Energy transfer between polyatomic molecules. 3. Energy transfer quantities and probability density functions in self-collisions of benzene, toluene, p-xylene and azulene

This paper is the third and last in a series of papers that deal with collisional energy transfer, CET, between aromatic polyatomic molecules. Paper 1 of this series (J. Phys. Chem. B 2005, 109, 8310) reports on the mechanism and quantities of CET between an excited benzene and cold benzene and Ar bath. Paper 2 in the series (J. Phys. Chem., in press) discusses CET between excited toluene, p-xylene and azulene with cold benzene and Ar and CET between excited benzene colliding with cold toluene, p-xylene and azulene. The present work reports on CET in self-collisions of benzene, toluene, p-xylene and azulene. Two modes of excitation are considered, identical excitation energies and identical vibrational temperatures for all four molecules. It compares the present results with those of papers 1 and 2 and reports new findings on average vibrational, rotational, and translational energy, , transferred in a single collision. CET takes place mainly via vibration to vibration energy transfer. The effect of internal rotors on CET is discussed and CET quantities are reported as a function of temperature and excitation energy. It is found that the temperature dependence of CET quantities is unexpected, resembling a parabolic function. The density of vibrational states is reported and its effect on CET is discussed. Energy transfer probability density functions, P(E,E'), for various collision pairs are reported and it is shown that the shape of the curves is convex at low temperatures and can be concave at high temperatures. There is a large supercollision tail at the down wing of P(E,E'). The mechanisms of CET are short, impulsive collisions and long-lived chattering collisions where energy is transferred in a sequence of short internal encounters during the lifetime of the collision complex. The collision complex lifetimes as a function of temperature are reported. It is shown that dynamical effects control CET. A comparison is made with experimental results and it is shown that good agreement is obtained.     

Energy transfer between polyatomic molecules II: Energy transfer quantities and probability density functions in benzene, toluene, p-xylene, and azulene collisions

Collisional energy transfer, CET, is of major importance in chemical, photochemical, and photophysical processes in the gas phase. In Paper I of this series (J. Phys. Chem. B 2005, 109, 8310) we have reported on the mechanism and quantities of CET between an excited benzene and cold benzene and Ar bath. In the present work, we report on CET between excited toluene, p-xylene, and azulene with cold benzene and Ar and on CET of excited benzene with cold toluene, p-xylene, and azulene. We compare our results with those of Paper I and report average vibrational, rotational, and translational energy quantities, , transferred in a single collision. We discuss the effect of internal rotation on CET and the identity of the gateway modes in CET and the relative role of vibrational, rotational, and translational energies in the CET process, all that as a function of temperature and excitation energy. Energy transfer probability density functions, P(E,E'), for the various systems are reported and the shape of the curves for various systems and initial conditions is discussed. The major findings for polyatomic-polyatomic collisions are: CET takes place mainly via vibration-to-vibration energy transfer assisted by overall rotations. Internal free rotors in the excited molecule hinder energy exchange while in the bath molecule they do not. Energy transfer at low temperatures and high temperatures is more efficient than that at intermediate temperatures. Low-frequency modes are the gateway modes for energy transfer. Vibrational temperatures affect energy transfer. The CET probability density function, P(E,E'), is convex at low temperatures and can be concave at high temperatures. A mechanism that explains the high values of and the convex shape of P(E,E') is that in addition to short impulsive collisions there are chattering collisions where energy is transferred in a sequence of short encounters during the lifetime of the collision complex. This also leads to the observed supercollision tail at the down wing of P(E,E'). Polyatomic-Ar collisions show mechanistic similarities to polyatomic-polyatomic collisions, but there are also many dissimilarities: internal rotations do not inhibit energy transfer, P(E,E') is concave at all temperatures, and there is no contribution of chattering collisions.     

A novel formal total synthesis of cephalotaxine

A formal total synthesis of cephalotaxine (CET), the parent structure of antileukemia Cephalotaxus alkaloids, was achieved through a novel synthesis of the pentacyclic amino enone 4 by a rapid annulation of readily available beta-(3,4-methylenedioxy)phenethylamine (2), delta-valerolactone, and bromoacetone.     

