Direct observation of photoinduced sequential spin transition in a halogen-bonded hybrid system by complementary ultrafast optical and electron probes.

A detailed understanding of the ultrafast dynamics of halogen-bonded materials is desired for designing supramolecular materials and tuning various electronic properties by external stimuli. Here, a prototypical halogen-bonded multifunctional material containing spin crossover (SCO) cations and paramagnetic radical anions is studied as a model system of photo-switchable SCO hybrid systems using ultrafast electron diffraction and two complementary optical spectroscopic techniques. Our results reveal a sequential dynamics from SCO to radical dimer softening, uncovering a key transient intermediate state. In combination with quantum chemistry calculations, we demonstrate the presence of halogen bonds in the low- and high-temperature phases and propose their role during the photoinduced sequential dynamics, underscoring the significance of exploring ultrafast dynamics. Our research highlights the promising utility of halogen bonds in finely tuning functional properties across diverse photoactive multifunctional materials.

Recurrent nocturnal hypoglycemic hemiplegia: a case report and review of the literature.

A 67-year-old man with type 1 diabetes, Cronkhite-Canada syndrome, and membranous nephropathy who received insulin therapy was admitted to our hospital with right hemiplegia and dysarthria. Brain magnetic resonance imaging revealed a lesion with a high diffusion-weighted imaging signal and low apparent diffusion coefficient signal in the posterior limb of the left internal capsule. He was hypoglycemic with a blood glucose level of 56 mg/dL (3.1 mmol/L). Following glucose administration, the patient's symptoms resolved within several hours. The patient experienced similar transient hypoglycemic hemiplegia at midnight, three times within 10 days. In a literature review of 170 cases of hypoglycemic hemiplegia, 26 cases of recurrent hemiplegia were investigated. Recurrent hypoglycemic hemiplegia occurs more frequently on the right side than on the left side, and most recurrences occur within approximately a week, almost exclusively at midnight and in the early morning. We speculate that hypoglycemia-associated autonomic failure may be involved in the nocturnal recurrence of episodes. In our patient, depleted endogenous insulin secretion and lipodystrophy at the injection site, may have acted as additional factors, leading to severe hypoglycemia despite the absence of apparent autonomic neuropathy. Clinically, it is important to recognize hypoglycemia as a cause of hemiplegia to avoid unnecessary intervention and to maintain an appropriate blood glucose level at midnight and early in the morning to prevent recurrent hypoglycemic hemiplegia.

Photoisomerization of "Partially Embedded Dihydropyridazine" with a Helical Structure.

Invited for the cover of this issue are the groups of Kazuteru Usui and Satoru Karasawa at Showa Pharmaceutical University and Yasuhiro Kobori of Kobe University. The image depicts chirality control of helical compounds through cycles of photocleavage and recombination under sunlight with a "Jack and the Beanstalk" motif. Read the full text of the article at 10.1002/chem.202302413.

Photoisomerization of "Partially Embedded Dihydropyridazine" with a Helical Structure.

Herein, we report the synthesis of two "partially embedded fused-dihydropyridazine N-aryl aza[5]helicene derivatives" (PDHs) and the demonstration of their intrinsic photo-triggered multi-functional properties based on a Kekulé biradical structure. Introducing bulky electron-withdrawing trifluoromethyl or pentafluoroethyl groups into the aza[5]helicene framework (PDH-CF3 and -C2 F5 ) gives PDH axial chirality based on the helicity of the P and M forms, even at room temperature. Upon photo-irradiation of PDH-CF3 in a frozen solution, an ESR signal from the triplet biradical with zero-field splitting values, generated by N-N bond dissociation, was observed. However, when the irradiation was turned off, the ESR signal became silent, thus indicating the existence of two equilibria: between the biradical and quinoidal forms based on the Kekulé structure, and between N-N bond cleavage and recombination. The observed photo- and thermally induced behaviors indicate that T-type photochromic molecules are involved in the photoisomerization mechanism involving the two equilibria. Inspired by the photoisomerization, chirality control of PDH by photoracemization was achieved. Multiple functionalities, such as T-type photochromism, photo-excitation-mediated triplet biradical formation, and photoracemization, which are attributed to the "partially embedded dihydropyridazine" structure, are demonstrated.

