Search

The 9-substituted anthracene derivative forms a spatially restricted dimer in the cavity of γ-cyclodextrin and exhibits circularly polarised luminescence with gCPL = +1.3 × 10−3 in the solid state.

Reactions of arylpropargyl amides of fumarate with a base by heating in xylenes under air gave benz[f]isoindolines. Heating the amides of fumarate and ethenetricarboxylate in DMSO gave aroyl-substituted pyrrolidines, probably via addition of water.

The relationship between the lactim-lactam tautomerization and the free-radical scavenging reaction in vitamin B9 [folic acid (FA)] was investigated by density functional theory calculations. 6-Methylpterin was also adopted for the detailed analyses of various reaction paths. For pterin, the transition state of the tautomerization with two water molecules (n = 2) was calculated to be of the lowest activation energy. The proton-transfer circuit of n = 2 is retained (not broken) even with the addition of outer water molecules, n = 2 + 2, 2 + 4, 2 + 8, and 2 + 14. At the oxidation of the system composed of 6-methylpterin + (H2O)2 + HO•, the radical character of HO• is directly transmitted to the pterin ring along with the C-O → H → O → H → O → H → OH proton transfer. The patterns of the electron transfer (pterin ring → OX•) and the concomitant proton transfer via the water dimer were commonly obtained for the oxidant (OX•) = HO•, Cl3C-O2•, N3•, or SO4-•. The hydrogen atom transfer mechanism was ruled out. Two conformations of the puckered form with the -C(═O)-OH···N intramolecular hydrogen bonds of FA were found to have the stability similar to that of the linear conformer. Both the tautomerization and the oxidation were calculated to occur competitively in the three conformers.

Circularly polarized luminescence (CPL) organic dyes are currently receiving a great interest, but there are still not many reported observations of CPL spectra of hydrophobic dyes from aqueous solution. We have prepared hydrophobic pyrene derivatives and dissolved them into aqueous solutions with γ-cyclodextrin (γ-CD) by using grinding technique. Among these derivatives, (pyrene-1-carbonyl)serine (PySer) forms a spatially restricted dimer in the hydrophobic chiral cavity of γ-CD and exhibits excimer emission with a high quantum yield of Φf = 0.68. In addition, circular dichroism and CPL signals were induced for the complex. The strong gCPL value of gCPL = + 2.2 × 10−3 was obtained, which may be attributed to the interaction between the hydroxyl groups in the side chain of PySer with those of γ-CD and it strengthens the chiral dimeric structure.

Intramolecular cycloaddition reactions of α-bromostyrene-functionalized amides of monomethyl fumarate were investigated. The reaction of the amides with Et

Exercise stress echocardiography has been used to assess myocardial reserve in various heart diseases. This study examined the ventricular myocardial response to exercise in Fontan patients using exercise stress echocardiography. Twenty-five Fontan patients and 19 control subjects underwent semi-supine bicycle exercise stress echocardiography in this prospective, single-center, cross-sectional study. Pulsed-wave Doppler tissue imaging peak systolic (s’) and diastolic (e’) velocities, longitudinal strain and systolic strain rate, and early diastolic strain rate data at rest and at peak exercise were obtained for the systemic ventricle. The myocardial reserve of functional parameters was calculated as the difference between peak exercise and rest. Inter- and intra-observer reliability were both high for exercise stress echocardiography measurements. Compared with controls, Fontan patients had significantly lower s’, e’, longitudinal systolic strain and strain rate, and early diastolic longitudinal strain rate at rest and at peak exercise as well as reduced myocardial reserve. Fontan patients have markedly reduced myocardial reserve during exercise. The use of exercise stress echocardiography assessment may improve the clinical management of Fontan patients.

A transamination reaction in the first stage from an internal aldimine ([PLP-model]) and (S)-alanine to pyridoxamine-5′-phosphate (PMP) and pyruvic acid was investigated by DFT calculations. An important role of the phosphate group was suggested.

