Preliminary study on the short-term changes of pulmonary perfusion after a single balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension.

BACKGROUND: Little is known about immediate responses of blood perfusion to the balloon pulmonary angioplasty (BPA) procedure. OBJECTIVES: To investigate the changes in pulmonary perfusion of balloon-dilated vessels and untreated vessels with before, immediately after a single BPA and at follow-up. DESIGN: Retrospective single-center cohort study. METHODS: Patients who had chronic thromboembolic pulmonary hypertension (CTEPH) and completed the pulmonary perfusion single photon emission computed tomography (SPECT) imaging before, immediately after BPA and at follow-up were included. We evaluated the perfusion defects of both-lung, BPA target (balloon dilated) and non-target (untreated) vessel segments according to Begic 3-point scale in each lung segment. RESULTS: Forty patients (40 BPA procedures) were included and were given next BPA after 89 (62-125) days. The hemodynamic parameters including mPAP, PVR, and RAP were significantly improved after a single BPA. Visual scoring results of pulmonary perfusion imaging in 40 BPAs showed the perfusion defect scores of target vessels reduced from 5.6 ± 2.6 to 4.2 ± 2.2 (p < 0.001) immediately after BPA, and then further diminished to 3.1 ± 1.9 (p < 0.001) at follow-up. While in the non-target vessels, the post-BPA perfusion defect scores did not change significantly (13.4 ± 4.7 versus 12.8 ± 4.6, p = 0.182), but tended to decrease at follow-up (12.2 ± 4.2). However, there were 17 BPAs of which the post-BPA perfusion defect scores of non-target vessels increased significantly (p < 0.001), but decreased at follow-up. CONCLUSION: In addition to improving the blood perfusion of target vessels, BPA also has a certain effect on the perfusion of some non-target vessels.

Ruthenium-Catalyzed Reductive Cleavage of Unstrained Aryl-Aryl Bonds: Reaction Development and Mechanistic Study.

Cleavage of carbon-carbon bonds has been found in some important industrial processes, for example, petroleum cracking, and has inspired development of numerous synthetic methods. However, nonpolar unstrained C(aryl)-C(aryl) bonds remain one of the toughest bonds to be activated. As a detailed study of a fundamental reaction mode, here a full story is described about our development of a Ru-catalyzed reductive cleavage of unstrained C(aryl)-C(aryl) bonds. A wide range of biaryl compounds that contain directing groups (DGs) at 2,2' positions can serve as effective substrates. Various heterocycles, such as pyridine, quinoline, pyrimidine, and pyrazole, can be employed as DGs. Besides hydrogen gas, other reagents, such as Hantzsch ester, silanes, and alcohols, can be employed as terminal reductants. The reaction is pH neutral and free of oxidants; thus a number of functional groups are tolerated. Notably, a one-pot C-C activation/C-C coupling has been realized. Computational and experimental mechanistic studies indicate that the reaction involves a ruthenium(II) monohydride-mediated C(aryl)-C(aryl) activation and the resting state of the catalyst is a η4-coordinated ruthenium(II) dichloride complex, which could inspire development of other transformations based on this reaction mode.

Cobalt-Catalyzed Intramolecular Alkyne/Benzocyclobutenone Coupling: C-C Bond Cleavage via a Tetrahedral Dicobalt Intermediate.

A Co(0)-catalyzed intramolecular alkyne/benzocyclobutenone coupling through C-C cleavage of benzocyclobutenones is described. Co2(CO)8/P[3, 5-(CF3)2C6H3]3 was discovered to be an effective metal/ligand combination, which exhibits complementary catalytic activity to the previously established rhodium catalyst. In particular, the C8-substituted substrates failed in the Rh system, but succeeded with the Co catalysis. Experimental and computational studies show that the initially formed tetrahedral dicobalt-alkyne complex undergoes C1-C2 activation via oxidative addition with Co(0), followed by migratory insertion and reductive elimination to give the ß-naphthol products.

"Cut and Sew" Transformations via Transition-Metal-Catalyzed Carbon-Carbon Bond Activation.

The transition metal-catalyzed "cut and sew" transformation has recently emerged as a useful strategy for preparing complex molecular structures. After oxidative addition of a transition metal into a carbon-carbon bond, the resulting two carbon termini can be both functionalized in one step via the following migratory insertion and reductive elimination with unsaturated units, such as alkenes, alkynes, allenes, CO and polar multiple bonds. Three- or four-membered rings are often employed as reaction partners due to their high ring strains. The participation of non-strained structures generally relies on cleavage of a polar carbon-CN bond or assistance of a directing group.

Release and Degradation of Microencapsulated Spinosad and Emamectin Benzoate.

The dynamics of release and degradation of the microencapsulation formulation containing spinosad (SP) and emamectin benzoate (EM) were evaluated in the present study. SP and EM were microencapsulated using biodegradable poly-lactic acid (PLA) as the wall material. Their release from and degradation within the prepared SP and EM microspheres (SP-EM-microspheres) were studied. It was found that the encapsulation significantly prolonged the insecticide release. The release could be further extended if the external aqueous phase was pre-saturated with the insecticides and the microspheres were additionally coated with gelatin. On the other hand, increasing the water content of the emulsion or the hydrophilic polycaprolactone (PCL) content in the PLA/PCL mixture accelerated the release. Due to the photolysis and hydrolysis of SP and EM by sunlight, the toxicity of the non-encapsulated insecticides in water declined continuously from 0 through the 9th day (d), and dissipated in 13 d. In contrast, an aqueous suspension containing 5% SP-EM-microspheres maintained a mostly constant toxicity to Plutella xylostella for 17 d. The biodegradable SP-EM-microspheres showed significantly higher long-term toxicity to P. xylostella due to lower release, reduced photolysis and hydrolysis of the encapsulated insecticides, which were affected by the varied preparation conditions.