Lipid peroxidation-derived modification and its effect on the activity of glutathione peroxidase 1.

Oxidative stress and the resulting lipid peroxidation are associated with various pathological states, including neurodegenerative diseases and cancer. The end products of lipid peroxidation, such as 4-oxo-2(E)-nonenal (ONE), 4-hydroxy-2(E)-nonenal (HNE), and methylglyoxal (MG), exert several biological effects through modification of various cellular components, including DNA and proteins. Glutathione peroxidase 1 (GPx1) is an intracellular antioxidant enzyme that uses glutathione (GSH) to reduce a variety of peroxides, thereby modulating cellular oxidative stress and redox-mediated responses. GPx1 contains nucleophilic amino acids at its active (one Sec) and GSH-binding (four Arg and one Lys) sites. We found that lipid peroxidation-derived reactive aldehydes (ONE, HNE, and MG) modified the GSH-binding site, resulting in the inhibition of GPx1 activity. Mass spectrometry-based proteomic analysis identified the sites modified by each aldehyde (ONE, 14 sites; HNE, 7 sites; MG, 9 sites). The GSH-binding sites modified were as follows: ONE, Arg57, 103, 184, and 185; HNE, Lys91; MG, Arg103. Upon incubation of GPx1 with each aldehyde, ONE reduced GPx1 activity more significantly than did HNE or MG in a dose- and time-dependent manner. The addition of GSH to GPx1 3 h after incubation with ONE prevented further inhibition by trapping ONE as a ONE-GSH adduct. However, the activity of GPx1 was not restored to the initial level, indicating that ONE modified GPx1 irreversibly. This study suggests that oxidative damage to lipids, resulting in the formation of reactive aldehydes, can amplify cellular oxidative stress via direct inactivation of GPx1, which increases the production of intracellular peroxides.

Cases of fulminant type 1 and type 2 diabetes mellitus whose HbA1c levels were unmeasurable due to increased labile HbA1c.

Although the measurement of hemoglobin A1c (HbA1c) using high-performance liquid chromatography (HPLC) is routinely used to estimate average blood glucose levels, it may not be accurately measured for various reasons, such as alteration of red blood cell lifespan and the existence of hemoglobin variants; including hemoglobin F (HbF). Here, we report cases of fulminant type 1 and type 2 diabetes mellitus in which HbA1c levels were unmeasurable because of increased labile HbA1c levels. Case 1 involved a 73-year-old man with fulminant type 1 diabetes mellitus, who was brought to our hospital with diabetic ketoacidosis. The patient's blood glucose level was 994 mg/dL, and HbA1c was unmeasurable, which turned out to be 6.2% on the next day when the blood glucose level was normalized. Case 2 involved a 72-year-old man with type 2 diabetes mellitus, whose blood glucose level was 767 mg/dL, and HbA1c was unmeasurable, which turned out to be 17.9% the following day. In both cases, the chromatograms showed that the HbA1c peaks overlapped with large labile HbA1c peaks, which decreased the next day. It is important to keep in mind that HbA1c levels may not be accurately measured in cases of extreme hyperglycemia because of an increase in labile HbA1c, regardless of the absolute HbA1c level.

A Pilot Study to Assess Glucose, Insulin, and Incretin Responses Following Novel High Resistant Starch Rice Ingestion in Healthy Men.

INTRODUCTION: A newly developed resistant starch (RS) rice line with double mutation of starch synthase IIIa and branching enzyme IIb (ss3a/be2b) exhibits a tenfold greater percentage RS value than the wild-type rice line. Currently, the effects of cooked rice with such high RS content on secretion and action of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are unclear. Therefore, we conducted a pilot study to assess postprandial responses of GLP-1 and GIP along with glucose and insulin and also gastric emptying after ingestion of the high-RS cooked rice with ss3a/be2b in healthy subjects. METHODS: In a non-randomized crossover design, five healthy men ingested two test foods, control (low-RS) and high-RS cooked rice, with at least 1-week washout period between testing days. Plasma glucose, serum insulin, plasma total GLP-1, plasma total GIP, and also gastric emptying rate were measured after ingestion of each test food, and the incremental area under the curves (iAUC) was calculated for each biochemical parameter using the values from 0 to 180 min after ingestion. RESULTS: The high-RS cooked rice ingestion tended to reduce iAUC-glucose (p = 0.06) and significantly reduced iAUC-insulin (p < 0.01) and iAUC-GLP-1 (p < 0.05) but not iAUC-GIP (p = 0.21) relative to control cooked rice ingestion. In addition, the high-RS cooked rice ingestion did not affect gastric emptying. CONCLUSIONS: The present results indicate that the suppressive effects of the high-RS cooked rice ingestion on postprandial responses of glucose and insulin may be provided through attenuation in GLP-1 secretion along with its low digestibility into glucose. We suggest that the high-RS rice with ss3a/be2b may serve as a better carbohydrate source and also as a novel functional food for dietary interventions to improve postprandial hyperglycemia and hyperinsulinemia without both enhancing GLP-1 secretion and affecting gastric emptying in patients with diabetes.

