Control of structures and sorption properties of ionic crystals of A2[Cr3O(OOCC2H5)6(H2O)3]2[alpha-SiW12O40] (A = Na, K, Rb, NH4, Cs, TMA)

The complexation of Keggin-type polyoxometalate [alpha-SiW 12O 40] (4-), macrocation [Cr 3O(OOCC 2H 5) 6(H 2O) 3] (+), and monovalent cation A (+) forms ionic crystals of A 2[Cr 3O(OOCC 2H 5) 6(H 2O) 3] 2[alpha-SiW 12O 40]. nH 2O [A = Na ( 1a), K ( 2a), Rb ( 3a), NH 4 ( 4a), Cs ( 5a), and tetramethylammonium (TMA) ( 6a)]. Single crystal (1a- 4a and 6a) and powder (5a) X-ray analyses have shown that the ionic crystals possess 2D layers of polyoxometalates and macrocations. Compounds 2a- 5a had almost the same structure, while the layers in 1a and 6a stack in different ways. The structures and sorption properties of 2b- 5b are investigated in more detail. The interlayer distances of guest free phases 2b- 5b increase with the increase in the ionic radii of the monovalent cations, which reside between the layers. Compounds 2b- 5b possess hydrophobic and hydrophilic channels, which exist between the layers and through the layers, respectively. The volumes of the hydrophobic channels increase in the order of 2b < 3b approximately 4b < 5b, and those of the hydrophilic channels increase in the order of 2b < or = 3b < or = 4b < 5b. Single-crystal X-ray structure analyses of 2a- 4a have shown that the water of crystallization resides in the hydrophilic channel. It is probable that the water of crystallization in 5a resides in the hydrophilic channel in the same manner as those in 2a- 4a since 2a- 5a have almost the same structure. The water vapor sorption profiles of 2b- 5b are approximately reproduced by a linear driving force model. Therefore, water molecules sorbed in 2b- 5b probably reside in the hydrophilic channel. The n-propanol sorption profiles are reproduced by the summation of the linear driving force model, showing that two independent barriers exist in the n-propanol sorption. The in situ IR spectra of n-propanol sorbed showed the presence of two n-propanol species. These data show that n-propanol is sorbed into both hydrophilic and hydrophobic channels. Compound 5b sorbs halocarbons in the hydrophobic channel, while 2b- 4b exclude them.     

(Eta5-pentamethylcyclopentadienyl)rhodium and -iridium complexes with weakly and strongly coordinating anions: isolation and first X-ray molecular structures of the tris(solvent) complexes [(C5Me5)M(acetone)2(H2O)][BF4]2 (M = Rh, Ir)

Several novel pentamethylcyclopentadienyl complexes of general formula [(C5Me5)IrL3][BF4]2 were prepared including the tris(solvent) precursors [(C5Me5)M(acetone)2(H2O)][BF4]2 (M = Rh, Ir) (1a,b). The X-ray molecular structures of 1a,b were determined at low temperature. Complexes 1a,b are isostructural, and both compounds crystallize in the monoclinic space group P2(1)/c with a = 10.157(3) A, b = 14.038(9) A, c = 16.335(2) A, beta = 99.73(2) degrees, and Z = 4 for 1a and with a = 10.107(9) A, b = 13.994(16) A, c = 15.996(34) A, beta = 99.61(12) degrees, and Z = 4 for 1b. The coordinated water molecule is hydrogen bonded to both BF4(-) anions. Reaction of 1a,b with pyridine (py) afforded the related tris(pyridine) complexes [(C5Me5)M(eta1-(N)-py)3][BF4]2 (M = Rh, Ir) (2a,b). Complex 2b was characterized by X-ray crystallography, monoclinic space group P2(1)/c with a = 8.665(3) A, b = 19.687(7) A, c = 18.408(5) A, beta = 94.17(3) degrees, and Z = 4. Moreover, we prepared the novel neutral compounds (C5Me5)M(eta2-NO3)(eta1-NO3) (M = Rh, Ir) (4a,b) where the anions are bonded to the metal center instead of a coordinating solvent as confirmed by X-ray study on the iridium complex 4b. The latter crystallizes in the orthorhombic space group Pcab with a = 13.032(4) A, b = 14.370(11) A, c = 14.839(18) A, and Z = 8.     

