An investigation on catalytic nitrite reduction reaction by bioinspired CuII complexes.

Catalytic nitrite reductions by CuII complexes containing anionic Me2Tp, neutral Me2Tpm, or neutral iPrTIC ligands in the presence of L-ascorbic acid, which served as an electron donor and proton source, were investigated. The results showed that auxiliary ligands are important for copper-mediated catalytic nitrite reduction. Furthermore, the electronic effects of the ligand govern the nitrite reduction efficiency, which should be considered at two control points: one is the susceptibility of the LCuI-nitrite species to protonation and the other is the susceptibility of LCuII to reduction giving LCuI. In addition, an external strong acid leads to the production of nitrous acid, which may suggest that the reactivity of nitrous acid toward the LCuI species is a third control point.

Improvement in aluminum complexes bearing a Schiff base in ring-opening polymerization of ε-caprolactone: the synergy of the N,S-Schiff base in a five-membered ring aluminum system.

A series of five-membered ring aluminum complexes bearing thiol-Schiff base ligands were synthesized, and their application in the ring-opening polymerization of ε-caprolactone (CL) was investigated. The complexes exhibited dramatically higher catalytic activity than the six-membered ring S2AlMe2 complex (approximately 4- to 10-fold higher) and the five-membered ring L5-PhAlMe2 complex (approximately 7- to 19-fold higher). Moreover, a shorter induction period was observed when the five-membered ring aluminum complexes bearing thiol-Schiff base ligands were used compared with the other types of aluminum complexes bearing Schiff base ligands. The electron-withdrawing groups enhanced the catalytic activity of the Al complexes compared with the electron donating groups. The thiol-Schiff base ligand and the five-membered ring aluminum catalysis had a synergistic effect that was stronger than the combination of their individual effects.

Structure and nitrite reduction reactivity study of bio-inspired copper(i)-nitro complexes in steric and electronic considerations of tridentate nitrogen ligands.

Two copper(i)-nitro complexes [Tpm3-tBuCu(NO2)] (1) and [(Ph3P)2N][Tp3-tBuCu(NO2)] (2), containing steric bulky neutral tris(3-tert-butylpyrazolyl)methane and anionic hydrotris(3-tert-butylpyrazolyl)borate ligands, have been synthesized and characterized. Complex 2 adopts a unique κ2-binding mode of Tp3-tBu around the copper(i)-nitro environment in the solid state and shows a four-coordinated tetrahedral geometry surrounded by a nitro and three pz3-tBu groups in solution. Both complexes 1 and 2 allow for the stoichiometric reduction of NO2- to NO with H+ addition. The results of this effort show that increasing steric bulk and electron donation properties on the nitrogen ancillary ligand will improve the nitrite reduction ability of the copper(i)-nitro model complexes.

Enhanced Catalytic Activity of Aluminum Complexes for the Ring-Opening Polymerization of ε-Caprolactone.

A series of dinuclear aluminum (Al2Pyr2) complexes bridged by two pyrazole ligands were synthesized, and their catalytic activity toward ring-opening polymerization of ε-caprolactone (CL) was investigated. Different types of the Al-N-N-Al-N-N skeletal ring were found among these Al2Pyr2 complexes. The butterfly form, LThio2Al2Me4, exerted the highest catalytic activity for CL polymerization. κ2-CL coordination with both Al centers within the butterfly form LThio2Al2Me4 facilitates the initiation process. Generally speaking, the Al2Pyr2 complexes exhibited substantially higher catalytic activity for CL polymerization than literature examples such as ß-diketiminate- or traiaza-bearing aluminum complexes. In fact, the Al2Pyr2 complexes can even carry out CL polymerization at room temperature.

Reactivity Study of Unsymmetrical ß-Diketiminato Copper(I) Complexes: Effect of the Chelating Ring.