A novel and efficient total synthesis of cephalotaxine

[reaction: see text] Total synthesis of cephalotaxine (CET), the parent member of a class of structurally unique antileukemia Cephalotaxus alkaloids, was accomplished on the basis of a conceptually novel strategy featuring transannular reductive skeletal rearrangements as the key transformations for the construction of the pentacyclic ring skeleton of CET. The synthetic potential of the designated Clemmensen-Clemo-Prelog-Leonard reductive rearrangement was demonstrated for the first time in a facile synthesis of the benzazepine subunit of CET. A novel endocyclic enamine (cyclopentenone) annulation was discovered and rationalized as an unusual azo-Nazarov-type cyclization.     

Cephalotaxine Inhibits the Survival of Leukemia Cells by Activating Mitochondrial Apoptosis Pathway and Inhibiting Autophagy Flow

Cephalotaxine (CET) is a natural alkaloid with potent antileukemia effects. However, its underlying molecular mechanism has not been well understood. In this study, we verified that CET significantly inhibited the viability of various leukemia cells, including HL-60, NB4, Jurkat, K562, Raji and MOLT-4. RNA-sequencing and bioinformatics analysis revealed that CET causes mitochondrial function change. Mechanism research indicated that CET activated the mitochondrial apoptosis pathway by reducing the mitochondrial membrane potential, downregulating anti-apoptotic Bcl-2 protein and upregulating pro-apoptotic Bak protein. In addition, the autophagy signaling pathway was highly enriched by RNA-seq analysis. Then, we found that CET blocked the fluorescence colocation of MitoTracker Green and LysoTracker Red and upregulated the level of LC3-II and p62, which indicated that autophagy flow was impaired. Further results demonstrated that CET could impair lysosomal acidification and block autophagy flow. Finally, inhibiting autophagy flow could aggravate apoptosis of HL-60 cells induced by CET. In summary, this study demonstrated that CET exerted antileukemia effects through activation of the mitochondria-dependent pathway and by impairing autophagy flow. Our research provides new insights into the molecular mechanisms of CET in the treatment of leukemia.     

七元瓜环对2'-羟基查尔酮溶解性、稳定性及抗氧化活性的影响

利用~1H NMR、紫外吸收光谱和荧光光谱等方法考察了七元瓜环(Q[7])对2'-羟基查尔酮(CET)的包结作用.结果表明,Q[7]与CET形成了摩尔比为1∶1的包结配合物,紫外吸收光谱和荧光光谱测得的结合稳定常数分别为1.0248×10~6和1.253×10~6.相溶解度法研究结果表明,当Q[7]的浓度为1×10~(-3)mol/L时,可使CET在水中的溶解度增加52倍.紫外吸收光谱随时间变化的研究结果表明,Q[7]使CET的稳定性增加3.5倍.采用体外抗氧化活性测定(ABTS法)考察了Q[7]对CET抗氧化活性的影响,发现CET@Q[7]包结配合物以及游离CET均对ABTS自由基有较好的清除作用.IC50值分别为3.4×10~(-5)和2.4×10~(-5)mol/L,表明Q[7]不仅能增加CET的溶解性和稳定性,同时对CET抗氧化活性的影响不大.     

In vivo metabolic investigation of cetilistat in normal versus pseudo-germ-free rats using UPLC-QTOFMS/MS and in silico toxicological evaluation of its metabolites

Cetilistat (CET) is a pancreatic lipase inhibitor approved for management of obesity after the serious adverse effects exhibited by its analogue orlistat. Exhaustive literature review reveals lack of comprehensive reports on its biotransformation. With a view to study the same, the present study reports the identification and characterization of metabolites of CET in rats using UPLC–MS/MS. As the small intestine is the site of action for CET, it is important that the role of microbial flora in the metabolism of CET be explored. To achieve this, the metabolic profile of CET was compared between normal and pseudo-germ-free rats. The study involved the administration of a drug suspension to male Sprague–Dawley pseudo-germ-free and normal untreated rats followed by collection of urine, feces, and blood at specific intervals. Sample preparation was performed using liquid–liquid extraction and concentration of samples followed by analysis using LC–MS/MS. Finally, an in silico study was performed on the drug and metabolites to predict their toxicological properties using ADMET Predictor^TM software. Four metabolites of CET were observed in in vivo matrices. As expected, significant changes were observed both qualitatively and quantitatively, implying that formation of metabolites was both CYP enzymes and gut microflora mediated.     

