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Persistent luminescence nanoparticles (PLNPs) are unique optical materials emitting long-lasting luminescence after ceasing excitation. Such a unique optical feature allows luminescence detection without constant external illumination to avoid the interferences of autofluorescence and scattering light from biological fluids and tissues. Besides, near-infrared (NIR) PLNPs have advantages of deep penetration and the reactivation of the persistent luminescence (PL) by red or NIR light. These features make the application of NIR-emitting PLNPs in long-term bioimaging no longer limited by the lifetime of PL. To take full advantage of PLNPs for biological applications, the versatile strategies for bridging PLNPs and biological system become increasingly significant for the design of PLNPs-based nanoprobes. In this Account, we summarize our systematic achievements in the biological applications of PLNPs from biosensing/bioimaging to theranostics with emphasizing the engineering strategies for fabricating specific PLNPs-based nanoprobes. We take surface engineering and manipulating energy transfer as the major principles to design various PLNPs-based nanoprobes based on the nature of interactions between nanoprobes and targets. We have developed target-induced formation or interruption of fluorescence resonance energy transfer systems for autofluorescence-free biosensing and imaging of cancer biomarkers. We have decorated single or dual targeting ligands on PLNPs for tumor-targeted imaging, and integrated other modal imaging agents into PLNPs for multimodal imaging. We have also employed specific functionalization for various biomedical applications including chemotherapy, photodynamic therapy, photothermal therapy, stem cells tracking and PL imaging-guided gene therapy. Besides, we have modified PLNPs with multiple functional units to achieve challenging metastatic tumor theranostics. The proposed design principle and comprehensive strategies show great potential in guiding the design of PLNPs nanoprobes and promoting further development of PLNPs in the fields of biological science and medicine. We conclude this Account by outlining the future directions to further promote the practical application of PLNPs. The novel protocols for the synthesis of small-size, monodisperse, and water-soluble PLNPs with high NIR PL intensity and superlong afterglow are the vibrant directions for the biomedical applications of PLNPs. In-depth theories and evidence on luminescence mechanism of PLNPs are highly desired for further improvement of their luminescence performance. Furthermore, other irradiations without tissue penetrating depth limit, such as X-ray, are encouraged for use in energy storage and re-excitation of PLNPs, enabling imaging in deep tissue in vivo and integrating other X-ray sensitized theranostic techniques such as computed tomography imaging and radiotherapy. Last but not least, PLNPs-based nanoprobes and the brand new hybrids of PLNPs with other nanomaterials show a bright prospect for accurate diagnosis and efficient treatment of diseases besides tumors. [ABSTRACT FROM AUTHOR]

A simple and practical procedure for the selective preparation of 3H-indol-3-one and indolo[1,2-c]quinazoline derivatives through copper-catalyzed aerobic oxygenation and intramolecular cyclization reactions of 2-(2-amidoaryl)-1H-indoles in the presence of acid has been disclosed. Interestingly, the reaction outcomes are exclusively dependent on the reaction medium employed. With DMF as the solvent, the amide moiety of indole substrates could act as an auxiliary to enable the indole's oxygenation reaction with molecular oxygen from air as the oxidant to give 3H-indol-3-one derivatives in a highly selective manner. On the other hand, when the reactions were performed in 1,4-dioxane, the amide moiety switched to participate in an intramolecular indolyl N1-cyclization to afford indolo[1,2-c]quinazolines as the predominating products. [ABSTRACT FROM AUTHOR]

Fluorescent sensors for mobile zinc are valuable for studying complex biological systems. Because these sensors typically bind zinc rapidly and tightly, there has been little temporal control over the activity of the probe after its application to a sample. The ability to control the activity of a zinc sensor in vivo during imaging experiments would greatly improve the time resolution of the measurement. Here, we describe photoactivatable zinc sensors that can be triggered with short pulses of UV light. These probes are prepared by functionalizing a zinc sensor with protecting groups that render the probe insensitive to metal ions. Photoinduced removal of the protecting groups restores the binding site, allowing for zinc-responsive changes in fluorescence that can be observed in live cells and tissues. [ABSTRACT FROM AUTHOR]

A novel synthesis of pyrrolidine-2-carbaldehydes or tetrahydropyridine-2-carbaldehydes from the cascade reactions of N-arylpiperidines or N-arylazepanes is presented. Mechanistically, the formation of the title compounds involves an unprecedented oxidative ring contraction of inactivated cyclic amines via Cu(OAc)2/KI/O2-promoted oxidative cleavage and reformation of the C–N bond. Interestingly, when PhI(OAc)2 was used in place of KI, 1,1-diacetates of the corresponding aldehydes were directly obtained with good efficiency. To the best of our knowledge, this is the first example of regioselective C(sp3)–H bond functionalization and C(sp3)–N bond activation of saturated cyclic amines using copper salt and oxygen. [ABSTRACT FROM AUTHOR]

A new one-pot strategy for the synthesis of quinoxalin-2-ones from the tandem nitrosation/cyclization reaction of N-aryl cyanoacetamides with tert-butyl nitrite has been developed. The dehydrogenative N-incorporation is achieved through a sequence of nitrosation, tautomerization, and cyclization, affording quinoxalin-2-ones in moderate to good yields with good functional group tolerance. [ABSTRACT FROM AUTHOR]

In this paper, we designed and synthesized three benzothiazole-based fluorescent probes L1, L2, and L3 for zinc ion detection. Among various metal ions, only the zinc ion exhibited fluorescence enhancement at 475 nm accompanied by the blue-shift emission wavelength in HEPES buffer solution containing probes. Through titration experiment, the detection limit of L1 for zinc ion sensing was calculated to be as low as 7 nM, which showed a high sensitivity. Furthermore, the confocal laser scanning micrographs of HeLa cells demonstrate good cell permeability of probe L1 and selective detection of zinc ion in living cells. The L1-Zn2+ complex was further used for pyrophosphate (PPi) sensing in HEPES buffer solution, the limit of detection was calculated to be as low as 60 nM. L1-Zn2+ can monitor the enzyme catalyzed degradation process of PPi, thus providing a meaningful way for tracking of zinc ion and pyrophosphate in biological systems. [ABSTRACT FROM AUTHOR]