ß-Diketiminato copper(I) complexes play important roles in bioinspired catalytic chemistry and in applications to the materials industry. However, it has been observed that these complexes are very susceptible to disproportionation. Coordinating solvents or Lewis bases are typically used to prevent disproportionation and to block the coordination sites of the copper(I) center from further decomposition. Here, we incorporate this coordination protection directly into the molecule in order to increase the stability and reactivity of these complexes and to discover new copper(I) binding motifs. Here we describe the synthesis, structural characterization, and reactivity of a series of unsymmetrical N-aryl-N'-alkylpyridyl ß-diketiminato copper(I) complexes and discuss the structures and reactivity of these complexes with respect to the length of the pyridyl arm. All of the aforementioned unsymmetrical ß-diketiminato copper(I) complexes bind CO reversibly and are stable to disproportionation. The binding ability of CO and the rate of pyridyl ligand decoordination of these copper(I) complexes are directly related to the competition between the degree of puckering of the chelate system and the steric demands of the N-aryl substituent.

Improvement in Titanium Complexes Bearing Schiff Base Ligands in the Ring-Opening Polymerization of L-Lactide: A Dinuclear System with Hydrazine-Bridging Schiff Base Ligands.

A series of titanium (Ti) complexes bearing hydrazine-bridging Schiff base ligands were synthesized and investigated as catalysts for the ring-opening polymerization (ROP) of L-lactide (LA). Complexes with electron withdrawing or steric bulky groups reduced the catalytic activity. In addition, the steric bulky substituent on the imine groups reduced the space around the Ti atom and then reduced LA coordination with Ti atom, thereby reducing catalytic activity. All the dinuclear Ti complexes exhibited higher catalytic activity (approximately 10-60-fold) than mononuclear L(Cl-H)-TiOPr2 did. The strategy of bridging dinuclear Ti complexes with isopropoxide groups in the ROP of LA was successful, and adjusting the crowded heptacoordinated transition state by the bridging isopropoxide groups may be the key to our successful strategy.

Comparative Study of Aluminum Complexes Bearing N,O- and N,S-Schiff Base in Ring-Opening Polymerization of ε-Caprolactone and L-Lactide.

A series of Al complexes bearing Schiff base and thio-Schiff base ligands were synthesized, and their application for the ring-opening polymerization of ε-caprolactone (CL) and l-lactide (LA) was studied. It was found that steric effects of the ligands caused higher polymerization rate and most importantly the Al complexes with N,S-Schiff base showed significantly higher polymerization rate than Al complexes with N,O-Schiff base (5-12-fold for CL polymerization and 2-7-fold for LA polymerization). The reaction mechanism of CL polymerization was investigated by density functional theory (DFT). The calculations predicted a lower activation energy for a process involved with an Al complex bearing an N,S-Schiff base ligand (17.6 kcal/mol) than for that of an Al complex bearing an N,O-Schiff base ligand (19.0 kcal/mol), and this magnitude of activation energy reduction is comparable to the magnitude of rate enhancement observed in the experiment. The reduction of activation energy was attributed to the catalyst-substrate destabilization effect. Using a sulfur-containing ligand to decrease the activation energy in the ring-opening polymerization process may be a new strategy to design a new Al complex with high catalytic activity.

Structural Elucidation and Structure-Anti-inflammatory Activity Relationships of Cembranoids from Cultured Soft Corals Sinularia sandensis and Sinularia flexibilis.

