoxia‐Sensitive MRI Probe

Tissue hypoxia occurs in pathologic conditions, such as cancer, ischemic heart disease and stroke when oxygen demand is greater than oxygen supply. An imaging method that can differentiate hypoxic versus normoxic tissue could have an immediate impact on therapy choices. In this work, the gadolinium(III) complex of 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA) with a 2‐nitroimidazole attached to one carboxyl group via an amide linkage was prepared, characterized and tested as a hypoxia‐sensitive MRI agent. A control complex, Gd(DO3A‐monobutylamide), was also prepared in order to test whether the nitroimidazole side‐chain alters either the water proton T₁ relaxivity or the thermodynamic stability of the complex. The stabilities of these complexes were lower than that of Gd(DOTA)^? as expected for mono‐amide derivatives. The water proton T₁ relaxivity (r₁), bound water residence lifetime (τ_M) and rotational correlation time (τ_R) of both complexes was determined by relaxivity measurements, variable temperature ¹⁷O NMR spectroscopy and proton nuclear magnetic relaxation dispersion (NMRD) studies. The resulting parameters (r₁=6.38 mM ^?1 s^?1 at 20 MHz , τ_M=0.71 μs, τ_R=141 ps) determined for the nitroimidazole derivative closely parallel to those of other Gd(DO3A‐monoamide) complexes of similar molecular size. In vitro MR imaging experiments with 9L rat glioma cells maintained under nitrogen (hypoxic) versus oxygen (normoxic) gas showed that both agents enter cells but only the nitroimidazole derivative was trapped in cells maintained under N₂ as evidenced by an approximately twofold decrease in T₁ measured for hypoxic cells versus normoxic cells exposed to this agent. These results suggest that the nitroimidazole derivative might serve as a molecular reporter for discriminating hypoxic versus normoxic tissues by MRI.     

Correcting for a density distribution: particle size analysis of core-shell nanocomposite particles using disk centrifuge photosedimentometry

Many types of colloidal particles possess a core-shell morphology. In this Article, we show that, if the core and shell densities differ, this morphology leads to an inherent density distribution for particles of finite polydispersity. If the shell is denser than the core, this density distribution implies an artificial narrowing of the particle size distribution as determined by disk centrifuge photosedimentometry (DCP). In the specific case of polystyrene/silica nanocomposite particles, which consist of a polystyrene core coated with a monolayer shell of silica nanoparticles, we demonstrate that the particle density distribution can be determined by analytical ultracentrifugation and introduce a mathematical method to account for this density distribution by reanalyzing the raw DCP data. Using the mean silica packing density calculated from small-angle X-ray scattering, the real particle density can be calculated for each data point. The corrected DCP particle size distribution is both broader and more consistent with particle size distributions reported for the same polystyrene/silica nanocomposite sample using other sizing techniques, such as electron microscopy, laser light diffraction, and dynamic light scattering. Artifactual narrowing of the size distribution is also likely to occur for many other polymer/inorganic nanocomposite particles comprising a low-density core of variable dimensions coated with a high-density shell of constant thickness, or for core-shell latexes where the shell is continuous rather than particulate in nature.     

Synthesis of new ESIPT-fluorescein: photophysics of pH sensitivity and fluorescence

ESIPT-inspired benzimidazolyl substituted fluorescein dyes were synthesized. PH-sensitivity was determined by the photophysical property measured at a physiological possible pH range. Fluorescence quantum efficiency values were calculated independently at two different emissions. A rational relationship is defined between fluorescence quantum efficiency and calculated HOMO energy.     

Convenient and simple synthesis of 2-aminothiazoles by the reaction of α-halo ketone carbonyls with ammonium thiocyanate in the presence of N-methylimidazole

Substituted 2-aminothiazole derivatives were obtained as a result of N-methylimidazole catalyzed cyclization of α-halo ketone carbonyls with ammonium thiocyanate in water-alcoholic media. The generality of the method has been demonstrated by screening a series of aromatic/heteroaromatic/aliphatic α-halo ketones, α-halo β-diketones, and α-halo β-ketoesters. The developed method is simple, mild, and general route for the preparation of diversely functionalized 2-aminothiazoles in good to moderate yields from readily available starting materials.     

Energy and photoinduced electron transfer in a wheel-shaped artificial photosynthetic antenna-reaction center complex

Functional mimics of a photosynthetic antenna-reaction center complex comprising five bis(phenylethynyl)anthracene antenna moieties and a porphyrin-fullerene dyad organized by a central hexaphenylbenzene core have been prepared and studied spectroscopically. The molecules successfully integrate singlet-singlet energy transfer and photoinduced electron transfer. Energy transfer from the five antennas to the porphyrin occurs on the picosecond time scale with a quantum yield of 1.0. Comparisons with model compounds and theory suggest that the F?rster mechanism plays a major role in the extremely rapid energy transfer, which occurs at rates comparable to those seen in some photosynthetic antenna systems. A through-bond, electron exchange mechanism also contributes. The porphyrin first excited singlet state donates an electron to the attached fullerene to yield a P(*+)-C(60)(*-) charge-separated state, which has a lifetime of several nanoseconds. The quantum yield of charge separation based on light absorbed by the antenna chromophores is 80% for the free base molecule and 96% for the zinc analogue.     