Banded spherulite resulting from lamellar twisting due to the imbalanced stresses at opposite fold surfaces can be formed by isothermal crystallization of chiral polylactide and its blends with poly(ethylene glycol) (PEG). Using a polarized light microscope, the handedness of the twisted lamella in banded spherulite is determined. With the same growth axis along the radial direction as evidenced by wide-angle X-ray diffraction (WAXD) for isothermally crystallized samples at different temperatures, the twisted lamellae of chiral polylactides (poly(l-lactide) (PLLA) and poly(d-lactide) (PDLA)) display opposite handedness. The split-type Cotton effect on the C=O stretching motion of vibrational circular dichroism (VCD) spectra helps determine the helix handedness (i.e., conformational chirality). The results indicate that the conformational chirality can be defined by the molecular chirality through intramolecular chiral interactions. Moreover, the preferred sense of the lamellar twist in the banded spherulite corresponds to the twisting direction identified by the C-O-C vibration motion of VCD spectra, reflecting the role of intermolecular chiral interactions in the packing of polylactide helices. Similar results are obtained in the blends of chiral polylactides and poly(ethylene glycol) (PEG, a polymer compatible with polylactide), indicating that the impact of chirality is intrinsic irrespective of the specific crystallization conditions. In contrast to the chiral polylactides, the spectrum of the crystalline stereocomplex that associates PLLA and PDLA shows VCD silence. The spectroscopic results are in line with the morphological observations. No banded spherulites are observed in the stereocomplex crystallites due to the symmetric packing of mirror L- and D-chain conformations in the fold surfaces and the crystallites core. [ABSTRACT FROM AUTHOR]

Conspectus: The significance of chirality transfer is not only involved in biological systems, such as the origin of homochiral structures in life but also in man-made chemicals and materials. How the chiral bias transfers from molecular level (molecular chirality) to helical chain (conformational chirality) and then to helical superstructure or phase (hierarchical chirality) from self-assembly is vital for the chemical and biological processes in nature, such as communication, replication, and enzyme catalysis. In this Account, we summarize the methodologies for the examination of homochiral evolution at different length scales based on our recent studies with respect to the self-assembly of chiral polymers and chiral block copolymers (BCPs*). A helical (H*) phase to distinguish its P622 symmetry from that of normal hexagonally packed cylinder phase was discovered in the self-assembly of BCPs* due to the chirality effect on BCP self-assembly. Enantiomeric polylactide-containing BCPs*, polystyrene-b-poly(l-lactide) (PS-PLLA) and polystyrene-b-poly(d-lactide) (PS-PDLA), were synthesized for the examination of homochiral evolution. The optical activity (molecular chirality) of constituted chiral repeating unit in the chiral polylactide is detected by electronic circular dichroism (ECD) whereas the conformational chirality of helical polylactide chain can be explicitly determined by vibrational circular dichroism (VCD). The H* phases of the self-assembled polylactide-containing BCPs* can be directly visualized by 3D transmission electron microscopy (3D TEM) technique at which the handedness (hierarchical chirality) of the helical nanostructure is thus determined. The results from the ECD, VCD, and 3D TEM for the investigated chirality at different length scales suggest the homochiral evolution in the self-assembly of the BCPs*. For chiral polylactides, twisted lamellae in crystalline banded spherulite can be formed by dense packing scheme and effective interactions upon helical chains from self-assembly. The handedness of the twisted lamella can be determined by using rotation experiment of polarized light microscopy (PLM). Similar to the self-assembly of BCPs*, the examined results suggest the homochiral evolution in the crystallized chiral polylactides. The results presented in this Account demonstrate the notable progress in the spectral and morphological determination for the examination of molecular, conformational, and hierarchical chirality in self-assembled twisted superstructures of chiral polymers and helical phases of block copolymers and suggest the attainability of homochiral evolution in the self-assembly of chiral homopolymers and BCPs*. The suggested methodologies for the understanding of the mechanisms of the chirality transfer at different length scales provide the approaches to give Supporting Information for disclosing the mysteries of the homochiral evolution from molecular level. [ABSTRACT FROM AUTHOR]

Developing highly sensitive and selective methods for HOCl/OCl- detection is of significant interest. In this work, two fluorescent probes based on mono- and bis-formylated fluorescein, FN-1 and FN-2, were developed. The probes exhibit rapid response and high selectivity to HOCl/OCl- over other reactive oxygen species (ROS)/reactive nitrogen species (RNS). Furthermore, a good linearity between the fluorescent intensity at 529 nm and the concentration of HOCl/OCl- in the range 0-10 µM were presented. The probes FN-1 and FN-2 showed detection limits as low as 0.21 and 0.23 µM, respectively. The confocal laser scanning micrographs of HeLa cells confirmed cell permeability of the two probes and their abilities to detect HOCl/OCl- in living cells. Compared to compound FN-1, FN-2 has lower background fluorescence and a higher speed of the reaction with HOCl/OCl- which made it a better option for the detection of HOCl/OCl- in aqueous solution. [ABSTRACT FROM AUTHOR]

A new cascade three-component haloazidation of benzene-tethered 1,7-enynes for the formation of biologically interesting azidylated 3,4-dihydroquinolin-2(1H)-ones has been achieved under mild and metal-free conditions using TMSN3 as a N3 source and NIS (or NBS or NCS) as a halogen source. The reaction pathway involves in situ-generated azidyl radical-triggered a,β-conjugated addition/6-exo-dig cyclization/radical coupling sequence, resulting in successive multiple bond-forming events, including carbon-nitrogen, carbon-carbon, and carbon-halogen bonds to rapidly construct complex heterocyclic molecules. Furthermore, the resulting products would be useful building blocks in the discovery of lead compounds and other biologically interesting N3-containing heterocycles. [ABSTRACT FROM AUTHOR]

A new cascade three-component haloazidation of benzene-tethered 1,7-enynes for the formation of biologically interesting azidylated 3,4-dihydroquinolin-2(1H)-ones has been achieved under mild and metal-free conditions using TMSN3 as a N3 source and NIS (or NBS or NCS) as a halogen source. The reaction pathway involves in situ-generated azidyl radical-triggered α,β-conjugated addition/6-exo-dig cyclization/radical coupling sequence, resulting in successive multiple bond-forming events, including carbon-nitrogen, carbon-carbon, and carbon-halogen bonds to rapidly construct complex heterocyclic molecules. Furthermore, the resulting products would be useful building blocks in the discovery of lead compounds and other biologically interesting N3-containing heterocycles. [ABSTRACT FROM AUTHOR]