New cembranoids 4-carbomethoxyl-10-epigyrosanoldie E (1), 7-acetylsinumaximol B (2), diepoxycembrene B (6), dihydromanaarenolide I (8), and isosinulaflexiolide K (9), along with 11 known related metabolites, were isolated from cultured soft corals Sinularia sandensis and Sinularia flexibilis. The structures were elucidated by means of infrared, mass spectrometry, and nuclear magnetic resonance techniques, and the absolute configurations of 1, 4, 9, and 15 were further confirmed by single-crystal X-ray diffraction analysis. The absolute configurations of these coral metabolites and comparison with known analogues showed that one hypothesis (that cembrane diterpenes possessing an absolute configuration of an isopropyl group at C1 obtained from Alcyonacean soft corals belong to the α series, whereas analogues isolated from Gorgonacean corals belong to the ß series) is not applicable for a small number of cembranoids. An in vitro anti-inflammatory study using LPS-stimulated macrophage-like cell line RAW 264.7 revealed that compounds 9-14 significantly suppressed the accumulation of pro-inflammatory proteins, iNOS and COX-2. Structure-activity relationship analysis indicated that cembrane-type compounds with one seven-membered lactone moiety at C-1 are potential anti-inflammatory agents. This is the first culture system in the world that has successfully been used to farm S. sandensis.

A closer look at ε-caprolactone polymerization catalyzed by alkyl aluminum complexes: the effect of induction period on overall catalytic activity.

Previous studies on the ring-opening polymerization of ε-caprolactone using structurally related aluminum complexes as pre-catalysts showed inconsistent trends in the total conversion time. We propose that an induction period for Al complexes for conversion to real catalytic species, Al alkoxide, should be considered because the total conversion time consists of both an induction period and polymer propagation time. Herein, the polymerization rate of a series of Al complexes bearing ketimine ligands was investigated. The catalytic results indicated complexes with more steric hindrance with an electron-withdrawing group on the ligands, or the fact that less chelating ligands demonstrated greater propagation activity. The opposite trend for these structural effects was observed on the measurement of induction periods. These features on ligands of aluminum complexes are responsible for facilitating the conversion process to Al alkoxides. The overall catalytic performance should consider both the induction period and the propagation time.

Anti-inflammatory anthraquinones from the crinoid Himerometra magnipinna.

Chemical investigation of a crinoid Himerometra magnipinna has afforded three anthraquinones (1-3), including one new metabolite, (+)-rhodoptilometrin (1). The structures of these compounds were elucidated on the basis of their spectroscopic data and the absolute configuration of 1 was further confirmed by single-crystal X-ray diffraction analysis. In the in vitro anti-inflammatory effects test, compound 2 was found to significantly inhibit the accumulation of the pro-inflammatory iNOS protein of the LPS-stimulated RAW264.7 macrophage cells.

Bioactive 6S-styryllactone constituents of Polyalthia parviflora.

Parvistones A-E (1-5), five new styryllactones possessing a rare α,ß-lactone moiety and a 6S configuration, were isolated from a methanolic extract of Polyalthia parviflora leaves. The structures and the absolute configuration of the isolates were elucidated using NMR spectroscopy, specific rotation, circular dichroism, and X-ray single-crystal analysis. Compounds 8, 9, 11, and 12 were isolated for the first time. The results were supported by comparing the data measured to those of 6R-styryllactones. Moreover, a plausible biogenetic pathway of the isolated compounds was proposed. The structure-activity relationship of the compounds in an in vitro anti-inflammatory assay revealed the 6S-styryllactones to be more potent than the 6R derivatives. However, the effect was opposite regarding their cytotoxic activity. In addition, 6S-styrylpyrones isolated showed more potent anti-inflammatory and cytotoxic activity when compared to the 1S-phenylpyranopyrones obtained.

Withanolide-based steroids from the cultured soft coral Sinularia brassica.

Seven novel withanolides, sinubrasolides A-G (1-7), have been isolated from the cultured soft coral Sinularia brassica. The structures of the new metabolites were determined by extensive spectroscopic analyses, and the absolute configuration of 1 was established by X-ray crystallographic analysis. The cytotoxicities of compounds 1-7 against a limited panel of cancer cell lines also were determined.

Towards the small and the beautiful: a small dibromotyrosine derivative from Pseudoceratina sp. sponge exhibits potent apoptotic effect through targeting IKK/NFκB signaling pathway.

