Direct Detection of a Chemical Equilibrium between a Localized Singlet Diradical and Its σ-Bonded Species by Time-Resolved UV/Vis and IR Spectroscopy.

Localized singlet diradicals are key intermediates in bond homolyses. The singlet diradicals are energetically much less stable than the σ-bonded species. In general, only one-way reactions from diradicals to σ-bonded species are observed. In this study, a thermal equilibrium between a singlet 1,2-diazacyclopentane-3,5-diyl diradical and the corresponding σ-bonded species was directly observed. The singlet diradical was more stable than the σ-bonded species. The solvent effect clarified key features, such as the zwitterionic character of the singlet diradical. The effect of the nitrogen atoms is discussed in detail.

Incorporation of a Doubly Functionalized Synthetic Amino Acid into Proteins for Creating Chemical and Light-Induced Conjugates.

Z-Lysine (ZLys) is a lysine derivative with a benzyloxycarbonyl group linked to the ε-nitrogen. It has been genetically encoded with the UAG stop codon, using the pair of an engineered variant of pyrrolysyl-tRNA synthetase (PylRS) and tRNA(Pyl). In the present study, we designed a novel Z-lysine derivative (AmAzZLys), which is doubly functionalized with amino and azido substituents at the meta positions of the benzyl moiety, and demonstrated its applicability for creating protein conjugates. AmAzZLys was incorporated into proteins in Escherichia coli, by using the ZLys-specific PylRS variant. AmAzZLys was then site-specifically incorporated into a camelid single-domain antibody specific to the epidermal growth factor receptor (EGFR). A one-pot reaction demonstrated that the phenyl amine and azide were efficiently linked to the 5 kDa polyethylene glycol and a fluorescent probe, respectively, through specific bio-orthogonal chemistry. The antibody was then tested for the ability to form a photo-cross-link between its phenylazide moiety and the antigen, while the amino group on the same ring was used for chemical labeling. When incorporated at a selected position in the antibody and exposed to 365 nm light, AmAzZLys formed a covalent bond with the EGFR ectodomain, with the phenylamine moiety labeled fluorescently prior to the reaction. The present results illuminated the versatility of the ZLys scaffold, which can accommodate multiple reactive groups useful for protein conjugation.

Kinetic stabilization and reactivity of π single-bonded species: effect of the alkoxy group on the lifetime of singlet 2,2-dialkoxy-1,3-diphenyloctahydropentalene-1,3-diyls.

Kinetic stabilization and reactivity of π single-bonded species have been investigated in detail by generating a series of singlet 2,2-dialkoxy-1,3-diphenyloctahydropentalene-1,3-diyls (DRs). The lifetime at 293 K in benzene was found to increase when the carbon chain length of the alkoxy groups was increased; 292 ns (DRb; OR = OR' = OCH3) <880 ns (DRc; OR = OR' = OC2H5) <1899 ns (DRd; OR = OR' = OC3H7) ≈2292 ns (DRe; OR = OR' = OC6H13) ≈2146 ns (DRf; OR = OR' = OC10H21). DRh (OR = OC3H7, OR' = OCH3; 935 ns) with the mixed-acetal moiety is a longer-lived species than another diastereomer DRg (OR = OCH3, OR' = OC3H7; 516 ns). Activation parameters determined for the first-order decay process reveal that the enthalpy factor plays a crucial role in determining the energy barrier of the ring-closing reaction, that is, from the π-bonding to the σ-bonding compounds. Computational studies using density functional theory provided more insight into the structures of the singlet species with π single-bonded character and the transition states for the ring-closing reaction, thereby clarifying the role of the alkoxy group on the lifetime and the stereoselectivity of the ring-closing reaction.

Substituent effect on reactivity of triplet excited state of 2,3-diazabicyclo[2.2.1]hept-2-enes, DBH derivatives: α C-N bond cleavage versus ß C-C bond cleavage.