Synergistic association of the copper/zinc ratio under inflammatory conditions with diabetic kidney disease in patients with type 2 diabetes: The Asahi Diabetes Complications Study.

AIMS/INTRODUCTION: We aimed to study the relationships among the copper (Cu)/zinc (Zn) ratio, inflammatory biomarkers, and the prevalence of diabetic kidney disease (DKD) in patients with type 2 diabetes. MATERIALS AND METHODS: A cross-sectional study was performed on 651 patients with type 2 diabetes. DKD was defined as a urinary albumin-to-creatinine ratio of ≥30 mg/g creatinine and/or an estimated glomerular filtration rate using cystatin C of < 60 mL/min/1.73 m2 . Areas under the curves (AUCs), cutoff values, and thresholds for detecting DKD were determined for the Cu/Zn ratio, soluble tumor necrosis factor-α receptor 1 (sTNFαR1), and high-sensitivity C-reactive protein (hsCRP). Patients were categorized by each cutoff value of sTNFαR1 and the Cu/Zn ratio. Odds ratios (ORs) and biological interactions for the prevalence of DKD were determined. RESULTS: DKD was identified in 220 patients. AUC/optimal cutoff values were 0.777/1300 pg/mL for sTNFαR1, 0.603/1.1648 for the Cu/Zn ratio, and 0.582/305 ng/mL for hsCRP. The ORs for DKD were higher, but not significantly, in the sTNFαR1 < 1300 and Cu/Zn ≥ 1.1648 group, significantly higher in the sTNFαR1 ≥ 1300 and Cu/Zn < 1.1648 group (P < 0.0001), and further synergistically elevated in the sTNFαR1 ≥ 1300 and Cu/Zn ≥ 1.1648 group (P < 0.0001) compared with the sTNFαR1 < 1300 and Cu/Zn < 1.1648 group after multivariable adjustment. Levels of sTNFαR1 were significantly higher in the sTNFαR1 ≥ 1300 and Cu/Zn ≥ 1.1648 group than in the sTNFαR1 ≥ 1300 and Cu/Zn < 1.1648 group (P = 0.0006). CONCLUSIONS: Under an inflammatory initiation signal of elevated serum sTNFαR1 levels, an increase in the Cu/Zn ratio may further exacerbate inflammation and is synergistically associated with a high prevalence of DKD in patients with type 2 diabetes.

Effect of non-alcoholic beer containing matured hop bitter acids on mood states in healthy adults: A single-arm pilot study.

This study aimed to investigate the effect of non-alcoholic beer containing matured hop bitter acids on mood states among healthy adults older than 20 years. This study was an open-label longitudinal intervention design in which each participant served as their control. For 3 weeks, we evaluated the effect of non-alcoholic beer containing 35 mg of matured hop bitter acids on mood, sleep quality, and work performance. The data of 97 participants (age range: 23-72 years, median age: 42) were analyzed. After the intervention, we found that matured hop bitter acids significantly improved total mood state, including anxiety, depression, fatigue, and vigor, compared with the baseline. Furthermore, sleep quality and absolute presenteeism were significantly improved after the intervention compared with the baseline. The present exploratory study suggested that 3-week supplementation with matured hop bitter acids improved mood and peripheral symptoms in persons of a wide range of ages. Although further investigation is needed, the findings suggested that non-alcoholic beer in daily life might become a choice for maintaining mood states.

Spin-Crossover-Triggered Linkage Isomerization by the Pedal-like Motion of the Azobenzene Ligand in a Neutral Heteroleptic Iron(III) Complex.