Size-resolved deposition rates and Brownian coagulation of particles between 20 and 900 nm (mobility diameter) were estimated in a well-mixed environmental chamber from a gasoline vehicle exhaust with a total peak particle concentration of 105-106 particles/cm³ at 12.24-25.22 °C. A deposition theory with modified friction velocity and coagulation model was also employed to predict particle concentration decay. Initially during particle decay, approximately 85% or more of the particles had diameters of <100 nm. Particle deposition rates with standard deviations were highly dependent on particle size ranges, and varied from 0.012 ± 0.003 to 0.48 ± 0.02 h-1. In the experiment, the friction velocity obtained was in the range 1.5-2.5 cm/s. The most explainable fractal dimension and Hamaker constant in coagulation model were 2.5-3 and 20 kT, respectively, and the contribution from coagulation dominated the total particle decay during the first 1 h of decay. It is considered that the modified friction velocity and best fitted fractal dimension and Hamaker constants could be further used to analyze gasoline vehicle exhaust particle dynamics and assess human exposure to vehicle particle pollutants in urban areas, tunnels, and underground parking lots. [ABSTRACT FROM AUTHOR]

Twonew pressure-dependent pseudo-polymorphism complexes, a 2D polymeric{[Cu2(TBA)]·2H2O}n(1) and a dinuclear [Cu2(TBA)(H2O)2]·2H2O (2), weresuccessfully obtained and demonstrated to possess weak antiferromagneticproperties. The synthesis has been achieved through a novel one-potreaction where four DMBA (DMBA = 1,3-dimethyl-barbitiric acid) moleculestetramerized in situ with EtOH to give (TBA)4-(H4TBA = 1,1',2,2'-tetra-barbiturate-ethene) ligand. This unprecedented tetramerization involves one-pot formation of onenew CC bond and four new C-C bonds. It was shown thatthe formation of 1strictly relied on the use of Cu(II)ion and EtOH and that reactions of oxidation, Knoevenagel condensation, and Michael addition probably induce the tetramerization. [ABSTRACT FROM AUTHOR]

The novel iron selenidostannates [Fe(bipy)3]Sn4Se9·2H2O (1) and [Fe(bipy)3]2[Sn3Se7]2·bipy·2H2O (2) (bipy = bipyridine) were prepared by the reactions of Sn, Se, FeCl2·4H2O, bipy, and dien with/without KSCN under hydrothermal conditions (dien = diethylenetriamine). In 1, four SnSe5 units condense via edge sharing to form the novel 3-D framework selenidostannate ∞³[Sn4Se92-] containing an interpenetrating channel system. The [Fe(bipy)3]2+ cations are accommodated in the different channels according to the conformation of the [Fe(bipy)3]2+ cation. In 2, three SnSe5 units share edges to form a 2-D ∞²[Sn3Se72-] layered anion, while two SnSe5 units and one SnSe4 unit are connected via edge sharing, forming a 1-D ∞¹[Sn3Se72-] chainlike anion. The ∞¹[Sn3Se72-], [Fe(bipy)3]2+, bipy, and H2O species are embedded between the ∞²[Sn3Se72-] layers. 2 is the first example of a selenidostannate constructed by both ∞²[Sn3Se72-]and ∞¹[Sn3Se72-] anions. The coexistence of 1-D ∞¹[Sn3Se72-] and 2-D ∞²[Sn3Se72-] anions in 2 might support the possible reaction mechanism that the ∞²[Sn3Se72-] anions are formed by condensation of the ∞¹[Sn3Se72-] chains. 1 and 2 exhibit band gaps at 1.43 and 2.01 eV, respectively [ABSTRACT FROM AUTHOR]

The introduction of the CF3 group on the C9 atom in quinidine can significantly increase the conformational interconversion barrier of the cinchona alkaloid scaffold. With this modification the conformational behavior of cinchona alkaloids in various solvents can be conveniently investigated via 19F NMR spectroscopy. Based on the reliable conformational distribution information obtained, the accuracy of both theoretical (PCM) and empirical (Kamlet—Taft) solvation models has been assessed using linear free energy relationship methods. The empirical solvation model was found to provide accurate prediction of solvent effects, while PCM demonstrated a relatively low reliability in the present study. Utilizing similar empirical solvation models along with Karplus-type equations, the conformational behavior of quinidine and 9-epi-quinidine has also been investigated. A model SN2 reaction has been presented to reveal the important role of solvent-induced conformational behavior of cinchona alkaloids in their reactivity. [ABSTRACT FROM AUTHOR]

Discrimination of glycoproteins with different glycans is a significant but difficult issue. We presented here a new strategy for strengthening the discrimination of glycoproteins by introducing a new signaling channel, fluorescence polarization (FP), into a "single probe with three signaling channels" sensor array. The single probe was aminophenylboronic-acid-conjugated poly (acrylic acid)-Mndoped ZnS quantum dots, and the three signaling channels were FP, room temperature phosphorescence and light scattering. Ten glycoproteins, including ovalbumin, fibrinogen, transferrin, horseradish peroxidase, vascular endothelial growth factor, immunoglobulin G, avidin, hyaluronidase, cellulase R- 10, and glucose oxidase, were involved for evaluating the discriminating capability. The introduction of the FP signaling channel improved the discriminating power of the sensor array, so that the 10 glycoproteins at 0.15 μM could be well discriminated both in PBS buffer and in the presence of human serum sample. The identification accuracy of the unknown samples was 96.25% (77 out of 80) at the 0.15 μM level and 97.50% (78 out of 80) at the 0.2 μM level. The integration of the signaling patterns with different responsive principles was demonstrated as the promising way to enhance the discrimination power of the single-probebased sensor arrays. [ABSTRACT FROM AUTHOR]

Three representative BINOL derivatives were examined for their chiral recognitions with D- and L-t-Boc-amino acid anions: an open system 1, which bears two urea groups and two pyrene groups; a dosed ring system 2, which bears two urea groups with a closed ring system; and a dimeric system 3, which bears two benzylic amine groups and two pyrene groups. Dimeric system 3 displayed a ΔID/ΔIL of 12.95 for t-Boc-alanine. [ABSTRACT FROM AUTHOR]