Synthesis and characterization of aluminum- and gallium-bridged [1.1]chromarenophanes and [1.1]molybdarenophanes

The synthesis and structural characterization of the first [1.1]chromarenophanes and the first [1.1]molybdarenophanes are described. A salt-metathesis reaction of [2-(Me 2NCH 2)C 6H 4]AlCl 2 with freshly prepared [Cr(LiC 6H 5) 2].TMEDA (TMEDA = N, N, N', N'-tetramethylethylenediamine) resulted in the dialumina[1.1]chromarenophane [{2-(Me 2NCH 2)C 6H 4}Al(eta (6)-C 6H 5) 2Cr] 2 ( 2a). The poor solubility of 2a in organic solvents prompted us to synthesize the new intramolecularly coordinated aluminum- and gallium dichlorides [5- tBu-2-(Me 2NCH 2)C 6H 3]ECl 2 [E = Al ( 3a), Ga ( 3b)] in which the phenyl group was equipped with a tert-butyl group. Salt-metathesis reactions of 3a and 3b, respectively, with freshly prepared [M(LiC 6H 5) 2].TMEDA (M = Cr, Mo) resulted in four new [1.1]metallarenophanes of the general type [{5- tBu-2-(Me 2NCH 2)C 6H 3}E(eta (6)-C 6H 5) 2M] 2 [E = Al, M = Cr ( 4a); E = Ga, M = Cr ( 4b); E = Al, M = Mo ( 5a); E = Ga, M = Mo ( 5b)]. 2a, 4a, b, and 5a, b have been structurally characterized by single-crystal analysis [ 2a.1/2C 6H 12: C 48H 56Al 2Cr 2N 2, monoclinic, P2 1/ c, a = 9.9117(9) A, b = 19.9361(16) A, c = 10.638(2) A, alpha = 90 degrees , beta = 112.322(5) degrees , gamma = 90 degrees , Z = 2; 4a.2C 6H 6: C 62H 72Al 2Cr 2N 2, monoclinic, P2 1/ c, a = 10.9626(9) A, b = 19.3350(18) A, c = 12.4626(9) A, alpha = 90 degrees , beta = 100.756(5) degrees , gamma = 90 degrees , Z = 2; 4b.2C 6H 6: C 62H 72Cr 2Ga 2N 2, monoclinic, P2 1/ c, a = 10.8428(2) A, b = 19.4844(4) A, c = 12.4958(2) A, alpha = 90 degrees , beta = 100.6187 degrees , gamma = 90 degrees , Z = 2; 5a.2C 6H 6: C 62H 72Al 2Mo 2N 2, triclinic, P1, a = 10.4377(4) A, b = 11.6510(4) A, c = 11.6514(4) A, alpha = 73.545(3) degrees , beta = 89.318(2) degrees , gamma = 76.120(2) degrees , Z = 1; 5b.2C 6H 6: C 62H 72Ga 2Mo 2N 2, triclinic, P1, a = 10.3451(5) A, b = 11.6752(6) A, c = 11.6900(5) A, alpha = 73.917(3) degrees , beta = 89.550(3) degrees , gamma = 76.774(2) degrees , Z = 1]. All five [1.1]metallarenophanes 2a, 4a, b, and 5a, b crystallize as anti isomers with both Me 2N donor groups in exo positions ( C i point group symmetry). The new [1.1]metallarenophanes show NMR spectra that can be interpreted as being caused by time-averaged C 2 h symmetrical species, which is consistent with the findings of their molecular structures in the solid state. Variable-temperature (1)H NMR measurements for 4a, b and 5a, b (500 MHz; -90 to 90 degrees C) revealed only peak broadening in the lower temperature range of -70 to -90 degrees C. (1)H NMR saturation transfer difference experiments did not show an expected anti-to-anti isomerization, rendering the new [1.1]metallacyclophanes rigid on the NMR time scale. Electrochemical measurements were performed for 4a, b and 5a, b. However, reproducible cyclic voltammograms could only be obtained for the two gallium species 4b and 5b, revealing the expected weak communication between the two transition-metal atoms in both compounds (class II).     