The temperature dependence of magnetic susceptibility of [FeIII(azp)(qsal-Me)]·0.5CH3OH [Hqsal-Me = 5-methyl-N-(8-quinoyl)salicylaldimine, H2azp = 2,2'-azobisphenol] demonstrated that the spin-crossover (SCO) transition behavior changed from an abrupt transition to consecutive gradual conversions, and moreover, the initial abrupt transition was recovered, keeping the complex at room temperature. The variable-temperature crystal structures revealed that an SCO-triggered linkage isomerization of the azobenzene ligand from one orientation to two disordered orientations and the relaxation from the disordered orientations to the original orientation occurred. The high-spin to low-spin relaxation kinetics and theoretical calculation indicate that the pedal-like motion of the azobenzene ligand can be on in the high-spin state whereas off in the low-spin state.

The Impact of the Next-Nearest Neighbor Dispersion Interactions on Spin Crossover Transition Enthalpy Evidenced by Experimental and Computational Analyses of Neutral π-Extended Heteroleptic Fe(III) Complexes.

A neutral heteroleptic Fe(III) complex 1 derived from a π-extension of the parent complex 2 was prepared and characterized. Complex 1 exhibited an abrupt spin crossover (SCO) transition exactly at room temperature (TSCO = 298 K). A crystal structure analysis of 1 revealed that the Fe(III) complex molecules formed a three-dimensional π-stacking interaction network. To thermodynamically clarify the mechanism of the SCO transition, the thermodynamic parameters of the SCO transitions for 1 and 2 were deduced from the temperature dependence of the magnetic susceptibility in the solid and solution states using the regular solution model. A comparison of the SCO enthalpy difference between the solid and molecule for 1 and 2 revealed that the lattice enthalpy difference would largely contribute to the SCO transition enthalpy difference. A computational evaluation of intermolecular interactions and lattice energies before and after the SCO transitions in 1 and 2 disclosed the significant contribution of the next-nearest neighbor dispersion interactions to the lattice enthalpy differences. This finding indicates that not only conventional nearest neighbor intermolecular interactions but also next-nearest neighbor dispersion interactions should be taken into account to understand the fundamental mechanism of a phase transition in molecular solids.

Effect of postprandial hyperglycemia at clinic visits on the incidence of retinopathy in patients with type 2 diabetes: An analysis using real-world long-term follow-up data.

AIMS/INTRODUCTION: There is little evidence on the role of postprandial glycemia in the incidence of diabetic retinopathy (DR) in a real-world setting. We aimed to assess the effect of postprandial hyperglycemia at clinic visits on the incidence of DR in patients with type 2 diabetes, and whether its effect differs depending on glycated hemoglobin (HbA1c) values and age. MATERIALS AND METHODS: Intrapersonal mean blood glucose levels at 1-2 h post-breakfast (1-2h-PBBG), post-lunch (1-2 h-PLBG) and both (1-2h-PBLBG) during 2 years from the first visit were used as baseline data. This retrospective cohort study enrolled 487, 323 and 406 patients who had 1-2h-PBLBG, 1-2h-PBBG and 1-2h-PLBG measurements, respectively. These three groups were followed from 1999 up through 2017. RESULTS: DR occurred in 145, 92 and 126 patients in the 1-2h-PBLBG, 1-2h-PBBG and 1-2h-PLBG groups, respectively. Multivariate Cox regression analysis showed that the mean 1-2h-PBLBG, 1-2h-PBBG and 1-2h-PLBG levels were significant predictors of DR, independent of mean HbA1c. In patients with mean HbA1c <7.0% and those with a baseline age <60 years, the mean 1-2h-PBLBG, 1-2h-PBBG and 1-2h-PLBG levels were significant predictors. CONCLUSIONS: Postprandial hyperglycemia at clinic visits might predict the incidence of DR, independent of HbA1c. The effect of postprandial hyperglycemia on DR is obvious in patients with well-controlled HbA1c and in younger patients. Even with the lower HbA1c level, correcting postprandial hyperglycemia is important for preventing DR, especially in middle-aged adults with type 2 diabetes.

Ligand mixed-valence and electrical conductivity in coordination complexes containing a redox-active phenalenol-substituted ligand.