Energy transfer between polyatomic molecules. 1. Gateway modes, energy transfer quantities and energy transfer probability density functions in benzene-benzene and Ar-benzene collisions

We report collisional energy transfer, CET, quantities for polyatomic-polyatomic collisions and use excited benzene collisions with cold benzene bath, B-B, as our sample system and compare our results with the CET of excited benzene with Ar bath. We find that the gateway mode for both systems is the out-of-plane modes and that in B-B CET, vibration to vibration, V-V, is the dominant channel. Rotations play a mechanistic role in the CET but the net rotational energy transfer is small compared to V-V. The shape of the down side of the energy transfer probability density function, P(E,E'), is convex for B-B collisions and it becomes less so as the temperature increases. In Ar-B collisions, P(E,E') is concave and it becomes less so as the temperature decreases. We report average vibrational, rotational, and translational energy transferred, , as function of temperature for various initial conditions.     

Fracture behavior of core-shell rubber-modified crosslinkable epoxy thermoplastics

The fracture behavior of a core-shell rubber (CSR) modified cross-linkable epoxy thermoplastic (CET) system, which exhibits high rigidity, highT _g, and low crosslink density characteristics, is examined. The toughening mechanisms in this modified CET system are found to be cavitation of the CSR particles, followed by formation of extended shear banding around the advancing crack. With an addition of only 5 wt.% CSR, the modified CET possesses a greater than five-fold increase in fracture toughness (G _IC) as well as greatly improved fatigue crack propagation resistance properties, with respect to those of the neat resin equivalents. The fracture mechanisms observed under static loading and under fatigue cyclic loading are compared and discussed.     

Enantioselective analysis of cetirizine in pharmaceuticals by cyclodextrin-mediated capillary electrophoresis

The present paper demonstrates the potential of cyclodextrin (CD)-mediated CE for the chiral analysis of a drug of zwitterionic nature, viz. cetirizine (CET). Various separation mechanisms were applied and several parameters affecting the separation were studied, including the type and concentration of chiral selector, coselector, and carrier ion, and pH of buffer. The optimal separation conditions were based on a medium buffer pH (approximately 5.2) (migration velocity of CET molecule was near to zero) and a highly substituted CD derivative, sulfated-beta-CD, serving as an analyte carrier in the anionic regime of the separation with suppressed electroosmotic flow. In this way, a baseline enantioseparation, reasonable separation efficiency, and short analysis time could be easily achieved. Acceptable validation criteria for sensitivity, linearity, precision, accuracy, and robustness were obtained using a hydrodynamically closed CE separation system. The proposed method was successfully applied to the enantioselective assay of CET in pharmaceutical formulations using fexofenadine (FEX) as an internal standard.     

Biodegradable PEO/cellulose‐based solid–solid phase change materials

A series of poly(ethylene oxide) (PEO) blends with cellulose (CEL) or cellulose derivatives—carboxymethyl cellulose (CMC), cellulose acetate (CAC), and cellulose ether (CET)—has been investigated as phase change materials for thermal energy storage. For PEO/CEL blends solid–solid phase transition has been observed in the whole concentration's range; for PEO/CMC and PEO/CET blends solid–solid phase transition has been found for PEO content 25 or 50 and 25 wt%, respectively. Otherwise, solid–liquid phase transition takes place. MTDSC investigations revealed that for PEO/CEL and PEO/CMC blends transition the strongest recrystallization effect (as evidenced by exothermic effect in reversing heat flow) as melting process occurred. FTIR analysis shows a shift of the stretching vibration bands of both the proton‐donor O? H groups from CEL and PEO due to intermolecular hydrogen interactions between the blends' components. Copyright © 2010 John Wiley & Sons, Ltd.     

