Project description:Currently, two-photon excitation microscopy is the method of choice for imaging living cells within thick specimen. A remaining problem for this technique is the damage caused by the high photon flux in the excitation region. To reduce the required flux, a promising solution is to use highly frequency-anticorrelated photon pairs, which are known to induce two-photon transitions much more efficiently. It is still an open question what the best scheme is for generating such photon pairs. Here we propose one simple general strategy for this task. As an example, we show explicitly that this general strategy can be realized faithfully within the widely applicable coherently pumped Jaynes-Cummings model. It is shown quantitatively that this strategy can generate highly frequency-anticorrelated photon pairs which can dramatically enhance two-photon excitation efficiency. We believe the proposed strategy can guide new designs for generating frequency-anticorrelated photon pairs.
Project description:Tetracyclic terpenoid-derived natural products are a broad class of medically relevant agents that include well-known steroid hormones and related structures, as well as more synthetically challenging congeners such as limonoids, cardenolides, lanostanes, and cucurbitanes, among others. These structurally related compound classes present synthetically disparate challenges based, in part, on the position and stereochemistry of the numerous quaternary carbon centers that are common to their tetracyclic skeletons. While de novo syntheses of such targets have been a topic of great interest for over 50 years, semisynthesis is often how synthetic variants of these natural products are explored as biologically relevant materials and how such agents are further matured as therapeutics. Here, focus was directed at establishing an efficient, stereoselective, and molecularly flexible de novo synthetic approach that could offer what semisynthetic approaches do not. In short, a unified strategy to access common molecular features of these natural product families is described that proceeds in four stages: (1) conversion of epichlorohydrin to stereodefined enynes, (2) metallacycle-mediated annulative cross-coupling to generate highly substituted hydrindanes, (3) tetracycle formation by stereoselective forging of the C9-C10 bond, and (4) group-selective oxidative rearrangement that repositions a quaternary center from C9 to C10. These studies have defined the structural features required for highly stereoselective C9-C10 bond formation and document the generality of this four-stage synthetic strategy to access a range of unique stereodefined systems, many of which bear stereochemistry/substitution/functionality not readily accessible from semisynthesis.
Project description:Computational models provide insight into the structure-function relationship in proteins. These approaches, especially those based on normal mode analysis, can identify the accessible motion space around a given equilibrium structure. The large magnitude, collective motions identified by these methods are often well aligned with the general direction of the expected conformational transitions. However, these motions cannot realistically be extrapolated beyond the local neighborhood of the starting conformation. In this article, the iterative cluster-NMA (icNMA) method is presented for traversing the energy landscape from a starting conformation to a desired goal conformation. This is accomplished by allowing the evolving geometry of the intermediate structures to define the local accessible motion space, and thus produce an appropriate displacement. Following the derivation of the icNMA method, a set of sample simulations are performed to probe the robustness of the model. A detailed analysis of beta1,4-galactosyltransferase-T1 is also given, to highlight many of the capabilities of icNMA. Remarkably, during the transition, a helix is seen to be extended by an additional turn, emphasizing a new unknown role for secondary structures to absorb slack during transitions. The transition pathway for adenylate kinase, which has been frequently studied in the literature, is also discussed.
Project description:Challenges in the assembly of glycosidic bonds in oligosaccharides and glycoconjugates pose a bottleneck in enabling the remarkable promise of advances in the glycosciences. Here, we report a strategy that applies unique features of highly electrophilic boron catalysts, such as tris(pentafluorophenyl)borane, in addressing a number of the current limitations of methods in glycoside synthesis. This approach utilizes glycosyl fluoride donors and silyl ether acceptors while tolerating the Lewis basic environment found in carbohydrates. The method can be carried out at room temperature using air- and moisture-stable forms of the catalyst, with loadings as low as 0.5 mol %. These characteristics enable a wide array of glycosylation patterns to be accessed, including all C1-C2 stereochemical relationships in the glucose, mannose, and rhamnose series. This method allows one-pot, iterative glycosylations to generate oligosaccharides directly from monosaccharide building blocks. These advances enable the rapid and experimentally straightforward preparation of complex oligosaccharide units from simple building blocks.