A dibromotyrosine derivative, (1'R,5'S,6'S)-2-(3',5'-dibromo-1',6'-dihydroxy-4'-oxocyclohex-2'-enyl) acetonitrile (DT), was isolated from the sponge Pseudoceratina sp., and was found to exhibit a significant cytotoxic activity against leukemia K562 cells. Despite the large number of the isolated bromotyrosine derivatives, studies focusing on their biological mechanism of action are scarce. In the current study we designed a set of experiments to reveal the underlying mechanism of DT cytotoxic activity against K562 cells. First, the results of MTT cytotoxic and the annexin V-FITC/PI apoptotic assays, indicated that the DT cytotoxic activity is mediated through induction of apoptosis. This effect was also supported by caspases-3 and -9 activation as well as PARP cleavage. DT induced generation of reactive oxygen species (ROS) and the disruption of mitochondrial membrane potential (MMP) as indicated by flow cytometric assay. The involvement of ROS generation in the apoptotic activity of DT was further corroborated by the pretreatment of K562 cells with N-acetyl-cysteine (NAC), a ROS scavenger, which prevented apoptosis and the disruption of MMP induced by DT. Results of cell-free system assay suggested that DT can act as a topoisomerase II catalytic inhibitor, unlike the clinical anticancer drug, etoposide, which acts as a topoisomerase poison. Additionally, we found that DT treatment can block IKK/NFκB pathway and activate PI3K/Akt pathway. These findings suggest that the cytotoxic effect of DT is associated with mitochondrial dysfunction-dependent apoptosis which is mediated through oxidative stress. Therefore, DT represents an interesting reference point for the development of new cytotoxic agent targeting IKK/NFκB pathway.

New Lignans from the Leaves and Stems of Kadsura philippinensis.

Three novel C19 homolignans, taiwankadsurins D (1), E (2) and F (4), and two new C18 lignans kadsuphilins N (3) and O (5) were isolated from the aerial parts of Taiwanese medicinal plant Kadsura philippinensis. The structures of compounds 1-5 were determined by spectroscopic analyses, especially 2D NMR techniques. The structure of compound 5 was further confirmed by X-ray crystallographic analysis. Compounds 1 and 2 have a 3,4-{1'-[(Z)-2''-methoxy-2''-oxoethylidene]}-pentano(2,3-dihydrobenzo[b]furano)-3-(2'''-methoxycarbonyl-2'''-hydroxy-2''',3'-epoxide) skeleton.

Cytotoxic cardenolide glycosides from the root of Reevesia formosana.

Bioassay-guided fractionation of the root tissue of Reevesia formosana led to isolation of 13 cardenolide glycosides, reevesiosides A-I and epi-reevesiosides F-I. Their structures were determined by means of spectroscopic analysis and single-crystal X-ray diffraction was performed using reevesioside A. Reevesioside A, reevesioside F, and epi-reevesioside F displayed especially potent cytotoxicity against the MCF-7 and NCI-H460 cancer cell lines, with IC(50) values of 63±2 and 19±1, 72±8 and 20±0, and 34±6 and 10±1 nM, respectively. Identification of the sugar constituents and unusual 18,20-epoxide cardenolide glycosides are described herein. Cardiac glycosides were previously unknown in the Sterculiaceae family.

A simple competition assay to probe pentacopper(I)-thiolato cluster ligand exchange.

Two pentanuclear copper(I) thiolato clusters of the formula [Cu(5)(L)(3)](-) (L = pyridine-2,6-dimethanethiolate (L1), (1); 4-methylpyridine-2,6-dimethanethiolate (L2), (2)) were synthesized utilizing a single-step procedure, and their structures were characterized by X-ray crystallography. The aforementioned pentanuclear complexes possess an interesting propeller-like Cu(5)S(6) core where all Cu centers are three-coordinate. Electrospray ionization mass spectrometry (ESI-MS) investigation of the pentanuclear copper(I) thiolato clusters with added hetero-ligands demonstrated interesting ligand exchange behavior. The product distribution resulting from ligand exchange not only depended on the quantity of added ligand, but also was sensitive to the coordination ability of the ligand. The ESI-MS method used in this study can serve as a useful tool for probing exchange behavior in coordination metal complexes that cannot otherwise be determined by NMR.