The photoreaction of a series of 2,3-diazabicyclo[2.2.1]hept-2-ene (DBH) derivatives, in which various substituents (X) were introduced at the methano bridge carbon of C(7), was investigated under direct (>290 nm) and triplet-sensitized (Ph2CO, >370 nm) irradiation conditions of the azo chromophore (−Cß­Cα­N═N­Cα­Cß−). The azo compounds offered a unique opportunity to see the substituent X effect at the remote position of the azo chromophore on the reactivity of the triplet excited state of bicyclic azoalkanes. The present study led to the first observation of the unusual Cα­Cß bond-cleavage reaction without the ring stiffness, that is, the structural rigidity, in the triplet state of the cyclic azoalkanes. The stereoelectronic effects were found to play an important role in lowering the activation energy of the Cα­Cß bond-cleavage reaction. NBO analyses at the M06-2X/cc-PVDZ level of theory confirmed the stereoelectronic effect.

Substituent effect on the energy barrier for σ-bond formation from π-single-bonded species, singlet 2,2-dialkoxycyclopentane-1,3-diyls.

BACKGROUND: Localized singlet diradicals are in general quite short-lived intermediates in processes involving homolytic bond-cleavage and formation reactions. In the past decade, long-lived singlet diradicals have been reported in cyclic systems such as cyclobutane-1,3-diyls and cyclopentane-1,3-diyls. Experimental investigation of the chemistry of singlet diradicals has become possible. The present study explores the substituents and the effect of their substitution pattern at the C(1)-C(3) positions on the lifetime of singlet octahydropentalene-1,3-diyls to understand the role of the substituents on the reactivity of the localized singlet diradicals. RESULTS: A series of singlet 2,2-dialkoxy-1,3-diaryloctahydropentalene-1,3-diyls DR were generated in the photochemical denitrogenation of the corresponding azoalkanes AZ. The ring-closed products CP, i.e., 3,3-dialkoxy-2,4-diphenyltricyclo[3.3.0.0(2,4)]octanes, were quantitatively obtained in the denitrogenation reaction. The first-order decay process (k = 1/τ) was observed for the fate of the singlet diradicals DR (λmax ≈ 580-590 nm). The activation parameters, ΔH (‡) and ΔS (‡), for the ring-closing reaction (σ-bond formation process) were determined by the temperature-dependent change of the lifetime. The energy barrier was found to be largely dependent upon the substituents Ar and Ar'. The singlet diradical DRf (Ar = 3,5-dimethoxyphenyl, OCH2Ar' = OCH2(3,5-dimethoxyphenyl)) was the longest-lived, τ293 = 5394 ± 59 ns, among the diradicals studied here. The lifetime of the parent diradical DR (Ar = Ph, OCH2Ar' = OCH3) was 299 ± 2 ns at 293 K. CONCLUSION: The lifetimes of the singlet 1,3-diyls are found to be largely dependent on the substituent pattern of Ar and Ar' at the C(1)-C(3) positions. Both the enthalpy and entropy effect were found to play crucial roles in increasing the lifetime.

Magnetic field effect on chemical wave propagation from the Belousov-Zhabotinsky reaction.

Effects of magnetic field (maximum field, 4 and 93 T(2) m(-1)) on the propagation speed of a chemical wavefront from the Belousov-Zhabotinsky reaction were studied in a thin glass tube. The downward and upward speed and the horizontal one are, respectively affected significantly by vertical and horizontal magnetic fields. Observations of the wavefront shape in magnetic fields showed that the magnetic force-induced convection causes the observed effects.

Photochemical cleavage reactions of 8-quinolinyl sulfonates in aqueous solution.

Photochemical cleavage reactions of 8-quinolinyl benzenesulfonate derivatives and related sulfonates in aqueous solutions are reported. The 8-quinolinyl benzenesulfonates undergo photolysis upon photoirradiation at 300-330 nm to give the corresponding 8-quinolinols and benzenesulfonic acids with the production of only negligible amounts of byproducts. The effects of substituent groups of the 8-quinolinyl moiety and the benzene ring on the photolysis reactions were examined. Based on steady-state mechanistic studies using a triplet sensitizer, a triplet quencher, and electron donors, it was suggested that the photolysis proceeds mainly via the homolytic cleavage of S-O bonds in the excited triplet state.