Inter- and intramolecular cycloaddition reactions of ethenetricarboxylates with styrenes and α-halostyrenes have been investigated. The reactions of ethenetricarboxylates with styrenes or α-bromostyrenes in the presence of SnCl4 or SnBr4 stereoselectively gave 2,4-cis-substituted cyclobutanes. The intramolecular cycloaddition reactions of a series of styrene-functionalized ethenetricarboxylate amides, including in situ generated derivatives, showed high diversity of reaction modes depending on the structures and substituents of the substrates. The regioselectivity and stereoselectivity of the reactions as well as reaction mechanisms were discussed based on the DFT calculations.

Background:High-dose chemotherapy and haematopoietic stem cell transplantation are essential for patients with paediatric haematologic diseases, although cardiotoxicity remains a concern. Heart rate variability analysis can evaluate autonomic nervous function interactions with cardiac function.Objective:This study aimed to characterise heart rate variability differences between patients undergoing chemotherapy and controls, and the effects of haematopoietic stem cell transplantation on the autonomic nervous system in patients with haematological malignancies.Methods:Nineteen patients (11 male, median age: 11.6 years) who received conventional chemotherapy followed by transplantation and 19 non-transplant patients (10 male, median age: 11.5 years) receiving chemotherapy only between 2006 and 2018 for haematological malignancies were retrospectively enrolled. Data from 24-hour Holter monitoring were recorded after chemotherapy and before and after transplantation. Heart rate variability was analysed in patients and 32 matched normal controls.Results:There were significant differences between patients and normal controls in all heart rate variability analysis parameters apart from coefficient of variation of RR interval and standard deviation of the average normal RR interval for all 5-minute segments during sleeping. There was a significant difference in the cumulative anthracycline dose and heart rate variability during sleep between the non-transplant and pre-transplant groups. We observed no remarkable differences in time-domain analysis parameters between before and after transplantation, although the low-frequency component of power-spectrum analysis during awake hours was significantly decreased after transplantation.Conclusion:Conventional chemotherapy for paediatric haematologic diseases may be a risk factor for autonomic dysfunction. Further declines in heart rate variability after transplantation appear minor.

Density functional theory (DFT) calculations of reactions between 2′-deoxyguanosine (dR-Gua) and hydroxyl radical (HO•) with water molecules (H2O)n, n = 0, 1, and 2, were carried out. The HO• addit...

Background Metabolic disorders are important pathophysiologies that can cause multiple organ dysfunction and worsen prognosis in Fontan patients. This study aimed to comprehensively evaluate the metabolomic profile of adult Fontan patients and characterize its pathophysiology in relation to 2 control groups. Methods and Results We performed metabolomic analysis of 31 plasma samples using capillary electrophoresis time-of-flight mass spectrometry. This observational cross-sectional study compared plasma metabolites of 14 heterogeneous adult Fontan patients with those of control groups, including 9 patients with congenital heart disease after biventricular repair and 8 normal healthy controls. Fontan patients exhibited significant differences in intermediate metabolite concentrations related to glycolysis, the tricarboxylic acid (TCA) cycle, and the urea cycle. The plasma concentrations of lactic acid, 2-oxoglutarate, isocitric acid, malic acid, cis-aconitic acid, arginine, citrulline, and the ratio of ornithine/citrulline showed significantly differences among the groups. Multiple logistic regression analysis with a stepwise selection-elimination method identified 2-oxoglutaric acid (odds ratio [OR] 1.98, 95% confidence interval [CI] 1.05–3.76) and cis-aconitic acid (OR 2.69, 95% CI 1.04–6.99) as independently associated with Fontan patients. After adjustment for the covariates of age and gender, 2-oxoglutaric acid (OR 1.97, 95% CI 0.98–3.93) and cis-aconitic acid (OR 3.88, 95% CI 0.99–15.2) showed remarkable relationships with Fontan patients. Conclusions The present findings suggest that abnormalities in the TCA cycle and amino acid metabolism are distinguishing features in the pathophysiology of Fontan patients. Future metabolomic studies will assist in developing biomarkers for the early prediction of “silent” Fontan pathophysiologies.

