Total synthesis of cyclopiamide A and speradine E

Described is a total synthesis of the related alkaloids, cyclopiamide A and speradine E, via a unified strategy that also delivers the natural product aspergilline A. Key steps include metal-free conversion of a malonyl chloride and propargylamine to an intermediate pyrrolinone and a palladium catalyzed decarboxylation/aromatization sequence that delivers the requisite tetracyclic core.     

Rapid Estimation of Thermodynamic Parameters and Vapor Pressures of Volatile Materials at Nanoscale

Non‐isothermal measurements of thermodynamic parameters and vapor pressures of low‐volatile materials are favored when time is a crucial factor to be considered, such as in the case of detection of hazardous materials. In this article, we demonstrate that optical absorbance spectroscopy can be used non‐isothermally to estimate the thermodynamic properties and vapor pressures of volatile materials with good accuracy. This is the first method to determine such parameters in nanoscale in just minutes. Trinitrotoluene (TNT) is chosen because of its low melting temperature, which makes it impossible to determine its thermodynamic parameter by other rising‐temperature techniques, such as thermogravimetric analysis (TGA). The well‐characterized vapor pressure of benzoic acid is used to calibrate the spectrometer in order to determine the vapor pressure of low‐volatile TNT. The estimated thermodynamic properties of both benzoic acid and TNT are in excellent agreement with the literature. The estimated vapor pressure of TNT is one order of magnitude larger than that determined isothermally using the same method. However, the values are still within the range reported in the literature. The data indicate the high potential for use of rising‐temperature absorbance spectroscopy in determining vapor pressures of materials at nanometer scale in minutes instead of hours or days.     

Fingerprinting Noncanonical and Tertiary RNA Structures by Differential SHAPE Reactivity

Many RNA structures are composed of simple secondary structure elements linked by a few critical tertiary interactions. SHAPE chemistry has made interrogation of RNA dynamics at single-nucleotide resolution straightforward. However, de novo identification of nucleotides involved in tertiary interactions remains a challenge. Here we show that nucleotides that form noncanonical or tertiary contacts can be detected by comparing information obtained using two SHAPE reagents, N-methylisatoic anhydride (NMIA) and 1-methyl-6-nitroisatoic anhydride (1M6). Nucleotides that react preferentially with NMIA exhibit slow local nucleotide dynamics and usually adopt the less common C2'-endo ribose conformation. Experiments and first-principles calculations show that 1M6 reacts preferentially with nucleotides in which one face of the nucleobase allows an unhindered stacking interaction with the reagent. Differential SHAPE reactivities were used to detect noncanonical and tertiary interactions in four RNAs with diverse structures and to identify preformed noncanonical interactions in partially folded RNAs. Differential SHAPE reactivity analysis will enable experimentally concise, large-scale identification of tertiary structure elements and ligand binding sites in complex RNAs and in diverse biological environments.     

Local influence of boundary conditions on a confined supercooled colloidal liquid

We study confined colloidal suspensions as a model system which approximates the behavior of confined small molecule glass-formers. Dense colloidal suspensions become glassier when confined between parallel glass plates. We use confocal microscopy to study the motion of confined colloidal particles. In particular, we examine the influence particles stuck to the glass plates have on nearby free particles. Confinement appears to be the primary influence slowing free particle motion, and proximity to stuck particles causes a secondary reduction in the mobility of free particles. Overall, particle mobility is fairly constant across the width of the sample chamber, but a strong asymmetry in boundary conditions results in a slight gradient of particle mobility.     

Metal–Organic Frameworks (MOFs) as Safer,Structurally Reinforced Energetics

Second‐generation cobalt and zinc coordination architectures were obtained through efforts to stabilize extremely sensitive and energetic transition‐metal hydrazine perchlorate ionic polymers. Partial ligand substitution by the tridentate hydrazinecarboxylate anion afforded polymeric 2D‐sheet structures never before observed for energetic materials. Carefully balanced reaction conditions allowed the retention of the noncoordinating perchlorate anion in the presence of a strongly chelating hydrazinecarboxylate ligand. High‐quality X‐ray single‐crystal structure determination revealed that the metal coordination preferences lead to different structural motifs and energetic properties, despite the nearly isoformulaic nature of the two compounds. Energetic tests indicate highly decreased sensitivity and DFT calculations suggest a high explosive performance for these remarkable structures.     

Heptyl α‐D‐Mannosides Grafted on a β‐Cyclodextrin Core To Interfere with Escherichia coli Adhesion: An In Vivo Multivalent Effect

n‐Heptyl α‐D ‐mannoside (HM) has previously been identified as a nanomolar FimH antagonist able to prevent Escherichia coli adhesion. We have designed mono‐ and heptavalent glycoconjugates in which HM is tethered to β‐cyclodextrin (β‐CD) through short and long spacers. One‐pot click or co‐clicking procedures were developed to directly obtain the glycoconjugates from unprotected HM and β‐CD precursors. These FimH antagonists were examined biophysically and in vivo. Reverse titrations by isothermal calorimetry led to trapping of the short‐tethered heptavalent β‐CD in a complex with three FimH lectins. Combined dynamic light scattering and small‐angle X‐ray solution scattering data allowed the construction of a model of the FimH trimer. The heptavalent β‐CDs were shown to capture and aggregate living bacteria in solution and are therefore also able to aggregate FimH when attached to different bacteria pili. The first in vivo evaluation of multivalent FimH inhibitors has been performed. The heptavalent β‐CDs proved to be much more effective anti‐adhesive agents than monovalent references with doses of around 2 μg instilled in the mouse bladder leading to a significantly decreased E. coli load. Intravenously injected radiolabeled glycoconjugates can rapidly reach the mouse bladder and >2 μg concentrations can easily be retained over 24 h to prevent fluxing bacteria from rebinding.     

玫瑰红与介孔二氧化硅生物光敏复合体的激发态性质

以光动力治疗药物玫瑰红( Rose Bengal,RB)与孔径为2.7nm的介孔二氧化硅MCM-41为主体材料进行结构组装,制备了具有生物光敏功能的介孔复合载体.对介孔复合载体的性质进行了表征,通过紫外吸收和荧光光谱对玫瑰红RB在介孔孔道内的光学性质进行了分析.由于介孔道表面与RB的相互作用,不同结构和性质的内孔道中的...