Albuminuria and Serum Tumor Necrosis Factor Receptor Levels in Patients with Type 2 Diabetes on SGLT2 Inhibitors: A Prospective Study.

INTRODUCTION: Large-scale clinical trials of sodium-glucose cotransporter 2 inhibitors (SGLT2i) demonstrate proteinuria-reducing effects in diabetic kidney disease, even after treatment with renin-angiotensin inhibitors. The precise mechanism for this favorable effect remains unclear. This prospective open-label single-arm study investigated factors associated with a reduction in proteinuria after SGLT2i administration. METHODS: Patients with type 2 diabetes (T2DM) who had glycated hemoglobin (HbA1c) levels ≥ 6.5% despite dietary and/or oral hypoglycemic monotherapy were recruited and administered the recommended daily dose of SGLT2i for 4 months. Dual primary outcomes were changes in the urine albumin-to-creatinine ratio (uACR) and urine liver-type fatty acid-binding protein (L-FABP)-to-creatinine ratio (uL-FABPCR) at month 4 from baseline. Changes in kidney injury, inflammation, and oxidative stress biomarkers were investigated as secondary endpoints to examine the effects of this treatment on the kidney. The correlation between renal outcomes and clinical indicators, including circulating tumor necrosis factor receptors (TNFR) 1 and 2, was evaluated using univariate and multivariate analyses. RESULTS: Participants (n = 123) had a mean age of 64.1 years (SD 13.4), with 50.4% being male. The median BMI was 25.8 kg/m2 (interquartile range (IQR) 23.1-28.9), and the median HbA1c level was 7.3% (IQR 6.9-8.3). After SGLT2i administration, the uACR declined from 19.2 mg/gCr (IQR 7.1-48.7) to 13.3 mg/gCr (IQR 7.5-31.6), whereas the uL-FABPCR was not influenced. In univariate analysis, the change in log-transformed uACR due to SGLT2i administration showed a positive correlation with the change in serum TNFR1 level (R = 0.244, p < 0.01). Multivariate regression analysis, including confounding factors, showed that the changes in serum TNFR1 level were independently associated with the changes in the log-transformed uACR (independent t = 2.102, p < 0.05). CONCLUSION: After the 4-month SGLT2i administration, decreased albuminuria level was associated with decreased serum TNFR level in patients with T2DM. TRIAL REGISTRATION NUMBER: UMIN000031947.

Previous studies have demonstrated the synergistic proteinuria-reducing effect of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in combination therapy with renin­angiotensin system blockers; however, the underlying mechanisms of this effect are poorly understood. This study was based on our hypothesis that the proteinuria-reducing effect is associated with the anti-inflammatory effects of SGLT2i beyond the effect on glycemic control. In total, 123 patients with type 2 diabetes mellitus (T2DM) were administered the recommended daily dose of SGLT2i for 4 months. Dual primary outcomes were changes in the urine albumin-to-creatinine ratio (uACR) and urine liver-type fatty acid-binding protein (L-FABP)-to-creatinine ratio (uL-FABPCR) as markers of glomerular and proximal tubular damage at 4 months from the baseline. Secondary outcomes included changes in kidney injury biomarkers, inflammation, and oxidative stress to examine the effects of treatment on the kidneys. The correlation between renal outcomes and clinical indicators, including circulating tumor necrosis factor receptors (TNFR) 1 and 2, was evaluated using univariate and multivariate analyses. We found that administration of SGLT2i decreased the urine albumin-to-creatinine ratio but did not affect the urine liver-type fatty acid-binding protein-to-creatinine ratio. Further, SGLT2i may exert a proteinuria-reducing effect dependent on the anti-inflammatory effect in patients with T2DM. The inflammation-reducing and renoprotective mechanisms of SGLT2i remain to be fully clarified, but this study provides novel evidence regarding the mechanism. The study findings can help in developing anti-inflammatory agents for metabolic diseases.

Kinetic Formation of Pt-Pt Dimers of Cationic and Neutral Platinum(II) Complexes under Rapid Freeze Conditions in Solution.