The oxidation reaction of thiamine (vitamin B1) to thiochrome was investigated by DFT calculations. Three reaction systems, [A] thiamine + methyl peroxy radical + (H2O)8, [B] thiamine + cyanogen bromide + HO-(H2O)8 and [C] thiamine + mercury(ii) chloride + HO-(H2O)8, were investigated. wB97X-D/6-311+G** for [A] and [B] and wB97X-D/SDD&6-311(+)G** for [C] geometry optimizations were carried out with the solvent effect (water). The effect is of the self-consistent reaction field (SCRF) with the polarizable continuum model (PCM). In [A], the H3C-O2˙ adduct of thiamine undergoes simultaneous cleavage of the C-H and O-O bonds, leading to a very stable 2(3H)-thiazolone intermediate. The same intermediate was obtained after the cleavage of the C-H and O-H bonds of the HO adduct of thiamine in [B] and [C]. After the formation of the key intermediate, the N-protonated thiochrome was afforded via three steps. In reflection of the water-soluble character of vitamin B1, proton transfers along hydrogen bonds of the water cluster enhance those steps.

Exercise stress echocardiography has been used to assess myocardial reserve in various heart diseases. This study examined the ventricular myocardial response to exercise in Fontan patients using exercise stress echocardiography.Twenty-five Fontan patients and 19 control subjects underwent semi-supine bicycle exercise stress echocardiography in this prospective, single-center, cross-sectional study. Pulsed-wave Doppler tissue imaging peak systolic (s') and diastolic (e') velocities, longitudinal strain and systolic strain rate, and early diastolic strain rate data at rest and at peak exercise were obtained for the systemic ventricle. The myocardial reserve of functional parameters was calculated as the difference between peak exercise and rest.Inter- and intra-observer reliability were both high for exercise stress echocardiography measurements. Compared with controls, Fontan patients had significantly lower s', e', longitudinal systolic strain and strain rate, and early diastolic longitudinal strain rate at rest and at peak exercise as well as reduced myocardial reserve.Fontan patients have markedly reduced myocardial reserve during exercise. The use of exercise stress echocardiography assessment may improve the clinical management of Fontan patients.

Objectives This study aimed to clarify the current implemented conditions of collaborations between regional and occupational health fields in secondary medical care zones, taking into account the difficulties, and to suggest measures to promote further collaboration.Methods Self-rating questionnaires were distributed to public health nurses (PHNs) who were responsible for collaboration at 464 regional health care centers (HCCs). We asked for answers on four cases regarding the implementation and results of 22 different collaboration activities.Results We analyzed 176 questionnaires from PHNs who had been in charge of conferences for an average of two years. We found the implementation rate of conferences promoting collaboration between regional and occupational health fields to be approximately 80%, with an average duration of four years since these conferences began. Collaborative activities between regional and occupational health fields were divided into three categories: A) "Information exchange among the people involved from regional and occupational fields," B) "Collaboration in health education and counseling," and C) "New health projects based on surveys." The first and third categories (A and C) were significantly higher in the "implemented" group than in the "not implemented" group. The results of the collaborations were organized into six categories: a) "PHNs and members of the conferences (members) could learn about various resources in the community," b) "PHNs and members could build a good relationship among one another and understand community health needs appropriately," c) "Sense of accomplishment and forward progress in the construction of information exchange systems as well as improved cost effectiveness," d) "Progress in health promotion efforts was made," e) "Improvement of health literacy," and f) "An increase in the quality and quantity of participants in health services." The first to three categories (a to c) were higher in cases where three or more conferences were held per year. In addition, we found significant associations between "Collaboration in health education and counseling" (B) and "New health projects based on surveys" (C) as well as with most collaboration result categories.Conclusion This study identified three collaborative activity categories and six cooperative achievement categories. We clarified their relation with the implementation of the council and the number of conferences held. In addition, we demonstrated the possibility that successful cooperation can be realized by active engagement in collaborative activities, such as planning of substantial collaboration and new projects.