A new redox-active hydrazone ligand bearing a phenalenol group is described (phpl), which produces neutral six-coordinate Fe and Co complexes (1 & 2) with the ligands identified in different oxidation states; an open-shell anion radical and closed-shell dianion. An intense and very low-energy intervalence charge transfer (IVCT) band is identified in solid-state and in solution in the complexes. Single crystals of 1 are semiconducting (at 300 K, σ = 3.05 × 10-4 S cm-1 with Ea = 245 meV).

Association between postprandial hyperglycemia at clinic visits and all-cause and cancer mortality in patients with type 2 diabetes: A long-term historical cohort study in Japan.

AIMS: To evaluate the effect of postprandial hyperglycemia at clinic visits on all-cause and cancer mortality independent of glycated hemoglobin (HbA1c) levels in a real-world setting in Japanese patients with type 2 diabetes. We also investigated age at death. METHODS: This historical cohort study included 1582 patients with type 2 diabetes who first visited our clinic from 1995 to 1998 and continued visiting for at least 1 year. The patients were followed up through 2017. Blood glucose levels at 2 h ±â€¯30 min post-breakfast (2h-PBBG) were measured in 926 patients during the first year. The first measurements of 2h-PBBG levels were used as a measure of postprandial hyperglycemia. RESULTS: A total of 233 patients died. The average age at death (men/women) was 75.6/80.8 years. A total of 139 patients who had 2h-PBBG levels measured died, including 46 deaths from cancer. Multivariate Cox regression analysis showed that 2h-PBBG levels significantly predicted all-cause and cancer mortality independent of HbA1c levels. CONCLUSIONS: Postprandial hyperglycemia at clinic visits may be associated with all-cause and cancer mortality in patients with type 2 diabetes independent of HbA1c levels. As this is a small observational study, further studies are warranted to confirm our findings.

Photogeneration of Microporous Amorphous Coordination Polymers from Organometallic Ionic Liquids.

Ruthenium-containing organometallic ionic liquids with the B(CN)4 anion were developed that generate microporous amorphous coordination polymers upon UV irradiation. UV light irradiation of [Ru(C5 H5 )(C6 H5 R)][B(CN)4 ] (R=butyl, ethyl, octyl) quantitatively generated a yellow powder of a coordination polymer with the formula [Ru(C5 H5 ){B(CN)4 }]n . In this reaction, the arene ligand is eliminated by UV irradiation and coordination polymer is formed by coordination of the cyano groups of the anion to the Ru ion. The photogenerated solids exhibited nitrogen absorption properties due to their microporous structure. This paper proposes a method to fabricate functional coordination polymers by photoirradiation of liquids.

Contribution of Coulomb Interactions to a Two-Step Crystal Structure Phase Transformation Coupled with a Significant Change in Spin Crossover Behavior for a Series of Charged FeII Complexes from 2,6-Bis(2-methylthiazol-4-yl)pyridine.

A series of [FeII(L)2](BF4)2 compounds were structurally and physically characterized (L = 2,6-bis(2-methylthiazol-4-yl)pyridine). A crystal structure phase transformation from dihydrate compound 1 to anhydrous compound 3 through partially hydrated compounds 2 and 2' upon dehydration was found. Compounds 1 and 3 exhibited a gradual spin crossover (SCO) conversion, whereas compounds 2 and 2' demonstrated two-step and one-step abrupt SCO transitions, respectively. An X-ray single-crystal structural analysis revealed that one-dimensional and two-dimensional Fe cation networks linked by π stacking and sulfur-sulfur interactions were formed in 1 and 3, respectively. A thermodynamic analysis of the magnetic susceptibility for 1, 2', and 3 suggests that the enthalpy differences may govern SCO transition behaviors in the polymorphic compounds 2' and 3. A structural comparison between 1 and 3 indicates that the SCO behavior variations and crystal structure transformation in the present [FeII(L)2](BF4)2 compounds can be interpreted by the relationship between the lattice enthalpies mainly arising from Coulomb interactions between the Fe cations and BF4 anions as in typical ionic crystals.

Paramagnetic ionic plastic crystals containing the octamethylferrocenium cation: counteranion dependence of phase transitions and crystal structures.