Synthesis and characterization of the "metallic salts" A5Pn4 (A = K, Rb, Cs and Pn = As, Sb, Bi) with isolated zigzag tetramers of Pn4(4-) and an extra delocalized electron

The isostructural title compounds were prepared by direct reactions of the corresponding elements, and their structures were determined from single-crystal X-ray diffraction data in the monoclinic space group C2/m, Z = 2 (K5As4, a = 11.592(2) A, b = 5.2114(5) A, c = 10.383(3) A, beta = 113.42(1) degrees; K5Sb4, a = 12.319(1) A, b = 5.4866(4) A, c = 11.258(1) A, beta = 112.27(7) degrees; Rb5Sb4, a = 12.7803(9) A, b = 5.7518(4) A, c = 11.6310(8) A, beta = 113.701(1) degrees; K5Bi4, a = 12.517(2) A, b = 5.541(1) A, c = 11.625(2) A, beta = 111.46(1) degrees; Rb5Bi4, a = 12.945(4) A, b = 5.7851(9) A, c = 12.018(5) A, beta = 112.78(3) degrees; Cs5Bi4, a = 12.887(3) A, b = 6.323(1) A, c = 12.636(1) A, beta = 122.94(2) degrees). The compounds contain isolated and flat zigzag tetramers of Pn4(4-) (Pnictide (Pn) = As, Sb, Bi) with a conjugated pi-electron system of delocalized electrons. All six compounds are metallic ("metallic salts") and show temperature-independent (Pauli-like) paramagnetism due to a delocalized electron from the extra alkali-metal cation in the formula. At low temperatures (around 9.5 K) and low magnetic fields the bismuthides become superconducting.     

Synthesis, 5-hydroxytryptamine1A receptor affinity and docking studies of 3-[3-(4-aryl-1-piperazinyl)-propyl]-1H-indole derivatives

A series of 3-[3-(4-aryl-1-piperazinyl)-propyl]-1H-indole derivatives (12a-h) was synthesized and evaluated for binding affinity at the human 5-hydroxytryptamine(1A) receptor (5-HT(1A)R) compounds (12b) and (12h) showed the highest 5-HT(1A) receptor affinity (IC(50)=15 nM). Molecular docking studies with all the compounds in a homology model of 5-HT(1A) showed that the main interaction anchoring the ligand in the receptor was a charge-reinforced bond between the protonated nitrogen atom (N-4) of the piperazine ring and Aspartate(3.32).     

Extended hypervalent 5c-6e interactions: linear alignment of five C-Se---O---Se-C atoms in anthraquinone and 9-methoxyanthracene bearing arylselanyl groups at the 1,8-positions

The structures of 1,8-bis(phenylselanyl)anthraquinone (1a), 1,8-bis(phenylselanyl)-9-methoxyanthracene (2a), and 1,8-bis(phenylselanyl)anthracene (3a) are determined by X-ray crystallographic analysis, together with the derivatives. The Se-C(i) (Ph) bonds in 1a are placed on the anthraquinone plane (both type B) and the phenyl planes are perpendicular to the anthraquinone plane. The structure around the Se atoms in 2a is very close to that of 1a: the conformations of the PhSe groups are both type B. Consequently, the five C(i)-Se- - -O- - -Se-C(i) atoms in 1a and 2a align linearly. The nonbonded Se- - -O distances in 1a and 2a are 2.673-2.688 and 2.731-2.744 A, respectively, which are about 0.7 A shorter than the sum of van der Waals radii of the atoms. The extended hypervalent sigma*(C(i)-Se)- - -n(p)(O)- - -sigma*(Se-C(i)) 5c-6e interactions are strongly suggested for the origin of the linear alignment of the five atoms in 1a and 2a. The 5c-6e must be constructed by the connection of the two hypervalent n(p)(O)- - -sigma*(Se-C(i)) 3c-4e interactions through the central n(p)(O). The five C(i)-Se- - -H- - -Se-C(i) atoms never align linearly in 3a. To reveal the nature of 5c-6e in 1a and 2a, QC calculations are performed on H(a)H(b)(A)Se- - -O([double bond]CH(2))- - -(B)SeH(a')H(b') (model a) and H(a)H(b)(A)Se- - -OH(2)- - -(B)SeH(a')H(b') (model b) with the B3LYP/6-311++G(3df,2pd) method, where the nonbonded Se- - -O distances are fixed at 2.658 A. Four conformers, a (AA-cis), a (AA-trans), a (AB), and a (BB), are optimized to be stable for model a, where a (AA) shows both type A for the (A)Se-H(b) and (B)Se-H(b') bonds in model a. Three conformers, b (AA-cis), b (AB), and b (BB), are stable for model b. The bonding models in AA, AB, and BB correspond to 3c-6e, 4c-6e, and 5c-6e, respectively. The models become more stable by 42 +/- 5 kJ mol(-1), if the type A conformation of each Se-H bond changes to type B. No noticeable saturation is observed in the stabilization for each change. QC calculations are also performed on 1a-3a at the B3LYP level. Three conformers are evaluated to be stable for 1a and 2a. The relative energies of 1a (AA-trans), 1a (AB), and 1a (BB) are 0.0, -31.5, and -60.6 kJ mol(-1), respectively, and those of 2a (AA-cis), 2a (AB), and 2a (BB) are 0.0, -24.4, and -36.5 kJ mol(-1), respectively. These results demonstrate that the origin of the linear alignment of the five C-Se- - -O- - -Se-C atoms in 1a and 2a is the energy lowering effect by the extended hypervalent 5c-6e interactions of the sigma*(C-Se)<--n(p)(O)-->sigma*(Se-C) type. The pi-conjugation between pi(C[double bond]O) and n(pz)(Se) through the pi-framework of anthraquinone must also contribute to stabilize the BB structure of 1a, where z is the direction perpendicular to the anthraquinone plane.     

