Application of Bayesian analysis to the doubly labelled water method for total energy expenditure in humans

Rationale

The doubly labelled water (DLW) method is the reference method for the estimation of free‐living total energy expenditure (TEE). In this method, where both ²H and ¹⁸O are employed, different approaches have been adopted to deal with the non‐conformity observed regarding the distribution space for the labels being non‐coincident with total body water. However, the method adopted can have a significant effect on the estimated TEE.

Methods

We proposed a Bayesian reasoning approach to modify an assumed prior distribution for the space ratio using experimental data to derive the TEE. A Bayesian hierarchical approach was also investigated. The dataset was obtained from 59 adults (37 women) who underwent a DLW experiment during which the ²H and ¹⁸O enrichments were measured using isotope ratio mass spectrometry (IRMS).

Results

TEE was estimated at 9925 (9106‐11236) [median and interquartile range], 9646 (9167–10540), and 9,638 (9220–10340) kJ·day⁻¹ for women and at 13961 (12851–15347), 13353 (12651–15088) and 13211 (12653–14238) kJ·day⁻¹ for men, using normalized non‐Bayesian, independent Bayesian and hierarchical Bayesian approaches, respectively. A comparison of hierarchical Bayesian with normalized non‐Bayesian methods indicated a marked difference in behaviour between genders. The median difference was −287 kJ·day⁻¹ for women, and −750 kJ·day⁻¹ for men. In men there is an appreciable compression of the TEE distribution obtained from the hierarchical model compared with the normalized non‐Bayesian methods (range of TEE 11234–15431 kJ·day⁻¹ vs 10786–18221 kJ·day⁻¹). An analogous, yet smaller, compression is seen in women (7081–12287 kJ·day⁻¹ vs 6989–13775 kJ·day⁻¹).

Conclusions

The Bayesian analysis is an appealing method to estimate TEE during DLW experiments. The principal advantages over those obtained using the classical least‐squares method is the generation of potentially more useful estimates of TEE, and improved handling of outliers and missing data scenarios, particularly if a hierarchical model is used.

     

Cleaving Direct‐Laser‐Written Microstructures on Demand

Using an advanced functional photoresist we introduce direct‐laser‐written (DLW) 3D microstructures capable of complete degradation on demand. The networks consist exclusively of reversible bonds, formed by irradiation of a phenacyl sulfide linker, giving disulfide bonds in a radical‐free step‐growth polymerization via a reactive thioaldehyde. The bond formation was verified in solution by ESI‐MS. To induce cleavage, dithiothreitol causes a thiol–disulfide exchange, erasing the written structure. The mild cleavage of the disulfide network is highly orthogonal to other, for example, acrylate‐based DLW structures. To emphasize this aspect, DLW structures were prepared incorporating reversible structural elements into a non‐reversible acrylate‐based standard scaffold, confirming subsequent selective cleavage. The high lateral resolution achievable was verified by the preparation of well‐defined line gratings with line separations of down to 300 nm.     

The Triplet State of 6‐thio‐2′‐deoxyguanosine: Intrinsic Properties and Reactivity Toward Molecular Oxygen

Thiopurine prodrugs are currently among the leading treatment options for leukemia, immunosuppression, and arthritis. Patients undergoing long‐term thiopurine treatment are at a higher risk of developing sunlight‐induced skin cancers than the general population. This side effect originates from the cellular metabolization of thiopurine prodrugs to form 6‐thio‐2′‐deoxyguanosine, which can absorb UVA radiation, populating its reactive triplet state and leading to oxidatively generated damage. However, the photo‐oxidation mechanism is not fully understood. In this contribution, the oxidation potential and the adiabatic triplet energy of 6‐thio‐2′‐deoxyguanosine are estimated computationally, whereas the intrinsic rate of triple‐state decay and the rate constant for triplet quenching by molecular oxygen are determined using time‐resolved spectroscopic techniques. A singlet oxygen quantum yield of 0.24 ± 0.02 is measured in aqueous solution (0.29 ± 0.02 in acetonitrile). Its magnitude correlates with the relatively low percentage of triplet‐O₂ collision events that generate singlet oxygen (S_Δ = 37%). This behavior is rationalized as being due to the exergonic driving force for electron transfer between the triplet state of 6‐thio‐2′‐deoxyguanosine and molecular oxygen (ΔG_ET = ?69.7 kJ mol^?1), resulting in the formation of a charge‐transfer complex that favors nonradiative decay to the ground state over triplet energy transfer.     