In recent years, ionic plastic crystals have attracted much attention. Many metallocenium salts exhibit plastic phases, but factors affecting their phase transitions are yet to be elucidated. To investigate these factors, we synthesized octamethylferrocenium salts with various counteranions [Fe(C5Me4H)2]X ([1]X; X- = B(CN)4-, C(CN)3-, N(CN)2-, FSA (= (SO2F)2N-), FeCl4-, GaCl4- and CPFSA (= CF2(SO2CF2)2N-)) and elucidated their crystal structures and phase behavior. Correlations between the crystal structures and phase sequences, and the shapes and volumes of the anions are discussed. Except for [1][CPFSA], these salts exhibit phase transitions to plastic phases at or above room temperature (TC = 298-386 K), and the plastic phases exhibit either NaCl- or anti-NiAs-type structures. X-ray crystal structure analyses of these salts at 100 K revealed that they have structures in which cations and anions are alternately arranged, with the exception of [1][CPFSA]. [1][CPFSA] exhibits a structure in which anions and cations are separately stacked to form columns. [1][N(CN)2] exhibits a polar crystal structure that undergoes a monotropic phase transition to a centrosymmetric structure. The magnetic susceptibilities of room-temperature plastic crystals [1][GaCl4] and [1][FeCl4] were investigated; the latter exhibits a small ferromagnetic interaction at low temperatures.

Cooperative spin-crossover transition from three-dimensional purely π-stacking interactions in a neutral heteroleptic azobisphenolate FeIII complex with a N3O3 coordination sphere.

A novel neutral heteroleptic FeIII complex from two kinds of π-extended tridentate ligands was designed and prepared. The π-ligands formed a three-dimensional purely π-stacking interaction network. The present complex proved to be the first neutral spin-crossover (SCO) FeIII complex with a N3O3 coordination sphere exhibiting an abrupt SCO transition with a thermal hysteresis of 10 K and the light-induced excited spin-state trapping effect.

Thermochromic Magnetic Ionic Liquids from Cationic Nickel(II) Complexes Exhibiting Intramolecular Coordination Equilibrium.

Among the various thermochromic materials, liquid thermochromic materials are comparatively rare. To produce functional thermochromic liquids, we have designed ionic liquids based on cationic nickel complexes with ether side chains, [Ni(acac)(Me2 NC2 H4 NR1 R2 )]Tf2 N ([1]Tf2 N: R1 =C3 H6 OEt, R2 =Me; [2]Tf2 N: R1 =C3 H6 OMe, R2 =Me; [3]Tf2 N: R1 =R2 =C3 H6 OMe), where acac=acetylacetonate and Tf2 N=(F3 CSO2 )2 N- . The side chains (R1 , R2 ) can moderately coordinate to the metal center, enabling temperature-dependent coordination equilibria in the liquid state. [1]Tf2 N is a liquid at room temperature. [2]Tf2 N is obtained as a solid (Tm =352.7 K) but remains liquid at room temperature after melting. [3]Tf2 N is a solid with a high melting point (Tm =422.3 K). These salts display thermochromism in the liquid state, appearing red at high temperatures and orange, light-blue, or bluish-green at lower temperatures, and exhibiting concomitant changes in their magnetic properties. This phenomenon is based on temperature-dependent equilibrium between a square-planar diamagnetic species and a paramagnetic species with intramolecular ether coordination.

Directional Electron Transfer in Crystals of [CrCo] Dinuclear Complexes Achieved by Chirality-Assisted Preparative Method.

The polarization switching mechanism is used in various devices such as pyroelectric sensors and memory devices. The change in polarization mostly occurs by ion displacement. The development of materials whose polarization switches via electron transfer in order to enhance operation speed is a challenge. We devised a synthetic and crystal engineering strategy that enables the selective synthesis of a [CrCo] heterometallic dinuclear complex with a polar crystal structure, wherein polarization changes stem from intramolecular charge transfer between Co and the ligand. Polarization can be modulated both by visible-light irradiation and temperature change. The introduction of chiral ligands was paramount to the successful polarization switching in the valence tautomeric compound. Mixing Cr and Co complexes with enantiopure chiral ligands resulted in the selective formation of only pseudosymmetric [CrCo] heterometallic complexes. Furthermore, the left-handed chiral ligands preferentially interacted with their right-handed counterparts, enabling molecules to form a polar crystal structure.