We prepared a monoprotonated compound series comprising dmphenHCl ([1H]Cl), dmbpyHCl ([2H]Cl), dmbpyHPF6 ([2H]PF6), bqnHCl ([3H]Cl), bqnHPF6 ([3H]PF6), dmbqnHPF6 ([4H]PF6), naphthyridineHPF6 ([5H]PF6) and phenazineHPF6 ([6H]PF6) and elucidated the crystal structures of [1H]Cl, [2H]Cl, [2H]PF6, [4H]PF6, [5H]PF6 and [6H]PF6. Density functional theory (DFT) calculations of the protonated compounds involving 1, [1H]Cl, [1H]PF6, 2, [2H]Cl, [2H]+, 3, [3H]Cl, [3H]+, 4, [4H]+, 5, [5H]+, 6 and [6H]+ were subsequently performed. Further, time-dependent DFT (TD-DFT) analyses were carried out to elucidate the excited singlet structure. Moreover, the atomic charges of these compounds were examined in detail, and the 1H NMR chemical shifts were correlated to atomic charges in the molecule. Notably, the attachment of one proton to a nitrogen atom in these compounds imparted ionic properties, which resulted in strong red-shifted emissions compared to those of their non-protonated counterparts. In particular, the protonated compound [4H]PF6, with two methyl substituents, displayed the strongest emission.

Density functional theory (DFT) calculations were performed to examine the excited triplet states of various eight iridium(III) complexes and the relationship between these states and the emission spectra. The complexes investigated were 1 [Ir(NO3)2(phen)2]PF6, 2 [IrCl2(phen)2]PF6, 3 [Ir(NO2)2(dmbpy)2]PF6, 4 [IrCl2(dmbpy)2]PF6, 5 [IrCl2(tmphen)2]PF6, 6 [IrCl2(bqn)(dmbpy)]PF6, 7 [IrCl2(bqn)2]PF6 and 8 [IrCl2(bqn)(phen)]PF6. Here, phen is 1,10-phenanthroline, dmbpy is 4,4’-dimethyl-2,2’-bipyridine, tmphen is 3,4,6,7-tetramethyl-1,10-phenanthroline and bqn is 2,2’-biquinoline. Complexes 1, 3, 5, 6 and 8 were newly synthesized for this study and exhibited pronounced phosphorescent emission for 5, 6 and 8. All complexes were calculated to possess excited triplet states. The excited states of the complexes are primarily associated with metal-to-ligand charge transfer (MLCT) and π-π* transitions.

This study presents new monoprotonated 1,10-phenanthroline derivatives that possess remarkable emission properties. We have prepared the monoprotonated compounds, [LH]PF6, by the reaction of L (L = mphen, dmphen, tmphen, NO2phen, bquin and dmdpphen) with concentrated HCl in water. Abbreviations used here are mphen = 5-methyl-1, 10-phenanthroline, dmphen = 2,9-dimethyl -1, 10-phenanthroline, tmphen = 3, 4, 7, 8-tetramethyl-1,10-phenanthroline, NO2phen = 5-nitro-1,10-phenanthroline, bquin = benzquinoline, dpphen = 4,7-diphenyl-1,10-phenanthroline and dmdpphen = 2, 9-dimethyl 4,7-diphenyl-1,10-phenanthroline. Density functional theory was used to investigate the ground and the excited singlet states in these derivatives. The attachment of one proton to the nitrogen atom leads to ionic characters of compounds. In the case of [dmdpphenH]PF6, hydrogen bond between the hydrogen atom in a methyl group and the adjacent F atom in PF6− anion increased molecular rigidity, resulted in a strong red-shifted emission (Φ = 0.197).