Quantitative Monitoring of Rutin in Human Urine by Flow Injection‐Chemiluminescence Analysis

In this paper, a rapid and sensitive flow injection‐chemiluminescence (FI‐CL ) method is proposed for the quantitative determination of rutin based on the inhibitory effect of rutin on the chemiluminescence intensity from the luminol–chymotrypsin (CT ) system. The decrease of CL intensity was found to be proportional to the logarithm of rutin concentration in the range 0.1–30.0 ng/mL . A method for the quantification of rutin is proposed, with the limit of detection (LOD ) of 0.03 ng/mL (3σ). A complete analytical process including sampling and washing for rutin determination, which was conducted at a flow rate of 2.0 mL /min, could be performed completely within 30 s, yielding a sample efficiency of 120 h⁻¹. The proposed procedure was successfully applied for the determination of rutin in human urine after oral intake, with recoveries varying from 93.9 to 108.1% and relative standard derivation <4.0% (n = 5). Results showed that urine reached the maximum concentration at ~2.5 h, and the total excretion ratios were (83.5 ± 0.6) and (86.8 ± 0.7)%, respectively, for two volunteers in 8 h. The pharmacokinetic parameters, including the half‐life (1.05 ± 0.02 h), absorption rate constant (1.18 ± 0.01 h⁻¹), and elimination rate constant (0.70 ± 0.01 h⁻¹), were obtained. The possible CL mechanism of the luminol–CT –rutin reaction is discussed by FI‐CL , fluorescence, and molecular docking methods.     

Switchable‐hydrophilicity solvent liquid‐liquid microextraction versus dispersive liquid‐liquid microextraction prior to HPLC‐UV for the determination and isolation of piperine from Piper nigrum L

Switchable‐hydrophilicity solvent liquid‐liquid microextraction and dispersive liquid‐liquid microextraction were compared for the extraction of piperine from Piper nigrum L. prior to its analysis by using high‐performance liquid chromatography with UV detection. Under optimum conditions, limits of detection and quantitation were found as 0.2–0.6 and 0.7–2.0 μg/mg with the two methods, respectively. Calibration graphs showed good linearity with coefficients of determination (R²) higher than 0.9962 and percentage relative standard deviations lower than 6.8%. Both methods were efficiently used for the extraction of piperine from black and white pepper samples from different origins and percentage relative recoveries ranged between 90.0 and 106.0%. The results showed that switchable‐hydrophilicity solvent liquid‐liquid microextraction is a better alternative to dispersive liquid‐liquid microextraction for the routine analysis of piperine in food samples. A novel scaled‐up dispersive liquid‐liquid microextraction method was also proposed for the isolation of piperine providing a yield of 102.9 ± 4.9% and purity higher than 98.0% as revealed by NMR spectroscopy.     

Theoretical Study of the Benzene Dimer by the Density‐Functional‐Theory Formalism Based on Electron‐Density Partitioning

The density‐functional approach based on the partition into subsystems was applied to study the benzene dimer. For several structures, the calculated interaction energy and intermolecular distance were compared with the previous theoretical results. A good agreement with high level ab initio correlated methods was found. For instance, the interaction energies obtained in this work and the CCSD(T) method agree within 0.1 – 0.6 kcal/mol depending on the structure of the dimer. The structure with the largest interaction energy is T‐shaped, in agreement with CCSD(T) results. The T‐shaped structure of benzene dimer was suggested by several experimental measurements. The calculated interaction energy of 2.09 kcal/mol agrees also well with experimental estimates based on the dissociation energy which ranges from 1.6±0.2 to 2.4±0.4 kcal/mol and the estimated zero‐point vibration energy of 0.3 – 0.5 kcal/mol.     

