Enantioselective Radical-Type 1,2-Alkoxy-Phosphinoylation to Styrenes Catalyzed by Chiral Vanadyl Complexes.

A series of vanadyl complexes bearing 3-t-butyl-5-bromo, 3-aryl-5-bromo, 3,5-dihalo-, and benzo-fused N-salicylidene-tert-leucinates was examined as catalysts for 1,2-alkoxy-phosphinoylation of 4-, 3-, 3,4-, and 3,5-substituted styrene derivatives (including Me/t-Bu, Ph, OR, Cl/Br, OAc, NO2 , C(O)Me, CO2 Me, CN, and benzo-fused) with HP(O)Ph2 in the presence of t-BuOOH (TBHP) in a given alcohol or cosolvent with MeOH. The best scenario involved the use of 5 mol % 3-(2,5-dimethylphenyl)-5-Br (i.e., 3-DMP-5-Br) catalyst at 0 °C in MeOH. The desired catalytic cross coupling reactions proceeded smoothly with enantioselectivities of up to 95 % ee of (R)-configuration as confirmed by X-ray crystallographic analysis of several recrystallized products. The origin of enantiocontrol and homolytic substitution of the benzylic intermediates by vanadyl-bound methoxide and radical type catalytic mechanism were proposed.

Metal-Ion Specific Recognition with Amplified Transcription from Subnanometer to Submillimeter or Real-Time Domain by Self-Assembled Vanadyl Quartets.

Vanadyl(V) complexes 1 and 2 bearing a nematic liquid crystal (LC) like a p-heptoxyphenyl group or a fluorous-tag p-nonafluoroheptoxyphenyl (NFH) group at the C5 position of the N-salicylidene template were designed and synthesized. Each complex was subjected to MVO3-induced self-assembly to form metal-ion, encapsulated quartet clusters 3-M and 3'-M. The Na+ in cluster complex 3-Na or 3'-Na can be readily replaced by Rb+, Ag+, or Hg2+ in an aqueous layer to form cluster complexes by ion swapping at the H2O/CDCl3 bilayer interface. Selectivity profiles were examined with alkali-metal ions, Ag+, and Hg2+ through metal-ion competition experiments. The 3'-Na has an exclusive selectivity for Hg2+ in the presence of Zn2+ and Cd2+. Cluster complexes 3-M were utilized as chiral dopants to nematic LC materials. The effects of the encapsulated metal ions within the alkali family and Ag+ on Cano's line widths and helical pitch changes were viewed in wedge cells under a polarized microscope. Their correlations with the ionic radius were identified. The subnano information of the metal ions can thus be asymmetrically amplified to Cano's line spacings of the submilimeter domain. Conversely, the effects of the encapsulated alkali metal ions and Hg2+ in 3'-M on the interactions of their NFH tails toward fluorous silica gel (FSG) were performed via HPLC analyses. Their retention times became longer as the sizes of encapsulated, alkali metal ions increased. The increasing ion size from Na+ to Cs+ caused the four lower rim NFH tags of the cluster to be closer due to reduced cone angles. Their interactions among NFH tail groups on FSG became larger, thus leading to distinctive separations with tR from 7.36 to 10.27 min. The retention time difference between 3'-Na and 3'-Hg on HPLC was ∼3.6 min, resulting in discernible separation. The individual ion size differences on the subnano scale can thus be amplified and unambiguously established in the real time domain.

Asymmetric Synthesis of Trifluoroethyl-Based, Chiral 3-Benzyloxy-1- and -2-Phenyl-quinazolinones of Biomedicinal Interest by Radical Type Cross-Coupling to Olefins.

Several 2-substituted (H, Ph, and S-Me) and 1-substituted (H, Ph, and Bn), 3-hydroxy-1,3-quinazolin(di)ones were utilized for the first time as radical trapping agents in asymmetric 1,2-oxytrifluoromethylation of styrenes catalyzed by chiral vanadyl methoxide complexes bearing 3,5-disubstituted-N-salicylidene-t-leucinate templates. The effects of catalysts and solvents on the asymmetric induction were systematically examined. The best and complementary scenarios involved the use of vanadyl complexes V(O)-1 and V(O)-2, which bear 3-(2,5-dimethyl)phenyl-5-bromophenyl and 3-t-butyl-5-bromophenyl groups in an i-propanol solvent at ambient temperature. The corresponding (R)-cross-coupling products by V(O)-1 were obtained in 45-71% (for 2-substituted series) and 59-93% yields (for 1-substituted series) for p-/m-methylstyrenes and m-halo/CF3/CO2Me-styrenes in 38-63% ees (the best in 2-H case) and 60-84% ees (the best in 1-benzyl cases), respectively. The corresponding (S)-cross-coupling products by V(O)-2 were obtained in 28-55% (for 2-substituted series) and 45-72% yields (for 1-substituted series) for the same substrate class in 50-91% ees (85-91% ees in 2-phenyl cases) and 64-75% ees (up to 74-75% ees for each 1-H, Ph, and Bn cases), respectively. Theoretical calculations were carried out to explain the origin and extent of enantiocontrols. They both may serve as potential inhibitors of acetohydroxyacid synthase and epidermal growth factor receptor (EGFR) kinases.