Project description:BackgroundMost neurosurgical photographs are limited to two-dimensional (2D), in this sense, most teaching and learning of neuroanatomical structures occur without an appreciation of depth. The objective of this article is to describe a simple technique for obtaining right and left 2D endoscopic images with manual angulation of the optic.MethodsThe implementation of a three-dimensional (3D) endoscopic image technique is reported. We first describe the background and core principles related to the methods employed. Photographs are taken demonstrating the principles and also during an endoscopic endonasal approach, illustrating the technique. Later, we divide our process into two sections containing explanations, illustrations, and descriptions.ResultsThe results of taking a photograph with an endoscope and its assembly to a 3D image has been divided into two parts: Photo acquisition and image processing.ConclusionWe conclude that the proposed method is successful in producing 3D endoscopic images.
Project description:The simultaneous polymerization and crystallization of monomers featuring directional bonding designs provides covalent organic frameworks (COFs), which are periodic polymer networks with robust covalent bonds arranged in two- or three-dimensional topologies. The range of properties characterized in COFs has rapidly expanded to include those of interest for heterogeneous catalysis, energy storage and photovoltaic devices, and proton-conducting membranes. Yet many of these applications will require materials quality, morphological control, and synthetic efficiency exceeding the capabilities of contemporary synthetic methods. This level of control will emerge from an improved fundamental understanding of COF nucleation and growth processes. More powerful characterization of structure and defects, improved syntheses guided by mechanistic understanding, and accessing diverse isolated forms, ranging from single crystals to thin films to colloidal suspensions, remain important frontier problems.
Project description:We present an algorithm to solve the linear response equations for Hartree-Fock, Density Functional Theory, and the Multiconfigurational Self-Consistent Field method that is both simple and efficient. The algorithm makes use of the well-established symmetric and antisymmetric combinations of trial vectors but further orthogonalizes them with respect to the scalar product induced by the response matrix. This leads to a standard, symmetric block eigenvalue problem in the expansion subspace that can be solved by diagonalizing a symmetric, positive definite matrix half the size of the expansion space. Numerical tests showed that the algorithm is robust and stable.
Project description:AIM: To prepare a novel formulation of phosphatidylcholine (PC)-bile salts (BS)-mixed micelles (MMs) loaded with silybin (SLB)-PC complex for parenteral applications. METHODS: SLB-PC-BS-MMs were prepared using the co-precipitation method. Differential scanning calorimetry (DSC) analysis was used to confirm the formation of the complex and several parameters were optimized to obtain a high quality formulation. The water-solubility, drug loading, particle size, zeta potential, morphology and in vivo properties of the SLB-PC-BS-MMs were determined. RESULTS: The solubility of SLB in water was increased from 40.83 ± 1.18 μg/mL to 10.14 ± 0.36 mg/mL with a high drug loading (DL) of 14.43% ± 0.44% under optimized conditions. The SLB-PC-BS-MMs were observed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) and showed spherical shapes. The particle size and zeta potential, as measured by photon correlation spectroscopy (PCS), were about 30 ± 4.8 nm and -39 ± 5.0 mV, respectively. In vivo studies showed that incorporation of the SLB-PC complex into PC-BS-MMs led to a prolonged circulation time of the drug. CONCLUSION: This novel formulation appears to be a good candidate for drug substances that exhibit poor solubility for parenteral administration.
Project description:In this study, the synthesis of a novel functionalized metal-organic-framework (MOF) [Cu(BDC-NH2)@Schiff-base-Pd(ii)] catalyst via post-synthetic modification of Cu(BDC-NH2) is reported. The targeted complex was prepared by chemically attaching N,N'-bis(5-formylpyrrol-2-ylmethyl) homopiperazine via a Schiff base reaction followed by complexation with Pd ions. Afterwards, the synthesized solid was applied as a very effective multifunctional catalyst in C-N coupling reactions. The synthesized compounds were identified by suitable techniques including N2 isotherms, EDX spectroscopy, FT-IR spectroscopy, XRD, SEM, ICP-OES and TG-DTA. This nanocatalyst was used in C-N cross-coupling reactions, and it showed its usage in a diverse range of different functional groups with good efficiency. The reasons for introducing this catalyst system are its advantages such as considerably high selectivity, almost complete conversion of products, high yields, and convenient separation of catalysts and products. The results indicate that the highest efficiency of the product in the reaction was obtained in the shortest possible time with the use of [Cu(BDC-NH2)@Schiff-base-Pd(ii)] catalysts. Overall, the high catalytic activity of the [Cu(BDC-NH2)@Schiff-base-Pd(ii)] catalyst may be due to the obtained high surface area and the synergistic features created between Lewis acidic Cu nodes and Pd ions.