Solvothermal reactions of As2O3 and S with CoCl2·6H2O or NiCl2·6H2O in an aqueous solution of dien produced novel thioarsenates [Co(dien)2]-[Co(As3S3)2] (1) and [Ni(dien)2][Ni(As3S3)2] (2) (dien = diethylenetriamine), and the reaction with COCl2·6H2O in an aqueous solution of en afforded complex [Hen]2[{Co(en)}6(μ3-S)4(AsS3)4] (3) (en = ethylenediamine). In 1 and 2, one transition-metal ion is coordinated by two dien ligands to form [TM(dien)2]2+ (TM = Co, Ni) complex cations. The As3S3 unit coordinates to the other TM(II) ion with both As- and S-donor atoms to form the [TM(As3S3)2]2- anionic duster, in which TMAS², TMAs2S2, and TMAs3S2 rings are formed. In 3, each Co3+ ion is coordinated by an en ligand. Six Co(en) units are interlinked by four //3-S and four AsS3 ligands to form a [{Co(en)}6(μ3-S)4(AsS3)4]2- cluster containing an adamantane-like Co6S4 core. The AsS3 unit coordinates to Co atom in the n¹-AS11n²-S coordination mode with As binding Co(1) and S(1) binding Co(1) and Co(2). The As3S3 and AsS3 ligands with both As- and S-donor atoms in 1--3 have never been obtained in amine solution before. The same reactions in pure dien and en solvents afforded compounds [Co(dien)2]3[As3S6]2 (4) and [Co(en)3]2As2S5 (5) containing discrete anions [As3S6]3- and [As2Ss]4-, respectively. The band gaps of 1--3 are in the range of 1.37--1.55 eV, and die band gaps of 4 and 5 are 2.24 and 2.26 eV, which show the influence of the coordination mode of thioarsenate ligands on the electronic transitions in the TM-thioarsenates. [ABSTRACT FROM AUTHOR]

A novel strategy was presented to construct the enhanced molecularly imprinted polymer (MIP)-based room temperature phosphorescence (RTP) probe by combining the RTP of Mn-doped ZnS quantum dots (Mn-ZnS QDs) and two-fragment imprinting. Two fragments or structurally similar parts of the target analytes were used as the dummy templates. Polyethyleneimine capped Mn-ZnS (PEI-Mn-ZnS) QDs, offering the binding sites to interact with the carboxyl groups of templates, were imbedded into MIPs by the hydrolysis of tetraethoxysilane. The rebinding of the target analytes to their fragments' cavities (recognition sites) modulated the selective aggregation of Mn-ZnS QDs in QDs-MIPs and resulted in the RTP enhancement. This new method was suitable for the selective enhanced RTP detection of nonphosphorescent analytes without any derivatization and inducers. The proposed methodology was applied to construct the high selective enhanced MIP-based RTP probe for domoic acid (DA) detection. The RTP enhancement of two-fragment imprinting silica was about 2 times of one-fragment imprinting silica and 4 times of the nonimprinting silica. The two-fragment imprinting silica exhibited the linear RTP enhancement to DA in the range of 0.25-3.5 μM in buffer and 0.25-1.5 μM in shellfish sample. The precision for 11 replicate detections of 1.25 μM DA was 0.65% (RSD), and the limit of detection was 67 nM in buffer and 2.0 μg g-1 wet weight (w/w) in shellfish sample. [ABSTRACT FROM AUTHOR]

A room-temperature phosphorescence (RTP) strategy was developed for direct, additive-free discrimination of catechol from resorcinol and hydroquinone based on sodium tripolyphosphate capped Mn-doped ZnS quantum dots (STPP-Mn-ZnS QDs). The RTP response of STPP-Mn-ZnS QDs to the three isomers was pH-dependent, and the greatest difference in the RTP response to the isomers was observed at pH 8.0: catechol enhanced the RTP intensity of the QDs, while resorcinol and hydroquinone had little effect on the RTP intensity of the QDs. The enhanced RTP intensity of 1 μM catechol was not affected by the coexistence of 30 μM resorcinol and 50 μM hydroquinone at pH 8.0. The detection limit of this RTP method was 53 nM catechol, and the precision was 3.2% (relative standard deviation) for five replicate detections of 1 μM catechol. The discrimination mechanism was ascribed to the weak bonded ligand of STPP-Mn-ZnS QDs and the different interaction between the three isomers and STPP-Mn-ZnS QDs. The strong binding of catechol to Zn resulted in the extraction of Zn from the surface of STPP-Mn-ZnS QDs and the generation of holes that were trapped by Mn2+ to form Mn3+. Catechol also promoted the reduction of Mn3+ into Mn2+ excited state, thus ultimately inducing the enhanced RTP response of STPP-Mn-ZnS QDs. [ABSTRACT FROM AUTHOR]

Nanosized rod-like, wire-like, and tubular α-MnO2 and flower-like spherical Mn2O3 have been prepared via the hydrothermal method and the CCI4 solution method, respectively. The physicochemical properties of the materials were characterized using numerous analytical techniques. The catalytic activities of the catalysts were evaluated for toluene oxidation. It is shown that α- MaO2 nanorods, nanowires, and nanotubes with a surface area of 45-83 m²/g were tetragonal in crystal structure, whereas flower-like spherical Mn2O3 with a surface area of 162 m²/g was of cubic crystal structure. There were the presence of surface Mn ions in multiple oxidation states (eg., Mn3+ , Mn4+, or even Mn2+) and the formation of surface oxygen vacancies. The oxygen adspecies concentration and low-temperature reducibility decreased in the order of rod-like α-MnO2 > tube-like α-MnO2 > flower-like Mn2O3 > wire-like α-MnO2 in good agreement with the sequence of the catalytic performance of these samples. The best-performing rod-like α-MnO2 catalyst could effectively catalyze the total oxidation of toluene at lower temperatures (T50% = 210 °C and T90% = 225 °C at space velocity = 20000 mL/(g h)). It is concluded that the excellent catalytic performance of α-MnO2 nanorods might be associated with the high oxygen adspecies concentration and good low-temperature reducibility. We are sure that such one-dimensional well-defined morphological manganese oxides are promising materials for the catalytic elimination of air pollutants. [ABSTRACT FROM AUTHOR]

A sulfonate-carboxylate ligand, 4,8-disulfonyl-2,6-naphthalenedicarboxylic acid (H4-DSNDA), and eight new lanthanide coordination polymers {[Pr4(OH)4(DSNDA)2(H2O)12](H2O)10}n (1), [Ln(H2-DSNDA)0.5(DSNDA)0.5(H2O)5]n (Ln = La(2), Nd(3), Sm(4), Eu(5), Gd(6), and Dy(7)), and {[Er(H-DSNDA)(H2O)4](H2O)}n (8) have been synthesized. Detailed crystal structures of these compounds have been investigated. Compound 1 has a 3D framework featuring the unique cubane-shaped [Pr4(μ3-OH)4] clusters and is a binodal 4,8-connected network with (416∙612)(44∙62)2 topology. Compounds 2-7 are isostructural and have 2D layered structures. Compound 8 is also a 2D layer but belongs to different structural types. The luminescence behavior of compound Eu(5) shows that the π-rich aromatic organic ligands efficiently transfer the absorbed light energy to the Eu(III) ions, thus enhancing the overall luminescent properties of compound Eu(5). The magnetic properties of all compounds except for the diamagnetic La(2) compound have been investigated. In addition, elemental analysis, IR spectra, and thermogravimetric analysis of these compounds are also described. [ABSTRACT FROM AUTHOR]