The In Vitro Anti-Cancer Activities and Mechanisms of Action of 9-Methoxycanthin-6-one from Eurycoma longifolia in Selected Cancer Cell Lines

An alkaloid compound from the hairy root culture of Eurycoma longifolia has been isolated and characterised as 9-methoxycanthin-6-one. The aims of these studies were to investigate the in vitro anti-cancer activities of 9-methoxycanthin-6-one against ovarian cancer (A2780, SKOV-3), breast cancer (MCF-7), colorectal cancer (HT29), skin cancer (A375) and cervical cancer (HeLa) cell lines by using a Sulphorhodamine B assay, and to evaluate the mechanisms of action of 9-methoxycanthin-6-one via the Hoechst 33342 assay and proteomics approach. The results had shown that 9-methoxycanthin-6-one gave IC₅₀ values of 4.04 ± 0.36 µM, 5.80 ± 0.40 µM, 15.09 ± 0.99 µM, 3.79 ± 0.069 µM, 5.71 ± 0.20 µM and 4.30 ± 0.27 µM when tested in A2780, SKOV-3, MCF-7, HT-29, A375 and HeLa cell lines, respectively. It was found that 9-methoxycanthin-6-one induced apoptosis in a concentration dependent manner when analysed via the Hoechst 33342 assay. 9-methoxycanthine-6-one were found to affect the expressions of apoptotic-related proteins, that were proteins pyruvate kinase (PKM), annexin A2 (ANXA2), galectin 3 (LGAL3), heterogeneous nuclear ribonucleoprotein A1 (HNRNP1A1), peroxiredoxin 3 (PRDX3), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from the differential analysis of 2-DE profiles between treated and non-treated 9-methoxycanthine-6-one. Proteins such as acetyl-CoA acyltransferase 2 (ACAA2), aldehyde dehydrogenase 1 (ALDH1A1), capping protein (CAPG), eukaryotic translation elongation factor 1 (EEF1A1), malate dehydrogenase 2 (MDH2), purine nucleoside phosphorylase (PNP), and triosephosphate isomerase 1 (TPI1) were also identified to be associated with A2780 cell death induced by 9-methoxycanthine-6-one. These findings may provide a new insight on the mechanisms of action of 9-methoxycanthin-6-one in exerting its anti-cancer effects in vitro.     