We report the formation of M-M dimers (M = Pt or Pd) of cationic [M(dpb)(CH3CN)]+ [dpbH = 1,3-di(2-pyridyl)benzene] and neutral [M(dpb)Cl] complexes resulting from the rapid freezing of solutions. Dimers based on M-M dz2 overlap were found to preferentially form rather than the thermodynamically favored head-to-tail π-stacking structures typically observed in the crystalline state. Kinetic dimers in glassy frozen solutions generated broad metal-metal-to-ligand charge-transfer emissions within the range of 600-800 nm at 77 K. These emissions were red-shifted relative to monomer emissions. As expected, the degree of aggregation of these complexes was affected by the concentration in each solution. Photoexcitation evidently accelerated Pt-Pt dimerization even at ambient temperature. Electrostatic attraction between [Pt(dpb)Cl]+ and [Pt(dpb)Cl]- ions resulting from disproportionation due to photoinduced electron transfer is thought to have driven excimer formation. [Pt(dpb)(CH3CN)]OTf (OTf- = trifluoromethanesulfonate ion) and its Pd(II) analogue were determined to have isostructural crystals, but a Pd-Pd stacked polymorph was not observed and the photophysics of the two complexes are evidently different.

Plasma Heparin Cofactor II Activity Is Inversely Associated with Hepatic Fibrosis of Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus.

AIMS: Thrombin exerts various pathophysiological functions by activating protease-activated receptors (PARs), and thrombin-induced activation of PARs promotes the development of non-alcoholic fatty liver disease (NAFLD). Since heparin cofactor II (HCII) specifically inactivates thrombin action, we hypothesized that plasma HCII activity correlates with the severity of NAFLD. METHODS: A cross-sectional study was conducted. Plasma HCII activity and noninvasive clinical markers of hepatic fibrosis including fibrosis-4 (FIB-4) index, NAFLD fibrosis score (NFS) and aspartate aminotransferase-to-platelet ratio index (APRI) were determined in 305 Japanese patients with type 2 diabetes mellitus (T2DM). The relationships between plasma HCII activity and the clinical markers were statistically evaluated. RESULTS: Multiple regression analysis including confounding factors showed that plasma HCII activity independently contributed to decreases in FIB-4 index (p＜0.001), NFS (p＜0.001) and APRI (p=0.004). In addition, logistic regression analysis for the prevalence of advanced hepatic fibrosis defined by the cutoff points of the clinical scores showed that plasma HCII activity was the sole and common negative factor for prevalence of advanced hepatic fibrosis (FIB-4 index: p=0.002, NFS: p=0.026 and APRI: p=0.012). CONCLUSIONS: Plasma HCII activity was inversely associated with clinical hepatic fibrosis indices including FIB-4 index, NFS and APRI and with the prevalence of advanced hepatic fibrosis in patients with T2DM. The results suggest that HCII can serve as a novel biomarker for assessment of hepatic fibrosis of NAFLD in patients with T2DM.

Vapochromism of an iridium(III) bis-terpyridine complex based on the modulation of halide-to-ligand charge transfer transition.

We report, for the first time, a color change originating from the shift of the halide-to-ligand charge transfer (XLCT) band of the Ir(III) bis-terpyridine complex crystal in response to the sorption/desorption of water of crystallization. Red and orange coloration reversibly takes place by heat and cool treatments, respectively. Single X-ray crystallography shows that the Ir(III) complex possesses two waters of crystallization constructing a dimer structure, rO-O = 2.911 Å, by hydrogen bonding. It was found that the water dimer connects to one of the iodide ions with rO-I = 3.664 Å by hydrogen bonding and comes into contact with another iodide ion with rO-I = 3.747 Å, suggesting that water desorption from the crystal easily changes the XLCT transition arising from the interaction between the iodide ion 5p orbital and tpy π* orbital. Thermogravimetry measurement reveals the stepwise water desorption from the crystal, and powder X-ray diffraction shows the robustness of the Ir(III) complex crystal framework during the sorption/desorption cycles. Nitrogen gas flow or presence of a polar organic solvent contributes to the red-shift of the XLCT absorption band due to the desorption of water molecules resulted by the shift of equilibrium between water molecules in the crystal and vaporized water molecules. Exposure to ammonia vapor from 25% aqueous ammonia is found not to contribute to the color change of the Ir(III) complex crystal.