Photochemical reactivity of sulfamethoxazole and other sulfa compounds with photodiode array detection

The photochemical activities of six sulfa compounds [sulfacetamide (CET), sulfadiazine (DIA), sulfaguanidine (GUA), sulfamerazine (MER), sulfamethoxazole (SMX), and sulfamethizole (MET)] under different experimental conditions such as photolysis time, solvent and buffer pH are investigated by photodiode array (PDA) spectrophotometry. With no photolysis, the sulfa drugs CET and DIA show no absorbance at 332 nm and the other compounds only modest absorbance. Upon photolysis for 4 min, absorbance enhancements at 332 nm of three to four times for GUA and MET and 12-15 times for SMX and MER are observed. For CET and DIA after photolysis, the (absorbance) l/mg is now approximately 0.01-0.02 units. Although two pH optima of approximately 3-4 and 7 are noted, the optimum solvent for photolysis is ethanol without pH adjustment. For flow injection (FI) with on-line photolysis and PDA detection, a mobile phase of 100% ethanol with a step flow rate from 0.1 to 1 ml/min is used providing a 4-min reaction time. The FI detection limit for SMX with photolysis at 330 nm is 1 mg/l. The relative standard deviation data (n=4) of seven individual points in a calibration curve from 5 to 150 mg/l are 0-4%. The recovery of SMX from pharmaceutical tablets is 99.7% indicating no interference from trimethoprim which is not photochemically active.     

Generation of a novel monoclonal antibody against cortisol-[C-4]-bovine serum albumin conjugate: application to enzyme-linked immunosorbent assay for urinary and serum cortisol.

Measurement of cortisol levels in body fluids is important for monitoring pituitary gland and adrenal functions. To develop a specific and standardized enzyme-linked immunosorbent assay (ELISA), a novel monoclonal anti-cortisol antibody has been generated using a reasonably designed haptenic derivative. Spleen cells were prepared from the BALB/c or A/J mouse, which had repeatedly been immunized with a conjugate of 4-(2-carboxyethylthio)cortisol (CET) and bovine serum albumin, to be fused with P3/NS1/1-Ag4-1 myeloma cells. After four fusion experiments, one hybridoma clone secreting a practical antibody has been established. The resulting monoclonal antibody CS#38 (isotype gamma1, kappa) showed an affinity constant (K(a)) for cortisol of 1 x 10(9) M(-1) and provided a practical calibration curve (detection limit, 0.26 ng per assay) in a homologous ELISA system employing horseradish peroxidase-labeled CET as a labeled antigen. Cross-reactivities with related C-21 steroids were acceptably low: 11-deoxycortisol (4.3%), cortisone (4.0%), corticosterone (1.9%), progesterone (1.6%), 17alpha-hydroxyprogesterone (12%), 6beta-hydroxycortisol (8.4%), and tetrahydrocortisol (< 0.1%). Urinary and serum cortisol levels of healthy volunteers were determined by this method after methylene chloride extraction to be 39.0 +/- 17.0 microg/day (n = 7) and 80.8 +/- 38.9 ng/mL (n = 10), respectively, both of which are in the reference range.     

Theoretical study of photodetachment processes of anionic boron clusters. I. Structure

Photo-induced electron detachment spectroscopy of anionic boron clusters, B(4)(-) and B(5)(-), is theoretically investigated by performing electronic structure calculations and nuclear dynamics simulations. While the electronic potential energy surfaces (X(1)A(g), ?(3)B(2u), b(3)B(1u), ?(1)B(2u), c(3)B(2g), and B(1)B(2g) of neutral B(4) and X(2)B(2), ?(2)A(1), B(2)B(2), C(2)A(1), D(2)B(1), and E(2)A(1) of neutral B(5)) and their coupling surfaces are constructed in this paper, the details of the nuclear dynamics on these electronic states are presented in Paper II. Electronic structure calculations are carried out at the complete active space self-consistent field-multi-reference configuration interaction level of theory employing the correlation consistent polarized valance triple zeta basis set. Using the calculated electronic structure data suitable vibronic Hamiltonians are constructed utilizing a diabatic electronic basis and displacement coordinates of the normal vibrational modes. The theoretical results are discussed in relation to those recorded in recent experiments.     