DFT calculations were carried out for alkene hydration reactions. A model, alkene + H3O+ (H2O)13 → alcohol + H3O+(H2O)12, was adopted to assure proton transfer routes. The second and larger one, alkene + H3O+(H2O)21 → alcohol + H3O+(H2O)20, was also employed for some key reactions. Alkene substrates adopted here are ethylene, propylene, isobutene, styrenes (α-methyl, para Z-C6H4-CH=CH2, Z=NO2, CN, CF3, Cl, H, Me, OMe, OH, NH2 and NMe2). Transition-state geometries were determined, and the subsequent intrinsic reaction coordinate (IRC) analyses were made. In contrast to the traditional scheme, the stepwise path including the carbocation is quite limited (only for the styrene with Z=OMe, OH, NH2 and NMe2). Even for the isobutene substrate, the tert-Bu+ cation intermediate was not found and a one-step path was obtained. Calculated activation energies, +32.52 kcal/mol (a) for ethylene, +27.10 kcal/mol (b) for propylene, +21.33 kcal/mol (c) for isobutene, +19.79 kcal/mol (d) for styrene and +23.79 kcal/mol (e) for para-nitrostyrene, are in good agreement with experimental values, +32.4±1 kcal/mol (a), +26.4±1 kcal/mol (b), +21.1±0.2 kcal/mol (c), +19.2±0.5 kcal/mol (d) and +23.2 kcal/mol (e), respectively. The solvent isotope effect k(H2O)/k(D2O) was calculated and was compared with the experimental data.

Intramolecular [2 + 2] and [4 + 2] cycloaddition reactions of cinnamylamides of ethenetricarboxylate in sequential processes have been studied. Reaction of 1,1-diethyl 2-hydrogen ethenetricarboxylate and trans-cinnamylamines in the presence of EDCI/HOBt/Et3N led to pyrrolidine products in one pot, via intramolecular [2 + 2], [4 + 2], and some other cyclizations. The types of the products depend on the substituents on the benzene ring and the reaction conditions. Reaction of cinnamylamines without substituents on the benzene ring and with halogens and OMe on the para position at room temperature gave cyclobutane-fused pyrrolidines as major products via [2 + 2] cycloaddition. The reaction at 80 °C in 1,2-dichloroethane gave δ-lactone fused pyrrolidines as major products, probably via ring-opening of the cyclobutanes. Interestingly, reaction of 1,1-diethyl 2-hydrogen ethenetricarboxylate and cinnamylamines bearing electron-withdrawing groups such as NO2, CN, CO2Me, CO2Et, and CF3 on ortho and para positions ...

Background: Intrauterine growth restriction is associated with arterial hypertension in adulthood; however, the underlying mechanism is unclear. Objectives: We hypothesized that serum insulin-like growth factor-1 (IGF-1) levels affect central aortic elastic properties and structure in small-for-gestational-age (SGA) infants. Methods: Eighteen SGA infants and 22 appropriate-for-gestational-age (AGA) infants were enrolled in this study. The serum IGF-1 level within 1 h of birth and abdominal aortic echo parameters at 1 week of age were retrospectively compared. Results: In the SGA infants, IGF-1 levels (27.6 ± 17.7 vs. 42.6 ± 15 ng/ml, p = 0.006), aortic strain (10.2 ± 3.1 vs. 12.8 ± 3.1%, p = 0.01), and aortic distensibility (0.73 ± 0.19 vs. 0.92 ± 0.34 cm2/dyn × 10-4, p = 0.05) were significantly lower compared with AGA infants. By contrast, blood pressure, aortic intima-media thickness (aIMT) in relation to body weight (383 ± 163 vs. 256 ± 43 μm/kg, p < 0.001), aortic stiffness index in relation to body weight (2.0 ± 1.7 vs. 1.1 ± 0.4, p = 0.005), and arterial pressure-strain elastic modulus (293 ± 72 vs. 242 ± 78 mm Hg, p = 0.04) were higher compared with AGA infants. In the SGA infants, IGF-1 levels were significantly correlated with aortic strain (r = 0.49, p = 0.04), aIMT in relation to body weight (r = -0.61, p = 0.007), and aortic stiffness index in relation to body weight (r = -0.63, p = 0.005). Conclusions: Decreased serum IGF-1 levels in SGA infants may affect the vascular compliance and structure of the central aorta.