Chiral Vanadyl(V) Complexes Enable Efficient Asymmetric Reduction of ß-Ketoamides: Application toward (S)-Duloxetine.

High-valent chiral oxidovanadium(V) complexes derived from 3,5-substituted-N-salicylidene-l-tert-leucine were used as catalysts in asymmetric reduction of N-benzyl-ß-ketoamides. Among six different solvents, three different alcohol additives, and two different boranes examined, the use of pinacolborane in tetrahydrofuran (THF) with a t-BuOH additive led to the best results at -20 °C. The corresponding ß-hydroxyamides can be furnished with yields up to 92% and an enantiomeric excess (ee) up to 99%. We have successfully extended this catalytic protocol for the synthesis of an (S)-duloxetine precursor.

Directed Self-Assembly of C4-Symmetric, Oxidovanadate-Centered, Vanadyl(V) Quadruplexes for Ba2+- and Hg2+-Specific Recognition, Transport, and Recovery.

Directed assembly of loosely, Na+-bound, oxidovanadate-centered quartets of C4-symmetry from tailor-made chiral N-salicylidene-vanadyl(V) complexes, for the first time, allows for highly efficient Ba2+- or Hg2+-specific detection (by 51V NMR and VCD), transport (forming a unique helical capsule or a capped square planar complex, respectively), and green recovery from an aqueous phase containing 4 different alkaline earth ions or from at least 10 different metal ions of similar size and charge capacity into the CHCl3 layer without interference from oxa- or oxophilic ions like Mg2+, Ca2+, Cu2+, Cd2+, and Pb2+.

Vanadyl species-catalyzed complementary ß-oxidative carbonylation of styrene derivatives with aldehydes.

A series of oxometallic species and metal acetylacetonates (acac) was examined as catalysts for oxidative carbonylation of styrene with benzaldehyde using t-butylhydroperoxide as the co-oxidant in warm acetonitrile. Among them, VO((acac)2 and vanadyl(IV) chloride were found to be the only catalyst class to achieve cross-coupling processes by judiciously tuning the ligand electronic attributes, leading to ß-hydroxylation- and ß-peroxidation-carbonylation of styrene, respectively, in a complementary manner. Mechanistic studies indicated that vanadyl-associated acyl radicals generated by t-butoxy radical-assisted, homolytic cleavage of the aldehyde C-H bond were involved in tandem processes with an exclusive syn diastereoselectivity in the case of ß-methylstyrene.

Expedient Azide-Alkyne Huisgen Cycloaddition Catalyzed by a Combination of VOSO4 with Cu(0) in Aqueous Media.

A series of vanadium(III), vanadyl(IV/V) species, inorganic metal oxides, and transition-metal oxides was examined as cocatalysts with Cu(0) powder for copper(I)-catalyzed azide-alkyne cycloaddition. Among them, vanadyl(IV) species bearing acetylacetonate, acetate, and sulfate, vanadyl(V) isopropoxide, and vanadate were suitable for the click reactions of per-acetyl and per-benzyl ß-azido glycosides with three different terminal alkynes in CH3CN. Water-soluble vanadyl(IV) sulfate was further selected for efficient click reactions for unprotected ß-glycosyl azides and even compatible with a thiol-containing substrate in aqueous media at ambient temperature.

Complementary helicity interchange of optically switchable supramolecular-enantiomeric helicenes with (-)-gel-sol-(+)-gel transition ternary logic.

A gallamide-containing pseudoenantiomeric helicene pair bearing a (10R,11R)-dimethoxymethyldibenzosuberane core can self-assemble by intermolecular amide H-bonding and π-π stacking into bundled helical fibers with helical tunnels of complementary helicity in CH2Cl2. The helicenes undergo excellent complementary photoswitchings of ternary logic at 280, 318, and 343 nm through (-)-gel-sol-(+)-gel interconversion.