Heterodivalent Linked Macrocyclic β-Sheets with Enhanced Activity against Aβ Aggregation: Two Sites Are Better Than One

This paper reports a series of heterodivalent linked macrocyclic β-sheets 6 that are not only far more active against amyloid-β (Aβ) aggregation than their monovalent components 1a and 1b but also are dramatically more active than their homodivalent counterparts 4 and 5. The macrocyclic β-sheet components 1a and 1b comprise pentapeptides derived from the N- and C-terminal regions of Aβ and molecular template and turn units that enforce a β-sheet structure and block aggregation. Thioflavin T fluorescence assays show that heterodivalent linked macrocyclic β-sheets 6 delay Aβ(1-40) aggregation 6-8-fold at equimolar concentrations and substantially delay aggregation at substoichiometric concentrations, while homodivalent linked macrocyclic β-sheets 4 and 5 and monovalent macrocyclic β-sheets 1a and 1b only exhibit more modest effects at equimolar or greater concentrations. A model to explain these observations is proposed, in which the inhibitors bind to and stabilize the early β-structured Aβ oligomers and thus delay aggregation. In this model, heterodivalent linked macrocyclic β-sheets 6 bind to the β-structured oligomers more strongly, because N-terminal-derived component 1a can bind to the N-terminal-based core of the β-structured oligomers, while the C-terminal-derived component 1b can achieve additional interactions with the C-terminal region of Aβ. The enhanced activity of the heterodivalent compounds suggests that polyvalent inhibitors that can target multiple regions of amyloidogenic peptides and proteins are better than those that only target a single region.     

Synthesis, characterization, and structure of macrocyclic mono- and C2-symmetric, binuclear nickel calixsalen complexes

Mono- (3a,b) and binuclear (4a,b) tetradentate NiII complexes of a series of 26-membered macrocyclic salen dimers, [salen(CH2)]2, are prepared in good yield by solvent-controlled reaction with Ni(OAc)2. The mononuclear complex 3b crystallizes in the trigonal space group 3P1(#144), a = 18.2566(2) A, c = 15.9244(2) A, V = 4596.57(8) A3, and Z = 3. Refinement converged with R = 0.054 and Rw = 0.049 for 6852 reflections with I > 2.003 sigma(I). The NiII in complex 3b coordinates in an approximate square planar geometry to one of the two available tetradentate salen sites. Complex 4b crystallizes in the orthorhombic space group P2(1)2(1)2(1)(#19), a = 19.531(2) A, b = 22.891(3), c = 13.373(1) A, V = 5960(1) A3, and Z = 4. The refinement converged with R = 0.067 and Rw = 0.065 for 3752 reflections with I > 2.003 sigma(I). Complex 4b coordinates two distorted square planar, cofacially oriented NiII-salen units held 7.1 A apart by a rigid, syn-folded macrocyclic structure. The solution spectroscopic data and solid-state crystallographic data of 3b and 4b demonstrate the presence of a molecular-sized cavity which shows host-guest properties. Reaction of the flexible 32-membered disalen macrocycle [salen(OCH2CH2O)]2 with Ni(OAc)2 resulted in formation of a binuclear complex, 5. Complex 5 crystallizes in the triclinic space group P1(#1), a = 10.366(4) A, b = 12.170(3) A, c = 10.021(2) A, alpha = 106.29(2) degrees, beta = 91.69(2) degrees, gamma = 68.63(2) degrees, V = 1126.3(5) A3, and Z = 1. The refinement converged with R = 0.052 and Rw = 0.053 for 2385 reflections with I > 2.003 sigma(I). The binuclear complex 5 contains two cofacially oriented, square planar NiII-salen groups lying 3.5 A apart in an anti-folded macrocyclic structure.     

Synthesis of TiRru2 heterobimetallic and TiRuM (M = Rh, Rr, Pd, Pt) heterotrimetallic sulfido clusters from a hydrosulfido-bridged titanium-ruthenium complex