A rapid HPLC‐ESI‐MS/MS method for determination of β‐asarone,a potential anti‐epileptic agent,in plasma after oral administration of Acorus calamus extract to rats

β‐Asarone (BAS), a phenylpropanoid from Acorus calamus Linn., has shown biological effects in the management of cognitive impairment conditions such as Alzheimer's disease. The present paper describes a selective and sensitive liquid chromatography–tandem mass spectrometric method (HPLC‐MS/MS) using electrospray ionization source (ESI) for quantification of BAS in rat plasma. Briefly, the plasma samples were pre‐treated using a simple solid‐phase extraction method. The separation of BAS and the internal standard, caffeine, was achieved on an Agilent Zorbax XDB C₁₈ column (50 × 2.1 mm i.d., 5 µm) using 0.2 mL/min isocratic mobile phase flow. The detection was performed using an Applied Biosystems Hybrid Q‐Trap API 2000 mass spectrometer equipped with an ESI source operated in positive mode. Also, the developed bioanalytical method was validated as per the US FDA bioanalytical guidelines over the concentration range of 9.79–4892.50 ng/mL (r² ≥ 0.9951) for BAS from rat plasma. The mean percentage recovery (n = 3) for the low, middle and high quality control samples was 86.92 ± 3.89, 85.30 ± 1.09 and 87.24 ± 4.03%, respectively. The applicability of the validated HPLC‐MS/MS method was demonstrated by successful measurement of BAS from plasma following oral administration of Acorus calamus rhizome extracts to three female albino Wistar rats. Copyright © 2012 John Wiley & Sons, Ltd.     

OH‐Initiated Photooxidations of 1‐Pentene and 2‐Methyl‐2‐propen‐1‐ol: Mechanism and Yields of the Primary Carbonyl Products

The products of the gas‐phase reactions of OH radicals with 1‐pentene and 2‐methyl‐2‐propen‐1‐ol (221MPO) at T=298±2 K and atmospheric pressure were investigated by using a 4500 L atmospheric simulation chamber that was built especially for this work. The molar yield of butyraldehyde was 0.74±0.12 mol for the reaction of 1‐pentene. This work provides the first product molar yield determination of formaldehyde (0.82±0.12 mol), 1‐hydroxypropan‐2‐one (0.84±0.13 mol), and methacrolein (0.078±0.012 mol) from the reaction of 221MPO with OH radicals. The mechanism of this reaction is discussed in relation to the experimental results. Additionally, taking into consideration the complex mechanism, the rate coefficients of the reactions of OH with formaldehyde, 1‐hydroxypropan‐2‐one, and methacrolein were derived at atmospheric pressure and T=298±2 K.; the obtained values were (8.9±1.6)×10^?12, (2.4±1.4)×10^?12, and (22.9±2.3)×10^?12 cm³ molecule^?1 s^?1, respectively.     

Investigation of the Removal of Lead by Adsorption onto 1‐(2‐Thiazolylazo)‐2‐Naphthol (TAN) Imbedded Polyurethane Foam from Aqueous Solution

A new preconcentration method is presented for lead on TAN‐loaded polyurethane foam (PUF) and its measurement by differential pulse anodic stripping voltammetry (DPASV). The optimum sorption conditions of 1.29 × 10^?5 M solution of Pb(II) ions on TAN‐loaded PUF were investigated. The maximum sorption was observed at pH 7 with 20 minutes equilibrated time on 7.25 mg mL^?1 of TAN‐loaded foam. The kinetic study indicates that the overall sorption process was controlled by the intra‐particle diffusion process. The validity of Freundlich, Langmuir and Dubinin ‐ Radushkevich adsorption isotherms were tested. The Freundlich constants 1/n and K_F are evaluated to be 0.45 ±0.04 and (1.03 +0.61) × 10^?3 mol g^?1, respectively. The monolayer sorption capacity and adsorption constant related to the Langmuir isotherm are (1.38 ± 0.08) × 10^?5 mol g^?1 and (1.46 ± 0.27) × 10⁵ L mol^?1, respectively. The mean free energy of Pb(II) ions sorption on‐TAN loaded PUF is 11.04 ± 0.28 kJ mol^?1 indicating chemisorption phenomena. The effect of temperature on the sorption yields thermodynamics parameters of ΔH, ΔS and ΔG at 298 K that are 15.0 ± 1.4 kJ mol^?1, 74 ±5 J mol^?1 K^?1 and ‐7.37 ± 0.28 kJ mol^?1, respectively. The positive values of enthalpy (ΔH) and entropy (ΔS) indicate the endothermic sorption and stability of the sorbed complexes are entropy driven. However, the negative value of Gibb's free energy (ΔG) indicates the spontaneous nature of sorption. On the basis of these data, the sorption mechanism has been postulated. The effect of different foreign ions on the sorption and desorption studies were also carried out. The method was successfully applied for the determination of lead from different water samples at ng levels.     