Reversible colour/luminescence colour changes of tetracyanoruthenium(II) complexes by sorption/desorption of water molecules in crystals.

We report colour/luminescence colour changes of M[Ru(bpy)(CN)4] crystal (M2+ = Ca2+, Sr2+, and Ba2+; bpy = 2,2'-bipyridine). The X-ray crystallographic study revealed that the crystals are constructed from linear-chains of {[Ru(bpy)(CN)4][Ca(H2O)5]}n, {[Ru(bpy)(CN)4][Sr(H2O)6]}n, and {[Ru(bpy)(CN)4]2[Ba(H2O)5]2(µ-H2O)2}n, respectively. Ru(II) complex linear chains and the hydrophilic channels composed of M2+ ion and water along them enable reversible water sorption/desorption without collapse of crystals responsible for the colour change. The emission spectra of Ca2+ and Sr2+ salts are remarkably shifted to the red side when the temperature was increased from 296 to 500 K, while Ba2+ salt shows a slight shift in the emission spectrum during the heating. The change in the interaction of M2+ ion to the equatorial CN ligand depending on the number of hydrated water molecules effectively contributes to the luminescence colour change for Ca2+ and Sr2+ salts. FT-IR spectra after heating at 473 K show the high-frequency shifts in the CN stretching mode for Sr2+ salt, while no remarkable peak shifts are observed for Ca2+ and Ba2+ salts. Thermogravimetry results indicate that heating over 470 K leads to the desorption of 5H2O from all salts, resulting in {[Ru(bpy)(CN)4][Ca]}n, {[Ru(bpy)(CN)4][Sr(H2O)]}n, and {[Ru(bpy)(CN)4]2[Ba]2(µ-H2O)2}n for linear chains. The change in the hydration structure for M2+ ions regulates the shift of CN stretching modes.

Plasma heparin cofactor II activity is inversely associated with albuminuria and its annual deterioration in patients with diabetes.

AIMS/INTRODUCTION: Thrombin exerts various pathophysiological functions by activating protease-activated receptors (PARs). Recent data have shown that PARs influence the development of glomerular diseases including diabetic kidney disease (DKD) by regulating inflammation. Heparin cofactor II (HCII) specifically inactivates thrombin; thus, we hypothesized that low plasma HCII activity correlates with DKD development, as represented by albuminuria. MATERIALS AND METHODS: Plasma HCII activity and spot urine biomarkers, including albumin and liver-type fatty acid-binding protein (L-FABP), were determined as the urine albumin-to-creatinine ratio (uACR) and the urine L-FABP-to-creatinine ratio (uL-FABPCR) in 310 Japanese patients with diabetes mellitus (176 males and 134 females). The relationships between plasma HCII activities and those DKD urine biomarkers were statistically evaluated. In addition, the relationship between plasma HCII activities and annual uACR changes was statistically evaluated for 201/310 patients (115 males and 86 females). RESULTS: The mean plasma HCII activity of all participants was 93.8 ± 17.7%. Multivariate-regression analysis including confounding factors showed that plasma HCII activity independently contributed to the suppression of the uACR and log-transformed uACR values (P = 0.036 and P = 0.006, respectively) but not uL-FABPCR (P = 0.541). In addition, plasma HCII activity significantly and inversely correlated with annual uACR and log-transformed uACR increments after adjusting for confounding factors (P = 0.001 and P = 0.014, respectively). CONCLUSIONS: The plasma HCII activity was inversely and specifically associated with glomerular injury in patients with diabetes. The results suggest that HCII can serve as a novel predictive factor for early-stage DKD development, as represented by albuminuria.

Increased Neurofilament Light Chain and YKL-40 CSF Levels in One Japanese IBMPFD Patient With VCP R155C Mutation: A Clinical Case Report With CSF Biomarker Analyses.