In this paper we describe an on-chip multiple-concentration method combining chitosan (CS) sweeping, reversed-field stacking, and field-amplified sample stacking for highly efficient detection of bacteria. Escherichia coli was selected as a model bacterium to investigate the efficiency of this multiple-concentration method. CS was the most suitable sweeping agent for microchip electrophoresis, replacing the usually used cetyltrimethylammonium bromide for capillary electrophoresis. The additive taurine had a synergistic effect by enhancing the interaction between CS and the surface of the bacteria, thus improving the analysis sensitivity. All steps of the concentration method and related mechanisms are described and discussed in detail. A concentration enhancement factor of approximately 6000 was obtained using this concentration method under optimal conditions as compared to using no concentration step, and the detection limit of E. coli was 145 CFU/mL. The multiple-concentration methodology was also applied for the quantification of bacteria in surface water, and satisfactory results were achieved. The application of this methodology showed that the concentration enhancement of bacteria clearly conferred advantageous sensitivity, speed, and sample volume compared to established methods. [ABSTRACT FROM AUTHOR]

The article outlines the developments of natural taxanes since 1828, specifically the potential of paclitaxel. It notes the evolution of diverse strategy and various approaches to study the synthesis of taxane framework as well as for paclitaxel. It also mentions the necessity of detailed understanding on the steps of taxane biosynthesis and the determination of related genes.

Density functional theory calculations were performed to find comprehensive relationships between the structures and performance of a series of highly energetic cyclic nitramines. The isodesmic reaction method was employed to estimate the heat of formation. The detonation properties were evaluated by using the Kamlet-Jacobs equations based on the theoretical densities and HOFs. Results indicate the N-NO2 group and aza N atom are effective substituents for enhancing the detonation performance. All cyclic nitramines except C11 and C21 exhibit better detonation performance than HMX. The decomposition mechanism and thermal stability of these cyclic nitramines were analyzed via the bond dissociation energies. For most of these nitramines, the homolysis of N-NO2 is the initial step in the thermolysis, and the species with the bridged N-N bond are more sensitive than others. Considering the detonation performance and thermal stability, twelve derivatives may be the promising candidates of high energy density materials (HEDMs). The results of this study may provide basic information for the further study of this kind of compounds and molecular design of novel HEDMs. [ABSTRACT FROM AUTHOR]

Room-temperature phosphorescence (RTP) turn-on assay of heparin with tunable sensitivity and detection window was demonstrated on the basis of the target induced self-assembly of polyethyleneimine capped Mn-doped ZnS (PEI-Mn-ZnS) QDs. The proposed method can cover the whole therapeutic dosing concentration range in postoperation and long-term therapy (0.2–1.2 U/mL, 1.7–10 μM) and cardiovascular surgery (2–8 U/mL, 17–67 μM) in 10 mM Tris–HCl (pH 7.4) buffer and can be applied for heparin determination in 100-fold diluted human serum samples. The tunable sensitivity and detection window was ascribed to the tunable particle size and ligand loading amount of PEI-Mn-ZnS QD arising from the chain length (or molecule weight) and feed amount of PEI. The chain length of PEI exhibited significant effect on the particle size and ligand loading amount and ultimately had important influence on both the sensitivity and detection window. The feeding amount of PEI, however, greatly affected the ligand loading amount alone and, in turn, affected only the detection window. [ABSTRACT FROM AUTHOR]

In this work, the properties of the synthesized high-nitrogen compounds 4,4',6,6'-tetra(azido)azo-1,3,5-triazine (TAAT) and 4,4',6,6'-tetra(azido)hydrazo-1,3,5-triazine (TAHT), and a set of designed bridged triazines with similar bridges were studied theoretically to facilitate further developments for the molecules of interests. The gas-phase heats of formation were predicted based on the isodesmic reactions by using the DFT-B3LYP/AUG-cc-PVDZ method. The estimates of the condensed-phase heats of formation and heats of sublimation were estimated in the framework of the Politzer approach. Calculation results show that the method gives a good estimation for enthalpies, in comparison with available experimental data for TAAT and TAHT. The crystal density has been computed using molecular packing calculations. The calculated detonation velocities and detonation pressures indicate that -NF2, -NO2, -N-N-, and -N-N(O)- groups are effective structural units for improving the detonation performance of the bridged triazines. The synthesized TAAT and TAHT are not preferred energetic materials due to their inferior detonation performance. The p→π conjugation effect between the triazine rings and bridges makes the molecule stable as a whole. The electrostatic behavior of the bridged triazines is characterized by an anomalous surface potential imbalance when incorporating the strongly electron-withdrawing -NF2 and -NO2 groups into the molecule. An analysis of the bond dissociation energies shows that all these derivatives have good thermal stability over RDX and HMX, and the -NH-NH- bridge is more helpful for improving the stability than -N-N(O)- and -N-N- bridges. Considering the detonation performance and thermal stability, three bridged triazines may be considered as the potential candidates of high-energy density materials (HEDMs). [ABSTRACT FROM AUTHOR]

Studies have suggested that octanitrocubane (ONC) is one of the most powerful non- nuclear high energy density material (HEDM) currently known. 2,4,6,8-Tetranitro- 1,3,5,7-tetraazacubane (TNTAC) studied in this work may also be a novel HEDM due to its high nitrogen content and crystal density. Density functional theory and molecular mechanics methods have been employed to study the crystal structure, IR spectrum, electronic structure, thermodynamic properties, gas-phase and condensed-phase heat of formation, detonation performance, and pyrolysis mechanism of TNTAC. The TNTAC has a predicted density of about 2.12 g/cm³, and its detonation velocity (10.42 km/s) and detonation pressure (52.82 GPa) are higher than that of ONC. The crystalline packing is P212121, and the corresponding cell parameters are Z = 4, a = 8.87 Å, b = 8.87 Å, and c = 11.47 Å. Both the density of states of the predicted crystal and the bond dissociation energy of the molecule in gas phase show that the cage C-N bond is the trigger bond during thermolysis. The activation energy of the pyrolysis initiation reaction obtained from the B3LYP/6-311++G(2df,2p) level is 125.98 kJ/mol, which indicates that TNTAC meets the thermal stability request as an exploitable HEDM. [ABSTRACT FROM AUTHOR]