Spirally Configured cis-Stilbene/fluorene (STIF), 10,11-Benzo-, and Imidazole-fused STIF Hybrids as Electron-Transporting Materials for Organic Light-Emitting Diode Applications.

A new class of cis-stilbene/fluorene (STIF) and 10,11-benzo- and imidazole-fused dibenzosuberane/fluorene (Bz-STIF and Imd-STIF) spiro hybrid systems with paired cyanophenyl, pyridyl, and/or pyrimidyl units was synthesized as electron transporting materials (ETMs) for blue fluorescent OLEDs (FOLEDs) and phosphorescent organic light emitting diodes (PhOLEDs). Their photophysical (UV-Vis absorption and emission), electrochemical (Eox /Ered ), morphological (glassy transition temperature, Tg ), and thermal stability (decomposition temperature, Td ) properties are systematical compared. Their correlations regarding the effects of the fused unit/substituent(s) in the STIF core on the morphological/thermal stability, HOMO/LUMO energy level, π-electron distribution profiles by DFT calculations, and electron mobility are established. Blue FOLEDs are fabricated by using them and TmPyPB (a control) as ETMs. The effects of their LUMO energy levels and electron mobilities on the device turn-on voltage, performance efficiencies including external quantum efficiency/current efficiency (EQE/CE), power efficiency (PE), and device lifetime at 5% luminescence decay (T95 ) are correlated. Among them, three best ETMs and TmPyPB (a control) are selected for further green and blue PhOLED fabrications. The effects of their LUMO energy levels and electron mobilities on the device turn-on voltage and performance efficiencies are confirmed, allowing for potential commercial applications.

Enantioselective Synthesis of 1-Aryl Tetrahydroisoquinolines by the Rhodium-Catalyzed Reaction of 3,4-Dihydroisoquinolinium Tetraarylborates.

The 1-aryl tetrahydroisoquinolines (1-aryl THIQs) are omnipresent in biologically active molecules. Here we report on the direct asymmetric synthesis of these valuable compounds via the reaction of 3,4-dihydroisoquinolinium tetraarylborates. The dual roles of anionic tetraarylborates, which function as both prenucleophiles and stabilizers of 3,4-dihydroisoquinolinium cations, enable this rhodium(I)-catalyzed protocol to convergently provide enantioenriched 1-aryl THIQs in good yields (≤95%) with ≤97% ee, as demonstrated by the formal synthesis of (-)-solifenacin and the facile synthesis of (-)-Cryptostyline I.

Fluorescent Nanohybrids from ZnS/CdSe Quantum Dots Functionalized with Triantennary, N-Hydroxy-p-(4-arylbutanamido)benzamide/Gallamide Dendrons That Act as Inhibitors of Histone Deacetylase for Lung Cancer.

N-Hydroxy-p-(4-arylbutanamido)benzamides (HABAB) belong to one class of histone deacetylase inhibitors (HDACi), which regulate deacetylation of lysine residue's amino group in histone, which results in chromatin constriction. In addition, transcriptional knockdown of the genetic loci possessing the suppressor genes of tumor occurs. A tripodal, HABAB-capped gallamide dendron possessing thiol anchoring unit was prepared by the click method. The resultant hydrophilic dendritic unit was easily attached on the outer layer of CdSe/ZnS (i.e., core/shell type) quantum dots by thiolate-Zn interaction, as supported via 1H NMR spectroscopic analysis of the conjugate with its original property of fluorescence. The resulting, water-miscible nanohybrid (nano-HTPB) which bore trivalent, peripheral HABABs as the HDACi was efficiently taken up by cells of lung cancer and transported into the nuclei of cells in 3 h, as confirmed by confocal microscopy analysis. The concentration levels of 50% inhibition (IC50) after 48 h incubation of the nano-HTPB for A549 and H1299 lung cancer cell lines were 14 and 18 nM, respectively, which were about 150-fold lower than those of the parent HTPB analogues. Nano-HTPB at 20 nM induced the knockdown of cell cycle at second growth/mitosis (i.e., G2/M) transition, which eventually led to apoptosis of lung cancer cells, demonstrating that the nano-HTPB was much more potent in inhibiting lung cancer cell growth in a synergistic manner than the parent HTPB analogues. In addition, the dendritic HABAB-capped nanohybrid, nano-HTPB, is more effective than the parent HTPB analogues both in vitro and in vivo. Furthermore, the nano-HTPB is more effective than the parent HTPB to increase the acetylation level of proteins related to histone and nonhistone like p53 and tubulin. Our results confirmed that covalent encapsulation of quantum dots with peripheral, triantennary HDACis represented a feasible strategy for synergistic drug delivery with enhanced biological effects.