Inclusion body myopathy (IBM) with Paget's disease of bone (PDB) and frontotemporal dementia (IBMPFD) presents with multiple symptoms and an unknown etiology. Valosin-containing protein (VCP) has been identified as the main causative gene of IBMPFD. However, no studies on neurofilament light chain (NFL) as a cerebrospinal fluid (CSF) marker of axonal neurodegeneration or on YKL-40 as a CSF marker of glial neuroinflammation have been conducted in IBMPFD patients with VCP mutations. A 65-year-old man presented with progressive muscle atrophy and weakness of all limbs, non-fluent aphasia, and changes in personality and behavior. Cerebral MRI revealed bilateral frontal and temporal atrophy. 99mTc-HMDP bone scintigraphy and pelvic CT revealed remodeling changes and active osteoblastic accumulations in the right medial iliac bone. Muscle biopsy demonstrated multiple rimmed vacuoles in muscle cells with myogenic and neurogenic pathological alterations. After the patient was clinically diagnosed with IBMPFD, DNA analysis of the VCP gene revealed a cytosine (C) to thymine (T) (C→ T) mutation, resulting in an amino acid exchange of arginine to cysteine (p.R155C mutation). The CSF levels of NFL at two time points (12 years apart) were higher than those in non-dementia controls (CTR) and Alzheimer's disease (AD); lower than those in frontotemporal dementia with motor neuron disease (FTD-MND); and comparable to those in patients with behavioral variant frontotemporal dementia (bvFTD), progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS). The CSF levels of YKL-40 were comparable at both time points and higher than those in CTR; lower than those in FTD-MND; and comparable to those in bvFTD, PSP, CBS, and AD. The CSF levels of phosphorylated tau 181 (P-Tau) and total tau (T-Tau) were not significantly different from those in CTR and other neurodegenerative diseases, except those in AD, which were significantly elevated. This is the first report that demonstrates increased NFL and YKL-40 CSF levels in an IBMPFD patient with a VCP mutation (p.R155C); NFL and YKL-40 levels were comparable to those in bvFTD, PSP, CBS, and AD and higher than those in CTR. Our results suggest that IBMPFD neuropathology may involve both axonal neurodegeneration and glial neuroinflammation.

Photoinduced swing of a diarylethene thin broad sword shaped crystal: a study on the detailed mechanism.

We report a swinging motion of photochromic thin broad sword shaped crystals upon continuous irradiation with UV light. By contrast in thick crystals, photosalient phenomena were observed. The bending and swinging mechanisms are in fact due to molecular size changes as well as phase transitions. The first slight bending away from the light source is due to photocyclization-induced surface expansion, and the second dramatic bending toward UV incidence is due to single-crystal-to-single-crystal (SCSC) phase transition from the original phase I to phase IIUV. Upon visible light irradiation, the crystal returned to phase I. A similar SCSC phase transition with a similar volume decrease occurred by lowering the temperature (phase IIItemp). For both photoinduced and thermal SCSC phase transitions, the symmetry of the unit cell is lowered; in phase IIUV the twisting angle of disordered phenyl groups is different between two adjacent molecules, while in phase IIItemp, the population of the phenyl rotamer is different between adjacent molecules. In the case of phase IIUV, we found thickness dependent photosalient phenomena. The thin broad sword shaped crystals with a 3 µm thickness showed no photosalient phenomena, whereas photoinduced SCSC phase transition occurred. In contrast, large crystals of several tens of µm thickness showed photosalient phenomena on the irradiated surface where SCSC phase transition occurred. The results indicated that the accumulated strain, between isomerized and non-isomerized layers, gave rise to the photosalient phenomenon.

Highly Efficient and Robust Photocatalytic Systems for CO2 Reduction Consisting of a Cu(I) Photosensitizer and Mn(I) Catalysts.