Virtual screening targeting the urokinase receptor (uPAR) led to (±)-3-(benzo[d][1,3]dioxol-5-yl)-N-(benzo[d][1,3]dioxol-5-ylmethyl)-4-phenylbutan-1-amine 1(IPR-1) and N-(3,5-dimethylphenyl)-1-(4-isopropylphenyl)-5-(piperidin-4-yl)-1H-pyrazole-4-carboxamide 3(IPR-69). Synthesis of an analogue of 1, namely, 2(IPR-9), and 3led to breast MDA-MB-231 invasion, migration and adhesion assays with IC50near 30 μM. Both compounds blocked angiogenesis with IC50of 3 μM. Compounds 2and 3inhibited cell growth with IC50of 6 and 18 μM and induced apoptosis. Biochemical assays revealed leadlike properties for 3, but not 2. Compound 3administered orally reached peak concentration of nearly 40 μM with a half-life of about 2 h. In NOD-SCID mice inoculated with breast TMD-231 cells in their mammary fat pads, compound 3showed a 20% reduction in tumor volumes and less extensive metastasis was observed for the treated mice. The suitable pharmacokinetic properties of 3and the encouraging preliminary results in metastasis make it an ideal starting point for next generation compounds. [ABSTRACT FROM AUTHOR]

Cyclic peptides (cLacs) are designed to mimic the natural phosphatidylserine (PS) binding protein lactadherin. Unlike annexin V or its small molecule mimics, the cLac peptides selectively target PS-presenting membranes with no need for metal cofactors. We further show that a fluorophore-labeled cLac effectively stains early apoptotic cells. The small size and facile conjugation with a variety of imaging tracers make the cLac design promising for imaging cell death in vitro as well as in living organisms. [ABSTRACT FROM AUTHOR]

The dilution method was used to research the interfacial composition, thermodynamic parameters, and structural parameters of [bmim][BF4] + Brij-35 + 1-butanol + toluene ionic liquid/oil (IL/O) microemulsion. The effects of the mole ratio of [bmim][BF4] to Brij-35 (R) and the addition of water on the above parameters were investigated. Studies of the interfacial composition revealed that cosurfactants at the interface (nai) increased with the increase of Rand decreased with the increase of additional water. This indicated that more cosurfactants were required to form a IL/O microemulsion than that of the traditional water/oil (W/O) microemulsion. The ΔGtovalues of transfer process of cosurfactants from the continuous oil phase to the interfacial region were all negative, which suggested that the IL/O microemulsion formed spontaneously. The absolute values of ΔGtoincreased with the increase of Rand additional water. The results showed that the IL/O microemulsion with additional water formed more spontaneously and more stably. The ΔStovalues were mostly positive, which implied that the formation processes of the IL/O microemulsions were entropy-driven. The greater number of cosurfactants at the interfacial layer contributed to form smaller ionic liquid droplets. Thus, smaller ionic liquid droplets were obtained with the increase in R, while larger droplets were obtained with the addition of water. [ABSTRACT FROM AUTHOR]

The trifluoromethyl substituent has been incorporated into quinidine as a conformational stabilizer and a probe to provide straightforward insight into the conformational behavior of cinchona alkaloids. By significantly decreasing the rotation rate of the quinoline-carbinol bond, the relatively bulky CF3 group enables the NMR signals of the syn and anti conformers to be differentiated at room temperature. In addition to the stabilizing effect, the introduction of the fluorinated moiety also facilitates the application of 19F NMR spectroscopy, thereby allowing conformational studies under various conditions without the use of deuterated solvents. [ABSTRACT FROM AUTHOR]

Bis-pyrene derivative 1, bearing two pyrene and pyridine groups, was synthesized as a ratiometric fluorescent chemosensor for Ag+ in aqueous solution. Fluorescent chemosensor 1 displayed a selective ratiometric change with Ag+, which was attributed to the excimer-monomer emissions of pyrenes. A mechanism for the binding mode was proposed based on fluorescence changes, NMR experiments, and theoretical calculations. [ABSTRACT FROM AUTHOR]

“Smart” peptides that lyse membranes in response to biological stimuli are of considerable interest. Herein, we report a facile synthesis of l-tetrafluorotyrosine (l-f4Y) and its utilization as a pH sensing element. The synthetic route affords gram quantities of l-f4Y within two days. Incorporation of this unnatural amino acid into magainin 2 gives a peptide that turns on its membrane-lytic activity upon mild acidification. [ABSTRACT FROM AUTHOR]

The present study was set out to characterize nanoparticle exposures in three selected workplaces of the packaging, warehouse, and pelletizing in a carbon black manufacturing plant using a newly developed modified electrical aerosol detector (MEAD). For confirmation purposes, the MEAD results were compared with those simultaneously obtained from a nanoparticle surface area monitor (NSAM) and a scanning mobility particle sizer (SMPS). We found that workplace background nanoparticle concentrations were mainly coming from the outdoor environment. Size distributions of nanoparticles for the three selected process areas during the work hours were consistently in the form of bimodel. Unlike nanoparticles of the second mode (simply contributed by the process emissions), particles of the first mode could be also contributed by the forklift exhaust or fugitive emissions of heaters. The percents of nanoparticles deposited on the alveolar (A) region were much higher than the other two regions of the head airway (H), tracheobronchial (TB) for all selected workplaces in both number and surface area concentrations. However, significant differences were found in percents of nanoparticles deposited on each of the three regions while different exposure metrics were adopted. Both NSAM and MEAD obtained quite comparable results. No significant difference can be found between the results obtained from SMPS and MEAD after being normalized. Considering the MEAD is less expensive, less bulky, and easy to use, our results further support the suitability of using MEAD in the field for nanoparticle exposure assessments. [ABSTRACT FROM AUTHOR]

Although overexpression and 15N enrichment facilitate the observation of resonances from disordered proteins in EscherichIa coli, 15N enrichment alone is insufficient for detecting most globular proteins. Here, we explain this dichotomy and overcome the problem while extending the capability of in-cell NMR by using 19F-labeled proteins. Resonances from small (∼10 kDa) globular proteins containing the amino acid analogue 3-fluoro-tyrosine can be observed in cells, but for larger proteins the 19F resonances are broadened beyond detection. Incorporating the amino acid analogue trifluoromethyl-L-phenylalanine allows larger proteins (up to 100 kDa) to be observed in cells. We also show that site-specific structural and dynamic information about both globular and disordered proteins can be obtained inside cells by using 19F NMR. [ABSTRACT FROM AUTHOR]