Single nucleotide polymorphisms of mitochondrial DNA HVS‐I and HVS‐II in Chinese Bai ethnic group

For forensic and population genetic purposes, a total of 125 unrelated volunteers’ blood samples were collected from Chinese Bai ethnic minority group to analyze sequence variation of two hypervariable segments (HVS‐I and HVS‐II) in the mitochondrial DNA control region. Comparing the HVS‐I and HVS‐II sequences of the 125 Chinese Bais to the Anderson reference sequence, we found 86 polymorphic loci in HVS‐I and 40 in HVS‐II in mitochondrial DNA sequences of the Chinese Bai ethnic minority group, which defined 93 and 53 different haplotypes, respectively. Haplotype diversity and the mean pairwise differences were 0.992 ± 0.003 and 6.553 in HVS‐I, and 0.877 ± 0.027 and 2.407 in HVS‐II, respectively. We defined four macrohaplogroups R, M, N and D with the proportions ranging from 9.6% to 40.0%. With the analysis of the hypervariable domain from nucleotide 16 180–16 193 in HVS‐I, our study revealed new haplotypes of sequence variations. In addition, the Fst metric, phylogenetic tree, and principal component analysis demonstrated a close genetic relationship between the Bai group and Chinese Han populations from South China, Changsha, and Guangdong. The results support that the Bai group is a multiorigin ethnic minority that has merged with the Chinese Han population.     

Gas‐phase ozonolysis: Rate coefficients for a series of terpenes and rate coefficients and OH yields for 2‐methyl‐2‐butene and 2,3‐dimethyl‐2‐butene

The kinetics of the gas‐phase reactions of O₃ with a series of selected terpenes has been investigated under flow‐tube conditions at a pressure of 100 mbar synthetic air at 295 ± 0.5 K. In the presence of a large excess of m‐xylene as an OH radical scavenger, rate coefficients k(O₃+terpene) were obtained with a relative rate technique, (unit: cm³ molecule^?1 s^?1, errors represent 2σ): α‐pinene: (1.1 ± 0.2) × 10^?16, ³Δ‐carene: (5.9 ± 1.0) × 10^?17, limonene: (2.5 ± 0.3) × 10^?16, myrcene: (4.8 ± 0.6) × 10^?16, trans‐ocimene: (5.5 ± 0.8) × 10^?16, terpinolene: (1.6 ± 0.4) × 10^?15 and α‐terpinene: (1.5 ± 0.4) × 10^?14. Absolute rate coefficients for the reaction of O₃ with the used reference substances (2‐methyl‐2‐butene and 2,3‐dimethyl‐2‐butene) were measured in a stopped‐flow system at a pressure of 500 mbar synthetic air at 295 ± 2 K using FT‐IR spectroscopy, (unit: cm³ molecule^?1 s^?1, errors represent 2σ ): 2‐methyl‐2‐butene: (4.1 ± 0.5) × 10^?16 and 2,3‐dimethyl‐2‐butene: (1.0 ± 0.2) × 10^?15. In addition, OH radical yields were found to be 0.47 ± 0.04 for 2‐methyl‐2‐butene and 0.77 ± 0.04 for 2,3‐dimethyl‐2‐butene. © 2002 Wiley Periodicals, Inc. Int J Chem Kinet 34: 394–403, 2002     

Oxidative Dearomatization of 4,5,6,7‐Tetrahydro‐1H‐indoles Obtained by Metal‐ and Solvent‐Free Thermal 5‐endo‐dig Cyclization: The Route to Erythrina and Lycorine Alkaloids

A facile one‐pot approach based on a thermally induced metal‐ and solvent‐free 5‐endo‐dig cyclization reaction of the amino propargylic alcohols in combination with Dess–Martin periodinane‐promoted oxidative dearomatization of 4,5,6,7‐tetrahydroindole intermediates provides an efficient and robust access to 5,6‐dihydro‐1H‐indol‐2(4H)ones. Green, relatively mild and operationally simple characteristics of the synthetic sequence are the major advantages, which greatly amplify the developed methodology. The utility of obtained indolones as unified key precursors is demonstrated by the application of these products to the formal total syntheses of a whole pleiad of Erythrina‐ and Lycorine‐type alkaloids, namely (±)‐erysotramidine, (±)‐erysotrine, (±)‐erythravine, (±)‐γ‐lycorane, and abnormal erythrinanes (±)‐coccoline and (±)‐coccuvinine.     

