Reverse micelles and microemulsions formed in liquid and supercritical carbon dioxide (CO 2 ) allow highly polar or polarizable compounds to be dispersed in this nonpolar fluid.1 However, since the polarizability per unit volume of dense CO 2 is quite low, it is difficult to overcome the strong van der Waals attractive interactions between particles in order to stably suspend macro-molecular species. Conventional surfactants by themselves do not form reverse micelles or microemulsions in CO 2 because the van der Waals interdroplet attractions are too high. The use of surfactants or cosurfactants with fluorinated tails provides a layer of a weakly attractive compound covering the highly attractive droplet cores, thus preventing their short-range interactions that would destabilize the system. Using this strategy, we describe a method to synthesize and stabilize metallic silver nanoparticles having diameters from 5 to 15 nm in supercritical CO 2 using an optically transparent, waterin-CO 2 microemulsion.In this work, the size of the particles in the microemulsion was estimated from the height and width of the surface plasmon resonance band in the UV-visible absorption spectra.2 TEM micrographs of offline samples confirmed the in situ measurements of Ag particle size. Microemulsions containing Ag particles had relatively long stability (>1 h) in supercritical CO 2 at 35 °C, 400 bar (T c = 31.2 °C). This is the first report of the stable suspension of nanometer-sized metallic particles in CO 2 and represents a significant advance for the future application of CO 2 solvent-based systems for a wide range of particle synthesis and catalytic reactions in this environmentally friendly solvent.There are numerous studies of reverse micelles or microemulsions in supercritical fluids starting from the late 1980s.3 Early studies showed that nanometer-sized water droplets could be thermodynamically stabilized in supercritical alkanes, hydrochloro-fluorocarbons, and more exotic fluids such as xenon. Over the past decade, there have been significant advances toward the formation of microemulsions in CO 2 by using a variety of different fluorinated surfactants.1 In a related area, fluorinated chelates have been used to "dissolve" a number of different metal ions in CO 2 .4 Another process that was used to produce nanomaterials involved dissolving a compound (on a molecular level) in a supercritical fluid © 1999 American Chemical Society * To whom correspondence should be addressed.. and then rapidly expanding this supercritical solution (RESS) through a nozzle whereby the nucleation processes produce nanometer-sized powders.5 A variation of this process has recently been reported6 for the production of Ag particles, in which the precursor AgNO 3 is dissolved in supercritical ammonia and then sprayed into a liquid ethanol solution containing a reducing agent. NIH Public AccessThere are only a few reported studies of reactions in supercritical fluid microemulsions. Nanometer-and micrometer-sized metal oxide and metal sulfide partic...

Recent efforts to identify treatments for myocardial ischemia reperfusion injury have resulted in the discovery of a novel series of highly potent α,α-disubstituted amino acid-based arginase inhibitors. The lead candidate, (R)-2-amino-6-borono-2-(2-(piperidin-1-yl)ethyl)hexanoic acid, compound 9, inhibits human arginases I and II with IC50s of 223 and 509 nM, respectively, and is active in a recombinant cellular assay overexpressing human arginase I (CHO cells). It is 28% orally bioavailable and significantly reduces the infarct size in a rat model of myocardial ischemia/reperfusion injury. Herein, we report the design, synthesis, and structure-activity relationships (SAR) for this novel series of inhibitors along with pharmacokinetic and in vivo efficacy data for compound 9 and X-ray crystallography data for selected lead compounds cocrystallized with arginases I and II.

Abstract:The chemical structure of a drug determines its physicochemical properties, further determines its ADME/Tox properties, and ultimately affects its pharmacological activity. Medicinal chemists can regulate the pharmacological activity of drug molecules by modifying their structure. Ring systems and functional groups are important components of a drug. The proportion of non-hydrocarbon atoms among non-hydrogen atoms reflects the heavy atoms proportion of a drug. The three factors have considerable potential for the assessment of the drug-like properties of organic molecules. However, to the best of our knowledge, there have been no studies to systematically analyze the simultaneous effects of the number of aromatic and non-aromatic rings, the number of some special functional groups and the proportion of heavy atoms on the drug-like properties of an organic molecule. To this end, the numbers of aromatic and non-aromatic rings, the numbers of some special functional groups and the heavy atoms proportion of 6891 global approved small drugs have been comprehensively analyzed. We first uncovered three important structure-related criteria closely related to drug-likeness, namely: (1) the best numbers of aromatic and non-aromatic rings are 2 and 1, respectively; (2) the best functional groups of candidate drugs are usually -OH, -COOR and -COOH in turn, but not -CONHOH, -SH, -CHO and -SO 3 H. In addition, the -F functional group is beneficial to CNS drugs, and -NH 2 functional group is beneficial to anti-infective drugs and anti-cancer drugs; (3) the best R value intervals of candidate drugs are in the range of 0. 05-0.50 (preferably 0.10-0.35), and R value of the candidate CNS drugs should be as small as possible in this interval. We envision that the three chemical structure-related criteria may be applicable in a prospective manner for the identification of novel candidate drugs and will provide a theoretical foundation for designing new chemical entities with good drug-like properties.

We have combined a stand-alone Bi2Sr2CaCu2O8 intrinsic Josephson junction stack, emitting terahertz radiation, with a YBa2Cu3O7 grain boundary Josephson junction acting as detector. The detector is mounted on a lens, positioned 1.2 cm away from the emitter on a similar lens. With the emitter radiating at 0.5 THz, we observed up to 7 Shapiro steps on the current-voltage characteristic of the detector. The ac current induced in this junction was 0.9 mA, and the dissipated power was 1.8 μW. The setup, although far from being optimized, may be considered as a first step towards an integrated high-Tc receiver.