Ultrasonographic data of cervical nerve roots diameter in 100 healthy adults.

Clinically significant evaluation of the diameters of nerve roots by ultrasonography requires the establishment of a normal reference range. Although there are multiple reports of nerve root diameters in normal subjects, none of them describe how to normalize and compare data derived from different facilities that may differ in their methodology, equipment, techniques, and recording sites during data acquisition. The aim of the present investigation was to establish a dataset of normal values using 100 healthy subjects, and to identify the factors that affect the normal ranges of cervical nerve root diameters with regard to age, sex, laterality, and root segments. Compared to previous reports, smaller standard deviations (0.07-0.21) were obtained, and the coefficient of variation ranged from 0.02 to 0.08, which facilitated the precise evaluation of cervical nerve roots. Age had a significant effect on the sixth cervical nerve root (C6) in male participants, and sex had a significant effect at C6 in participants in their 60s. To establish the normal values suitable for use across different facilities, acquired using different equipment, further development of various aspects, including the sophisticated recording techniques and data-sharing capabilities, is essential.

Magnetic orientation of single-walled carbon nanotubes or their composites using polymer wrapping.

The magnetic orientation of single-walled carbon nanotubes (SWNTs) or the SWNT composites wrapped with polymer using poly[2-methoxy-5-(2'-ethylhexyloxy)-1,4-phenylene vinylene] (MEHPPV) as the conducting polymer were examined. The formation of SWNT/MEHPPV composites was confirmed by examining absorption and fluorescence spectra. The N,N-dimethylformamide solution of SWNT/MEHPPV composites or the aqueous solution of the shortened SWNTs was introduced dropwise onto a mica or glass plate. The magnetic processing of the composites or the SWNTs was carried out using a superconducting magnet with a horizontal direction (8 T). The AFM images indicated that the SWNT/MEHPPV composites or the SWNTs were oriented randomly without magnetic processing, while with magnetic processing (8 T), they were oriented with the tube axis of the composites or the SWNTs parallel to the magnetic field. In polarized absorption spectra of SWNT/MEHPPV composites on glass plates without magnetic processing, the absorbance due to semiconducting SWNT in the near-IR region in horizontal polarized light was almost the same as that in vertical polarized light. In contrast, with magnetic processing (8 T), the absorbance due to semiconducting SWNT in the horizontal polarization direction against the direction of magnetic field was stronger than that in the vertical polarization direction. Similar results were obtained from the polarized absorption spectra for the shortened SWNTs. These results of polarized absorption spectra also support the magnetic orientation of the SWNT/MEHPPV composites or the SWNTs. On the basis of a comparison of the composites and the SWNTs alone, the magnetic orientation of SWNT/MEHPPV composites is most likely ascribable to the anisotropy in susceptibilities of SWNTs.

The natural history of hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) in 97 Japanese patients.

Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) is a motor and sensory neuronopathy with autosomal dominant inheritance, adult onset, slowly progressive course, and is associated with TRK-fused gene (TFG) mutation. At advanced stages, respiratory failure and dysphagia becomes life-threatoning, and patients typically die by their 70s. Although there is currently no evidence for effective treatment, a therapy may be found by elucidation of the function of TFG. Recently its pathomechanism has been proposed to be associated with abnormalities in protein transfer from the endoplasmic reticulum. Such pathomechanisms might involve a similar process in amyotrophic lateral sclerosis; thus, its pathomechanisms and treatment strategy might make it a good model for neurodegenerative disorders. It is of great value to clarify the natural history of HMSN-P, in oder to judge the treatment effect. By evaluating 97 patients (79 out of 97 were examined and all confirmed with p.Pro 285 Leu mutation) in this study, it was confirmed that this disease follows a uniform course in the earlier stages, and there are individual differences in the onset between 20 and 30 years. Such uniformity might be due to the proposed single gene abnormality. At advanced stages, there are larger individual differences in the progression, but the reasons for these are unknown. Longer survival might be achieved with a better care for respiratory failure and dysphagia if such cares were undertaken at appropriate times.