High throughput method for the analysis of cetrizine hydrochloride in pharmaceutical formulations and in biological fluids using a tris(2,2'-bipyridyl)ruthenium(II)-peroxydisulphate chemiluminescence system in a two-chip device

A fast, economic and sensitive chemiluminescence (CL) method has been developed for the analysis of cetrizine hydrochloride (CET) in pharmaceutical formulations and in biological fluids. The CL method is based on the oxidation of tris(2,2′-bipyridyl)ruthenium(II) (Ru (bipy)₃²⁺) by peroxydisulphate in a two-chip device. Up to 180 samples can be analysed per hour, consuming only minute quantities of reagents. Three instrumental setups were tested to find the most economical, sensitive and high throughput setup. In the first setup, a continuous flow of sample and CL reagents was used, whereas in the second setup, a fixed volume (2 μL) of (Ru (bipy)₃²⁺) was introduced into a continuous infusion of peroxydisulphate and the sample. In the third design, a fixed volume of sample (2 μL) was injected while the CL reagents were continuously infused. Compared to the first setup, a 200% signal enhancement was observed in the third setup. Various parameters that influence the CL signal intensity, including pH, flow rates and reagent concentrations, were optimized. A linear response was observed over the range of 50 μg L⁻¹ to 6400 μg L⁻¹ (R² = 0.9959) with RSD values of 1.1% (n = 15) for 1000 μg L⁻¹. The detection limit was found to be 15 μg L⁻¹ (S/N = 3). The amount of consumed sample was only 2 μL, from which the detected amount of CET was found to be 6.5 × 10⁻¹⁴ mol. This procedure was successfully applied to the analysis of CET in pharmaceutical formulations and biological fluids.     

Structure and ethanol complexation of cyclic tetrasaccharide in aqueous solution studied by NMR and molecular mechanics

The structure and ethanol complexation of a cyclic tetrasaccharide (CTS) in aqueous solution were investigated by proton NMR spectroscopy and molecular mechanics calculations. Two glucose units, A and B, of CTS are alternatively bonded by alpha-1,3 and alpha-1,6 linkages. The overlapped signals of protons A5, A6S, A6R, B3, B6S and B6R were resolved by spectral simulations to determine their chemical shifts and vicinal coupling constants. All vicinal coupling constants except for the A5-A6 spin system are consistent with the dihedral angles in the X-ray crystal structure. Each of protons A5, A6S, and A6R in the two units of A is equivalent with respect to the chemical shift. The vicinal coupling constants of (3)J(5-6S) and (3)J(5-6R) for unit A are close to the average of two rotamers that are present in crystals. The intensities of cross-peaks in the rotating frame nuclear Overhauser effect spectroscopy (ROESY) spectrum were rather well correlated with the effective distances calculated for the X-ray structure and molecular mechanics structures calculated in vacuo and water, although they are slightly better correlated with molecular mechanics structure in vacuo than with the other structures. From the changes of the chemical shifts of several CTS protons with increasing ethanol concentration, it was suggested that adsorption sites of ethanol on the plate structure of CTS are protons B2 and B4 (site B) in the concave face side and protons A1 and A2 (site A) in the convex back side. The binding constants for sites A and B are 0.0061 and 0.0176 M(-1), respectively. These binding constants are much smaller than a value of 4.1 M(-1) for the ethanol-alpha-cyclodextrin complex.     

甲基丙烯酸二甲氨基乙酯溴代烷季铵盐与苯乙烯共聚合的研究

以甲基丙烯酸二甲氨基乙酯溴代乙烷（ Ｍ Ａ Ｅ Ｂ） 或丁烷（ Ｍ Ａ Ｂ Ｂ） 季胺盐与苯乙烯（ Ｓｔ）为单体,采用溶液自由基共聚合方法,合成了一类新型阳离子两亲共聚物．详细地研究了聚合条件及共聚物的溶解性．共聚物“亲油”和“亲水”单元的无规结构被 Ｉ Ｒ、１ Ｈ Ｎ Ｍ Ｒ 及１３ Ｃ Ｎ Ｍ Ｒ所证实．最后,用线性化（ Ｙ Ｂ Ｒ） 法分别求得 Ｍ Ａ Ｅ Ｂ／ Ｓｔ 和 Ｍ Ａ Ｂ Ｂ／ Ｓｔ 的单体竞聚率,ｒ Ｍ Ａ Ｂ Ｂ ＝０４４ ,ｒ Ｓｔ ＝ ０１５ ,ｒ Ｍ Ａ Ｅ Ｂ＝ ０６６ ,ｒ Ｓｔ＝ ０３６ ．     

The structure of arachno-[B6H11]-, at -25 degrees C in (CD3)2O,is resolved via the ab initio/IGLO-GIAO/NMR procedure