The development of highly efficient, selective, and durable photocatalytic CO2 reduction systems that only use earth-abundant elements is key for both solving global warming and tackling the shortage of energy and carbon resources. Here, we successfully developed CO2 reduction photocatalysts using [Cu2(P2bph)2]2+ (CuPS) (P2bph = 4,7-diphenyl-2,9-di(diphenylphosphinotetramethylene)-1,10-phenanthroline) as a redox photosensitizer and fac-Mn(X2bpy)(CO)3Br (Mn(4X)) (X2bpy = 4,4'-X2-2,2'-bipyridine (X = -H and -OMe) or Mn(6mes) (6mes = 6,6'-(mesityl)2-2,2'-bipyridne)) as the catalyst. The most efficient photocatalysis was achieved by Mn(4OMe): The total quantum yield of CO2 reduction products was 57%, the turnover number based on the Mn catalyst was over 1300, and the selectivity of CO2 reduction was 95%. Electronic and steric effects of the substituents (X) in the Mn complexes largely affected both the photocatalytic efficiency and the product selectivity. For example, the highest selectivity of CO formation was achieved by using Mn(6mes) (selectivity SCO = 96.6%), whereas the photocatalytic system using Mn(4H) yielded HCOOH as the main product ( SHCOOH = 74.6%) with CO and H2 as minor products ( SCO = 23.7%, SH2 = 1.7%). In these photocatalytic reactions, CuPS played its role as an efficient and very durable redox photosensitizer, while remaining stable in the reaction solution even after a turnover number of 200 had been reached (the catalyst used had a turnover number of over 1000).

Photosalient Phenomena that Mimic Impatiens Are Observed in Hollow Crystals of Diarylethene with a Perfluorocyclohexene Ring.

A diarylethene with a perfluorocyclohexene ring formed hollow crystals by sublimation under normal pressure. Upon UV irradiation of the crystals, they showed remarkable photosalient phenomena and scattered into small pieces. The speed of the flying debris released from the crystal by UV irradiation exceeded several meters per second. To clearly show a photosalient effect resembling the scattering behavior of Impatiens on a smaller scale, small fluorescent beads (1-µm diameter) were inserted into the hollow crystal. Consequently, scattering of the beads was observed as UV irradiation caused deformation and bursting of the hollow structure. This phenomenon is unique to hollow crystals, and the ability to effectively induce remarkable photosalient phenomena is similar to the behavior of hollow-structured Impatiens in nature.

Identification of novel SNORD118 mutations in seven patients with leukoencephalopathy with brain calcifications and cysts.

BACKGROUND: Leukoencephalopathy with brain calcifications and cysts (LCC) is neuroradiologically characterized by leukoencephalopathy, intracranial calcification, and cysts. Coats plus syndrome is also characterized by the same neuroradiological findings together with defects in retinal vascular development. Indeed, LCC and Coats plus were originally considered to be the same clinical entity termed cerebroretinal microangiopathy with calcifications and cysts, but evidence suggests that they are genetically distinct. Mutations in CTS telomere maintenance complex component 1 (CTC1) and small nucleolar RNA, C/D box 118 (SNORD118) genes have been found to cause Coats plus and LCC, respectively. MATERIALS AND METHODS: Eight unrelated families with LCC were recruited. These patients typically showed major neuroradiological findings of LCC with no signs of extra-neurological manifestations such as retinal abnormality, gastrointestinal bleeding, or hematological abnormalities. SNORD118 was examined by Sanger sequencing in these families. RESULTS: Seven out of eight probands carry compound heterozygous mutations, suggesting that SNORD118 mutations are the major cause of LCC. We identified a total of eight mutation, including four that were novel. Some of the variants identified in this study present heterozygously in public databases with an extremely rare frequency (<0.1%). CONCLUSION: Biallelic SNORD118 mutations were exclusively found in most unrelated families with LCC.

A Case of Optic Neuritis Concomitant with Pituitary Tumor During Pregnancy.

BACKGROUND: Optic neuritis (ON) is unilateral painful optic nerve inflammation in a young healthy female diagnosed by excluding glaucoma. ON onset during pregnancy is rare, with only 2 cases reported to date. CASE DESCRIPTION: A 35-year-old previously healthy parous woman who was pregnant with her second child suffered rapidly progressive visual acuity loss. Magnetic resonance imaging (MRI) revealed a pituitary tumor. Emergency surgery was performed for optic nerve compression; however, her visual impairment worsened. Postoperative diffusion-weighted MRI showed high intensity in the bilateral optic nerves, and ON was diagnosed. Administration of methylprednisolone was effective, and her visual acuity recovered over 6 months. CONCLUSIONS: Associated pituitary macroadenoma complicated the true diagnosis of ON, because contrast medium cannot be used in pregnant women. The diffusion-weighted MRI findings were useful for diagnosing this complex clinical condition.