Efficient Benzimidazolidinone Synthesis via Rhodium-Catalyzed Double-Decarbonylative C-C Activation/Cycloaddition between Isatins and Isocyanates.

The first decarbonylative cycloaddition of less-strained cyclic ketones (isatins) with isocyanates is reported. Initiated by C-C activation, this distinct [5-2+2] transformation provides a rapid entry to access various benzimidazolidinone derivatives, through which a wide range of isocyanates can be efficiently coupled with broad functional group tolerance. A modified one-pot process, combining Curtius rearrangement and C-C activation, was also achieved by using acyl azides as the starting materials. Detailed mechanistic study revealed a surprising double-decarbonylative reaction pathway. The novel reactivity discovered in this basic research is expected to shed light on developing new heterocycle formation methods through a C-C/isocyanate coupling.

Cyclobutenones and Benzocyclobutenones: Versatile Synthons in Organic Synthesis.

Cyclobutenones, four-membered ketones bearing an unsaturated carbon-carbon double bond, and their structural sibling benzocyclobutenones, possess unique reactivity. Owing to their inherent high ring strain, such structures readily undergo ring opening under a variety of conditions, including thermolysis, photolysis, and transition metal catalysis, to afford reactive intermediates that can be trapped with nucleophiles, dienophiles, and unsaturated bonds. Their electron-deficient enone moieties are good electrophiles for facile nucleophilic addition. Such properties render cyclobutenones versatile synthons, serving as excellent coupling partners in a vast array of synthetically valuable transformations.

Rh-catalyzed Reagent-Free Ring Expansion of Cyclobutenones and Benzocyclobutenones.

Here we report a reagent-free rhodium-catalyzed ring-expansion reaction via C-C cleavage of cyclobutenones. A variety of poly-substituted cyclopentenones and 1-indanones can be synthesized from simple cyclobutenones and benzocyclobutenones. The reaction condition is near pH neutral without additional oxidants or reductants. The potential for developing a dynamic kinetic asymmetric transformation of this reaction has also been demonstrated. Further study supports the proposed pathway involving Rh-insertion into the cyclobutenone C-C bond, followed by ß-hydrogen elimination, olefin insertion and reductive elimination.

Concise Synthesis of Functionalized Benzocyclobutenones.

A concise approach to access functionalized benzocyclobutenones from 3-halophenol derivatives is described. This modified synthesis employs a [2+2] cycloaddition between benzynes generated from dehydrohalogenation of aryl halides using LiTMP and acetaldehyde enolate generated from n-BuLi and THF, followed by oxidation of the benzocyclobutenol intermediates to provide benzocyclobutenones. The [2+2] reaction can be run on a 10-gram scale with an increased yield. A number of functional groups including alkenes and alkynes are tolerated. Coupling of benzynes with ketene silyl acetals to give 8-substituted benzocyclobutenones is also demonstrated.

Divergent syntheses of fused ß-naphthol and indene scaffolds by rhodium-catalyzed direct and decarbonylative alkyne-benzocyclobutenone couplings.

A tunable rhodium-catalyzed intramolecular alkyne insertion reaction proceeding through the CC cleavage of benzocyclobutenones is described. Selective formation of either the direct or decarbonylative insertion product can be controlled by using different catalytic systems. A variety of fused ß-naphthol and indene scaffolds were obtained in good yields with high functional group tolerance. This work illustrates a divergent approach to synthesize fused-ring systems by CC activation/functionalization.

Preparation and physicochemical characteristics of polylactide microspheres of emamectin benzoate by modified solvent evaporation/extraction method.

Emamectin benzoate is highly effective against insect pests and widely used in the world. However, its biological activity is limited because of high resistance of target insects and rapid degradation speed in fields. Preparation and physicochemical characterization of degradable microcapsules of emamectin benzoate were studied by modified solvent evaporation/extraction method using polylactide (PLA) as wall material. The influence of different compositions of the solvent in internal organic phase and external aqueous phase on diameter, span, pesticide loading, and entrapment rate of the microspheres was investigated. The results indicated that the process of solvent extraction and the formation of the microcapsules would be accelerated by adding water-miscible organic solvents such as ethyl ether, acetone, ethyl acetate, or n-butanol into internal organic phase and external aqueous phase. Accelerated formation of the microcapsules would result in entrapment rates of emamectin benzoate increased to as high as 97%. In addition, by adding ethanol into the external aqueous phase, diameters would reduce to 6.28 µm, whereas the loading efficiency of emamectin benzoate did not increase. The PLA microspheres prepared under optimum conditions were smoother and more spherical. The degradation rate in PLA microspheres of emamectin benzoate on the 10th day was 4.29 ± 0.74%, whereas the degradation rates of emamectin benzoate in methanol solution and solid technical material were 46.3 ± 2.11 and 22.7 ± 1.51%, respectively. The PLA skeleton had combined with emamectin benzoate in an amorphous or molecular state by using differential scanning calorimetry (DSC) determination. The results indicated that PLA microspheres of emamectin benzoate with high entrapment rate, loading efficiency, and physicochemical characteristics could be obtained by adding water-miscible organic solvents into the internal organic phase and external aqueous phase.