Treatment of the hydrosulfido-bridged titanium-ruthenium heterobimetallic complex [Cp2Ti(mu2-SH)2RuCl(eta5-C5Me5)] (1; Cp = eta5-C5H5) with an excess of triethylamine followed by addition of [RuCl2(PPh3)3] and [[(cod)M]2(mu2-Cl)2] (M = Rh, Ir; cod = 1,5-cyclooctadiene) led to the formation of the TiRu2 and TiRuM mixed-metal sulfido clusters [(CpTi)[(eta5-C5Me5)Ru][Ru(PPh3)2](mu3-S)2(mu2-Cl)2] (3) and [(CpTi)[(eta5-C5Me5)Ru][M(cod)](mu3-S)2(mu2-Cl)] (M = Rh (4a), Ir (4b)), respectively. On the other hand, the reactions of 1 with [M(PPh3)4] (M = Pd, Pt) afforded the TiRuM trinuclear clusters [(CpTiCl)[(eta5-C5Me5)Ru][M(PPh3)2](mu3-S)(mu2-S)(mu2-H)] (M = Pd (5a), Pt (5b)) with an unprecedented M3(mu3-S)(mu2-S) core. The detailed structures of these triangular clusters 3-5 have been determined by X-ray crystallography. Crystal data: 3, triclinic, P1, a = 12.448(4) A, b = 12.773(4) A, c = 17.270(4) A, alpha = 100.16(2) degrees, beta = 99.93(2) degrees, gamma = 114.11(3) degrees, V = 2373(1) A(3), Z = 2; 4a, triclinic, P1, a = 7.714(2) A, b = 11.598(3) A, c = 14.802(4) A, alpha = 80.46(2) degrees, beta = 82.53(2) degrees, gamma = 71.47(2) degrees, V = 1234.0(6) A3, Z = 2; 4b, triclinic, P1, a = 7.729(1) A, b = 11.577(2) A, c = 14.766(3) A, alpha = 80.14(1) degrees, beta = 82.71(1) degrees, gamma = 71.55(1) degrees, V = 1231.1(4) A3, Z = 2; 5a, monoclinic, P2(1)/c, a = 11.259(4) A, b = 16.438(4) A, c = 26.092(5) A, beta = 102.23(3) degrees, V = 4719(2) A(3), Z = 4; 5b, monoclinic, P2(1)/n, a = 11.369(2) A, b = 16.207(3) A, c = 26.116(2) A, beta = 102.29(1) degrees, V = 4701(1) A3, Z = 4.     

On the synthesis and isolation of chlorocarbazoles obtained by chlorination of N-substituted carbazoles

Chloro derivatives of N-methylcarbazole ( 1 ), N-phenylcarbazole ( 2 ), N-acetylcarbazole ( 3 ), N-benzoylcarbazole ( 4 ) and 2-methoxy-N-methylcarbazole are synthesized. They are compounds 1a, 1b, 1c, 1d, 1e, 2a, 2b, 3a, 3b, 3c, 3d, 4a, 4b, 5a, 5b, 5c, 5d and 5e . Some of them are described for the first time. By using semiempirical PM3 method theoretical substituent effects on the chlorinating reaction are calculated. A chlorination mechanism of carbazoles and N-substituted carbazoles are compared.     

Modeling of Shape Memory Induction and Recovery in Heat‐Shrinkable Polymers

Summary: A mechanical model was developed to describe qualitatively and quantitatively the stress‐strain‐time behavior of a prepared shape memory crosslinked polyethylene during hot stretching, stress relaxation under 200% strain at high temperature and strain recovery of the heat shrinkable polymer. The stress‐strain, the stress relaxation and the irrecoverable strain behavior of the model were established by driving the constitutive equation, which could qualitatively represent the behavior of the real material. By choosing significant values for the parameters of the proposed model, an excellent fit was obtained between the experimental behavior of the polymer and that predicted by the model. It was also revealed that the main source responsible for the imperfect recovery of the induced strain observed was the stress relaxation occurring during the stretch holding‐cooling time step.

Stress relaxation of crosslinked polyethylene under 200% strain at 160 °C.     

Water-soluble phosphines. 17.(1) novel water-soluble secondary and tertiary phosphines with disulfonated 1,1'-biphenyl backbones and dibenzophosphole moieties