Effect of chronic kidney disease on outcomes following proximal humerus fragility fracture surgery in diabetic patients: A nationwide population-based cohort study.

BACKGROUND: The proximal humerus fracture (PHF) is the third most common fragility fracture. Diabetes mellitus (DM) and chronic kidney disease (CKD) are both risks for fragility fractures; however, the interplay of DM and CKD makes treatment outcomes unpredictable. This study aimed to investigate and compare early and late outcomes following proximal humerus fracture fixation surgery in diabetic patients with different renal function conditions. METHODS: DM patients receiving PHF fixation surgery during 1998-2013 were recruited from Taiwan's National Health Insurance Research Database. According to their renal function, patients were divided into three study groups: non-chronic kidney disease (CKD), non-dialysis CKD, and dialysis. Outcomes of interest were early and late perioperative outcomes. Early outcomes included in-hospital newly-onset morbidities. Late outcomes included infection, revision, readmission, and all-cause mortality. RESULTS: This study included a total of 10,850 diabetic patients: 2152 had CKD (non-dialysis CKD group), 196 underwent permanent dialysis (dialysis group), and the remaining 8502 did not have CKD (non-CKD group). During a mean follow-up of 5.56 years, the dialysis group showed the highest risk of overall infection, all-cause revision, readmission, and mortality compared to the non-dialysis CKD group and non-CKD group. Furthermore, subgroup analysis showed that CKD patients had a higher risk of surgical infection following PHF surgery than non-CKD patients in cases with a traffic accident or fewer comorbidities (Charlson Comorbidity Index, CCI <3) (P for interaction: 0.086 and 0.096, respectively). Also, CKD patients had an even higher mortality risk after PHF surgery than non-CKD patients, in females, those living in higher urbanization areas, or with more comorbidities (CCI ≥3) (P for interaction: 0.011, 0.057, and 0.069, respectively). CONCLUSION: CKD was associated with elevated risks for infection, revision, readmission, and mortality after PHF fixation surgery in diabetic patients. These findings should be taken into consideration when caring for diabetic patients.

Modulation of photoswitching profiles by 10,11-dialkoxymethyl substituents in c(2)-symmetric dibenzosuberane-based helicenes.

A series of C(2)-symmetric, 10,11-disubstituted dibenzosuberane (DBS)-based helicenes 6 a-c with a common 7-bromo-α-tetralin-based bottom fragment were synthesized. Their absolute stereochemistry was determined to be 10R,11R,P after reductive desulfurization of the corresponding (10R,11R,1'S)-episulfides with complete stereospecificity. Photoisomerization of the diastereomerically pure (P)-6 c in hexane led to virtually exclusive formation of the opposite M-form diastereomer (P/M', <1:>99) at 290 nm. The preferential return of (M')-6 c to (P)-6 c was also achieved with high selectivity (P/M', 90:10) at 330 nm. Molecular simulations of (P)-6 c and (M')-6 c with both DBS conformations suggest that the selectivities of photoswitching are controlled by the conformation of the top DBS template as evidenced by their (1)H NMR spectra. Doping 6 c into a nematic liquid crystal (E7) led to a cholesteric mesophase with modulated pitches, reversible helical senses, and with a switch memory of ternary logic.

Emission mechanism of doubly ortho-linked quinoxaline/diphenylfluorene or cis-stilbene/fluorene hybrid compounds based on the transient absorption and emission measurements during pulse radiolysis.

A series of bipolar OLED materials were subjected to pulsed radiolysis experiments to determine their transient absorption and lifetime profiles of the independently in situ generated radical cations and anions in solutions. Moreover, their emission behaviors from the charge recombination of their radical ions were also determined by the pulse radiolysis method. It was found the absorption bands in doubly ortho-linked quinoxaline/diphenylfluorene hybrids 1a-e are red-shifted progressively with increasing electron-donating nature at the C5 and C8 positions of the quinoxaline template. The incipient radical anions in 1a-e are mainly localized on the quinoxaline heterocyclic moiety, whereas the incipient radical cations are mainly distributed onto the attached electron-donating groups at the C5 and C8 positions of the quinoxaline template. For other doubly ortho-linked cis-stilbene derivatives 3d, 3f, and 4f, the radical anions are mainly localized on the cis-stilbene central moiety and the radical cation is mainly distributed onto both para substituents of the cis-stilbene templates. It was also shown that there is a correlation between their optoelectronic emission efficiencies and the radiolysis induced emission intensities. In addition, the charge transporting behaviors within an OLED device were found to show the relationship with transient absorption half-lives (tau(1/2)) of the radical ions. Charge recombination mechanisms in both the OLED and pulsed radiolysis experiments were proposed to rationalize these observations, allowing us to establish some guidelines for an ultimate molecular design of ideal bipolar optoelectronic materials with a judicious choice of local charge appendages in the optoelectronic templates.