The Structure of Bis[N‐6‐aminopyridyl‐N‐(1S)‐(+)‐10‐camphorsulfonylamino]palladium in the Solid State and in Solution

The complex, bis[N‐6‐aminopyridyl‐N‐(1S)‐(+)‐10‐camphorsulfonylamino]palladium, Pd[(S)‐APCS]₂, 1 , was prepared by reaction of 2‐[(1S)‐(+)‐10‐camphorsulfonamino]‐6‐aminopyridine with PdCl₂ in THF. Complex 1 has been characterized by spectroscopic methods and its structure has been determined by X‐ray crystallography. Crystal data: space group C2, a= 16.082 (2), b = 17.104 (2), c = 13.051 (2)Å, β = 99.95 (1)°, V = 3535.9 (8) ų, Z = 2 with final residuals R1 = 0.0491 and wR2 = 0.0944. Two independent molecules, (S,S)‐Pd[(S)‐APCS]2, 1a , and (R,R)‐Pd[(S)‐APCS]2, 1b , were found in each asymmetric unit, which exchange to each other via a series of nitrogen inversion and C‐C bond rotation. The inversion energy (ΔGc₁^≠) and the energy barrier (δGc₂^≠) were 11.5 ± 0.1 Kcal mol^?1 at 246 K and 9.8 ± 0.1 Kcal mol^?1 at 199 K, respectively, calculated by dynamic NMR data.     

Radical heterogeneous polymerization behavior of N‐methyl‐α‐fluoroacrylamide in benzene

The polymerization of N‐methyl‐α‐fluoroacrylamide (NMFAm) initiated with dimethyl 2,2′‐azobisisobutyrate (MAIB) in benzene was studied kinetically and with electron spin resonance. The polymerization proceeded heterogeneously with the highly efficient formation of long‐lived poly(NMFAm) radicals. The overall activation energy of the polymerization was 111 kJ/mol. The polymerization rate (R_p) at 50 °C is given by R_p = k[MAIB]^0.75±0.05 [NMFAm]^0.44±0.05. The concentration of the long‐lived polymer radical increased linearly with time. The formation rate (R_p?) of the long‐lived polymer radical at 50 °C is expressed by R_p? = k[MAIB]^1.0±0.1 [NMFAm]^0±0.1. The overall activation energy of the long‐lived radical formation was 128 kJ/mol, which agreed with the energy of initiation (129 kJ/mol), which was separately estimated. A comparison of R_p? with the initiation rate led to the conclusion that 1‐methoxycarbonyl‐1‐methylethyl radicals (primary radicals from MAIB), escaping from the solvent cage, were quantitatively converted into the long‐lived poly(NMFAm) radicals. Thus, this polymerization involves completely unimolecular termination due to polymer radical occlusion. ¹H NMR‐determined tacticities of resulting poly(NMFAm) were estimated to be rr = 0.34, mr = 0.48, and mm = 0.18. The copolymerization of NMFAm(M₁) and St(M₂) with MAIB at 50 °C in benzene gave monomer reactivity ratios of r₁ = 0.61 and r₂ = 1.79. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 2196–2205, 2001     

Laboratory studies of the ·OH‐initiated photooxidation of ethyl‐n‐butyl ether and di‐n‐butyl ether

Oxygenated compounds such as ethers and alcohols are used as gasoline additives and industrial solvents. However, despite their widespread use, the atmospheric reaction mechanisms of some of these compounds are unknown. This study examines the ^·OH‐initiated gas‐phase removal mechanisms of ethyl‐n‐butyl ether (ENBE) and di‐n‐butyl ether (DNBE) utilizing gas chromatography–mass spectrometry techniques. The primary products and molar yields from the hydroxyl‐radical–initiated photooxidation of ENBE in the presence of nitric oxide were acetaldehyde (0.173 ± 0.012), ethyl formate (0.219 ± 0.033), butyraldehyde (0.076 ± 0.004), butyl formate (0.241 ± 0.009), butyl acetate (0.032 ± 0.001), and ethyl butyrate (0.0044 ± 0.0006). From the calculated molar yields, approximately 45.5% of the reacted carbon were recovered. The primary products and molar yields from the DNBE and hydroxyl radical reaction in the presence of nitric oxide were propionaldehyde (0.379 ± 0.022), butyraldehyde (0.119 ± 0.003), butyl formate (0.410 ± 0.009), and butyl butyrate (0.019 ± 0.001). Approximately 47.7% of the reacted DNBE were recovered. The chemical mechanisms are presented to explain the formation of these products. In addition, the importance of the isomerization and nitrate/nitrite formation pathways in the reactions of large ethers are discussed. © 2001 John Wiley & Sons, Inc. Int J Chem Kinet 33: 328–341, 2001     