Profiling of Piper betle Linn. cultivars by direct analysis in real time mass spectrometric technique

Piper betle Linn. is a traditional plant associated with the Asian and southeast Asian cultures. Its use is also recorded in folk medicines in these regions. Several of its medicinal properties have recently been proven. Phytochemical analysis showed the presence of mainly terpenes and phenols in betel leaves. These constituents vary in the different cultivars of Piper betle. In this paper we have attempted to profile eight locally available betel cultivars using the recently developed mass spectral ionization technique of direct analysis in real time (DART). Principal component analysis has also been employed to analyze the DART MS data of these betel cultivars. The results show that the cultivars of Piper betle could be differentiated using DART MS data.     

Role of surface modification of colloidal CdSe quantum dots on the properties of hybrid organic–inorganic nanocomposites

In this work, tri-octyl phosphine/tri-octyl phosphine oxide (TOPO)-capped cadmium selenide (CdSe) quantum dots (QDs) of varied sizes (5–9 nm), prepared by varying the input Cd:Se precursor ratio using chemical route, were dispersed in conducting polymer matrices viz. poly[2-methoxy, 5-(2-ethyl-hexyloxy)-1,4-phenylene vinylene] (MEH-PPV) and poly(3-hexylthiophene) (P3HT). By using a binary solvent mixture (pyridine–chloroform), homogeneous dispersion of CdSe nanocrystals in polymers (MEH-PPV, P3HT) could be realized. The properties of the resulting dispersions could be tailored by the composition and concentration of QDs in polymer. The emission and structural properties of polymer–CdSe nanocomposites are found to be dependent on the crystallite size and morphology of CdSe nanocrystallites. An effective quenching of photoluminescence emission in the polymer nanocomposite was observed for smaller CdSe quantum dots (size ∼6 nm) as compared to larger CdSe quantum dots (size ∼9 nm), thus ensuring efficient charge transfer process across the polymer–CdSe interface in the former case. The incomplete quenching, particularly for MEH-PPV:CdSe nanocomposites, could be as a result of insufficient coverage of polymers on the surface of CdSe nanocrystallites, mainly due to phase segregation for TOPO-stripped CdSe nanocrystallites. The superior morphology and optical properties of polymer nanocomposite (P3HT:CdSe QDs) could play a pivotal role for the realization of effective charge separation and transport in hybrid solar cells.     

Scheduling projects with heterogeneous resources to meet time and quality objectives

In service organizations, heterogeneity in workforce skills can lead to variation in end-product/service quality. The multi-mode, resource-constrained, project scheduling problem (MRCPSP), which assumes similar skills among resources in a given resource pool, accounts for differences in quality levels of individuals by assigning different activity durations depending on the skill level used. This approach is often inadequate to model the problem type investigated here. Using typical projects from the customer training division of a large telecommunications company (which motivated this research), a labor assignment problem using a successive work–time concept is formulated and solved using integer programming optimization procedures. The setting represents a multiple-project environment where projects are separate and independent, but require the same renewable resource mix for their completion. The paper demonstrates how the output of the model can be used to identify bottlenecks (or critical resource skills), and also demonstrates how cross-training the appropriately skilled groups or individuals can increase throughput. The approach guides decision-making concerning which workers to cross-train in order to extract the greatest benefits from worker-flexibility.     

Higher-order adaptive finite-element methods for orbital-free density functional theory

In the present work, we study various numerical aspects of higher-order finite-element discretizations of the non-linear saddle-point formulation of orbital-free density-functional theory. We first investigate the robustness of viable solution schemes by analyzing the solvability conditions of the discrete problem. We find that a staggered solution procedure where the potential fields are computed consistently for every trial electron-density is a robust solution procedure for higher-order finite-element discretizations. We next study the convergence properties of higher-order finite-element discretizations of orbital-free density functional theory by considering benchmark problems that include calculations involving both pseudopotential as well as Coulomb singular potential fields. Our numerical studies suggest close to optimal rates of convergence on all benchmark problems for various orders of finite-element approximations considered in the present study. We finally investigate the computational efficiency afforded by various higher-order finite-element discretizations, which constitutes the main aspect of the present work, by measuring the CPU time for the solution of discrete equations on benchmark problems that include large Aluminum clusters. In these studies, we use mesh coarse-graining rates that are derived from error estimates and an a priori knowledge of the asymptotic solution of the far-field electronic fields. Our studies reveal a significant 100–1000 fold computational savings afforded by the use of higher-order finite-element discretization, alongside providing the desired chemical accuracy. We consider this study as a step towards developing a robust and computationally efficient discretization of electronic structure calculations using the finite-element basis.