The arachno-[B6H11]- solution structure at -25 degrees C was clarified as fluxional compound 2 by applying the ab initio/IGLO/NMR method. The anion 2 can be derived from arachno-B6H12, 1, by the removal of the B2/B3 bridging hydrogen (2). No minimum on the potential energy surface could be found for an asymmetric complex, a, between [B5H8]- and BH3, which had been proposed originally. A Cs-symmetric [mu-(BH3)B5H8]- complex, A, only 3.2 kcal mol-1 higher in energy than 2, is the intermediate in the fluxional rearrangement observed on the NMR time scale. The transition structure [D] connecting 2 (Erel = 0.0) and A (Erel = 3.2) has a relative energy of 9.7 kcal mol-1. The elimination of both a and A as "most stable structure" candidates of arachno-[B6H11]- reinforces the early geometrical bonding systematics for boranes and carboranes.     

Structure of 1-(arylselanyl)naphthalenes. 2. G dependence in 8-G-1-(p-YC(6)H(4)Se)C(10)H(6).

The structures of 8-G-1-(p-YC(6)H(4)Se)C(10)H(6) (1 (G = Cl) and 2 (G = Br): Y = H (a), OMe (b), Me (c), Cl (d), Br (e), COOEt (f), and NO(2) (g)) were investigated by X-ray crystallographic analysis, NMR spectroscopy, and ab initio MO calculations. The structures of all members in 1 and 2 are concluded to be type B, which is in striking contrast to the type A structure for 4d-g (4 (g(n)), where G = H). The Se-C(i) bond of the p-YC(6)H(4)Se group in 8-G-1-(p-YC(6)H(4)Se)C(10)H(6) is almost perpendicular to the naphthyl plane in type A, and it is located on the plane in type B. The chlorine and bromine substitution at the 8-position in 1 and 2 dramatically changes the type A structure of 4 (g(n)) to type B. The nonbonded G- - -Se-C 3c-4e type interaction must contribute to stabilize the type B structure. The type B structure in 1 and 2 should also be more stabilized than the same structure in 4 by the 3c-4e type interaction: The structure of 4b is type B in the crystals and type B would be more stable for 4c and might be for 4a in solutions. Ab initio MO calculations are performed on 8-G-1-(p-YC(6)H(4)Se)C(10)H(6), 8-G-C(10)H(6)SeH-1, and models HG- - -SeH(2), where G = Cl, Br, and F, to clarify the reason for the dramatic change in the structures. The type B structure is optimized to be more stable than the type A for all species examined, which supports the observations. The energy differences between type B and type A are larger for the models than for the naphthalenes. While the superiority of the type B for the former is Br > Cl > F, that of the latter is Br approximately Cl >/= F. These results show that the main factor of the structural change from type A to type B is the nonbonded G- - -Se-C 3c-4e interaction. The electronic effect of halogens through the naphthalene pi-framework would also contribute to some extent, although the direct comparison of the evaluated values between the naphthalene systems and the models is not so easy. Factors to stabilize the two structures of 1, 2, 4, and 8-(MeSe)-1-(p-YC(6)H(4)Se)C(10)H(6) are reexamined from a viewpoint of the nonbonded G- - -Se-C 3c-4e interaction (G dependence), together with the electronic effect of Y (Y dependence).     

Beyond two-state conical intersections. Three-state conical intersections in low symmetry molecules: the allyl radical

Using multireference configuration interaction expansions comprised of over 7 million configuration state functions, three-state conical intersections are reported for the closely spaced, spectroscopically observed (tilde)B(2A1), (tilde)C(2B1), and (tilde)D(2B2) states (in C(2v) symmetry) of the allyl radical. These conical intersections of states which were previously assigned as the 3,4,5(2)A states and are here reassigned as the 4,5,6(2)A states, are expected to be accessible using optical probes. This conclusion is obtained from the structure of the minimum energy point on the 4,5,6(2)A three-state conical intersection seam which is similar to the equilibrium structure of the ground (tilde)X(2A2) state and only 1.1 eV above the (tilde)D(2B2) state at its equilibrium geometry. The seam of three-state degeneracies joins two two-state seams of conical intersection, the 4,5(2)A and 5,6(2)A conical intersection seams. The energy of the minimum energy point on the 4,5(2)A two-state seam is only 0.15 eV above that of the (tilde)D(2B2) state at its equilibrium structure. Three-state intersections are also reported for the 3,4,5(2)A states.