5alpha,8alpha-epidioxysterols from a Formosan sponge, Axinyssa sp.

One new 5alpha,8alpha-epidioxysterol, 3-acetylaxinysterol (1), along with one known sterol, axinysterol (2), were isolated from a Formosan sponge, Axinyssa sp.. The structures of the compounds were determined by spectroscopic methods and the absolute configuration of 2 was further confirmed by single-crystal X-ray diffraction analysis for the first time. Compound 2 exhibited significant cytotoxicity against K562 and Molt 4 cancer cell lines.

Copper(I) nitro complex with an anionic [HB(3,5-Me2Pz)3]− ligand: a synthetic model for the copper nitrite reductase active site.

The new copper(I) nitro complex [(Ph(3)P)(2)N][Cu(HB(3,5-Me(2)Pz)(3))(NO(2))] (2), containing the anionic hydrotris(3,5-dimethylpyrazolyl)borate ligand, was synthesized, and its structural features were probed using X-ray crystallography. Complex 2 was found to cocrystallize with a water molecule, and X-ray crystallographic analysis showed that the resulting molecule had the structure [(Ph(3)P)(2)N][Cu(HB(3,5-Me(2)Pz)(3))(NO(2))]·H(2)O (3), containing a water hydrogen bonded to an oxygen of the nitrite moiety. This complex represents the first example in the solid state of an analogue of the nitrous acid intermediate (CuNO(2)H). A comparison of the nitrite reduction reactivity of the electron-rich ligand containing the CuNO(2) complex 2 with that of the known neutral ligand containing the CuNO(2) complex [Cu(HC(3,5-Me(2)Pz)(3))(NO(2))] (1) shows that reactivity is significantly influenced by the electron density around the copper and nitrite centers. The detailed mechanisms of nitrite reduction reactions of 1 and 2 with acetic acid were explored by using density functional theory calculations. Overall, the results of this effort show that synthetic models, based on neutral HC(3,5-Me(2)Pz)(3) and anionic [HB(3,5-Me(2)Pz)(3)](-) ligands, mimic the electronic influence of (His)(3) ligands in the environment of the type II copper center of copper nitrite reductases (Cu-NIRs).

Secondary metabolites from the root of Ehretia longiflora and their biological activities.

Bioassay-guided fractionation of the methanolic extract of the root of Ehretia longiflora (Boraginaceae) afforded eight compounds, ehretiquinone (1), ehretiolide (2), ehreticoumarin (3), ehretilactone A (4), ehretilactone B (5), ehretiamide (6), ehretine (7), and ehretiate (8), together with 12 known compounds (9-20). The relative configuration of 1 was determined by single crystal X-ray diffraction. Among the isolates, 1 and prenylhydroquinone (14) showed antitubercular activity against Mycobacterium tuberculosis strain H37Rv with MIC values of 25.0 and 26.2 µg/mL, respectively. Moreover, 1 exhibited inhibitory effects on N-formylmethionylleucylphenylalanine (fMLP)-induced superoxide production, with IC50 value of 0.36±0.03µM.

Secondary metabolites from the roots of Neolitsea daibuensis and their anti-inflammatory activity.

Bioassay-guided fractionation of the roots of Neolitsea daibuensis afforded three new ß-carboline alkaloids, daibucarbolines A-C (1-3), three new sesquiterpenoids, daibulactones A and B (4 and 5) and daibuoxide (6), and 20 known compounds. The structures of 1-6 were determined by spectroscopic analysis and single-crystal X-ray diffraction. Daibucarboline A (1), isolinderalactone (7), 7-O-methylnaringenin (8), and prunetin (9) exhibited moderate iNOS inhibitory activity, with IC50 values of 18.41, 0.30, 19.55, and 10.50 µM, respectively.