Photocatalytic CO2 Reduction Using Cu(I) Photosensitizers with a Fe(II) Catalyst.

Photocatalytic systems developed from complexes with only abundant metals, i.e., Cu(I)(dmp)(P)2(+) (dmp =2,9-dimethyl-1,10-phenanthroline; P = phosphine ligand) as a redox photosensitizer and Fe(II)(dmp)2(NCS)2 as a catalyst, produced CO as the main product by visible light irradiation. The best photocatalysis was obtained using a Cu(I) complex with a tetradentate dmp ligand tethering two phosphine groups, where the turnover number and quantum yield of CO formation were 273 and 6.7%, respectively.

Trinuclear and Tetranuclear Re(I) Rings Connected with Phenylene, Vinylene, and Ethynylene Chains: Synthesis, Photophysics, and Redox Properties.

A series of highly luminescent trinuclear and tetranuclear ring-shaped Re(I) complexes wherein the Re units are linked with rigid bidentate phosphine ligands, namely, bis(diphenylphosphino)-p-phenylene, -trans-vinylene, and -ethynylene, were synthesized and fully characterized. Their strong emissive properties and the long lifetimes of their triplet metal-to-ligand charge transfer excited states originate primarily from enhanced, rigidity-induced interligand interactions between the 2,2'-bipyridine (bpy) ligand and the phenyl groups of the phosphine ligands. In addition, another type of interligand interaction was also observed between the bpy ligand and the phosphine-bridging group; this interaction also strongly affected the photophysical and redox properties of the Re-rings.

[A case of filamentous fungal infection showing tumor-like expansion in the cisterns].

A 67-year-old woman was admitted for headache. The initial MRI showed a gadolinium-enhanced lesion in the prepontine area. Initial and repeated CSF examinations were negative for the fungal infection. Since the enhanced lesion expanded in the cisterns, and showed tumor-like appearance, brain biopsy was performed at 3 months from her first admission. Histological studies revealed filamentous fungal infection probably caused by the pseudallescheria boydii. Intrathecal miconazole injection through the Ommaya reservoir successfully ameliorated patient's symptoms and the MRI findings. Primary cisternal fungal infection showing tumor-like expansion typically fails to demonstrate its supportive findings by the CSF examination. Therefore, histopathological assessment after brain biopsy should be considered in cases that are not conclusive by means of conventional laboratory examinations.

Relation between photochromic properties and molecular structures in salicylideneaniline crystals.

The crystal structures of the salicylideneaniline derivatives N-salicylidene-4-tert-butyl-aniline (1), N-3,5-di-tert-butyl-salicylidene-3-methoxyaniline (2), N-3,5-di-tert-butyl-salicylidene-3-bromoaniline (3), N-3,5-di-tert-butyl-salicylidene-3-chloroaniline (4), N-3,5-di-tert-butyl-salicylidene-4-bromoaniline (5), N-3,5-di-tert-butyl-salicylidene-aniline (6), N-3,5-di-tert-butyl-salicylidene-4-carboxyaniline (7) and N-salicylidene-2-chloroaniline (8) were analyzed by X-ray diffraction analysis at ambient temperature to investigate the relationship between their photochromic properties and molecular structures. A clear correlation between photochromism and the dihedral angle of the two benzene rings in the salicylideneaniline derivatives was observed. Crystals with dihedral angles less than 20° were non-photochromic, whereas those with dihedral angles greater than 30° were photochromic. Crystals with dihedral angles between 20 and 30° could be either photochromic or non-photochromic. Inhibition of the pedal motion by intra- or intermolecular steric hindrance, however, can result in non-photochromic behaviour even if the dihedral angle is larger than 30°.