Reaction of 2,2'-difluoro-1,1'-biphenyl with chlorosulfonic acid and subsequent hydrolysis followed by neutralization with potassium or sodium hydroxide affords disodium or dipotassium 5,5'-disulfonato-2,2'-difluoro-1,1'-biphenyl (1a, 1b). On treatment of 1b with diphenyl- or phenylphosphine in the superbasic medium DMSO/KOH, phosphine ligand 2 or 3 with a disulfonated 1,1'-biphenyl backbone or a dibenzophosphole moiety is formed. The structure of the oxide of 5-phenyldibenzophosphole 3, which crystallizes as 4.2.5H(2)O in the monoclinic space group P2(1)/n with a = 13.799(3) A, b = 19.246(4) A, c = 17.764(4) A, beta = 105.63(3) degrees, and Z = 4, has been determined by X-ray analysis. Nucleophilic phosphination of 1a with NaPH(2) in liquid ammonia yields the sodium phosphide 5a which on protonation gives the water-soluble 5H-dibenzophosphole 5. Reaction of 1b with PH(3) in the superbasic medium DMSO/KOtBu affords 5b in addition to the oxidation product 6a. On oxidation of 5a or 5b with H(2)O(2), the sodium or potassium salts of the sulfonated phosphinic acids 6a or 6b, respectively, are formed. Alkylation of the sodium dibenzophospholide 5a with 2,2'-bis(chloromethyl)-1,1'-biphenyl or 1,4-di-O-p-toluenesulfonyl-2,3-O-isopropylidene-D-threitol yields the chiral water-soluble bidentate phosphine ligands 8 and 9, respectively.     

High pressure pyrolysis of toluene. 1. Experiments and modeling of toluene decomposition

The pyrolysis of toluene, the simplest methyl-substituted aromatic molecule, has been studied behind reflected shock waves using a single pulse shock tube. Experiments were performed at nominal high pressures of 27 and 45 bar and spanning a wide temperature range from 1200 to 1900 K. A variety of stable species, ranging from small hydrocarbons to single ring aromatics (principal soot precursors such as phenylacetylene and indene) were sampled from the shock tube and analyzed using standard gas chromatographic techniques. A detailed chemical kinetic model with 262 reactions and 87 species was assembled to simulate the stable species profiles (specifically toluene, benzene and methane) from the current high-pressure pyrolysis data sets and shock tube-atomic resonance absorption spectrometry (ARAS) H atom profiles obtained from prior toluene pyrolysis experiments performed under similar high-temperature conditions and lower pressures from 1.5 to 8 bar. The primary steps in toluene pyrolysis represent the most sensitive and dominant reactions in the model. Consequently, in the absence of unambiguous direct experimental measurements, we have utilized recent high level theoretical estimates of the barrierless association rate coefficients for these primary reactions, C6H5 + CH3 --> C6H5CH3 (1a) and C6H5CH2 + H --> C6H5CH3 (1b) in the detailed chemical kinetic model. The available data sets can be successfully reconciled with revised values for deltaH0f(298K)(C6H5CH2) = 51.5 +/- 1.0 kcal/mol and deltaH0f(298K)(C6H5) = 78.6 +/- 1.0 kcal/mol that translate to primary dissociation rate constants, reverse of 1a and 1b, represented by k(-1a,infinity) = (4.62 x 10(25))T(-2.53)exp[-104.5 x 10(3)/RT] s(-1) and k(-1b,infinity) = (1.524 x 10(16))T(-0.04)exp[-93.5 x 10(3)/RT] s(-1) (R in units of cal/(mol K)). These high-pressure limiting rate constants suggest high-temperature branching ratios for the primary steps that vary from 0.39 to 0.52 over the temperature range 1200-1800 K.     

双分子维生素B_(12)模型分子的合成及表征

维生素B_(12)经醇解得到的七甲基钴啉酯1作为起始原料，经酸性水解分别得 到b,c,d,e,f-单酸钴啉酯2b～2f, 2b～2f与3-咪唑基丙胺盐酸盐反应合成了相应的 酰胺钴啉酯衍生物3b～3f, 3b～3f在乙酸的作用下合成了双分子络合维生素B_(12) 模型化合物双-单腈六甲基-N-（3-咪唑基）丙酰胺钴啉酯高氯酸盐5b～5f，并对其 化学结构进行了表征。     

Synthesis and chiroptical analysis of optically active chiral shell dendrons

We have prepared a series of chiral dendrons (1-4) in which chiral subunits are placed in individual generational shells at varying distances from the focal point. The optical activity of these chiral dendritic structures is successfully modeled using structurally similar low-molecular weight model compounds. In dendrons 1a and 1b a chiral subunit is directly adjacent to the focal point, whereas in dendrons 2, 3, and 4a,b the chiral subunits are incorporated in the interior of the dendron. A marked difference in optical activity between the former 1a and 1b) and latter (2, 3, 4a,b) dendrons is mirrored in the optical activities of model compounds 12a, 12b, 19a, and 19b. These model compounds directly mimic the surrounding constitution of the chiral subunits in the dendrons. This successful analysis of the chiroptical data using low-molecular weight model compounds suggests that these dendrons do not possess conformational order in solution.     