Directed assembly of chiral oxidovanadium(V) methoxides into C4-symmetric metal(I) vanadate-centered quadruplexes: synergistic K+- and Ag+-specific transport.

A directed assembly process to form C4-symmetric, vanadate-centered quadruplexes, for the first time, from a given chiral oxidovanadium(V) complex allows for highly efficient K+- and Ag+-specific transport from aqueous phase containing three other alkali metal cations into organic solvents, reminiscent of the K+ specific transport exerted by four homochiral glycine residues of the opening site in KcsA membrane protein.

Globotriose-functionalized gold nanoparticles as multivalent probes for Shiga-like toxin.

Compared to monovalent carbohydrates, multivalent carbohydrate ligands exhibit significantly enhanced binding affinities to their interacting proteins. Here, we report globotriose (P(k) ligand)-functionalized gold nanoparticle (AuNP) probes for the investigation of multivalent interactions with the B(5) subunit of Shiga-like toxin I (B-Slt). Six P(k)-ligand-encapsulated AuNPs (P(k)-AuNPs) of varying particle size and linker length were synthesized and evaluated for their potential as multivalent affinity probes by using a surface plasmon resonance competition assay. The affinity of these probes for the interacting proteins was greatly affected by nanoparticle size, linker length, and ligand density on nanoparticle surface. For example, the 20-nm 20-P(k)-l-AuNP, which had a relatively long linker showed a >10(8)-fold increase in affinity compared with the mono P(k) ligand. This intrinsic high-affinity AuNP probe specifically captured the recombinant B-Slt from Escherichia coli lysate, and the resulting purity of the B-Slt was >95 %. We also developed a robust P(k)-AuNP-based detection method for Slt-I by combining the technique with silver enhancement.

Spirally Configured ( cis-Stilbene) Trimers: Steady-State and Time-Resolved Photophysical Studies and Organic Light-Emitting Diode Applications.

This article reports for the time-resolved photophysical studies of spirally configured ( cis-stilbene) trimers and their spin-coated organic light-emitting diode (OLED) device performances. Transient absorption profiles of spirally configured, ter-( cis-stilbene) were studied by pulse radiolysis. The emission profiles after charge recombination of their incipient radical ions in benzene provides insights into the emission mechanism and efficiency in OLED devices. Blue-, sky blue-, and green-emitting OLED devices for a maximum external quantum efficiency are 4.32%, 4.70%, and 2.77%, respectively, by solution process.

Catalytic conjugate additions of nitrogen-, phosphorus-, and carbon-containing nucleophiles by amphoteric vanadyl triflate.

A series of carbamates, amides, N-tosyl amides, (hetero)arenes, and hydrogen phosphines/phosphites has been examined as nucleophiles for (hetero)Michael-type additions to enones and enamides catalyzed by amphoteric vanadyl triflate under mild and neutral conditions. The newly developed C-N, C-P, and C-C bond-formation protocols were carried out smoothly in good to high yields without intervention of any 1,2-additions.

Enantiodivergent Steglich rearrangement of O-carboxylazlactones catalyzed by a chirality switchable helicene containing a 4-aminopyridine unit.

A pseudo-enantiomeric pair of optically switchable helicenes containing a catalytic 4-N-methylaminopyridine (MAP) bottom unit and a C2-symmetric, (10R,11R)-dimethoxymethyl-dibenzosuberane top template was synthesized. They underwent complementary photoswitching at 290 nm (P/M', <1/>99) and 340 nm (P/M', 91/9) and unidirectional thermo-rotation at 130 °C (P/M', >99/<1). They were utilized to catalyze enantiodivergent Steglich rearrangement of O- to C-carboxylazlactones, with formation of either enantiomer with up to 91% ee (R) and 94% ee (S), respectively.

Highly Diastereoselective thioglycosylation of functionalized peracetylated glycosides catalyzed by MoO2Cl2.

Among 18 oxometallic species, MoO2Cl2 was found to be the most reactive in catalytic thioglycosylation of O-acetylated glycosides with functionalized thiols in CH2Cl2, leading cleanly to 1,2-trans-thioglycosides with exclusive diastereocontrol. The new catalytic protocol is applicable to a monoglycoside building block and beta-(1-->6)-S-linked-thiodisaccharide synthesis. [reaction: see text].