Absolute chirality of the γ-polymorph of glycine: correlation of the absolute structure with the optical rotation.

Crystal specimens of the γ-polymorph of achiral glycine which crystallize in space groups P31 and P32 as determined by the anomalous X-ray scattering method are shown to be laevorotatory and dextrorotatory, respectively, as determined by optical rotation of the crystals.

Direct observation of arylnitrene formation in the photoreaction of arylazide crystals.

Seven crystal structures of arylazides, 2-azidobiphenyl (2), 4-(4-azidophenyl)butanoic acid (3), 3-azidobenzoic acid (4), N-(4-azidophenyl)acetamide (5), 2,4,6-trichlorophenyl azide (6), 2,5-dibromophenyl azide (7) and 2,4,6-tribromophenyl azide (8), have been analyzed by X-rays. When the crystals were irradiated with UV light at ≃ 80 K, only 2-azidobiphenyl gradually changed its cell dimensions with the retention of the single-crystal form. The crystal structure after photo-irradiation was analyzed by X-rays under the same conditions as those before photo-irradiation. Approximately 20% of the 2-azidobiphenyl molecule was converted to the triplet 2-biphenylnitrene and dinitrogen molecules. The existence of the triplet nitrene was confirmed by ESR and IR measurements. Although the structure of dinitrogen was clearly determined, the nitrene structure was obscure because the nitrene produced was almost superimposed on the original 2-azidobiphenyl. The other six crystals were non-reactive or easily broken when they were exposed to UV light. The different reactivity between 2-azidobiphenyl and the other compounds was successfully explained by the reaction cavity of the azido group.

Direct observation of various reaction pathways of arylnitrenes in different crystal environments caused by acid-base complex formation.

The structures of reaction intermediates, arylnitrenes and their final products have been successfully analyzed by X-rays using acid-base complex formation. The acid-base complexes of 2-azidobenzoic acid (2a), 3-azidobenzoic acid (3a) and 4-azidobenzoic acid (4a) were made with dibenzylamine (db), N-benzyl-2-phenylethylamine (bp) and dicyclohexylamine (dc). For the complex crystals of (3a) and db (3a-db), and (4a) and db (4a-db) two forms of (I) and (II) were obtained. Eight types of complex crystals, (2a-db), (3a-db-I), (3a-db-II), (3a-dc), (4a-db-I), (4a-db-II), (4a-bp) and (4a-dc), suitable for X-ray analysis were obtained. When the crystals were irradiated with UV light at low temperatures, the reactions proceeded keeping the single-crystal form in the five crystals (2a-db), (3a-db-I), (3a-db-II), (3a-dc) and (4a-bp). Less than 25% of each azidobenzoic acids was transformed into an arylnitrene and dinitrogen. In three crystals the arylnitrenes produced gave new final products; 2,1-benzisoxazolone was observed for (2a-db) and trans-azobenzenes (i.e. dimerized nitrenes) were obtained for (3a-db-II) and (4a-bp). For (3a-db-I) and (3a-dc) the intermediate arylnitrenes were observed but did not transform to new products. All the structural changes were directly observed by X-ray analysis because the incomplete reactions occurred with retention crystallinity. The crystal environment, including the hydrogen bonding between the benzoic acid and the amine, places restrictions on the movement of the arylnitrene and influences the reaction pathway followed for conversion of the arylnitrene to its final product.

Potassium clavulanate.

The title salt, K(+)·C(8)H(8)NO(5) (-) [systematic name: potassium (2R,5R,Z)-3-(2-hy-droxy-ethyl-idene)-7-oxo-4-oxa-1-aza-bicyclo-[3.2.0]heptane-2-carb-oxyl-ate], a widely used ß-lactam anti-biotic, is usually chemically unstable even in the solid state owing to its tendency to be hydrolysed. In the crystal structure, the potassium cations are arranged along the a axis, forming inter-actions to the carboxyl-ate and hy-droxy groups, resulting in one-dimensional ionic columns. These columns are arranged along the b axis, connected by O-H⋯O hydrogen bonds, forming a layer in the ab plane.