Intake of different chemical species of dietary arsenic by the japanese,and their blood and urinary arsenic levels

We calculated the intake of each chemical species of dietary arsenic by typical Japanese, and determined urinary and blood levels of each chemical species of arsenic. The mean total arsenic intake by 35 volunteers was 195±235 (15.8-1039) μg As day^?1, composed of 76% trimethylated arsenic (TMA), 17.3% inorganic arsenic (As_i), 5.8% dimethylated arsenic (DMA), and 0.8% monomethylated arsenic (MA): the intake of TMA was the largest of all the measured species. Intake of As_i characteristically and invariably occurred in each meal. Of the intake of As_i, 45-75% was methylated in vivo to form MA and DMA, and excreted in these forms into urine. The mean measured urinary total arsenic level in 56 healthy volunteers was 129±92.0 μg As dm^?3, composed of 64.6% TMA, 26.7% DMA, 6.7% As_i and 2.2% MA. The mean blood total arsenic level in the 56 volunteers was 0.73±0.57 μg dl^?1, composed of 73% TMA, 14% DMA and 9.6% As_i. The urinary TMA levels proved to be significantly correlated with the whole-blood TMA levels (r = 0.376; P<0.01).     

Photoswitchable Tetraethynylethene‐Dihydroazulene Chromophores

The synthesis, characterization, and photophysical as well as electrochemical properties of the photochromic hybrid systems 11 – 16 and 18 , which contain photoswitchable tetraethynylethene (TEE; 3,4‐diethynylhex‐3‐ene‐1,5‐diyne) and dihydroazulene (DHA) moieties, are presented. The molecular photoswitches were synthesized by a Sonogashira cross‐coupling reaction between an appropriate TEE precursor ( 6 – 10 and 17 ) and an iodinated DHA 1 or its vinylheptafulvene (VHF) isomer ( 4 ) (Schemes 5 – 7). X‐Ray crystal structures of five DHA derivatives ( 1 , trans‐ 11a , cis‐ 11a , 12 , and 13 ) are discussed (Figs. 2 – 5). In all compounds, the cyclohexatriene moiety of the DHA chromophore adopts a clear boat conformation (Table 1). Presumably due to crystal‐packing effects, the arylated TEE moieties in the hybrid systems show substantial distortions from planarity, with the dihedral angles between the planes of the central TEE core and the adjacent aryl substituents amounting to 44°. The switching properties were investigated by electronic absorption spectroscopy. Upon light absorption, DHAs 1 , 12 – 16 , and 18 underwent retro‐electrocyclization in solution to give the corresponding VHFs (Figs. 6, 11, and 12). The reaction is thermally reversible, with half‐lives τ_1/2 between 3.9 and 5.8 h at 25° in CH₂Cl₂ (Figs. 7 and 13 and Table 3). A comparatively slower (E)→(Z) isomerization process about the central C=C bond of the TEE moiety was also observed. The N,N‐dimethylanilino‐(DMA) substituted TEE‐DHA hybrid systems trans‐ 11a and cis‐ 11a did not react to the corresponding VHFs upon irradiation (Scheme 9). Instead, only the reversible (E)→(Z) photoisomerization of the TEE core occurred (Fig. 16 and Table 4). This process was further investigated for photofatigue by electronic‐emission spectroscopy (Fig. 17). After protonation of the DMA group, the usual DHA→VHF photoreaction took place. Compound 11 represents a three‐way chromophoric molecular switch with three addressable sub‐units (TEE core, DHA/VHF moiety, and proton sensitive DMA group) that can undergo individual, reversible switching cycles (Scheme 9). A process modeling the function of an `AND' logic gate (Fig. 19) and three write/erase processes could be performed with this system. Cyclic and linear sweep‐voltammetry studies in CH₂Cl₂ (+Bu₄NPF₆) revealed the occurrence of characteristic first‐reduction steps in the TEE‐DHA hybrid systems between −1.6 and −1.8 V vs. Fc/Fc⁺ (ferrocene/ferricinium couple) (Table 5). Oxidations occur at ca. +1.10 V. After photoisomerization to the VHF derivatives, reduction steps at more positive and oxidation steps at more negative potentials were recorded. No DHA→VHF isomerization took place upon electrochemical oxidation or reduction (Fig. 20).     