Catalytic cyclization of allyl amides of ethenetricarboxylate leading to pyrrolidines has been examined. Reaction of allyl amides of ethenetricarboxylate with Sc(OTf) 3 (0.2 equiv) gave 4-hydroxymethyl-2-oxopyrrolidine derivatives as major products. The formation of hydroxymethylpyrrolidines may arise from participation of adventitious water in situ. Sc(OTf) 3 -catalyzed cyclization reactions of the allyl amides with TMSX (X = Cl, Br) proceeded efficiently to give halogenated 2-oxopyrrolidine derivatives. Sc(OTf) 3 -catalyzed cyclization reactions of the allyl ester with TMSX (X= Cl, Br) also proceeded to give halogenated 2-oxotetrahydrofuran derivatives.

A fundamental reduction reaction, nitrobenzene to aniline in SnCl2 and hydrochloric acid, was investigated by density functional theory (DFT) calculations. First, the change of SnCl2 → SnCl42− → Cl4SnH− was discussed, and the reaction path of SnCl42− + H3O+ → Cl4SnH− + H2O was obtained. Starting from nitrobenzene, six elementary processes were found so as to arrive at the protonated aniline. The hydride ion from Cl4SnH− is connected always to the cationic nitrogen, and the proton is always to oxygens. An intermediate PhN+H2OH was obtained, which is isomerized to the para OH adduct protonated imine via the Bamberger rearrangement. This species may undergo the H− acceptance at the sp2 N+H2 center. In the nitrobenzene reduction, the proton enhances the electrophilicity of the nitrogen center, which makes the hydride shift ready. NH bonds are formed, and NO bonds are cleaved both by the proton attach and subsequent H2O elimination and by the formal [1,5] OH shift. Copyright © 2016 John Wiley & Sons, Ltd.

Objective To evaluate the impact of serum insulin-like growth factor-1 (IGF-1) levels on cardiac function in small for gestational age (SGA) infants. Study Design This is a prospective, observational study. Serum IGF-1 levels at birth and echocardiography measurements at 1 week of age were compared between SGA and appropriate for gestational age (AGA) infants. Results Thirty-one SGA infants and 27 AGA infants were enrolled. Serum IGF-1 levels were lower in the SGA infants than in the AGA infants. SGA infants had lower mitral lateral annular systolic (S') and early diastolic (E') tissue Doppler imaging velocities compared with AGA infants (S', 5.1 ± 0.9 vs 5.7 ± 1.2 cm/s; E', 6.1 ± 1.5 cm/s vs 7.1 ± 1.3 cm/s; p Conclusion Decreased serum IGF-I levels could account for cardiac diastolic dysfunction in SGA infants.

The stereospecificity of the cyclization reaction of (E)- and (Z)-2-alkenyl esters and amides of ethenetricarboxylate has been examined. The reaction of (E)/(Z)-2-butenyl esters with AlCl3 or FeCl3 gave trans-substituted chlorinated γ-lactone diastereomers stereospecifically. (E)/(Z)-2-butenyl and pentenyl amides undergo an intramolecular ene reaction at room temperature gradually. At 80 °C, the (Z)-alkenyl amides were transformed to cis-substituted ene adducts and the (E)-amides were transformed to cis- and trans-substituted ene adduct mixtures. The reaction of (E)/(Z)-2-alkenyl amides with ZnI2 gave trans-substituted γ-lactam diastereomers stereospecifically along with the ene adducts.

DFT calculations were carried out to investigate reaction paths of L-ascorbic acid (AAH2), hydroxyl radicals and water clusters. Frontier-orbital analyses were also performed to examine the regioselectivity of the OH˙ addition. Transition states of the electrolytic dissociation of AAH2 and intermediate carboxylic acids were found to have very small activation energies through proton transfers along hydrogen bonds. The ionized species (anions) are subject to the electrophilic attack of OH˙. The elementary processes of AAH2 → A˙(-) → dehydroascorbic acid → diketogulonic acid → threonic, oxalic, xylonic and lyxonic acids were investigated and discussed. The processes involved in the conversion of dehydroascorbic acid into a bicyclic hemiketal were also examined as a side-chain participating reaction. The oxidation and degradation of vitamin C up to threonic acid were described mainly as a donor (AAH2)-acceptor (OH˙) reaction.