Evidence for a transition state model compound of in-plane vinylic SN2 reaction.

[reaction: see text] To isolate a transition state model compound of an in-plane vinylic S(N)2 reaction, vinyl bromide 6 bearing a newly synthesized tridentate ligand derived from 1,8-dimethoxythioxanthen-9-one (5) was prepared as a precursor. Although irradiation of 6 gave demethylated benzofuran 12, a transient broad peak which indicates formation of the desired transition state model compound was observed in the laser flash photolytic study.

Fullerene sensors based on calix[5]arene.

A new class of fullerene sensors based on calix[5]arenes has produced the highly sensitive detection of C60 and C70.

Electrocardiogram measurement during sleep with wearing clothes using capacitively-coupled electrodes.

The electrocardiogram (ECG) was measured by non-contact, non-restraint and unconscious method using capacitively-coupled electrodes made of electro-conductive cloth while subjects lay on bed wearing their clothes. These electrodes are very sensitive so measure not only signals but noise. The seat grounded, which arranged under the electrode could suppress noise. Two types of electrode different in length were used, that is long type and short type. Results showed that both electrodes could sense ECG. Noise generated from e.g. commercial power source was almost the same for both electrodes though the length of electrode was longer than the subject for the long type electrode. Setting position was rather serious and noise component changed greatly by the part of body that touches the electrode. Next, ECG was measured on these condition participants lay with supine position, prone position, right lateral position and left lateral position. The ECG was measured on each condition.

Non-restrictive heart rate monitoring using an acceleration sensor.

Daily long-term monitoring of heart rates is important for health management. An analysis of heart rate variability can facilitate the early discovery of illnesses. In this study, we paid attention to the method of measuring resting heart rate over long term. An acceleration sensor was set inside the down kilt as it opposing to subject's left chest. Mechanical vibration from heart activity is carried to the acceleration sensor through the down quilt. As a result, periodic vibration was measured successfully and this vibration was proved to be in high correlation with the R wave of ECG. The same results were obtained even in case of lying in a left lateral position.

Proposal for a method of non-restrictive measurement of resting heart rate in a lying position.

Daily monitoring of heart rates is important in health management. Many researchers have analysed heart rate variability by using the resting heart rate because such an analysis can facilitate the early discovery of a variety of illnesses and health conditions. Some problems that arise in measuring heart rate are the feeling of confinement. Therefore, we required a system that could measure the resting heart rate in a static position in such a way that the subject is completely unaware that the measurement is being recorded. We propose a non-restrictive measurement method that uses only an acceleration sensor placed inside a down quilt. This method is easy for home use. The acceleration sensor was placed inside the quilt such that it was positioned opposite to the left-hand side of the subject's chest. Six healthy subjects were requested to lie in the supine position and were covered with the quilt equipped with the acceleration sensor. Mechanical vibrations that resulted from heart activity were carried through the quilt to the acceleration sensor. As a result, periodic vibrations were measured successfully, and in the six subjects, these vibrations were proved to be highly correlated with the R wave of electrocardiograms. The same results were obtained even when the subjects were lying in the left lateral position. The results indicated that our new method, which used an acceleration sensor placed inside a down quilt, was simple and could be used to measure the resting heart rate in a lying position.

Basic Study for Optimal Control of In-Bed Temperature during Sleep.

It is important to create a comfortable environment to restful sleep. In this study, we trial-produced an in-bed temperature control system. At first, we statically controlled the temperature in the subject's bed at 32°C by using the system, and examined how this control affected sleep. We were able to confirm that the ratio of slow-wave sleep (SWS) increased in comparison to cases in which the temperature in the bed was not controlled. Next, the temperature in the subject's bed was dynamically controlled at temperature change patterns according to sleep cycles that is as follows; Heating during the REM sleep period and cooling during the SWS sleep period were conducted n the range of 32±2°C, and the case of the opposite phase. The result showed that cooling during the REM period increased the REM sleep share rate. Based on these results, an increase of the REM sleep share rate at around 30°C could be confirmed, indicating a possibility that the REM period thermoneutrality zone shifted to a lower temperature, compared with that of SWS.