Kinetics Study on Oxidation of β‐Isophorone Using Molecular Oxygen

The oxidation kinetics of β‐isophorone (β‐IP) using molecular oxygen catalyzed by iron(III) acetylacetonate was investigated in a lab‐scale agitator bubbling reactor. β‐IP was found to give keto‐isophorone (KIP) and 4‐hydroxy‐3,5,5‐trimethyl‐2‐cyclohexen‐1‐one (HIP) along with little isomerization product α‐isophorone (α‐IP). The results show that the oxidation reaction took place in the pseudo–first‐order fast reaction regime. The experiment was conducted under the mass transfer reaction regime as the mass transfer resistances could not be easily eliminated. The intrinsic kinetics was obtained through apparent kinetics. The activation energy of oxidation of β‐IP to KIP is 70.5 ± 4.1 kJ mol^–1, and the value of ln A_KIP is 33.53 ± 1.22. Meanwhile, the activation energy of oxidation of β‐IP to HIP is 86.4 ± 5.4 kJ mol^–1 and the value of ln A_HIP is 36.23 ± 1.52, which could provide theoretical basis for industrial design, amplification of reactor, and the optimization of reaction.     

Rapid quantitative analysis of etoricoxib in human plasma by UPLC‐MS/MS and application to a pharmacokinetic study in Chinese healthy volunteers

A selective and sensitive liquid chromatography–tandem mass spectrometry method was developed for simultaneous determination of etoricoxib in human plasma. Chromatography was performed on an Acquity UPLC HSS T3 column (1.8 μm, 50 × 2.1 mm), with a flow rate of 0.600 mL/min, using a gradient elution with acetonitrile and water which contained 2 mm ammonium acetate as the mobile phase. Detection was carried out on Triple QuadTM 5500 mass spectrometer under positive‐ion multiple reaction monitoring mode. The respective mass transitions used for quantification of etoricoxib and etoricoxib‐d3 were m/z 359.0 → 280.1 and m/z 362.0 → 280.2. Calibration curves were linear over the concentration range of 5–5000 ng/mL. The validated method was applied in the pharmacokinetic study of etoricoxib in Chinese healthy volunteers under fed and fasted conditions. After a single oral dose of 120 mg, the main pharmacokinetic parameters of etoricoxib in fasted and fed groups were respectively as follows: peak concentration, 2364.78 ± 538.01 and 1874.55 ± 367.90 ng/mL; area under the concentration–time curve from 0 to 120 h, 44,605.53 ± 15,266.66 and 43,516.33 ± 12,425.91 ng h/mL; time to peak concentration, 2.00 and 2.50 h; and half‐life, 24.08 ± 10.06 and 23.64± 6.72 h. High‐fat food significantly reduced the peak concentration of etoricoxib (p = 0.001) but had no effect on the area under the concentration–time curve.     

Sub‐Picosecond Singlet Exciton Fission in Cyano‐Substituted Diaryltetracenes

Thin films of 5,11‐dicyano‐6,12‐diphenyltetracene ( TcCN ) have been studied for their ability to undergo singlet exciton fission (SF). Functionalization of tetracene with cyano substituents yields a more stable chromophore with favorable energetics for exoergic SF (2E(T₁)?E(S₁)=?0.17 eV), where S₁ and T₁ are singlet and triplet excitons, respectively. As a result of tuning the triplet‐state energy, SF is faster in TcCN relative to the corresponding endoergic process in tetracene. SF proceeds with two time constants in the film samples (τ=0.8±0.2 ps and τ=23±3 ps), which is attributed to structural disorder within the film giving rise to one population with a favorable interchromophore geometry, which undergoes rapid SF, and a second population in which the initially formed singlet exciton must diffuse to a site at which this favorable geometry exists. A triplet yield analysis using transient absorption spectra indicates the formation of 1.6±0.3 triplets per initial excited state.