A sequential one-pot two-step tandem reaction for efficient synthesis of polysubstituted cyclopropanes has been developed. The three-component reaction of α-halogenated methylene compounds, aromatic aldehydes, and acetonitrile derivatives produced first the intermediates pyridinium salts and electron-deficient olefins, followed by cyclopropanation of pyridinium ylide with electron-deficient olefins in situ to afford polysubstituted cyclopropanes. Target compounds were obtained in high yields and were diastereomerically pure after recrystallization. [ABSTRACT FROM AUTHOR]

An efficient synthetic procedure for the preparation of fused 2,3-dihydrofuran derivatives was developed with the assistance of pyridinium ylide. A sequential one-pot, two-step tandem reaction starting from pyridine, aromatic aldehyde, dimedone, or 4-hydroxycoumarin and α-phenacyl bromide or p-nitro- benzyl bromide with triethylamine as catalyst proceeded smoothly in acetonitrile. ¹H NMR spectroscopy and single-crystal analysis demonstrated that the obtained 2,3-dihydrofurans are trans isomers. [ABSTRACT FROM AUTHOR]

A new rhodamine-based derivative bearing a pyrene group (PRC) was synthesized as a ratiometric and “off−on” chemosensor for Cu2+. PRC displayed a selective and chelation enhanced ratiometric fluorescence change and colorimetric change with Cu2+among the metal ions examined. [ABSTRACT FROM AUTHOR]

A fluorescent indicator-displacement molecular imprinting sensor array based on phenylboronic acid functionalized mesoporous silica was developed for discriminating saccharides. D-Fructose imprinted material (FruIM), D-xylose imprinted material (XyIIM) together with a control blank nonimprinted material (NIM) were synthesized as the elements of the imprinting sensor array. Spectrofluorimetric titrations of the three materials with eight selected saccharides were carried out, and Stem-Vohner quenching constants (KSV,) of NIM, FruIM, and XyIIM with the eight selected saccharides were obtained to investigate the interaction of the materials with saccharides. The present approach couples molecular imprinting technique to indicator-displacement strategy with the use of one conventional saccharide receptor (phenylboronic acid) and one commercially available fluorescent dye (Alizarin Red S., ARS) as the indicator, and allows identifying two template saccharides (u-fructose and D-xylose) plus eight nontemplate saccharides (D-arabinose, n-glucose, D-galactose, D-mannose, L-sorbose, D-ribose, L-rhamnose and sucrose). The principal component analysis (PCA) plot shows a clear discrimination of the 10 tested saccharides at 100 mM and the first principal component possesses 94.8% of the variation. Besides, the developed saccharide imprinted sensor array is successfully applied to discriminating three brands of orange juice beverage. [ABSTRACT FROM AUTHOR]

Micromixing is a crucial step for biochemical reactions in microfluidic networks. A critical challenge is that the system containing micromixers needs numerous pumps, chambers, and channels not only for the micromixing but also for the biochemical reactions and detections. Thus, a simple and compatible design of the micromixer element for the system is essential. Here, we propose a simple, yet effective, scheme that enables micromixing and a biochemical reaction in a single microfluidic chamber without using any pumps. We accomplish this process by using natural convection in conjunction with alternating heating of two heaters for efficient micromixing, and by regulating capillarity for sample transport. As a model application, we demonstrate micromixing and subsequent polymerase chain reaction (PCR) for an influenza viral DNA fragment. This process is achieved in a platform of a microfluidic cartridge and a microfabricated heating- instrument with a fast thermal response. Our results will significantly simplify micromixing and a subsequent bio- chemical reaction that involves reagent healing in microfluidic networks. [ABSTRACT FROM AUTHOR]

A new type of molecularly imprinted polymer (MIP)-based room-temperature phosphorescence (RTP) optosensor was developed by anchoring the MIP layer on the surface of Mn-doped ZnS quantum dots (QDs) via a surface molecular imprinting process. The synergetic combination of the RTP property of the Mn-doped ZnS QDs and the merits of the surface imprinting polymers not only improves the RTP selectivity of the Mn-doped ZnS QDs but also makes the MIP-based RTP optosensor also applicable to selective detecting of those nonphosphorescent analytes without the need for any inducers and derivatization. The new MIP-based RTP sensing protocol was applied to detect trace pentachlorophenol (PCP) in water samples without the interference of autofluorescence and scattering light of matrixes. The detection limit for PCP was 86 nM, and the precision for five replicate detections of 0.4 μM PCP was 2.8% (relative standard deviation). The recovery of spiked PCP in river water samples ranged from 93% to 106%. [ABSTRACT FROM AUTHOR]

Polysubstituted pyrido[1,2-α]benzimidazole derivatives are efficiently produced in moderate yields in a novel one-pot, four-component reaction from pyridine or 3-picoline, chloroacetonitrile, malononitrile, and aromatic aldehyde in refluxing acetonitrile. The mechanism of this novel reaction was believed involving the formation of polysubstituted benzenes with subsequent substitution and annulation reaction of pyridine. All pyrido[1,2-α]benzimidazoles, polysubstituted benzenes, polysubstituted indoles, and some key reaction intermediates are characterized by 1H and 13C NMR, MS, IR spectra, and elemental analysis as well as X-ray crystallography. [ABSTRACT FROM AUTHOR]

Three indoor sources (a gas stove, an electric stove, and an electric toaster oven) of ultrafine particles (UFPs) have been studied in an instrumented test house on the campus of the National Institute of Standards and Technology (NIST). Previous studies have reported the concentration of ultrafine particles indoors due to cooking, but have been limited to particles with diameters greater than 10 nm. New technology now makes it possible to measure particles as small as 2 nm. Therefore, NIST conducted a study to measure typical concentrations and estimate emission rates and coagulation rates of UFPs in the size range from 2 to 64 nm. More than 150 tests were completed. Peak concentrations from the gas and electric stovetop burners/coils occurred at a particle size of approximately 5 nm. Total number concentrations were as much as 10 times greater than reported in previous studies of particle sizès above 10 nm. Because of these high concentrations of very small particles, coagulation was the dominant process affecting the evolution of the size distribution after the source was turned off. The observed number concentration changes due to coagulation were fit by models including corrections for van der Waals and viscosity forces and fractal shapes. Indoor/outdoor ratios indicated that less than 5% of the <10 nm particles penetrated the house. This suggests that outdoor sources of these ultrafine particles will not contribute substantially to human exposure if indoor sources are present. [ABSTRACT FROM AUTHOR]