Medicinal foodstuffs. XXXIV. Structures of new prenylchalcones and prenylflavanones with TNF-alpha and aminopeptidase N inhibitory activities from Boesenbergia rotunda

The methanolic extract from the rhizomes of Boesenbergia rotunda (Zingiberaceae) was found to show inhibitory effect on tumor necrosis factor-alpha (TNF-alpha)-induced cytotoxicity in L929 cells (IC(50)=6.1 microg/ml). By bioassay-guided separation, four new prenylcalcones, (+)-krachaizin A (1a), (-)-krachaizin A (1b), (+)-krachaizin B (2a), and (-)-krachaizin B (2b), and four new prenylflavanones, rotundaflavones Ia (3a), Ib (3b), IIa (4a), and IIb (4b), were isolated together with 18 known constituents (5a-7b and 8-19). The structures of eight new compounds were elucidated on the basis of physicochemical evidence. Among them, (+)-krachaizin B (2a), (-)-krachaizin B (2b), (+)-4-hydroxypanduratin A (6a), (-)-4-hydroxypanduratin A (6b), (+)-isopanduratin A (7a), (-)-isopanduratin A (7b), alpinetin (10), cardamonin (14), and 2,6-dihydroxy-4-methoxydihydrochalcone (15) significantly inhibited TNF-alpha-induced cytotoxicity in L929 cells at 10 microM. In addition, 2a, 2b, (+)-panduratins A (5a), (-)-panduratin A (5b), 6a, 7b, and geranyl-2,4-dihydroxy-6-phenylbenzoate (17) were found to show strong inhibitory effects on aminopeptidase N activity.     

5-Methoxybenzothiophene-2-Carboxamides as Inhibitors of Clk1/4: Optimization of Selectivity and Cellular Potency

Clks have been shown by recent studies to be promising targets for cancer therapy, as they are considered key regulators in the process of pre-mRNA splicing, which in turn affects every aspect of tumor biology. In particular, Clk1 and -4 are overexpressed in several human tumors. Most of the potent Clk1 inhibitors reported in the literature are non-selective, mainly showing off-target activity towards Clk2, Dyrk1A and Dyrk1B. Herein, we present new 5-methoxybenzothiophene-2-carboxamide derivatives with unprecedented selectivity. In particular, the introduction of a 3,5-difluoro benzyl extension to the methylated amide led to the discovery of compound 10b (cell-free IC₅₀ = 12.7 nM), which was four times more selective for Clk1 over Clk2 than the previously published flagship compound 1b. Moreover, 10b showed an improved growth inhibitory activity with T24 cells (GI₅₀ = 0.43 µM). Furthermore, a new binding model in the ATP pocket of Clk1 was developed based on the structure-activity relationships derived from new rigidified analogues.     

α-Glucosidase Inhibitory and Antimicrobial Benzoylphloroglucinols from Garcinia schomburgakiana Fruits: In Vitro and In Silico Studies

α-Glucosidase plays a role in hydrolyzing complex carbohydrates into glucose, which is easily absorbed, causing postprandial hyperglycemia. Inhibition of α-glucosidase is therefore an ideal approach to preventing this condition. A novel polyprenylated benzoylphloroglucinol, which we named schomburgkianone I (1), was isolated from the fruit of Garcinia schomburgkiana, along with an already-reported compound, guttiferone K (2). The structures of the two compounds were determined using NMR and HRESIMS analysis, and comparisons were made with previous studies. Compounds 1 and 2 exhibited potent α-glucosidase inhibition (IC_50s of 21.2 and 34.8 µM, respectively), outperforming the acarbose positive control. Compound 1 produced wide zones of inhibition against Staphylococcus aureus and Enterococcus faecium (of 21 and 20 mm, respectively), compared with the 19 and 20 mm zones of compound 2, at a concentration of 50 µg/mL. The MIC value of compound 1 against S. aureus was 13.32 µM. An in silico molecular docking model suggested that both compounds are potent inhibitors of enzyme α-glucosidase and are therefore leading candidates as therapies for diabetes mellitus.