Ethanol oxidation on Pt is a typical multistep and multiselectivity heterogeneous catalytic process. A comprehensive understanding of this fundamental reaction would greatly benefit design of catalysts for use in direct ethanol fuel cells and the degradation of biomass-derived oxygenates. In this work, the reaction network of ethanol oxidation on different Pt surfaces, including close-packed Pt{111}, stepped Pt{211}, and open Pt{100}, is explored thoroughly with an efficient reaction path searching method, which integrates our new transition-state searching technique with periodic density functional theory calculations. Our new technique enables the location of the transition state and saddle points for most surface reactions simply and efficiently by optimization of local minima. We show that the selectivity of ethanol oxidation on Pt depends markedly on the surface structure, which can be attributed to the structure-sensitivity of two key reaction steps: (i) the initial dehydrogenation of ethanol and (ii) the oxidation of acetyl (CH3CO). On open surface sites, ethanol prefers C-C bond cleavage via strongly adsorbed intermediates (CH2CO or CHCO), which leads to complete oxidation to CO2. However, only partial oxidizations to CH3CHO and CH3COOH occur on Pt{111}. Our mechanism points out that the open surface Pt(100) is the best facet to fully oxidize ethanol at low coverages, which sheds light on the origin of the remarkable catalytic performance of Pt tetrahexahedra nanocrystals found recently. The physical origin of the structure-selectivity is rationalized in terms of both thermodynamics and kinetics. Two fundamental quantities that dictate the selectivity of ethanol oxidation are identified: (i) the ability of surface metal atoms to bond with unsaturated C-containing fragments and (ii) the relative stability of hydroxyl at surface atop sites with respect to other sites. [ABSTRACT FROM AUTHOR]

While most research works focus on the development of quantum dots (QDs)-based fluorescence sensors, much less attention is paid to the phosphorescence properties of QDs and their potential for phosphorescence detection. In this work, the phosphorescence property of Mn-doped ZnS QDs is explored to develop a novel room-temperature phosphorescence (RTP) method for the facile, rapid, cost-effective, sensitive, and selective detection of enoxacin in biological fluids. The Mn-doped ZnS QDs-based RIP method reported here does not need the use of deoxidants and other inducers and allows the detection of enoxacin in biological fluids without interference from autofluorescence and the scattering light of the matrix. The Mn-doped ZnS QDs offer excellent selectivity for detecting enoxacin in the presence of the main relevant metal ions in biological fluids, biomolecules, and other kinds of antibiotics. Quenching of the phosphorescence emission due to the addition of enoxacin at 1.0 μM is unaffected by 5000-fold excesses of Na+ and 10000-fold excesses of K+, Mg2+, and Ca2+. Amino acids such as tryptophan, histidine, and L-cysteine at 1000-fold concentration of enoxacin do not affect the detection of enoxacin. Glucose does not affect the detection at 10000-fold concentration of enoxacin. Typical coadministers (mainly other types of antibiotics) such as ceftezole, cefoperazone, oxacillin, and kalii dehydrographolidi succinas are permitted at 50-, 10-, 100-, and 50-fold excesses, respectively, without interference with the detection of enoxacin. The precision for 11 replicate detections of 0.4 μM enoxacin is 1.8% (RSD). The detection limit for enoxacin is 58.6 nM. The recovery of spiked enoxacin in human urine and serum samples ranges from 94 to 104%. The developed Mn-doped ZnS QDs-based RTP method is employed to monitor the lime-dependent concentration of enoxacin in urine from a healthy volunteer after the oral medication of enoxacin. The investigation provides evidence that doped QDs are promising for RTP detection in further applications. [ABSTRACT FROM AUTHOR]

The interfacial and thermodynamic properties of aqueous HCl + cetyltrimethylammonium chlorine (CTAC) + alkanol + diesel oil w/o microemulsion systems were investigated by the method of dilution. Aqueous hydrochloric acid solution (mass fraction 20 %) was used to investigate the effect of HCl on the formation of microemulsion. The composition of the cosurfactant and the surfactant in the interfacial region, the distribution of the cosurfactant between the interfacial region and the continuous oil phase, the energetics of transfer of the cosurfactant from the oil to the interface, and the structural parameters of the microemulsion were estimated at (303, 313, and 323) K. [ABSTRACT FROM AUTHOR]

Eighteen structures of new organic alkalides (Mn6adz)M‘-(M, M‘ Li, Na, K; n2, 3) with the alkali-metal cation Mlying near the center of the adz cage and the alkali-metal anion M‘-located outside are obtained with all real frequencies. They exhibit very large static first hyperpolarizabilities (0) up to 3.2 × 105au, which exceeds the record value of 01.7 × 105au for nonlinear optical compounds Chem.Eur. J.1997, 3, 1091. All potassides (Mn6adz)K-(M Li, Na, K; n2, 3) have considerably large 0values (1.6 × 105−3.2 × 105au) much larger than the 0value (3.6 × 104au) of the previously designed cuplike alkalide Li(calix4pyrrole)K-J. Am. Chem. Soc. 2006, 128, 1072. This shows that the 26adz and 36adz cage complexants are preferable to cuplike calix4pyrrole complexant in enhancing the first hyperpolarizability. The effect of cage size of the complexant on the first hyperpolarizability is also presented here:  in most cases, the smaller cage complexant corresponds to the larger 0value. Moreover, the crucial role by the alkali-metal anion in the large first hyperpolarizability of these alkalides is revealed. These results may provide new means for designing high-performance nonlinear optical materials. [ABSTRACT FROM AUTHOR]

The potent new antiviral inhibitor GRL-98065 (1) of HIV-1 protease (PR) has been studied with PR variants containing the single mutations D30N, I50V, V82A, and I84Vthat provide resistance to the major clinical inhibitors. Compound 1had inhibition constants of 17-fold, 8-fold, 3-fold, and 3-fold, respectively, for PRD30N, PRI50V, PRV82A, and PRI84Vrelative to wild type PR. The chemically related darunavir had similar relative inhibition, except for PRD30N, where inhibitor 1was approximately 3-fold less potent. The high resolution (1.11−1.60 Å) crystal structures of PR mutant complexes with inhibitor 1showed small changes relative to the wild type enzyme. PRD30Nand PRV82Ashowed compensating interactions with inhibitor 1relative to those of PR, while reduced hydrophobic contacts were observed with PRI50Vand PRI84V. Importantly, inhibitor 1complexes showed fewer changes relative to wild type enzyme than reported for darunavir complexes. Therefore, inhibitor 1is a valuable addition to the antiviral inhibitors with high potency against resistant strains of HIV. [ABSTRACT FROM AUTHOR]